Hepatitis C virus (HCV) is a major health problem in hemodialysis patients, which leads to significant morbidity and mortality through progressive hepatic fibrosis or cirrhosis. Percutaneous liver biopsy is the gold standard to stage hepatic fibrosis. However, it is an invasive procedure with postbiopsy complications. Because uremia may significantly increase the risk of fatal and nonfatal bleeding events, the use of noninvasive means to assess the severity of hepatic fibrosis is particularly appealing to hemodialysis patients. To date, researchers have evaluated the performance of various biochemical, serological, and radiological indices for hepatic fibrosis in hemodialysis patients with HCV infection. In this review, we will summarize the progress of noninvasive indices for assessing hepatic fibrosis and propose a pragmatic recommendation to diagnose the stage of hepatic fibrosis with a noninvasive index, in hemodialysis patients with HCV infection. Hepatitis C virus (HCV) infection, which may result in fibrosis, cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC), is a leading cause of chronic liver disease in patients receiving hemodialysis ,2,3,4. IAlthough the introduction of DAAs has tremendously advanced HCV care, accurate staging of hepatic fibrosis remains essential for therapeutic and prognostic purposes. The presence of cirrhosis may affect the treatment duration, the need for ribavirin (RBV) coadministration, and the sustained virologic response (SVR) rates in certain groups of patients ,20,21. FAn elevated AAR has been known to suggest cirrhosis in nonuremic HCV patients, with a positive predictive value (PPV) and specificity of 100% when the cut-off value is ≥1 . UstündaSchmoyer et al. assessed the diagnostic power of the AAR in predicting significant hepatic fibrosis (≥F2), according to the METAVIR scores in hemodialysis patients with HCV infection, which revealed that the area under the receiver operating characteristic (AUROC) was only 0.59. The PPV and negative predictive value (NPV) were 27.0% and 92.3% at a cut-off value of 0.70 . BecauseWai et al. correlated various biochemical parameters with the stage of hepatic fibrosis in 270 nonuremic patients with HCV infection. They found that the levels of platelet count, AST, ALT, and alkaline phosphatase (ALP) were highly associated with patients with ≥F2 and cirrhosis (F4). A novel biochemical index, APRI, was developed by amplifying the different effects of the platelet count and AST level on hepatic fibrosis stage . The AURSchiavon and Liu et al. independently assessed the diagnostic accuracy of the APRI in 203 and 209 hemodialysis patients with HCV infection, who received percutaneous liver biopsy ,35. The Schmoyer et al. validated the performance of the APRI in 139 hemodialysis patients with HCV infection and found that the AUROC to predict a fibrosis stage of ≥F2 was 0.68, which was lower than Schiavon’s and Liu’s reports. The AUROC in patients with elevated ALT levels was higher than that in patients with normal ALT levels (0.74 versus 0.42), if the clinicians defined the normal limits of ALT as 35 U/L for men and 25 U/L for women . This fiBased on the APRI results, the fibrosis stage can be correctly diagnosed without requiring liver biopsy in around 50% of hemodialysis patients with HCV infection ,35,36. BPestana and Lee et al. independently evaluated the clinical utility of APRI in 70 and 116 hemodialysis patients with HCV infection, taking transient elastography (TE) as the reference standard. They used the same cut-off values of liver stiffness as those in nonuremic patients to stage hepatic fibrosis ,38 Tabl. The AURFIB-4, an index that combined four biochemical parameters including age, AST, ALT, and platelet count, was initially developed to predict the severity of hepatic fibrosis in 832 patients with HCV and human immunodeficiency virus (HIV) coinfection . The AURSchmoyer et al. showed that the AUROC of FIB-4 to predict hemodialysis patients with HCV infection with a fibrosis stage of ≥F2 was 0.71, which was comparable to the AUROC of the APRI (0.68) . The PPVIn addition to the AAR, APRI, and FIB-4 indices, Schmoyer et al. applied King’s score and the Fibrosis index, which have been tested in nonuremic patients with HCV, to diagnose the severity of hepatic fibrosis in hemodialysis patients with HCV infection ,46. The In early 2000, the MULTIVIRC group developed a novel index, named FibroTest, to grade the severity of hepatic fibrosis in patients with HCV infection. They combined α2 macroglobulin, haptoglobin, apolipoprotein A1, γ-glutamyl transpeptidase, total bilirubin, age, and sex into a regression model to reach a final score ranging from 0.00 to 1.00 . The samHA is a chief extracellular matrix (ECM) component and continues to deposit in the liver in response to hepatic inflammation, leading to hepatic fibrosis or cirrhosis . Serum lSchiavon et al. assessed the utility of HA in 185 hemodialysis patients with HCV infection, which revealed a modest AUROC of 0.65 in predicting a fibrosis stage of ≥F2. Although the serum HA level of 64 ng/mL had an NPV of 86%, the PPV was only 42% at a cut-off value of 205 mg/mL . Avila eSince HA is not specific to liver fibrosis, the serum levels of HA in hemodialysis patients are expected to be higher that nonuremic patients because of the coexistence of systemic inflammatory/fibrotic reactions. Based on the published data, HA is of little clinical utility in predicting the severity of hepatic fibrosis in hemodialysis patients with HCV infection.YKL-40, also known as chitinase-3-like protein 1 (CHI3L1), is a glycoprotein expressed and secreted by various cells, including macrophages, chondrocytes, fibroblast-like synovial cells, hepatic stellate cells, and vascular smooth muscle cells. The serum levels of YKL-40 correlate with the severity of hepatic fibrosis of various etiologies . In nonuIn contrast to the high AUROC of YKL-40 in assessing the stage of hepatic fibrosis in HCV patients without kidney failures, Schiavon et al. showed that the AUROC of YKL-40 in predicting a fibrosis stage of ≥F2 in hemodialysis patients with HCV infection was only 0.607 . DespiteTE is a noninvasive tool that assesses hepatic fibrosis by measuring liver stiffness . To dateLiu et al. prospectively assessed hepatic fibrosis with TE in 284 hemodialysis patients with HCV infection who received liver biopsy. The AUROCs of TE in predicting a fibrosis stage of ≥F2, ≥F3, and F4 were 0.96, 0.98, and 0.99, which were significantly higher than the AUROCs of the APRI . The PPVBecause the portal flow increases in hemodialysis patients with food intake and excess fluid accumulation, clinicians should perform TE in hemodialysis patients who are fasting and complete a session of hemodialysis to avoid overestimating the severity of hepatic fibrosis ,72,73,74A pragmatic recommendation of applying noninvasive indices based on the diagnostic accuracy in predicting the severity of hepatitis fibrosis is depicted, to optimize the clinical practice for hemodialysis patients with HCV infection .In medical institutions where TE is readily available and accessible, directly measuring liver stiffness by this sonography-based technique can offer an excellent diagnostic yield, to predict the severity of hepatic fibrosis and avoid invasive liver biopsy in up to 90% of hemodialysis patients with HCV infection . BecauseFor medical institutions where TE is unavailable, the APRI can be the choice to stage hepatic fibrosis because of its ease of use and access. Three independent studies, which adopted liver biopsy as the reference standard, have shown that the AUROCs of the APRI were 0.80 to 0.84 in predicting a fibrosis stage of ≥F2 and ≥F3. An APRI of 0.40 and 0.95 can have NPVs of 85% to 93% and PPVs of 66% to 82% to predict F2 ,35,36. BAlthough the FIB-4 index has superior diagnostic accuracy to the APRI to predict the severity of hepatic fibrosis in nonuremic HCV patients, the performance of FIB-4 in hemodialysis patients with HCV infection is not ideal or stable ,37,42. FBecause most hemodialysis patients present with systemic inflammation/fibrosis from nonhepatic origins, all serological indices targeting ECM dynamics, including FibroTest, hyaluronic acid, and YKL-40, are not recommended in clinical practice to predict the stage of hepatic fibrosis in hemodialysis patients with HCV infection.To date, data regarding the application to monitor the evolution of fibrotic changes following antiviral treatment are scarce. In nonuremic patients with HCV who achieve SVR with antiviral therapy, studies have shown that the APRI, FIB-4, and TE had low diagnostic accuracies in assessing the evolution of hepatic fibrosis ,78. CurrHCV infection remains prevalent in patients receiving hemodialysis. The introduction of DAAs has revolutionized the care of HCV in this special clinical setting, based on the excellent viral clearance rate and tolerance. Assessing hepatic fibrosis before and after antiviral treatment is essential for therapeutic and prognostic implications. Although percutaneous liver biopsy is the gold standard for assessing liver histology in patients with chronic liver diseases, the postprocedural complications, as well as the sampling and interpretation variability, limit the widespread use of this invasive technique. Because a noninvasive index of hepatic fibrosis has a preponderance of safety and a potential to monitor disease evolution by repeated measurements, it would be of great help in diagnosing the stage of hepatic fibrosis in hemodialysis patients with HCV infection.Current evidence suggests that TE is the preferred tool to stage hepatic fibrosis in hemodialysis patients with HCV infection. Although the diagnostic accuracy of TE is higher than other noninvasive indices, only one study has been published to date. Therefore, independent research to validate the performance of TE is still needed. The APRI may be feasible in these patients when TE is not available or accessible. We do not recommend the AAR, FIB-4, King’s score, Fibrosis index, FibroTest, hyaluronic acid, and YKL-40 in assessing the severity of hepatic fibrosis in these patients because of low diagnostic yields. However, the roles of King’s score and the Fibrosis index remain uncertain because the number of studies is limited. More work is needed to confirm the feasibility of applying noninvasive indices to monitor hepatic fibrosis evolution in hemodialysis patients with HCV infection.


COQ8B nephropathy is a relatively rare autosomal recessive kidney disease characterized by proteinuria and a progressive deterioration of renal function, eventually leading to end-stage renal disease (ESRD). The objective is to study the characteristics and correlation between the genotype and the clinical phenotype of COQ8B nephropathy.This is a retrospective study focusing on the clinical characteristics of seven COQ8B nephropathy patients diagnosed by gene sequencing. Basic clinical information, clinical manifestations, examinations, imaging, genomes, pathology, treatments, and prognosis of the patients were reviewed.Of the seven patients, two were male children and five were female children. The median age at the disease onset was 5 years and 3 months. The initial main clinical manifestations were proteinuria and renal insufficiency. Four patients had severe proteinuria, four had focal segmental glomerulosclerosis (FSGS) diagnosed by a renal biopsy, and two had nephrocalcinosis after an ultrasound was performed on them. There were no other clinical manifestations such as neuropathy, muscle atrophy, and so on in all of them. Their gene mutations were all exon variants, which were classified as heterozygous or homozygous variants by performing family verification analysis. Compound heterozygous variants were predominant in all, and all gene variants were inherited from their parents. One novel mutation, c.1465c>t, was found in this study. This gene mutation resulted from changes in the amino acid sequence, thus leading to an abnormal protein structure. Two patients with early diagnosis of COQ8B nephropathy presented with no renal insufficiency and were treated with oral coenzyme Q10 (CoQ10), and they maintained normal renal function. For the remaining five who were treated with CoQ10 following renal insufficiency, the deterioration of renal function could not be reversed, and they progressed to ESRD within a short time (median time: 7 months). A follow-up of these patients showed normal renal function with a CoQ10 supplement.For unexplained proteinuria, renal insufficiency, or steroid-resistant nephrotic syndrome, gene sequencing should be considered, in addition to renal biopsy, as early as possible. Timely diagnosis of COQ8B nephropathy and early supplementation of sufficient CoQ10 can help control the progression of the disease and significantly improve the prognosis. Coenzyme Q10  is a small lipophilic molecule that participates in a series of key cellular processes. CoQ10, a cofactor of several mitochondrial dehydrogenases, shuttles electrons from complexes I and II to complex III in the mitochondrial respiratory chain. It is also one of the most important cellular antioxidants due to its redox potential (COQ8B (ADCK4)-associated nephropathy is related to mitochondrial dysfunction, which is caused by COQ8B gene variants. It is mainly characterized by moderate to severe proteinuria but rarely by hematuria, edema, chronic kidney disease (CKD), resistance to steroid therapy, and multiple system involvement such as neurodegeneration, dystonia, spasticity, seizures, intellectual disability, hypertrophic cardiomyopathy, retinopathy or optic atrophy, and sensorineural hearing loss as well as Crohn's disease –5. It isChildren with COQ8B nephropathy were diagnosed at the Children's Hospital of Chongqing Medical University and the University of Hong Kong-Shenzhen Hospital between 1 January 2013 and 30 November 2021. This study was approved by the Ethics Committee of the Children's Hospital of Chongqing Medical University (number 2018-95).The basic clinical information, clinical manifestations, laboratory tests, imaging, treatments, and prognosis of the patients were collected and analyzed.The peripheral blood samples of the patients were collected after obtaining informed consent from them and their families. The genomic DNA was extracted from these samples by using the Blood Genomic Column Medium Extraction Kit  according to the manufacturer's instructions.in silico. All diagnostic variants were confirmed by using Sanger sequencing with segregation. All variants were evaluated and classified according to the American College of Medical Genetics (ACMG) clinical practice guidelines . The libraries were sequenced at an average depth of more than 100× on the high-throughput NGS platform, Illumina NovaSeq 6000 , according to the manufacturer's instructions. The sequencing of raw data was filtered to remove poor-quality reads through quality control, which was then followed by the process of alignment to the reference genome (human) sequence using BWA software. After excluding the duplicated reads and performing a statistical analysis of the remaining reads, variants were called by using GATK software. The called variants were annotated on the basis of public databases for mutation records and population frequency in HGMD, ClinVar, Exome Sequencing Project, 1000 Genomes Project, and gnomAD databases. The deleterious effects of the variants were predicted idelines .Excel application was used to analyze data. Continuous variables were described by median, and categorical variables were described by proportion.A total of 233 patients with unexplained proteinuria, CKD, or SRNS underwent whole-exome sequencing. We identified 70 (30%) pediatric patients with single-gene mutation. Seven of them who had COQ8B nephropathy were included in this study . The median age at disease onset was 5 years and 3 months, and the minimum age was 1 year and 1 month, and all of them were of Han nationality . Four paWhite blood cell, red blood cell, platelet, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, blood lipids, prothrombin time, activated partial thromboplastin time, immunoglobulin, complement, antinuclear antibody, myeloperoxidase, protease 3, and hepatitis B markers were normal . All sevAll gene mutations of the seven pediatric patients were located in the exon , and theAll patients were treated with CoQ10 at a dosage of 5–30 mg/kg. The case 1 female patient presented with nephrotic syndrome, which was steroid-resistant. In the initial stages, neither gene testing nor a renal biopsy was done because of poor compliance. The disease progressed to CKD-V within 2 years and 6 months. The case 4 patient was treated with CoQ10 following failure of steroid treatment. However, there was no reduction in proteinuria levels. Renal function was found to be normal after a 1-month follow-up, but the follow-up period was too short to arrive at any certainty in this diagnosis. The case 7 patient was treated with CoQ10, and the renal function was found to be normal after a 5-year follow-up. Of the seven patients, there was one patient with CKD-V, two with CKD-IV, and the remaining four with renal insufficiency at the disease onset. The condition of the case 6 patient deteriorated to CKD-V after 2 months. The condition of the case 3 patient deteriorated to CKD-V after only 1 month, and unfortunately, this patient died of heart failure. The kidney function of the case 5 patient, who was diagnosed with CKD-II without a CoQ10 supplement, deteriorated 1 year after the diagnosis. These patients also underwent maintenance hemodialysis following ESRD, and the treatment procedure for one of these patients was changed to peritoneal dialysis. Four patients received renal transplantation and a continuous CoQ10 supplement, as also other immunosuppressants and antihypertensive drugs after transplantation. They were regularly followed up, following which they showed good hypertension control with no renal insufficiency nor extrarenal symptoms. The eGFR follow-up is shown in COQ8B (ADCK4) is one of the genes involved in the biosynthesis of COQ10. It is located on chromosome 19q13.2 and expressed in podocytes, which are located in mitochondria inside the foot process . SalviatKakiuchi et al. reported the first ADCK4-associated nephritis with Crohn's disease . Park etCOQ8B nephropathy usually leads to CKD-V , and in It was reported that an empirical dosage of 15–30 mg/kg/day was an ideal treatment for COQ8B nephropathy  SRNS or a significant family history of renal disease; (2) congenital (<3 months) or early-onset nephrotic syndrome (<1-year old). Some experts recommend that all individuals who exhibit SRNS before the age of 25 years undergo genetic sequencing; (3) a lack of response to immunosuppression; (4) FSGS or renal diffuse mesangial sclerosing glomerulonephritis; (5) extrarenal manifestations (syndrome); and (6) decreased glomerular filtration rate or renal failure . If thisBecause our study is a retrospective one, there are a few gaps in the amount of data presented. First, only a few cases of neurological complications are presented, as exemplified by the fact that we report only two cases of patients with results of cranial CT examination. Second, we show only four cases of patients with completed kidney biopsies, which could be attributed to an insufficient understanding of the risks by the patients’ families. Third and last, we could not obtain genetic information on the other family members of these patients, except that on their linear ascendants. We could also not find any related inherited family history.


In solar heating, ventilation, and air conditioning (HVAC), communications are designed to create new 3D mathematical models that address the flow of rotating Sutterby hybrid nanofluids exposed to slippery and expandable seats. The heat transmission investigation included effects such as copper and graphene oxide nanoparticles, as well as thermal radiative fluxing. The activation energy effect was used to investigate mass transfer with fluid concentration. The boundary constraints utilized were Maxwell speed and Smoluchowksi temperature slippage. With the utilization of fitting changes, partial differential equations (PDEs) for impetus, energy, and concentricity can be decreased to ordinary differential equations (ODEs). To address dimensionless ODEs, MATLAB’s Keller box numerical technique was employed. Graphene oxide Copper/engine oil (GO-Cu/EO) is taken into consideration to address the performance analysis of the current study. Physical attributes, for example, surface drag coefficient, heat move, and mass exchange are mathematically processed and shown as tables and figures when numerous diverse factors are varied. The temperature field is enhanced by an increase in the volume fraction of copper and graphene oxide nanoparticles, while the mass fraction field is enhanced by an increase in activation energy. The benefits of solar energy technology are that this type of energy is limitless, clean, and has no fuel to burn. The most common types of solar energy are photovoltaic (PV) systems15, thin-film solar cells18, solar power plants20, and passive solar heating22. The Photovoltaic applications were reported in the field of telecommunications23, agriculture24, used with livestock/cattle25, street lighting26, and rural electrification27. The usage of thin-film solar cells was in rooftops at the institutional and commercial buildings28, solar farms29, power traffics30, and solar steam generation31. Passive solar heating is implemented in circulation spaces such as lobbies, hallways, and break rooms that allow occupants to avoid the sun.Researchers have concentrated on new energy measuring to meet the requirements and needs of companies in this period. Researchers are interested in developing a few devices with the highest rate of heating and cooling. These might save and maintain optimal energy efficiency. Furthermore, poor heat transmission and flowing base liquid conducting have an impact on the performance and operation of solar collectors. Many efforts have been made in this respect to improve the thermal characteristics of base liquids. Solar energy is the renewable energy source from the sun for industrial applications such as electricity generation32. Besides, the primary purpose of HVAC system for residential34 and commercial buildings36 is to provide a heating mode in the winter and cooling mode in the summer. This system also filters smoke, odors, dust, airborne bacteria, carbon dioxide, and other harmful gases to improve air indoors38. In addition, HVAC system acts as a humidity controller of air indoors40. Meanwhile, the HVAC system powered by solar energy is known as solar-HVAC (S-HVAC), where it is installed by PV panels to capture the sunlight and convert it into electricity. John Hollick is one of S-HVAC innovators, and he patented the method and apparatus for cooling ventilation air for a building41. The solar PV panel is connected to the HVAC to convert the solar energy into electricity to power all the parts responsible for the heating or cooling mode in the HVAC. The benefits of the S-HVAC system, instead of traditional HVAC, are lower utility bills, preserve the environment, and ease of installation. HVAC systems have moving parts such as fans and vibrating coils that often break, whereas S-HVAC have fewer moving parts and these systems have fewer breakage risks.HVAC stands for heating, ventilation, and air conditioning, whereas AC is defined as conditioning. AC is designed to cool the air and control humidity in the house and was invented by Willis Carrier in 190242.Among the several renewable resources that may be put practically anywhere in the globe, solar power promises to be the major technology for the transition to a decarbonized energy supply. The efficacy of a photovoltaic (PV) system is directly proportional to the amount of solar energy available. Many governments see renewables and energy conservation measures as a viable method to reduce coal consumption. The primary solar devices that can convert sunlight into electricity are PV system and concentrated solar power (CSP). CSP concentrates sun radiation to increase the temperature of a working fluid, and this fluid drives a heat engine and electric generator. CSP generates alternating current (AC), which has a high distribution rate on the power network. Besides, PV collects sunlight through the photoelectric effect to generate electricity in the form of a direct electric current (DC). The DC generated by the PV system is then transformed to AC through the inverters to ensure that the electricity is distributed on the power network. CSP stores energy by using Thermal Energy Storage technologies (TES), and it is not subjected to weather restrictions: This means that CSP can be used at all times  to generate electricity. On the other hand, PV system only stores low thermal energy compared to CSP, since it only uses a battery instead of the storage technology like TES. Therefore, CSP has more qualities over PV by performing more noteworthy efficiencies, lower speculation costs, gives warm capacity limit, and a superior mixture activity ability with different energizes to satisfy baseload need around evening time44, air-conditioning46, and solar-aircraft51. PTSC consists of a reflector with a reflecting surface (parabolic-shaped mirror) and a receiver. The reflector collects the incident solar radiation and reflects it onto a receiver located in the focal line of the parabola. The working fluid inside the receiver absorbs the heat from the solar radiation, causing the fluid temperature to increase. Finally, high-pressure superheated steam is generated from this working fluid in a conventional reheat steam turbine-generator to produce electricity. The running fluid in PTSC should have those features: (a) excessive thermal potential and thermal conductivity, (b) low thermal growth and occasional viscosity, (c) strong charge of thermal and chemical properties, (d) minimal charge of corrosive interest and (e) low toxicity52. One of the simplest operating fluids in PTSC is innovated nanofluid referred to as hybrid nanofluid and is ready via way of means of submerging specific nanoparticles withinside the equal base fluid. Therefore, there are recent studies regarding the hybrid nanofluid as a working fluid in PTSC installed in solar aircraft51, and when PTSC is equipped with turbulators58. The following types of hybridizing nanofluid were implemented in the PTSC solar aircraft: Casson hybrid nanofluid47, Reiner Philippoff hybrid nanofluid49, and tangent hyperbolic hybrid nanofluid51. Meanwhile, A turbulator is a tool that transforms a laminar boundary layer right into a turbulent boundary layer to optimize heat transfer. Hence, various patterns of turbulators inserted in PTSC were reported, such as single twisted turbulator53, obstacles act as turbulator54, finned rod turbulator55, two twisted tape acts as turbulator56, inner helical axial fins as turbulator57, and conical turbulator58.Parabolic trough solar collector (PTSC) is one type of CSP system that has been used proficiently in water heating2O3/H2O65, Cu-Al2O3/EG66, Cu-Ag/EG68, Cu-TiO2/H2O70, Cu-Ag/H2O71, Cu-Go/H2O72, Cu-Ti/H2O, CuO-TiO2/H2O and C71500-Ti6Al4V/H2O73, Cu-Fe3O4/EG74, Cu-CuO/blood75, Ag-MgO/H2O76, Ag-Gr/H2O77, CuO-TiO2/EG78, Fe3O4–Co/kerosene79, MWCNT-Fe3O4/H2O80, and MWCNT-MgO/H2O81. The thermal properties of hybrid nanofluid over an elastic curved surface59, stretching sheet78, disk64, stretching disk62, and wedge79 were reported. In addition, the flow of a hybrid nanofluid in a cavity was investigated under the following conditions: square cavity68, porous open cavity69, and vented complex shape cavity81. The investigation of a hybrid nanofluid flow through a channel66 and microchannel77 have been performed, where these channels are rotating66, placed vertically73, and recharging77. The flow of a hybrid nanofluid in an enclosure was studied by Alsabery et al.60, Ghalambaz et al.65, and Abu-Libdeh et al.76. Alsabery et al.60 implemented the wavy enclosure containing the inner solid blocks, whereas Ghalambaz et al.65 considered an enclosed cavity with vertical and horizontal parts in their fluid model. On the other hand, Abu-Libdeh et al.76 selected a porous enclosure with a trapezoid geometry where this type of geometry is used for cooling purposes on the hybrid nanofluid. Meanwhile, Xia et al.67 and Khan et al.72 developed the fluid flow model bounded by two rotating parallel frames. The heat analysis of the peristaltic flow of hybrid nanofluid internal a duct become studied through McCash et al.71. The electroosmotic pump is involved in the hybrid nanofluid flow studied by Munawar and Saleem75, with ohmic heating. Shah et al.80 chose a porous annulus to study the characteristics of a hybrid nanofluid model.When it comes to thermodynamic rules, the second law of thermodynamics is far more dependable than the first law due to its limits of efficiency in heat transmission in industrial applications. This second law is applied to reduce the irreversibility of thermal constructions. Irreversibility is observed in a variety of thermofluidic apparatuses, including thermal solar, air separators, and reactors, and that competence loss is entirely inter-related with it. This generated irreversibility is determined by the rate of entropy production. The extinction of functional energy is measured by entropy generating. Any system's generated irreversibility creates continuous entropy, which eviscerates the functional energy required to execute the job. Such energy loss might be produced by heat transport by convective, conductive, and radiative fluxing. Furthermore, magnetic fields, buoyancy, and fluid friction all contribute to the generation of entropy. As a result, entropy generation minimization is required for diverse thermal equipment to acquire an optimal quantity of energy. The degree of entropy generating in crossbreed nanofluid is impacted by the expansion of twofold nanomaterials into the base liquid. The non-Newtonian cross breed nanofluid heavily influenced by entropy age have been examined, where this type of nanofluid contains the following double nanomaterials and base-fluid: Cu-Al86, Maxwell fluid91, nanofluid 81, etc. Sutterby fluid model is one type of non-Newtonianism fluid92, and it describes the viscosity of dilute polymer solutions93. Polymer solutions have been applied in related industrial phenomena or products, such as turbulent pipe flows95, stability of polymer jets97, and oil recovery enhancement99. The heat and mass transfer withinside the flow of magnetohydrodynamics (MHD) Sutterby nanofluid over a stretching cylinder, with the impact of temperature-structured thermal conductivity have been explored by Sohail et al.100 and Raza et al.101. The bioconvection of Sutterby fluid flow was reported when this fluid flows across the wedge102 and between two rotating disks103. Gowda et al.104, Yahya et al.105, and Khan et al.106 incorporated the Cattaneo-Christov heat flux model in their mathematical Sutterby fluid model to archive effective thermal properties. The Cattaneo-Christov heat flux model was developed when the fluid was bounded by a rotating disk104, flat surface105, and wedge106. The effect of entropy generation and activation energy were considered by Hayat et al.107. In contrast, El-Dabe et al.108 incorporated the boundaries of the attractive field, compound response, permeable media, heat radiation, gooey dissemination, and couple pressure. Parveen et al.109, Arif et al.110, Jayadevamurthy et al.111, Nawaz112, and Waqas et al.113 investigated the thermal performance of the Sutterby fluid model with the presence of various hybrid nanoparticles. The base fluid that has become selected was blood110, water111, and ethylene glycol113. These researchers113 implemented the dual nanoparticles in their Sutterby hybrid nanofluid, namely as: (i) Au and Al2O3109, (ii) CuO and Al2O3110, (iii) Cu and SiO2111, (iv) MoS2 and SiO2112, and (v) first fluid contained SiO2 and SWCNT, and second fluid used MoS2 and MWCNT113.Non-Newtonian fluid models are much more different than those of Newtonianism fluids. The stress values for non-Newtonian fluid are nonlinear functions against strain, yield stress, or time-dependent viscosity. Examples of this type of fluid are Casson fluidThe effect of ultrafine strong nanoparticles (copper and graphene oxide) at the Sutterby hybrid fluid has yet to be contemplated.In the extant literature, no 3D kind of Sutterby nanofluid has been built and explored.The results of Maxwell speed slippery and Smoluchowski heat slippery bounder situations on hybrid nanofluid impacting on an extensible floor are but to be investigated.The goal of this study is to look at a Sutterby hybrid fluid traveling along a stretchy surface with copper and graphene oxide nanoparticles. The following are the main points of the current study:The governing model was created on the premise of a boundary layer.The controlling PDEs are converted into ODEs using appropriate similarity transformation.The ODEs are adapted to 1st-ordered and resolved a usage of the Keller container numerical method included in MATLAB.Physical portions along with the pores and drag force factor and Nusselt number are mathematically decided and demonstrated in tables.Mathematical model's velocity, temperature, and awareness elements are numerically calculated and represented withinside the shape of figures.The following is a summary of the paper's structure.3D model ,,1162\docThe 117:Under the restriction as stated above, the modeled equations are premeditated byEquations –10) are are10) a118 is added:In Eq. , Rossela119 have been selected, as shown in (The appropriate transformationsshown in :13\documThe transformations  are implAfter implementing  in 11),,11), the120 as below:The final dimensionless governing parameters in –17) hav hav17) h121 have been tabulated in Table Thermophysical properties of copper and graphene oxide nanoparticles122 are expressed in Eq. , t, t25), tThe Sherwood number and the mass flux are given in Eqs.  and 28)28), respAfter manipulation of Eq.  into Eq.123 is selected as the current numerical technique to perform the solutions for the ODEs the ODEs –17), to, to123 ithe ODEs . The codthe ODEs –(17) folthe ODEs  is solve124, with the various values of rotating parameter The comparative analysis of the numerical values skin friction coefficient values entclass1pt{minimaentclass1pt{minimaThis segment shows and discusses the impact of diverse parameters at the floor frictional factor, Nusselt value, speed, energy, and concentricity outlines with the use of tables and figures. In the case of separated boundaries, Table The impact of f′β Fig. . When shFigure mentclasspt{minima125. The impact of Figure The profile Magnification withinside the factors Intensification in The value of the Nusselt wide variety decreases below amplification in It is essential that A positive variant in The mass fractional size discipline outline reduces for the chemically response factor 3-D rotating Sutterby hybrid fluid with copper-Graphene oxide nanomolecules, active energy, impetus, heat slippery bounder constraints, and radiative heat flow is defined in this paper. The numerical solution to the simulated problem was achieved using the MATLAB KBM built-in technique. The following are some of the most important aspects of the results:139.The Keller-box method could be applied to a variety of physical and technical challenges in the future


Tityus  present multi-chromosomal meiotic associations and failures in the synaptic process, originated from reciprocal translocations. Holocentric chromosomes and achiasmatic meiosis in males are present in all members of this genus. In the present study, we investigated synapse dynamics, transcriptional silencing by γH2AX, and meiotic microtubule association in bivalents and a quadrivalent of the scorpion Tityus maranhensis. Additionally, we performed RT-PCR to verify the expression of mismatch repair enzymes involved in crossing-over formation in Tityus silvestris gonads. The quadrivalent association in T. maranhensis showed delay in the synaptic process and long asynaptic regions during pachytene. In this species, γH2AX was recorded only at the chromosome ends during early stages of prophase I; in metaphase I, bivalents and quadrivalents of T. maranhensis exhibited binding to microtubules along their entire length, while in metaphase II/anaphase II transition, spindle fibers interacted only with telomeric regions. Regarding T. silvestris, genes involved in the recombination process were transcribed in ovaries, testes and embryos, without significant difference between these tissues. The expression of these genes during T. silvestris achiasmatic meiosis is discussed in the present study. The absence of meiotic inactivation by γH2AX and holo/telokinetic behavior of the chromosomes are important factors for the maintenance of the quadrivalent in T. maranhensis and the normal continuation of the meiotic cycle in this species.Several species of  The centromere is the region of the genome in which the kinetochore is inserted, whose function is to allows the union of the spindle microtubules to the chromosomes and promote their segregation during cell division . In seveTityus (Buthidae) have holocentric chromosomes, with extensive karyotype reorganization generated by reciprocal translocations and fusions/fissions [Tityus genus [Tityus and other arthropods can also be inferred by the structural maintenance of chromosome protein 3 (SMC3) immunofluorescence, a component of the cohesins axis that bind to the lateral elements during prophase I [Tityus prophase I. This phenomenon has been investigated in mice [Scorpions fissions ,6,7. Dirfissions ,8,9,10, fissions . Thus, tus genus . In thesophase I . Despite in mice , pigs [1 in mice , birds [ in mice , anurans in mice , and ins in mice , among o in mice .Tityus has been demonstrated through the analysis of cells in metaphase II [The alternate segregation of elements of these meiotic associations in phase II ,7. In orphase II . In planphase II , redistrphase II , or restphase II .Zabius (Buthidae) [Tityus, as in other genera, is considered an adaptation to the high incidence of rearrangements, since the decrease in the rate of crossing-over favors the correct segregation of homologous components of meiotic multivalents [Drosophila, male achiasmia may result from the differential expression of several recombination genes between the sexes [Tityus silvestris, initial events of the recombination process, such as the formation of DSBs and their association with Rad51, occur during zygotene and pachytene [Achiasmate meiosis was previously confirmed to be associated only with heterogametic sex in plants, tardigrades, crustaceans, insects, and arachnids or in both gonads (testis and ovary) of some annelids, flatworms, and hermaphroditic mollusks . Among suthidae) ,25,26. Tivalents ,13. The he sexes . In the achytene .Tityus (Archaeotityus) maranhensis. Additionally, we investigated by RT-PCR the expression of meiotic proteins involved in the process of crossing-over formation in Tityus (Archeotityus) silvestris. The results obtained contributed to a better understanding of the molecular and cytological mechanisms that maintain the achiasmatic and holocentric system of Buthidae scorpions.In the present study, we evaluated through immunocytogenetics the synaptic behavior, occurrence of MSUC by γH2AX, and the distribution pattern of tubulin along bivalents and quadrivalents of the scorpion T. maranhensis did not show primary constriction, typical of holocentric condition  were polarized in the cell nucleus   .T. silvestris from the municipalities of Manaus-AM and Belém-PA showed a karyotype consisting of 2n = 24  between sexes and different developmental stages, we performed RT-PCR in embryos and between both adult gonads (testis and ovary) of  studied . Neverthlvestris .T. maranhensis and T. silvestris are in agreement with those already described in the literature [T. maranhensis, are frequently documented [T. maranhensis showed delay in the synaptic process of quadrivalent compared to bivalent. This feature has been previously reported in other species of scorpions [The diploid numbers recorded in the present study for terature ,13. In scumented ,12,27. Tcumented . Analysicorpions ,11, insecorpions , mammalscorpions ,31, and corpions . This phcorpions . Additiocorpions .γH2AX, the main epigenetic mark of meiotic chromatin silencing [γH2AX signals are present in terminal regions during zygotene and pachytene, but do not co-localize with asynaptic regions of the quadrivalent in T. maranhensis. In other arthropods, despite the occurrence of γH2AX during the early stages of prophase I, transcriptional activity of autosomes remains constant from leptotene to diakinesis, differing from the pattern observed in vertebrates [T. maranhensis. On the other hand, similar distribution pattern of this epigenetic mark was observed during meiosis in T. silvestris [T. silvestris, in the present study, γH2AX was associated with chromosomal regions that initiate the synapse process and were not observed at late pachytene stages, where the quadrivalent is not yet fully synapsed  showed chromosomes with telokinetic behavior in metaphase II/anaphase II. Restriction of kinetic activity is observed in both metaphases I and II in nematodes and insects of the orders Hemiptera and Odonata [Tityus bahiensis, the kinetochore is present in both metaphase I and II, but does not completely cover the chromosomes [T. maranhensis is not yet understood, but it may be related to an intrinsic process of degradation of the cohesin complex present between the sister chromatids of the chromosomes of this species, which allow their correct arrangement in the metaphase plate and segregation to daughter cells, similar to that described previously for C. elegans [Triatoma infestans [In  pairing . In metaomosomes ,40. Regaomosomes ,41. Howe Odonata . The mol Odonata ,44,45. Tomosomes . The fun elegans  and Trianfestans .T. silvestris; despite this, we did not detect a significant difference in the expression levels of these genes between sexes  and females (chiasmatic) [T. silvestris and Drosophila may originate and be maintained by distinct processes. During meiosis I of various eukaryotes, MLH1, MLH3, MSH4, and MSH5 are components of recombination nodules, and they perform the processing of DSBs by homologous recombination, generating chiasma in bivalents during prophase I [Tityus bahiensis and Tityus fasciolatus, corroborating the achiasmia in Tityus males [Tityus males, we conclude that mismatch repair genes are expressed in T. silvestris testis, but their functions related to the recombination process may be inhibited in gonads of this scorpion. The expression of Mus81 was detected in T. silvestris; this resolvase is not a component of recombination nodules and may promote crossing-over formation by cleaving the Holliday junction in a manner distinct from other repair enzymes [T. silvestris may be related to DNA repair in spermatogonia and spermatozoa [Our results revealed transcription of mismatch repair enzymes in gonads and embryos of exes see . This reasmatic) . This inophase I . Recombius males . Similarus males  and achius males . Thus, c enzymes . Thus, irmatozoa .T. maranhensis and T. silvestris, with the presence of a quadrivalent meiotic association in the former, resulting from reciprocal translocation in heterozygosity. Our data allow us to conclude that (1) there is a delay in the synaptic process of quadrivalent during pachytene and post-pachytene; (2) γH2AX does not act in the inactivation of non-synapsed chromatin of multivalents of T. maranhensis; (3) the chromosomes of T. maranhensis exhibit holo- and telokinetic behavior, respectively, in metaphases I and II; (4) expression of mismatch repair genes is observed in both sexes in T. silvestris, despite the absence of chiasmata. Collectively, our data highlight that Tityus may be a model taxon for studies of achiasmatic meiosis in holocentric organisms.Our results confirmed the karyotype characteristics described previously for Tityus were considered in this study. Information regarding the species, number, and sex of individuals and collection localities of the sample used in the present are described in Two species of Probe of arthropod telomeric repeats (TTAGG) was obtained by polymerase chain reaction (PCR) using described primers . The PCRObtaining synaptonemal complexes was performed according to the literature . Gonads The primary antibodies used and their respective dilutions in PBS were rabbit anti-SMC3  in 1:200; mouse anti-α-tubulin  in 1:50; rabbit anti-γH2AX  in 1:50. For immunodetection of meiotic proteins, blocking with 5% BSA  was performed for 30 min. Then, the slides were incubated with primary antibodies for 2 h (37 °C). After washing in PBS1X, they were incubated with appropriate secondary antibodies, diluted 1:100, at 37 °C for 2 h. Finally, chromosomes were counterstained with DAPI, contained in VECTASHIELD antifading (Vector). Images were captured using a DS-Qi1Mc camera  attached to a Nikon H550S epifluorescence microscope ; all images were photographed using 100× magnification objective lenses.Immuno-FISH with telomeric probe was performed sequentially to the immunodetection of meiotic proteins, according to the protocol described . DenaturT. silvestris using Trizol reagent according to the manufacturer’s guidelines. After quantification and quality analysis of the RNA samples, they were treated with DNAse I. Reverse transcription was performed using the High Capacity cDNA Reverse Transcription kit from Applied Biosystems. Quantitative PCR was performed using the GoTaq qPCR Master Mix kit (Promega), using the primer sets as illustrated in RT-PCR analysis was performed to investigate the expression of MLH1, MLH3, MSH5, and MUS81 enzymes. Total RNA was isolated from embryos (n = 4), testes (n = 4), and ovaries (n = 4) of


Convolutional Neural Network(CNN) is increasingly being applied in the diagnosis of gastric cancer. However, the impact of proportion of internal data in the training set on test results has not been sufficiently studied. Here, we constructed an artificial intelligence (AI) system called EGC-YOLOV4 using the YOLO-v4 algorithm to explore the optimal ratio of training set with the power to diagnose early gastric cancer.A total of 22,0918 gastroscopic images from Yixing People’s Hospital were collected. 7 training set models were established to identify 4 test sets. Respective sensitivity, specificity, Youden index, accuracy, and corresponding thresholds were tested, and ROC curves were plotted.1. The EGC-YOLOV4 system completes all tests at an average reading speed of about 15 ms/sheet; 2. The AUC values in training set 1 model were 0.8325, 0.8307, 0.8706, and 0.8279, in training set 2 model were 0.8674, 0.8635, 0.9056, and 0.9249, in training set 3 model were 0.8544, 0.8881, 0.9072, and 0.9237, in training set 4 model were 0.8271, 0.9020, 0.9102, and 0.9316, in training set 5 model were 0.8249, 0.8484, 0.8796, and 0.8931, in training set 6 model were 0.8235, 0.8539, 0.9002, and 0.9051, in training set 7 model were 0.7581, 0.8082, 0.8803, and 0.8763.EGC-YOLOV4 can quickly and accurately identify the early gastric cancer lesions in gastroscopic images, and has good generalization.The proportion of positive and negative samples in the training set will affect the overall diagnostic performance of AI.In this study, the optimal ratio of positive samples to negative samples in the training set is 1:1~ 1:2. Gastric cancer is the third leading cause of cancer-related mortality and one of the most common malignant tumors in the world. Over one million new cases of gastric cancer are diagnosed each year, resulting in over 780000 deaths , 2. The via gastroscopy is highly dependent on their diagnostic competency, and inexperienced endoscopic physicians frequently misdiagnose patients. Atrophic gastritis is a precancerous condition that accounts for approximately 95% of stomach adenocarcinomas . The algorithm is a region-based CNN with high speed, adaptability, and a low rate of detection of background errors.Several studies that used CNN to train and recognize images of gastric cancer have yielded positive results –11. HoweThis multidisciplinary (AI and endoscopy) topic is attracting an increasing number of research institutes. While the field appears promising, it raises concerns about the flexibility and stability of these algorithms. When the algorithm design cannot be improved further, there is a tendency to seek new images and win through data volume.In our previous work, we developed the EGC-YOLO with the YOLO-v3 algorithm  using neWe collected gastroscopic cases in Yixing People’s Hospital between 2018 and 2021 and divided them into 2 categories based on pathological types, including images of early gastric cancer and images of non-gastric cancer . There were 1200 early gastric cancer images and 219,718 non-gastric cancer images. There were a total of 220918 gastroscopic images obtained. The images were selected by four endoscopists, each with more than 10 years of experience in endoscopy and more than 10000 gastroscopy cases. In addition, 568 gastroscopic images (268 early gastric cancer images and 300 non-gastric cancer images) were obtained from the Department of Gastroenterology, Nanjing Drum Tower Hospital; 1340 images (403 images of early-stage gastric cancer and 937 images of non-gastric cancer) were obtained from the Department of Gastroenterology, The Second Affiliated Hospital of Soochow University; 4453 gastroscopic images (366 for early-stage gastric cancer and 4087 for non-gastric cancer) were obtained from The Endoscopy Center of Civil Aviation Hospital of Shanghai.https://image-exp.dev.zhishiq.com:8443/. In the second module, the results of all test sets were displayed immediately after the test. On each tested image, the sites suspected of having early gastric cancer lesions were marked with red boxes, which is very intuitive.We created an online test platform and data storage server specifically for this experiment, which has two modules. In the first module, each test worker can upload data and use the online image box selection and marking tool to mark and save each image. The platform website is PYTHON programming language, LINUX OS system, GPU: NVIDIA RTX 2080TI+NVIDIA GTX 1080TI. A total of 220918 gastroscopic images, 1200 endoscopic images of early gastric cancer, and 219718 non-gastric cancer images were provided by Yixing People’s Hospital. Hereinafter collectively referred to as training sources.Training set 1: 1200 images of early gastric cancer were selected as positive samples from training sources, and 0 images of non-gastric cancer were randomly selected as negative samples from training sources, with a positive to negative ratio of 1:0.Training set 2: 1200 images of early gastric cancer were selected as positive samples from training sources, and 1200 images of non-gastric cancer were randomly selected as negative samples from training sources, with a positive to negative ratio of 1:1.Training set 3: 1200 images of early gastric cancer were selected as positive samples from training sources, and 2400 images of non-gastric cancer were randomly selected as negative samples from training sources, with a positive to negative ratio of 1:2.Training set 4: 1200 images of early gastric cancer were selected as positive samples from training sources, and 4800 images of non-gastric cancer were randomly selected as negative samples from training sources, with a positive to negative ratio of 1:4.Training set 5: 1200 images of early gastric cancer were selected as positive samples from training sources, and 9600 images of non-gastric cancer were randomly selected as negative samples from training sources, with a positive to negative ratio of 1:8.Training set 6: 1200 images of early gastric cancer were selected as positive samples from training sources, and 19200 images of non-gastric cancer were randomly selected as negative samples from training sources, with a positive to negative ratio of 1:16.Training set 7: 1200 images of early gastric cancer were selected as positive samples from training sources, and 38400 images of non-gastric cancer were randomly selected as negative samples from training sources, with a positive to negative ratio of 1:32Test set 1: This test set consists of a single external test set. All the 268 positive samples were gastroscopic images of early gastric cancer provided by the Department of Gastroenterology of Nanjing Drum Tower Hospital, whereas 300 negative samples were non-gastric cancer gastroscopic images provided by this hospital.Test set 2: This test set consists of a single external test set. All the 366 positive samples were gastroscopic images of early gastric cancer from the Endoscopy Center of Gubei Branch of Shanghai Ruijin Hospital, whereas 4087 negative samples were randomly selected non-gastric cancer images.Test set 3: This test set consists of a single external test set. All the 403 positive samples were gastroscopic images of early gastric cancer from the Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, whereas 937 negative samples were non-gastric cancer images.Test set 4: This test set consists of a mixed external test set. All the 717 positive samples were images randomly selected by the system after mixing images of early gastric cancer from the three hospitals mentioned above, whereas 1002 negative samples were images randomly selected by the system after mixing images of non-gastric cancer from the three hospitals.The training set 1 model was tested individually on test sets 1, 2, 3, and 4, respectively, with an average reading speed of 15 milliseconds/sheet. As shown in The training set 2 model was tested individually on test sets 1, 2, 3, and 4, respectively, with an average reading speed of 15 milliseconds/sheet. As shown in The training set 3 model was tested separately for test sets 1, 2, 3, and 4, respectively, with an average reading speed of 14 milliseconds/sheet. As shown in The training set 4 model was tested separately for test sets 1, 2, 3, and 4, respectively, with an average reading speed of 14 milliseconds/sheet. As shown in The training set 5 model was tested individually on test sets 1, 2, 3, and 4, respectively, with an average reading speed of 14 milliseconds/sheet. As shown in The training set 6 model was tested individually on test sets 1, 2, 3, and 4, respectively, with an average reading speed of 15 ms/sheet. As shown in The training set 7 model was tested individually on test sets 1, 2, 3, and 4, respectively, with an average reading speed of 16 milliseconds/sheet. As shown in According to the change trend of AUC in The variation tendency in In the test results of each group in this study, we listed the maximum Youden index and maximum accuracy rate of each group in In this study, we constructed and developed the EGC-YOLOV4 system with the YOLO-v4 algorithm, trained AI according to different sample ratios using gastroscopic images from Yixing People’s Hospital, obtained seven training set models, created four test sets with gastroscopic images from three different hospitals, and tested four test sets using seven training set models, respectively, which could efficiently and accurately screen for early gastric cancer in gastroscopic images. YOLO-v4 is capable of properly diagnosing gastroscopy pictures from various hospitals and has excellent generalizability. The percentage of positive and negative samples in the training set influences the overall diagnostic performance of AI, and an excessive number of negative samples decreases the diagnostic performance.The rapid advancement of artificial intelligence’s picture identification capability has given the area of medical illness diagnostics significant technological advantages. In clinical practice, the primary diagnostic procedures for gastric cancer are gastroscopy + mucosal pathological biopsy and imaging detection, which are employed for qualitative, localisation diagnosis and staging assessment, respectively. In the last two years, AI has conducted a number of studies in the area of gastroscopic image recognition, and more and more evidence indicates that a gastroscopic AI system may be used in clinical practice.Ishioka et al. , for insCurrently, the quality of endoscopic equipment and video collection devices in hospitals of all levels in China is inconsistent, high-definition acquisition cards are not widely used, and not all gastroscopic pictures can achieve 1080p resolution. Even though this field has great application potential, the stability and generalization of artificial intelligence in detecting endoscopic images from various medical institutions are still worth verifying, as overfitting issues frequently arise during the construction of AI systems, and how to obtain good generalization of AI systems is the most pressing issue at present. In order to deal with this issue, the training set we constructed in this study contains many images with varying resolutions to simulate the uneven image quality encountered in daily work. We then constructed four test sets with gastroscopic images from three different hospitals to test the diagnostic performance of each training set model separately and independently, and the results demonstrated that EGC-YOLOV4 could still demonstrate good diagnostic performance and was able to fully demonstrate its effectiveness.People often train AI systems with more photos in the hopes of winning by volume when the algorithm architecture cannot be much further improved. But are AI systems that have been trained on more photos better tested? The findings of this investigation clearly refute this theory.The findings of this research show that an excessive number of negative samples in the training set reduces the diagnostic performance of AI, but an optimum number of negative samples may maximize AI power. The highest generalization performance in the EGC-YOLOV4 system is achieved by AI trained with a training set sample ratio from 1:1 to 1:2. To guarantee that the AI system performs the best in terms of diagnostic performance, it is thus a good idea to use pre-experiments to estimate the ratio of positive samples to negative samples in the most appropriate training set. We also discovered that when the same training set model was used for testing, the four test sets’ optimal threshold values varied from one another, and in practice, a mature AI diagnostic software had to first set the threshold when screening for early gastric cancer. The determination of the specific set values of threshold had to be preset and corrected in accordance with various source datasets before AI testing, and the appropriate training set model had to be used.Even though our study yielded favorable test results, there are still limitations, including: 1. In this research, during the process of manually labeling the lesion site of gastric cancer, all lesions are labeled in the shape of rectangular boxes, which is likely to result in a small amount of non-gastric cancer stomach mucosa inside the rectangular box. During the process of artificial intelligence system learning, this portion of non-gastric cancer mucosal images will be misidentified as early gastric cancer by AI, and their mucosal characteristics will be extracted, leading to the possibility that the trained artificial intelligence system will misdiagnose non-gastric cancer mucosa as gastric cancer. If the labeling tool can be modified to a polygonal lasso, it will precisely match the lesion mucosal border and optimize the decrease of the original lesion boundary. 2. Since this research only employed retrospective data and photos, further multicenter prospective studies might be conducted to remove selective bias and increase the study’s reliability; 3. To analyze the trend of AI system performance when there are fewer negative samples than positive samples, we will add more sample proportion gradients in the design process of the training set model, such as 1:0.125, 1:0.25, and 1:0.5.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Conceptualization, TJ, ZY and BL. Methodology, ZY. Software, BL. Formal analysis, ZY and BL. Investigation, TJ, YZ, SL, YJ, XW, YS, JQ, HZ, TM. Resources, BM. Data curation, BL. Writing—original draft preparation, ZY. Writing—review and editing, TJ, YJ. Visualization, ZY, TJ, YJ and BL. Supervision, ZY and BM. Project administration, ZY. Funding acquisition, ZY and JQ. All authors have read and agreed to the publication of this manuscript.This research was funded by the Foundation of Clinical Science and Technology of Wuxi, No. Q202062 and No. Q201924.We thank Professor Weichang Chen for his constant advice and guidance regarding the design of this project and Professor Xiaoping Zou, who provided us with valuable gastroscopic images. Additional thanks go to Bo Lu for his contribution to the construction of EGC-YOLOV4 system. Finally, I wish to express my gratitude to the three hospitals  for providing us with endoscopic images.Author BL is an employee of Microsoft Ltd, however, he was neither assigned or asked by Microsoft Ltd to participate in this research, nor did Microsoft Ltd have any interest in the current research or future application of this study. The author did not use any resource of Microsoft Ltd or work time to conduct this research.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Studies have reported compatibility between hearing and electrophysiological thresholds in the auditory brainstem response (ABR) with tone burst stimuli.to verify waves I, III, V and their latency times for tone bursts at 500, 1000, 2000 and 4000 Hz and at 80 dB HL, and to compare tone burst electrophysiological thresholds with those obtained from audiological and psychoacoustic evaluations.audiological, psychoacoustic and electrophysiological evaluations of 40 male and female normal hearing individuals aged between 18 and 40 years were undertaken.only wave V was visualized at 80 dB HL and its latency values decreased with increased frequencies in both genders. At 1000, 2000 and 4000 Hz male subjects presented higher electrophysiological thresholds values than females at all frequencies. At 500, 1000 and 2000 Hz, electrophysiological, hearing, and psychoacoustic thresholds were statistically different in both genders.although ABR with tone burst stimulus is clinically applicable, further research is needed to standardize test techniques and results. The central nervous system generates bioelectric activity while performing its tasks, which may be read by electrodes on the scalp. These low-amplitude potentials (100 millivolts) may be amplified, recorded and measured by techniques such as electroencephalography.Auditory evoked potentials may be subdivided into early, middle and late components.These responses consist of a series of seven waves generated by one or more structures along the auditory pathways that have the following generating sites: wave I: the portion of the auditory nerve distal to the brainstem; wave II: the portion of the auditory nerve proximal to the brainstem; wave III: cochlear nucleus; wave IV: superior olivary complex; wave V: lateral lemniscus; wave VI: inferior colliculus; wave VII: medial geniculate body.BAER testing is used routinely in medical practice, given its reproducibility and locating properties. The main aim is to support routine audiological procedures, aiding in the diagnosis of auditory problems that are difficult to assess reliably.A variety of acoustic stimuli may be used to obtain electrical responses from the brainstem. Clicks are the most frequently used stimuli; clicks may be produced in a wide frequency range, which makes it possible to stimulate more fibers. Frequency selectivity, however, is not possible; the working range is higher frequencies .1 Acoustic stimuli such as tone bursts and tone pips may be used in order to obtain frequency-specific responses.Tone bursts make it possible to obtain relatively narrow frequency range responses, particularly at lower frequencies.A few authorsOn the other hand, various papers7-10 have reported the poor quality of BAER responses based on tone bursts, particularly at 500 Hz, where waves are complex, difficult to see and with significantly variable responses. These studiesThe response quality at 1,000 Hz obtained from tone bursts appears to be somewhat superior to the response quality at 500 Hz. It is still necessary, however, to use a 30 to 40 dBHL correction factor for the resulting thresholds, 10 suggesting that tone bursts appear to be inadequate for routine clinical use, considering the compatibility between pure tone and electrophysiological thresholds.Various published papers have used clicks in BAER testing. There are, however, few papers on the standardization of tone burst responses.The aims of this study were to verify the occurrence of waves I, III and V, and their latency times for a tone burst acoustic stimulus at 500, 1,000, 2,000 and 4,000 Hz at 80 dB NA in audiologically normal subjects aged between 18 and 40 years. Another aim was to compare the electrophysiological thresholds obtained from tone burst stimulation with those obtained in audiologic and psychoacoustic assessments.The Research Ethics Committee (CAPPesq) of the clinical board of the Sao Paulo Medical School Clinical Hospital (FMUSP) approved this study on 27/01/05, under the research protocol number 1089/04.Audiological, electrophysiological and psychoacoustic evaluations were done of 40 adult subjects, 20 male and 20 female, aged between 18 and 40 years.Participants signed a free informed consent form that described the procedures. Clinical history taking was followed by the audiological evaluation, composed by the procedures below: inspection of the external auditory canal with a Heine otoscope, tone and voice audiometry, and acoustic immittance measurement with Grason-Stadler GSI 61 and GSI 68 audiometers and a GSI 33 immittance meter. Normal auditory thresholds were those values between 0 and 25 dBHL at 250 to 8,000 Hz.The electrophysiological assessment was done with BAER testing using tone bursts at 500, 1,000, 2,000 and 4,000 Hz. A Biologic Traveler Express device, calibrated according to ANSI S3.7-1996 norms, was used.Abrasive paste was used to clean the skin and electrodes were placed using an electrolytic paste and adhesive tape on the vertex and right and left mastoids.Electrode impedance values, which were to be below 5 Kohms, were checked. The acoustic stimulus was presented through TDH 39 supra-aural headphones.The initial tone burst stimulus was 80 dBHL to measure waves I, III and V and their latency times. The intensity was reduced in 20 dB steps until wave V was no longer visible, to investigate the electrophysiological thresholds. We then increased the intensity in 10 dB steps until reaching the lowest intensity in which wave V became visible at its lowest amplitude; this was considered the electrophysiological threshold. There were 1,500 stimuli presented per stimulation. Stimulation was done twice for each intensity to check the reproducibility of tracings and the presence of a response.Investigation of the tone burst psychoacoustic threshold was done during the electrophysiological testing procedure. This was done to check whether subjects were hearing the acoustic stimulus even in the absence of a BAER; the psychoacoustic threshold was defined as the lowest intensity at which subjects heard tone bursts at 500, 1,000, 2,000 and 4,000 Hz.The ANOVA test and the equality of two proportions test were used to analyze the data. The confidence interval technique for the mean and the proportion was used to complement the descriptive analysis.A significance level of 0.05 (5%) was used and intervals were constructed based on a 95% statistical confidence level.Waves I and III at 80 dBHL were not observed at 500, 1,000, 2,000 and 4,000 Hz in both sexes.There were no proportional differences between ears in both sexes in the percentage of occurrence of wave V at 80 dBHL at 500, 1,000, 2,000 and 4,000 Hz. The occurrence of wave V, therefore, was done for both sexes at all of the frequencies that were investigated. A response was considered as absent for a specific frequency when no response was seen in at least one ear . There wThere was no statistically significant difference between right and left ear wave V latency in both sexes at the frequencies that were investigated. There were statistically significant mean differences in wave V latency between males and females at 1,000, 2,000 and 4,000 Hz . The mean wave V latency was higher in males compared to females at all of these frequencies.There was no statistically significant difference in the audibility, electrophysiological and psychoacoustic thresholds between right and left ears in males and females at the frequencies that were tested.We were thus able to group together data from both ears to yield final mean audibility, electrophysiological and psychoacoustic thresholds. A comparison of audibility, electrophysiological and psychoacoustic thresholds in males and females at 500, 1,000, 2,000 and 4,000 Hz is presented below .Table 3CMean electrophysiological and psychoacoustic thresholds were higher in males compared to females at 500 Hz . Males had the highest mean electrophysiological thresholds at 1000 and 2000 Hz . Mean electrophysiological and auditory thresholds in males were higher compared to females at 4,000 Hz .A last analysis compared electrophysiological, psychoacoustic and audibility thresholds in males and females at each frequency that was tested  and 10.TThe audibility, electrophysiological and psychoacoustic thresholds were statistically different from each other in males and females at 500, 1,000 and 2,000 Hz . The electrophysiological threshold was statistically different from the audibility and psychoacoustic threshold at 4,000 Hz , however the last two thresholds were statistically equal to each other in males and females.In this study waves I and III were not seen at 80 dBHL, as in a paper by Ribeiro (2002),11 who also did not find waves I and III and interpeaks I-III, III-V and I-V in term and preterm newborns, even at high intensities.There were no statistically significant differences between right and left ears in any of the analyses.In the current study the occurrence rate of wave V at 1,000 and 2,000 Hz was 100% in both sexes. At 500 Hz the response rate was 90% in both sexes; the response rate at 4,000 Hz was 97.5% in males and 100% in females. Davis e Hirsh (1976),There is a significant statistical difference in wave V latency at 80 dBHL between sexes at frequencies over 1,000 Hz with lower mean values in females, as shown on The wave V latency value decreased as the frequency increased in both sexes. Neely et al. (1988),In the current study electrophysiological thresholds decrease as the frequency increases in both sexes ; these results are similar to those of Beattie et al. (1996)Our data show that males had statistically significant higher electrophysiological thresholds compared to females at all frequencies. Sininger and Abdala (1998)Electrophysiological, audibility and psychoacoustic thresholds were compared with each other in all of the four frequencies that were investigated  and 10. Mean electrophysiological and psychoacoustic threshold differences in males and females increased as the frequency was raised. In the current study this may be explained by the finding that psychoacoustic thresholds decrease as frequencies increase, which may be compared to electrophysiological threshold decreases.The difference between mean electrophysiological and audibility thresholds decreases as frequencies increase in both male and females. Audibility thresholds had constant values at all frequencies, while electrophysiological thresholds decreased. No published paper was found that included the comparisons between the three thresholds made in the current study. We therefore compared these results partially according to findings in other papers.Our findings are similar to those of Davis and Hirsh 1976),6,7, 9, 1In our study we also found differences between psychoacoustic and audibility thresholds, where psychoacoustic thresholds were higher. This may be due to the fact that the BAER testing room was not completely acoustically isolated and environmental noise may have altered psychoacoustic thresholds.Not only was the acoustic room not completely isolated from external noise, but also most of the subjects were awake during testing; there may have been electrical interference due to movement during the test, given that testing lasted over one hour. These issues may have interfered on electrophysiological and psychoacoustic thresholds.Conijn et al. (1993),The technical issues and the time taken to record electrophysiological thresholds using tone bursts reduce the clinical applicability of this test in adults. Ribeiro (2002),1-Waves I and III at 80 dBHL at 500, 1,000, 2,000 and 4,000 Hz were not seen in males and females.2-The occurrence of wave V in males and females at 1,000 Hz and 2,000 Hz was 100%. The response rate was 90% in males and females at 500 Hz; the response rate was 97.5% in males and 100% in females at 4,000 Hz.3-Wave V latency and the electrophysiological threshold decreased as the frequency increased in males and females.4-Electrophysiological thresholds were higher in males compared to females at all frequencies. Psychoacoustic thresholds were higher in males compared to females at 500 Hz.5-Auditory, electrophysiological and psychoacoustic threshold were statistically different in males and females at 500, 1,000 and 2,000 Hz. Auditory and psychoacoustic thresholds did not differ from each other at 4,000 Hz, although both were different from the electrophysiological threshold.6-Although BAER testing using tone bursts is applicable to the clinical setting, our results show a significant difference between electrophysiological and audibility thresholds in an adult population. Further studies are needed to standardize testing techniques and the results of BAER testing using tone bursts.The following conclusions were reached based on the data in this paper:


Workers outside and inside confined spaces receive alerts every second to immediately initiate the rescue operation in the event of a hazard. The test results of a confined environment (wastewater treatment unit) highlighted that concentrations of CH4 and H2S were predominant (13 ppm). Compared to normal atmosphere, CH4 concentration was 122- and 130-fold higher in the landfill and digestion tanks, respectively, while H2S was 36- and 19-fold higher in the primary and secondary clarifiers, respectively. The oxygen content (18.2%) and humidity (33%) were below the minimum required limits. This study will benefit future research to target appropriate toxic gas monitoring and alert workers by studying the existing issues and associated factors in confined places.Occupational health and safety hazards associated with confined places are mainly caused by exposure to toxic gases and oxygen deficiency. Lack of awareness, inappropriate monitoring, and improper evacuation methods can lead to worker fatalities. Although previous studies have attempted to develop systems to solve this issue, limited research is available on their application in confined places. In this study, a real-time helmet-mounted system was developed to monitor major toxic gases (methane (CH The increasing fatality rate of construction workers in confined workplaces is becoming a growing concern. Confined places have been classified as limited or restricted for entry and exit , with onSeveral previous studies have focused on confined place accidents and fatality rates. Naghavi et al.  found th2S), methane (CH4), carbon monoxide (CO), and ammonia (NH3) are the major gases to which workers are often exposed [Construction workers frequently encounter numerous harmful gases while performing activities in confined spaces ,8,9. Pre exposed ,13,14,15 exposed . Ammonia exposed ,17. Carb exposed , while m exposed ,22,23,24Thus, appropriate monitoring and preventive measures should be considered to reduce the health effects of toxic gas inhalation and resulting accidents in confined places. Previous studies developed systems to measure toxic gases and alert workers in various fields. Yang et al.  monitore2), oxygen (O2), CH4, CO, and nitrogen (N2) and monitored personnel safety in underground mines. Crucial working environment factors (such as temperature and humidity) were not considered by the system; in addition, the system was not designed for confined spaces. Kuhar et al. [Sinha et al.  utilizedr et al.  used smoVijay Kumar et al.  created Monitor the real-time concentrations of primary toxic gases in confined places, such as methane, hydrogen sulfide, ammonia, and carbon monoxide, using a smart helmet.Measure environmental parameters such as oxygen level, temperature, and humidity.Provide alerts to workers inside and outside the confined place based on decision criteria.Testing the helmet-mounted system in a confined environment to gauge its working performance.This study aimed to develop a helmet-mounted system that can monitor hazardous gases efficiently and precisely in confined spaces. Considering existing information and limitations ,35, AlphThe remainder of this paper is organized as follows. The overall study methodology is illustrated in 2S, CH4, NH3, and CO were among the most dangerous gases in confined areas. In parallel with the selection of gases, the choice of gas sensors is critical for designing a monitoring system. Electrochemical gas sensors developed by Alphasense Ltd. were employed in this study to enhance system effectiveness because of their accuracy, wide range of temperature and humidity, low power consumption, low cost, fast response, and regular calibration [After a literature review, the primary gases found in confined places were selected; Hibration ,35,36. IThe designed helmet-mounted safety system was tested under normal, toxic, and confined atmospheric conditions. The test results obtained were analyzed based on the standard exposure limits of the concerned authorities. Finally, the conclusions and future recommendations are provided.The effectiveness of a helmet-mounted system depends on the selection of the monitoring unit, which should be able to report real-time gas concentrations precisely and promptly to inform the worker. In this study, a helmet-mounted system was designed and developed to simultaneously measure the major toxic gases in confined places and the atmospheric conditions of the toxic gas environment. 2), CO, sulfur dioxide (SO2), H2S, and particulate matter (PM10), suggesting that the sensor system is cost-effective and can be used for portable air quality monitoring. These sensors have the advantage of being effectively used in smart sensor networks in smart cities. Oletic and Bilas [2, and NO2 using AlphaSense sensors. Using the analog front end (AFE), the output current from the sensor is converted to voltage; thus, the gas concentration is obtained from the output voltage. This study showed that the sensors were accurate within ±0.6 ppm CO and the power consumption was lower.Alphasense electrochemical gas sensors were used in this study to measure the gases. Several publications have advocated using these sensors for occupational and environmental gas monitoring. Penza et al.  used Alpnd Bilas  measured3), NO2, and CO and evaluated low-cost electrochemical sensors produced by Alphasense, Ltd. . A strong linear relationship was observed between the output voltages and gas concentrations . CO sensors were considered suitable for occupational and environmental CO monitoring because of their field-ready calibration capabilities. Marinov et al. [2, O3, CO, and SO2 levels in the atmosphere using four-electrode amperometric gas sensors manufactured by Alphasense, with a four-sensor AFE board used for analog-to-digital conversion. These sensors were found to be applicable for low-power, low-cost, and fast-response air quality monitoring. The developed sensor interface was tested, and its accuracy was compared with that of the multichannel data acquisition (DAQ) system.Afshar-Mohajer et al.  developev et al.  conducte2, O3, and PM2.5 levels in urban air. The findings of this study highlighted that the raw sensor data showed a determination coefficient (R2) of >0.80. The power consumption of the sensor system was under 0.5 W, leading to the authors recommending a sensor network for wireless systems in the field of air quality monitoring. Arroyo et al. [2, CO, O3, PM2.5, and PM10 concentrations in an outdoor environment. The R2 values obtained for the sensor data were in the range of 0.83–0.95, suggesting that the sensor system is suitable for portable air quality monitoring, with higher accuracy and noise reduction achievable by carefully designing the sensor interface.Sharma et al.  developeo et al.  measuredIn this study, a printed circuit board (PCB) was designed to combine gas sensors into a single unit. The output current from the Alphasense gas sensors was converted by employing an LMP91000 AFE, which helps signal communication between the sensor and microcontroller and converts the output cell current proportional to the output voltage. In addition, it supports programming with multiple electrochemical gas sensors and has a gas sensitivity range of 0.5–9500 nA/ppm, operating temperature between −40 °C to 85 °C, and voltage supply of 2.7–5.25 V. LMP91000 consumes a total current of 10μA and helps in noise reduction [The sensor unit was maintained inside a 3D mold and placed on the front side of the helmet. Workers were directly exposed to hazardous gases near their breathing zones. Regarding the safe level of breathing, sensors should be placed near the typical breathing zone, i.e., 4–6 feet from the ground . Hence, The temperature and humidity of the confined environment are essential factors to be considered in the monitoring unit. The DHT11 temperature and humidity sensor was chosen for this purpose, with previous publications highly recommending using these sensors. The accuracy of the temperature and humidity measurements were ±2 °C and ±5% RH, respectively . This seSimilar to the gas sensor unit, the DHT11 sensor was mounted on the front of the helmet near it because the atmospheric parameters experienced by workers must be measured simultaneously. The exposure conditions and corresponding alert information must be relayed to the worker outside the confined place to avoid danger. For this purpose, the HC-05 Bluetooth module is utilized, which works on Serial Port Protocol (SPP) . This moYadav and Vohra  analyzed4, the maximum threshold limit is 1000 ppm during an 8 h working shift, as set by NIOSH. The alert system is activated when the toxic gas levels are higher and the oxygen concentration is lower than the recommended limits. If the levels are safe according to the standards, the alert system will be turned off, and the process will continue.An LED was provided at the front of the safety helmet to alert the worker inside the confined area. The decision criteria for the toxic gas exposure prevention system, based on the gas levels, are shown in The developed helmet-mounted system is illustrated in The helmet-mounted system was tested in normal and confined environments to compare the fluctuations in the sensor readings, with a wastewater treatment plant used for testing. The Jangrim wastewater treatment plant in Busan is a major municipal and industrial wastewater treatment plant in South Korea that collects and treats approximately 450 tons of wastewater. 2S, 0.29 ppm and 0.35 ppm for CO, 0.19 ppm and 0.26 ppm for NH3, and 0.07 and 0.1 ppm for CH4  were lower than the recommended minimum limit. Thus, these results indicated fluctuations in gas concentrations and other exposure conditions of confined atmospheres compared with normal environments.Testing was conducted in four units of the wastewater treatment plant: landfill, primary sedimentation tank, secondary clarifier, and digestion tank. A higher concentration of CHThe current study included safety monitoring of toxic gas exposure for workers involved in confined spaces. The findings of this study will allow future researchers to broaden the safety monitoring system to a health and safety monitoring system by integrating workers’ health conditions such as pulse rate, blood oxygen level, body temperature, and EEG or brainwave analysis. The effects of humidity and temperature on sensor readings, comparison of sensor data with bench march devices, short- and long-term exposure assessments, sensor dynamics analysis, and displaying system status can enhance the performance and efficiency of the monitoring system. Combining toxic gas monitoring and the measurement of other major pollutants in the construction industry, such as particulate matter, can mitigate occupational health impacts at construction sites.


Patients with endometrial cancer (EC) frequently have metastases to lungs, extra-pelvic nodes, and liver. Although an uncommon occurrence, cases of EC metastasis to bone, prevalently in vertebral bone, have also been reported. The objective of this study was to analyze clinical and pathological profiles of patients with EC metastatic to vertebral bone. We carried out a retrospective case series on surgically treated patients for this pathology. From 2001 to 2021, out of 775 patients with bone metastasis, 1.6% had bone metastasis from EC. The median time between the diagnosis of primary tumor and that of bone metastases was 31.5 months. Solitary bone lesion was present in 7 patients and lumbar vertebrae were the segments most affected. Pathological fractures in 46.2% of patients and spinal pain in all were present. In terms of location, 46.2% of bone metastases resided within the anterior section of the vertebra, while the remaining presented an extension within the anterior and posterior sections, with 46.1% of cases showing an extradural extra-osseous extension and paraspinous envelope. Median survival after diagnosis of bone metastasis was 11.5 months. Vertebral bone metastasis in EC is a rare phenomenon, with severe prognosis. An in-depth understanding of this topic may guide future management and treatment decisions, thus improving life expectancy and quality. Endometrial cancer (EC) is the fourth most common cancer in women, with 604,000 new cases reported worldwide in 2020 and a mortality of 7.7% ,2. By exThe present study is a retrospective case-series performed in accordance with relevant guidelines and regulations, performed from the data available from the Department of Oncological and Degenerative Spine Surgery of our Institution and approved by the Local Ethics Committee of the Emilia Romagna Region . Informed consent was obtained from all participants. The study involved a total of 775 patients with vertebral bone metastases who were surgically treated and managed from 2001 to 2021. Out of them, 13 patients had EC vertebral bone metastasis. In these patients’ indications for surgery were (1) presence of progressively worsening pain, not controlled by painkillers; (2) presence of spinal instability; (3) progressive or abrupt neurologic deterioration due to spinal cord compression, in case of failure of conservative therapy (such as radiotherapy and chemotherapy); and (4) estimated survival of more than 3 months and a general condition that allowed surgery. All surgical procedures were performed by 3 senior surgeons.An extensive review of medical records was performed for all patients to obtain specific clinical data and overall outcomes. Patient demographics, age, body mass index (BMI), primary EC histological type and grade, comorbidities, smoking habits, menopausal status, and pre-operative hematological parameters at diagnosis of bone metastasis were reviewed and collected. Furthermore, specific data on bone metastases, i.e., bone metastasis diagnostic tool, time from EC primary diagnosis to bone metastasis, main bone lesion level, presence of other bone metastasis lesions, presence of fracture, presence of extraosseous metastases, pre- and post-operative pain, pre- and post-operative chemo-radiotherapy, pre- and post-operative neurologic function, surgical staging of bone metastasis and months to death/last follow-up after bone metastasis and last follow-up status were reviewed and collected.Pre- and post-operative pain was evaluated using a numeric rating scale (NRS): each patient was asked to grade the pain from 0 = no pain to 10 = highest pain experienced . The pre- and post-operative and the latest follow-up neurologic functions were evaluated using the Frankel Grade, according to the degree of spinal cord injury, as follows: Grade A (complete loss of sensation and motor function below the level of injury); Grade B ; Grade C ; Grade D ; Grade E  .Surgical staging of bone metastasis was evaluated according to Weinstein–Boriani–Biagini classification . In brieAll data were collected in a Microsoft Excel spreadsheet. Statistical analyses were made using MATLAB(R) . Results were reported as mean ± standard deviation (SD) if normally distributed, or median (interquartile range (IQR)). A survival curve was estimated using the Kaplan–Meier estimator ,20. Furt2) data, present for six patients, ranged from 18 to 36, with one underweight patient, two overweight patients and one patient with class 1 obesity. Clear cell carcinoma was present in 30.7% of patients on histological examination, while the remaining had an adenocarcinoma. Most patients (76.9%) had histological Grade 3 for primary tumor at diagnosis, while the others had Grade 1 (15.4%) and 2 (7.7%). At the time of EC bone metastases, 46.1% of patients had one or more comorbidities, and hypertension was the most common (66.6%) in these patients. No comorbidities were present for 30.7% of patients and three patients’ data on comorbidities were not reported. Two patients were smokers at the time of EC bone metastases, seven patients had never smoked and four patients’ data on smoking habits were not reported. All patients were in menopausal status. At the time of EC bone metastases diagnosis, altered blood hematological parameters were detected, i.e., white blood cells (WBC), hematocrit, hemoglobin (Hb), and lymphocytes, as well as C-reactive protein (CRP) and γ-glutamyltransferase (GGT). Four patients’ data on hematological parameters were not reported.In the current study, 13 patients (1.6%) with EC vertebral bone metastases were included. Out of the thirteen patients, only two of them were younger than 50 years (age range: 31–75). The median age of the patients was 62 (IQR 56.0–69.0) . BMI (kgp = 0.0006) , while for the remaining four patients, data were not reported . Bone me 0.0006) . In tota 0.0006) . Pre-ope 0.0006) . Concern 0.0006) . Concern 0.0006) . The mea 0.0006) . The medAs previously reported, pain symptoms due to instability or fracture were present in all patients treated in our series and surgical treatment was performed specifically for progressive pain or when either vertebral collapse or metastatic growth caused spinal cord compression. In one case, the surgery was palliative, while in the remaining cases, intralesional curettage of “active” forms and extracapsular curettage (or en bloc resection) in “aggressive” forms was used (92.3%) . The aim2 = 0.45), indicating a weak statistical correlation between the survival curve and the estimate. This is due to the limited number of cases in our study and to the high survival of these patients. Looking at the data in Statistical results for the construction of the survival curve using the Kaplan–Meier method are shown in EC is one of the most common women’s cancers, with steadily increasing incidence that seems to be correlated with obesity, comorbidities, and fragility ,24. BoneIn our series, we found EC vertebral bone metastasis in 1.6% of patients; patients with age ranging from 31 to 75 years, with a prevalence of Grade 3, were present in this series. As reported in recent studies, and differently from old studies, most of the patients of our series (53.8%) had solitary metastatic bone lesion, and this is probably due to the advances in diagnostic techniques that have led to an increase in earlier diagnosis . AdditioBecause vertebral bone metastases can lead to bone instability and spinal cord compression, these patients can present with intractable pain, impaired ambulatory ability, and neurologic dysfunction. More than 90% of patients with spinal metastases reported pain and approximately 20% had cord compression . In our We acknowledge that this study had some limitations. First, as a retrospective study, potential biases were unavoidable. Second, the number of cases was relatively small, but due the rarity of EC vertebral metastases, a large-sample study could not be performed. For this reason, our study did not include subgroup analyses of histological subtypes or other variables. A large-sample multi-center study would probably be necessary. Third, the number of accessible variables provided for some patients were limited. For example, some information on BMI, comorbidities and blood tests, type of adjuvant chemotherapy, details of chemotherapy drugs and sequence of treatments were missing. In conclusion, our study shows that, although rare, EC vertebral bone metastases continue to gain relevance in the wake of an ever-growing life expectancy of patients, underlining that increased attention should be paid to the mechanisms and prognostic value of site-specific EC bone metastases. The study, for the first time, examined a series of patients with a specific gynecological primary tumor, EC, that metastasized to a specific bone site, vertebrae. Our findings on bone metastasis localization and on the outcomes of surgical procedures can provide important information for the treatment of these patients, since the wide heterogeneity of primary cancer and of bone metastases require personalized and targeted treatments by type of primary tumor and site of metastasis. The results of this study may help clinicians form the metastatic workup of these cancers, relate important prognostic information to patients, and provide insight on the most likely gynecologic malignancy by metastatic site at presentation.