Visceral leishmaniasis (VL) is a parasitic disease with an estimated 30 000 new cases occurring annually. There is an observed variation in the efficacy of the current first-line therapies across different regions. Such heterogeneity could be a function of host, parasite and drug factors. An individual participant data meta-analysis (IPD-MA) is planned to explore the determinants of treatment outcomes.The Infectious Diseases Data Observatory (IDDO) VL living systematic review (IDDO VL LSR) library is an open-access resource of all published therapeutic studies in VL since 1980. For this current review, the search includes all clinical trials published between 1 January 1980 and 2 May 2021. Studies indexed in the IDDO VL LSR library were screened for eligibility for inclusion in this IPD-MA. Corresponding authors and principal investigators of the studies meeting the eligibility criteria for inclusion were invited to be part of the collaborative IPD-MA. Authors agreeing to participate in this collaborative research were requested to share the IPD using the IDDO VL data platform. The IDDO VL data platform currently holds data sets from clinical trials standardised to a common data format and provides a unique opportunity to identify host, parasite and drug determinants of treatment outcomes. Multivariable regression models will be constructed to identify determinants of therapeutic outcomes using generalised linear mixed-effects models accounting for within-study site clustering.This IPD-MA meets the criteria for waiver of ethical review as defined by the Oxford Tropical Research Ethics Committee (OxTREC) granted to IDDO, as the research consists of secondary analysis of existing anonymised data  Ethics approval was granted by the ICMR-Rajendra Memorial Research Institute of Medical Sciences ethics committee (Letter no: RMRI/EC/30/2022) on 04-07-2022. The results of this IPD-MA will be disseminated at conferences, IDDO website and any peer-reviewed publications. All publications will be open source. Findings of this research will be critically important for the control programmes at regional/global levels, policy makers and groups developing new VL treatments.CRD42021284622. In any single visceral leishmaniasis (VL) clinical trial, only few relapses are observed which limits the ability to identify predictors associated with it. An individual participant data meta-analysis (IPD-MA) will increase the statistical power to detect the predictors and moderators of treatment outcome.The identification of studies eligible for inclusion in the IPD-MA has been made through a comprehensive literature search of all published studies since 1980 with predefined inclusion–exclusion criteria. However, retrieval of data from trials published prior to 2000 can be a major challenge.This IPD-MA will use the VL repository of IPD hosted by Infectious Diseases Data Observatory (The IDDO VL data platform). A major strength of this study is that data on the IDDO VL data platform is harmonised to a common standard based on an extensive consultation with the VL research community.A particular scientific challenge is that distinction of relapse from reinfection is seldom carried out in VL therapeutic trials and hence would not be considered in this analysis.Visceral leishmaniasis (VL), also known as kala-azar, is a parasitic disease with anthroponotic and zoonotic modes of transmission.The efficacy of antileishmanial regimens in VL varies across geographical regions. For example, single-dose liposomal amphotericin B (L-AmB) has demonstrated a high efficacy (≥94%) in the Indian subcontinent while its efficacy is suboptimal (58%) in East Africa.Several studies have reported on the determinants of therapeutic outcomes in studies conducted across different geographical regions and patient populations.The objectives of this IPD-MA are a :To identify host, parasite and drug determinants of initial cure after the completion of treatment schedule.To identify host, parasite and drug determinants of definitive cure at 6 months after treatment completion.To identify host, parasite, and drug determinants of relapse at 6 months after treatment completion.To identify host, parasite, and drug determinants of mortality outcome at any time point during the study.Primary and secondary endpoints relating to these objectives are defined in the outcomes section.Population: any patient enrolled in an interventional study with a confirmed or suspected diagnosis of VL defined by serological and/or parasitological testing.Interventions: Any antileishmanial therapyComparator: Not restricted by the use of a comparator drug.Outcome: at least one of the following outcomes reported: initial cure, definitive cure, relapse or mortalityTime: Studies published on or after 1980.The following eligibility criteria must be fulfilled for study inclusion:Prospective clinical efficacy studies on patients with confirmed or suspected VL either using microscopy/serology/molecular method Information on constituent drug(s), dose and duration of treatment regimen is availableAt least one of the following clinical outcomes are measured: initial cure, definitive cure, relapse or mortalityThe following minimum information are required for inclusion of a patient in the IPD meta-analysis:Details of antileishmanial treatment(s) administeredBaseline information on age and genderOutcome is recordedThe primary endpoint adopted is cure at 6 months following treatment completion. This is commonly referred to as ‘definitive’ or ‘final’ cure. The precise definition and timing of definitive cure will vary according to study design. As a minimum, it is expected that a definitive cure is achieved if the patient remains alive and is no longer be manifesting symptoms and/or signs of VL.Further analysis of this endpoint will be carried out using a stricter definition of definitive cure, defined as: achievement of initial cure (as defined below) and no subsequent rescue treatment or evidence of clinical or parasitological relapse, and no death associated with VL during the 6 months following treatment completion.The following secondary endpoints are adopted.Initial cure is defined at the time of initial assessment adopted in the original study after completion of the therapy along with clinical improvement. The timing of initial cure assessment would typically take place within 28 days of treatment completion but this varies slightly across studies.Further analysis of this endpoint will be carried out using a stricter definition of initial cure, defined as: cure at day 28 or at time-point defined in the original study following treatment, defined as clinical improvement of VL, absence of parasites in the spleen or bone marrow using microscopy and no rescue therapy on or before day 28 or before the timepoint of initial cure assessment adopted in the original study.Relapse is defined as the recurrence of signs and symptoms of VL at any time point during the study follow-up among those who had achieved initial cure. The assessment typically takes place at 6 months but this varies slightly across studies.Tissue aspirates for confirming parasitological presence are usually carried out based on clinical suspicion of relapse during the follow-up.This is defined as deaths reported as related to the study interventions or due to the progressive worsening of the disease itself at any time during the study. Further analysis of this endpoint will be carried out by considering all-cause mortality.The assessment of initial cure and definitive cure is usually undertaken at 28-days and 180-days post-treatment. However, the exact time of these assessment will vary across the studies. Assessments undertaken between 15 and 60 days will be considered as time of initial cure. For assessments of definitive cure and relapse, assessments made between 150 210 days will be considered as 180 days.Eligible studies were identified from the infectious diseases data observatory (IDDO) library of all prospective therapeutic studies that have systematically indexes all published therapeutic efficacy studies in VL published from 1980 onwards.10.1136/bmjopen-2023-074679.supp1Supplementary dataAuthors  of the studies in the IDDO VL LSR library eligible for the inclusion in this IPD-MA were invited to be part of this collaborative research. Researchers agreeing to the terms and conditions of the submission were then requested to upload IPD to the IDDO VL data platform through a secured web portal.Raw data from individual studies shared with IDDO VL data platform are currently being standardised using the Clinical Data Interchange Standards Consortium (CDISC) compliant curation standards.The following variables will be considered for inclusion in the analysis of primary and secondary endpoints:The following host variables are considered: age, gender, body weight, nutritional status, comorbidity status (such as HIV) and duration of illness prior to study enrolment. The following baseline clinical measurements will be considered: haemoglobin/anaemia status, spleen size, immunological biomarkers (CD4+ count), alanine transaminase (ALT) and aspartate transaminase (AST), platelets and neutrophils. If data are available, the following baseline characteristics will be considered: history of blood transfusion, bilirubin, creatinine, urea, and albumin concentrations.The following parasite-related baseline factors will be considered: parasite load and information regarding the nature of infection (primary vs previously treated cases). Any cases described as previously untreated (or ‘fresh’) cases for leishmaniasis will be considered as primary VL. The enumeration of parasite density is usually carried out by evaluating bone marrow or splenic aspirates or through quantitation of parasites in unit quantity of specimen or parasite DNA equivalence per PCR reaction across studies;The following drug-related variables will be considered for inclusion in analysis: mg/kg total dose (or target dose) administered,The following study or arm level variables will be considered in the analysis of primary and secondary endpoints: country, study site, and calendar year of the study conduct.There is a known regional variation in treatment response in VL,A summary of included studies will be presented with respect to study design, study location, year of study conduct, characteristics of study population, duration of follow-up, details of drug regimens including supervision of drug administration, and methodological details adopted for disease confirmation and treatment outcomes.Summary of baseline characteristics of the patients included in the analysis will be presented by geographical region and overall. These include the following: age, weight, parasite grade at enrolment, temperature, haemoglobin (or haematocrit) concentration, anaemia and severe anaemia status, spleen size, description of severity of infection (severe/mild/uncomplicated) if available, total mg/kg dose for each treatment and supervision of drug administration. The distribution of the baseline characteristics will be summarised either as a proportion for categorical variables, as mean (with SD) or median (with IQR) for continuous variables.A mixed effects logistic regression model will be used for identifying the risk factors for definitive cure in a one-stage IPD-MA. Given a relatively low number of expected events (for relapse) in each included study,If information regarding the time of occurrence of event is available, Kaplan-Meier (K-M) method will be used to estimate the probability of definitive cure at the end of the study follow-up, and a Cox regression model will be considered with study sites fitted as a frailty term to account for between-study site heterogeneity. The following outcomes will be censored in the survival analysis: lost to follow-up, death due to causes adjudicated as unrelated to the study drug, voluntary withdrawal from the study.The following set of variables are the risk factors reported in clinical literature for treatment outcomes in VL: age, sex, baseline parasite density and HIV coinfection. These variables along with the drug regimen will form the minimal adjustment set for assessment of other risk factors and will be kept in the regression model regardless of statistical significance.et al.The association between the remaining candidate predictors and therapeutic outcomes will be assessed by adjusting for the core predictor sets identified. Multivariable model construction will follow the recommendations of Heinze The proportion of missing observation for each of the variables considered in the analysis will be summarised and any missingness patterns will be explored. Multiple imputation,Patients living with HIV who are treated for VL typically have worse outcomes and higher mortality risk than those who are not living with HIV.et al.Stability investigations will be undertaken to account for uncertainty introduced in multivariable modelling through bootstrap resampling. The robustness of the derived estimates and their variance will be summarised using the recommendations in Heinze The proportion of patients achieving initial cure (as defined previously) in each of the studies will be presented. The construction of univariable and multivariable regression models will follow the same approach as for the primary endpoint.The proportion of patients achieving relapse (as defined previously) in each of the studies will be presented. The construction of univariable and multivariable regression models will follow the same approach as for the primary endpoint.The proportion of deaths reported in each of the studies will be presented. The construction of univariable and multivariable regression models will follow the same approach as for the primary endpoint.All analyses will be carried out using R software or Stata V.17 software.Risk of bias was assesed using the Cochrane risk of bias tool (RoB 2) for randomised studies.et al.To examine the risk of bias in IPD-MA, the first four domains of the quality in prognosis studies (QUIPS) tool and the first three domains of the prediction model risk of bias assessment tool (PROBAST) will be considered as recommended in Riley Despite best possible efforts, it is anticipated that raw data from all the identified studies will not be available. The characteristics of patient population and study meta-data from the missing studies will be summarised to explore if the missing studies are systematically different from the studies that are included in the meta-analysis. A two-stage IPD may be conducted if sufficient details (or any covariate adjustment) are reported in the original studies.This IPD-MA meets the criteria for waiver of ethical review as defined by the Oxford Tropical Research Ethics Committee (OxTREC) granted to IDDO, as the research consists of secondary analysis of existing anonymised data . Ethical approval was granted to each study included in this pooled analysis by their respective ethics committees. This IPD-MA will address research questions similar to that of included studies. Findings of this IPD-MA will be reported in open-access, peer-reviewed journals following the PRISMA-IPD guidelines.The research questions considered in this IPD-MA is based on a research agenda developed by the global VL research community.Major statistical analyses have been included in this plan. Amendments to the current plan or additional statistical analyses may be required as data accrual is in progress and will be transparently reported in subsequent reports of the results.Global commitment over the past few decades has led to significant progress in the control and elimination of VL. In the Indian subcontinent (ISC), the VL burden has greatly reduced in the past 15 years.Several clinical trials and meta-analyses have highlighted the therapeutic efficacy and safety of one or more antileishmanial therapies.The identification of studies eligible for inclusion in the IPD-MA has been made through a comprehensive literature search of all published studies since 1980 with predefined inclusion–exclusion criteria. A major strength of this study is that data from several studies will be harmonised to a common standard based on an extensive consultation with the VL research community,A major challenge is that a substantial proportion of the studies in the IDDO library were conducted prior to the year 2000; the retrieval of data from historical trials is a major challenge. A particular scientific challenge is that misclassification of reinfection as ‘true’ relapse can potentially introduce bias in relapse estimates. A distinction of relapse and reinfection is seldom carried out in VL therapeutic trials and hence would not be considered in this IPD-MA. Evidence form a study in Nepal suggested late relapses were less likely to be new infections,This IPD-MA will combine data from the studies in the IDDO VL data platform to identify the determinants of therapeutic outcomes. Findings of this research will generate important information for the control programmes at regional and global levels, policy-makers and groups developing new VL treatments.


A three-step qualification framework including material, process and product-based qualification was then proposed against these maximum stresses and failure modes. The proposed framework revolves around the destructive testing of specimens initially as per ASTM standards D 7264 and D 2344, followed by defining the autoclave process parameters and customized testing of thick specimens to evaluate material strength against the maximum stresses in specific failure modes of the main landing gear strut. Once the desired strength of the specimens was achieved based on material and process qualifications, qualification criteria for the main landing gear strut were proposed which would not only serve as an alternative to drop test the landing gear struts as defined in air worthiness standards during mass production, but would also give confidence to manufacturers to undertake the manufacturing of main landing gear struts using qualified material and process parameters.The determination of suitable testing and qualification procedures for fiber-reinforced polymer matrix composite structures is an active area of research due to the increased demand, especially in the field of aerospace. This research illustrates the development of a generic qualification framework for a composite-based main landing gear strut of a lightweight aircraft. For this purpose, a landing gear strut composed of T700 carbon fiber/epoxy material was designed and analyzed for a given lightweight aircraft having mass of 1600 kg. Computational analysis was performed on ABAQUS CAE Composite materials are extensively utilized in aerospace, marine, civil, automotive, and sporting applications  owing to® and ANSYS 10.0®. The results presented in their research work showed that the deflection of the steel leaf spring was better than the composite leaf spring but at the cost of weight. A significant weight reduction of 84.4% was achieved by using a composite leaf spring suspension system. Xue et al.  can can20] cHowever, this product qualification method only applies to the full-scale prototype during the development phase. No studies are available in the literature for the qualification of landing gear struts during mass production after drop test qualification. In the case of composite struts, these criteria become even more complex keeping in view the sensitivity of material properties and process limitations. Therefore, a comprehensive three-step qualification method is proposed in this research work. After material- and process-based qualification as discussed in detail above, an alternate qualification criterion to the drop test for the final product is also recommended. As the prototype of the landing gear strut has not been developed, the product would therefore be declared qualified by destructive testing of the specimens cured with the complete landing gear strut in the same autoclave cycle to validate the required strengths in bending and shear modes. In this context, maximum stresses encountered by the landing gear strut under one-point landing condition in bending and shear modes as calculated by computational analysis have been taken as the main design requirements of the final product. As destructive testing of the specimens provides the break force, lower limits of experimentally obtained break forces, therefore, need to be evaluated against the maximum bending and shear stresses with values of 729.29 MPa and 51.39 MPa, respectively, against the finalized dimensions of specimens as mentioned in Based on the satisfactory results of the three-step qualification framework as proposed in this research work, manufacturing tasks of both of the composite main landing gear struts are recommended using T700 carbon fiber/epoxy material. The same autoclave cycle as defined in A novel framework for the qualification of a composite-based main landing gear strut of a lightweight aircraft has been formulated based on material, process, and product qualification.The qualification framework is focused on enhancing the load-carrying capability of the strut in terms of bending and shear loads which are the key loads for a uniform cross-section beam.The framework evaluates the load-carrying capability using a systematic two-pronged approach by leveraging computational and experimental testing for the selection of appropriate material and process parameters.The proposed framework, which is based on sample/coupon testing, can be utilized for the full-scale prototyping of a main landing gear strut.The major conclusion of the research work are as follows:


Lateralization is the functional dominance of one of the dual organs of the body: eyes, arms, legs and even ears, during their spontaneous or purposeful actions. The handedness is influenced by many factors like geographic region, genetic and cultural factors as well as sex. The most used assessment for functional lateralization is hand dominance. When assessing foot and eye dominance, however, we find significantly higher left foot dominance as well as very strong left eye dominance in schizophrenic patients versus controls. We consider the explanation of this results is because in Bulgaria, during the communist regime (before 1990) left hand writing was under cultural pressure. Also handedness itself is influenced by other cultural factors as mentioned already. All of the above made us conclude that foot and eye dominance may assess much better the lateralization than hand dominance.The aim of the study was to investigate the relaibility  of a combined Foot and Eye Dominance Scale in women- patients with schizophrenia and healthy subjects.A sample of 94 women- scizophrenia patients and healthy controls were assessed with a Combined afaoot and Eye Dominance Scale. It consisted of two subscales Foot Dominance Subscale and Eye Dominance Subscale. The Foot Dominance Subscale included a modified Chapman & Chapman Foot Dominance Scale and a new Complex Task Scales with four foot tests, reflecting on complex tasks. The Eye Dominance Subscale included three eye tests. Scale reliability statistics , non-parametric Mann-Whitney test and Spearman’s rank correlation coefficient were used.Considerable differences were found in the contribution of the single items to the Combined Foot and Eye Dominance Scale. Some items show greater means than other items , which suggested greater phenogenetic component and consequently greater contribution of these items to the total scale mean. The mean correlation between the items of the Combined Foot and Eye Dominance Scale was positive , indicating good internal consistency of the scale.The Combined Foot and Eye Dominance Scale more strongly and objectively reflect leftedness and could be a more useful tool for the assessment of lateralization irrespectively of culture and nation. The Combined Scale allows cross-cultural worldwide equivalence to the different studies in different neuroontogenetic diagnoses with presumed abnormal cerebral asymmetry.None Declared


Editorial on the Research TopicCardiac outflow tract development and diseasesConotruncal anomalies are the group of congenital heart defects involving malformations of the outflow tract (conus arteriosus) and the great vessels (truncus arteriosus) that have abnormal ventriculo-arterial relationships. Conotruncal (or outflow tract) defects are among the most common congenital heart diseases found at birth, and are the leading cause of mortality and morbidity in the first year of life. Tetralogy of Fallot (ToF), transposition of the great arteries (TGA), double outlet right ventricle (DORV), truncus arteriosus (TA), interrupted aortic arch (IAA) and anatomically corrected transpositions are some of the most common conotruncal anomalies.A detailed understanding of the embryogenesis is key to understand the conotruncal anomalies. The role of neural crest and second heart field derivatives has been established during outflow tract development. Thus, defective neural crest or second heart field deployment results in a spectrum of conotruncal anomalies ranging from outflow tract alignment to septation defects .This research topic focuses on recent advances in understanding the pathogenesis, diagnosis, treatment, and outcome of the most common conotruncal malformations. This collection includes four original articles that provide a global and detailed overview of some of the key concepts and recent advances related to these entities. The authors of the collection provide an in-depth review of some of the most important malformations included in this group of defects.Bell-cheddar et al. have prepared an interesting review of DORV providing a general overview including history, description of key morphologic features and anatomical classifications and, a thorough description of the different surgical options. In their review, the authors highlight the importance of a meticulous morphologic assessment prior to deciding the best-suited surgical technique. Particularly important are those anatomical features related to ventricular alignment, ventricular size and coronary anatomy. A detailed list of the most commonly expected surgical complications as well as a practical approach on pre- and post-surgical management is also provided. Overall, Bell-cheddar et al. have done a beautiful job addressing a complex group of CHD in a very organized and practical approach. Moreover, the excellent iconography supporting this manuscript will help readers to engage and better understand the anatomical classifications and different surgical options.DORV was first described in the mid-sixties. This term does not encompass a single congenital heart defect but rather a wide range of phenotypes , 3. Due Harvey et al. extend this knowledge by investigating possible mutations in genes related to myocyte contraction and ventricular septum development in non-syndromic ToF patients. Using one of the largest series of patients who have undergone exome analysis to study de novo variants, their analysis revealed a significant enrichment of variants in pathways involved in aortic and ventricular development, including a specific enrichment in patients with ToF. They also show the importance of chromatin remodeling genes in cardiac development and report overlap with genes involved in autism spectrum disorders and neurodevelopmental disorders.ToF is the most common cyanotic congenital heart disease . As withOne of the emerging fields in pediatric cardiology is prenatal diagnosis. The identification of cardiac malformations during fetal life has led to an improved survival and perinatal management, as well as increased knowledge and acceptance of the condition by families.Gomez et al. addresses the role of some cord blood biomarkers in two of the main conotruncal entities, D-TGA and ToF, studying their correlation with fetal echocardiography and perinatal outcome. The authors reported increased levels of transforming growth factor β1  is a common form of left ventricular outflow tract obstruction that can lead to aortic valve damage. It has a broad spectrum of disease, ranging from a small fibrous ridge on the sub-valvular ventricular septum to a narrow fibromuscular tunnel . The maiIn their cohort, survival rates were 90.8% at 10 years and 88.7% at 20 and 30 years. Main risk factors for mortality were age less than 1 year at the time of surgery, pre-existing Shone's complex condition, mitral stenosis and concomitant surgery on the mitral valve.The incidence of reoperation for SAS was 21.6% at 10 years and 28.2% at later stages.No difference in reoperation was detected regarding the surgical approach. The authors conclude that while most patients have a favorable long-term outcome, the recurrence rate of SAS after surgical repair is not negligible.In conclusion, the manuscripts included in this collection will certainly help to better understanding the conotruncal anomalies, a complex group of CHD with a wide spectrum of morphological types as well as clinical presentations. Early identifications of critical morphological features and the use of new prognostic tools might play an important role in overall postnatal management. Moreover, expanding our current knowledge on genetics and whole exome sequence might provide new insights in the diagnosis and parental counseling. Finally, innovation and development of new surgical approaches and minimally invasive techniques tailored to specific diseases will help to path the way of this complex group of heart anomalies.


The rapid evolution of wireless communication systems toward 6G demands efficient antennas with the features of adaptability and versatility. Liquid antennas have gained significant research interest due to their unique features in realizing small, flexible, transparent, and reconfigurable antennas for promising applications in future wireless systems. In this paper, in order to find a suitable metallic liquid for effective antennas, we design and compare the performance of metallic liquid antennas using Mercury, gallium indium alloy (EGaIn), and Graphene metallic liquid in the sub-6 GHz frequency. The antenna is realized by the metallic liquid in a poly methyl methacrylate microfluidic channel over a liquid crystal polymer substrate at 5.6 GHz frequency. The performance of these metallic liquid antennas is analyzed by their electromagnetic and radiation performance. The Graphene-based metallic liquid antenna shows better electromagnetic performance in comparison to Mercury and EGaIn metallic liquid antennas. For a point-to-point link, the mm-wave communication systems generally suffer more loss than sub-6 GHz systems3. Sub-6 GHz is substantially reasonable for carriers to implement because the range below 6 GHz is longer and penetrates objects in a better way.Communication technologies are undergoing a revolutionary shift due to the rapid progress of communication applications. Cellular mobile communication systems have gone through five generations of development. 5G is the latest generation of wireless networks. 5G has already been introduced in some regions of the world and officially became commercially available in 2019, employing sub-6 GHz and mm-wave frequency bands4. The rigid nature of metallic antennas limits their use in applications that require flexibility. On the other hand, the flowing property and having no deformation limits of metallic liquid make them an ideal alternative for flexible antenna applications. Without sacrificing their electrical properties, liquid metals in microfluidic channels develop extremely flexible and mechanically stable antennas5. Modern fabrication techniques for antennas, such as 3D printing, injecting, or spraying metallic liquid onto rigid or flexible substrates, are made possible by the fluidic property of metallic liquids. In contrast to conventional techniques like high-frequency switching, liquid antennas can be easily achieved reconfigurability through electrochemically controlled capillary action or micro pumping. Liquid antennas take advantage of the fluid’s mechanical properties. The presence of metallic liquid in fluidic channels enables the formation of the shape of a fluidic channel due to its low viscosity6. Liquid antennas on flexible substrates can bend, fold, stretch, and twist. Therefore, they can stand up to all kinds of mechanical deformation. Due to their high degree of reversibility, they are capable of regaining their original form7.In today’s wireless communications system, adaptability and diversified functionality have become the most appealing features of any communications device. The antenna has great importance for the communication system because the design of the air interface largely depends on the design of the antenna. The rapid evolution of wireless communication systems towards 6G demands efficient antennas. As conventional antennas are mostly made up of conductive metals on rigid substrates, they offer remarkable performance but lack mechanical flexibility. Furthermore, bending or stretching these antennas beyond certain limits causes irreversible structural deformation and even destruction9. A comprehensive literature review reveals that Mercury, and alloys of gallium and tin, are utilized in the design of metallic liquid antennas12. Mercury is the first used metallic liquid for antenna design. The fluidic and conductive property of Mercury enables the design of reconfigurable metallic liquid antenna. However, Mercury is toxic in nature and expensive. These facts boost the use of other metallic liquid materials gallium-based alloys12. Alloys based on gallium have remarkable electrical and thermal conductivity, non-toxicity and low viscosity14. In addition to these properties, gallium indium alloy (EGaIn) has mechanical stability and significantly prevents evaporation14. These features of EGaIn help in the improvement of antenna performance without having any effect on the conductivity and efficiency of the antenna. The most recent material that has been reported for antenna design is Graphene. Graphene is emerging as a promising candidate in several applications due to its electrical, thermal, and optical properties. It has excellent material properties for electronic applications. Graphene antennas perform much better than conventional copper metal antennas17. However, the Graphene metallic liquid for antenna design is not yet found in the literature. Finding the best metallic liquid material for metallic antenna design is vital for the antenna community. This information is pertinent from the perspective of the antenna designer.Liquid metal antennas were introduced in the 1990s to make flexible and reconfigurable antennasWe consider three antennas using metallic liquids of Mercury (Hg), an alloy of gallium and indium (EGaIn), and Graphene. The metallic liquid is injected in a poly methyl methacrylate (PMMA) microfluidic channel and the antenna is placed over a metallic grounded liquid crystal polymer (LCP) substrate.We investigate the numerical analysis of three different metallic liquid antennas and compare the radiation performance of these antennas in terms of gain, efficiency, and bandwidth.We design metallic liquid based antennas for sub-6 GHz systems by using the electromagnetic (EM) simulator Ansys HFSS.In this paper, we design and numerically analyze metallic liquid antennas by using Mercury, EGaIn, and Graphene liquid. We compare the electromagnetic performance of these metallic liquid antennas. A metallic liquid antenna with a working frequency of 5.6 GHz is designed as the candidate antenna to verify the suitability of a specific metallic liquid. In particular, the main contributions of the paper are summarized as follows:18. The fluidic properties of metallic liquids enable a wide range of metallic liquid antennas12. The fluid nature of liquid materials provides additional degrees of freedom to achieve better reconfigurability, even when the radiative elements are created on rigid substrates.Due to their inherent flexibility, liquid materials are a good substitute for stiff or solid conductors in flexible electronicsThe basis for creating effective liquid antennas is liquid materials. The antenna design and performance mainly result from the properties of the liquid. The liquid materials that are readily available for antenna design can generally be divided into three categories: metallic, non-metallic, and partially metallic liquids. This work primarily focuses only on metallic liquids. Electrical conductivity is typically high in metallic liquids, which is suitable for use as radiating elements in antennas.Due to their solid-like oxide coating on the surface, metallic liquids give elastomeric antennas with mechanical stability and flexibility. The high conductivity of metallic liquid makes it ideal for antenna applications. The use of metallic liquids as radiative elements enables the design of a considerably highly reconfigurable and flexible antenna than solid conductors like copper. The metallic liquid antenna is ideal for antenna applications due to its high flexibility and deformability, as well as its high conductivity.The first metallic liquid at room temperature is Mercury (Hg). Alternative metallic liquid materials are mostly in the form of alloys of conductive nanoparticles. Gallium-based alloys exhibit low viscosities, high electrical and thermal conductivities, and non-toxicity. These metallic liquids typically have conductivities of the order of Mercury is found in its liquid phase at room temperature; Mercury does conduct electricity because it has a metallic property and excellent volume expansion properties with the rise in temperature. The electrons of Mercury are free to move to conduct the flow of electric flux on the surface of the matter. A sufficient amount of electric flux penetrates through the Mercury per unit cross-section area. Mercury can carry electricity when it’s in liquid or molten form. The electrical conductivity of liquid Mercury is due to the transfer of electrons that takes place in the liquid or molten state.19. In addition, due to its high stiction and low oxidation properties, it is a suitable material for the development of a liquid antenna10. Mercury, on the other hand, is very toxic and has to be handled very carefully. Therefore, it has limited usage in antenna design.Mercury has a melting point of 13. One of the most commonly used alloys based on gallium is the EGaIn alloy, which is composed of 75% gallium (Ga) and 25% indium (In). EGaIn has an electrical conductivity of 14. The resistivity of EGaIn is 14. When the liquid alloy is exposed to air, it reacts with oxygen to create a thin oxide layer on the surface, which enhances mechanical stability and surface tension, and significantly inhibits evaporation. These benefits enhance EGaIn performance in metallic liquid antennas without having any effect on the conductivity and efficiency of antennas. The most significant feature of EGaIn metallic liquid is non-toxicity. The unique feature of EGaIn helps in designing reconfigurable and flexible antennas12.Gallium-based alloys exhibit remarkable electrical and thermal conductivities, low viscosity, and non-toxicity. These materials have a melting point that’s either lower than or near room temperature20. It is directly dependent on the electron mobility in the matter. The resistivity of Graphene remains between A carbon-based new metallic liquid material is the liquid form of Graphene. Graphene liquid can be employed for the design of metallic liquid antennas. Because of the high mobility of electrons in the hexagonally arranged carbon atoms of Graphene, it has an electrical conductivity of 21. The superior properties of Graphene, including high electrical conductivity, high mechanical strength, adsorption capability, thermal resistance, etc., have led to a great deal of current research interest and a wide range of practical applications. Pristine Graphene has remarkable physical properties, including high electronic mobility -based electromagnetic (EM) solver, is used to validate the proposed designed antennaThe feeding mechanism of the proposed metallic liquid antenna can be illustrated with the help of Fig. 32. The soft lithographic processes can be used to fabricate microfluidic channel33. The microfluidic channel of PMMA elastomer can be sealed with a thin and flat sheet of LCP-based substrate layer34. The position of metallic liquid in the microfluidic channel can be chosen as per the need of the desired result. The position of metallic liquid in different locations leads to modification in antenna results in terms of frequency and/or radiation pattern. In the present work, the position of metallic liquid is created at the center of the microfluidic channel.The fabrication feasibility of the proposed metallic liquid antenna can be explained with the help of Fig. 34. Digital microfluidics is also a new consideration for the physical displacement of metallic liquid in microfluidic channel35. Another way to set the metallic liquid at a certain position in the microfluidic channel is by filling the empty sections with de-ionized water34. Since the total volume of water is very small, the frequency/radiation pattern modifications and efficiency reduction due to the water and losses are not significant34.The injection of metallic liquid at a certain position in the microfluidic channel can be possible in the following way. Initially, a syringe can inject the metallic liquid into the PMMA channel to fill the microfluidic that defines the radiating element. A bidirectional micropump unit is needed to reconfigure the physical length of the antenna by retracting a portion of the metallic liquid volume. Physical displacement of metallic liquid can be achieved through microfluidic techniques like pumping or electrowettingIn addition to flexibility, another advantage of a metallic liquid antenna in a microfluidic channel is its reconfigurability. The properties of the metallic liquid, such as its volume and shape, can be adjusted to tune the antenna’s operating frequency. The movement of liquid inside the microfluidic channel in different locations can reconfigure the radiation pattern. The antenna can achieve reconfigurability by changing the metallic liquid configuration within the microfluidic channel.


The human kinome comprises 518 protein kinases, of which approximately 10% lack one or more of the conserved amino acids necessary for catalytic activity. These proteins are categorized as pseudokinases and are predicted to be inactive enzymatically . Severaltrbl) and protein were originally identified [Resistance to therapy stands as a leading cause of cancer-related deaths and a significant obstacle to effective cancer treatment. Accumulating evidence suggests that Tribbles proteins play a crucial role in mediating drug resistance in cancer cells. Several articles in this Special Issue focus on how different members of the Tribbles protein family influence drug response in cancer patients. The review article by Mayoral-Varo et al. summarizes our evolving understanding of the implications of TRIB2, the most ancestral member of the Tribbles family, in mechanisms of drug resistance . The autentified . The autCollectively, the articles presented in this Special Issue provide valuable insights into the complex interplay between pseudokinases, specifically the Tribbles family, and cancer. By unraveling the molecular mechanisms underlying cell signaling mediated by Tribbles pseudokinases, the researchers aim to pave the way for the development of novel therapeutic strategies that can overcome drug resistance and enhance the effectiveness of cancer treatments. Likewise, the research presented in this Special Issue may also contribute to setting the bases for the potential exploration of Tribbles proteins as potential biomarkers in cancer.


ObjectivesThe aim of this study was to investigate the short-term outcomes of knotless barbed sutures used for both closures of myometrium and subcuticular tissues in patients with various operative indications and who underwent cesarean delivery (CD) in a single tertiary center.Materials and methodsA retrospective cohort study was conducted, and the patients were divided into two groups. The barbed suture group consisted of patients who underwent CD using barbed sutures for uterine closure  and subcuticular closure . The non-barbed group consisted of patients who underwent CD using monofilament sutures for uterine closure  and subcuticular closure .ResultsWhite blood cell count on post-operative day 1 was statistically lower in the barbed suture group (p=0.01), while there were no other significant differences between the two groups.ConclusionBarbed sutures can be used without major complications in patients who have undergone CD, including high-risk pregnancies. Cesarean delivery (CD) is one of the most common medical procedures performed on women all over the world, and it is essential for healthcare providers to keep improving operative techniques, including medical devices, in order to achieve better patient outcomes and decreased maternal morbidity . The knoA case-control study was conducted at the Osaka City University Graduate School of Medicine, Osaka, Japan. The patients were divided into two groups. The barbed suture group consisted of patients who underwent CD using a barbed suture for uterine closure  and subcuticular closure  between December 2019 and December 2020. The non-barbed group consisted of patients who underwent CD using a monofilament suture for uterine closure  and subcuticular closure  between October 2018 and October 2019. Patients with multiple pregnancies were excluded from this study.All patients received prophylactic intravenous antibiotics  before the initial skin incision to reduce the rate of SSI. Povidone iodine or chlorhexidine gluconate was used for the disinfection of the abdominal surgical site and vagina. The type of anesthesia was determined by the anesthesiologist. Abdominal entries were made by a Pfannenstiel or vertical incision, and a low transverse uterine incision was then made. Vertical skin incision was selected when the previous operation scar was vertical or massive bleeding during CD was expected. Following the delivery of the fetus and placenta, the uterine incision was sutured in a double-layer technique either with a barbed suture or a non-barbed suture. When additional sutures were required for sufficient hemostasis of the uterine incision, 0 PDS Plus (Ethicon) was used in a figure-of-eight suture for both groups. Hyaluronic acid/carboxymethylcellulose  was placed on the uterine closure site to prevent post-operative adhesion in cases with intact membranes . The perStatistical analysis was performed using SPSS software Version 24.0 . Categorical data were presented as numbers and percentages, while continuous valuables were presented as mean and standard deviation. The chi-squared test was used to analyze categorical data, and the Mann-Whitney U test was used to analyze continuous valuables. P-values of <0.05 were considered significant.This study was approved by the Ethical Committee of Osaka Metropolitan University Graduate School of Medicine .A total of 221 women were included in the barbed group, and 211 were included in the non-barbed group. Table The present study is one of the largest scale studies to demonstrate the capability of using barbed sutures in CD including high-risk pregnancies without major complications. Less knots were made in the barbed suture group, possibly resulting in a favorable outcome to reduce the chance of infection at the suture site. Stratafix is coated with triclosan, which is recommended for the prevention of infection by the Centers for Disease Control and Prevention (CDC) and the American College of Surgeons Surgical Infection Society ,9, and tSome authors expressed concerns about the use of barbed sutures. Firstly, bowel obstruction and perforation might be caused by the proximity of their sharp barbs . In the Barbed suture can be used for wound closure in CD without severe post-operative complications. Further investigation is necessary to elucidate the advantage of Stratafix in CD operation.


Peripheral neuropathy (PNP) in feet and/or hands and sexual dysfunction are common side effects of cancer therapies. In patients with other diseases, there is evidence of an association between peripheral nervous system disorders and sexual dysfunction due to the impact of impaired neuronal control on genital organ sensitivity. In cancer patient interviews, it has now been observed that PNP and sexual dysfunction may be related. The aim of the study was to investigate the potential association between PNP, sexual dysfunction, and physical activity behavior. Ninety-three patients with PNP of the feet and/or hands were interviewed in August/September 2020 in a cross-sectional study regarding medical history, sexual dysfunction and functionality of the genital organs. Thirty-one persons who participated in the survey provided seventeen evaluable questionnaires . Nine women (69%) and three men (75%) reported sensory disorders of the genital organs. Three men (75%) had erectile dysfunction. All men who had sensory symptoms of the genital organs received chemotherapy, and one man also received immunotherapy. Eight women were sexually active. Five (63%) of them reported genital organ symptoms and mainly lubrication disorders. Four (80%) of the five sexually inactive women reported genital organ symptoms. Eight of the nine women with sensory symptoms of the genital organs received chemotherapy, and one woman received immunotherapy.  Our limited data suggest genital organ sensory symptoms in chemotherapy and immunotherapy patients. Genital organ symptoms do not appear to be directly related to sexual dysfunction, and the association between PNP and genital organ symptoms appears to be more pronounced in sexually inactive women. Chemotherapy could cause sensory symptoms of the genital organs and sexual dysfunction by damaging genital organ nerve fibers. Chemotherapy and anti-hormone therapy (AHT) could trigger a disturbance of the hormone balance, which in turn could be causative for sexual dysfunction. It remains open whether the cause of these disorders is the symptomatology of the genital organs or the altered hormone balance. The significance of the results is limited due to the small number of cases. To our knowledge, this study is the first of its kind in cancer patients and allows a better understanding of the association between PNP, sensory symptoms of the genital organs, and sexual dysfunction.  In order to be able to narrow down the cause of these initial observations in cancer patients more precisely, larger studies are needed that can relate the influence of cancer therapy-induced PNP, physical activity level and hormone balance to sensory symptoms of the genital organs and sexual dysfunction. The methodology of further studies should take into account the frequent problem of low response rates in surveys on sexuality.  Peripheral neuropathy (PNP) occurs in 19–85% of cancer patients due to chemotherapy and immunotherapy. It mostly affects sensory nerve fibers, but may also affect the motor and autonomic nerves , 3], , . ErectilIn our care structure, some patients with proven PNP in feet and/or hands additionally reported symptoms in the genital organs similar to those of PNP in feet and hands. To our knowledge, this symptom has not been reported in cancer patients in the literature, and this could be the first paper about this symptom in cancer patients. The aim was to investigate a potential relationship between PNP, sexual dysfunction, and physical activity behavior in cancer patients. Medical records of cancer patients that have been treated at the Oncological Training and Exercise Therapy (OTT) of the University Hospital Cologne were retrospectively screened for inclusion criteria of cancer diagnosis, adult age, and proven PNP in feet and/or hands. The next step was to assess whether they also had or have sexual dysfunction and symptoms of the genital organs similar to those of PNP in feet and hands. Therefore, a cross-sectional survey was conducted, and ninety-three PNP patients of the OTT were contacted via online questionnaire in August/September 2020 regarding potential PNP associated sexual dysfunction of the genital organs. The reporting of PNP, symptoms of the genital organs, and sexual dysfunction was based on patients’ self-report using assessments which were compiled from standard PNP (EORTC QLQ-CIPN20) and sexuality  questionnaires as well as from newly generated questions for symptoms of the genital organs. The survey had a pilot character. Since there was no questionnaire covering the three topics PNP, symptoms of the genital organs, and sexual dysfunction, and since compliance of the participants had to be ensured, only parts of existing questionnaires were used. For organizational reasons as well as due to the COVID-19 pandemic, clinical neurologic PNP validation or nerve function measurement were not performed additionally. Of the ninety-three persons contacted, n=31 (33%) patients participated in the survey. N=21 (68%) completed the questionnaires. Two women had to be excluded because their PNP could not be related temporally to chemotherapy due to the onset of PNP fourteen years and one year after the end of chemotherapy, respectively. Two men were excluded because they were not receiving chemotherapy or immunotherapy and thus could not have PNP symptoms of the genital organs due to these therapies. Consequently, n=17 (55%) evaluable questionnaires (four men Table 1  and thirThree (75%) of the four men with PNP reported sensitive disorders of the genital organs Table 3 . The penSensitive symptoms of the genital organs were reported by nine (69%) of thirteen women Table 4 , most seSeven (54%) of the thirteen women had received anti-hormone therapy (AHT) previously and/or did so at the time of the study. Three (50%) of the six women with previous AHT and six (60%) of the five women on AHT at the time of the study reported sensitive symptoms of the genital organs, whereas five (83%) of the six women without AHT reported these symptoms. Eight (89%) of the nine women with sensitive symptoms of the genital organs had received chemotherapy previously and/or did so at the time of the study, and one (11%) had undergone previous immunotherapy as well as receiving it at the time of the study. Seven (54%) of the thirteen women were under fifty-two and thus defined as premenopausal, whereas six (46%) women were fifty-two or older and defined as postmenopausal. Premenopausal women were more likely to report sexual activity (pre=5 (71%) vs. post=3 (50%)) and sensitivity symptoms (pre=5 (71%) vs. post=4 (67%)) after chemotherapy or immunotherapy. Five (71%) of the premenopausal women were non-overweight and two (29%) were overweight. Among postmenopausal women, five (83%) were non-overweight and one (17%) was overweight. Of the ten non-overweight women, six (60%) were sexually active and seven (70%) had symptoms of the genital organs. Two (67%) of the three overweight women were sexually active and had symptoms of the genital organs.The aim of the study was to investigate the potential association between PNP, sexual dysfunction, and physical activity behavior. The main findings can be summarized as follows: Our limited data may indicate sensory symptoms of the genital organs in patients undergoing chemotherapy and immunotherapy. This is supported by the reported symptoms of the skin cancer patient who received immunotherapy and no chemotherapy. This kind of genital organ symptomatology does not seem to be directly related to sexual dysfunction. Nevertheless, the association between PNP and symptoms of the genital organs seems to be much more pronounced in sexually inactive women. However, due to the small number of subjects, no correlation analysis but descriptive statistics were performed.PNP is caused by the destruction of nerve fibers due to chemotherapy and immunotherapy . ChemothThe small number of cases is a limitation of the study, since it reduces the significance of the results. Moreover, the menopausal status of the women before therapy onset was not recorded. In addition, the effect of sexual activity on men could not be investigated, as all patients were sexually active in the last four weeks. Another limitation was that not all questions of the FSFI and the EORTC questionnaires were used, but only a selection. Future surveys should include complete questionnaires or subcategories of such questionnaires. A strength of the study is that this is the first investigation of this kind in cancer patients. Thus, sexual dysfunction, sensory symptoms of the genital organs, and PNP in cancer therapy could now be better understood in the context of each other. Future studies need to include more patients and measure physical activity behavior of patients to assess and analyse an association between physical activity level and occurrence of PNP symptomatology as well as sexual dysfunction. From this, correlation analyses can be generated, and physical activity therapy prevention and rehabilitation programs can follow. Exercise therapy can improve PNP through sensorimotor exercise and whole-body vibration exercise, and sexual dysfunction can be improved through pelvic floor muscle exercise , 15], , .Our limited data suggest the possible existence of genital organ sensitive symptoms in chemotherapy and immunotherapy patients. Larger-scale studies are needed that can assess the influence of cancer therapy-induced PNP, physical activity level, and hormonal balance on genital organ sensitive symptoms and sexual dysfunction, which is necessary to be able to narrow down the reasons for the present observations. Our study addresses the problem that response rates to surveys on sexual difficulties and dysfunction are often low , which nAll patients gave informed consent to participate.The ethics votes of the IST University (PNPGB20200620) and the University Hospital Cologne (17-165) are available.The authors declare that they have no competing interests. Sections of this publication are part of Dirk Brodesser’s master thesis.


There are numerous vaginal and abdominal surgical approaches for the treatment of pelvic organ prolapse (POP). Even the standard techniques show great variability due to modifications depending on anatomy, available instruments and materials. Recently, the role of hysterectomy in prolapse surgery as well as the use of synthetic meshes have been questioned. Here, we present a standardised mesh-free minimally invasive pelvic floor reconstruction technique with uterus preservation.Unilateral pectineal suspension (UPS) is carried out in five defined steps with the use of the da Vinci Xi® surgical system. The desired anatomical result is simulated by intraoperative uterus manipulation. The cranial part of the pectineal ligament is used for lateral fixation. A non-absorbable suture is placed between the pectineal ligament and the anterior cervix to suspend the uterus in its natural anatomical position.For outcome measurement, degree of prolapse was assessed pre- and postoperatively according to the POP-Q system.Unilateral pectineal suspension offers several advantages. Medial tension-free positioning of the uterus is achieved. The use of the cervix as fixation structure allows for excellent pelvic floor support and stable results. Normal pelvic floor mobility and natural axis of the vagina are restored.Unilateral pectineal suspension is an efficient minimal-invasive mesh-free procedure which allows uterus preservation and offers reliable level I support respecting the physiological pelvic anatomy. In addition, there is no need for ureteral dissection or bowel manipulation. The technique offers clinical standardization and can easily be integrated into the spectrum of modern surgical POP repair. The unilateral pectineal suspension (UPS) concept provides a mesh-free option for Level I correction preserving the uterus. It is a standardised and easily reproducible method due to the exact definition of the relevant surgical landmarks and the option for intra-operative simulation of the desired result. The suspension technique allows for preservation of the natural vaginal axis and physiologic pelvic floor mobility. The reduction of variability as provided by the standardised 5-step procedure shows a fast- learning curve and is easily adoptable for teaching and training purposes in every modern pelvic floor center.Pelvic organ prolapse (POP) affects 30-50% of the female population depending on definition . SurgeryHowever, the role of hysterectomy in prolapse surgery has been increasingly questioned. Hysteropexy may be a viable alternative to hysterectomy in women with uterine prolapse. It can be performed either transvaginally by sacrospinous fixation, or abdominally or laparoscopically by placing a mesh or biologic graft form the cervix to the anterior longitudinal ligament, or by shortening of the uterosacral ligament. In addition, mesh- supported pectopexy can also be successfully performed preserving the uterus .In recent years, the use of synthetic meshes for POP correction has become a matter of concern, leading to the classification of transvaginal mesh products as high-risk devices by the FDA in 2016 , followeHere we present UPS as a novel minimal invasive method for the operative treatment of apical POP fulfilling a broad range of quality criteria for POP correction. UPS provides anatomical reconstruction in a standardized 5-step procedure.The work presented was conducted at the maximum care University Women’s Hospital of Klinikum Nuremberg, Paracelsus Medical University, in accordance with the ethical standards of the Declaration of Helsinki. All patients were informed that a case description as well as documentation of their intraoperative situs might be used for publication purposes and gave their explicit consent.Patients presented with apical prolapse of POP-Q 2 or higher as quantified according to the pelvic organ prolapse quantification system (POP-Q) described by ICS/IUGA . SurgeryThe patients were examined vaginally two days postoperatively and during a follow-up visit scheduled three months after surgery to evaluate the outcome of their pelvic floor repair. Primary outcome parameters were defined as no recurrence of apical prolapse after three months according to the POP-Q criteria as specified above and subjective overall satisfaction with the status of the pelvic floor as assessed by a simple yes or no answer.A set of quality parameters for POP surgery was defined and the intra- and postoperative results were compared to the proposed set.UPS is performed in 5 defined steps. The uterus is intraoperatively guided to its desired position by two rotunda vulsellum forceps. The main anatomical landmarks for UPS are the pectineal (Cooper) ligament on the right side and the anterior cervix at the isthmo-cervical transition. The two structures are exposed Figure , 1b, folPOP-Q two days after surgery resembled the intraoperative result of POP-Q 0-1. During the follow-up examination three months after surgery the result of the apical fixation remained stable, and the patients confirmed their subjective overall satisfaction with their prolapse repair.We have compiled a set of intra- and perioperative as well as general quality criteria for POP correction . All posWe demonstrate UPS as a novel, minimally invasive, unilateral, mesh free suspension technique for isolated or combined apical POP correction in five defined steps. The procedure respects the physiological direction and angulation of the vaginal axis using an alternative fixation point. Reliable apical fixation is effectively accomplished in all POP stages, including stage 4 total prolapse. The uterus can be preserved unless uterine pathology warrants hysterectomy. The method provides midline positioning of the uterus and physiologic pelvic floor mobility. UPS can be combined with additional vaginal and abdominal procedures for the correction of POP and / or SUI during the same or a subsequent procedure. In summary, UPS fulfills a large panel of quality criteria for POP surgery, making it a strong candidate for a new standard of care.The clinical justification for this technique is based on the combination of two thoroughly analysed principles: lateral suspension to the pectineal ligament and sacrospinous unilateral fixation of the uterus. As opposed to bilateral fixation we intentionally chose unilateral suspension since it avoids tension on the suspended structures and allows physiologic mobility. Respecting the direction of the round ligament for suspension a physiologic position of the suspended uterus is achieved. The use of the cervix as a stable fixation structure provides excellent pelvic floor support. The procedure avoids dissection along the ureter as well as bowel manipulation. Furthermore, it is assumed that the concomitant tension-free repositioning of the urethra due to restoration of the vaginal axis could avoid the appearance of de novo SUI.The application of robotic technology offers a significant reduction of surgical compromise and adds value due to the simplification of suture and knot application. It facilitates anatomical dissection and minimises blood-loss, combining accuracy and surgical ergonomy. Nevertheless, the procedure can be standardised and performed by conventional laparoscopy to be broadly integrated into urogynaecology practice.Extensive search of the international literature has shown that apical POP correction can be performed using various different approaches including sacrocolpopexy, vault suspensions, sacrospinous fixation and vaginal obliterative procedures . In rece.In recent trials using pelvic MRI follow-up to compare postoperative results after various approaches for pelvic floor reconstruction, sacrocolpopexy (SCP) as well as sacrospinous fixation (SSF) have both been shown to deviate the vaginal axis in its medium and inferior portions . As oppoIn this study we describe the UPS technique as a novel approach for apical POP repair with intraoperative and immediate postoperative as well as short-term results. We are confident that this new method will find its place within the spectrum of recognised methods for apical POP correction due to its major advantages of being a standardised procedure without mesh application and the option to preserve the uterus. Certainly, intermediate and long-term outcomes have to be investigated in a larger cohort of patients. Retrospective as well as prospective studies are currently underway to address these issues, and long-term outcomes regarding the analysis of the sustainability of the anatomic results have to be awaited. We conclude that UPS fulfills a broad range of quality criteria for apical POP correction, making it a prime candidate for a new and innovative standard of care.https://vimeo.com/esge/review/687906690/1250f7db1d


A 66-year-old female presented in the emergency department with Blue-Toe-Syndrome (BTS) and signs of osteitis of her left big toe. Imaging workup of the peripheral vasculature showed no findings. Upon invasive angiography, severe focal stenosis of the dorsalis pedis artery (DPA) could be seen at the talonavicular joint. Complete regression of the stenosis was inducible by dorsal extension in the ankle joint. Further imaging revealed an underlying subluxation of the talonavicular joint as cause of the arterial compression. Entrapment of the DPA is a rare condition and most often described in relation to connective tissue bands or variant muscular tendons . In the presented case, bony compression of the PDA due to cranial subluxation of the talus was seen as the cause of BTS and osteitis of the phalanx of the first toe. Entrapment of the lower extremity vessels may lead to ischemia associated symptoms such as pain and intermittent foot claudication. In case of sole ischaemia of the digitus I, blue toe syndrome (BTS) may be present. BTS is defined as intermittent malperfusion of the big toe caused by vascular obstruction, resulting in pain and blue discoloration of the big toe. Studies report space-occupying lesions as underlying causes for this syndrome. One of the most commonly seen entrapment syndromes involves the popliteal artery, and here abnormally surrounding musculoskeletal structures such as the proximal part of the gastrocnemius muscle lead to functional arterial compression . Cases oA 66-year-old female presented with intermittent pain of the phalanx of the first toe for one year, especially while walking, increasingly limiting her mobility. Her past medical history included hypothyroidism adjusted by Levothyroxin, varices of the great saphenous vein treated by radiofrequency ablation 8 months priorly and an inguinal hernia which was minimally invasively repaired more than ten years ago. Upon clinical inspection, her big toe was seen to be swollen and of blue colour. No wounds or ulcerations were seen. Focussed imaging assessment of the left big toe was done with MRI, which showed intraosseous edema and loss of bone marrow signal suggesting osteitis Fig. . InitialUpon interdisciplinary review of the remaining symptoms and inconclusive diagnostic findings, indication for an invasive digital-subtraction-angiography (DSA) for imaging of the left-sided pedal arteries was set. The popliteal artery, the tibiofibular trunk as well as the fibular artery and the anterior and posterior tibial arteries showed normal contrast-media dynamics in DSA imaging. During the procedure, the patient developed vasospasms of the calf vasculature, which could be resolved with intra-arterial administration 0.2 mg nitroglycerin. Upon DSA imaging of the left ankle and foot, a relevant high-grade stenosis of the DPA could be clearly depicted with vessel diameter narrowing and contrast media stagnation. This finding was located precisely at the level of the talonavicular joint gap. Considering the unusual location for circumscribed atherosclerotic changes, dynamic DSA runs were performed with the patient’s foot firstly in neutral position and then in dorsal extension and plantar flexion of the ankle joint. In dorsal extension, the stenosis of the DPA was seen to resolve completely Fig. . SubsequInterdisciplinary review of these findings was done by interventional radiologists, angiologists and vascular and orthopedic surgeons. After careful discussion with the patient on basis of shared decision making, no feasible interventional or operative treatment could be conceptualized. Conservative treatment with local vasodilatative ointment was initiated.Among vascular compression syndromes, functional entrapment of the DPA is a rare condition. In the literature, only few cases of functional compression of the DPA are described, whereby compression was often present mainly in plantarflexion and located at different levels , 5. One Symptoms of BTS may be caused by many underlying conditions which are characterized by either decreased arterial inflow, impaired venous outflow or abnormal blood circulation , 7. MostTreatment of DPA entrapment is depending on its pathogenesis. In the cases presented by Weichmann et al. and Griffin et al., arterial compression was caused by the extensor hallucis brevis tendon, which could be resolved by transection and reinsertion of the tendon . In the This report describes a functional osseous compression syndrome of the dorsalis pedis artery due to a subluxation in the talonavicular joint in a patient presenting with blue-toe-syndrome and forefoot pain. Functional arterial compression syndromes of the pedal arteries are a rare pathology, and this report is the first to describe an osseous pedal arterial compression as etiology.


Negative symptoms represent a fundamental aspect of schizophrenia: they have a substantial impact on patients’ real-life functioning and do not respond satisfactorily to currently available treatments. Therefore, a better understanding of the pathophysiological mechanisms underlying these symptoms could favor the development of new treatments.To date, the most validated pathophysiological hypothesis indicates an association between the Motivational domain  and alterations in the neuronal circuits involved in motivation. The Expressive Deficit domain  would be subtended by widespread alterations of cortical connectivity and associated with impaired neurocognition, social cognition, and the presence of neurological soft signs.The aim of the present study is to examine the neurobiological correlates of the two domains of negative symptoms, starting from the brain areas that have been most commonly found in the literature to be associated with negative symptoms.Resting-state (rs) fMRI data were acquired in 62 subjects with schizophrenia (SZ) and 46 healthy controls (HC). The two negative symptom domains were assessed using the Brief Negative Symptom Scale. In addition, the following assessment tools were used: the Positive and Negative Syndrome Scale for the assessment of positive symptoms and disorganization, the Calgary Depression Scale for Schizophrenia for depression and the St. Hans Rating Scale for extrapyramidal symptoms. The study of the possible relationships between rs-brain activity and the negative symptoms domains was conducted through partial correlations, checking for possible confounding factors .The SZ, compared to the HC, showed higher rs-brain activity of the right inferior parietal lobule and of the right temporoparietal junction and lower rs-brain activity of the right dorsolateral prefrontal cortex, bilateral anterior dorsal cingulate cortex, bilateral ventral caudate and bilateral dorsal caudate. Furthermore, in the group of patients, the rs-brain activity of the left ventral caudate showed a moderate negative correlation with the Expressive deficit domain , but not with the Motivational domain.The results of the present study, in line with the literature, demonstrated how the two domains of negative symptomatology are subtended by different pathophysiological mechanisms. Given the role played by the ventral caudate in neurocognitive processes, these results are in line with the hypothesis that Expressive deficit may have a common etiopathogenesis with cognitive deficits. A better understanding of the neurobiology of negative symptoms could foster the development of innovative treatment strategies targeting the two negative symptom domains.None Declared


Ultrasound (US) imaging has been widely used for tumor tracking in image-guided radiotherapy. The quality of US images using conventional probes highly depends on user proficiency and anatomical changes, which has severely hindered the use of US-based organ motion monitoring for pancreatic cancer. The flexible array transducer is a novel and promising solution to address the limitation of conventional US probes. At the same time, its strength and flexible geometry also makes the image reconstruction and delay-and-sum (DAS) beamforming very challenging. Inaccuracy in delay calculation results in defocused and distorted US images. In this study, we proposed a novel shape estimation for flexible array transducer to enhance abdomen motion monitoring.Pancreatic cancer with less than 10% 3-year survival rate is one of deadliest cancer types and greatly benefits from enhanced radiotherapy. Organ motion monitoring helps spare the normal tissue from high radiation and, in turn, enables the dose escalation to the target that has been shown to improve the effectiveness of RT by doubling and tripling post-RT survival rate. The flexible array transducer is a novel and promising solution to address the limitation of conventional US probes. We proposed a novel shape estimation for flexible array transducer using two sequential algorithms: (i) an optical tracking-based system that uses the optical markers coordinates attached to the probe at specific positions to estimate the array shape in real-time and (ii) a fully automatic shape optimization algorithm that automatically searches for the optimal array shape that results in the highest quality reconstructed image. We conducted phantom and in vivo experiments to evaluate the estimated array shapes and the accuracy of reconstructed US images. The proposed method reconstructed US images with low full-width-at-half-maximum (FWHM) of the point scatters, correct aspect ratio of the cyst, and high-matching score with the ground truth. Our results demonstrated that the proposed methods reconstruct high-quality ultrasound images with significantly less defocusing and distortion compared with those without any correction. Specifically, the automatic optimization method reduced the array shape estimation error to less than half-wavelength of transmitted wave, resulting in a high-quality reconstructed image. The organ and tumor movement during radiotherapy (RT) treatment delivery has negative adverse impact on the effectiveness of the RT and its clinical outcome . To compThe major cause of intrafraction OAR and target motion is respiratory-induced motion. Respiratory-related tumor motion in pancreatic cancer can reach up to 35 mm . This coDirect tumor tracking methods are highly accurate, but use of X-ray imaging or electromagnetic sensing can result in exposing patients to extra radiation dose or implanting invasive electromagnetic markers, and the associated cost is high, and they cannot retrofit MR imaging to existing RT treatment machines. On the other hand, ultrasound-based direct approach has several advantages ,33,38:  beamformer is commonly for B-mode image reconstruction from radiofrequency (RF) channel data. DAS requires an accurate array shape to calculate the time-of-flight (ToF) between elements and focal point, and accordingly, apply proper time delays to each channel . As a reNumerous approaches have been proposed to address the beamforming problem. De Oliveira et al.  and BoerIn this study, we propose a novel shape-estimating method for a flexible array transducer using a sequential approach. The optical-based shape-estimation algorithm uses the optical tracking system to collect the spatial coordinates of the array and estimate its shape, while the shape optimization algorithm further optimizes the estimated shape by searching for the array shape that can reconstruct the beamformed image with highest quality without any external device. We conducted phantom and in vivo experiments and evaluated the accuracy of the estimated array shapes and reconstructed ultrasound images. The infrared (IR) optical tracker can emit and detect the reflected IR light from the passive marker spheres and triangulate the real-time spatial coordinates of the spheres in 3D space . SeveralAs the abdominal surface shape of the human is similar to an arc, the shape of the flexible array was first simplified as a concave circular arc with a specific radius. With x-z coordinates of all the spheres, a circle can be fitted to the data points based on the least-squares fitting algorithm developed by Pratt , and theT is the number of transmitting elements, With the knowledge of the array shape, the DAS beamforming can be performed to reconstruct the beamformed image. Specifically, the time-of-flight or  follows :(8)δt,r. Therefore, the optical-based shape estimation algorithm may not achieve the expected accuracy of array shape. To further improve the accuracy, we developed a shape optimization algorithm that could describe the array shape with a more detailed model and search for the optimal shape to reconstruct ultrasound images with the highest quality.A more detailed mathematical model was designed to describe the flexible array shape. As the center-to-center distance between two successive elements is fixed as the pitch With the knowledge of azimuth angles An evaluation method for the beamformed image lgorithm , studieslgorithm , and autlgorithm ,66, we ulgorithm . The beaWhen performing the test scans on different imaging targets, the flexible array transducer was set in a flat shape to make the ground truth of the array shape known. Then, different array shape assumptions were randomly generated and used for reconstructing the beamformed image. The mean absolute errors between the assumptions and ground truth were plotted versus the entropy of their corresponding beamformed images. The results show that the entropy of the beamformed image tends to be larger when the array shape error is smaller. Therefore, we set the principle that the beamformed image using an array shape of higher accuracy would have a larger entropy. More in-depth discussions about the effect of entropy in ultrasound images will be presented in the discussion.The circular arc array shape estimated using the optical-based shape estimation algorithm is used as the initial shape assumption for further optimization. The optimal shape parameters With the knowledge of azimuth angle and center position of each element, the angle and origin position of each transmission scan-line can be determined. Scan conversion is performed to transform the polar coordinate ultrasound data into Cartesian coordinate data. Bilinear interpolation is applied to the scan conversion task. The method uses four adjacent data points in the beamformed image  follows ,69:(14)TThe NDI Polaris Spectra System , rigid body tools, and passive marker spheres were all used for optical-based shape estimation. Five passive marker spheres were attached to the back surface of a flexible array transducer . Parameters of the transducer are listed in Three cylinder-shaped objects with known radius The flexible array transducer was also attached to the surface of the abdominal region of an ABDFAN Abdominal Ultrasound Phantom  in lateral direction. The cross-sectional X-ray image of the phantom and transducer was captured using a Cios Alpha C-arm imaging system . Then, the transducer array was segmented from the X-ray image and fitted into a curve shape. This segmented array shape was considered as the ground truth and compared with the optical-based estimated and optimized array shape.The flexible array transducer connected with the Vantage System  was used to scan a CIRS General Purpose Ultrasound Phantom , liver area of an ABDFAN Abdominal Ultrasound Phantom , and a healthy volunteer under Johns Hopkins Institutional Review Board approval. Ultrasound gel was used to create a random curvature for the scanning surface of flexible array transducer, which is depicted in The DAS beamforming, scan conversion, and image post-processing were implemented in MATLAB. The RF channel data and estimated array shape parameters were used to reconstruct the “corrected” ultrasound images. In addition, the RF channel data was wrongly delayed and reconstructed under the assumption that the flexible array is flat and linear. These “uncorrected” results stand for the images reconstructed without any correction on array shape. The RF channel data from the linear array transducer was also reconstructed as the ground truth, which will be evaluated and compared with the “corrected” and “uncorrected” results of the flexible array transducer.The shape optimization algorithm was implemented in the MATLAB with the “surrogateopt” function, which is a global solver for time-consuming objective functions. To achieve a faster convergence, the initial shape parameters The bounding values were set based on the abdominal surface shape of the human. The shape optimization was terminated after 200 iterations. The array shape parameters As defocusing and distortion are the two major problems of the reconstructed ultrasound image without the knowledge of array shape, the following metrics were used to evaluate the quality and accuracy of the results. For the CIRS phantom results, the defocusing effect was assessed by evaluating the lateral full-width-at-half-maximum (FWHM) of all the point scatters, while the image distortion was evaluated by the aspect ratio of the cyst. The aspect ratio is the ratio of lateral and axial axes of the cyst. An ellipse with aspect ratio of 1 is a circle:GCNR = 1, the distributions are completely independent, which represents a high contrast.For the ABDFAN phantom and liver scan results, the cysts, blood vessels, and muscles were manually segmented. The image distortion was evaluated by computing the Sørensen–Dice coefficient (Dice score) , JaccardR (GCNR)  were useThe ground truth radius of the cylinder-shaped objects The uncorrected, optical-based estimation, and optimization results of the CIRS phantom are shown in The uncorrected, optical-based estimation, and optimization results of the ABDFAN phantom and liver scan are shown in The evaluation results showed that the proposed optical-based shape estimation algorithm could successfully estimate the array shape of the flexible array transducer with reasonable accuracy and reconstruct ultrasound images with significantly less defocusing and distortion than those without any shape correction. The proposed shape optimization algorithm could further improve the accuracy of the array shape estimation. The mean absolute error of the element positions was less than half-wavelength of the transmitted wave, which means the algorithm could reconstruct ultrasound images with optimal accuracy and quality. In addition, the computation time of the shape estimation algorithm was less than 0.01 s, while that of the shape optimization algorithm for 200 iterations was about 1000 s. Therefore, the proposed shape estimation algorithm could achieve real-time ultrasound imaging with acceptable accuracy and frame rate. For specific frames that require higher accuracy and quality, the shape optimization algorithm could be used to further improve the reconstructed images.The Shannon entropy is a measurement of information and uncertainty in random variables . Hughes As the RF channel data is delayed and summed based on the array shape to form the beamformed image, errors in array shape will make the delayed RF data sum in the opposite phase, which causes significant signal loss. It would lead to a smaller backscattered amplitude and the signal’s entropy would increase. In addition to our testing of the correlation between the array shape accuracy and beamformed image entropy, we also tested the effect of entropy by maximizing and minimizing the entropy in our shape optimization algorithm and compared the results. Here, we presented a shape estimation approach that consists of two sequential methods to estimate the array shape and reconstruct B-mode images acquired by flexible array transducer using deep learning method. One potential application of our method is to improve the ultrasound imaging reconstruction technique for in vivo tumors shape and size calculations . With cuThere are some limitations of this study: First, the computation time of the shape optimization algorithm is long. As it is explained in the methods, the Kronecker delta function terature , a futurIn this study, we proposed a novel shape estimation approach that consists of two sequential methods to estimate the array shape and reconstruct B-mode images acquired by flexible array transducer. The optical-based shape estimation algorithm used the optical tracking system to collect the spatial coordinates of the array and estimate the array shape as a circular arc with specific radius. The shape optimization algorithm searched for the array shape that maximized the entropy of its beamformed image. The evaluation results showed that the estimation algorithm could reconstruct ultrasound images with significantly less defocusing and distortion than those without any correction, while the optimization algorithm could further reduce the array shape error to less than half-wavelength of the transmitted wave and improve the accuracy and quality of the reconstructed images. Therefore, the proposed algorithms have the potential to enable high-quality real-time ultrasound imaging with the flexible array transducer. Additionally, as no holders are required for probe fixation, the real-time reconstitution enables US-based gastrointestinal organ motion monitoring during the radiotherapy.


Editorial on the Research TopicInsights in cardiovascular biologics and regenerative medicine: 2022The cardiovascular Biologics and Regenerative Medicine field is rapidly evolving with recognition of new pathogenetic mechanisms and targets for treatment. One major challenge, however, is represented by the dichotomy between mechanistic studies and clinical applications. The goal of this special edition Research Topic is to shed light on the progress made in the past decade in the field of cardiovascular biologics and on its future challenges to provide a thorough overview of the field and to help moving on toward clinical studies.Adelino et al. elegantly assessed the safety profile of the adipose graft transposition procedure (AGTP). This approach consists of placing an autologous pericardial adipose pedicle over the infarct scar  surgery. In this small clinical study known as MiHeart/IHD, patients with severe coronary artery disease who underwent CABG procedure were injected with autologous bone marrow-derived cells. This trial showed that cell therapy as an adjuvant to CABG was safe and improved regional stress-induced myocardial ischemia after 30 days, compared to placebo treatment. The authors postulated a potential mechanism of action being the paracrine release of extracellular vesicles. This work highlights the potential benefit of stem cell therapy for treating stress-induced myocardial ischemia in the setting of CABG and should be validated by longer term studies with mechanistic underpinnings.In the field of cellular biologics for the adjuvant treatment of myocardial ischemia, a number of cell types have been clinically tested for the treatment of myocardial infarction and heart failure, including stem cells, progenitor cells, and mononuclear cells derived from the bone marrow . WhereasWang et al. provide an extensive and accurate report of a research field that goes back to 2022 and is still open to effective pharmacological modulation. The authors highlight the pathophysiological role of the PRR and downstream pathway in the brain, where the PPR can have strong implications for arterial hypertension development. The soluble form of the PRR is seemingly implicated in obesity-associated hypertension and sodium retention at the kidney level. Despite treatments for arterial hypertension are well developed, a significant proportion of patients on multi-drug therapy do not reach recommended levels of blood pressure renin and its receptor (PRR) exert complementary control of fibrotic remodelling in many human diseases . In a repressure . Inhibitpressure . The revpressure .Varghese et al. provides a summary of aging-associated molecular alterations to cardiovascular cell types that include telomeric shortening, epigenetic modifications, mitochondrial dysfunction, and cellular senescence  and long noncoding RNAs (lnc-RNAs) provide instructive cues that regulate physiological tissue function as well as disease pathology. Since non-coding RNAs regulate gene expression, they play key roles in cardiac aging and the progression of cardiovascular disease. This review article by nescence . The sigIn conclusion, this thematic issue has the merit to underscore common pathogenetic mechanisms that can be targeted either pharmacologically or through novel tissue engineering solutions to foster endogenous repair. Organ reconstitution represents the optimal outcome, yet the less ambitious target of stabilizing the disease through modulation of fibrosis or cell therapy could result in tangible improvement of life quality and expectancy of patients with cardiovascular disease. Hopefully, this article collection will inspire, inform and provide direction and guidance to researchers in the field.