In this cross-sectional study, 84 children with autism spectrum disorder (ASD) and 77 healthy subjects showing typical development (TD) were reviewed. Parents reviewed the age of introduction of complementary foods (CFs), completed a demographic, diet behavior questionnaire and the Autism Behavior Checklist (ABC). The results showed that the age of introduction of CFs was later in children with ASD than their TD counterparts. The age of introduction of CFs in ASD group was positively correlated with feeding problem. While the correlation was not observed in TD group. Children in the ASD group had higher total scores of the diet behavior questionnaire and all four subdomains . ASD symptoms were clearly associated with feeding problems. The sensory subdomain score in ABC was positively correlated with poor eating ability, mealtime behavior and total score of the diet behavior questionnaire. The social self-care subdomain score was positively correlated with food selectivity. The interaction subdomain score was negative correlated with parental feeding behavior and total score of the diet behavior questionnaire. Further studies are required to establish the utility of delayed CFs introduction and/or early feeding problems as potential indicators of ASD. Autism spectrum disorder (ASD) is a heterogeneous neurological developmental disorder typically characterized by difficulties in communication and socialization, frequently presenting traits including fewer interests, abnormal sensory processing, and repetitive behaviors . The preEating is a primary function in the human development. The period of early childhood is key in nutrition. Especially during the infancy phase, the children learn to ingest the fluid and solid food. It is not only crucial to the nutritional programming or metabolic programming, but also important to intellectual potential and physical fitness. The children should learn to ingest specific food and accept new tastes at specific age. Disruption of the process of learning to eat and accept new tastes during the critical “window” of opportunity can result in both oral-sensory and oral-motor dysfunction . The phyAt present, the researches on feeding problem of ASD children mostly focus on children over 3 years old. Research on early feeding disorders in ASD has been limited. Brzóska et al.  highlighN = 84) and healthy controls (N = 77). The data were collected from clinical notes of children between the ages of 2 and 5 who were diagnosed with ASD in the Department of Developmental and Behavioral Pediatrics  from October 2018 to April 2019. They were diagnosed by a multidisciplinary team following the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria. Regarding ASD severity level, 42 children (50%) had mild ASD, 33 children (39%) had moderate ASD, 9 children (11%) had severe ASD. Seventy-nine children (94%) had coexisting global developmental delay. The data of healthy controls that were collected from the clinical notes of the healthy children who were routine check-ups in the same hospital during the same time. Children with a history of other neurological and severe somatic disease, head trauma and uncontrolled seizures were excluded from study. The study protocol was approved by the ethics committee of the First Hospital of Jilin University and informed consent obtained from all parents.This was a cross-sectional study of children with ASD . Parents also completed a diet behavior questionnaire developed by Zhou et al. based on the Children's Eating Behavior Inventory (CEBI), Mealtime Behavior Questionnaire (MBQ), Children's Eating Behavior Questionnaire (CEBQ), Chinese version of the Identification and Management of Feeding Difficulties (IMFED), and adjusted according to Chinese dietary habits . Cronbact-test used for comparison between groups. Continuous variables with abnormal distributions are represented as the medians (P25–P75) and the Mann-Whitney U test used for comparison between groups. Categorical variables are represented as frequencies (percentages) and the χ2 test used for comparison between groups. Correlation tests were performed using Spearman's correlation analysis. Differences were considered statistically significant at P < 0.05.SPSS23.0 software was used for statistical analysis of data. Continuous variables with normal distributions are represented as the means ± standard deviations (SDs) and the two independent samples To manage possible differences between the two groups, we used generalized linear model (GLM) for further group comparisons to minimize the impact of other factors. We used the age of introduction of CFs and the scores of the diet behavior questionnaire as dependent variables, respectively, included categorical  on which the two groups differed significantly as factors and covariates, respectively and ran the regression models.p = 0.001) , birth weight, feeding patterns, family income, and degree of maternal and paternal education were observed between ASD and TD groups. The ASD group contained more boys than the TD group  .P > 0.05). The age of introduction of CFs of the TD group were lower than those of the ASD group   .B = −8.178, P < 0.05). Furthermore, subjects in the TD group had significantly lower scores for all four subdomains  compared to those in the ASD group . The age of introduction of CFs was positively correlated with the total diet behavior questionnaire score in the ASD group. Correlation analysis was further performed to determine the association between age of introduction of CFs and the four subdomains of the diet behavior questionnaire in the ASD group. Statistically significant correlation was observed only for mealtime behavior. Specifically, the age of introduction of CFs was positively correlated with the score for mealtime behavior  compared to subjects with TD, most children with ASD were introduced to CFs at a later stage, (2) age of introduction of CFs was positively correlated with total score of the diet behavior questionnaire and mealtime behavior in the ASD group, and (3) children with ASD showed more feeding problems than the TD group, which were associated with symptoms of ASD.Compared to children showing TD, those with ASD were introduced to CFs later, inconsistent with the report of Huxham et al.  showing We observed that the age of introduction of CFs was positively correlated with the total diet behavior questionnaire and eating behavior scores in the ASD group. While this correlation was not observed in TD group. Further investigation of the potential relationship between age of CFs introduction and symptoms of ASD (assessed via ABC scores) revealed no significant correlations. Delayed introduction of CFs may also be an early sign of eating and feeding problems in children with ASD.In our study, children with ASD presented with more eating and feeding problems than their same-age non-ASD peers. Total scores along with scores for all four subdomains  of children in the ASD group were consistently higher relative to the TD group, in keeping with empirical findings reported in the literature , 23–28. To our knowledge, this study is one of the first to report a significant association between age of introduction of CFs and feeding issues in children with ASD. The age of CFs introduction was positively associated with feeding problems in ASD group, not associated with feeding problems in TD group. The feeding problems were positively associated with symptoms of ASD. There may be some correlation between age of CFs introduction and symptoms of ASD. But our study did not find the correlation between age of CFs introduction and symptoms of ASD. It requires further investigation. Previous studies suggest that detection of early-life feeding problems is relevant for early diagnosis of ASD and could be potentially included as an ASD-specific screening tool (24). Our results may provide a preliminary point that the introduction of CFs can be included in detection of early-life feeding problems. Not just the time of introduction of CFs, but details of introduction of CFs. It requires further exploration. Feeding problems are additionally associated with symptoms of ASD. Accordingly, in clinical practice, the impact of ASD symptoms on feeding problems should be considered in comprehensive assessment and intervention approaches for children with ASD .Our study has several limitations that should be taken into consideration. Firstly, the sample size was relatively small and differences in the male-female ratio were observed between the two sample groups. Since ASD is generally more prevalent in boys, our clinical sample was not equally distributed between the sexes. Although we made adjustments in statistics, future studies including the sex matched control group will be better. Secondly, we only analyzed the age of introduction of CFs and did not include more detailed information. Thirdly, our study was performed at a single center and involved a relatively small number of subjects. Further detailed multicenter, large-scale clinical studies on samples with well-matched sex ratios are warranted. In addition, we did not include parents' eating habits which also affect feeding. Further studies including factors of parents' eating habits are needed.Our data reveal a delayed time of introduction of CFs in children with ASD. The age of CFs introduction is associated with later feeding problems. ASD subjects present more feeding problems than TD subjects, which are clearly associated with symptoms of ASD. Based on the collective findings, we propose that clinicians should pay attention to infants presenting with difficulties in adjusting to introduction of dietary CFs who may have more feeding problems later and give the parents some guidance.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of the First Hospital of Jilin University. The parents of participants provided written informed consent to participate in this study.XY and TW devised the project and the main conceptual ideas, worked out almost all of the technical details, and performed statistical analyses with assistance from FJ. XY, TW, LS, YX, and JF performed data collections and measurements. TW wrote the manuscript, with assistance from XY. All authors contributed to the article and approved the submitted version.The study was supported by the National Nature Science Foundation of China (81973054), Key Scientific and Technological Projects of Guangdong Province (2018B030335001), Effect of vitamin D regulating glutamate NMDA receptor on symptoms of autism rat model and its mechanism (20200201507JC).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.


Soft robots can create complicated structures and functions for rehabilitation. The posture perception of soft actuators is critical for performing closed-loop control for a precise location. It is essential to have a sensor with both soft and flexible characteristics that does not affect the movement of a soft actuator. This paper presents a novel end-to-end posture perception method that employs flexible sensors with kirigami-inspired structures and long short-term memory (LSTM) neural networks. The sensors were developed with conductive sponge materials. With one-step calibration from the sensor output, the posture of the soft actuator could be calculated by the LSTM network. The method was validated by attaching the developed sensors to a soft fiber-reinforced bending actuator. The results showed the accuracy of posture prediction of sponge sensors with three kirigami-inspired structures ranged from 0.91 to 0.97 in terms of  In recent years, with the development of compliant materials, soft robotics has been a research hotspot, especially for robots inspired by nature . Soft roThere are two main categories of on-board soft sensors based on the working mechanisms: (1) soft sensors that make use of electrical properties  neural network was used to perceive the strain of the attached objects. LSTM neural networks are unique recurrent neural networks (RNN) that can deal with sequential data, and such methods have already been adopted in soft sensor calibration for pressure/force sensing , robot pThis paper describes a set of flexible strain sensors incorporating a kirigami-inspired structure that were made from a piece of conductive sponge material, and a machine learning approach was used for calibration. In The kirigami-inspired structure and 3D porous structure were combined in our design to increase the stretching ability and reduce the tensile resistance. Classical flat-cutting kirigami patterns were designed using AutoCAD  with the main body dimensions of 15 × 20 mm. Two connector squares on the two ends of the main body were designed for the wire connection . By chanThe sensors were fabricated based on the planar fabrication paradigm ,37,38. LA soft fiber-reinforced bending actuator was designed and fabricated to test the performance of the kirigami-inspired sponge bending sensor. The design and fabrication of the actuator were the same as in our previous work  The actuThe relationship between the deformation of the kirigami-inspired flexible sensors and the bending angles of the actuator was developed. A schematic diagram of the actuator integrated with sensors is shown in h, for the length of the actuator’s top side L represent the overall length of the unstretchable layer.Since there is an unstretchable steel layer, the length of the actuator’s bottom side would be constant during deformation. When the thickness of the actuator is L = 75 mm and h = 16 mm. Based on Equations  SetupFinite element analysis (FEA) was performed to determine sensors’ stress/strain distribution during stretching. The finite element software Abaqus 2021  was used to examine the strain within the kirigami structure. The Yeoh 3rd-order hyperelastic model with the coefficients from Szurgott’s work in 2019  were useExperimental Setup to Determine the Resistance Responses of SensorsThe resistance responses of kirigami-inspired flexible bending sensors with respect to the bending angles of the soft actuator were explored. For sensors with the same kirigami pattern, two sensors with identical appearances were stuck to the top and bottom surfaces of the bending actuator shown in  and connIn this experiment, the performances of kirigami-inspired flexible sensors were determined. The experimental setup is shown in Mechanical Properties of Kirigami-Inspired Flexible SensorsThe resisting force generated by kirigami-inspired flexible sensors with respect to the deformation ratio is shown in Finite Element Analysis (FEA) ResultsThe results of the finite element analysis (FEA) are presented in Resistance Response of Kirigami-Inspired Flexible SensorsThe resistance response of the kirigami-inspired flexible sensors is shown in As mentioned in By comparing the performances of sensors with three kirigami-inspired structures, it could be concluded that the sensor with the “three-unit” kirigami cutting pattern had the best performance. Therefore, the sensors with such kirigami patterns were selected in the experiment for the prediction of the finger-joint angle. The wooden finger model was installed and connected to the soft bending actuator using Velcro. F is the resistive force  the flexible sensor should be flexible enough to minimize any resistive torque that affects the movement of the attached actuators; (2) the sensor should provide high enough accuracy to capture both the dynamic motion and the static posture of the attached actuators.The main advantage of the technology introduced in this paper is that the combination of a kirigami-inspired structure and 3D porous structure makes the sponge sensor have low resistance to actuator motion and provides excellent performance in stretching. Therefore, the posture prediction accuracy is higher than that of the kirigami-inspired conductive silicon sensor ,23 and eThe limitation of this method is that the sensor is required to be trained with a neural network before application. Data collection from the sensor to cover the measuring space in our current setup was 15 min, and the neural network training was 10 min (PC specification: Intel Core 10700 (CPU), Nvidia GeForce RTX 2080 Super (GPU)). Then, the system was ready to use.The sensor’s performance on actuators that can undergo three-degree-of-freedom (DOF) motion can be explored in a future study. Different materials could be compared to enhance the performance of the sensor.We used conductive sponge materials with kirigami-inspired structures and LSTM neural networks to monitor the dynamic motion of a bending actuator. Off-the-shelf materials and planar fabrication methods make it more convenient for these techniques to be applied to soft robotic systems. The usage of the calibration neural network provides an end-to-end calibration method and handles the nonlinear and hysteresis problems of the viscoelastic material with acceptable prediction accuracy. Postures for a wooden finger model were predicted, indicating an enormous opportunity to apply the kirigami-inspired flexible sponge sensors to various flexible exoskeleton systems. Overall, the sensory system developed in this paper is significant for soft robot posture perception and closed-loop control. We genuinely expect our work could be adopted and explored by other researchers to benefit the development of soft robotics.


Peripartum depression is a common complication of pregnancy with the potential for dangerous consequences to maternal and infant health if left untreated. The disorder was previously classified as a global public health issue due to the high prevalence of the disorder and the mismatch between available treatment options and successful completion of those options. The coronavirus disease 2019 (COVID-19) pandemic increased the incidence of mental health disorders globally, with an even greater effect on peripartum mothers. A preliminary study on fetal implications suggests the resulting increased maternal stress and depressive mood symptoms correlates to worsened fetal brain development. The pandemic highlighted existing barriers to the treatment of peripartum mood disorders. The drastic increase in the use of telemedicine as a modality of treatment in response to the public health crisis has the potential to address some of these barriers. Future global disasters are inevitable with peripartum mothers highly susceptible to worsened mental health outcomes. We are thus highlighting the responsibility of clinicians, professional organizations, and policymakers to support, identify, and facilitate the treatment of postpartum depression for this vulnerable population to prevent short-term and long-term repercussions. Although peripartum depression (PPD) was one of the most prevalent complications before the start of the coronavirus disease 2019 (COVID-19) pandemic, affecting roughly one in seven pregnancies, it remained vastly underdiagnosed and undertreated . PPD hasDuring the COVID-19 pandemic, the mental health of the general population in developed countries was negatively affected, with the prevalence of depression increasing seven-fold, from 3.34% in 2017 to a pooled 25% in 2020 . While tThe dangers of PPD on the patient and infant have been well-documented before the pandemic. Negative maternal outcomes involve substance abuse and self-harming behaviors, including suicide. Implications for the infant include poorer outcomes with social, emotional, language, and cognitive development, decreased infant safety practices, as well as maladapted maternal-infant bonding . ImportaBarriers to initiating treatment include the fear of the stigma that a patient is unable to appropriately function as a mother if diagnosed with a mental health disorder, travel and childcare restrictions, past poor experiences with healthcare professionals, and individuals of low socioeconomic status and racial/ethnic groups -6. IncreMental health is a traditionally underfunded and under-resourced field of medicine. Increased attention to mood symptoms is required for pregnant patients at even the best of times but particularly during global crises such as the COVID-19 pandemic. The responsibility for PPD identification and treatment falls on the shoulders of all healthcare system levels. Individual clinicians and healthcare systems must integrate administering a validated screening tool  into the clinic workflow to increase the identification and monitoring of the disorder; strategies include providing the tool for completion in the waiting room or during nurse intake. Telehealth is a potential resource to counteract certain barriers to care as well as minimize postpartum visit no-show rates and increase the opportunity to diagnose PPD. Healthcare systems can track PPD screening compliance and integrate reward programs for clinical teams with high rates of screening tool administration. Healthcare clinicians must have awareness of available resources offered by professional organizations. ACOG currently provides a Postpartum Toolkit containing information for the identification, education, and treatment of PPD . AdditioPostpartum depression is easily identifiable and treatable. If the pregnant population is neglected, the dire health consequences for both mother and infant are proportionally affected and cannot be ignored. Global crises similar to the COVID-19 pandemic are likely to occur again in the future. The healthcare system should be collectively prepared to take appropriate action for the increased prevalence of PPD now and in the future.


The impact of matrix material on the mechanical properties of natural-fiber-reinforced hybrid composites was studied by comparing their experimental, and numerical analysis results. In the present work hemp and flax fibers were used as reinforcement and epoxy resin and ecopoxy resin along with hardener were used as matrix materials. To study the influence of the matrix material, two sets of hybrid composites were fabricated by varying the matrix material. The composite samples were fabricated by using the compression-molding technique followed by a hand layup process. A total of five different composites were fabricated by varying the weight fraction of fiber material in each set based on the rule of the hybridization process. After fabrication, the mechanical properties of the composite samples were tested and morphological studies were analyzed by using SEM-EDX analysis. The flexural-test fractured specimens were analyzed by using a scanning electron microscope (SEM). In addition, theoretical analysis of the elastic properties of hybrid composites was carried out by using the Halpin–Tsai approach. The results showed that the hybrid composites had superior properties to individual fiber composites. Overall, epoxy resin matrix composites exhibited superior properties to ecopoxy matrix composites. Natural fiber composites have gained much popularity in recent times due to concerns about the environmental impact of synthetic fiber composites ,2. CompoIn a composite material both the reinforcement and matrix materials play a crucial role. The reinforcement material acts as the load-carrier whereas the matrix material acts as the load-distributer when an external load is applied to the composite ,13. The The static and dynamic mechanical properties of the polymer composites reinforced with natural fibers are mostly the result of the quality and quantity of fiber materials ,20, in aThe chemical composition of natural fibers plays a prominent role in plant-based fiber composites, but environmental conditions such as climate dissimilarity and geographical changes influence the composition of natural fibers . Hence, Recently, several researchers have shown an interest in working with natural fiber composites in the presence of thermoset polymers. Although there are many advantages with natural fiber composites the applications are still limited due to moisture uptake and flame-retardancy properties. Yihui et al.  developeZhong et al.  reviewedFrom the above literature, two significant points are perceived. One is that the mechanical properties of natural fibers can be improved by using a hybridization process and the second is that the numerical and theoretical analysis of natural fibers can be done by assuming definite properties through finite element analysis and micromechanics. With this this information, the main objective of our research on the effect of matrix materials on natural fiber hybrid composites was defined. This objective was to understand the impact of matrix material on the mechanical properties of the natural-fiber-reinforced epoxy and ecopoxy hybrid composites. For this study, hemp and flax fibers were used as reinforcements, and to draw the contrast between matrix materials, epoxy and ecopoxy materials were used as matrix materials. The results are assessed by using experimental and numerical methods. The mechanical properties of hybrid composites were tested by using flexural and interlaminar shear properties. The wettability properties are tested by using contact angle measurement and the morphological studies were carried out with SEM-EDX spectrum analysis. Theoretical analysis of composite materials was estimated by using Halpin–Tsai method and the effect of matrix material on mechanical properties of natural fibers hybrid composites was addressed.To carry out the current research work, hemp and flax fibers were procured from Naturalus Pluostas UAB, Vilnius, Lithuania. The epoxy resin and its hardener were procured from Composite 24, Riga, Latvia and the ecopoxy (the bio-based resin contained 36% of bioactivity) resin along with hardener was procured from EcoPoxy EU. Warsaw, Poland. Teak wood was used for the preparation of mold material.The reinforcement materials were available in the form of a bundle. Each fiber was carefully chosen by eliminating the unwanted materials, such as the thick stems and small pellets by using the hand sitting process. Once the waste materials had been separated from the fibers, water treatment was carried out and the fibers were dried until the moisture was eliminated. However, the fibers were still not ready for fabrication due to their smooth surface finish and poor adhesive properties. Therefore the separated fibers underwent a chemical treatment process. The fibers were treated with a 5% NaOH solution and then cleaned with distilled water. After alkaline treatment, the fibers were dried in an oven ready for the fabrication process.The matrix materials used for the fabrication process were epoxy and ecopoxy resin along with hardener material. The weight portion of both the matrices was considered a 2:1 ratio as per the material description provided by the company from which they were procured. The required amount of resin and hardener were put into a plastic container and stirred with a plastic stirrer for 4 minutes and the walls of the container were scratched properly to get the proper mix and left for two minutes to allow the clear solution to settle. The process was repeated for both matrix materials. Once the mixed solution had settled it was taken for the fabrication process.The weight fractions of the reinforcement and matrix materials were considered as per the rule of the hybridization process. This states that a composite sample is fabricated by using two or more fiber laminates under the same resin material with a 0.4 Wf.% ,51. In tTo measure the flexural properties such as flexural strength and modulus of the composite samples, a universal testing machine (Tinus Olsen H10K) was used. To test the samples, the 3-point bending test was preferred over the 4-point bending test because the external load acts at the center of the composite so load distribution was uniform . The tesTo calculate the interlaminar shear strength of composite material, a universal testing machine with a full load capacity of 10 KN was used. To test the samples, the composite was fixed on both ends in between the jaws of the testing machine, and the load was applied in an axial direction from one end and the lower end was fixed. The samples were tested as per standard ASTM D-3846 . The recThe wettability properties of composite material were tested by using the contact angle measurement process. This provides quantitative information on interfacial energy between a fluid drop and composite surface . A varieA scanning electron microscope (SEM) from Bruker, Billerica, MA, USA was used to investigate the morphology of both the composite surface and the fractured sample. The element composition the surface of each composite sample and the facture position were evaluated by using SEM-EDX spectroscopy. The error % connected with the elemental composition analysis was evaluated.Numerical analysis of natural fiber composites was carried out by the using micromechanical method i.e., the Halpin–Tsai approach. Although there are many methods available to predict theoretical analysis, these are easy to apply to natural fiber composites. To calculate the elastic properties the basic assumptions must be considered as the composite sample was isotropic and homogeneous, as well as being linear elastic in nature ,59. We mη isHalpin–Tsai method ,61,62 the final equation will be as follows:fE and mE are the Young’s modulus of fiber and matrix material, respectively. fV and mV are volume fractions of fiber and matrix material, respectively. ζ is an arbitrary variable, also called an empirical factor considered based on the assumptions. The ζ values are taken as 0, 1, 2, and so on. The modified Halpin’s equation is as follows:By substituting the fE1, fE2, and mE are Young’s modulus of hemp fiber and flax fiber, and the matrix material, respectively. fV1, fV2, and mV are the volume fractions of hemp fiber, flax fiber, and matrix material, respectively. In the present work, an attempt has been made to check the extent of the modified Halpin’s equation to the natural fiber hybrid composites. The test was conducted by assigning properties such as Poisson’s ratio, young’s modulus, density, bulk modulus, and shear modulus to the material. The values are given in The flexural strength and flexural modulus of hemp and flax hybrid composites with various weight fractions in the presence of epoxy resin matrix and ecopoxy resin matrix are shown in Scanning electron microscope analysis of flexural test specimens of epoxy matrix composites is illustrated in The experimental results of epoxy and ecopoxy-based hybrid composites obtained from interlaminar shear tests are presented in To analyze the wettability properties of a composite material a contact angle measurement was conducted on the hemp and flax fiber composites and the results are illustrated in Morphological studies on individual hemp- and individual flax-fiber-reinforced epoxy composites at the surface position and the fracture position were carried out by using the scanning electron microscope energy dispersive X-ray spectroscopy and the results are shown in To determine the chemical composition and element analysis of the composite material, EDX spectrum analysis is usually preferred. The chemical composition and error % of the hemp and flax fiber epoxy composites are given in The morphological studies on individual hemp- and individual flax-fiber-reinforced ecopoxy matrix composites at the surface position and fracture position were carried out by using SEM-EDX spectroscopy and the results are shown in The chemical composition and error % of the hemp and flax fiber ecopoxy composites are given in Overall, the defect percentage was greater in the ecopoxy composites than in the epoxy composites; hence, the strength of the composite was decreased in the ecopoxy case. Due to the biological nature of the ecopoxy resin material the percentage of oxygen was greater in ecopoxy composites than in the epoxy composites.Numerical analysis was carried out by using the modified Halpin’s method. The values are presented in The data presented in The percentage error was calculated for epoxy and ecopoxy hybrid composites. The error was calculated by taking the ratio of the difference between numerical values and experimental results. The maximum error % of elastic properties was observed in pure composites such as 0H/40F and 40H/0F in both epoxy and ecopoxy hybrid composites and the lowest was observed in 25H/15F epoxy hybrid composites. In the case of hybrid composites, the error % was similar whereas in pure composites it was different.Most of the previous research work has have been carried out on natural fiber reinforced thermosetting or thermoplastic hybrid composites. Natural fibers such as banana, okra, jute, bamboo, and pineapple were used as a constituent of composite material ,65,66. TThe hemp- and flax-fiber-reinforced epoxy composites showed superior properties to the ecopoxy hybrid composites. In addition, hybrid composites exhibited superior properties to individual fiber composites. The results showed that epoxy-based hybrid composites had flexural strength properties ranging from 58 MPa to 80 MPa whereas in the previous research this was between 45 MPa to 64 MPa. Similarly, there was also a considerable development in the interlaminar shear properties. From contact angle measurement analysis, previous results showed that all the natural fiber composites exhibited hydrophilic surface properties (contact angle less than 70 degrees). However, in the current research, ecopoxy hybrid composites showed a contact angle close to 90 degrees which means that composites tend to show hydrophobic surface properties.In the present research work, the effect of matrix material on the mechanical properties of composite material was investigated by drawing a comparison between the epoxy-resin-matrix natural fiber composites and ecopoxy (bio-resin)-resin-matrix natural hybrid fiber composites. The results are given below.Epoxy-matrix-based hybrid composites showed superior mechanical properties to ecopoxy-matrix-based hybrid composites. It was observed that the mechanical properties of epoxy-resin hybrid composites were almost two times greater than ecopoxy composites. In both cases, pure composites showed the poorest mechanical properties such as flexural strength and interlaminar shear strength and hybrid composites exhibited the maximum strength and shear properties. In the case of epoxy composites, the maximum flexural and shear strength were observed as 78 MPa and 13MPa, respectively, whereas in the case of ecopoxy composites, values were 30MPa and 10 MPa, respectively. The wettability properties of natural fiber hybrid composites were investigated by conducting contact angle measurement. The results showed that all the composites showed hydrophilic (θ < 90˚) surface properties. The morphological studies and chemical composition presented in the composites were investigated by using SEM-RDX spectrum analysis.To validate this research work, a numerical analysis was carried out including the experimental analysis. Theoretical studies were carried out to determine the elastic properties based on the modified Halpin–Tsai method. It was observed that the error % was less with the numerical methods but in the case of Halpin’s method, it was more. Hence Halpin’s method is not suitable for predicting the elastic properties of natural fiber polymer composites.Overall epoxy-based natural hybrid composites showed improved mechanical properties compared to ecopoxy-based hybrid composites. Hence the hemp and flax fiber reinforced epoxy matrix composites could be a potential replacement for synthetic fiber composites in various industries such as the automobile, construction, microfluidics, and biomedical industries.


When listening to music, people are excited by the musical cues immediately before rewarding passages. More generally, listeners attend to the antecedent cues of a salient musical event irrespective of its emotional valence. The present study used functional magnetic resonance imaging to investigate the behavioral and cognitive mechanisms underlying the cued anticipation of the main theme’s recurrence in sonata form. Half of the main themes in the musical stimuli were of a joyful character, half a tragic character. Activity in the premotor cortex suggests that around the main theme’s recurrence, the participants tended to covertly hum along with music. The anterior thalamus, pre-supplementary motor area (preSMA), posterior cerebellum, inferior frontal junction (IFJ), and auditory cortex showed increased activity for the antecedent cues of the themes, relative to the middle-last part of the themes. Increased activity in the anterior thalamus may reflect its role in guiding attention towards stimuli that reliably predict important outcomes. The preSMA and posterior cerebellum may support sequence processing, fine-grained auditory imagery, and fine adjustments to humming according to auditory inputs. The IFJ might orchestrate the attention allocation to motor simulation and goal-driven attention. These findings highlight the attention control and audiomotor components of musical anticipation. Arousal and attention to reward cues play a substantial role in human reward pursuit. Spectators on the golf course focus on the long putt and almost forget to breathe. When listening to music, people tend to be excited by the musical cues prior to rewarding passages. For example, the peak pleasurable experiences of electronic dance music (EDM) are linked to two musical sections: the build-up and the ensuing drop. The rewarding drop section was found to elicit maximal skin conductance responses in listeners, while some listeners experienced chills and an urge to move their bodies during the final bars of the build-up section that announce the coming of the drop . The antThe anticipation of a salient musical passage may entail audiomotor processes irrespective of its emotional valence. Tracking the sequence of antecedent cues and the salient passage may be performed via motor simulation such as covert humming along with the music, especially when the listener is familiar with the piece. This is analogous to the anticipation of the motion of a table tennis ball, in which anticipation performance is based on the recruitment of sensorimotor representations in the premotor cortex . AlthougOne kind of salient event in music is the recurrence of a main theme, which is often easy to memorize and imagine. In Western classical music, the main theme’s recurrences manifest significant structural and emotional effects. Notably, the musical cues immediately before the main theme’s recurrences are designed to foster the listener’s motivation and cognitive organization towards anticipating the main theme. Using functional magnetic resonance imaging (fMRI), the present study aimed to identify the neural correlates of the cued anticipation of the main themes during listening to familiar music. All musical stimuli in the present study were selected from compositions written in sonata form. Developed in the late eighteenth century, the sonata form became one of the most important forms in Western classical music. The most dramatic moment of this form is typically around the coincidence of the main theme’s recurrence and the harmonic resolution at the start of the recapitulation section . The pasThe thematic and harmonic resolution at the recapitulation’s start can be regarded as a goal of the listening experience of sonata form. Smith  drew parThe participants were recruited via a public announcement on the internet, which stated that the research goal was to examine the neural responses to sonata form and that a requirement of participants was a high familiarity with Western classical music. To evaluate this requirement, we asked volunteers to express and explain their feelings in response to the musical stimuli in the present study. An online questionnaire was used to collect these data. This questionnaire began with a brief introduction to the musical structure of the first-movement sonata form. The introduction mentioned that (1) this musical form consists of three main sections ; (2) the themes presented in the exposition recur in the recapitulation; and (3) the passage prior to the recapitulation often intensifies the moving power of the main theme’s recurrence. Eight musical stimuli were presented in a fixed order, with the minor-mode excerpts alternating with the major-mode excerpts. After listening to each stimulus, the volunteers were asked to write down their feelings in response to the retransition and their feelings in response to the main theme’s recurrence. They were also asked to explain their feelings in terms of musical features, such as tempo, tonality/mode, melody, rhythm, timbre, articulation, and dynamics. The volunteers were allowed to listen to the stimulus repeatedly before answering these questions. This online questionnaire was expected to familiarize the volunteers with the experimental stimuli, and the data collected were used for participant screening. The correspondence author of this article selected participants according to the following inclusion criteria: (1) more than five passages immediately before the recapitulation evoked a keen sense of anticipation; (2) the recurrence of more than five themes evoked a feeling of resolution; and (3) their feelings were appropriately explained in terms of musical features for more than five excerpts.Thirty-one adult volunteers completed this questionnaire. Twenty-seven volunteers met our screening criteria. Twenty participants completed the fMRI experiment. They were free from neurological, psychiatric, or auditory problems and there were no abnormalities in their structural MRI. Fifteen of them had studied musical instruments for six years or more. Written informed consent was obtained from each participant prior to participation in the study. The participants were compensated with approximately USD 16 after the completion of the fMRI scan. Data from two participants were discarded because of excessive head movements. Therefore, the final sample analyzed in this study consisted of 18 participants . All the research procedures were performed in accordance with a protocol approved by the Institutional Review Board of National Taiwan University (201611HM008). This study was conducted in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki).The musical stimuli consisted of four minor-mode and four major-mode excerpts from masterpieces in Western classical music. It was presumed that the minor-mode and major-mode excerpts possess tragic and joyful characters, respectively. The correspondence author of this article (a musicologist) selected the music excerpts from the first movements of famous symphonies and concertos composed in the classical or early romantic period. The following selection criteria for the musical stimuli were used: (1) the first movement was written in sonata form; (2) the tempo was faster than 90 beats per minute; (3) the final passage of the development produced high musical tension; (4) the main theme (first theme) was played at a moderate to high intensity level; and (5) the main theme was of a joyful character (in a major-mode key) or a tragic character (in a minor-mode key). The selected musical stimuli included eight excerpts .All the musical excerpts were extracted from commercially available recordings, digitized  and edited by GoldWave . They were taken from the first movements of symphonies and concertos composed between 1772 and 1858 and written in sonata form. Each excerpt in the present study consisted of an 18 s passage of the concluding portion of the development leading back to the first theme (main theme) and a 12 s passage of the ensuing recapitulation . A briefWe followed a prior study  to use rPrior to the MRI scan, the participants listened to all of the musical stimuli in the same order as that in the online questionnaire. They were asked to rate their agreement with four statements on a seven-point Likert scale  after the presentation of each stimulus: (1) I am very familiar with this music; (2) I felt strong anticipation before the theme came out; (3) the theme is very tragic sounding; and (4) the theme is very joyful sounding.There were five fMRI scanning sessions separated by 1 min rest intervals, as schematically illustrated in The experiments were performed using a Siemens 3T MRI Prisma at National Taiwan University. A gradient-echo echo-planar imaging (EPI) sequence was used in the functional data scanning. Approximately 2.5 mm slices of axial images were acquired in the functional scans using gradient-echo planar imaging with the following parameters: time to repetition = 2500 ms, echo time = 30 ms, flip angle = 87°, in-plane field of view = 192 × 192 mm, and acquisition matrix = 78 × 78 × 45, to cover all the cerebral areas. Magnetization-prepared rapid gradient echo T1-weighted imaging with an isotropic spatial resolution of 0.9 mm was acquired for each participant for spatial individual-to-template normalization.t-tests were used to examine whether the sound intensity and brightness varied significantly across the antecedent cues of the main themes and the middle-last part of the main themes.We used MIRtoolbox  to estimp < 0.05/6 = 0.0083 was used to account for these comparisons.Wilcoxon rank sum tests were used to examine whether the participants’ scores regarding familiarity with musical excerpts, anticipation of all of the themes, the tragic character of the minor-mode themes, the joyful character of the minor-mode themes, the tragic character of the major-mode themes, and the joyful character of the major-mode themes differed significantly from a neutral score of 4. A Bonferroni-corrected significance threshold of The preprocessing and analyses of the fMRI data were performed using SPM12  and the Artifact Detection Tools (ART) toolkit. The first four volumes of each run were discarded to allow for magnetic saturation effects. The remaining functional images were corrected for head movement artefacts and timing differences in the slice acquisitions. The preprocessed functional images were coregistered to the individual’s anatomical image, normalized to the standard MNI brain template, and resampled to a 2 mm isotropic voxel size. The normalized images were spatially smoothed using a Gaussian kernel of 5 mm full-width at half maximum to accommodate any anatomical variability across participants. The ART toolkit was used to check the spikes and motion of each dataset. Eighteen functional datasets showed head motion below 2.5 mm of the maximal translation (in any direction), below 1° of maximal rotation throughout the course of scanning, and no outliers occurred. These images were used in the following analyses.t-tests for (1) the contrast of theme anticipation minus control, (2) the contrast of the middle-last part of the main themes minus control, and (3) the contrast of theme anticipation minus the middle-last part of the main themes. Results were reported as significant at a voxel-wise threshold level of p < 0.001 uncorrected and cluster-level threshold of p < 0.05 false discovery rate corrected.Statistical inference was based on a random effect approach at two levels. The data of each participant were analyzed using the general linear model via fitting the time series data with the canonical hemodynamic response function (HRF) modelled at the relevant blocks in the stimulation paradigm . The blop > 0.5, detailed in The sound intensity and brightness did not significantly differ across the antecedent cues of the main themes and the middle-last part of the main themes  were associated with significantly greater activity in the bilateral superior temporal gyri, right anterior insula, left putamen, bilateral pre-supplementary motor area (preSMA), bilateral middle frontal gyrus , and left posterior cerebellum as compared to the control. The middle-last part of the main themes was associated with significantly greater activity in the anterior portion of the bilateral superior temporal gyri as compared to the control. The right anterior thalamus, right putamen, right caudate, bilateral preSMA, bilateral posterior cerebellum, bilateral inferior frontal junction (IFJ), and left superior temporal gyrus (auditory cortex) showed significantly increased activity for the theme anticipation condition, relative to the middle-last part of the main themes . The timDuring exposure to familiar music, the listener often attentively tracks the main theme’s recurrences that have structural and affective significance in musical pieces. Motor simulation and attention control processes may be engaged in the cued anticipation of the main theme’s recurrences. To better understand the behavioral and cognitive mechanisms underlying this anticipation, we used fMRI to examine the neural responses to the concluding bars of retransitions in sonata form. A retransition encompasses musical cues that foster the listener’s motivation and cognitive organization of the main theme’s recurrence. Compared to the control condition of atonal random music, the cued anticipation of the main themes during the retransitions was associated with enhanced activity in the anterior insula, premotor regions, and posterior cerebellum. This finding bore a remarkable similarity to the network that commonly subserves predictive coding in action perception, language, and music . MoreoveA novelty of the present study was the use of both positively and negatively valenced musical excerpts as stimuli. The greater activity in the right anterior thalamus during the anticipation of joyful and tragic main themes than during the middle-last part of these themes may reflect its role in the anticipation of salient events. The right anterior thalamus has been found to be involved in itch processing , anticipSince the participants were familiar with the sonata-form stimuli, they were likely to track the sequence of antecedent cues and theme recurrence via covert humming along with music. As expected, we observed greater activity in the premotor cortex, preSMA, and posterior cerebellum during the theme anticipation condition relative to the control stimuli. These areas have been implicated in covert or overt rehearsal of familiar music ,27,28 anThe preSMA and posterior cerebellum showed greater activity for the theme anticipation condition than for the middle-last part of the main themes. It is well recognized that the preSMA supports domain-general sequence processing . The posThe cerebellum is implicated in the prediction of sensory outcomes as a consequence of motor command, and this predictive computation is known as an internal forward model . During An interesting finding of the present study was the involvement of the bilateral IFJ in theme anticipation. Accumulating evidence suggests that the IFJ plays an essential role in tasks requiring cognitive control such as working memory and task switching ,42,43. TWhen comparing the theme anticipation condition to the middle-last part of the main themes, exclusively left-sided activation was observed in the auditory cortex and dorsal premotor cortex. It has been found that responses of the human auditory cortex to rapid temporal information were weighted towards the left ,47. MoreIn light of the incentive-sensitization theory of addiction , our resThere were several limitations of this study that need to be pointed out. First, the final sample of the fMRI data consisted of 18 participants, and the sonata-form stimuli were extracted from only eight compositions. Future research should increase the sample size of participants and musical stimuli. Second, the present study lacked behavioral data about the participants’ affective/motivational states and the vividness of the auditory imagery during fMRI scanning. We did not ask the participants to respond after stimulus presentation because we were concerned about the distracting effect of self-monitoring for rating tasks. Third, we did not analyze the IFJ’s functional connectivity to the thalamus, premotor regions, posterior cerebellum, or auditory cortex. Therefore, the IFJ’s specific contributions to driving and coordinating cognitive and audiomotor processes remain unclear. We suggest that future research could be devoted to the parcellation of the bilateral IFJ using musical stimuli imbued with incentive salience.In conclusion, the present study focused on listeners’ cued anticipation of the main theme’s recurrence. While partially consistent with the putative prediction network underlying action perception, language, and music , our res


Today, the rational combination of materials and design has enabled the development of bio-inspired lattice structures with unprecedented properties to mimic biological features. The present study aims to investigate the mechanical performance and energy absorption capacity of such sophisticated hybrid soft–hard structures with gradient lattices. The structures are designed based on the diversity of materials and graded size of the unit cells. By changing the unit cell size and arrangement, five different graded lattice structures with various relative densities made of soft and hard materials are numerically investigated. The simulations are implemented using ANSYS finite element modeling (FEM)  considering elastic-plastic and the hardening behavior of the materials and geometrical non-linearity. The numerical results are validated against experimental data on three-dimensional (3D)-printed lattices revealing the high accuracy of the FEM. Then, by combination of the dissimilar soft and hard polymeric materials in a homogenous hexagonal lattice structure, two dual-material mechanical lattice statures are designed, and their mechanical performance and energy absorption are studied. The results reveal that not only gradual changes in the unit cell size provide more energy absorption and improve mechanical performance, but also the rational combination of soft and hard materials make the lattice structure with the maximum energy absorption and stiffness, in comparison to those structures with a single material, interesting for multi-functional applications. Mechanical meta-materials demonstrate unprecedented mechanical properties that directly originate in their geometrical designs at different scales, in particular, small scales that are engineered to achieve unusual properties at the bulk  ,2,3. SomArchitected mechanical (multi) meta-materials, possessing a combination of several properties such as light weight, toughness, stiffness, damage tolerance and energy absorption have recently received the most attention for multifunctional applications in biomedicine, aerospace, automotive and civil engineering . MechaniToday, to produce advanced mechanical meta-materials, additive manufacturing (AM) technology  printing) opens a new window in the production of such sophisticated structures. The most popular AM methods for fabricating lattice structures with geometrical complexity are powder-based ) and filament-based ) . MoreoveFrom the design point of view, there are various architectures with different cell topology such as auxetic and honeycomb, which already are being used in the literature ,31,32,33Considering the open literature, there are a lot of studies on the investigation of mechanical performance and energy absorption of single material lattice structures and even with FG properties. However, multi-material mechanical lattice structures recently have increasingly gained attention as they provide more design freedom for tuning structural behavior. Therefore, the combination of different materials (soft and hard) and graded size could make promising light-weight structures with tunable and distinctive mechanical properties. In the present study, the mechanical performance  and energy absorption capacity of five types of graded cellular structures with soft and hard materials and two types of dual-material lattice structures are investigated. Mechanical lattice structures are made of thermoplastic co-polymer (TPC) as a soft material and polyamide (PA12) as a hard material with diversified mechanical properties. Five types of graded structures are rationally designed based on the gradual changes in the unit cells size and arrangement. Then, the mechanical performance and energy absorption capacity of each topologically designed structures are investigated by FEM for each material and verified by the experimental data on 3D printed lattice structures.To design the structures in the present paper, hexagonal cells with different unit cell length sizes and the same overall dimensions of Furthermore, two dual-material lattices structures are designed by changing the distribution of materials  which are shown in 3D finite element analysis is carried out using ANSYS Explicit Dynamics . The explicit dynamics module used in the numerical software method controls the environment to ensure the simulations remain quasi-static, and the physics of the problem do not change. The criterion is through time scaling to speed-up the explicit solver; there is an energy summary which was checked. The kinetic energy is only a small portion of the internal energy suggesting that the inertia forces are small, and the simulation does in fact maintain a quasi-static scenario with the given explicit speed. One major advantage of this tool over static structural is the penetration mechanics of a higher structural penetration detection. In explicit dynamics, it is easier and more efficient to detect self-contact interaction within the energy absorbing lattice structure. Originally the static structural tool on ANSYS was used to carry out the quasi-static compression of all five samples. The simulations roughly required three hours each; however, one major problem that occurred was the inability of the solver to apply self-contacts on large deformations of the lattice, and this led to self-penetration of the structure being compressed eventually distorting the mesh greatly reducing accuracy and causing other solver errors. The improvement of shifting to the explicit dynamics tool resolves the mesh distortion and self-penetration problem where the lattice was able to be compressed and experience large deformations.5 Pa and 5.223 × 106 Pa, respectively. The incompressibility parameter To setup the quasi-static simulation, first the material data are imported using uniaxial test data of the both types of materials . To model TPC, a hyperelastic constitutive model, Mooney–Rivlin with two terms  to achieve a faster solving time by reducing the number of elements within the mesh. However, an additional displacement condition was applied across the X direction to account for the central part moving along both the X and Y directions, which ensures the sample nodes are not restricted in the X-position and are free to move in Y. It was noted that there is no difference in using either a full model or a half model as they both result in the same deformation. To obtain the total force, further post processing in doubling the final force displacement graph to achieve the simulation of the lattice compression for the full model is required. The advantage this provided is a major reduction in the quantity of nodes and elements used which reduces the solver time to half the amount required to complete the 50% model. In addition, having the number of elements reduced allowing for improvement in the mesh quality and using a denser mesh such as one having 3–4 elements across the thickness of the wall. This ensures more accurate data are obtained across each element, and deformations are easier to detect at distinct points around the nodal locations of the lattice structure. Another possible idea that is considered during the simulation is using the mid-surface feature. Since there are quite a few thin solid beams on the lattice structure, the mid-surface allows conversion from solid to shell elements hence greatly reducing solver time and providing an improvement in detecting deflection across the lattice energy absorber. It should be mentioned that regarding the mesh type used in the present study, mesh type QUAD 4, solid linear elements with a medium span angle center and smoothing set to high were used  condition where the stability of a time step for explicit dynamics analysis is In this section, all the results of mechanical compression test and energy absorption capacity of the five graded size lattice structures for single material (TPC and PA12) and dual-material mechanical lattice structures are presented. Since TPC and PA12 are very different from a material point of view, we aimed first to investigate the mechanical performance of the rational designed structures made by each material. Additionally, it is worthwhile to add both materials together in a dual-material structure for which the corresponding results are presented in Here, the mechanical tensile test and energy absorption of the five types of graded size lattice structures for TPC and PA12 are separately presented. The numerical results including mechanical uniaxial force-displacement and energy absorption and their comparison with the experimental data of the TPC-based structures are shown in In the force-displacement plots see , there aThe numerical results comparison with the experimental data and their configuration during the loading of the PA12-based structures are shown in In this part, the mechanical compression test and energy absorption of the two types of dual-material mechanical lattice structures based on the combination of TPC and PA12 are presented  have higher energy absorption compared to their corresponding single material. Meanwhile, the present numerical results for such complex structures and non-linearity have a good agreement with the corresponding experimental data. Moreover, the coupled phenomena including geometrical non-linearity, densification and plastic deformation cause overall hardening up to the end of the loading. In conclusion, although  graded size lattice structures have a higher mechanical performance in comparison with regular lattice structures, functionally graded soft-hard lattice structures give the highest potential for energy absorption applications.


Therefore, TADs are proposed as structural scaffolds for the establishment of regulatory landscapes (RLs). In this review, we discuss recent advances in the connection between TADs and gene regulation, their relationship with gene RLs and their dynamics during development and differentiation. Moreover, we describe how restructuring TADs may lead to pathological conditions, which explains their high evolutionary conservation, but at the same time it provides a substrate for the emergence of evolutionary innovations that lay at the origin of vertebrates and other phylogenetic clades.Animal genomes are folded in topologically associating domains (TADs) that have been linked to the regulation of the genes they contain by constraining regulatory interactions between  In the last years, the development of chromosome conformation capture (3C) techniques, together with remarkable advances in live cell imaging, have expanded our knowledge about the structural organization of animal genomes . 3C techcis-regulatory elements (CREs) and their target promoters, which otherwise would not occur at enough frequency to ensure a robust target gene expression  would oligomerize from the enhancer to the promoter; or looping, in which factors bound to both sides of the loop (enhancer and promoter) would interact with each other  were removed by CRISPR-mediated genome editing in mice. Strikingly, the lack of these CTCF binding sites reduced the interaction between ZRS and Shh promoter, as well as the expression of the latter  of rac3b and rfng in the rhombomeres margins, thus promoting the formation of actomyosin cables characteristic of these structures (Drosophila genus, D. melanogaster and D. triauraria. Only 25% of the TADs are orthologous between both species, and importantly these genomic rearrangements could be related with changes in gene expression (Apart from TAD restructuring early in the evolution of vertebrates, other cases have been documented when comparing relatively close species. Thus, the regulatory cluster formed by etrapods . Such reructures . Moreoveructures . Similarructures . These dpression . These fAlthough the recent technological advances have allowed an increasingly detailed understanding of the 3D organization of the genome, many questions remain unanswered. How CREs operate within the context of TADs over their target genes in a mechanistic level remains incompletely understood, and to what extent the alterations of TADs lead to gene miss-expression is still an open debate. Moreover, our knowledge of how the restructuring of TADs leads to evolutionary innovations is limited to a few reported examples and the scarce availability of genome-wide chromosome conformation experiments in different species limits the comparative analyses of the 3D genome from an evolutionary perspective. Finally, the increasing applicability of the single cell technologies to chromosome conformation experiments will hopefully make possible to discern between chromatin structure in particular cell types and its association with cell type-specific gene expression during development and differentiation.JS-P and JT reviewed the articles and wrote the manuscript. Both 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.


Background: The number of spinal cord stimulator (SCS) units sold in the United States (US) for the treatment of chronic pain has increased with a corresponding expansion in the number of different SCS platforms available. Each marketed stimulator has several unique features, indications, and limitations, which distinguish one from the other and makes the selection of appropriate hardware possible for optimal patient care. There are an even greater number of similar and overlapping features between SCS.Measures: We used market analysis techniques to survey the currently available SCS technology. We then reviewed published device specifications and manuals for comparison of features.Outcomes: As of 2020, there are nine commonly used SCS platforms made by four manufacturers including four SCS units from Abbott, three from Boston Scientific, and one each from Medtronic and Nevro.Conclusions: A working understanding of each SCS product's nuances is needed for selecting the most appropriate device with which to manage chronic pain patients. Here we present a brief survey of currently available SCS hardware in the US and the features that make each product unique. The point prevalence of chronic low back pain (cLBP) among all adults in the United States (US) is 13.1% . There iThe treatment of cLBP pain represents a major financial burden on the US health-care system. The 12 month health-care expenditures of adult patients with LBP in the US was found to be $25,613  among patients who underwent spine surgery compared to $795 ($790–800) among patients who chose non-surgical treatments . The twoThe utilization of SCS therapy for the treatment of chronic painful conditions continues in the US due to well-documented efficacy. The rapid development of SCS systems over time necessitate continuously updated reviews of available hardware . There eThis study only gathered data that was publicly available. As such, the study did not require Internal Review Board approval. Internet search tools including MEDLINE, EMBASE, Google scholar, and Google were used to identify SCS products. Searches included terms such as “spinal cord stimulation” “dorsal column stimulation.” Title and abstracts were iteratively reviewed for relevance with particular emphasis placed on high-quality health-care market assessments and product details provided by either device manufactures or independent, non-biased sources . Data was excluded if it described products that were not approved and available for patients to use in the United States in 2020 for the intended implantation in spine. This resulted in the exclusion of SCS devices available in other countries as well as for other indications, such as vagal nerve stimulators, which were not relevant to our analysis. Additionally, reviews focusing on mechanism of action or clinical effectiveness were not included as this was not the primary goal of the manuscript. All authors were involved in gathering and interpreting information. Unique features of products were then confirmed using from several sources, including product manuals, medical conference proceedings, published investor and business development reports, publicly available company due diligence reports, peer-reviewed medical literature, and device manufacturer-produced literature. When necessary, clarification was made through requesting additional documentation from device manufacturer sales teams and engineering support personnel. Endnote X9 was used to manage references and data sources .There are currently nine different SCS units commonly-available for the treatment of pain in the United States. The features of each device are presented in The ongoing development of SCS technology has led to the commercialization of several products on the US market, each with unique properties. This ever-expanding armamentarium allows physicians to individualize pain treatment and overcome previously existing treatment barriers. The current selection of SCS technologies has improved over previous generations through the refinement of SCS technologies including the miniaturization of IPGs, extended battery life, unique/novel waveforms and programming options, improved designs to ease trials and implantation, and a reduction in limitations of use, such as the expansion of MRI compatibility. We anticipate that this market will continue to be develop.The technology for SCS is continuously improved with the goals of refining current treatment applications and expanding therapeutic indications. In 2019, there was a decrease in the US SCS market overall. However, by 2025 the US SCS market is expected to increase by 5–10% compounded annual growth .The most common new trend is the development of multiple waveform-capable product lines and individual products, such as the non-rechargeable Abbott Proclaim  and the Nevro Omnia . The optimal waveform and programming for the treatment of different painful phenotypes is currently being investigated in several ongoing clinical trials with results expected in 2022 or later . Currently there is a paucity of evidence from direct comparison of different waveforms in pragmatic clinical trial settings to adequately inform healthcare decisions.The development of future SCS technology, including novel platforms and programming, will continue to occur in order to satisfy ongoing and unmet patient needs. Predictions of any new technology remains would be vague for two reasons. First, any new SCS technology would need to be formally evaluated in clinical trials for both safety and effectiveness prior to commercialization. Second, the need for protections of novel intellectual property makes very little information available to the public. Future iterations of this or similar manuscripts will strive to provide details of such new and emerging technology. SCS leads are a crucial component of an implantable SCS system. The use of different numbers and types of leads  can result in significant changes in the clinical profile of many SCS systems and is an additional important consideration for implanting physicians to consider.The evidence on SCS for the treatment of pain is expanding. While the focus of this manuscript was to survey the characteristics of the hardware, unique clinical outcomes and head-to-head comparisons are extremely important considerations. The currently published reviews of SCS clinical utility do not allow for several practical questions to be answered such as the ability to decrease opioid use or increase in functional capacity. There is also a dearth of large-scale and long-term data regarding the utilization of high-cost health-care resources after implantation of a spinal cord stimulator, such as the avoidance of spine surgery. With the increased utilization of SCS to treat LBP in non-previously operated spines, additional data will be needed to delineate the most effective SCS treatment algorithms in these patients. Physicians who use SCS to treat pain are now faced with several options in the US market with both unique and overlapping features.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.All authors contributed equally and meet the criteria for authorship based on International Committee of Medical Journal Editors.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.


Peritoneal metastasis is associated with poor prognosis, with studies in the literature reporting the survival of peritoneal metastasis without treatment to be three to six months. Hyperthermic intraperitoneal chemotherapy (HIPEC) has shown positive outcomes by improving the prognosis in patients with gastrointestinal malignancies. This systematic review of randomized controlled trials was done to determine the prophylactic role of hyperthermic intraperitoneal chemotherapy in preventing and controlling peritoneal metastasis gastrointestinal origin. Randomized controlled trials published between January 2019 to June 2021 were included. The databases used were MEDLINE (PubMed), EMBASE (Ovid), and the Cochrane library. Cochrane handbook for systematic review of intervention was used to assess the risk of bias in included trials. The results were reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of five trials met the inclusion criteria. Two studies were on patients with gastric cancer, and the other three studies were on patients with colorectal cancer. HIPEC was given to a total of 116 gastric cancer patients and 308 colorectal cancer patients. In all the included studies on patients with gastric cancer, the peritoneal recurrence-free survival was significantly higher in the group that received HIPEC. There was no significant improvement in peritoneal-free survival in patients with colorectal cancer who received HIPEC. HIPEC appears to be effective in preventing peritoneal metastasis in patients with locally advanced gastric cancer without minimal postoperative complications. However, in patients with advanced colorectal malignancy, HIPEC does not seem to play a crucial role in preventing and controlling peritoneal metastasis. Peritoneal metastatic disease is a condition of the peritoneum characterized by multiple foci of metastatic tumors, usually of gastrointestinal or gynecological origin. It can occur through various mechanisms. These include implantation of the cancer cells onto the peritoneum with the help of adhesion molecules, direct extension of the tumor cells into the peritoneum through the serosa, through lymphatic or hematogenous spread , right-sided tumors, radical dissection of the tumor  had stuThough there are various studies published in the literature, including reviews about the efficacy, safety, and outcomes of HIPEC, there are no systematic reviews of the randomized controlled trials published in the literature that evaluated the effectiveness of HIPEC in the prevention and control of peritoneal metastasis of gastrointestinal origin to the best of our knowledge. Therefore, this systematic review of randomized controlled trials was done to determine whether prophylactic HIPEC can prevent or reduce peritoneal metastasis in patients with gastrointestinal cancers.This systematic review was designed, and its results were reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines , EMBASE (Ovid), and the Cochrane library. These databases were exhaustively searched for published studies from January 1, 2019, through June 1, 2021. Suitable keywords and medical subject heading (MeSH) terms were used in PubMed to fetch all pertinent articles that studied the outcomes of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastasis and primary peritoneal tumors. The keywords used include "HIPEC", "hyperthermic intraperitoneal chemotherapy", "hot chemotherapy", "peritoneal malignancies", "peritoneal cancers", "peritoneal neoplasm", "peritoneal metastasis", and "outcomes". The Boolean search method was used in PubMed to combine the keywords and MeSH words. The full search strategy followed in PubMed is as follows: HIPEC OR Hyperthermic Intraperitoneal Chemotherapy OR Hot Chemotherapy OR  AND  AND Peritoneal Malignancies OR Peritoneal Cancers OR Peritoneal Neoplasm OR Peritoneal Metastasis OR  AND outcomes. We applied filters for study type in PubMed, including articles categorized as a clinical trial, clinical trial phase I-IV, controlled trial, and randomized controlled trial. We also applied other filters such as studies involving humans only, studies in English language, and studies on cancer patients. In the Cochrane library, in addition to the year of the study mentioned above, we applied the filters including study type as trials and source as EMBASE. The searches were run twice by two authors (JLD and AK) before we retrieved the final set of articles, and we included any additional studies that were identified. All retrieved articles were scrutinized for relevance to our study and to exclude potentially irrelevant articles. Study selection was carried out independently by two reviewers (JLD and AK). It was done in two phases. In phase A, after applying all the filters based on the inclusion and exclusion criteria, JLD and AK individually and independently screened the titles and abstracts of search results in all databases. Full-text articles were obtained for studies recognized as pertinent to this systematic review. In phase B, AK reviewed all full-text articles for eligibility and relevance. The articles that did not have information relevant to the objective of this study were excluded by AK. To avoid excluding pertinent articles, the articles excluded by AK were scrutinized again by JLD based on inclusion and exclusion criteria. JLD and AK thoroughly examined the full text of the studies that met the inclusion criteria independently to extract the data. Other authors independently checked and assessed the chosen articles for relevance. From the included study, the following data were extracted: number of patients in the HIPEC group and non-HIPEC group, number of patients with metastatic peritoneal disease in each group, survival rate, peritoneal recurrence-free survival (PRFS) rate, postoperative complications in each group. These data were entered in the Microsoft Excel sheet for analysis.Cochrane handbook for the systematic review of interventions was used to quality check the randomized controlled trials. Each domain was scored as low risk, high risk, or unclear accordingly for the chosen studies. JLD, AK, PT, and GK assessed all the selected randomized controlled trials. The initial database searches identified a total of 1,203 articles. Of these, 195 articles were found to be duplicates which were removed. We conducted the preliminary screening of these articles by reading the titles and abstracts and excluded 952 articles that were not relevant and did not meet the inclusion criteria. The full texts of the remaining 56 articles were reviewed for relevance and bias. After extensive evaluation of these 56 articles, 51 studies were excluded, thereby reaching a total number of five trials that were included for this systematic review. The PRISMA flow diagram is illustrated in Figure 2Out of the five included studies, two studies were on patients with gastric cancer, and the other three studies were on patients with colorectal cancer. Three out of the five studies used adjuvant chemotherapy along with HIPEC. HIPEC was given to a total of 424 patients . The characteristics of the included studies are summarized in Table 1In both the included studies on patients with gastric cancer, the PRFS was significantly higher in the group that received HIPEC as a prophylactic therapy to prevent recurrence. Both the studies reported 3-year PRFS. In Beeharry et al. (2019) study, Of the studies on patients with colorectal cancer, the COLOPEC trial by Klaver et al. (2019) studiedOf the included studies on patients with gastric cancer, the data presented on postoperative complications varied among the studies. In the Reutovich et al. (2019) study, In the included studies on patients with colorectal cancer, the postoperative complications were higher in the group that received HIPEC. Klaver et al. (2019), in theBias assessment was done using the Cochrane handbook for systematic reviews of intervention. Out of the five included studies, Beeharry et al. (2019) trial uThis systematic review of recently published randomized controlled trials was done to provide up-to-date information and the highest level of evidence regarding the role of HIPEC in the prevention and reduction of recurrence of peritoneal metastasis to the medical literature. Gastric cancer and colorectal cancer are the commonly diagnosed gastrointestinal malignancies worldwide. While HIPEC therapy is also given for other gastrointestinal malignancies like mucinous appendiceal cancer, we could not retrieve any recently published RCTs that evaluated the role of HIPEC in those patients. One of the most important reasons for poor prognosis in gastric cancer is recurrence . The coAll the included trials also reported that the overall survival rate was significantly higher in the patients who received HIPEC. Similar results were reported by Mi et al.'s meta-analysis of randomized controlled trials published in the year 2013. The resWhen it comes to colorectal cancer, prophylactic HIPEC therapy appears to be controversial, and data regarding the same are scarce in the medical literature. The first pilot study to determine the prophylactic role of HIPEC in colorectal cancer is by Virzì et al. (2013). The auAll the recently published RCTs have reported contradicting results on the prophylactic and therapeutic use of HIPEC to prevent and limit peritoneal recurrence in patients with colorectal cancer. All the trials included in this review reported that there was no significant improvement in the PRFS in patients who received HIPEC. In the COLOPEC trial, the 18-month PRFS in the HIPEC group was 80.9 %, whereas, in the control group, it was 76.2 %. The HIPEC group received both adjuvant chemotherapy and HIPEC. The control group received only adjuvant chemotherapy. One of the limitations reported by the authors was the administration of adjuvant chemotherapy later in the experimental group than in the control group though all patients received adjuvant chemotherapy within the recommended period . The PRIn PRODIGE 7 trial, the PRFS did not show any significant difference between the HIPEC and the non-HIPEC group, which received cytoreductive surgery along with systemic chemotherapy . In allIn addition, the complications were higher among the patients who received HIPEC. In the COLOPEC trial, postoperative complications occurred in 12 patients who received HIPEC. Two patients had an anastomotic leak. One patient who received HIPEC developed encapsulating peritoneal sclerosis that was subsequently treated . AverbaOne of the most important limitations of this review is the number of studies and the type of studies chosen. Our primary objective was to provide the highest level of evidence of updated information in the field of surgical oncology and HIPEC therapy. Considering the level of biases in other types of studies and the level of evidence available, only RCTs were chosen. HIPEC therapy is not available worldwide, and even in the available places, only a few experienced and trained experts are available to do the procedure. The number of RCTs available in the literature involving HIPEC is very scarce. Most of the RCTs get called off due to a considerable loss of patient follow-up and leading to deficiency in the data. Considering the fact of the presence of other systematic reviews and meta-analyses of previously published RCTs, we chose to systematically analyze only the recently published RCTs to provide up-to-date information, which may serve as the highest level of evidence to the medical literature.In conclusion, HIPEC appears to be effective in preventing peritoneal metastasis in patients with locally advanced gastric cancer with minimal postoperative complications. However, in patients with advanced colorectal malignancy, HIPEC does not seem to play a crucial role in preventing and controlling peritoneal metastasis. Moreover, the risk of postoperative complications is higher and thus further contributing to morbidity and mortality. The ongoing and future RCTs need to prove the prophylactic effectiveness of HIPEC in patients with colorectal cancer.None.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.


Anatomic total shoulder arthroplasty (ATSA) is widely used to treat the diseases of the glenohumeral (GH) joint. However, the incidence of rotator cuff tears after ATSA increases during follow-up. The effects of rotator cuff deficiencies after ATSA on the biomechanics of the GH joint are to be investigated. In this study, a musculoskeletal multibody dynamics model of ATSA was established using a force-dependent kinematics (FDK) method. The biomechanical effects were predicted during arm abduction under different rotator cuff deficiencies. The deltoid forces were increased under the rotator cuff deficiencies, the maximum deltoid forces were increased by 36% under the subscapularis deficiency and by 53% under the supraspinatus, infraspinatus, subscapularis, and teres minor deficiencies. The maximum GH contact forces were decreased by 11.3% under supraspinatus and infraspinatus deficiencies but increased by 24.8% under subscapularis deficiency. The maximum subscapularis force was decreased by 17% under only infraspinatus tear during arm abduction. The results suggested that the changes in the biomechanics of the GH joint induced by rotator cuff deficiencies after ATSA increase the deltoid muscle energy expenditure and joint instability, which result in postoperative less satisfactory clinical outcomes. The changes in rotator cuff muscle forces deserve more attention for understanding the evolution of rotator cuff tear after ATSA. Shoulder arthroplasty has become the third most common orthopedic procedure after hip and knee joint arthroplasties . Two entIn the clinic, supraspinatus tears are frequently involved in rotator cuff tears with a similar rate as supraspinatus and infraspinatus tears . Teres min vitro experimental studies can provide valuable information regarding joint loading with  based on the BIOMODULAR implant . A local reference frame was defined at the joint center of the GH joint as indicated in PV in N/m3 in the default FDK computational framework of AnyBody ].A generic upper extremity musculoskeletal model was extracted from Anybody Managed Model Repository  to establish the musculoskeletal multibody dynamics model of ATSA in AnyBody Modeling System . There were 118 muscle-tendon units and five joints  in the musculoskeletal shoulder model. The deltoid muscles included two parts, deltoideus_clavicular and deltoideus_scapular. The acromioclavicular joint and the sternoclavicular joint were modeled as ball-and-socket joints only allowing three rotational degrees of freedom (DoFs), the elbow joint and wrist joint were modeled as revolute joints only allowing flexion-extension rotation. The DoFs of the GH joint in directions of anterior-posterior, superior-inferior, and medial-lateral translations were released using the FDK method . A linea AnyBody . The con3 were calculated and used in this study [as shown in Equation (2)]. Where v and h are Poisson’s ratio and the thickness of polyethylene insert, Ai and pi are the contact area and contact pressure of the opponent triangle for the ith vertex. Non-linear polyethylene material parameters of εo = 0.0597, po = 18.4 MPa, and n = 3 derived in a previous experimental study . It took 90 s to perform the whole arm abduction motion. The DoFs of thorax, head, and pelvis segments were constrained. The scapula was restrained by simulating a permanent contact between the thorax and the angulus inferior landmark of the scapula  < 59.2 N], superior-inferior component force (RMSE < 90.8 N), medial-lateral component force (RMSE < 28.3 N), and GH contact force (RMSE < 60.9 N) with reasonable accuracy in trend and amplitude.The predicted GH contact force and component forces of ATSA by the established musculoskeletal model are compared with the reported range and mean value of the measured patients  in Figurpatients , the comCompared with the intact rotator cuff, the infraspinatus force was increased under only the supraspinatus deficiency (Q2) in A musculoskeletal multibody dynamics model of ATSA was established using the FDK method in this study. The contact mechanics and joint kinematics of the GH joint were considered in the inverse dynamic simulation of the musculoskeletal shoulder model. The contact forces and muscle forces could be calculated simultaneously during arm abduction simulation. The predicted GH contact forces using the musculoskeletal model of ATSA were indirectly evaluated by comparing with the previous reports . Due to Rotator cuff deficiency results in an increase of deltoid efficiency during arm abduction . The preAlthough the deltoid force was increased along with the supraspinatus and infraspinatus deficiencies, the GH contact force was decreased. From this, the supraspinatus and infraspinatus are major contributors to the compressive forces of the GH joint. The infraspinatus deficiency and supraspinatus deficiency influenced each other in this study. The mechanical interaction between infraspinatus and supraspinatus may be the main cause of deterioration of infraspinatus and supraspinatus tears. There was no influence of the subscapularis deficiency on the infraspinatus force. However, the subscapularis force was decreased under the infraspinatus deficiency compared with the intact rotator cuff. While there was no influence of the supraspinatus deficiency on the subscapularis force. But the subscapularis deficiency influenced the amplitude fluctuations of the supraspinatus force. From this, the infraspinatus tear would increase the supraspinatus force and decreased the subscapularis force. The decreased subscapularis force further induced the amplitude fluctuations of the supraspinatus force. Therefore, the effect of the infraspinatus tear on the supraspinatus force was compounded. The changes in rotator cuff muscle forces deserve more attention for understanding the evolution of rotator cuff tear in the clinic after ATSA.Several limitations are ought to be discussed. First, only five situations of rotator cuff deficiencies were considered to investigate the biomechanics of ATSA, the other combined rotator cuff tears and reconstructions were not considered. Second, the arm abduction motion was defined by a simple driver without considering other motion inputs. The motion capture data of the patient should be used to obtain a realistic joint translation. Only abduction motion was simulated in this study, and other more meaningful activities of daily living were not considered. The deltoid forces were increased under the rotator cuff deficiencies, which may induce potential clinical pain and strenuous arm elevation. The GH contact force was decreased under supraspinatus and infraspinatus deficiencies but increased under subscapularis deficiency. Infraspinatus tear would increase the supraspinatus force and decrease the subscapularis force. The decreased subscapularis force further induced the amplitude fluctuations of the supraspinatus force. So, the effect of the infraspinatus tear on the supraspinatus was compounded. The changes in rotator cuff muscle forces deserve more attention for understanding the evolution of rotator cuff tear in the clinic after ATSA.The original contributions presented in the study are included in the article/ZC, XF, YG, JZ, and ZJ conceived and designed the study. ZC and XF performed the simulation and prepared the manuscript. LG, SC, and ZJ reviewed and edited the manuscript. All authors read and approved the manuscript.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.