Comprehensive review of hepatocellular carcinoma with portal vein tumor thrombus:State of art and future perspectives

Background:Despite advances in the diagnosis of patients with hepatocellular carcinoma(HCC),70%-80%of patients are diagnosed with advanced stage disease.Portal vein tumor thrombus(PVTT)is among the most ominous signs of advanced stage disease and has been associated with poor survival if untreated.Data sources:A systematic search of MEDLINE(PubMed),Embase,Cochrane Library and Database for Systematic Reviews(CDSR),Google Scholar,and National Institute for Health and Clinical Excellence(NICE)databases until December 2022 was conducted using free text and MeSH terms:hepatocellular carcinoma,portal vein tumor thrombus,portal vein thrombosis,vascular invasion,liver and/or hepatic resection,liver transplantation,and systematic review.Results:Centers of surgical excellence have reported promising results related to the individualized surgical management of portal thrombus versus arterial chemoembolization or systemic chemotherapy.Critical elements to the individualized surgical management of HCC and portal thrombus include precise classification of the portal vein tumor thrombus,accurate identification of the subgroups of patients who may benefit from resection,as well as meticulous surgical technique.This review addressed five specific areas:(a)formation of PVTT;(b)classifications of PVTT;(c)controversies related to clinical guidelines;(d)surgical treatments versus non-surgical approaches;and(e)characterization of surgical techniques correlated with classifications of PVTT.Conclusions:Current evidence from Chinese and Japanese high-volume centers demonstrated that patients with HCC and associated PVTT can be managed with surgical resection with acceptable results.

Simultaneous portal and hepatic vein embolization is better than portal embolization or ALPPS for hypertrophy of future liver remnant before major hepatectomy: A systematic review and network meta-analysis

Background:Post-hepatectomy liver failure(PHLF)is the Achilles’heel of hepatic resection for colorectal liver metastases.The most commonly used procedure to generate hypertrophy of the functional liver remnant(FLR)is portal vein embolization(PVE),which does not always lead to successful hypertrophy.Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)has been proposed to overcome the limitations of PVE.Liver venous deprivation(LVD),a technique that includes simultaneous portal and hepatic vein embolization,has also been proposed as an alternative to ALPPS.The present study aimed to conduct a systematic review as the first network meta-analysis to compare the efficacy,effectiveness,and safety of the three regenerative techniques.Data sources:A systematic search for literature was conducted using the electronic databases Embase,PubMed(MEDLINE),Google Scholar and Cochrane.Results:The time to operation was significantly shorter in the ALPPS cohort than in the PVE and LVD cohorts by 27 and 22 days,respectively.Intraoperative parameters of blood loss and the Pringle maneuver demonstrated non-significant differences between the PVE and LVD cohorts.There was evidence of a significantly higher FLR hypertrophy rate in the ALPPS cohort when compared to the PVE cohort,but non-significant differences were observed when compared to the LVD cohort.Notably,the LVD cohort demonstrated a significantly better FLR/body weight(BW)ratio compared to both the ALPPS and PVE cohorts.Both the PVE and LVD cohorts demonstrated significantly lower major morbidity rates compared to the ALPPS cohort.The LVD cohort also demonstrated a significantly lower 90-day mortality rate compared to both the PVE and ALPPS cohorts.Conclusions:LVD in adequately selected patients may induce adequate and profound FLR hypertrophy before major hepatectomy.Present evidence demonstrated significantly lower major morbidity and mortality rates in the LVD cohort than in the ALPPS and PVE cohorts.

Machine Learning With Data Assimilation and Uncertainty Quantification for Dynamical Systems:A Review

Data assimilation(DA)and uncertainty quantification(UQ)are extensively used in analysing and reducing error propagation in high-dimensional spatial-temporal dynamics.Typical applications span from computational fluid dynamics(CFD)to geoscience and climate systems.Recently,much effort has been given in combining DA,UQ and machine learning(ML)techniques.These research efforts seek to address some critical challenges in high-dimensional dynamical systems,including but not limited to dynamical system identification,reduced order surrogate modelling,error covariance specification and model error correction.A large number of developed techniques and methodologies exhibit a broad applicability across numerous domains,resulting in the necessity for a comprehensive guide.This paper provides the first overview of state-of-the-art researches in this interdisciplinary field,covering a wide range of applications.This review is aimed at ML scientists who attempt to apply DA and UQ techniques to improve the accuracy and the interpretability of their models,but also at DA and UQ experts who intend to integrate cutting-edge ML approaches to their systems.Therefore,this article has a special focus on how ML methods can overcome the existing limits of DA and UQ,and vice versa.Some exciting perspectives of this rapidly developing research field are also discussed.Index Terms-Data assimilation(DA),deep learning,machine learning(ML),reduced-order-modelling,uncertainty quantification(UQ).

Dental impact of anti-fibroblast growth factor 23 therapy in X-linked hypophosphatemia

Elevated fibroblast growth factor 23(FGF23)in X-linked hypophosphatemia(XLH)results in rickets and phosphate wasting,manifesting by severe bone and dental abnormalities.Burosumab,a FGF23-neutralizing antibody,an alternative to conventional treatment(phosphorus and active vitamin D analogs),showed significant improvement in the long bone phenotype.Here,we examined whether FGF23 antibody(FGF23-mAb)also improved the dentoalveolar features associated with XLH.Four-week-old male Hyp mice were injected weekly with 4 or 16 mg·kg−1 of FGF23-mAb for 2 months and compared to wild-type(WT)and vehicle(PBS)treated Hyp mice(n=3–7 mice).Micro-CT analyses showed that both doses of FGF23-mAb restored dentin/cementum volume and corrected the enlarged pulp volume in Hyp mice,the higher concentration resulting in a rescue similar to WT levels.FGF23-mAb treatment also improved alveolar bone volume fraction and mineral density compared to vehicle-treated ones.Histology revealed improved mineralization of the dentoalveolar tissues,with a decreased amount of osteoid,predentin and cementoid.Better periodontal ligament attachment was also observed,evidenced by restoration of the acellular cementum.These preclinical data were consistent with the retrospective analysis of two patients with XLH showing that burosumab treatment improved oral features.Taken together,our data show that the dentoalveolar tissues are greatly improved by FGF23-mAb treatment,heralding its benefit in clinics for dental abnormalities.

The haplotype-resolved T2T reference genome highlights structural variation underlying agronomic traits of melon

Melon(Cucumis melo L.)is an important vegetable crop that has an extensive history of cultivation.However,the genome of wild and semi-wild melon types that can be used for the analysis of agronomic traits is not yet available.Here we report a chromosome-level T2T genome assembly for 821(C.melo ssp.agrestis var.acidulus),a semi-wild melon with two haplotypes of∼373 Mb and∼364 Mb,respectively.Comparative genome analysis discovered a significant number of structural variants(SVs)between melo(C.melo ssp.melo)and agrestis(C.melo ssp.agrestis)genomes,including a copy number variation located in the ToLCNDV resistance locus on chromosome 11.Genome-wide association studies detected a significant signal associated with climacteric ripening and identified one candidate gene CM_ac12g14720.1(CmABA2),encoding a cytoplasmic short chain dehydrogenase/reductase,which controls the biosynthesis of abscisic acid.This study provides valuable genetic resources for future research on melon breeding.

Light-controlled phosphorylation in the TrkA-Y785 site by photosensitive UAAs activates the MAPK/ERK signaling pathway

Background:This paper aims to establish a light-controlled phosphorylation detection method at the Y785 site of tropomyosin receptor kinase A(TrkA)receptor in mammalian cells by using genetic code expansion technology and detecting the effects of optical activation of this site on the downstream MAPK/ERK pathway.The study is based on the current situation that the regulatory mechanism of TrkA phosphorylation has not been fully elucidated.Methods:Two photosensitive unnatural amino acids,p-azido-L-phenylalanine(AzF)and photo-caged tyrosine(ONB)were introduced into the TrkA-Y785 site by genetic code expansion technology and site-directed mutagenesis.Western blotting and laser confocal imaging were conducted to analyze the effects of this site on activating the MAPK/ERK pathway and nerve cell differentiation before and after photostimulation.Results:Our results supplemented the light-controlled results of the TrkA-Y785 site based on our previous research and verified that Y785 also makes important contributions in regulating the MAPK/ERK pathway.Conclusion:This study demonstrated the significant contributions of the TrkAY785 site in regulating the ERK pathway by precisely controlling the phosphorylation state of a single tyrosine site.

Differences and similarities between mesenchymal stem cell and endothelial progenitor cell immunoregulatory properties against T cells

Bone-marrow-derived mesenchymal stem cells and endothelial progenitor cells have some interesting biological properties that make them unique for cell therapy of degenerative and cardiovascular disorders.Although both cell populations have been already studied and used for their regenerative potentials,recently their special immunoregulatory features have brought much more attention.Mesenchymal stem cells and endothelial progenitor cells have both proangiogenic functions and have been shown to suppress the immune response,particularly T cell proliferation,activation,and cytokine production.This makes them suitable choices for allogeneic stem cell transplantation.Nevertheless,these two cells do not have equal immunoregulatory activities.Many elements including their extraction sources,age/passage,expression of different markers,secretion of bioactive mediators,and some others could change the efficiency of their immunosuppressive function.However,to our knowledge,no publication has yet compared mesenchymal stem cells and endothelial progenitor cells for their immunological interaction with T cells.This review aims to specifically compare the immunoregulatory effect of these two populations including their T cell suppression,deactivation,cytokine production,and regulatory T cells induction capacities.Moreover,it evaluates the implications of the tumor necrosis factor alpha-tumor necrosis factor receptor 2 axis as an emerging immune checkpoint signaling pathway controlling most of their immunological properties.

Lifesaving transarterial embolization using absorbable gelatin sponge particles for massive bleeding of ruptured metastatic hepatic melanoma

To the Editor:Melanoma is an aggressive malignant tumor that arises from melanocytic cells. It usually originates from the epithelial tissues of the skin, retina and anorectal canal. Melanoma is characterized by early metastases, even from thin primary tumors. The most common sites of distant metastasis are: skin, lung, brain, liver, bone and intestine. Liver involvement occurs in 14% to 20% of cases [1] , but the diagnosis is usually performed incidentally on imaging studies, since these lesions are seldom symptomatic. Rarely, metastatic hepatic melanoma can manifest as an acute condition of massive bleeding due to spontaneous rupture of one or more hepatic lesions, with disastrous outcomes for patients in most cases. In the current literature, very few cases of spontaneous rupture of metastatic hepatic melanoma have been reported, all with fatal outcomes [2–5] . Indeed, when such a condition occurs, prompt management and bleeding control strategies are essential for long-term survival of these patients.

Editorial:Special Topic on Reconfigurable Intelligent Surface(RIS)

Over the past two years,reconfigurable intelligent surface(RIS),as a promising emerging technology for Beyond 5 G(B5 G) and 6 G mobile communications systems,has attracted enormous interest from both academia and industry worldwide.In IMT-2030(6 G) Promotion Group of China,the RIS task force was created in June 2020.

Some contributions to mechanical behaviors of lacustrine deposit in Bogota, Colombia

This paper presents the mechanical behaviors of the lacustrine deposit,a representative soil in Bogota,Colombia.Initially,the physical characterization of the deposit is performed via laboratory tests (grain size distribution,scanning electron microscopy,Atterberg limits and water content).This characterization intends to explain the special characteristics of the mechanical behaviors of this soil.Then,various triaxial tests are carried out with controlled loading path,strain rate change,relaxation,extensile stress,and cyclic loading.The test results reveal the shape of the yield curve for Bogotá soil (in a natural state),and also show that an increasing effect of the strain rate depends on the liquid limit.This effect is also preserved with extensile stresses (which are poorly studied in soil mechanics).Finally,other effects,such as the loss of structure in the reconstituted samples and the effect of shear modulus at low strains,are studied for Bogota soil.

Delayed-release oral mesalamine tablet mimicking a small jejunal gastrointestinal stromal tumor:A case report

BACKGROUND Enteric-coated medications are supposed to pass intact through the gastric environment and to release the drug content into the small intestine or the colon.Before dissolution of the enteric coating,they may appear hyperdense on computed tomography(CT).Unfortunately,few reports have been published on this topic so far.In this case report,the hyperdense appearance on contrastenhanced CT of an enteric-coated mesalamine tablet was initially misinterpreted as a jejunal gastrointestinal stromal tumor(GIST).CASE SUMMARY An asymptomatic 81-year-old male patient,who had undergone laparoscopic right nephrectomy four years earlier for stage 1 renal carcinoma,was diagnosed with a jejunal GIST at the 4-year follow-up thoraco-abdominal CT scan.He was referred to our hub hospital for gastroenterological evaluation,and subsequently underwent 18-fluorodeoxyglucose positron emission tomography,abdominal magnetic resonance imaging,and video capsule endoscopy.None of these examinations detected any lesion of the small intestine.After reviewing all the CT images in a multidisciplinary setting,the panel estimated that the hyperdense jejunal image was consistent with a tablet rather than a GIST.The tablet was an 800 mg delayed-release enteric-coated oral mesalamine tablet(Asacol®),which had been prescribed for non-specific colitis,while not informing the hospital physicians.CONCLUSION Delayed-release oral mesalamine(Asacol®),like other enteric-coated medications,can appear as a hyperdense image on a CT scan,mimicking a small intestinal GIST.Therefore,adetailed knowledge of the patients’medications and a multidisciplinary review of the images areessential.

WIRELESS COMMUNICATIONS WITH RECONFIGURABLE INTELLIGENT SURFACES

With the commercialization of the fifth generattion(5G)of wireless networks in 2019,the development of the next generation of wireless standards is currently under discussion.To cope with the target 1000x improvement of system capacity,5G wireless standards have adopted massive MIMO as a key enabling physical layer technology to boost the spectral efficiency.

Borehole Heat Budget Calculator: A New Tool for the Quick Exploitation of High-Resolution Temperature Profiles by Hydrogeologists

Distributed temperature sensing is known to provide sharp signals which are very efficient for mapping hydraulically active fractures in wellbores. High-resolution temperature sensing has specifically demonstrated its capacity to characterize very low flows in wellbores. But as sharp as they can be, temperature profiles are often difficult to decipher. The aim of the present work is to provide and to test the “Borehole Heat Budget Calculator” (BHB Calculator), which is implemented as a fast and easy to use tool for the quantitative analysis of depth-temperature profiles. The Calculator is suitable for most pumping and draining configurations, as the heat budget is generalized for modelling multidirectional flow systems within the same wellbore. The formatted worksheet allows the quick exploitation of temperature logs, and is applicable for the characterization of distributed fractures in long screened wellbores. Objectives of the heat modelling are to enhance the readability of complex depth-temperature data, as well as to quantify distribution of inflow intensities and temperatures with depth. The use of heat budget helps to clearly visualize how heat conduction and heat advection contributions are distributed along wellbores profiles. Calculations of inflow temperatures and their evolution through pumping duration is a prerequisite to infer about the nature of aquifer properties (i.e. conduits, distributed or discrete fractures, porous media), as well as to give insight information about the mapping of effective flow paths draining the aquifer. The efficiency and limitations of the BHB Calculator are being tested through high-resolution temperature logging, along with complementary flowmetering and televiewing logging in fractured aquifers located in the St-Lawrence Lowlands, Quebec, Canada.

Should we use full analgesic dose of opioids for organ procurement in brainstem dead?

Families facing the growing demand for organ removal from their loved ones are questioning the possible suffering of the brainstem dead patient.A frequent question they ask to coordinating doctors is:Are you sure he will not feel anything?Currently due to the risk of exacerbation of spinal reflexes and abnormal movements following surgical stimuli,it is recommended to use a curarization and an analgesic agent(most often morphine).The doses of opioids are less important than during usual anaesthesia,whereas the person is considered brainstem dead and there is no longer any cerebral integration of the pain.But what assures us that absolutely no more sensibility exists at this precise moment?Should the use of full analgesic dose of opioids not be continued anyway?Could this make the levies more"ethical"?

Experience of Management of Anorexia Nervosa Patients with Extremely Severe Malnutrition in a Transdisciplinary Clinical Nutrition-Eating Disorders Inpatient Unit

Background: The question of where to hospitalize extremely malnourished patients with anorexia nervosa (AN) is a real dilemma. On one hand, psychiatrists have to deal with severe medical complications that are not within their competences and that justify hospitalization in an internal medicine ward. On the other hand, medical doctors have to face psychic decompensations that would justify admission to a psychiatric ward. In this context, we share our experience of management of severely malnourished AN adult patients in a transdisciplinary specialized eating disorders (ED) unit, referral center for AN associated with somatic severity. Method: First, we described the modalities of care proposed to patients with AN hospitalized in the medical unit. Intensive medical care, both somatic and psychiatric, are provided thanks to a transdisciplinary therapeutic program, where objectives are to: medically stabilize the patient, initiate progressive refeeding and start supportive psychotherapy before being transferred to a psychiatric ED unit. Secondly, we conducted a retrospective descriptive study that included all adult patients with AN admitted for the first time to the unit, between November 1997 and January 2014, for severe malnutrition and/or complications of the ED. Objective was to specify patients’ characteristics: demographic, nutritional status, history of ED, care pathway. Results: Among a cohort of 386 adult patients with AN (21 males and 365 females) admitted for the first time in the unit, mean age was 29.4 (±11.5) years, mean BMI was 12.7 (±2.2) kg/m2. Before being supported in the unit, 78.2% of patients had already been hospitalized in other hospitals. Mean length of stay was 35.2 days. Patients were clinically serious and unstable because of life-threatening somatic complications due to a low BMI. During hospital stay, a temporary transfer to medical intensive care unit was necessary for 25.6% of patients. Average patient weight gain was 0.777 kg per week and 81.9% of patients benefited from enteral nutrition. Conclusion: This specialized transdisciplinary unit where physician nutritionists and psychiatrists coordinate medical care together, allow a better understanding and management of extreme malnutrition associated with AN. Thanks to their expertise, care teams are less critical and less rejecting towards patients. Thus, therapeutic alliance could be optimized.

Numerical study of convective heat transfer in static arrangements of particles with arbitrary shapes:A monolithic hybrid lattice Boltzmann-finite difference-phase field solver

A compressible lattice Boltzmann-finite difference method is extended by the phase-field approach into a monolithic scheme to study fluid flow and heat transfer through regular arrangements of solid bodies of circular,elliptical and irregular shapes.The advantage of using the phase-field method is demon-strated both in its simplicity of accounting for flow and thermal boundary conditions at solid surfaces with irregular shapes and in the capability of generating such complex-shaped objects.For an array of discs,numerical results for the overall solid-to-gas heat transfer rate are validated via experiments on flow through arrays of hot cylinders.The thus validated compressible LB-FD-PF hybrid scheme is used to study the dependence of heat transfer on flow and thermal boundary conditions(Reynolds number,temperature difference between the hot solid bodies and the inlet gas),porosity as well as on the shape of solid objects.Results are rationalized in terms of the residence time of the gas close to the solid body and downstream variations of gas velocity and temperature.Perspective for further applications of the proposed methodology are also discussed.

Spatially resolved investigation of flame particle interaction in a two dimensional model packed bed

This study investigates the interaction between a premixed methane-air flame and particles inside a model packed bed.The opacity of the spherical packed beds to visible light poses a major barrier to the implementation of highly resolved optical diagnostics,so that no detailed experimental data were so far available for the validation of numerical simulation.Here,a two-dimensional cylindrical packed bed design is set up,which enables direct line-of-sight optical measurements without loss of spatial reso-lution over the fluid region between the particles.In this study,the case of cold metallic cylindrical particles(T=377 K)relevant to start-up of a reactor is investigated using internal particle cooling,which also allows cylinder specific heat transfer rate measurements by differential temperature measurements on the coolant streams.The two dimensional assumption is first verified by measuring the inflow ve-locity and cylinder temperature profile along the cylinders.Chemiluminescence imaging is then per-formed using a telecentric lens to observe the position and geometry of the two-dimensional flame front with respect to the surrounding cylinders without loss of resolution.Simultaneously,the cylinder-specific flame to cylinder heat transfer rates and cylinder surface temperature are measured.As the flame is closely surrounded by the three cooled cylinders,intense heat transfer is observed in this region corresponding to 25±2.5%of the flame thermal power.Flames were stabilised at different positions depending on inflow velocity and equivalence ratio,and a direct correlation between flame to cylinder stand-off distance and the heat transfer rate normalised to the flame thermal power was found for both top and side cylinders.Also,sidewall quenching distances to the curved cylinder surfaces were evaluated,and seem to be influenced by the presence of a warm recirculation zone behind the cylinders.This investigation provides fully resolved flame front position and heat transfer rates for a known geometry and cylinder thermal boundary conditions,and provides validation data for numerical simulations of this high flame particle coupling case.

Multi-point temperature measurements in packed beds using phosphor thermometry and ray tracing simulations

Packed bed reactors are commonly found in the process industry,for example in flame-assisted calci-nation for cement production.Understanding the heat transfer inside the bed is essential for process control,product quality and energy efficiency.Here we propose a technique to determine the internal temperature distribution of packed beds based on a combination of lifetime-based phosphor ther-mometry,ray tracing simulations,and assimilation of temperature data using finite element heat transfer simulations.To establish and validate the technique,we considered a reproducible regular packing of 6 mm diameter aluminum spheres,with one of the spheres in the top layer being electrically heated.If a sphere inside the packing is coated with thermographic phosphors and excitation light is directed to-wards the packing,luminescence from the coated sphere exits the packed bed after multiple reflection and the sphere's temperature can be determined.Isothermal measurements showed that the temper-ature obtained by phosphor thermometry is independent of the luminescent sphere location.When imaging the luminescence on a camera,the luminescence distribution in recorded image depended,however,on the position of the sphere.Therefore,in setups with multiple phosphor-coated spheres,their signals can be separated using a least squares fit.We demonstrate the approach using a setup with three luminescent spheres and validated the temperature readings against thermocouple measurements.To obtain the spatial signatures for individual sphere positions required for the least squares fit,ray tracing simulations were used.These provide an efficient alternative to single sphere measurements that are only practical for regular spherical packed beds.Multi-point measurements were used as input to a finite element heat transfer simulations to determine parameters such as particle-to-particle air gap distance.With these,the full temperature distribution inside the bed could be assimilated from the measured values.

Phenotyping floral attractiveness to pollinators using volatilomics,3D imaging,and insect monitoring

PLANTS,POLLINATORS,AND BIODIVERSITY:THESTATUSQUO Plant-pollinator coevolution has played a crucial role in shaping the biodiversity of ecosystems that we know today.Moreover,plants and pollinators are key to agriculture,contributing to the production of most fruits and vegetables necessary for healthy human diets.Unfortunately,over the last decades,there is mounting evidence of pollinator decline all over the world,which constitutes a major threat to food security(European Commission,2020).To pollinators,nectar and pollen are the main rewards:pollen is essentially their only source of proteins,lipids,and vitamins,while nectar is a carbohydrate-rich solution that they use to fuel somatic functions(Ollerton,2021).However,nectar is much more than just a sweet solution:it comprises a plethora of secondary metabolites and volatiles of major importance for plant-pollinator communication.Unfortunately,by neglecting these traits and reducing genetic diversity,plant breeding has potentially increased the risk of losing the traits beneficial to pollinators.

PLCG2 Mutation in a Patient Presenting with Type 2 Autoimmune Hepatitis

The combination of defective immune tolerance and external triggers is thought to underlie the pathophysiology of autoimmune hepatitis.1,2 Some polymorphisms associated with susceptibility to autoimmune hepatitis have been reported,and some cases have been described in patients with monogenic primary immune deficiencies or systemic diseases.