Plant metabolomics is an important research area in plant science. Chemometrics is a useful tool for plant metabolomic data analysis and processing. Among them, high-order chemometrics represented by tensor modeling provides a new and promising technical method for the analysis of complex multi-way plant metabolomics data. This paper systematically reviews different tensor methods widely applied to the analysis of complex plant metabolomic data. The advantages and disadvantages as well as the latest methodological advances of tensor models are reviewed and summarized. At the same time, application of different tensor methods in solving plant science problems are also reviewed and discussed. The reviewed applications of tensor methods in plant metabolomics cover a wide range of important plant science topics including plant gene mutation and phenotype, plant disease and resistance, plant pharmacology and nutrition analysis, and plant products ingredient characterization and quality evaluation. It is evident from the review that tensor methods significantly promote the automated and intelligent process of plant metabolomics analysis and profoundly affect the paradigm of plant science research. To the best of our knowledge, this is the first review to systematically summarize the tensor analysis methods in plant metabolomic data analysis. Metabolomics is a rapidly growing field that gains more and more attention from both industry and scientific communities. By integrating the capabilities of different disciplines such as analytical chemistry and statistics, metabolomics aims to gain a systematic understanding of quantitative changes in the level of metabolites from the biology or chemical system . Plant mPlant metabolomics analysis generally falls into two categories: targeted metabolomics analysis and untargeted metabolomics analysis . In targChromatography coupled with mass spectroscopy and Nuclear Magnetic Resonance (NMR) are the main types of instruments that are widely used for performing plant metabolomics analysis. NMR is a well-known technology that is capable of producing robust, reproducible and structural metabolite information when used in metabolomics studies . CompareIn recent years, tensor methods, also known as multi-way models, has been proven to be a promising high-order chemometrics tool for solving or alleviating the practical and challenges of complex metabolomics data analysis , 12. TenThe rest of the review is organized as follows. Section 2 presents the widely used tensor models in plant metabolomics data analysis and discusses the advances and limitations of various tensor models. In Section 3, we briefly introduce the recent application of tensor models in plant metabolomics investigations and summarize the plant metabolomics problems that tensor models are used to solve. In the end, we conclude the review and discuss some future perspectives on plant metabolomics data analysis coupled with tensor modeling methods.PARAFAC is an important tensor model for analyzing multi-way data with a multilinear structure. It was first proposed by Harshman , a psychwhere where It is vital to note that the PARAFAC model is multilinear. In other words, if the underlying profiles change shape or shift in one mode across another mode, then such data will violate the multi-linearity assumption of PARAFAC model, thus applying PARAFAC model will not lead to chemically meaningful tensor solution. When using PARAFAC model on large scale GC-MS or LC-MS data, the data has to be preprocessed or aligned. This is because chromatographic data is always shifted run by run and such shift violates the multilinear assumption of PARAFAC model. Under mild condition , it is pIn recent years, some potential solutions have been proposed to attack the problems of alternating based PARAFAC algorithm. Zeng et al. proposed an alternating minimization-based method for incremental PARAFAC decomposition , and it PARAFAC2 is a useful method for complex high-order tensor analysis. The proposal of PARAFAC2 model can be dated back to the work of Harshman . The PARThe definitions of the symbols in Eq. 3 are the same as those in PARAFAC model. The only difference is that each sample now has an individual loading matrix her mode . In planSimilar to the PARAFAC model, the solutions of the PARAFAC2 model are also unique under certain conditions . The uniThe PARAFAC2 model is advantageous in many other aspects. For example, compared to the two-way methods , the PARAFAC2 fully explores the multi-way structure of the high-order shifted tensor and yields the model with unique solutions and more interpretability. Unlike PARAFAC model, the PARAFAC2 model does not need the cumbersome preprocessing and alignment procedure when analyzing the shifted multi-way GC-MS data . The rotThere are still some limitations in PARAFAC2 modeling when it is used for complex plant metabolomics data analysis. The computation of PARAFAC2 model is inherently an NP-hard problem as it is for other tensor decomposition problems . It meanRecently, there has been some work that has been dedicated to tackling the numerical issue of PARAFAC2. Cohen et al. proposed a flexible coupling Non-negativity PARAFAC2 model by relaxing the constraints of the normal PARAFAC2 model and adding the regularization term to the normal loss function of PARAFAC2 model . More reData fusion is defined as the joint analysis of multiple inter-related datasets that provide complementary views of the same phenomenon . The intNew advances in tensor-based data fusion algorithms have been achieved over the years. Evrim et al. proposed the so-called advanced CMTF(ACMTF) model . The ACMApart from the widely used PARAFAC, PARAFAC2 and tensor-based data fusion models, there are some other tensor models being developed and used for plant metabolomics applications. Some of the tensor models are developed as a variant of an existed chemometrics model. For example, PARAFAC2×N model is a variant of PARAFAC2 model . It is pMany of the tensor models are designed for a specific analytical and numerical purpose. PARAllel profiles with LINear Dependencies (PARALIND) is one of such models that is established for analyzing the multi-linear tensor data with linear dependency factors . By intrChromatographic metabolomics has been widely used to perform plants genetic mutant and phenotyping studies. As a powerful tool, tensor methods play an important role in understanding the importance of metabolites traits and associated genetic factors. Khakimov et al. explored the seed phenotyping of barley by using PARAFAC2 model on multi-way metabolomics data . The relTensor methods provide new insights for metabolites characterization-based plant phenotyping study. PARAFAC2 modeling coupled with PLS-DA was capable of achieving high precision classification of the wild-type and genetically engineered poplars with a success rate more than 99% . By charPlant disease and resistance are the eternal research themes of plant science. Investigating plant disease from a metabolomics point of view is important for understanding the complex mechanism of plant disease. Hantao et al. analyzed the volatile metabolites of hybrids of Eucalyptus globulus to determine the Eucalyptus samples susceptibility to rust disease . They coThe investigations on plant resistance against to insects is vital for protecting plant growth. Tensor methods have been applied in plant metabolomics to help understand the plant resistance mechanism. Khakimov et al. employed PARAFAC2 model on the LC-MS metabolomics data of Barbarea vulgaris plants . By combThe pharmacological components analysis of plants is an important topic that cannot be ignored in plant science research, as well as in plant industry. However, due to the complexity of medicinal and edible plant systems, accurate characterization of their pharmacological components is not straightforward. Metabolomics technology provides an inspiring solution for the analysis and quality assessment of plant pharmacological components. In particular, the coupling of tensor methods and metabolomics technology further promotes the exploration on this issue. Schmidt et al. applied PARAFAC model on the aligned HPLC metabolomics data generated from Hypericum perforatum used for producing herbal preparations . The difThe coupling of tensor modeling and nutrient composition analysis can be observed from the plant metabolomics literature. Khakimov et al. conducted a detailed nutrient value analysis of the main northern European cereal crop plants by comparing the metabolites profiles of different cereal crop plants . ComparePlants provide values to humans and society in the form of plant products in many cases. Along the years, the study of plant products has attracted increasing interests from both plant scientists and analytical scientists. Favilla et al. employed the discriminant version of N-way PLS-DA model (NPLS-DA) and Variable Importance in Projection (VIP) method to efficiently evaluate the authenticity of extra virgin olive oils . The tenThe rapid development of metabolomics technology has profoundly affected the field of plant science. The advances in chemometrics provide the key tools for data analysis and processing in plant metabolomics research. Among them, advanced chemometrics tools represented by tensor analysis methods have undoubtedly further promoted the automated and intelligent process of plant metabolomics analysis. Although the tensor analysis method has been widely used in plant metabolomics research, its potential is far from being reached. The synergy between tensor analysis methods and high-throughput metabolomics data analysis summarized in this review is just the tip of the iceberg. In the future, there will be more opportunities for tensor-based advanced chemometrics methods in solving complex plant metabolomic analysis problems. More advanced tensor chemometrics tools will continue to emerge in order to continuously adapt to the increasing needs of plant metabolomics research during its evolution process.


Protein-protein and protein-peptide recognition are among the most important processes that make signal transmission and transduction possible in a cell; they also play a role in cellular processes involving diseases. Theoretical approaches in the study of these processes from a structural and thermodynamic viewpoint have focused on computational methods aimed at modelling, predicting, and characterizing the interface between the interacting proteins. Indeed, computational techniques represent potent tools for understanding PPI mechanisms at the atomic level: this information can then be exploited for designing molecules able to interfere with them.However, designing molecules to directly targeting protein-protein interactions (PPI) is a difficult task. Differently from other computationally driven small molecule discovery efforts, PPI targeting presents unique challenges: high resolution structural information on targets is not easily available or predictable; PPI surfaces deviate from the conventional druggable sites targeted by therapeutic small molecules, being more hydrophobic, shallow and larger, thus having higher degree of conformational freedom. The unique nature of PPI is also reflected by known PPI inhibitors, which tend to have different physicochemical features from typical small compound drugs.In this Research Topic, a few approaches are presented that try to overcome the complexity of designing PPI inhibitors or modulators by providing new computational methods or analysis tools to assist PPI drug discovery, as well as facilitate integration with experimental data.Ranaudo et al. addressed this problem for affitins, a class of easily engineerable proteins that can be used as molecular probes able to specifically recognize biomarkers, for the diagnosis of serious diseases. In their work, they proposed a protocol for discriminating the correct from incorrect predictions of binding poses of different affitins in complex with several protein partners, obtained through an initial stage of rigid docking calculations. They demonstrated that a consensus approach based on Molecular Dynamics simulations and the prediction of potential interacting residues, through the Matrix of Local Coupling Energies method, leads to the identification of the correct binding pose. Their approach represents an effective tool for engineering affitins which are specific for different protein targets and, therefore, that could be used for diagnosis applications.Currently, no computational method can reliably predict the three-dimensional structure of protein complexes. Molecular docking is still an open challenge for protein-protein interactions, with one of the critical steps being the post-docking processing for determining the correct binding modes among the different models. He et al. studied an oncogenic system for which regulation is mediated by protein-protein interactions in a ternary complex. They explored the molecular and atomistic details of long-range allosteric effects in the G13D oncogenic mutant of K-Ras4B in complex with Son of Sevenless (SOS) protein. Their results suggest that in the ternary complex K-Ras4BG13D•SOScat•K-Ras4BG13D–GTP, a GTP-bound version of Ras can allosterically activate the distal Ras bound to SOS. The authors used a set of well-established computational methods including network analysis to investigate conformational changes associated with the long-range allosteric mechanism. The novel insights provided by this study contribute to the current efforts to understand allosteric regulation in oncogenic protein complexes with the goal of informing drug development of inhibitors and modulators of protein-protein interaction.Catalytic activity in proteins is often allosterically regulated. Ikeda et al. present a novel chemical library database system (DLiP) to design PPI inhibitors, consisting of more than 32,000 PPI-related compounds. Among them, a significant component derives from in silico screening of a diverse set of protein-protein interfaces, through computational docking, while the rest is a Research Topic of experimental information from the literature or retrieved from other databases. Coming with a web interface that currently allows for several analyses and search, it promises to provide users with a download tool to be used in the future for prediction models.The advanced application of drug discovery methods, among which of AI-assisted approaches, critically relies on the availability of annotated databases of compounds with given features such as chemical structures and physicochemical properties to drive the design of new hits. This is particularly true for the challenges posed by designing inhibitors targeting protein-protein interfaces, which typically deviate from the common features of small molecule inhibitors, e.g., in terms of molecular weight. Vasile et al. the transmembrane protein E-cadherin is the principal actor in inter-cell adhesion and its downregulation gives the possibility for cancer cells to spread across the body and form metastasis. The formation of the complex between the extracellular moieties of E-cadherin could be a good target to prevent the reassociation of cancer cells. Towards this aim, the research of a new class of molecules able to interfere with E-cadherin homophilic interaction was carried out by combining in silico and experimental techniques. The in silico study was conducted with an initial analysis of the cavities and fragment-based drug discovery (FBDD). This technique allows us to identify which class of chemical fragment have a good chance to establish stable and strong interaction with the amino acids in the target protein. The Saturation-Transfer Difference Nuclear Magnetic Resonance (STD-NMR) experiments were used to validate the result obtained during the in silico simulations. With this experimental technique, it is possible to identify which part of the molecule interacts with the target protein. This research lays the foundation for further investigations towards the discovery of potent inhibitors.Finally, an application stresses the importance of experimental validation of interaction predictions in the context of a pharmacologically fundamental problem. The protein-protein interaction lies at the heart of cell adhesion and the aberrant behavior of this mechanism is responsible for the spread of cancer cells and metastasis formation. As discussed in the paper by Overall, this Research Topic presents a variety of problems and approaches, demonstrating a lively research area: the strategies and concepts suggested herein are likely to prove precious in increasing the possibility of generating new chemical tools useful in the biomedical and therapeutic fields. The increase in computational power and the development of new algorithms and computational strategies has significantly improved our understanding of experimental data on PPI targeting. In turn, experimental techniques have provided novel stimuli for the development and improvement of computational methods focused on the challenges of PPI targeting.


Livestock production and animal health systems at the farm level need to identify challenges, risks and limitations that may hinder their compliance with animal health prerequisites as well as value chain participation . LivestoThe 5th ISESSAH conference aimed to improve understanding of animal health and welfare challenges and possible solutions through a more nuanced application of concepts and tools from economics and social science disciplines. By bringing them together with experts in economics and social sciences of anima health, ISESSAH provided opportunities for animal health professionals worldwide to achieve wider societal benefits from animals. The experts discussed their findings, solutions to the problems, and how to put these solutions into action. There is an increasing demand to assess the economic justifications of animal disease control programs and policies using current economic and social science approaches, while also taking important factors such as animal welfare and human health into account. During this conference, the results of many interesting research projects carried out were presented, sparking discussions among participants of the conference. This Research Topic compiles a number of these presentations.The 5th ISESSAH hybrid conference 2021 focused on livestock and aquaculture production, consumption, and welfare. The hybrid conference was held on the 17th and 18th of November 2021 in Kuala Lumpur, Malaysia. Universiti Putra Malaysia (UPM) and the Malaysian Agricultural Economics Association (PETA) supported the conference. A hybrid conference is a conference meeting that includes both in-person and remote attendees who connect through a virtual meeting platform. Papers that investigated these issues in light of the current challenges as well as broader discussions about the transition to a One Health approach, were of particular interest. The Research Topic is divided into three sections: (1) livestock production economics; (2) economic consequences of diseases and related control; and (3) livestock systems and one health.Han et al. investigated the technical inefficiency of dairy input, and its association with cattle longevity under Dutch commercial dairy production conditions. The authors used a two-stage data envelopment analysis (DEA) approach to examine the performance and accounting records of 1,037 commercial Dutch dairy herds from 2007 to 2014. They emphasized that prolonging cattle longevity can improve a dairy farm's efficiency performance as long as the milk yield per cow remains unchanged.Two studies in these proceedings highlight the value of economics and social sciences in improving animal health decisions in livestock production by focusing on the utility of production economic analysis in improving animal health decisions. Viidu et al. reported the attitudes, satisfaction, and personality of calf care workers (CCWs) in large Estonian dairy herds, as well as investigated their associations with herd calf mortality. A total of 108 large Estonian dairy farms with more than 100 cows were studied. The authors calculated herd-level calf mortality risk (MR) and used cluster analysis and variance partitioning analysis to determine the explanatory capacity of CCWs' attitudes and personalities on calf mortality. The study revealed the significance of CCW attitudes and satisfaction in allocating proficient assistance to herds and mitigating calf health problems and calf mortality.The study by Dejyong et al. described farm characteristics and milking practices associated with high somatic cell count  to identify risk factors and assess economic loss due to high SCC in three dairy cooperatives in Chiang Mai, Thailand. A retrospective cost assessment of high SCC was used in the study on 208 dairy cattle farms to estimate the losses in affected farms in relation to two potential coping strategies (culling and treating the cow). The authors indicate that treating infected cows was more cost effective than culling. Another study strengthens the important of understanding the economic consequences of disease and related control. Yue et al. conducted a case-control study on a Bovine Viral Diarrhea Virus (BVDV) in Dutch Dairy Herds. Based on longitudinal annual accounting and herd performance data from Dutch dairy herds between 2014 and 2019, the authors investigated the economic (gross margin) and production effects  of the herds obtaining BVDV-free certification. The study emphasized the importance of providing incentives for farms to participate in the pest control program.Four papers address the translation of disease consequences into policy, decisions, and actions. Two papers focused on the farm level. Livestock production issues are frequently linked with animal diseases on farms. One of the papers by Jean-Pierre et al. The study developed a partial equilibrium model for the Haitian pig sector (HPM-2021) to assess the economic impacts of a 2021 Haitian African swine fever (ASF) outbreak of a similar size to the 1980s outbreak. The dynamic model examined ASF impacts from 2021 to 2024, through 100 iterations of stochastic supply shocks, and three specific demand shocks. A supply shock is an unexpected event that abruptly changes the supply of a product or commodity, resulting in an unanticipated change in price. A demand shock, on the other hand, is an unexpected event that dramatically changes demand for a product or service, resulting in an observable economic effect. The swine industry recovery alternatives was predicted for the year 2030, and outbreaks and recovery outcomes are compared to a 2019 baseline. The authors highlight ASF impacts on prices will benefit certain producers and disincentivize on-farm disease reporting. Chanchaidechachai et al. conducted a regional level study between 2015 and 2016 to investigate the epidemiological consequences of foot and mouth disease (FMD) outbreaks in four Thai districts. The researchers examined epidemiological data from FMD-affected dairy, beef, and pig farms. The differences in FMD outbreak management strategies in each area were investigated to determine the cause of a significant difference in morbidity rates between dairy farms in each area. The authors stress the importance of FMD control in reducing FMD's significant epidemiological and economic impact on Thai farms.Two other papers investigated the economic impact of animal disease at the regional level. Animal disease impacts on rural economies and on smallholders was studied by Technology is a powerful tool for improving farm production and managing animal diseases. Nowadays, investments in digital technologies are not limited to any particular farm management practices. The application of technology includes disease controls based on good biosecurity practices from the farm to the entire supply chain. The digital technology will improve value chain economics and governance. Digital technologies can help enabling several important changes in livestock systems, such as defining multi-disease strategies and food safety controls that improve one's health.Baker et al. discussed the broader context of digital farming, including not only farm production management, but also supply chain and livestock systems. The authors discussed the opportunities and value propositions of digital technology in various types of livestock supply chain systems. Individual accounts of digital agriculture in livestock systems are organized into four broad types: commodity-based, value-seeking, subsistence-based, and nature-based. According to the study, the adoption of digital technology will result in an equitable and significant diversification of supply chains, increased monetization of animal product quality, and more sensitive management to meet customer demands and environmental threats.The papers presented in the 5th ISESSAH conference proceedings provide excellent examples of how various economic approaches and social science perspectives can contribute to improve animal health management in livestock production, as well as disease control programs and policies. These studies will improve our understanding of the economics of animal health and fill gaps in the literature, allowing us to make better decisions about animal health. It is concluded that more emphasis on multidisciplinary approaches and continuous technique improvement are required for control and prevention of diseases. The ISESSAH, in collaboration with other experts from various disciplines, enables those working in the field of animal production and farm health management to contribute to society more broadly, through annual conferences and a variety of other projects. Our organization's goal is to combine our resources and expertise in order to improve animal health and welfare.DI drafted the editorial. NM and BV provided input at the designing stage of the Research Topic. DR, DP, MB, WS, JR, and HH reviewed and revised the editorial. BV, NK, and HH contributed to the editing of the papers published in the proceedings of the 5th ISESSAH conference 2021. All authors contributed to the article and approved the submitted version.


The depletion of fossil fuels and increased amount of atmospheric/environmental pollution associated with the excessive use of fossil fuels to power our economies have intensified the efforts of academia and industry worldwide to seek sustainable technological solutions to meet the global energy demand. Among all the renewable energy resources available on Earth, solar light is by far the most abundant and durable primary source of energy. Indeed, natural photosynthesis, which evolved over 3.5 billion years ago, provides an elegant blueprint of solar-driven conversion technologies dubbed as artificial photosynthesis. Inspired by the molecular principles of natural photosynthesis, solar-converting technologies have emerged as a promising solution to provide not just green electricity, but also energy vectors in the form of solar fuels and chemicals. This Special Issue on “Biomolecular and Biohybrid Systems for Solar Energy Conversion” aims to provide an up-to-date compendium on the recent advances and challenges in the direct solar conversion field, focusing on the recent progress towards the development of rational strategies to achieve the highest power conversion efficiency.For the biomolecular solar conversion technologies to become viable, it is of paramount importance to understand and investigate the current limitations of these systems. Whilst the structure and function of photosynthetic macromolecular machines have been optimized through billions of years of evolution, their optimal implementation as efficient biocatalysts remains to be realized. This challenge was addressed by the comprehensive and rational nano-engineering of the biophotocatalyst and the catalyst/electrolyte interface described in the paper by Szewczyk et al. . By combII/III complexes as direct redox mediators, they improved the power conversion efficiency in two types of BSSCs with two different bio-photosensitizers, PSI and bacteriorhodopsin. Such a universally biocompatible system showed stable performance over a period longer than two weeks.In addition to the optimal bio-photoelectrochemical cell configuration, other important considerations include applying the principles of sustainability, cost-effectiveness and use of environmentally friendly materials in the biomolecular system’s design. Indeed, commonly used strategies to improve the interfacial electron transfer in biohybrid electroactive systems rely on the use of large amounts of toxic redox mediators, as well as expensive conductive substrates based on noble and rare elements. To address these design limitations, the groups of B. D. Bruce and C. Villarreal have collaborated to develop a new class of optimized biohybrid dye-sensitized solar cells (BSSCs) . By usinThe long-term stability of biohybrid solar-converting systems is a crucial aspect that must be addressed in order to compete with the current silicon-based photovoltaic technologies. Biological photosensitizers often suffer from photodamage (photobleaching) through prolonged irradiation exposure, in particular under aerobic conditions. In this context, Szalkowski et al.  investigTheoretical predictions that arise from quantum mechanical/molecular mechanics calculations can provide valuable information to guide the rational design of the biosolar systems, notably via de novo modeling of various molecular interfaces employed to electrically wire biophotocatalysts in an oriented and well-controlled manner on various types of conductive surfaces. Thus, Kaźmierczak et al.  studied 6 affinity tag on the specific structural domain of the highly robust PSI complex, which aided the strong and oriented binding of this biophotocatalyst to the appropriately functionalized graphene surface. This approach yielded a spectacular improvement of the electron transfer process while maintaining the simplicity of the system’s configuration and easiness of the device manufacturing.Last but not least, a highly promising strategy was described in the article by Izzo et al.  to signiWe would like to thank all the authors who have contributed to this Special Issue. We are convinced that this Special Issue will provide an excellent reference to the most recent advances in the biomolecular solar conversion field and will inspire the community to develop efficient and rational strategies for the much-needed significant improvement of biosolar systems’ performance.


The cerebellum has been the focus of attention for many decades regarding its essential role in motor control. Indeed, cerebellar circuitry dysfunction leads to a range of symptoms such as limb movement difficulties, alteration of posture and gait, and difficulties in eye movement and speech control , as the areas involved in the regulation. These areas presumably work together with amygdala, medial prefrontal cortex, hypothalamus, hippocampus, and periaqueductal gray, which are in the fear-related brain circuit. At the conclusion of the review, they suggest several additional areas of study, such as cerebellar efferent pathways and the precise role of the cerebellum in fear learning and memory.Ribeiro and Sherrard discuss the contribution of cerebellar dysfunction in neuro-developmental disorders (NDDs). They propose the transcription factor Retinoid-related Orphan Receptor alpha (RORα) as a protein with a major causative role in NDDs through cerebellar developmental defect. Notably, RORα regulates multiple events during cerebellar development, including Purkinje cell development and the refinement of synaptic connections, as well as cerebellar maintenance throughout life. In fact, the authors summarize comprehensively the research findings about the relationship between the deficiency of RORα and NDDs. The hypothesis of RORα as a possible candidate for the NDDs pathophysiology via influencing cerebellar development opens the way to act therapeutically on this risk gene target, upregulating the low expression and improving the NDDs symptoms.Choi et al. in their original research studied whether the exposure to lead during pregnancy alter cerebellar development in mice and induce ASD-like behaviors in the offspring. The authors found that maternal lead exposure caused sex-dependent alterations in cerebellar glial cells and ASD-like behaviors in the offspring: male offspring exhibited microgliosis and repetitive behaviors, whereas female offspring showed astrogliosis but no abnormal repetitive behaviors. The authors also suggested that the sex-dependent difference of the GABA levels in the cerebellum is one of the mechanisms explaining the ASD-like behaviors. These findings highlight the importance of minimizing lead exposure during pregnancy to prevent abnormal cerebellar development and consequent NDDs in offspring.Prenatal exposure to heavy metals can lead to NDDs, such as autism spectrum disorders (ASD). Considering the correlation between the occurrence of ASD and abnormal cerebellar development  in mdx mice, particularly during high-frequency activity. Moreover, they reported changes in the excitability of CbN neurons in mdx mice with an increased spontaneous firing and a reduced evoked firing. The overall effect of these alterations is a less sensitivity of CbN neurons to both excitatory and inhibitory influences, suggesting an impairment of the output signals from the cerebellar circuits. The altered signals from the cerebellum during development might be the reason of the high association between DMD and NDDs.Duchenne Muscular Dystrophy (DMD) is caused by the mutation in the DMD gene encoding for the dystrophin protein which stabilizes the cellular membrane of muscle cells. Besides the progressive muscle degeneration and weakness which are the main symptoms, DMD patients display also cognitive deficits. Cerebellar Purkinje cells have the highest levels of dystrophin expression in mice, suggesting that cerebellar circuit could be significantly impaired by loss of dystrophin, possibly explaining, at least in part, the motor and cognitive deficits associated with DMD. This Research Topic gathered many studies that highlight the multiple roles of the cerebellum in addition to the motor control. These studies emphasize the necessity of further studies to understand how the changes of specific microcircuits of the cerebellum can lead to a variety of different diseases.PL and EH designed the first draft of the manuscript and revised the manuscript. PL, FM, KT-Y, and EH reviewed and finalized the manuscript. All authors have read and approved the final version of the article for publication.


A high-fat diet plays a key role in the pathogenesis of colorectal cancer, and this effect on the gut can also occur in the offspring of mothers with a high-fat diet. In this review, we discuss the role of a high-fat diet in the pathogenesis of colorectal cancer and summarize the effects of a maternal high-fat diet on the activation of inflammation and development of colorectal cancer in offspring. Studies have found that a maternal high-fat diet primarily induces an inflammatory response in the colorectal tissue of both the mother herself and the offspring during pregnancy. This leads to the accumulation of inflammatory cells in the colorectal tissue and the release of inflammatory cytokines, which further activate the NF-κb and related inflammatory signaling pathways. Research suggests that high levels of lipids and inflammatory factors from mothers with a high-fat diet are passed to the offspring through the transplacental route, which induces colorectal inflammation, impairs the intestinal microecological structure and the intestinal barrier, and interferes with intestinal development in the offspring. This in turn activates the NF-κb and related signaling pathways, which further aggravates intestinal inflammation. This process of continuous inflammatory stimulation and repair may promote the uncontrolled proliferation of colorectal mucosal cells in the offspring, thus increasing their susceptibility to colorectal cancer. According to the global cancer statistics published by the World Health Organization (WHO) in 2020, CRC was the third most commonly diagnosed cancer (incidence: 10.0%) and the second most deadly cancer  . NotablyObesity is a common public health issue worldwide and is recognized as a major risk factor for cancer . In the In this review, we used the keywords “high fat diet” or “obesity,” “offspring,” and “colorectal” to summarize the literature on the Pubmed website2.A high-fat diet has been linked to an increased incidence of CRC , 17. A mThe susceptibility to colorectal carcinogenesis caused by a high-fat diet may be associated with inflammation caused by increased serum levels of inflammatory cytokines . ChronicAccording to the above reports, intestinal inflammation is an important step in the CRC induction mechanism of a high-fat diet. Macrophages, as important immune cells, secrete the inflammatory cytokines IL-1β, IL-6 and TNF, which are involved in the NF-κb pathway, an important signaling pathway involved in the pathogenesis of CRC . In addi3.A high-fat diet not only increases blood lipid levels and causes visceral fat accumulation in parents but also affects lipid metabolism in offspring during pregnancy. Epidemiological studies have found that maternal obesity and weight gain during pregnancy increase the risk of adverse outcomes, such as obesity, in infants –35, and Firmicutes (mainly Lactococcus), a decrease in the abundance of γ-Proteobacteria (mainly Escherichia) and a partial increase in the abundance of Betaproteobacteria (mainly Comamonas), which are associated with a high-fat environment in the intestine (The intestinal flora also plays an important role in lipid metabolism disorder. A high-fat diet strongly affects the intestinal flora, and the intestinal flora further has a feedback effect on the process of lipid metabolism. Intestinal microbes can regulate the function of fat cells and affect the nutritional intake and metabolism of the host to regulate the energy balance in the body . A high-ntestine . Furtherntestine . It can The exact mechanism of lipid metabolism disorder in offspring caused by a maternal high-fat diet is not clear. Research indicates that some of the energy in the pregnant woman is converted to and stored as fat in the fetus. Mothers with pre-existing metabolic disorders or metabolic disorders developed during pregnancy have elevated blood lipid levels. This metabolic imbalance leads to excessive energy storage in the fetus during pregnancy. The insulin resistance caused by metabolic imbalance during pregnancy further elevates maternal blood glucose and blood lipid levels, resulting in excessive transplacental transfer of glucose, triglycerides and fatty acids to the fetus . The plaThe above studies suggest that a maternal high-fat diet disrupts lipid metabolism in the offspring via the transplacental transport of high levels of lipid into fetal circulation. In addition, metabolic disorders in the offspring may be related to placental function. The disrupted maternal lipid metabolism activates inflammation in the placenta, which damages placental function and in turn impairs offspring lipid metabolism. In addition, intestinal dysbacteriosis caused by maternal lipid metabolism disorder is also reflected in the offspring intestinal microecology, which further affects lipid metabolism in the offspring. However, the specific mechanism of lipid metabolism disorder in offspring caused by a maternal high-fat diet still needs to be clarified.4.A maternal high-fat diet can disrupt lipid metabolism in offspring, increasing their susceptibility to intestinal inflammation, and has been shown to promote the early onset of intestinal inflammation in offspring . For exaA maternal high-fat diet may promote the progression of intestinal inflammation and induce intestinal carcinogenesis in the offspring through vertically transmitted disturbance of the intestinal flora. The establishment of the intestinal flora begins in the fetus. Studies have found that the intestinal microecological state can be passed directly from mother to offspring, and this intestinal colonization often occurs during fetal intrauterine development, delivery and lactation , 63. The5.The offspring of mothers fed a high-fat diet show an increased risk of cancer such as breast cancer, pancreatic cancer and CRC compared with the offspring of mothers fed a normal diet –14. A laThe intestinal growth and development of the fetus begins during pregnancy. A maternal high-fat diet may affect the intestinal growth and development of offspring through inflammation. In rats, it was found that a maternal high-fat diet not only increased the levels of intestinal inflammatory factors but also significantly changed the intestinal tissue morphology in the offspring . StudiesThe molecular mechanism of action of a maternal high-fat diet on the offspring’s gut is not completely clear. Studies have demonstrated that a maternal high-fat diet activates the NF-κb pathway in the offspring’s nervous system, leading to nervous system inflammation . SimilarTaken together, these studies suggest that carcinogenesis in the colorectal tissue of the offspring of parents fed a high-fat diet may be due to mucosal barrier destruction, intestinal dysbacteriosis, and abnormal intestinal growth and development caused by high-fat-diet-induced intestinal inflammation. The activation of the NF-κb pathway may play an important role in this process. This persistent and progressive inflammatory response may be an important factor in the increased susceptibility to CRC in the offspring of parents fed a high-fat diet .6.This review discusses the association of a high-fat diet with CRC development and summarizes the role of a maternal high-fat diet in colorectal inflammation and CRC development in offspring. Our review reveals that a high-fat diet increases visceral fat accumulation in the host, which induces inflammatory cell aggregation and inflammatory cytokine release. This further activates the NF-κb and related signaling pathways, thereby increasing susceptibility to CRC. A maternal high-fat diet also elevates blood lipids and visceral fat accumulation in the offspring via the transplacental transfer of high levels of lipid from the maternal serum, and may impair placental function, causing metabolic disorders in the offspring. These changes also lead to intestinal dysbacteriosis in the offspring, which further aggravates lipid metabolism disorder. The impaired lipid metabolism and maternal and placental inflammatory factors in offspring circulation cause colorectal and systemic inflammation in the offspring. Colorectal inflammation impairs the intestinal barrier, hinders the normal growth and development of the intestine, accelerates the proliferation and differentiation of intestinal pluripotent stem cells and further aggravates intestinal dysbacteriosis. This process of continuous inflammatory stimulation and repair leads to the activation of the NF-κb signaling pathway, the uncontrolled proliferation of colorectal mucosal cells and, eventually, CRC onset .At present, the age of diagnosis of CRC in the world is gradually getting younger, and the therapeutic effect of CRC is not ideal. This may be closely related to the diverse pathogenesis of CRC. Few studies have focused on the effect of maternal high-fat diet on offspring colorectal. A series of changes caused by high fat diet in parents may increase colorectal carcinogenesis in offspring, but the related mechanism is not clear at present. Further research to understand the cellular and molecular mechanisms of action of a high-fat diet in CRC development and the role of a maternal high-fat diet in colorectal inflammation and increased CRC susceptibility in offspring is warranted. These studies contribute to the discovery of potential therapeutic targets for CRC and the development of new therapeutic strategies for CRC based on these targets, which may be helpful to improve the efficacy of CRC. Such studies could contribute to the discovery and development of new therapeutic strategies for CRC.SZ, HY, and LL contributed to conception and design of the study. SZ and JY collect and organize the literature. SZ wrote the first draft of the manuscript. JY, HY, and LL wrote sections of the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Background: Antimicrobial stewardship programs (ASPs) seek to reduce the prevalence of antimicrobial-resistant and healthcare-associated infections. There are limited infectious disease (ID) physicians and pharmacists to support these ASPs, particularly in rural areas. The Veterans Health Administration has a robust telehealth program in place. Our previous work has demonstrated the feasibility of using telehealth modalities to support ASPs at rural Veterans Affairs medical centers (VAMCs) by pairing them with an ID expert from a larger, geographically distant, VAMC. This program, dubbed the Videoconference Antimicrobial Stewardship Team (VAST), emphasizes discussion of patients undergoing treatment for an active infection and additional relevant clinical topics with a multidisciplinary team at the rural VA. VAST implementation is ongoing at VAMCs. To understand and compare the qualitative differences in implementation, we used process maps to describe the VAST at 3 VAMC dyads. Methods: Team members from each dyad participated in interviews at 3, 6, and 9 months after beginning their VAST sessions. Questions addressed several aspects of VAST implementation and included identifying cases and topics to discuss; advance preparation for meetings; the frequency and general structure of VAST meetings; and documentation including workload capture. The research team used the responses to develop process maps to permit visual display and comparison of VAST implementation. Results: The first dyad began in January 2022 and the third in March 2022. The sessions had 3 phases: preparation, team meeting, and documentation of experts’ recommendations. Tasks were shared between VAST champions at the rural VAMC and the ID experts . The preparation phase showed the most variation among the 3 dyads. In general, champions at the rural VA identified cases and topics for discussion that were sent to the ID expert for review. The approaches used to find cases and the type of preparatory work by the ID expert differed. Team meetings differed in both frequency and participation by professionals from the rural site. Documentation of expert recommendations processes appeared similar among the dyads. Discussion: Each of the 3 dyads implemented VAST differently. These results suggest that the overall structure of the VAST is readily adaptable and that each site tailored VAST to suit the clinical needs, workflow, and culture of their partner facility. Future work will seek to determine which aspects in the preparation, team meeting, or documentation phases are associated with successful ASPs, including assessment of quantitative and qualitative outcomes.Disclosures: None


Hemangioma is congenital or traumatic in origin, and it is caused due to atypical build-up of the blood vessel. It is a painless benign condition with typical characteristic clinical features. These generally occur in the first three decades of life with no gender predispositions. A plain soft tissue radiograph can demonstrate phleboliths and aid in diagnosing an intramuscular hemangioma. The present report is a rare deep-seated facial hemangioma involving various facial muscles with multiple phleboliths; characteristics clinical and radiological features. A 22-year-old male patient reported a complaint of swelling on the right side of the jaw. Conventional radiography showed the right cheek’s soft tissue and multiple round, target-like radiopacities of variable sizes. The word "hemangioma" originates from Greek literature where haema is "blood"; angeio means "vessel," and oma is "tumour." The hemangioma can be congenital or traumatic in origin and is an atypical build-up of blood vessels in the skin or internal organs. It is also known as vascular nevus containing unorganized blood vessels connected to the central vein. Intramuscular hemangioma (IMH) has about 1% of cases and is typically seen in the trunk or limb's skeletal muscles . Only 8%Initial diagnosis is commonly considered a parotid tumour due to the location, whereas hemangiomas are barely suspected . The patA 22-year-old male patient reported swelling without pain on the right side of his face since childhood as the chief complaint. On further interrogation, the patient said that the swelling had been growing gradually over the years and has now become of the present size, which was approximately fist-sized. The patient did not recall any history of trauma. The extraoral examination demonstrated a swelling on the face's right side, extending supero-inferiorly from the right eye's outer canthus to the mandible's lower border and anteroposteriorly from the right corner of the mouth to the pre-tragus region Figure .The painless swelling was fluctuant, compressible, and soft in consistency on palpation. There was a slight rise in temperature over the surface of the swelling. On temporomandibular joint examination, the deviation was present towards the left side while closing the jaw without any pain, crepitus, or clicking sound. Intra-oral examination revealed bluish-red discolouration in the posterior part of the right side buccal mucosa extending up to the right side soft palatal region Figure .Maxillo-mandibular bony morphology was within the standard limit in the vicinity of the swelling. On bimanual palpation, the lesion was soft and compressible, non-tender, and had a diffuse periphery with evident pulsation. While palpating, the lesion was exaggerated, and an elevated red-purplish lesion appeared in the posterior part of the mucosa Figure .All the teeth were in good condition. Only extrinsic stains and calculus were there. Panoramic and submentovertex radiographs showed the presence of multiple concentric calcifications in the soft tissue shadow of the lesion suggestive of phleboliths Figures , 5.Assuring the benign nature of the disease and possible definite treatment, the patient was referred to the department of interventional radiology for management.Scott reported a series of 393 IMHs in 1957; 12% were reported in the head and neck region . The masThe Wattle sign that the size of the tumour increases by lowering the position of the head helps in diagnosis was positive in this case. Precautions should be taken while examining the facial region as new vascularised tissue is more torturous and fragile as compared to the native vessels, and this may lead to submucosal bleeding and may lead to subepithelial hematoma formation . We expeThe vascularity of the mass can be confirmed by EchoDoppler, but cannot accurately decide contours and associations with surrounding tissue, which can be done with contrast-enhanced computed tomography and exclusively on magnetic resonance imaging (MRI): these investigations have become essential before the treatment . Biopsy Hemangioma of the face, in this case, was diagnosed based on the typical clinical presentation and using conventional radiography. The presence of small hard nodules that are compressible and diffuse should alert a clinician to the possible presence of an intramuscular hemangioma. X-ray images can show phleboliths and help diagnose them, whereas to identify the exact location of the calcification, non-ionizing techniques such as MRI and ultrasound can be helpful. The management is usually conservative, and surgery is the last treatment of choice.


Background and Objectives: The aim of this study was to evaluate the correlation between the mandibular arch shape and the vertical skeletal pattern in growing patients. Materials and Methods: A total of 73 Caucasian patients  were retrospectively enrolled from a pool of patients treated in chronological order at the Department of Orthodontics, University of Foggia, Italy, from April 2018 to December 2021. Each patient received a laterolateral radiograph and a digital scan of the dental arch. Eight cephalometric parameters  and five dental measurements  were analyzed and then compared. A Spearman’s rho correlation test between the cephalometric measurements and the dental measurements was performed. Statistical significance was set at p < 0.05. Results: A negative statistically significant correlation was found between the Jarabak ratio and the intermolar angle; a statistically significant correlation was also observed between the Wits index, the posterior mandibular width, and the occlusal mandibular angle; the ANB angle and the occlusal mandibular angle; the intermaxillary angle (PP-PM) and the mandibular occlusal angle, posterior mandibular width on the disto-vestibular cusp, and the intermolar angle; and the OP-MP angle and mandibular occlusal angle and the posterior mandibular width on the disto-vestibular cusp. Conclusions: The mandibular arch form may be related to certain predisposing features in craniofacial morphology, such as jaw divergence, the Jarabak ratio, and the intermaxillary angle. Dental arch growth is a process involving multiple factors. Arch development depends on both genetic and epigenetic components, including muscular, functional, and local factors . Jaw groTherefore, the aim of this study was to evaluate the correlation between the mandibular arch shape and the vertical skeletal pattern in growing patients. Moreover, the relationship between arch form and sagittal growth pattern was evaluated. The null hypothesis is that no correlation exists between the vertical and sagittal skeletal pattern and the mandibular arch shape.This study was reported following the Strengthening The Reporting of Observational Studies in Epidemiology (STROBE) guidelines for observational studies .All the procedures of this research protocol have adhered to the Declaration of Helsinki and have been approved by the Ethics Committee of the University of Foggia . The records were retrieved retrospectively, were analyzed anonymously, and the patients signed a written informed consent. The inclusion and exclusion criteria are listed in A power analysis  , with a mean age of 9.4, were retrospectively enrolled in the present study from a pool of patients treated in chronological order at the Department of Orthodontics, University of Foggia, Italy, from April 2018 to December 2021.-Orthopantomography and lateral cephalogram;-Photographs: intraoral and extraoral photos;-Digital scans of the dental arches.All the following documentation was collected for each patient:Lateral head films (Gendex GXDP-700) were obtained, with the patient’s head positioned in a cephalostat, in centric occlusion, with adequate visualization of the reference structures, and without appreciable head rotation. All the lateral radiographs were captured by the same technician and on the same machine in the same radiology department. A cephalometric analysis was performed on the lateral cephalograms ,18. The p < 0.05. The data were analyzed using GraphPad Prism software 6.0 .Data distribution analysis was conducted using the Shapiro–Wilk normality test . DescripS = ∑ d2/2N), where d is the difference between the first and second measurements and N the number of radiographs evaluated [To reduce random errors, the cephalometric and dental measurements were calculated twice. The random error of each measurement was calculated using Dahlberg’s formula ;The Wits index and the posterior mandibular width ;The Wits index and the mandibular occlusal angle ;The intermaxillary angle (PP-PM) and the mandibular occlusal angle ;The intermaxillary angle (PP-PM) and the posterior mandibular width on the disto-vestibular cusp .The Jaraback ratio and the intermolar angle  was observed between:p < 0.05);The ANB angle and the mandibular occlusal angle ;The intermaxillary angle (PP-PM) and the intermolar angle ;Shudy’s angle and the mandibular occlusal angle .Shudy’s angle and the posterior mandibular width on the disto-vestibular cusp  was observed between: The study’s objective was to assess the correlation between mandibular arch shape and the vertical and sagittal skeletal pattern in growing patients. This evaluation aimed to emphasize early clinical signs detected on mandibular arches for diagnosing nonphysiological occlusal conditions associated with altered growth patterns. Furthermore, the study sought to supply supplementary data to assist in the selection of the arch shape during straight-wire treatment.Craniofacial growth follows a defined development timing . The traVarious studies have analyzed the correlation between vertical pattern, using mandibular plane angle, and arch form in class II patients ,23,24,25In the present study, a significant correlation was observed between the intermaxillary angle (PP-PM) and the mandibular occlusal angle, as well as between the posterior mandibular width on the disto-vestibular cusp and the intermolar angle. Hyperdivergent subjects showed an increase in the posterior mandibular width resulting in a V-shaped mandibular arch. Anwar et al.  reportedA possible role of the musculature should be taken into consideration when studying the relationship between the transverse arch dimensions and the vertical skeletal pattern. Few studies associating facial musculature with craniofacial growth have reported that muscle hyperfunction was evident in hypodivergent subjects ,30. IncrAccording to the results shown in the present study, in hyperdivergent subjects treated with fixed multibracket therapy, a tapered mandibular arch should be used; on the contrary, in hypodivergent subjects, an ovoid arch shape should be used. The mandibular arch shape is determined by the interaction between functional capabilities, masticatory muscles action , and basOne limitation of this study is the result of the retrospective nature of patient recruitment, although care was taken to avoid any selection bias, thanks to the use of a rigid chronological criterion. A further limitation is related to the bi-dimensional characteristics of the cephalometric exam used. Due to the retrospective nature of this study, it is difficult to determine any other unanalyzed variables that might have influenced the relationship between the mandibular arch measurement and the cephalometric parameters. As the untreated subjects were not recruited from a population sample, but from a university dental clinic, some inherent bias might be possible.Increased jaw divergence correlates with an increased posterior width of the mandibular dental arch, measured at the disto-buccal cusp of the lower first molar;Increased jaw divergence is associated with a tapered (V-shaped) mandibular dental arch shape, with a narrower anterior part and a wider posterior part.The findings of the present study can be summarized as follows:The distal positioning of the mandible  is associated with a tapered (V-shaped) mandibular dental arch shape and an increase in the posterior mandibular dental arch width.


Pediculosis capitis predominantly affects child populations. During the COVID-19 pandemic, various types of social limitations such as social isolation and limitations on educational facilities’ functionalities were introduced worldwide, including in Poland. The impact of these pandemic restrictions on the prevalence of pediculosis capitis has not been extensively investigated so far. Existing data on this topic are limited mainly to indirect evaluation methods, such as online surveys or Internet analysis. In this study, we directly examined a cohort of over five thousand children to assess the influence of COVID-19 pandemic restrictions on the prevalence of head lice infestation among school and kindergarten attendees in Poland. Our findings demonstrate that the restrictions imposed during the COVID-19 pandemic led to a decrease in the number of children infested with head lice compared to pre-pandemic data. These results confirm that head lice infestations remain an ongoing epidemiological concern and warrant continued monitoring. P. humanus capitis) are ectoparasites of humans [P. humanus capitis consists of the following: egg, three nymphal stages, and adult form. Nymphs, like the adult forms, live on human scalps and feed on blood at each stage of development [Human head lice , head lice infestations are the most common among kindergarten children, elementary school students, and members of households with children . AlthougIn Poland, head lice infestation does not fall under sanitary surveillance, which implies that there is no mandatory requirement to report cases of pediculosis capitis to the National Sanitary Inspectorate. Consequently, the absence of a national data collection system hinders the estimation of the magnitude of the issue. The lack of systematic reporting and data collection for head lice infestations in Poland presents a challenge in understanding the prevalence and distribution of the problem, making it difficult to implement targeted interventions and monitor trends effectively.Based on direct examinations performed in 2009–2012 in 30 schools in Lublin Province, Poland the prevalence of pediculosis capitis in schoolchildren was estimated at 2.01%Hhigher prevalence was noted in rural schools than in urban schools. Children between 8 and 12 years old were most frequently infested . Pediculus humanus capitis and the implementation of measures like social distancing and the closure of educational institutions during the COVID-19 pandemic, we formulated a hypothesis that a reduction in direct contact among children would impact the prevalence of head lice infestations.Based on the indirect surveys performed so far, pediculosis capitis was reported in the majority of tested schools in Poland (87.5%), while the greatest number of cases was reported in children aged 6–9 (68%) . Data frHowever, this topic has not been studied extensively either in Poland or in other countries yet. If any studies were performed on this topic, indirect methods of investigation such as surveys or Internet searching were used. For example, Internet analysis performed in the United Kingdom showed that there was a significant drop in Internet searching of the term “head louse” from March 2020 onwards, coinciding with COVID-19 restrictions, and a large difference between pre- and post-pandemic search volumes . FindingChildren’s examinations in primary schools and kindergartens were conducted by certified nurses between 24 September 2018 and 29 June 2021. The examinations lasted 1 day and were performed “for cause”, which means that they were planned by the management of the institution. Participation of all children in the examination was voluntary and supported by the consent given by their parents to the management of the educational facility. The study was carried out in 64 kindergartens and 28 elementary schools in Warsaw, Krakow, and Poznan. According to the decision n°. AKBE/99/2021 of the Bioethics Committee of the Medical University of Warsaw, this study did not require any additional favorable opinion as it does not constitute a medical experiment.The study group consisted of children from 3 to 14 years old attending primary schools and kindergartens. The pandemic restrictions introduced were the same for all educational facilities in Poland, so there should be no differences caused by this factor presumably. For logistical and financial reasons, the study was conducted in three cities, with most of the data collected in Warsaw. To mitigate this uneven sample stratification, we compared the total pediculosis capitis prevalence at pre-pandemic schools/kindergartens to the total prevalence at schools/kindergartens during the pandemic and assessed it statistically.The direct examinations were conducted by certified nurses equipped with specialized magnifying glasses and combs according to CDC guidelines. Each child’s scalp was visually examined and combed with an individual comb and then carefully examined under a magnifying glass. The presence of live lice and/or eggshells/nits alone was an accepted criterion for the identification of an infestation. A group of the same nurses performed all of the examinations included in this study.https://www.graphpad.com/quickcalcs/contingency1/ (accessed on 29 May 2023) ) statistical package. The infestation prevalence depending on the period of the pandemic and the type of educational facility was compared with the 2-tailed Fisher’s exact test. The test probability at the level of p < 0.05 was considered significant.The statistical analysis was performed using the GraphPad There were 3255 children from kindergartens and 1753 children from primary schools directly examined, which means that a total of 5008 children were evaluated.The pre-COVID study in kindergartens covered the period from 24 September 2018 to 28 February 2020. During this time, 2060 children were screened, of whom 248 were infested with head lice. The COVID-19 pandemic period of the study began on 14 September 2020 and ended on 29 July 2021. During this period, 1195 children were screened, of whom 116 were infested with head lice.The pre-COVID study in schools covered the period from 4 September 2019 to 10 March 2020. During this time, 1027 children were screened, of whom 107 were infested with head lice. The COVID-19 pandemic period, during which the research was conducted, began on 24 September 2020 and ended on 17 June 2021. During this period, 726 children were screened, of whom 39 children were infested with head lice.The granular data are shown in The obtained results provide insights into how social restrictions introduced in Poland during the COVID-19 pandemic affected the prevalence of human head lice infestation among the tested child population. The presented results indicate that the infestation prevalence during the COVID-19 pandemic significantly changed compared to the pre-COVID-19 pandemic period. In kindergartens, the prevalence during the pre-COVID-19 period reached 12.03%. During the COVID-19 period the prevalence was reduced to 9.7%. Even clearer differences in the results were obtained in the population of schoolchildren, among which the prevalence changed from 10.41% to 5.37% only. Both differences were considered statistically significant.Head lice are primarily transmitted through direct contact between individuals, making it reasonable to hypothesize that measures taken to reduce the transmission of COVID-19 could also have an impact on the prevalence of head lice infestations.A cross-sectional descriptive study where an online survey was used determined the effect of isolation on pediculosis capitis infestations during quarantine and before the pandemic in Argentina, Buenos Aires. Data from 1118 children obtained from 627 surveys were analyzed. The overall prevalence of head lice decreased significantly from 69.6% before the COVID-19 pandemic to 43.9% during the COVID-19 pandemic. In addition, head lice infestations were more effectively controlled in households with up to two children than in households with three or more children. The restrictions that were applied consisted of the interruption of regular activities, which directly affected contact between children and thus the spread of head lice infestation .The situation in the USA was different from that in Argentina. A significant increase in the number of diagnosed cases of head lice infestation was observed during the lockdown period, in 2020. Head lice clinics in the USA reported an increase in the number of head lice infestations in the spring of 2020 by an average of 25% over pre-pandemic COVID-19 values. Head lice infestations affected entire families and were more severe during the pandemic due to prolonged cohabitation in households. The numbers reported are based on reports from 112 out of 200 clinics opened in April and May 2020. The stay-at-home order resulted in the spread of head lice infestation among households . Other dThe effect of lockdown on the spread of head lice infestation has also been tested in France. A population-based study was conducted by the indirect method of monitoring the sale of anti-lice drugs. The study period was 5 years including periods before and during the COVID-19 pandemic. Analysis of the database of the healthcare science company IQVIA Pharmaone LMPSO, which covers 14,000 pharmacies in France, was utilized. A clear decrease in sales, up to 50%, of topical anti-lice drugs and a less significant decrease in sales of ivermectin was observed during the periods of national isolation. However, other treatment options for lice infestation such as combing were not explored in this study. Additionally, the anti-lice treatments sold online were not included in the database ,33.In Israel, data comparing pediculicide sale numbers before and during the COVID-19 pandemic were used, as a possible marker for changing the epidemiology of head lice during the COVID-19 pandemic. The results of this study suggest that the extended isolation of children due to the COVID-19 pandemic significantly influenced the infestation rate of children with head lice .In the present study, we directly examined 5008 children from educational institutions. We revealed that the prevalence of infested children in kindergartens and schools decreased significantly during the COVID-19 outbreak period. The data presented in our study correlate with the results obtained by other authors and indicate that the restrictions applied during the COVID-19 pandemic had an influence on the head lice infestation prevalence among the studied children population. However, when analyzing the results and drawing conclusions, one should consider factors such as the study methodology used (direct or indirect examinations of the study population), the specificity of the tested population (adults or children and their socio-economic status), and the extent of restrictions introduced locally during the COVID-19 pandemic . The data on COVID-19 and pediculosis capitis presented by other authors and discussed in this study are based mainly on indirect methods of evaluation such as online surveys or the monitoring of prescriptions for lice treatment or sales of lice treatment medicaments. These methods of pediculosis capitis prevalence measurement are less reliable and loaded with more variables and bias elements than the direct examination that was utilized in our study. However, there are also limitations of our approach that we would like to bring forward. We did not choose the educational facilities randomly. Visits to the schools and kindergartens were performed “for cause”, which means that we visited facilities where infestations were suspected or initially detected by the educational staff. This methodological approach was necessitated by the widespread perception of direct examination of children’s heads expressed by the parents and might have influenced (overestimated) the obtained result of the overall pediculosis capitis prevalence. Another factor that might have influenced the prevalence rate was the accepted criteria for the positive identification of an infestation. As a positive sign of infestation, we counted both: the presence of live lice and/or the presence of eggshells/nits found alone. Therefore it is possible that the infestation rate was overestimated slightly, because if the parents had used an effective treatment, they may not have removed the eggs, and therefore, a “false” infestation diagnosis could have been made by the nurse. However, as the same methodology has been used by our nurses before and during the COVID-19 outbreak, the data obtained are comparable and valuable from an epidemiological perspective.It is also known that the studied population’s socio-economic status and other underlying conditions may influence the head lice infestation rate ,27,35. ITo the best of our knowledge, this study represents the first attempt to assess the influence of COVID-19 pandemic restrictions on the prevalence of head lice infestation among children using direct examination as the primary method of investigation, particularly on such a large population of children. The findings of this study revealed a statistically significant association between the prevalence of head lice infestation among the examined children and the period of the COVID-19 pandemic in Poland. The results of this study contribute to the growing body of knowledge on the effects of pandemic restrictions on various health issues, including pediculosis capitis. They highlight the importance of implementing effective measures to control head lice infestations and emphasize the need for ongoing monitoring and awareness efforts to address this persistent epidemiological concern.The restrictions implemented during the COVID-19 pandemic, which limited interpersonal contact, had an impact on the spread of head lice infestations among the tested groups of children. However, it remains unclear whether factors such as the separation of children into smaller groups or increased parental attention during lockdown contributed to the reduction in infestation rates compared to the period prior to the COVID-19 outbreak. The data obtained from our study affirm that head lice infestations continue to be an ongoing epidemiological concern that requires monitoring. Due to the lack of a standardized data collection system for tracking the prevalence of pediculosis capitis in Poland, periodic inspections of children in schools and kindergartens, similar to the ones carried out in this study, can serve as an important source of epidemiological data.


Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) is gaining popularity for the quantification of tissue perfusion, including foot perfusion in patients with lower extremity arterial disease (LEAD). However, the absolute fluorescence intensity is influenced by patient—and system-related factors limiting reliable and valid quantification. To enhance the quality of quantitative perfusion assessment using ICG NIR fluorescence imaging, normalization of the measured time-intensity curves seems useful.®. The effect of normalization on repeatability was measured in the nontreated foot in patients undergoing unilateral revascularization preprocedural and postprocedural (repeatability group). The effect of normalization on region selection was performed in patients without LEAD (region selection group). Absolute and normalized time-intensity curves were compared.In this cohort study, the effect of normalization on 2 aspects of ICG NIR fluorescence imaging in assessment of foot perfusion was measured: the repeatability and the region selection. Following intravenous administration of ICG, the NIR fluorescence intensity in both feet was recorded for 10 mins using the Quest Spectrum platformP = .002). Following normalization, the time-intensity curves in both feet were comparable for all 3 regions.Successful ICG NIR fluorescence imaging was performed in 54 patients . For the repeatability group, normalization of the time-intensity curves displayed a comparable inflow pattern for repeated measurements. For the region selection group, the maximum fluorescence intensity (Imax) demonstrated significant differences between the 3 measured regions of the foot (This study shows the effect of normalization of time-intensity curves on both the repeatability and region selection in ICG NIR fluorescence imaging. The significant difference between absolute parameters in various regions of the foot demonstrates the limitation of absolute intensity in interpreting tissue perfusion. Therefore, normalization and standardization of camera settings are essential steps toward reliable and valid quantification of tissue perfusion using ICG NIR fluorescence imaging. The feasibility of ICG for the assessment of tissue perfusion is explained by the binding to plasma proteins combined with a short half-life due to rapid clearance by the liver. Following intravenous administration of ICG, information about tissue perfusion can be obtained using either a qualitative or quantitative interpretation of the fluorescence intensity. Applications of qualitative interpretation include the assessment of skin viability in reconstructive surgery and the evaluation of bowl perfusion in gastrointestinal surgery.11 However, the qualitative and therefore subjective interpretation of the fluorescence intensity leads to different surgical outcomes and impedes comparison between studies. Quantitative assessment of perfusion focuses on describing the fluorescence intensity change over time in a region of interest (ROI), representing the dynamic properties of blood flow. Although the benefits of reliable quantitative analysis are evident, several factors influence the stability of the measured fluorescence intensity.8 These factors are either related to the patient or the camera system. Patient-related factors include skin type, edema, ICG concentration, and the presence of ulcers.15 The change in tissue properties can lead to an alteration in excitation energy and quantum yield, influencing the measured fluorescence intensity. Furthermore, the configuration of the camera system affects the measured intensity in several ways, including distance and angle to the target area, the distribution of illumination amongst the field of view, and the optical settings comprising the exposure time and gain.17 This abundance of influencing factors raises questions as to whether analysis of the absolute intensity is appropriate for reliable assessment of tissue perfusion.5 An emerging analyzing method for the assessment of tissue perfusion that adjusts for absolute intensity is normalization. Normalization sets the maximum fluorescence intensity at 100% and displays the fluorescence intensity over time as a percentual change. It is hypothesized that this method decreases the influence of aforementioned influencing factors and allows for more reliable and valid quantification. Therefore, the aim of this study was to investigate the influence of normalization on repeatability and region selection of ICG NIR fluorescence imaging for assessment of foot perfusion.Near-infrared (NIR) fluorescence imaging has been used as an imaging modality for various indications, including tumor visualization, identification of vital structures, and assessment of tissue perfusion.This cohort study was approved by the Medical Research and Ethics Committee of the Leiden University Medical Center and registered in the Dutch Trial Register (#NL7531). Patients undergoing unilateral revascularization procedures and non-lower extremity arterial disease (LEAD) control patients were included. Patients were included in a single academic hospital in the Netherlands from December 2018 until April 2021. Patients were excluded based on contraindications to ICG: allergy or hypersensitivity to ICG or (sodium) iodide; hyperthyroidism, autonomous thyroid adenoma, pregnancy, kidney failure (estimated glomerular filtration rate [eGFR] < 45), or severe liver failure. Informed consent was obtained from all individual participants included in the study.ICG NIR fluorescence imaging measurements were performed using the Quest Spectrum Platform . This system consists of an LED laser combined with a camera measuring light in the visible and NIR light spectrum (700-900 nm). All patients underwent ankle-brachial index (ABI)—and toe pressure (TP) measurements prior to the ICG NIR fluorescence imaging measurement. Upon ICG  administration, the camera registered the NIR fluorescence intensity change over time in both feet for 10 mins. All measurements were performed with the patient in a supine position in a darkened room. The camera was placed at approximately 50 cm of the foot, perpendicular to the dorsum of the foot. All videos were recorded using an exposure time of 145 ms and a gain of 22 db. ICG NIR fluorescence imaging was performed before—and after the procedure (<3 days), and patients were administered an intravenous bolus injection of 0.1 mg/kg ICG. Three ROIs were analyzed: (1) the dorsum of the foot, (2) the forefoot, and (3) the hallux.The effect of normalization on repeatability was measured in the nontreated foot of patients undergoing unilateral revascularization. It was hypothesized that the time-intensity curves in the nontreated contralateral foot remained unchanged. A subset of this group was described in an earlier study in which only normalized data were used.The effect of normalization on region selection was measured in non-LEAD control patients because this group is most likely to display a homogenous perfusion pattern in various regions of the foot. This group consisted of patients undergoing liver metastasectomy who were administered ICG intravenously 1 day before surgery. In this group, a bolus injection of 10 mg ICG was administered intravenously as part of the noninvestigational treatment protocol. Three regions were selected based on differences in camera distance and angle of the surface area to the camera. These regions included: (1) the hallux, (2) the first ray of the foot, and (3) the lateral foot.®  software was used for the quantification of the measured NIR fluorescence intensity. Following manual selection of an ROI, the software creates a curve of the fluorescence intensity change over time. The measured fluorescence intensity is displayed as arbitrary units (a.u.). When normalization is applied, the software sets the maximum fluorescence intensity in the selected ROI at 100% and displays the fluorescence intensity over time as a percentual change of this maximum fluorescence. The absolute time-intensity curves and normalized time-intensity curves with the extracted parameters are displayed in Supplementary Figure 1 and Supplementary Table 1. After normalization, absolute parameters including ingress and ingress rate are depleted. The normalized slope for the ingress and egress are defined as percentage per second. A tracker was used to ensure that the ROI was synchronized with foot movement, and baseline subtraction was applied. Starting time of the time-intensity curves was defined as an increase of 1 a.u. for the absolute time-intensity curves and 1% for the normalized time-intensity curves. Statistical analyses were performed using IBM SPSS Statistics 25 . Parameters in the repeatability group were compared with the Wilcoxon rank-sign test for paired analyses. Results for the region selection group were compared using the Kruskal-Wallis test.The Quest Research FrameworkIndocyanine green NIR fluorescence imaging was successfully performed in 54 patients. The patient characteristics for both the repeatability group and region selection group are displayed in P = .806; TP: 76 vs 72, P = .466). The results on repeated measurements for both the absolute and normalized time-intensity curves in the repeatability group are displayed in P = .587, ROI 2: 0.4 vs 0.6, P = .404). After normalization, the slope in all ROIs were comparable .For the repeatability group, no significant differences were found for the ABI and TP preprocedural and postprocedural . After normalization, a significant difference was seen for the slope egress in both feet . The normalized ingress slope was comparable for all ROIs .The absolute and normalized time-intensity curves for the region selection group are visualized in  This study found time-intensity curves to be repeatable and focused on time as well as absolute parameters. However, repeated measurements were performed in the same setting by the same investigator, thus reducing the impact of influencing factors of measurement setup on the NIR signal. Regarding the region selection, absolute inflow parameters in this study were all significantly different between various areas of the foot. After normalization, the slope ingress was comparable. For the interpretation of tissue perfusion with ICG NIR fluorescence imaging, these are important findings because absolute parameters can thus lead to an incorrect interpretation of actual tissue perfusion. In the search for reliable quantification of tissue perfusion with ICG NIR fluorescence imaging, an abundance of parameters have been studied in various target tissues. For the quantification of skin perfusion in patients with LEAD, for example, time-related and normalized parameters appear to be superior to measurements of maximum intensity.22 In reconstructive surgery, a commonly performed analyzing method for tissue quantification is the use of relative parameters. However, this method does not take into account the camera angle and distance, leading to a misperception of actual perfusion. In gastrointestinal surgery, the effect of normalization on quantification of bowl perfusion was measured in several studies.23 In a series of studies by Nerup et al on gastrointestinal perfusion in porcine models, the normalized slope ingress was significantly correlated with regional blood flow and local lactate levels.23 Although reliable quantification of tissue perfusion seems to tend toward the use of normalized parameters, several items have to be discussed. First of all, normalization of the time-intensity curves leads to alteration of data, which precludes the use of absolute parameters that can be useful in the prediction of tissue necrosis. Furthermore, normalization can be unreliable when the measured fluorescence intensity levels are below a certain threshold. Magnification of the signal can then lead to high fluctuations in the percentual change, which is the presumable cause of the significant increase in normalized egress slope in the region selection group in this study. In addressing the effect of normalization on region selection, the cohort in this study consisted of patients without known LEAD who were administered ICG as part of the treatment protocol for liver metastasectomy. By selecting this group of patients, this study avoided the exposure of healthy volunteers to ICG. However, due to comorbidities, there might have been changes in regional circulation of the foot that could have influenced the measured fluorescence intensity. Therefore, future studies on ICG NIR fluorescence imaging for foot perfusion assessment should ideally be performed in a control group that has a significantly lower risk of possible unknown underlying LEAD. Concerning the repeatability group, this study is limited by the small sample size. Besides, measurements were performed on different days postprocedural, which might have led to interpatient variability. Furthermore, changes in hemodynamic status, including blood pressure and pulse could have influenced the measured fluorescence intensity. Despite these limitations, this study describes a new perspective on assessment of tissue perfusion in the foot using ICG NIR fluorescence imaging. Improving reliability and validity of ICG NIR fluorescence imaging in quantification of tissue perfusion using normalization can promote comparability between studies. To compare standardized quantification methods between studies, it is also of paramount importance to report on the used camera system and—settings, including exposure time and gain. Addressing these aspects in future studies on perfusion assessment using ICG NIR fluorescence imaging is an essential step toward reliable quantification. Whether this quantification will lead to a better understanding of actual inflow and outflow of foot perfusion has yet to be determined. However, reliable quantification will be a crucial factor in the value of future studies on perfusion assessment with ICG NIR fluorescence imaging. Therefore, normalization should be a standard procedure in the analysis of the measured fluorescence intensity in these studies. The valid and reliable assessment of tissue perfusion using ICG NIR fluorescence imaging could then potentially aid in the prediction of clinical outcome following revascularization or in assessing the probability of wound healing.This study demonstrates the effect of normalization of time-intensity curves on both the repeatability and region selection in the quantification of tissue perfusion using ICG NIR fluorescence imaging. Concerning repeatability, time-intensity curves display a more similar pattern following normalization. Although not significant, absolute parameters including ingress rate and slope varied between measurements and displayed a wider distribution. These findings suggest that absolute parameters are less reliable and more susceptive to fluctuations on repeated measurements. The repeatability of ICG NIR fluorescence imaging for assessment of tissue perfusion in patients with LEAD was described in one earlier study.This study shows the effect of normalization of time-intensity curves on both the repeatability and region selection for the quantification of foot perfusion using ICG NIR fluorescence imaging. The significant difference between absolute parameters in various regions of the foot demonstrates the limitation of absolute intensity in interpreting tissue perfusion. Therefore, normalization and standardization of camera settings are essential steps toward reliable and valid quantification of tissue perfusion using ICG NIR fluorescence imaging.Click here for additional data file.Supplemental material, sj-docx-1-jet-10.1177_15266028221081085 for Normalization of Time-Intensity Curves for Quantification of Foot Perfusion Using Near-Infrared Fluorescence Imaging With Indocyanine Green by Pim Van Den Hoven, Floris Tange, Jurrian Van Der Valk, Nikolaj Nerup, Hein Putter, Catharina Van Rijswijk, Jan Van Schaik, Abbey Schepers, Alexander Vahrmeijer, Jaap Hamming and Joost Van Der Vorst in Journal of Endovascular TherapyClick here for additional data file.Supplemental material, sj-jpg-1-jet-10.1177_15266028221081085 for Normalization of Time-Intensity Curves for Quantification of Foot Perfusion Using Near-Infrared Fluorescence Imaging With Indocyanine Green by Pim Van Den Hoven, Floris Tange, Jurrian Van Der Valk, Nikolaj Nerup, Hein Putter, Catharina Van Rijswijk, Jan Van Schaik, Abbey Schepers, Alexander Vahrmeijer, Jaap Hamming and Joost Van Der Vorst in Journal of Endovascular Therapy


It is important to train gynecologists and urologists on the principles of urogynecological surgery.To report our recent experience in developing a curriculum, application, and the learning outcome of a urogynecology workshop using cadaver training.A full day structured urogynecology cadaver-based educational hands-on course was developed. The theoretical component consisted of lectures on female urinary incontinence and genital prolapse. Hands-on training was on three cadaver stations: First to instruct and guide through the surgical steps of transobturator vaginal tape; second to perform sacrospinous fixation; and third to insert of vaginal mesh. Knowledge gained was evaluated using multiple choice questions. The course was evaluated using a structured seven-point Likert type questionnaire.There was an a statistically significant improvement in the post-test MCQ marks compared with the pre-test marks (P <0.01) and in the pass percentage . The overall rating of the workshop was 6.7 out of 7.Our course was highly valued by the participants who came from all over the Middle East. The course was enjoyable and achieved its objectives while the participants gained new knowledge and surgical skills. Urogynecology, a subspecialty within obstetrics and gynecology, focuses on disorders of the female pelvic floor. Symptoms of pelvic floor prolapse, and female urinary incontinence are common among women Mannequins and training boxes are used to train surgeons of different specialties in performing new surgical skillsth Emirates International Urological Conference 2016 and was sponsored by the Coloplast Company, Dubai, UAE.A full day urogynecology cadaver workshop was held during December 2016 at University of Sharjah Clinical Training Center, United Arab Emirates. The workshop was announced as part of the 5Seventeen participants from the Middle east and North Africa having different specialties and levels of experience attended the workshop. Ten were urologists, five gynecologist and two obstetricians and gynecologists. Eleven participants were consultants, and six specialists. The theoretical component of the course was held in the morning. Its content is shown in The Practical sessions were held in the afternoon on three soft tissue preserved cadavers. . There wEach participant rotated around these three stations to practice each skill. Depending on the learning needs and individual interest, some participants spent more time at some stations. This was intended so that the curriculum offers a flexible and tailored course that matches the requirements of each participant.Harden et alThe participants provided baseline information regarding their gender, medical degree, country of origin, job title and attendance at previous relevant courses. The participants answered 20 multiple choice questions (MCQs) before and after completion of the course which were developed to cover the course content having face validity. Each item had 5 answer options. At the end of the course, participants responded anonymously to a structured questionnaire to evaluate the course. The questionnaire consisted of 14 statements and 3 open comments covering different aspects of the course. The participants answered each question on a seven-point Likert type scale .Data were presented as median (range) and mean (SD) as appropriate. We have used nonparametric statistical methods because of the small sample size and ordered nature of the answers of the questionnaire. These methods are suitable for sample size less than 20, ordinal data, and they do not need a normal distribution All participants filled the course evaluation. Fifteen out of 17 candidates completed the pre-and post-test MCQs. One of them passed the pertest MCQs while all 15 participants passed the post-test MCQs (P< 0.001). There was a statistically significant improvement in the post-test MCQ marks compared with the pre-test marks (median (IQ range) 86 (70-95) compared with 35 (15-55); p <0.01) .The participants' open-ended positive comments were as follows: excellent lectures and speakers, very polite trainers with humble attitude and great experience, good hands-on training, new procedures and techniques learned, excellent and practical training. They also gave the following suggestions to improve the workshop: more practical training, reducing the number of participants on each station, more training on genital prolapse surgery, and hands-on training in the hospital,To our knowledge, our structured urogynecology cadaver-based educational hands-on course is the first of its kind in the literature. This course was highly valued by the participants who came from all over the Middle East. The course was enjoyable and achieved its objectives while the participants gained new skills. Their prior knowledge on female urinary incontinence and pelvic floor prolapse was weak although half of them reported attending previous relevant courses. The knowledge on the topics of interest significantly improved after the course. MCQs are objective, reliable, and valid for assessing knowledge gained by educational programs Live operating theatres should not be the place to start learning surgical skills but rather to consolidate them. Gynecologist and urologist should reach competency before operating on live patients. This may be achieved by training on human cadaver which allows performing surgery in a real-life setting without stress or fear of causing injuries. Small groups allow individual candidates to have a good opportunity to be trained on specific surgical tasks. This was reflected on the highly positive evaluation of our course by the participants. Previous urogynecology cadaver workshops have focused solely on understanding anatomy while it was used to improve surgical skills in other specialties. Levine et al 2009 reported their experience in laparoscopic cadaver workshop which improved the surgical skillsCondous et al found, in a prospective observational study, that inexperienced participants benefit the most from skills training One of the limitations of our study is that we did not assess the clinical skills gained by the participants in the operating theatre Gynaecologists and urologists need knowledge and practical skills for less invasive techniques in urogynecology surgery. Our structured urogynecology cadaver-based educational hands-on course was highly valued by the participants who came from all over the Middle East. The course was enjoyable and achieved its objectives while the participants gained new skills.