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The integumentary system of the leatherback sea turtle (Dermochelys coriacea) is the most visible and defining difference of the species, with its smooth and waxy carapace and finely scaled skin, distinguishing it from the other six sea turtle species. The skin is the body's largest organ and serves as a primary defense against the outside world and is thus essential to health. To date, we have begun to understand that the microorganisms located on the skin aid in these functions. However, many host–microbial interactions are not yet fully defined or understood. Prior to uncovering these crucial host–microbial interactions, we must first understand the communities of microorganisms present and how they differ through life-stage classes and across the body. Here, we present a comprehensive bacterial microbial profile on the skin of leatherbacks. Using next-generation sequencing (NGS), we identified the major groups of bacteria on the skin of neonates at emergence, neonates at 3–4 weeks of age (i.e., post-hatchlings), and nesting females. These data show that the predominant bacteria on the skin of the leatherback are different at each life-stage class sampled. This suggests that there is a shift in the microbial communities of the skin associated with life-stage class or even possibly age. We also found that different sample locations on the nesting female (i.e., carapace and front appendages = flipper) have significantly different communities of bacteria present. This is likely due to differences in the microhabitats of these anatomic locations and future studies should explore if this variation also holds true for neonates. These data define baseline skin microbiota on the leatherback and can serve as a foundation for additional work to broaden our understanding of the leatherbacks' host–microbial interactions, the impacts of environmental changes or stressors over time, and even the pathogenicity of disease processes. [ABSTRACT FROM AUTHOR]

Soil amendments such as humic acid (HA), a biochar-based microbial agent (M), and vermicompost (V) can improve soil quality and promote crop growth. However, it remains unclear whether the co-application of the three soil amendments (HMV) has a synergistic effect on alleviating soil quality deterioration obstacles caused by dry sowing and wet emergence technology in Xinjiang cotton fields. A three-year field experiment was conducted in saline–alkali soils using plastic-film-mulched drip irrigation in Xinjiang, China. Through the orthogonal experiment method, the application amounts of HA, M and V were 75 kg ha−1, 75 kg ha−1 and 225 kg ha−1 respectively in 2021. In 2022, three application amount gradients were used for HA, M and V: 60 kg ha−1, 90 kg ha−1 and 120 kg ha−1 respectively. In 2023, the application amounts of HA, M, and V were 60 kg ha−1, 120 kg ha−1, and 120 kg ha−1. It should be pointed out that V contains HA in the range of 20–35%. This study aimed to explore the improvement effect of a single or combined application of HA, M, and V on soil quality and cotton emergence rate using dry sowing and wet emergence technology in Xinjiang cotton fields. The results showed that the single and combined applications of HA, M, and V improved the soil quality and water–heat–salt environment of the cultivated layer. In the combined application, the cotton seedling emergence rate and yield increased by 1.9–22.8% and 7.0–54.1%. Therefore, it is recommended to jointly apply HA, M, and V to promote cotton seedling emergence and increase yield using dry sowing and wet emergence technology in Xinjiang cotton fields. [ABSTRACT FROM AUTHOR]

Primary cardiac tumours are relatively uncommon (75% are benign). Across the other 25%, representing malignant neoplasia, sarcomas account for 75–95%, and primary cardiac intimal sarcoma (PCIS) is one of the rarest findings. We aimed to present a comprehensive review and practical considerations from a multidisciplinary perspective with regard to the most recent published data in the specific domain of PCIS. We covered the issues of awareness amid daily practice clinical presentation to ultra-qualified management in order to achieve an adequate diagnosis and prompt intervention, also emphasizing the core role of MDM2 immunostaining and MDM2 genetic analysis. An additional base for practical points was provided by a novel on-point clinical vignette with MDM2-positive status. According to our methods (PubMed database search of full-length, English publications from January 2021 to March 2023), we identified three studies and 23 single case reports represented by 22 adults (male-to-female ratio of 1.2; male population with an average age of 53.75 years, range: 35–81; woman mean age of 55.5 years, range: 34–70) and a 4-year-old child. The tumour-related clinical picture was recognized in a matter of one day to ten months on first admission. These non-specific data (with a very low index of suspicion) included heart failure at least NYHA class II, mitral regurgitation and pulmonary hypertension, acute myocardial infarction, ischemic stroke, obstructive shock, and paroxysmal atrial fibrillation. Awareness might come from other complaints such as (most common) dyspnoea, palpitation, chest pressure, cough, asthenia, sudden fatigue, weakness, malaise, anorexia, weight loss, headache, hyperhidrosis, night sweats, and epigastric pain. Two individuals were initially misdiagnosed as having endocarditis. A history of prior treated non-cardiac malignancy was registered in 3/23 subjects. Distant metastasis as the first step of detection (n = 2/23; specifically, brain and intestinal) or during follow-up (n = 6/23; namely, intestinal, brain and bone, in two cases for each, and adrenal) required additional imagery tools (26% of the patients had distant metastasis). Transoesophageal echocardiography, computed tomography (CT), magnetic resonance imagery, and even 18F-FDG positronic emission tomography-CT (which shows hypermetabolic lesions in PCIS) represent the basis of multimodal tools of investigation. Tumour size varied from 3 cm to ≥9 cm (average largest diameter of 5.5 cm). The most frequent sites were the left atrium followed by the right ventricle and the right atrium. Post-operatory histological confirmation was provided in 20/23 cases and, upon tumour biopsy, in 3/23 of them. The post-surgery maximum free-disease interval was 8 years, the fatal outcome was at the earliest two weeks since initial admission. MDM2 analysis was provided in 7/23 subjects in terms of MDM2-positive status (two out of three subjects) at immunohistochemistry and MDM2 amplification (four out of five subjects) at genetic analysis. Additionally, another three studies addressed PCISs, and two of them offered specific MDM2/MDM2 assays (n = 35 patients with PCISs); among the provided data, we mention that one cohort (n = 20) identified a rate of 55% with regard to MDM2 amplification in intimal sarcomas, and this correlated with a myxoid pattern; another cohort (n = 15) showed that MDM2-positive had a better prognostic than MDM2-negative immunostaining. To summarize, MDM2 amplification and co-amplification, for example, with MDM4, CDK4, HMGA3, CCND3, PDGFRA, TERT, KIT, CCND3, and HDAC9, might improve the diagnosis of PCIS in addition to MDM2 immunostaining since 10–20% of these tumours are MDM2-negative. Further studies are necessary to highlight MDM2 applicability as a prognostic factor and as an element to be taken into account amid multi-layered management in an otherwise very aggressive malignancy. [ABSTRACT FROM AUTHOR]

Myxofibrosarcomas (MFS) present as slowly enlarging superficial masses in elderly patients. Even though these tumors fail to exhibit a distinct immunophenotype, diagnosis is straightforward when they present in subcutaneous tissue. Intramuscular MFS, however, are more challenging to diagnose as the differential also includes dedifferentiated liposarcoma with myxoid features. The vast majority of dedifferentiated liposarcomas show MDM2 amplification, whereas limited data exists as to the MDM2 status of MFS. We sought to explore the rate of MDM2 amplification in cases of classic MFS. Our archives were searched for MFS; only subcutaneous well-sampled resections were included. FISH for MDM2 amplification was performed on each tumor. A cohort of myxoid dedifferentiated liposarcoma resections was studied for comparison. Twenty-two MFS arose in patients aged 44 to 85 years. All tumors contained an infiltrative population of atypical cells embedded in a myxoid stroma with curvilinear blood vessels. MDM2 amplification by FISH was identified in 3 (of 22; 14%) tumors. Available follow up on 17 patients (range 1-96 months; median 13 months) revealed 6 patients with local recurrence and 1 with distant metastasis. Of 3 patients with MDM2- amplified MFS, 1 experienced recurrence and died of unrelated causes, while the second was alive without disease 12 months after diagnosis. Even though the rate of MDM2 amplification by FISH in MFS appears to be low, a subset of cases may show this genetic alteration, which pathologists should be aware of to avoid misclassification as myxoid dedifferentiated liposarcomas. Further studies are necessary to determine if amplification status adds prognostic value. [ABSTRACT FROM AUTHOR]

The identification of gene fusions has become an integral part of soft tissue and bone tumour diagnosis. We investigated the added value of targeted RNA‐based sequencing (targeted RNA‐seq, Archer FusionPlex) to our current molecular diagnostic workflow of these tumours, which is based on fluorescence in situ hybridisation (FISH) for the detection of gene fusions using 25 probes. In a series of 131 diagnostic samples targeted RNA‐seq identified a gene fusion, BCOR internal tandem duplication or ALK deletion in 47 cases (35.9%). For 74 cases, encompassing 137 FISH analyses, concordance between FISH and targeted RNA‐seq was evaluated. A positive or negative FISH result was confirmed by targeted RNA‐seq in 27 out of 49 (55.1%) and 81 out of 88 (92.0%) analyses, respectively. While negative concordance was high, targeted RNA‐seq identified a canonical gene fusion in seven cases despite a negative FISH result. The 22 discordant FISH‐positive analyses showed a lower percentage of rearrangement‐positive nuclei (range 15–41%) compared to the concordant FISH‐positive analyses (>41% of nuclei in 88.9% of cases). Six FISH analyses (in four cases) were finally considered false positive based on histological and targeted RNA‐seq findings. For the EWSR1 FISH probe, we observed a gene‐dependent disparity (p = 0.0020), with 8 out of 35 cases showing a discordance between FISH and targeted RNA‐seq (22.9%). This study demonstrates an added value of targeted RNA‐seq to our current diagnostic workflow of soft tissue and bone tumours in 19 out of 131 cases (14.5%), which we categorised as altered diagnosis (3 cases), added precision (6 cases), or augmented spectrum (10 cases). In the latter subgroup, four novel fusion transcripts were found for which the clinical relevance remains unclear: NAB2::NCOA2, YAP1::NUTM2B, HSPA8::BRAF, and PDE2A::PLAG1. Overall, targeted RNA‐seq has proven extremely valuable in the diagnostic workflow of soft tissue and bone tumours. [ABSTRACT FROM AUTHOR]

Transcription factor 12 (TCF12) is a known oncogene in many cancers. However, whether TCF12 can regulate malignant phenotypes and angiogenesis in osteosarcoma is not elucidated. In this study, we demonstrated increased expression of TCF12 in osteosarcoma tissues and cell lines. High TCF12 expression was associated with metastasis and poor survival rate of osteosarcoma patients. Knockdown of TCF12 reduced the proliferation, migration, and invasion of osteosarcoma cells. TCF12 was found to bind to the promoter region of sphingosine kinase 1 (SPHK1) to induce transcriptional activation of SPHK1 expression and enhance the secretion of sphingosine-1-phosphate (S1P), which eventually resulted in the malignant phenotypes of osteosarcoma cells. In addition, S1P secreted by osteosarcoma cells promoted the angiogenesis of HUVECs by targeting S1PR4 on the cell membrane to activate the STAT3 signaling pathway. These findings suggest that TCF12 may induce transcriptional activation of SPHK1 to promote the synthesis and secretion of S1P. This process likely enhances the malignant phenotypes of osteosarcoma cells and induces angiogenesis via the S1PR4/STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

Bone regeneration using Bone Morphogenetic Proteins (BMPs) alongside various engineered scaffolds has attracted considerable attention over the years. The field has seen extensive research in preclinical animal models, leading to the approval of two products and guiding the quest for new materials. Natural and synthetic polymers, ceramics, and composites have been used to fabricate the necessary porous 3D scaffolds and delivery systems for BMPs. Interestingly, all reported applications in the literature are triumphant. Evaluation of the results is typically based on histologic assessment after appropriate staining and radiological modalities, providing morphological identification of the newly formed bone and describing cells and the organic compound. Remarkably, while these evaluation methods illustrate mineralization, they are not capable of identifying hydroxyapatite crystals, the mineral component of the bone, which are crucial for its mechanical properties, structure, integrity, and long-term stability of regenerated bone tissue. This review aims to focus on the different scaffolds used in bone tissue engineering applications and underline the pressing need for techniques that could recognize the presence of hydroxyapatite crystals as well as their characteristics in bone tissue engineering, which will provide a more complete and comprehensive assessment of the successful results. [ABSTRACT FROM AUTHOR]

This study aims to assess in situ the impact of effluents originating from an Atlantic salmon (Salmo salar) farm on a nearby slender sea pen (Virgularia mirabilis) field. We evidenced (1) the presence and persistence of emamectin residues (i.e. a common chemotherapeutants used for treating ectoparasites in salmons) in V. mirabilis tissue 56 days after treatment and (2) lethal and sublethal responses of V. mirabilis to effluents discharged by the salmon farm. Particularly, sea pens near the fish farm exhibited significant overproduction of mucus, contraction of polyps' tentacles, and disappearance of associated fauna. Furthermore, sea pens located directly underneath the farm showed substantial tissue necrosis and, in the most severe case, complete tissue loss and mortality. Our results suggest that lethal damages on sea pens occur directly below the farm, and that sublethal effects are visible up to 500 m from the farm. However, the presence of V. mirabilis below the studied farm, which has been active for more than twenty years, suggests that V. mirabilis population possesses the capacity to recover from the impacts of the farm, thereby preventing the complete disappearance from the area. In this context, it would be particularly interesting to run a temporal survey following the health state of V. mirabilis during an entire production cycle to have a more precise overview of fish farm impacts on this species, including during and after the post-production fallowing period. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we investigate the availability and access to orphan drugs for rare cancers in Bulgaria, aiming to address the urgent need for improved treatment access for this vulnerable population. By comparing data from European and national sources, we aimed to assess the availability, delays, and budgetary impact of these drugs. Our findings reveal significant disparities in their access and highlight the pressing need for targeted policies to address these inequalities. This research contributes valuable insights into the challenges faced by rare cancer patients and we call for focused efforts at both the European and national levels to ensure equitable access to treatment. Rare cancers are defined by an annual incidence of fewer than 6 per 100,000. Bearing similarities to rare diseases, they are associated with substantial health inequalities due to diagnostic complexity and delayed access to innovative therapies. This situation is further aggravated in Southeastern European countries like Bulgaria, where limited public resources and expertise underscore the need for additional policy and translational research on rare cancers. This study aimed to explore the availability and access to orphan drugs for rare cancers in Bulgaria for the period of 2020–2023. We cross-compared data from both the European Union and national public sources to evaluate the number of available and accessible orphan drugs for rare cancers, the delay from market authorization to reimbursement, the dynamics of public expenditures, and regional disparities in access across the country. We juxtaposed the main characteristics of oncological and non-oncological orphan drugs as well. Only 15 out of 50 oncological orphan drugs that were authorized by the European Medicine Agency were accessible for rare cancer patients in Bulgaria. The median delay between market authorization and inclusion in the Bulgarian Positive Drug List was 760 days. The total expenditures for all orphan drugs for rare cancers amounted to EUR 74,353,493 from 2020 to 2023. The budgetary impact of this group rose from 0.24% to 3.77% of total public medicinal product expenditures for the study period. Rare cancer patients represent a vulnerable population that often faces limited to no access to treatment. We call for targeted European and national policies to address this major inequality. [ABSTRACT FROM AUTHOR]

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The breeding of laying hens and broilers in China has increased tremendously. Wet organic fertilizer prepared from hen manure using high-temperature container fermentation preserves high levels of nutrients and a diverse microbial community. We applied low doses of organic fertilizer to peanuts in the black soil area of China's northeastern region. Based on the calculation of nitrogen content, treatments were set as follows: chemical fertilizer (PCF), organic fertilizer (POF, 4500 kg·ha−1), and replacement of 50% chemical fertilizer with organic fertilizer (PR, 2250 kg·ha−1). Compared to the plots with chemical fertilizers, the use of organic fertilizer and replacing 50% of the chemical fertilizers with organic fertilizer significantly increased peanut yields. Both the organic fertilizer and replacing 50% of the chemical fertilizers with organic fertilizer did not significantly affect the activities of the most tested soil enzymes related to carbon transformation and the absolute abundance of microorganisms. However, they did significantly enhance soil dehydrogenase and α-glucosidase. The community abundance ratio of fungi/bacteria trended downward, leading to soil with a high-fertility bacterial composition. The replacement of 50% chemical fertilizer with organic fertilizer significantly enhanced the species richness and diversity of the bacterial and fungal communities. Organic fertilizer treatment significantly increased the relative abundance of Gemmatimonas and Sphingomonas. The relative abundance of Mycobacterium in the treatment where 50% of the chemical fertilizers were replaced with organic fertilizer was significantly lower than that in the organic fertilizer treatment. PCoA results showed that the low-dose organic fertilizer treatment, replacing 50% of the chemical fertilizers with organic fertilizer, had a significant impact on the composition of soil bacterial communities. [ABSTRACT FROM AUTHOR]

Simple Summary: The quality of resection after unplanned excision of soft tissue sarcoma (STS) performed outside of a reference center or at second resection potentially impacts local and metastatic recurrence and survival. The French cohort NETSARC prospectively collected data from patients with unplanned excision outside reference centers from 2010 to 2019 and reported survival in patients reexcised (RE) or not (No-RE). Patients who would most benefit from RE need to be identified. A total of 2371 patients had unplanned excision for STS outside reference centers, including 1692 patients with no multidisciplinary board review (RE: 913; No-RE: 779). Discrepancies in RE/No-RE subgroups were observed regarding age, tumor site, size, depth, grade and histotype. R0 final resection associated with better MFS; R1 initial resection showed better MFS than R0 initial resection. The study identified RE as an independent favorable factor for MFS (HR 0.7, 95% CI 0.53–0.93; p = 0.013). All subgroups except patients > 70 years, and patients with large tumors (>10 cm) showed better MFS with RE. RE in patients with STS of limb or trunk after macroscopic complete resection out of NETSARC reference center, and also in R0 resections to improve LRFS and MFS. Systematic RE should not be advocated for patients ≥ 70 years, or tumor size ≥ 10 cm. Background: Whether re-excision (RE) of a soft tissue sarcoma (STS) of limb or trunk should be systematized as adjuvant care and if it would improve metastatic free survival (MFS) are still debated. The impact of resection margins after unplanned macroscopically complete excision (UE) performed out of a NETSARC reference center or after second resection was further investigated. Methods: This large nationwide series used data from patients having experienced UE outside of a reference center from 2010 to 2019, collected in a French nationwide exhaustive prospective cohort NETSARC. Patient characteristics and survival distributions in patients reexcised (RE) or not (No-RE) are reported. Multivariate Cox proportional hazard model was conducted to adjust for classical prognosis factors. Subgroup analysis were performed to identify which patients may benefit from RE. Results: Out of 2371 patients with UE for STS performed outside NETSARC reference centers, 1692 patients were not reviewed by multidisciplinary board before treatment decision and had a second operation documented. Among them, 913 patients experienced re-excision, and 779 were not re-excised. Characteristics were significantly different regarding patient age, tumor site, size, depth, grade and histotype in patients re-excised (RE) or not (No-RE). In univariate analysis, final R0 margins are associated with a better MFS, patients with R1 margins documented at first surgery had a better MFS as compared to patients with first R0 resection. The study identified RE as an independent favorable factor for MFS (HR 0.7, 95% CI 0.53–0.93; p = 0.013). All subgroups except older patients (>70 years) and patients with large tumors (>10 cm) had superior MFS with RE. Conclusions: RE might be considered in patients with STS of limb or trunk, with UE with macroscopic complete resection performed out of a reference center, and also in originally defined R0 margin resections, to improve LRFS and MFS. Systematic RE should not be advocated for patients older than 70 years, or with tumors greater than 10 cm. [ABSTRACT FROM AUTHOR]

Floods are the primary natural hazard in the French Mediterranean area, causing damages and fatalities every year. These floods are triggered by heavy precipitation events (HPEs) characterized by limited temporal and spatial extents. A new generation of regional climate models at the kilometer scale have been developed, allowing an explicit representation of deep convection and improved simulations of local-scale phenomena such as HPEs. Convection-permitting regional climate models (CPMs) have been scarcely used in hydrological impact studies, and future projections of Mediterranean floods remain uncertain with regional climate models (RCMs). In this paper, we use the CNRM-AROME CPM (2.5 km) and its driving CNRM-ALADIN RCM (12 km) at the hourly timescale to simulate floods over the Gardon d'Anduze catchment located in the French Mediterranean region. Climate simulations are bias-corrected with the CDF-t method. Two hydrological models, a lumped and conceptual model (GR5H) and a process-based distributed model (CREST), forced with historical and future climate simulations from the CPM and from the RCM, have been used. The CPM model confirms its ability to better reproduce extreme hourly rainfall compared to the RCM. This added value is propagated on flood simulation with a better reproduction of flood peaks. Future projections are consistent between the hydrological models but differ between the two climate models. Using the CNRM-ALADIN RCM, the magnitude of all floods is projected to increase. With the CNRM-AROME CPM, a threshold effect is found: the magnitude of the largest floods is expected to intensify, while the magnitude of the less severe floods is expected to decrease. In addition, different flood event characteristics indicate that floods are expected to become flashier in a warmer climate, with shorter lag time between rainfall and runoff peak and a smaller contribution of base flow, regardless of the model. This study is a first step for impact studies driven by CPMs over the Mediterranean. [ABSTRACT FROM AUTHOR]

Long-term historical data and their interpretation are crucial aspects of understanding any kind of variation that exists as a result of changing environmental behaviour. The focus of the study is to characterize precipitation properties in the middle subdivision of the Mahanadi River basin (MRB). An eigen-based technique, also known as the maximum loading value approach, and gridded precipitation data with a resolution of 0.25° × 0.25° are presented to analyze the spatiotemporal properties of precipitation at different timeslot intervals. The meteorological data (gridded precipitation for 117 years from 1901 to 2017) has a special "k" field for spatial and temporal modes of spatial pattern analysis, which aids in the recognition of precipitation properties. The identified characteristics of the exclusive timeslot periods have been assessed for any dispersion as a function of annual precipitation. To cross-validate the identified patterns for distinctness and pairwise comparison, the Kolmogorov–Smirnov's D test was used. Southwest Mahanadi does not experience much variation in pattern size (± 3–5%), with a maximum variance of 39.09% during timeslot 2 (1940–1978). Similarly, the southeast Mahanadi observed a continuous increase in pattern size and was above 10% with a maximum variance of 28.53% during timeslot 3 (1979–2 017). While north-eastern Mahanadi experienced a continuous and significant decrease of > 14% of the total variance, with a maximum (42.48%) during timeslot 1 (1901–1939) and a minimum (28.14%) during timeslot 3 (1979–2017). There is no spatial pattern variability from summer to any of the timeslot intervals. [ABSTRACT FROM AUTHOR]

A clean environment is an essential component of sustainable development, which is based on a comprehensive understanding of the behavior of water, soil, and air. The soil water retention (SWR) curve is a crucial function that describes how soil retains water, playing a fundamental role in irrigation and drainage, soil conservation, as well as water and contaminant transport in the vadose zone. This study evaluates the accuracy, performance, and prediction capabilities of 15 SWR models. A total of 140 soil samples were collected from different sites, covering all textural classes. Standard suction tests, using both hanging column and ceramic pressure plate extractors, were conducted to compile the SWR databank. 15 SWR models were selected and fitted to the SWR data points. Soil texture, bulk density, and organic matter were used to determine their effect on the performance of the SWR models. The results indicate that the Tani and Russo models exhibit the lowest levels of accuracy and performance among the selected models. Based on the Akaike and Bayesian information criteria analysis, the van Genuchten model exhibits the lowest values among the selected models, with poor prediction capabilities in estimating the SWR curve. The significance test at the 0.05 level (95% confidence interval) shows that according to the calculated p-values for the Pearson correlation coefficient between RMSE and texture, the Brooks-Corey and van Genuchten models are poorly influenced by soil properties. The performance of the models is not significantly affected by the soil organic matter. Similarly, bulk density does not significantly affect model performance except for the Brooks–Corey, van Genuchten, Tani, and Russo models. Among the SWR models considered, the double exponential, Groenevelt and Grant, and Khlosi et al. models demonstrate superior accuracy and performance in predicting the SWR curve. This is supported by lower values for RMSE, Akaike, and Bayesian information criteria. [ABSTRACT FROM AUTHOR]

Introduction: Intense histological research has been conducted on human bone and teeth for a long period of time. Histological evaluation of these highly mineralised tissues demands a thorough decalcification process using different chemical agents, which might alter some aspects of tissue architecture and staining properties. Aim: To assess the impact of four decalcifying agents on rat teeth and bone, focusing on the rate of decalcification, staining effectiveness, and tissue structure preservation. Materials and Methods: An in-vitro animal study was conducted in the Department of Oral Diagnosis at the College of Dentistry, University of Baghdad, Bab Almoaadim, Baghdad, Iraq from October 2022 to March 2023. Four decalcification agents, namely 10% Neutral Ethylenediaminetetraacetic Acid (EDTA), 10% formic acid, 3% nitric acid, and 5% nitric acid, were used to decalcify 24 molar teeth with their surrounding alveolar bone obtained from healthy male rats, which were randomly divided into four groups, each group consisting of six teeth. The decalcified sections underwent regular processing, and staining was performed using Haematoxylin and Eosin (H&E). Grading was conducted after two separate observers examined the stained sections under a light microscope. Data were presented using Mean±Standard Deviation (SD), number, and percentage. A one-way Analysis of Variance (ANOVA) (F-test) was used to compare the decalcification times within groups. Several group comparisons, including categorical data, were examined using the Chi-square test. Results: Nitric acids (3% and 5%) exhibited the fastest decalcification with a mean value of (2±0.89) days, while Formic acid required (3.5±0.54) days, and EDTA was the slowest, with (19±1.09) days. These differences in decalcification time were found to be statistically significant (p<0.00001). Formic acid 10% demonstrated superior tissue preservation and staining quality, with excellent staining results, minimal dentin-pulp separation, and preservation of pulp zones, cementum, and osteoblasts. In contrast, nitric acid 5% resulted in severe dentinpulp separation, absence of pulp zones, absence of osteoblast, and significant osteocyte retraction. Statistical significance was observed across all agents for dentin-pulp separation, pulp organisation, cementum destruction, Periodontal Ligament (PDL) separation, and osteocyte retraction (p-values of 0.004, 0.02, 0.02, 0.04, and 0.03, respectively). Conclusion: Consequently, 10% formic acid emerged as the most efficient decalcifying solution, ensuring rapid decalcification with favourable staining intensity and tissue architecture. [ABSTRACT FROM AUTHOR]

Giant cell tumor of bone (GCTB) is characterized by uncertain biological behavior due to its local aggressiveness and metastasizing potential. In this study, we conducted a meta-analysis of the contemporary literature to evaluate all management strategies for GCTB metastases. A combination of the terms "lung metastases", "giant cell tumor", "bone", "treatment", and "oncologic outcomes" returned 133 patients meeting our inclusion criteria: 64 males and 69 females, with a median age of 28 years (7–63), at the onset of primary GCTB. Lung metastases typically occur at a mean interval of 26 months (range: 0–143 months) after treatment of the primary site, commonly presenting as multiple and bilateral lesions. Various treatment approaches, including surgery, chemotherapy, radiotherapy, and drug administration, were employed, while 35 patients underwent routine monitoring only. Upon a mean follow-up of about 7 years (range: 1–32 years), 90% of patients were found to be alive, while 10% had died. Death occurred in 25% of patients who had chemotherapy, whereas 96% of those not treated or treated with Denosumab alone were alive at a mean follow-up of 6 years (range: 1–19 years). Given the typically favorable prognosis of lung metastases in patients with GCTB, additional interventions beyond a histological diagnosis confirmation may not be needed. Denosumab, by reducing the progression of the disease, can play a pivotal role in averting or delaying lung failure. [ABSTRACT FROM AUTHOR]

Curettage is recommended for the treatment of Campanacci stages 1–2 giant cell tumor of bone (GCTB) in the extremities, pelvis, sacrum, and spine, without preoperative denosumab treatment. In the distal femur, bone chips and plate fixation are utilized to reduce damage to the subchondral bone and prevent pathological fracture, respectively. For local recurrence, re-curettage may be utilized when feasible. En bloc resection is an option for very aggressive Campanacci stage 3 GCTB in the extremities, pelvis, sacrum, and spine, combined with 1–3 doses of preoperative denosumab treatment. Denosumab monotherapy once every 3 months is currently the standard strategy for inoperable patients and those with metastatic GCTB. However, in case of tumor growth, a possible malignant transformation should be considered. Zoledronic acid appears to be as effective as denosumab; nevertheless, it is a more cost-effective option. Therefore, zoledronic acid may be an alternative treatment option, particularly in developing countries. Surgery is the mainstay treatment for malignant GCTB. [ABSTRACT FROM AUTHOR]

The North Sea (NS) is changing rapidly. Temporal variations in fishing intensity and eutrophic conditions, along with the ongoing impact of climate change, act in synergy resulting in modifications in marine communities. Although zooplankton has been extensively investigated, studies often ignore the large-sized meso- and macro-zooplankton (>500 µm), including holoplankton and meroplankton taxa. Here, we examined changes in abundances and community structure of these organisms between 1975 and 2018, using univariate and multivariate analysis, at different taxonomic levels. Abrupt changes in the abundances of (sub)communities occurred during different time periods and resulted in a significant restructuration of the entire community in 2006. These changes were consistent with the regime shifts reported in the NS and were a consequence of the environmental pressures on the whole community or on specific subcommunities. In the long term, the community shifted from higher abundances of hydrozoans and holoplankton taxa to an increasing abundance of decapods. Furthermore, we reveal the environmental variables that most explain the variability in the community dynamics, highlighting the importance of temperature and top-down processes. Our study underlines the relevance of investigations at different taxonomic levels, which elucidates how distinct responses to environmental changes ultimately shape the entire community structure. [ABSTRACT FROM AUTHOR]

This article presents a description of an analytical, stable, and flexible initial background state for both dry and moist baroclinic wave simulation on an aquaplanet in order to test the dynamical core of numerical weather prediction models and study the dynamics and evolution of extratropical cyclones. The initial background state is derived from an analytical zonal wind speed field, or jet structure, and the hydrostatic primitive equations for moist adiabatic and frictionless flow in spherical coordinates. A baroclinic wave can develop if a perturbation is added to the zonal wind speed field. This new baroclinic wave configuration has been implemented in the Open Integrated Forecasting System (OpenIFS) CY43R3, a global numerical weather prediction model developed by the European Centre for Medium-Range Weather Forecasts. In total, seven parameters can be used to control the generation of the initial background state and hence the development of the baroclinic waves in the OpenIFS configuration file: the jet's width, the jet's height, the maximum zonal mean wind speed of the jet, the horizontal mean of the surface virtual temperature, the surface relative humidity, the lapse rate, and the surface roughness. Nine dry and nine moist initial background states have been generated to test their stability without perturbations. The meteorological stability of the initial states is investigated by examining the spatial distributions of the equivalent potential temperature, the absolute vorticity, and the Brunt–Väisälä frequency. Moreover, the root mean square error (RMSE) of the zonal wind speed has been computed to assess their numerical stability. Finally, six dry and six moist initial background state have been used with an unbalanced perturbation to ensure that the baroclinic life cycles that develop are physically realistic. The resulting baroclinic wave is shown to be sensitive to the jet's width. This configuration for baroclinic wave simulations will be used to create a large ensemble of baroclinic life cycles to study how extratropical cyclones may evolve in the future. [ABSTRACT FROM AUTHOR]

Background: Solitary fibrous tumors (SFT) of the central nervous system are rare and treatment options are not well established. The aim of this study was to evaluate the clinical outcomes of radiotherapy (RT) and re-radiotherapy (re-RT) for de novo intracranial SFT and recurrent intracranial SFT. Methods: This retrospective study analyzed efficacy and toxicity of different RT modalities in patients who received radiotherapy (RT) for intracranial SFT at Heidelberg University Hospital between 2000 and 2020 following initial surgery after de novo diagnosis ("primary group"). We further analyzed the patients of this cohort who suffered from tumor recurrence and received re-RT at our institution ("re-irradiation (re-RT) group"). Median follow-up period was 54.0 months (0–282) in the primary group and 20.5 months (0–72) in the re-RT group. RT modalities included 3D-conformal RT (3D-CRT), intensity-modulated RT (IMRT), stereotactic radiosurgery (SRS), proton RT, and carbon-ion RT (C12-RT). Response rates were analyzed according to RECIST 1.1 criteria. Results: While the primary group consisted of 34 patients (f: 16; m:18), the re-RT group included 12 patients (f: 9; m: 3). Overall response rate (ORR) for the primary group was 38.3% (N = 11), with 32.4% (N = 11) complete remissions (CR) and 5.9% (N = 2) partial remissions (PR). Stable disease (SD) was confirmed in 5.9% (N = 2), while 41.2% (N = 14) experienced progressive disease (PD). 14% (N = 5) were lost to follow up. The re-RT group had 25.0% CR and 17.0% PR with 58.0% PD. The 1-, 3-, and 5-year progression-free survival rates were 100%, 96%, and 86%, respectively, in the primary group, and 81%, 14%, and 14%, respectively, in the re-RT group. Particle irradiation (N = 11) was associated with a lower likelihood of developing a recurrence in the primary setting than photon therapy (N = 18) (OR = 0.038; p = 0.002), as well as doses ≥ 60.0 Gy (N = 15) versus < 60.0 Gy (N = 14) (OR = 0.145; p = 0.027). Risk for tumor recurrence was higher for women than for men (OR = 8.07; p = 0.014) with men having a median PFS of 136.3 months, compared to women with 66.2 months. Conclusion: The data suggests RT as an effective treatment option for intracranial SFT, with high LPFS and PFS rates. Radiation doses ≥ 60 Gy could be associated with lower tumor recurrence. Particle therapy may be associated with a lower risk of recurrence in the primary setting, likely due to the feasibility of higher RT-dose application. [ABSTRACT FROM AUTHOR]

The Ningdong coalfield has played a pivotal role in advancing local economic development and meeting national energy. Nevertheless, mining operations have engendered ecological challenges encompassing subterranean water depletion, land desertification, and ground subsidence, primarily stemming from the disruption of coal seam roof strata. Consequently, the local ecosystem has incurred substantial harm. Water-preserved coal mining presently constitutes the pivotal technology in mitigating this problem. The primary challenge of this technique lies in identifying critical aquifer layers and understanding the heights of water-conducting fracture zones. To obtain a precise comprehension of the seepage patterns within the upper coal seam aquifer during mining, delineate the extent of water-conducting fracture zones, non-invasive geophysical techniques such as time-lapse electrical resistivity tomography (TL-ERT), magnetic resonance sounding (MRS), and spontaneous potential (SP) have been employed to monitor alterations within the shallow coalfield's aquifer throughout the mining process in the Ningdong coalfield. By conducting meticulous examinations of fluctuations in resistivity, moisture content, and self-potential within the superjacent strata during coal seam extraction, the predominant underground water infiltration strata were ascertained, concurrently enabling the estimation of the development elevation of water-conducting fracture zones. This outcome furnishes a geophysical underpinning for endeavors concerning local water-preserved coal mining and ecological rehabilitation. [ABSTRACT FROM AUTHOR]

The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, established new approaches to both CNS tumor nomenclature and grading, emphasizing the importance of integrated diagnoses and layered reports. This edition increased the role of molecular diagnostics in CNS tumor classification while still relying on other established approaches such as histology and immunohistochemistry. Moreover, it introduced new tumor types and subtypes based on novel diagnostic technologies such as DNA methylome profiling. Over the past decade, molecular techniques identified numerous key genetic alterations in CSN tumors, with important implications regarding the understanding of pathogenesis but also for prognosis and the development and application of effective molecularly targeted therapies. This review summarizes the major changes in the 2021 fifth edition classification of pediatric CNS tumors, highlighting for each entity the molecular alterations and other information that are relevant for diagnostic, prognostic, or therapeutic purposes and that patients' and oncologists' need from a pathology report. [ABSTRACT FROM AUTHOR]

Osteofibrous dysplasia (OFD) is a rare, benign, self-limited bone disorder with a relatively low incidence, accounting for approximately 0.2% of all primary bone tumors. It was frequently found intra-cortical of the mid-shaft of the tibia. OFD can also occur in other skeletal regions, including the fibula, ulna, radius, femur, humerus, ischium, rib, tarsus, metatarsals, vertebral, and capitate. OFD can present with asymptomatic, mass, pain, swelling, deformity, and even pathological fracture. OFD might be misdiagnosed as adamantinoma (AD) and because they are three subtypes origin from the same family of bone tumors and have similar imaging features. Moreover, pathology could provide evidence for an accurate diagnosis of OFD, but misdiagnosis may occur due to small sampling materials. To date, few studies have comprehensively introduced the epidemiology, clinical manifestations, pathogenesis, radiological features, pathology, and treatment for OFD. We herein discuss clinical signs, diagnosis methods, and treatment options of OFD to improve the understanding of OFD, which is helpful for accurate diagnosis and appropriate treatment. [ABSTRACT FROM AUTHOR]

The parameters of the GR4J-CemaNeige coupling model (GR4neige) are typically treated as constants. However, the maximum capacity of the production store (parX1) exhibits time-varying characteristics due to climate variability and vegetation coverage change. This study employed differentiable parameter learning (dPL) to identify the time-varying parX1 in the GR4neige across 671 catchments within the United States. We built two types of dPL, including static and dynamic parameter networks, to assess the advantages of the time-varying parameter. In the dynamic parameter network, we evaluated the impact of potential evapotranspiration (PET), precipitation (P), temperature (T), soil moisture (SM), and normalized difference vegetation index (NDVI) datasets on the performance of dPL. We then compared dPL with the empirical functional method (fm). The results demonstrated that the dynamic parameter network outperformed the static parameter network in streamflow estimation. There were differences in streamflow estimation among the dynamic parameter network driven by various input features. In humid catchments, simultaneously incorporating all five factors, including PET, P, T, SM, and the NDVI, achieved optimal streamflow simulation accuracy. In arid catchments, it was preferable to introduce PET, T, and the NDVI separately for improved performance. dPL significantly outperformed the empirical fm in estimating streamflow and uncalibrated intermediate variables, like evapotranspiration (ET). Both the derived parX1 from dPL and the empirical fm exhibited significant spatiotemporal variation across 671 catchments. Notably, compared to parX1 obtained through the empirical fm, parX1 derived from dPL exhibited a distinct spatial clustering pattern. This study highlights the potential of dPL in enhancing model accuracy and contributes to understanding the spatiotemporal variation characteristics of parX1 under the influence of climate factors, soil conditions, and vegetation change. [ABSTRACT FROM AUTHOR]

Fiber-reinforced polymer matrix composites are increasingly considered for lightweight cryogenic pressure vessels due to their excellent combination of tailorability, specific mechanical properties, and relatively low coefficients of thermal expansion. However, significant challenges must be overcome to fully utilize PMCs for cryogenic fuel tanks in terms of transverse microcracking and subsequent permeation of cryogenic fuel. Gas permeation and microcrack densities of cryogenically cycled composites are highly influenced by their layup, ply thickness, load case, and manufacturing defects like voids and resin rich zones. There has been a significant amount of research on measuring gas permeation of composites fatigued under pure thermal or uniaxial thermo-mechanical stresses. However, results demonstrate that the gas permeability should be measured under biaxial thermo-mechanical stresses to properly gauge the leakage characteristics of damaged composites. This paper summarizes the results from over a hundred papers on the key parameters that influence the gas permeability of composites, appropriate testing methods to cycle composites for permeability measurement, methods to limit the evolution of transverse microcracks, and materials traditionally used for the fabrication of all-composite cryogenic fuel tanks. Thin plies and nanofiller-toughening of the matrix have been shown to provide significant improvements in transverse microcrack suppression within cryogenically cycled composites. [ABSTRACT FROM AUTHOR]

Introduction: Health disparities represent a crucial factor in cancer survival rates, awareness, quality of life, and mental health of people receiving a cancer diagnosis and their families. Income, education, geographic location, and ethnicity are some of the most important underlying reasons for health disparities in cancer across Europe. Costs of healthcare, access to information, psycho-oncological support options, integration of cancer research and innovative care, and multidisciplinary cancer teams are the main target areas when it comes to addressing disparities in the cancer context. As part of the Beacon Project (BEACON), we developed a protocol for a qualitative study to explore and identify any relevant reasons for cancer inequalities and disparities in Europe. Methods: Our four stakeholders namely, cancer patients, healthcare providers, researchers, and policymakers will be recruited online, facilitated by collaborative efforts with cancer organizations from various European countries, including but not limited to Italy, Croatia, Estonia, and Slovenia. Qualitative online focus group discussions for each stakeholder will be conducted and transcribed. Subsequently, thematic analysis will be used to identify reasons and aspects that may contribute to the existing disparities in cancer outcomes at various levels of engagement and from different stakeholders' perspectives. Results from focus groups will inform a subsequent Delphi study and a SWOT analysis methodology. Discussion: Although advances in medical research, cancer screening and treatment options are constantly progressing, disparities in access to and awareness of healthcare in cancer patients are even more noticeable. Thus, mapping the capacity and capability of cancer centres in the European Union, creating decision support tools that will assist the four stakeholders' information needs and improving the quality of European cancer centres will be the main objectives of the BEACON project. The current protocol will outline the methodological and practical procedures to conduct online focus group discussions with different stakeholders. [ABSTRACT FROM AUTHOR]

The study of brain connectivity has been a cornerstone in understanding the complexities of neurological and psychiatric disorders. It has provided invaluable insights into the functional architecture of the brain and how it is perturbed in disorders. However, a persistent challenge has been achieving the proper spatial resolution, and developing computational algorithms to address biological questions at the multi-cellular level, a scale often referred to as the mesoscale. Historically, neuroimaging studies of brain connectivity have predominantly focused on the macroscale, providing insights into interregional brain connections but often falling short of resolving the intricacies of neural circuitry at the cellular or mesoscale level. This limitation has hindered our ability to fully comprehend the underlying mechanisms of neurological and psychiatric disorders and to develop targeted interventions. In light of this issue, our review manuscript seeks to bridge this critical gap by delving into the domain of mesoscale neuroimaging. We aim to provide a comprehensive overview of conditions affected by aberrant neural connections, image acquisition techniques, feature extraction, and data analysis methods that are specifically tailored to the mesoscale. We further delineate the potential of brain connectivity research to elucidate complex biological questions, with a particular focus on schizophrenia and epilepsy. This review encompasses topics such as dendritic spine quantification, single neuron morphology, and brain region connectivity. We aim to showcase the applicability and significance of mesoscale neuroimaging techniques in the field of neuroscience, highlighting their potential for gaining insights into the complexities of neurological and psychiatric disorders. [ABSTRACT FROM AUTHOR]

Our knowledge regarding the role of the microbiome in fish health has been steadily increasing in the last decade, especially for species of commercial interest. Conversely, relatively few studies focus on the microbiomes of wild fish, especially apex predators like sharks, due to lower economic interest and greater difficulty in obtaining samples. Studies investigating microbiome differences between diverse anatomical locations of sharks are limited, and the majority of the available studies are focused on the microbial diversity present on shark teeth, with the aim of preventing infections due to bites of these animals or evaluating the presence of certain pathogens in healthy or diseased specimens. Here, we investigated the skin, mouth, gills, and cloaca microbiomes of five individuals of two phylogenetically distant species of sharks (Prionace glauca and Somniosus rostratus) to obtain a better understanding of the diversity regarding the microbiomes of these animals, how they change throughout different body parts, and how much they are influenced and determined by the ecology and evolutionary relationship between host and microbiome. To confirm the taxonomy of the sharks under study, we barcoded the specimens by sequencing the mtDNA COI from a biopsy of their skin. Microbial diversity based on the 16S rRNA gene reveals that partially overlapping microbiomes inhabit different body parts of each shark species, while the communities are distinct between the two species. Our results suggest that sharks' microbiome species-specific differences are controlled by the ecology of the shark species. This is the first study comparatively analyzing the microbiome diversity of different anatomical locations in two shark species of the Mediterranean Sea. [ABSTRACT FROM AUTHOR]

Hybridization between organisms from evolutionarily distinct lineages can have profound consequences on organismal ecology, with cascading effects on fitness and evolution. Most studies of hybrid organisms have focused on organismal traits, for example, various aspects of morphology and physiology. However, with the recent emergence of holobiont theory, there has been growing interest in understanding how hybridization impacts and is impacted by host‐associated microbiomes. Better understanding of the interplay between host hybridization and host‐associated microbiomes has the potential to provide insight into both the roles of host‐associated microbiomes as dictators of host performance as well as the fundamental rules governing host‐associated microbiome assembly. Unfortunately, there is a current lack of frameworks for understanding the structure of host‐associated microbiomes of hybrid organisms.In this paper, we develop four conceptual models describing possible relationships between the host‐associated microbiomes of hybrids and their progenitor or 'parent' taxa. We then integrate these models into a quantitative '4H index' and present a new R package for calculation, visualization and analysis of this index.We demonstrate how the 4H index can be used to compare hybrid microbiomes across disparate plant and animal systems. Our analyses of these data sets show variation in the 4H index across systems based on host taxonomy, host site and microbial taxonomic group.Our four conceptual models, paired with our 4H index and associated visualization tools, facilitate comparison across hybrid systems. This, in turn, allows for systematic exploration of how different aspects of host hybridization impact the host‐associated microbiomes of hybrid organisms. [ABSTRACT FROM AUTHOR]

Background/Aim: Hybrid nerve sheath tumor (HNST) is a benign peripheral nerve sheath tumor with combined features of more than one histological type, such as schwannoma, neurofibroma, and perineurioma. It remains under-recognized in routine clinical practice. Herein, we describe an unusual case of intramuscular HNST of the thigh. Case Report: The patient was a 41-year-old man with no history of trauma who presented with a 3-month history of a palpable mass in the right thigh. Physical examination revealed a 4-cm, elastic hard, mobile, nontender mass. Magnetic resonance imaging exhibited a well-circumscribed intramuscular mass with low-to-intermediate signal intensity on T1-weighted sequences and higher signal intensity peripherally and lower signal intensity centrally, representing a target sign, on T2-weighted sequences. Complete surgical excision of the tumor was carried out. Microscopically, the tumor showed dual histological components of both schwannoma and neurofibroma. Immunohistochemically, the schwannomatous component was strongly and diffusely positive for S-100 protein and negative for CD34, while the neurofibromatous component contained CD34-positive fibroblasts and S-100 protein-positive Schwann cells. Epithelial membrane antigen was negative for both components. These findings were consistent with a diagnosis of HNST (hybrid schwannoma/neurofibroma). The patient had no evidence of local recurrence and no neurological deficit at the final follow-up. Conclusion: Although extremely rare, HNST should be included in the extended differential diagnosis of a well-circumscribed, intramuscular soft-tissue mass in the extremities, particularly in young and early middle-aged adults. [ABSTRACT FROM AUTHOR]

Extreme rainfall events frequently cause hazardous floods in many parts of the world. With growing human exposure to floods, studying conditions that trigger floods is imperative. Flash floods, in particular, require well-defined models for the timely warning of the population at risk. Intensity–duration–frequency (IDF) curves are a common way to characterize rainfall and flood events. Here, the copula method is employed to model the dependence between the intensity and duration of rainfall events flexibly and separately from their respective marginal distribution. Information about the localization of 93 flash floods in Jamaica was gathered and linked to remote-sensing rainfall data, and additional data on location-specific yearly maximum rainfall events were constructed. The estimated normal copula has Weibull and generalized extreme value (GEV) marginals for duration and intensity, respectively. Due to the two samples, it is possible to pin down above which line in the intensity duration space a rainfall event likely triggers a flash flood. The parametric IDF curve with an associated return period of 216 years is determined as the optimal threshold for flash flood event classification. This methodology delivers a flexible approach to generating rainfall IDF curves that can directly be used to assess flash flood risk. [ABSTRACT FROM AUTHOR]

Background: Chondrosarcomas rank as the second most common primary bone malignancy. Characterized by the production of a cartilaginous matrix, these tumors typically exhibit resistance to both radiotherapy (RT) and chemotherapy (CT), resulting in overall poor outcomes: a high rate of mortality, especially among children and adolescents. Due to the considerable resistance to current conventional therapies such as surgery, CT, and RT, there is an urgent need to identify factors contributing to resistance and discover new strategies for optimal treatment. Over the past decade, researchers have delved into the dysregulation of genes associated with tumor development and therapy resistance to identify potential therapeutic targets for overcoming resistance. Recent studies have suggested several promising biomarkers and therapeutic targets for chondrosarcoma, including isocitrate dehydrogenase (IDH1/2) and COL2A1. Molecule-targeting agents and immunotherapies have demonstrated favorable antitumor activity in clinical studies involving patients with advanced chondrosarcomas. In this systematic review, we delineate the clinical features of chondrosarcoma and provide a summary of gene dysregulation and mutation associated with tumor development, as well as targeted therapies as a promising molecular approach. Finally, we analyze the probable role of the tumor microenvironment in chondrosarcoma drug resistance. Methods: A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 10 November 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "chondrosarcomas", "target therapies", "immunotherapies", and "outcomes". The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of target therapies for the treatment of chondrosarcoma in human subjects. Results: Of the initial 279 articles identified, 40 articles were included in the article. The exclusion of 140 articles was due to reasons such as irrelevance, non-reporting of selected results, systematic literature review or meta-analysis, and lack of details on the method/results. Three tables highlighted clinical studies, preclinical studies, and ongoing clinical trials, encompassing 13, 7, and 20 studies, respectively. For the clinical study, a range of molecular targets, such as death receptors 4/5 (DR4 and DR5) (15%), platelet-derived growth factor receptor-alpha or -beta (PDGFR-α, PDGFR-β) (31%), were investigated. Adverse events were mainly constitutional symptoms emphasizing that to improve therapy tolerance, careful observation and tailored management are essential. Preclinical studies analyzed various molecular targets such as DR4/5 (28.6%) and COX-2 (28.6%). The prevalent indicator of antitumoral activity was the apoptotic rate of both a single agent (tumor necrosis factor-related apoptosis-inducing ligand: TRAIL) and double agents (TRAIL-DOX, TRAIL-MG132). Ongoing clinical trials, the majority in Phase II (53.9%), highlighted possible therapeutic strategies such as IDH1 inhibitors and PD-1/PD-L1 inhibitors (30.8%). Conclusions: The present review offers a comprehensive analysis of targeted therapeutics for skull base chondrosarcomas, highlighting a complex landscape characterized by a range of treatment approaches and new opportunities for tailored interventions. The combination of results from molecular research and clinical trials emphasizes the necessity for specialized treatment strategies and the complexity of chondrosarcoma biology. [ABSTRACT FROM AUTHOR]

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is commonly used in clinical practice to detect tumor blood supply, and it has recently been applied to assess skeletal vasculature. In this study, we retrospectively analyzed DCE-MRI data from 37 patients with osteonecrosis of the femoral head to evaluate alterations in microvascular circulation of the femoral head. Time-intensity curves (TICs) in the region of interest were classified into different lesion stages. In the greater trochanter area, extracellular space volume per unit volume of tissue was significantly higher in Association Research Circulation Osseous (ARCO) stage III than in ARCO stage II (P<.05 and power ≥ 0.8), while other parameters showed no statistical difference (P>.05 and/or power < 0.8). In the necrotic area, contrast enhancement ratio and maximum slope of increase were significantly lower in ARCO stage III than in ARCO stage II (P<.05 and power ≥ 0.8), while other parameters showed no statistical difference (P>.05 and/or power < 0.8). In the repair reaction area, all parameters were significantly higher in ARCO stage III than in ARCO stage II (P<.05 and power ≥ 0.8). TIC classification showed that the greater trochanter area mainly exhibited type C (plateau type), the necrotic area mainly exhibited type B (out-flow type), and the repair reaction area mainly exhibited type A (inflow type). We believe that the exchange capacity of the vessels has a much greater impact on femoral head necrosis than the number of vessels, while the generation of the repair area greatly affects the prognosis of femoral head necrosis. These findings suggest that DCE-MRI can provide a good assessment of osteonecrosis of the femoral head perfusion and can serve as a new reference for clinical treatment decisions. [Orthopedics. 2024;47(2):e73–e78.] [ABSTRACT FROM AUTHOR]

The objective of this study is to examine the rainfall-runoff relationship in the Wadi Mekerra watershed located in northwest Algeria, in order to propose effective solutions for flood protection. The methodology is based on the processing of meteorological and physical data in the geographical environment and on the extraction of data using remote sensing techniques (Landsat satellite imagery) and GIS. Using this database, we were able to develop a hydrological flood model for Mekerra watershed using the hydrological modeling software HEC-HMS. In this study the frequency storm was used for the meteorological model, the SCS curve numbers was used to determine the hydrological losses of the study area and the SCS unit hydrograph method have been applied to simulate the runoff rate. After calibration and validation, the simulated peak discharges were very close with observed values. The Nash-Sutcliffe efficiency coefficient was 0.869, indicates that the hydrological modeling results are satisfactory and accepted for simulation of rainfall-runoff. [ABSTRACT FROM AUTHOR]

This document provides a comprehensive analysis of subterranean biodiversity, specifically focusing on caves and other subterranean habitats. The authors identify and document 28 subterranean biodiversity hotspots worldwide, with a concentration in Europe and North America. The document discusses different approaches to identifying and categorizing subterranean species, as well as challenges in defining them. It also explores the distribution and richness of species in different hotspots and highlights the need for further research. The document also discusses the vulnerabilities of subterranean fauna and various protection strategies. Additionally, the document includes tables that provide information on cave systems, troglobionts, and the distribution of arachnids and beetles in hotspot caves. [Extracted from the article]

Statement of the Problem: Fibro-osseous lesions (FLs), may rarely exhibit malignant features likewise undergo malignant transformation. Awareness of these features can assist in screening for potentially malignant cases and identifying low-grade central osteogenic sarcoma (LGCOS) that may mimic FLs. Purpose: The objective of this study was to determine the usability of an index in predicting malignant changes in jaw FLs. Materials and Method: This was a retrospective study where hematoxylin and eosin (H&E) slides and archival records of fibrous dysplasia (FD) and ossifying fibroma (OF) cases were reviewed. The sections were assessed for permeation of marrow spaces, stromal growth pattern, cytologic atypia, mitotic activity, and pattern of bone growth, which are parameters for diagnosing LGCOS. The predictive histologic index of malignancy (PHIM) was determined by a sum of the scores and graded as 0=nil, 1=low, 2 & 3=moderate, and 4 & 5=high. Data were presented using descriptive analysis. Results: Ninety-three cases of FLs met the inclusion criteria, consisting of 40(43%) cases of FD and 53(57%) cases of OF. The peak age of presentation for FD and OF was 2nd and 3rd decade. There was a female preponderance of 1:1.6. The maxilla was the most common site affected by FD, while the mandible was most commonly affected by OF. For FD cases, the PHIM was moderate in 10(25%) cases and low in 21(52.5%) cases. Similarly, for OF cases, 30(56.6%) cases had low grade PHIM while 10(17%) cases had moderate grade PHIM. Conclusion: The PHIM depicted low to moderate malignancy grade in some of the cases studied. Follow up studies would be necessary to assess the PHIM. [ABSTRACT FROM AUTHOR]

Non-conventional processes are considerably important for the machining of hard-to-cut alloys in various demanding applications. Given that the surface quality and integrity, dimensional accuracy, and productivity are important considerations in industrial practice, the prediction of the outcome of the material removal process should be able to be conducted with sufficient accuracy, taking into consideration the computational cost and difficulty of implementation of the relevant models. In the case of AWJ, various types of approaches have been already proposed, both relying on analytical or empirical models and developed by solving partial differential equations. As the creation of a model for AWJ pocket milling is rather demanding, given the number of parameters involved, in the present work, it is intended to compare the use of three different types of efficient modeling approaches for the prediction of the dimensions of pockets milled by AWJ technology. The models are developed and evaluated based on experimental results of AWJ pocket milling of a titanium workpiece by an eco-friendly walnut shell abrasive. The results indicate that a semi-empirical approach performs better than a two-step hybrid analytical/semi-empirical method regarding the selected cases, but both methods show promising results regarding the realistic representation of the pocket shape, which can be further improved by a probabilistic approach. [ABSTRACT FROM AUTHOR]

Fishes are hosts for many microorganisms that provide them with beneficial effects on growth, immune system development, nutrition and protection against pathogens. In order to avoid spreading of infectious diseases in aquaculture, prevention includes vaccinations and routine disinfection of eggs and equipment, while curative treatments consist in the administration of antibiotics. Vaccination processes can stress the fish and require substantial farmer's investment. Additionally, disinfection and antibiotics are not specific, and while they may be effective in the short term, they have major drawbacks in the long term. Indeed, they eliminate beneficial bacteria which are useful for the host and promote the raising of antibiotic resistance in beneficial, commensal but also in pathogenic bacterial strains. Numerous publications highlight the importance that plays the diversified microbial community colonizing fish (i.e., microbiota) in the development, health and ultimately survival of their host. This review targets the current knowledge on the bidirectional communication between the microbiota and the fish immune system during fish development. It explores the extent of this mutualistic relationship: on one hand, the effect that microbes exert on the immune system ontogeny of fishes, and on the other hand, the impact of critical steps in immune system development on the microbial recruitment and succession throughout their life. We will first describe the immune system and its ontogeny and gene expression steps in the immune system development of fishes. Secondly, the plurality of the microbiotas (depending on host organism, organ, and development stage) will be reviewed. Then, a description of the constant interactions between microbiota and immune system throughout the fish's life stages will be discussed. Healthy microbiotas allow immune system maturation and modulation of inflammation, both of which contribute to immune homeostasis. Thus, immune equilibrium is closely linked to microbiota stability and to the stages of microbial community succession during the host development. We will provide examples from several fish species and describe more extensively the mechanisms occurring in zebrafish model because immune system ontogeny is much more finely described for this species, thanks to the many existing zebrafish mutants which allow more precise investigations. We will conclude on how the conceptual framework associated to the research on the immune system will benefit from considering the relations between microbiota and immune system maturation. More precisely, the development of active tolerance of the microbiota from the earliest stages of life enables the sustainable establishment of a complex healthy microbial community in the adult host. Establishing a balanced host-microbiota interaction avoids triggering deleterious inflammation, and maintains immunological and microbiological homeostasis. [ABSTRACT FROM AUTHOR]

Introduction: The goal of this study is to compare the prognostic performance of NETPET scores, based on gallium-68 DOTANOC (68Ga-DOTANOC) and fluorine-18 fluorodeoxyglucose (18F-FDG) Positron Emission Tomography-Computed Tomography (PET-CT), and PET-CT metabolic parameters in metastatic gastrointestinal neuroendocrine tumors (GI-NET), while constructing and validating a nomogram derived from dual-scan PET-CT. Methods: In this retrospective study, G1–G3 GI-NET patients who underwent 68Ga-DOTANOC and 18F-FDG PET scans were enrolled and divided into training and internal validation cohorts. Three grading systems were constructed based on NETPET scores and standardized uptake value maximum (SUVmax). LASSO regression selected variables for a multivariable Cox model, and nomograms predicting progression-free survival (PFS) and overall survival (OS) were created. The prognostic performance of these systems was assessed using time-dependent receiver-operating characteristic (ROC) curves, concordance index (C-index), and other methods. Nomogram evaluation involved calibration curves, decision curve analysis (DCA), and the aforementioned methods in both cohorts. Results: In this study, 223 patients (130 males; mean age ±  SD: 52.6 ± 12 years) were divided into training (148) and internal validation (75) cohorts. Dual scans were classified based on NETPET scores (D1–D3). Single 68Ga-DOTANOC and 18F-FDG PET-CT scans were stratified into S1-S3 and F1-F3 based on SUVmax. The NETPET score-based grading system demonstrated the best OS and PFS prediction (C-index, 0.763 vs. 0.727 vs. 0.566). Nomograms for OS and PFS exhibited superior prognostic performance in both cohorts (all AUCs > 0.8). Conclusions: New classification based on NETPET score predicts patient OS/PFS best. PET-CT-based nomograms show accurate OS/PFS forecasts. [ABSTRACT FROM AUTHOR]

Background: Curcumin is a plant polyphenol with antitumor properties and inhibits the development of colorectal cancer (CRC). However, as the molecular mechanism associated is still unclear, our study aimed to explore the underlying molecular mechanisms by which curcumin inhibits CRC. Methods: HT29 and SW480 cells were treated with curcumin or/and Doxycycline (DOX), and cell viability, colony forming ability, migration and invasion were confirmed by cell counting kit-8 (CCK-8), colony forming, Transwell assays. And Yes-associated protein 1 (YAP) and PDZ-binding motif (TAZ) signaling-related genes or proteins were analyzed using reverse transcription quantitative real-time PCR (RT-qPCR), western blot, and immunofluorescence assays. Then nude mice xenograft tumor model was constructed, YAP and Ki67 expressions were tested by immunohistochemistry (IHC) staining. Results: In our study, we proved that curcumin significantly inhibited the CRC cell viability, cell migration, and cell invasion abilities. In addition, curcumin inhibited YAP and Transcriptional coactivator with TAZ or the YAP/TAZ signaling axis in CRC cells. Further, in the nude mice model, curcumin treatment significantly decreased the size and weight of xenotransplant tumors. Conclusion: Therefore, curcumin significantly inhibited CRC development and invasion by regulating the YAP/TAZ signaling axis. [ABSTRACT FROM AUTHOR]

This study aims to investigate the impact of spatial rainfall distribution scenarios from ground observation stations on runoff simulation using hydrological modeling specific to the Rainfall-Runoff-Inundation (RRI) model. The RRI model was applied with six different spatial distribution scenarios of input rainfall, including Inverse Distance Weight (IDW), Thiessen polygon (TSP), Surface Polynomial (SPL), Simple kriging (SKG), and Ordinary kriging (OKG), to simulate the runoff of a 13,000 km2 watershed, namely the Nan River Basin in Thailand. This study utilized data from the 2014 storm event, incorporating temporal information from 28 rainfall stations to estimate rainfall in the spatial distribution scenarios. The six statistics, Volume Bias, Peak Bias, Root Mean Square Error, Correlation, and Mean Bias, were used to determine the accuracy of the estimated rainfall and runoff. Overall, the Simple kriging (SKG) method outperformed the other scenarios based on the statistical values to validate with measured rainfall data. Similarly, SKG demonstrated the closest match between simulated and observed runoff, achieving the highest correlation (0.803), the lowest Root Mean Square Error (164.48 cms), and high Nash-Sutcliffe Efficiency coefficient (0.499) values. This research underscores the practical significance of spatial interpolation methods, such as SKG, in combination with digital elevation models (DEMs) and landuse/soil type datasets, in delivering reliable runoff simulations considering the RRI model on the river basin scale. [ABSTRACT FROM AUTHOR]

Health service referrals are a form of health service that regulates the delegation of duties and responsibilities for health services with the aim of healing and restoring the patient's health status. One important aspect in human life is health referrals which require fast, practical, efficient and accurate and reliable information. The purpose of this study was to determine to what extent the implementation of the web-based community health center patient referral application (SISRUTE) in Pamekasan can overcome obstacles in medical referrals, making it easier for health workers to optimize health services. The method used in this research is a qualitative approach which is defined as a research procedure that produces descriptive data which aims to reveal the in-depth meaning behind a phenomenon. Data were collected using Purposive Sampling with in-depth interview techniques by asking 13 questions consisting of 8 nurses and 5 midwife accompanied by 1 Triangulator, head of the Pamekasan district referral department. Data collection techniques use observation, interviews, documentation and case studies. From the results of this research it is known that the implementation of the use of the integrated referral system application (SISRUTE) in Pamekasan district for individual health service referrals can improve the quality, coverage, effectiveness and efficiency of integrated health services with the help of supporting facilities and infrastructure as well as the ability of human resources to operate, and with the web referral application, health workers feel that it is very helpful in speeding up patient referrals to the next level of health facilities. [ABSTRACT FROM AUTHOR]