Siderophores are a class of small molecules renowned for their high iron binding capacity, essential for all life forms requiring iron. This article provides a detailed review of the diverse classifications, and biosynthetic pathways of siderophores, with a particular emphasis on siderophores synthesized via nonribosomal peptide synthetase (NRPS) and non-NRPS pathways. We further explore the secretion mechanisms of siderophores in microbes and plants, and their role in regulating bioavailable iron levels. Beyond biological functions, the applications of siderophores in medicine, agriculture, and environmental sciences are extensively discussed. These applications include biological pest control, disease treatment, ecological pollution remediation, and heavy metal ion removal. Through a comprehensive analysis of the chemical properties and biological activities of siderophores, this paper demonstrates their wide prospects in scientific research and practical applications, while also highlighting current research gaps and potential future directions. Full article

Background: A negative lifestyle is reported to be related to cognitive problems. However, there is little information about this in relation to university students. The objective of the present study was to investigate the association between executive functions (EFs) and lifestyle parameters (i.e., physical activity (PA), sleep duration, screen time (ST), and food habits) among Chilean university students. Methods: This cross-sectional study included a total of 150 university students (94 females and 56 males, aged 21.28 ± 3.15 and 22.18 ± 2.90 years, respectively). Cognitive outcomes were measured using the CogniFit assessment battery. Lifestyle was measured through validated questionnaires. Results: Across the total sample, attention exhibited a positive association with PA h/week (β: 24.34 95% CI: 12.46 to 36.22, p = 0.001). Additionally, coordination was positively associated with PA h/week (β: 15.06 95% CI: 0.62 to 29.50, p < 0.041). PA h/week was positively linked with reasoning (β: 20.34 95% CI: 4.52 to 36.17, p = 0.012) and perception (β: 13.81 95% CI: 4.14 to 23.49, p = 0.005). Moreover, PA h/week was significantly linked to memory (β: 23.01 95% CI: 7.62 to 38.40, p = 0.004). In terms of the EFs, PA h/week showed a positive association with cognitive flexibility (β: 45.60 95% CI: 23.22 to 67.69, p = 0.001). Conclusions: In conclusion, lifestyle (PA h/week) was positively associated with EFs. Therefore, an increase in PA levels among these students should be a target for community- and university-based interventions in order to promote cognitive development such as attention, coordination, reasoning, perception, memory, and cognitive flexibility. Full article

The emergence of combination antiretroviral therapy (cART) has greatly transformed the life expectancy of people living with HIV (PWH). Today, over 76% of the individuals with HIV have access to this life-saving therapy. However, this progress has come with a new challenge: an increase in age-related non-AIDS conditions among patients with HIV. These conditions manifest earlier in PWH than in uninfected individuals, accelerating the aging process. Like PWH, the uninfected aging population experiences immunosenescence marked by an increased proinflammatory environment. This phenomenon is linked to chronic inflammation, driven in part by cellular structures called inflammasomes. Inflammatory signaling pathways activated by HIV-1 infection play a key role in inflammasome formation, suggesting a crucial link between HIV and a chronic inflammatory state. This review outlines the inflammatory processes triggered by HIV-1 infection and aging, with a focus on the inflammasomes. This review also explores current research regarding inflammasomes and potential strategies for targeting inflammasomes to mitigate inflammation. Further research on inflammasome signaling presents a unique opportunity to develop targeted interventions and innovative therapeutic modalities for combating HIV and aging-associated inflammatory processes. Full article

The Jerusalem artichoke (Helianthus tuberosus) is a high-yield crop, and a great source of fermentable sugars, which gives the plant the potential to be used as raw material for economical fuel alcohol production. In this article, the authors focus on the technological aspect of the biofuel manufacturing process and its properties. First, the fuel alcohol manufacturing process is described, afterwards assessing its characteristics such as kinematic viscosity, density and octane number. The amount of fuel alcohol obtained from 10 kg of biomass equals to 0.85 L. Afterwards, the mixtures of gasoline and obtained fuel alcohol are prepared and studied. Optimal alcohol and gasoline mixtures are determined to obtain biofuels with octane ratings of 92, 95 and 98. The kinematic viscosity of obtained mixtures does not differ significantly from its values for pure gasoline. The obtained biofuel mixture with 25% alcohol content yielded a decrease of sulfur content by 38%, an increase of vaporized fuel amount by 17.5% at 70 °C and by 10.5% at a temperature of 100 °C, which improves engine startup time and ensures its stable operation in comparison to pure gasoline. The alcohol obtained can be successfully used as a high-octane additive for gasolines. Full article

Multiple research directions have been proposed to study the information structure of Reddit. One of them is to model inter-subreddit relations but modeling user interactions in the form of a graph. Building upon prior work centered on political subreddits using pre-2020 data, we expand this investigation to include a more extensive dataset spanning 2022 and encompassing diverse topic areas. Employing NLP techniques such as text embeddings, we model subreddit content directly and construct a subreddit graph network based on cosine similarity. Community detection using the Louvain method reveals distinct subreddits and allows the analysis of inter-community connections via previous works’ concepts of “bridges” and “gateways”. Surprisingly, our findings indicate redundancy between bridges and gateways in the utilized dataset. Therefore, we introduce a new concept, “highways”. Highways, representing the most traversed paths between subreddits, unveil insights not captured by previous analyses, underscoring the significance of novel conceptual frameworks in uncovering latent knowledge within Reddit’s online community structures. Full article

This study aimed to compare the impact of CAD/CAM closed systems and open systems on the marginal gap of monolithic zirconia-reinforced lithium silicate (ZLS) ceramic crowns, as both systems are used in everyday dentistry, both chair-side and laboratory. For the closed system, 20 plastic teeth were scanned by a Primescan intra-oral scanner (IOS), and for the open system, the same number of plastic teeth were scanned by Trios 4 IOS. For the closed system, CEREC software was used, and for the open system, EXOCAD software was used. All 40 ZLS crowns were grinded by the same four-axis machine and cemented with Temp-bond, followed by self-adhesive resin cement. For each type of cement, an evaluation of the marginal gap was conducted by scanning electron microscopy (SEM). Before comparisons between the groups, a Kolmogorov–Smirnov test was performed on the study variables showing a normal distribution (p > 0.05). Independent T tests (α = 0.05) and paired-sample T tests (α = 0.05) were used. The independent T test found no significant mean marginal gap differences in the zirconia-reinforced lithium silicate crowns bonded with Temp-bond and scanned by Primescan (28.09 μm ± 3.06) compared to Trios 4 (28.94 μm ± 3.30) (p = 0.401), and there was no significant mean marginal gap differences in zirconia-reinforced lithium silicate crowns bonded with self-adhesive resin cement (Gcem ONE) and scanned by Primescan (46.70 μm ± 3.80) compared to Trios 4 (47.79 μm ± 2.59) (p = 0.295). Paired-sample T tests showed significantly higher mean marginal gaps with Gcem ONE compared to Temp-bond for the total mean marginal gap when scanning with Primescan (p = 0.0005) or Trios 4 (p = 0.0005). In everyday dentistry, both closed systems (Primescan with Cerec) and open systems (Trios 4 with Exocad) can be used to achieve an acceptable (<120 µm) marginal gap for ZLS CELTRA^® DUO single crowns. There is a significant difference between cementation with Temp-bond and Gcem ONE self-adhesive resin cement (p < 0.05). Full article

Amino acids are organic compounds that enter the protein structure, being involved in the proper functioning of the body. The role of amino acids in the onset of autism spectrum disorder (ASD) is yet to be established. Our aim was to identify correlations between urine amino acids and their derivatives and ASD. Methods: We designed a case–control study that consisted of 75 boys and girls, aged between 2 and 12 years. For amino acid profile, we used urine samples that were analyzed using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Results: Descriptive analysis showed higher values for glutamine, hydroxyproline, tyrosine, aspartic acid, and tryptophan and lower values for serine in the autism group than in the control group. Also, we found that boys with autism had higher values than the boys in the control group for serine, threonine, and aspartic acid. For girls from both groups, we did not find statistically significant values. In terms of age groups, we found significantly higher values for histidine, threonine, valine, methionine, aspartic acid, glutamic acid, alpha amino-adipic acid, sarcosine, alanine, and beta-alanine and significantly lower values for proline for both the autism and control groups under 5 years. Conclusions: The findings of this study support the assumption that amino acids may have a role in the expression of ASD. Full article

The sustainability of the food production achieved with the help of irrigation systems and the sustainability of their energy consumption are major challenges of the current century. Pumping systems currently account for approximately 30% of global electrical energy consumption. As electricity prices rise, there is a growing need for technological advancements to enhance energy efficiency and reduce consumption costs effectively. This study focuses on operating centrifugal pumps at variable frequency as an effective means of achieving this goal. Most centrifugal pump manufacturers/providers traditionally assume that pump efficiency remains constant across various operating frequencies, often equating the efficiency at various frequencies to that at the standard frequency (50/60 Hz). In contrast, this paper introduces a new formula for estimating pump efficiency, crucial to precise power consumption determination, particularly in variable-frequency scenarios. The formula parameters are identified by using experimental data acquired from an existing pumping system. The tests and results presented in this paper demonstrate that the proposed formula outperforms the formulas of the current industry standards in accuracy. Practically, the new relation assures enhanced accuracy in estimating pump efficiency and absorbed power, allowing for the design of a more precise model used for control systems synthesis required for operating centrifugal pumps at variable frequency. This research offers a new way of calculating pump efficiency, which could be very useful for industry practitioners seeking to optimize energy consumption in pumping systems. Full article

Crosstalk regulation is widespread in Streptomyces species. Elucidating the influence of a specific regulator on target biosynthetic gene clusters (BGCs) and cell metabolism is crucial for strain improvement through regulatory protein engineering. PteF and PteR are two regulators that control the biosynthesis of filipin, which competes for building blocks with avermectins in Streptomyces avermitilis. However, little is known about the effects of PteF and PteR on avermectin biosynthesis. In this study, we investigated their impact on avermectin biosynthesis and global cell metabolism. The deletion of pteF resulted in a 55.49% avermectin titer improvement, which was 23.08% higher than that observed from pteR deletion, suggesting that PteF plays a more significant role in regulating avermectin biosynthesis, while PteF hardly influences the transcription level of genes in avermectin and other polyketide BGCs. Transcriptome data revealed that PteF exhibited a global regulatory effect. Avermectin production enhancement could be attributed to the repression of the tricarboxylic acid cycle and fatty acid biosynthetic pathway, as well as the enhancement of pathways supplying acyl-CoA precursors. These findings provide new insights into the role of PteF on avermectin biosynthesis and cell metabolism, offering important clues for designing and building efficient metabolic pathways to develop high-yield avermectin-producing strains. Full article

The use of autonomous and unmanned systems continues to increase, with uses spanning from package delivery to simple automation of tasks and from factory usage to defense industries and agricultural applications. With the proliferation of unmanned systems comes the question of how to secure the command-and-control communication links among such devices and their operators. In this work, we look at the use of the Messaging Layer Security (MLS) protocol, designed to support long-lived continuous sessions and group communication with a high degree of security. We build out MAUI—an MLS API for UxS Integration that provides an interface for the secure exchange of data between a ScanEagle unmanned aerial vehicle (UAV) and an unmanned surface vehicle (USV) in a multi-domain ad-hoc network configuration, and experiment on system limits such as the ciphersuite set-up time and message handling rates. The experiments in this work were conducted in virtual and physical environments between the UAV, USV, and a controller device (all of different platforms). Our results demonstrate the viability of capitalizing on MLS’s capabilities to securely and efficiently transmit data for distributed communication among various unmanned system platforms. Full article

Healthcare human resource planning is one of the biggest challenges facing the healthcare systems in many countries. Inadequate decisions in human resource planning can lead to an insufficient number of healthcare professionals then healthcare inequalities. One of the components of resource planning in the healthcare system is long-term data monitoring and the identification of potential trends. Since 1990, the number of physicians in Lithuania has decreased by 15.3% (−2266), but the decrease in the population has led to a 13.61% increase in the number of physicians per 10,000 inhabitants (5.32). During the analyzed period, the largest decrease in the number of physicians workforce by specialty was the number of medical physicians (−73.08%), epidemiology and hygiene (−69.30%), children’s diseases (−49.08%), the most increased number was of family/general practitioners (GPs), geneticists, physical medicine, and rehabilitation specialists. Since 1992, the number of visits to physicians in Lithuania, which has been decreasing for a long time, began increasing, and in 2022 (9.3 visits) it has almost reached the number of visits (9.5) per capita as in 1991. The aim of this research was to collect long-term data from various databases, summarize them, and identify possible trends and the reasons for data changes. The study analyzed data from the Lithuanian healthcare system from the Declaration of Independence of Lithuania to the last 30 years. The data includes or affects the indicators of the healthcare system, changes in population and doctors, the number of visits to doctors, the number of medical students and residents, and data determining inequalities in the healthcare system. Long-term data analysis is useful for developing a model of healthcare human resource planning and for planning healthcare resources. Full article

The gasification of residues into syngas offers a versatile gaseous fuel that can be used to produce heat and power in various applications. However, the application of syngas in engines presents several challenges due to the changes in its composition. Such variations can significantly alter the optimal operational conditions of the engines that are fueled with syngas, resulting in combustion instability, high engine variability, and misfires. In this context, this work presents an experimental investigation conducted on a port-fuel injection spark-ignition optical research engine using three different syngas mixtures, with a particular focus on the effects of CO/H₂ and diluent ratios. A comparative analysis is made against methane, considered as the baseline fuel. The in-cylinder pressure and related parameters are examined as indicators of combustion behavior. Additionally, 2D cycle-resolved digital visualization is employed to trace flame front propagation. Custom image processing techniques are applied to estimate flame speed, displacement, and morphological parameters. The engine runs at a constant speed (900 rpm) and with full throttle like stationary engine applications. The excess air–fuel ratios vary from 1.0 to 1.4 by adjusting the injection time and the spark timing according to the maximum brake torque of the baseline fuel. A thermodynamic analysis revealed notable trends in in-cylinder pressure traces, indicative of differences in combustion evolution and peak pressures among the syngas mixtures and methane. Moreover, the study quantified parameters such as the mass fraction burned, combustion stability (COVIMEP), and fuel conversion efficiency. The analysis provided insights into flame morphology, propagation speed, and distortion under varying conditions, shedding light on the influence of fuel composition and air dilution. Overall, the results contribute to advancing the understanding of syngas combustion behavior in SI engines and hold implications for optimizing engine performance and developing numerical models. Full article

Vitamin D₃ is a steroid hormone that confers anti-tumorigenic properties in prostate cells. Serum vitamin D₃ deficiency has been associated with advanced prostate cancer (PCa), particularly affecting African American (AA) men. Therefore, elucidating the pleiotropic effects of vitamin D on signaling pathways, essential to maintaining non-malignancy, may provide additional drug targets to mitigate disparate outcomes for men with PCa, especially AA men. We conducted RNA sequencing on an AA non-malignant prostate cell line, RC-77N/E, comparing untreated cells to those treated with 10 nM of vitamin D₃ metabolite, 1α,25(OH)₂D₃, at 24 h. Differential gene expression analysis revealed 1601 significant genes affected by 1α,25(OH)₂D₃ treatment. Pathway enrichment analysis predicted 1α,25(OH)₂D_3- mediated repression of prostate cancer, cell proliferation, actin cytoskeletal, and actin-related signaling pathways (p < 0.05). Prioritizing genes with vitamin D response elements and associating expression levels with overall survival (OS) in The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA PRAD) cohort, we identified ANLN (Anillin) and ECT2 (Epithelial Cell Transforming 2) as potential prognostic PCa biomarkers. Both genes were strongly correlated and significantly downregulated by 1α,25(OH)₂D₃ treatment, where low expression was statistically associated with better overall survival outcomes in the TCGA PRAD public cohort. Increased ANLN and ECT2 mRNA gene expression was significantly associated with PCa, and Gleason scores using both the TCGA cohort (p < 0.05) and an AA non-malignant/tumor-matched cohort. Our findings suggest 1α,25(OH)₂D₃ regulation of these biomarkers may be significant for PCa prevention. In addition, 1α,25(OH)₂D₃ could be used as an adjuvant treatment targeting actin cytoskeleton signaling and actin cytoskeleton-related signaling pathways, particularly among AA men. Full article

The generation of high-quality wideband frequency sweeps presents a significant challenge, particularly in modern telecommunication, radar, and measurement systems where miniaturization is paramount. While phase-locked loops (PLLs) have become the dominant technique for signal generation, their application in broadband sweeps necessitates fractional-N operation. This, in turn, degrades phase noise and introduces unwanted spurs. This paper proposes a novel approach for broadband signal generation. By cascading two PLLs and utilizing a coaxial resonator, we achieve a high-performance oscillator that operates without the excessive fractional spurs, maintaining their level below −80 dBc across the entire frequency band. The prototype demonstrates non-degraded phase noise performance, reaching −102 dBc/Hz at 100 kHz offset and −121 dBc/Hz at 1 MHz offset for signals at 10 GHz. Despite significant frequency jumps, our design achieves lock times below 41 µs. These results, supported by theoretical analysis, validate the proposed method’s effectiveness in generating low-noise broadband frequency sweeps, ideal for local oscillator applications. Full article

Breast cancer represents a significant health concern, particularly in Saudi Arabia, where it ranks as the most prevalent cancer type among women. This study focuses on leveraging eXplainable Artificial Intelligence (XAI) techniques to predict benign and malignant breast cancer cases using various clinical and pathological features specific to Saudi Arabian patients. Six distinct models were trained and evaluated based on common performance metrics such as accuracy, precision, recall, F1 score, and AUC-ROC score. To enhance interpretability, Local Interpretable Model-Agnostic Explanations (LIME) and SHapley Additive exPlanations (SHAP) were applied. The analysis identified the Random Forest model as the top performer, achieving an accuracy of 0.72, along with robust precision, recall, F1 score, and AUC-ROC score values. Conversely, the Support Vector Machine model exhibited the poorest performance metrics, indicating its limited predictive capability. Notably, the XAI approaches unveiled variations in the feature importance rankings across models, underscoring the need for further investigation. These findings offer valuable insights into breast cancer diagnosis and machine learning interpretation, aiding healthcare providers in understanding and potentially integrating such technologies into clinical practices. Full article

In the manufacturing sector, tool wear substantially affects product quality and production efficiency. While traditional sequential deep learning models can handle time-series tasks, their neglect of complex temporal relationships in time-series data often leads to errors accumulating in continuous predictions, which reduces their forecasting accuracy for tool wear. For addressing these limitations, the parallel convolutional and recurrent neural networks with attention-modulated residual learning (ParaCRN-AMResNet) model is introduced. Compared with conventional deep learning models, ParaCRN-AMResNet markedly enhances the efficiency and precision of feature extraction from time-series data through its innovative parallel architecture. The model adeptly combines dilated convolution neural network and bidirectional gated recurrent units, effectively addressing distance dependencies and enriching the quantity and dimensions of extracted features. The strength of ParaCRN-AMResNet lies in its refined ability to capture the complex dynamics of time-series data, significantly boosting the model’s accuracy and generalization capability. The model’s efficacy was validated through comprehensive milling experiments and vibration signal analyses, showcasing ParaCRN-AMResNet’s superior performance. In evaluation metrics, the model achieved a MAE of 2.6015, MSE of 15.1921, R² of 0.9897, and MAPE of 2.7997%, conclusively proving its efficiency and accuracy in the precise prediction of tool wear. Full article

Cover crops in no-tillage systems may alter soil mineral N and influence the N fertilizer use efficiency (NFUE) of subsequent maize. The hypothesis of this work is that no-tillage systems with cover crops affect nitrate, ammonium and maize NFUE availability in the Brazilian Cerrado. The objective was to evaluate the cover crop mineralization effect on soil N mineral and maize NFUE in a no-tillage system, with and without N topdressing. The experiment was arranged in a randomized block split-plot design. The plots were represented by cover crops (Cajanus cajan, Crotalaria juncea, Raphanus sativus and Mucuna aterrima). The subplots consisted of the application (WN) or non-application (NN) of N topdressing to maize. The soil was sampled in six layers (up to 60 cm) at the end (April) and at the beginning of the rainy season (November). NH₄⁺ was lower for all cover crops and WN and NN management in April. NO₃⁻ differed between seasons and cover crops in WN and NN. The lignin concentration and N uptake of M. aterrima were the highest compared to other species. The highest NFUE was on R. sativus, showing higher fertilizer dependency. In a no-tillage system with cover crops, the N topdressing fertilization needs to be improved, considering mineralization. Full article

The emergence of CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment paradigm for R/R B-cell NHLs. However, challenges persist in accurately evaluating treatment response and detecting early relapse, necessitating the exploration of novel biomarkers. Circulating tumor DNA (ctDNA) via liquid biopsy is a non-invasive tool for monitoring therapy efficacy and predicting treatment outcomes in B-NHL following CAR-T therapy. By overcoming the limitations of conventional imaging modalities, ctDNA assessments offer valuable insights into response dynamics, molecular mechanisms of resistance, and early detection of molecular relapse. Integration of ctDNA monitoring into clinical practice holds promise for personalized therapeutic strategies, guiding the development of novel targeted therapies, and enhancing patient outcomes. However, standardization of assay methodologies and consensus on clinical response metrics are imperative to unlock the full potential of ctDNA in the management of B-NHL. Prospective validation of ctDNA in clinical trials is necessary to establish its role as a complementary decision aid. Full article

Emotional labor is a crucial yet often overlooked aspect of effective leadership. To address this, the current study adopts the Emotion as Social Information (EASI) model as a theoretical framework to investigate the influence of leaders’ emotional labor and perceived appropriateness on employees’ emotional labor. A two (leaders’ emotional labor strategies: surface acting vs. deep acting) by two (perceived appropriateness: appropriate vs. inappropriate) between-subjects experiment was designed with a sample of 120 front-line service employees from hotels in Shanghai. The results showed that regardless of whether the perception of a leader’s surface acting was deemed appropriate or not, employees tended to perform surface acting, while the impact of the perceived appropriateness regarding the leader’s deep acting was different, wherein an appropriate display of deep acting by the leader significantly influenced employees to engage in deep acting themselves. The managerial implications and limitations of the findings are also discussed. Full article

Probiotic microorganisms are used in a variety of food supplements and medical formulations to promote human health. In periodontal therapy, probiotics are mainly used in the form of gels, tablets or rinses that often tend to leak from the periodontal pocket, resulting in a strongly reduced therapeutic effect. In this pilot in vitro study, we present biodegradable alginate-based particles as an alternative, highly efficient system for a periodontal delivery of probiotic bacteria to the inflammation site. For this purpose, Lactococcus (L.) lactis was encapsulated using a standardized pump-controlled extrusion-dripping method. Time-dependent bacterial release in artificial saliva was investigated over 9 days. The effect of freeze drying was explored to ensure long-term storage of L. lactis-loaded particles. Additionally, the particles were bound to dentin surface using approved bioadhesives and subjected to shear stress in a hydrodynamic flow chamber that mimics the oral cavity in vitro. Thus, round particles within the range of 0.80–1.75 mm in radius could be produced, whereby the diameter of the dripping tip had the most significant impact on the size. Although both small and large particles demonstrated a similar release trend of L. lactis, the release rate was significantly higher in the former. Following lyophilization, particles could restore their original shape within 4 h in artificial saliva; thereby, the bacterial viability was not affected. The attachment strength to dentin intensified by an adhesive could resist forces between 10 and 25 N/m². Full degradation of the particles was observed after 20 days in artificial saliva. Therefore, alginate particles display a valuable probiotic carrier for periodontal applications that have several crucial advantages over existing preparations: a highly stable form, prolonged continuous release of therapeutic bacteria, precise manufacturing according to required dimensions at the application site, strong attachment to the tooth with low risk of dislocation, high biocompatibility and biodegradability. Full article

Due to the present worldwide economic development, there is an increasing need to follow the financial health of companies in individual sectors to avoid possible decline and bankruptcy. The goal of this contribution is to find out the influence of the pandemic on the economic situation in the mining industry as the primary sector, in connection with the construction industry as the secondary sector. The research is carried out through economic and financial indicators, which mostly influence the potential crisis of companies. The results show that the mining industry and construction sectors managed to avoid the heavy decline and bankruptcy of certain organizations in the industries. Such results can be used for forecasting and modeling the socio-economic development of regions and countries. The growth of the analyzed industries could contribute to the sustainable development in the country. Full article

The main subject of the current review is a specific subtype of headache, which is related to shunt over-drainage and slit ventricle syndrome, in pediatric patients harboring an implanted shunt device for the management of hydrocephalus. This clinical entity, along with its impairment regarding the quality of life of the affected individuals, is generally underestimated. This is partly due to the absence of universally agreed-upon diagnostic criteria, as well as due to a misunderstanding of the interactions among the implicated pathophysiological mechanisms. A lot of attempts have been performed to propose an integrative model, aiming at the determination of all the offending mechanisms of the shunt over-drainage syndrome, as well as the determination of all the clinical characteristics and related symptomatology that accompany these secondary headaches. This subcategory of headache, named postural dependent headache, can be associated with nausea, vomiting, and/or radiological signs of slim ventricles and/or subdural collections. The ultimate goal of our review is to draw clinicians’ attention, especially that of those that are managing pediatric patients with permanent, long-standing, ventriculoperitoneal, or, less commonly, ventriculoatrial shunts. We attempted to elucidate all clinical and neurological characteristics that are inherently related to this type of headache, as well as to highlight the current management options. This specific subgroup of patients may eventually suffer from severe, intractable headaches, which may negatively impair their quality of daily living. In the absence of any other clinical condition that could be incriminated as the cause of the headache, shunt over-drainage should not be overlooked. On the contrary, it should be seriously taken into consideration, and its management should be added to the therapeutic armamentarium of such cases, which are difficult to be handled. Full article