Pivotal research led by Louis Harold Gray in the 1950s suggested that oxygen plays a vital role during radiotherapy. By proving that tumours have large necrotic cores due to hypoxia and that hypoxic cells require significantly larger doses of ionising radiation to achieve the same cell kill, Thomlinson and Gray inspired the subsequent decades of research into better defining the mechanistic role of molecular oxygen at the time of radiation. Ultimately, the work pioneered by Thomlinson and Gray led to numerous elegant studies which demonstrated that tumour hypoxia predicts for poor patient outcomes. Furthermore, this subsequently resulted in investigations into markers and measurement of hypoxia, as well as modification strategies. However, despite an abundance of pre-clinical data supporting hypoxia-targeted treatments, there is limited widespread application of hypoxia-targeted therapies routinely used in clinical practice. Significant contributing factors underpinning disappointing clinical trial results include the use of model systems which are more hypoxic than human tumours and a failure to stratify patients based on levels of hypoxia. However, translating the original findings of Thomlinson and Gray remains a research priority with the potential to significantly improve patient outcomes and specifically those receiving radiotherapy. The origins of radiotherapy date back to 1896 when Emil Herman Grubbé utilised X-rays, less than 60 days after their discovery by Wilhelm Conrad Röntgen, to treat a case of advanced ulcerative breast cancer in Chicago with little knowledge of their physical properties or biological effects , 3.In 1955, Gray published a research paper in collaboration with Raymond Hugh Thomlinson titled “The histological structure of some human lung cancers and the possible implications for radiotherapy” in the British Journal of Cancer . At thisThese seminal findings from Thomlinson and Gray in 1955 built upon the prior pivotal research of Gray et al., which demonstrated that tumour cells experiencing anoxia at the time of irradiation are ~2.5–3 times more radioresistant to a given dose of X-rays or γ-rays than oxygenated tumour cells [In addition, Thomlinson and Gray noted that a given dose of radiation, sufficient to cause cell death in the outer radiosensitive cells, will increase the supply of oxygen and other nutrients to the central necrotic cells, allowing the cells to continue proliferation if they have retained the capacity to replicate following the period of oxygen deprivation . Today, At the time of this pivotal research, the influence of oxygen tension at the time of irradiation on the biological response to radiotherapy had not been mechanistically evaluated . HoweverAs previously, the pioneering work of Thomlinson and Gray highlighted central cores of necrotic cells as the first indicator of tumour hypoxia. Necrosis of tumour cells occurs as a result of chronic or diffusion-limited hypoxia at distances >180 μM from functional blood vessels , 9. As p18F-fluoromisonidazole (FMISO) is one of several 18F-labelled tracers more recently utilised in oncology to specifically detect hypoxic tumour regions. Lipophilic FMISO diffuses into a cell where its nitro group is reversibly reduced via the addition of two electrons by nitroreductase enzymes [2) [After Thomlinson and Gray highlighted that hypoxia could be visualised through necrosis, significant effort was invested in developing probes for hypoxia in both the laboratory and clinical settings. For example, the 2-nitroimidazole compounds Pimonidazole and EF5 act as predictive biomarkers for hypoxia by being reduced and covalently binding intracellular macromolecules specifically at low oxygen concentrations <10 mmHg , 14. Pim enzymes . In oxyg enzymes . However enzymes   . FMISO PConversely, endogenous markers of tumour hypoxia are genes or proteins whose expression is selectively induced in conditions of hypoxia. The most studied are the hypoxia-inducible factors (HIFs), the master orchestrator of the biological response to physiological hypoxia, whose transcriptional activity is highly dependent on cellular oxygen concentration , 20. As More recently, it has become apparent that not only does hypoxia exist as a gradient, but the biological response to hypoxia differs in an oxygen-dependent manner , 26. ForAs a hallmark characteristic of solid tumours, the clinical importance of tumour hypoxia as a strong predictive biomarker indicating a likely poor response to both chemotherapy and radiotherapy treatments is well-established, with the latter being first revealed as significant by Gray et al. in 1953 . In addiOver the recent decades, several hypoxia modification strategies have been developed and investigated in an attempt to improve patient outcomes , howeveIn addition, the first proposed some decades ago was hypoxia modification through the development of hypoxia-activated prodrugs (HAPs). HAPs are compounds that are selectively reduced by reductase enzymes exclusively in regions of hypoxia to yield cytotoxic agents. Examples include tirapazamine , 45, TH-A more recent strategy to eliminate tumour hypoxia by correcting the imbalance between oxygen supply and demand is via decreased oxygen consumption resulting in increased availability of oxygen to hypoxic cells . This stToday, tumour hypoxia is well-established as a critical characteristic of the majority of solid tumours and is closely associated with negative treatment outcomes in a clinical setting. Data generated in the 1950s, including that published by Thomlinson and Gray, suggested a critical role of oxygen in radiation therapy efficacy and identified regions of necrosis as a consequence of tumour hypoxia. Importantly, both of these key findings have since been mechanistically validated.Inspired by this pivotal research, extensive studies have been undertaken to better define hypoxic regions, develop measurement and quantification methods, as well as propose targeted modification strategies . Issues


To evaluate the surgical results of revision canal wall down (CWD) surgery for chronically discharging mastoid cavities and to compare the non-obliteration approach to mastoid obliteration with canal wall reconstruction.This is a retrospective cohort study. All adult patients (≥ 18 years) who underwent revision surgery for chronically draining mastoid cavities between January 2013 and January 2020 were included. Primary outcome measures included the dry ear rate, complications and postoperative hearing.p = .002). There were no differences in audiological outcome and incidence of complications between the two techniques.79 ears were included; 56 ears received revision CWD with mastoid obliteration and posterior canal wall reconstruction and 23 ears received CWD without mastoid obliteration. The dry ear rate at the most recent outpatient clinic visit (median 28.0 months postoperative) was significantly higher in the obliteration group with 96.4% compared to 73.9% for the non-obliteration group (We show that in our study population revision CWD surgery with mastoid obliteration and posterior canal wall reconstruction is superior to revision CWD surgery without mastoid obliteration in the management of chronically discharging mastoid cavities. In the obliteration group, a dry ear was achieved in 96.4% as this was 73.9% in the non-obliteration group. We found no differences in audiological outcome and in incidence of complications between the two techniques.The online version contains supplementary material available at 10.1007/s00405-021-07138-0. While obliteration techniques in the surgical management of cholesteatoma gain popularity , cholestIn our tertiary referral center, obliteration of the mastoid with posterior canal wall reconstruction for the management of chronically discharging mastoid bowls was introduced in 2013 and gradually replaced the revision canal wall down mastoidectomy without obliteration and canal wall reconstruction. As these different approaches were performed by the same otologic surgeons, this cohort lends well for comparison of the surgical outcome of the two techniques. Therefore, the aim of this study is to evaluate the surgical results of revision surgery for chronically discharging mastoid cavities and to compare the non-obliteration approach to mastoid obliteration with posterior canal wall reconstruction.A retrospective cohort study was performed at our department with approval of the medical research ethical committee. All adult patients (≥ 18 years) who underwent revision surgery for chronically draining mastoid cavities between January 2013 and January 2020 were included. All patients were previously adequately but unsuccessfully treated with topical therapy. The following variables were retrieved from electronic patient records: patient characteristics, indication for surgery , pre-operative symptoms , tympanic membrane status, date of surgery, surgeon, whether or not mastoid obliteration with posterior canal wall reconstruction was performed, reasons for previous surgical failure , administration of antibiotics perioperatively, ossicular chain status , ossicular chain reconstruction , total ossicular replacement prosthesis (TORP), tympanic membrane to stapes (type III reconstruction), tympanic membrane directly to footplate), pre- and postoperative hearing (air conduction (AC), bone conduction (BC) and air–bone gap (ABG) for 0.5, 1, 2 and 4 kHz), post-operative symptoms , postoperative frequency of maintenance cleaning at outpatient clinic, postoperative otoscopy at the outpatient clinic at different timepoints. The postoperative otoscopy was scored as 1) fully dry, 2) minimal discharge or 3) infection.®, Bonalive Biomaterials Ltd., Turku, Finland) were used. In most cases when no obliteration was performed, the mastoid was smoothened with some bone dust. In these cases, a mastoid cavity persisted. If possible an ossicular chain reconstruction was performed and if necessary the tympanic membrane was reconstructed with cartilage or temporal fascia. The ear canal was packed with a gauze with hydrocortisone/oxytetracycline/polymyxin B for at least 1 week and was usually re-packed after 1 week.The surgical technique for mastoid obliteration with posterior canal wall reconstruction was performed as described by Vercruysse et al . SurgeryU test was used to assess differences between the surgical techniques. P-values < 0.05 were considered statistically significant.Statistical analyses were performed using IBM SPSS Statistics 26  and Graphpad Prism 7.0 . The Chi-square test of independence was performed to examine for differences in surgical outcome between the surgical techniques. For hearing outcome and data on time intervals for postoperative maintenance cleaning , the Mann–Whitney Between January 2013 and January 2020, 79 ears of 76 patients received revision surgery due to a chronically draining mastoid cavity. The median follow-up time was 28 months (inter quartile range (IQR) 17–55 months). Pre-operatively, 78 patients (98.7%) suffered from chronic discharge, 11 patients (13.9%) from vertigo, 6 patients (7.6%) from pain and 1 patient (1.3%) from bothersome recurrent cleaning. Obliteration of the mastoid with posterior canal wall reconstruction was performed in 56 cases (70.9%) whilst no obliteration was performed in 23 cases (29.1%). The most frequently used obliteration material was autologous bone dust (80.4%), followed by autologous bone dust together with bioactive glass granules (16.1%) and bioactive glass granules alone (3.6%). The posterior canal wall was reconstructed with bone chips in 71.4%, cartilage in 12.5% and bone chips with cartilage in 16.1%. Patient characteristics are shown in supplemental Table The reasons for previous surgical failure are shown in Table p = 0.007 and p = 0.002, respectively). At most recent follow-up, vertigo and pain was not present in any cases in the obliteration and non-obliteration group. There was persistent need for regular maintenance cleaning in 82.1% of patients with mastoid obliteration and 100% in the non-obliteration group (p = 0.039) and the median time interval for maintenance cleaning at the outpatient clinic was significantly longer in the obliteration group compared to the non-obliteration group .The surgical outcome per technique is shown in Table To achieve a dry ear, revision surgery was needed in 8 cases 14.3%) in the obliteration group and in 4 cases (17.4%) in the non-obliteration group  and a recurrent cholesteatoma in 2 cases , resulting in a residual cholesteatoma rate of 7.1% and a recurrent cholesteatoma rate of 14.3%.p = 0.022).As shown in supplemental Table Postoperative hearing tests were available for 52 patients (92.8%) in the obliteration group and 21 (91.3%) patients in the non-obliteration group Table . There wA postoperative otitis externa within 3 months post-surgery was observed in 3 cases (5.4%) in the obliteration group and in 4 cases (17.4%) in the non-obliteration group. Six infections were successfully controlled with topical therapy as in 1 case oral antibiotics were administered. In 2 cases (3.6%) in the obliteration group, liquorrhea occurred due to an iatrogenic defect in the cranial fossa. In 1 case, this was successfully closed during the initial procedure and in 1 case revision surgery was needed to close a defect in the posterior cranial fossa.The current literature on revision mastoidectomy for troublesome cavities is relatively scarce, as shown in a literature overview in Table In this study, we retrospectively compared revision canal wall down surgery with mastoid obliteration and posterior canal wall reconstruction to revision canal wall down surgery without obliteration in the management of chronically discharging mastoid cavities. We show that in our study population, the obliteration technique is superior to the non-obliteration technique with regards to the dry ear rate, need for regular maintenance cleaning and interval between maintenance cleaning sessions. We found no differences in audiological outcome and in incidence of complications between the two techniques.The incidence of discharging mastoid cavities after canal wall down surgery is estimated at 10–30% . Whilst As previous studies reported outcome on either the obliteration , 16, 17 We identified the reasons for previous surgical failure to be remaining mastoid air cells with infected mucosa, a high facial ridge, a narrow meatus, remaining bony overhang, cholesteatoma, a tympanic membrane perforation or exposed bone in the mastoid bowl. These findings confirm previous research in which the same factors were identified –11 and aThere were no significant differences in ossicular chain status and in postoperative hearing between the two groups. With a median postoperative AC threshold level of 46.3 dB HL in the obliteration group and 42.5 dB HL in the non-obliteration group, the hearing results are to some degree disappointing. However, when interpreting these results one should take into account that the cohort consisted of very challenging chronically discharging ears of which most had several surgical interventions before. Therefore, the aim was to preserve hearing and not necessarily to improve hearing, which was achieved with a median change in AC threshold of 2.5 dB HL in the obliteration group and 0.0 dB HL in the non-obliteration group. Especially patients in the obliteration group should be able to wear hearing devices without any problems because of the restored anatomy. Unfortunately, it was not systematically reported in the patient records whether patients were able to.Limitations of this study include the retrospective design and the possible indication bias. The mastoid obliteration with posterior canal wall reconstruction procedure was introduced in 2013 in our clinic and gradually replaced revision CWD without obliteration. Especially in the beginning of this transition, the choice to perform one of the two techniques was made by the surgeon based on preferences and experience. Later on, all surgeons adopted the obliteration technique and in principle no non-obliteration techniques were used anymore. Further limitations include the follow-up: the median follow-up duration was 20 months for the obliteration group and 67 months for the non-obliteration group. A shorter follow-up period may potentially overestimate the dry ear rate as long-term failures may not be included. However, no long-term failure was observed in the non-obliteration group and previous research has shown excellent long-term results after the obliteration technique , 13.We show that in our study population revision CWD surgery with mastoid obliteration and posterior canal wall reconstruction is superior to revision CWD surgery without mastoid obliteration in the management of chronically discharging mastoid cavities. In the obliteration group, a dry ear was achieved in 96.4% as this was 73.9% in the non-obliteration group. We found no differences in audiological outcome and in incidence of complications between the two techniques.Supplementary file1 (DOCX 15 KB)Below is the link to the electronic supplementary material.


The first-line colon cancer chemotherapies oxaliplatin and 5-fluorouracil were assessed in a syngeneic colon cancer model, either as monotherapies or in combination with PD1, comparing radiopharmaceutical uptake to memory-associated immune cells in the tumour. [18F]AlF-NOTA-KCNA3P reliably separated tumours with immunological memory responses from non-responding tumours and could be used to measure Kv1.3-expressing TEM cells responsible for durable immunological memory response to combination therapy in vivo.Often, patients fail to respond to immune checkpoint inhibitor (ICI) treatment despite favourable biomarker status. Numerous chemotherapeutic agents have been shown to promote tumour immunogenicity when used in conjunction with ICIs; however, little is known about whether such combination therapies lead to a lasting immune response. Given the potential toxicity of ICI–chemotherapy combinations, identification of biomarkers that accurately predict how individuals respond to specific treatment combinations and whether these responses will be long lasting is of paramount importance. In this study, we explored [ We used flow cytometry to determine which tumour-infiltrating immune cell populations were associated with response to these treatment combinations in a murine syngeneic colorectal cancer model.Immune checkpoint inhibitors (ICIs) have transformed the field of immunotherapy; however, many patients do not respond to ICI monotherapy, despite favourable biomarker status  ,3. The e T-cells ,11,12,13 T-cells ,14,15. T T-cells ,16. Howe T-cells ,18,19; iM cells) . TEM celmulation . Furthersurvival . ActivatO+CCR7+) ,24,25; h18F]AlF-NOTA-KCNA3P was isolated with a non-decay-corrected radiochemical yield of 12 ± 6 % within 50 min (n = 6) from aqueous [18F]fluoride. The radiochemical purity was greater than 99% and molar activity was 59 ± 16 GBq/µmol at the end of synthesis (n = 6).The precursor NOTA-KCNA3P peptide was custom synthesized by Chinese Peptide Company (CPC) and radiolabelling was performed as previously described . [18F]Al5 cells prepared in a 1:1 v:v ratio in Matrigel, Sigma-Aldrich, Singapore) into the right shoulder. Callipers were used to assess tumour volumes for the duration of the experiment (modified ellipsoid formula 1/2Length × Width2 AlF-NOTA-KCNA3P tumour retention (>0.8%ID/g) and TNR animals with low [18F]AlF-NOTA-KCNA3P tumour retention (<0.5%ID/g) were re-challenged, implanting CT26 tumour cells  into the contralateral left shoulder. Contralateral tumour re-growth was measured using callipers for a further 15 days.After the animals had been separated into treatment responders (TR) and treatment non-responders (TNRs) based on their response to therapy, TR animals with high [18F]AlF-NOTA-KCNA3P (~10 MBq) via the lateral tail vein, static PET acquisitions were acquired and analysis of reconstructed calibrated images was performed using Amide software . Volumes of interest, delineated by CT imaging, were used to determine uptake in tissues. Data are expressed as percentages of the injected dose per gram (%ID/g).Tumoured animals underwent imaging using a Siemens Inveon PET-CT 13 days after tumour implantation as previously described . BrieflyThe flow cytometry procedure has been reported previously . BrieflyTime-gated, size-gated, live, singlet CD45-positive cells from the fcs files were exported from FlowJo and used for dimension reduction analysis as reported previously  for fur.www.graphpad.com, accessed from 1 January 2022). p < 0.05 was considered statistically significant. Data are expressed as means ± S.D. unless otherwise indicated.Kruskal Wallis one-way ANOVA was used to assess the non-parametric datasets, with a Dunn’s post-test for multiple comparisons. All statistics were evaluated using GraphPad Prism version 8.3.4 . Treatment arms including oxaliplatin, 5-FU and αPD1 were administered on their own or in pairwise ICI–chemotherapy combinations . Combined ICI–chemotherapy treatment arms had both greater response rates and response magnitudes than αPD1 or chemotherapy monotherapy arms . The control-treated arm and TNRs showed little tumour retention for [18F]AlF-NOTA-KCNA3P. The ⍺PD1- and 5-FU-responsive tumours both showed significant increases compared to TNRs (** p < 0.01 for both). The OXA responders (*** p < 0.001) and the ⍺PD1 + OXA and ⍺PD1 + 5-FU responders (*** p < 0.001 for both) showed significantly higher tumour uptake of [18F]AlF-NOTA-KCNA3P when compared to TNRs  in the contralateral shoulder and tumour growth was measured for 15 days after implantation. TR animals with high tumour uptake of [18F]AlF-NOTA-KCNA3P on day 13 (>0.8%ID/g) showed negligible tumour regrowth after re-challenge up to 15 days post-re-implantation in the contralateral shoulder, whereas TNR animals with low tumour uptake of [18F]AlF-NOTA-KCNA3P showed significant tumour growth after re-implantation  compared to tumours that did not respond to therapy TNR; . Earlier T-cells ,11,12,13 T-cells ,14,15. HEM cells . In contEM cells .18F]AlF-NOTA-KCNA3P has previously been shown to reliably stratify tumours responding to immune checkpoint inhibitors from non-responding tumours, measuring tumour-associated Kv1.3-expressing TEM cells responsible for durable immunological memory response to combination therapy in vivo; however, little is known about whether adjuvant therapies that modulate the immune environment will synergise with the effects of PD1 blockade to promote a lasting immunological memory response at the tumour. Immunological memory occurs when naïve T-cells are repeatedly exposed to antigens and differentiate into memory T-cells, antigen-specific T-cells that remain long-term and rapidly proliferate in response to antigen re-exposure. Effector memory T-cells (TEM), in particular, are associated with durable tumour response to ICIs AlF-NOTA-KCNA3P  [18F]AlF-NOTA-KCNA3P could be a useful addition to [18F]FDG imaging in the clinic, aiding in therapy management and helping distinguish tumour response from pseudoprogression or immune-related adverse events.5-FU treatment led to increases in tumour-infiltrating NK cells as previously reported , but no observed B. FurtheEM cells D. Unlikehaustion . Despite events) ,36, and  events) . Overall+ TEM tumour infiltration induced by PD1 blockade. Imaging with [18F]AlF-NOTA-KCNA3P accurately measured Kv1.3-expressing TEM cells associated with durable response to combination therapy in vivo. With further development, [18F]AlF-NOTA-KCNA3P may serve as a clinical biomarker to support investigations into new therapy combination strategies to enhance responsiveness to ICIs.Although the chemotherapeutic agents assessed in this study affected the tumour microenvironment in different ways, both led to effective immunological memory responses in tumours and complemented the CD8


This article analyzes the significance of linear and quadratic convection on the dynamics of micropolar fluid due to a stretching surface in the presence of magnetic force and a rotational frame. Modern technological implementations have attracted researchers to inquire about non-Newtonian fluids, so the effect of linear and nonlinear convection conditions is accounted for in the dynamics of non-Newtonian fluid. The highly nonlinear governing equations are converted into a system of dimensionless ODEs by using suitable similarity transformations. The bvp4c technique is applied in MATLAB software to obtain a numerical solution. This investigation examines the behavior of various parameters with and without quadratic convection on the micro-rotation, velocity, and temperature profiles via graphical consequences. The velocity profile decreases with a higher input by magnetic and rotating parameters, and fluid velocity is more elevated in the nonlinear convection case. However, the temperature profile shows increasing behavior for these parameters and quadratic convection increases the velocity profile but has an opposite tendency for the temperature distribution. The micro-rotation distribution is augmented for higher magnetic inputs in linear convection but reduces against thermal buoyancy. The mixing and flowing of fluids are generated through density variation caused by differences in temperature within the fluid, known as natural convection. The fluid density near the heated surface is lower than that of the cold fluid. Gravity raises the hot fluid upward, causing the buoyant force to manifest. The convective flux problems of working liquid have various engineering implementations, such as food preservation, cryogenic devices, solar collectors, energy storage, and nuclear reactor technology. Nonlinear convection exists in the buoyancy force because of temperature fluctuations substantially affecting flux characteristics. Awan et al.  analyzedThe fluids class showing microscopic change induced by micro-rotation and the local formation of fluid molecules are known as microfluids. The notion of this type of fluid was firstly offered by Eringen et al. . In receThe study of magnetohydrodynamics (MHD) in liquid flux gains importance in handling flux characteristics. Essentially, MHD is concerned with the magnetic properties of electrically conductive liquid. The effects of MHD on fluid flow have been observed in several real-world instances in chemistry, physics, and industry such as stream meters, crystal growth, pumps, power plants, controlled thermonuclear reactors, wire drawing, MHD generators, and oil recovery techniques. Experimental and theoretical analysis of magnetohydrodynamic pumps is explored by Jang et al. . Ali et Recently, analyzing energy and fluid transport problems in a rotational frame has been widely studied in various mathematics models and turned into a fascinating phenomenon. It is due to their tremendous applications in the food industry, cosmic liquid dynamics, viscometry, and computer stockpiling devices. Since rotational flux is critical, researchers attempt to comprehend the underlying science. The foremost endeavor of this pathway was developed by Wang . Dessie (i)incorporate the micropolar fluid as host fluid,(ii)analyze with and without quadratic convection on the dynamic of micropolar fluid, and(iii)consider the significant effects of magnetohydrodynamics subject to a rotating frame of reference.This analysis investigates the significance of linear and nonlinear convection on the dynamics of micropolar fluid and heat transfer across a horizontal expanding surface. The current study has the following novelties:Since the authors pointed out that none of the cited studies above are focused on the elaborated problem, the bvp4c technique is applied, and differentiated outcomes for micro-rotation, velocity, temperature, skin friction, and Nusselt number are obtained.(1)To explore the significance of material, magnetic, and rotating parameters on the dynamic of microplar fluid: the case of linear and quadratic convection.(2)To observe the influence of Lorentz and Coriolis forces on micro-rotation profile: the case of linear and quadratic convection.(3)To observe the variations in skin friction coefficients and Nusselt number against growing values of rotating, magnetic, thermal buoyancy, and material parameters in the case of linear and quadratic convection.This analysis gives scientific answers to the following research questions:x-axis to stretch the sheet at a velocity of z-direction, and under the small magnetic field Reynolds number assumption, the induced magnetic field is negligible. Further, Ohmic dissipation and Hall current impacts are neglected because the applied magnetic field is not very strong , where The above first-order differential equations with seven initial conditions are solved via the shooting technique. The numerical computation has been performed for various physical emerging parameters for the appropriate computational domain  instead of [0,Case 1: with linear convection  parameter, rotating (K), thermal buoyancy  parameters in quadratic convection case.The fluid particles’ temperature increases with higher inputs of rotating and magnetic parameters in linear convection case but is reduced against growing strength of rotating (x direction, the skin friction coefficient decreases with the amplified value of magnetic, rotating, and material parameters in the linear convection case. Along the y direction, the skin friction coefficient is raised by enlargement in magnetic and material parameters without quadratic convection case. However, it decreases for thermal buoyancy and rotating parameters in the quadratic convection case.Along the The magnitude of the Nusselt number is reduced with a higher contribution of rotating and magnetic parameters in the linear convection case. However, it increases against material and thermal buoyancy in the nonlinear convection case.The linear and quadratic convection flux of non-Newtonian fluid in 3D on extending surfaces in the presence of magnetohydrodynamics is investigated in this study. Fluid velocity, micro-rotation, temperature distribution, skin friction factor, and Nusselt number are conducted using the technique of bvp4c. A few significant consequences are summarized as follows:


The objectives of this study were to develop an automated method for 3D tumour measurement and compare it with the radiologist’s manual assessment, as well as to investigate the impact of 3D tumour measurement on Prostate Imaging-Reporting and Data System version-2.1 (PI-RADS v2.1) scoring of prostate cancer. Tumour maximum diameter and volume were calculated using automated ellipsoid-fit method. For all PI-RADS scores, mean ± standard deviation range of tumour maximum diameter and volume measured using ellipsoid-fit method were 1.36 ± 0.28 to 1.97 ± 0.67 cm and 0.49 ± 0.31 to 1.05 ± 0.78 cc and manual assessment were in range of 0.73 ± 0.12 to 1.14 ± 0.25 cm and 0.36 ± 0.21 to 0.93 ± 0.39 cc, respectively. Ellipsoid-fit method showed significantly ( Tumour maximum diameter (TMD) and tumour volume (TV) are well established prognostic factors to assess the risk of a clinically significant PCa (csPCa)4. Advances in MRI have provided a non-invasive method of evaluating TV, although this may be underestimated with measurement from MRI as was reported previously7. The overall underestimation of TV with MRI may be understood from the study of Langer et al.6, where histologic findings identified sparse areas of PCa containing normal tissue intermixed with malignant epithelium, which may not be distinguished on MR images.Accurate measurement of tumour size in patients with prostate cancer (PCa) is becoming important to guide treatment planning8. The revised PI-RADS v2.1 relies mainly upon subjective analysis of MRI findings with quantitative features, including: tumour-size, TV and mean apparent-diffusion coefficient (ADC)9. PI-RADS v2.1 incorporates a tumour-size based decision-criterion (cut-off = 1.5 cm) to differentiate between assessment of score-4 and score-59. PI-RADS v2.1 recommends upon minimal requirements for the measurement of TV, whereas insists to report the maximum tumour diameter of a lesion on an axial images9. TMD represents the actual tumour dimension, which can be in any plane, where axial two-dimensional (2D) might or might not be the correct representation. Thus three-dimensional (3D) assessment of tumour is highly desirable for practical purposes10. Based on the applications of MRI, csPCa is defined as Gleason score > 7 and TV > 0.5 cc9. Martorana et al. found that as PI-RADS score increases the probability of detecting a csPCa proportionally increases with increase in TV11. Bratan et al. identified the accuracy of volume assessment was influenced by the size of lesions, Gleason score, and PI-RADS score12.Prostate Imaging-Reporting and Data System version 2 (PI-RADS v2) provides assessment scores for PCa on a scale of 1 to 5, in which score-5 is most likely to represent csPCa5. Diameter-based tumour-size measurement has been the clinical standard method to assess maximum diameter and volume13. This method is easy and fast to perform in a busy clinical routine but may be less accurate because PCa may spread through the tissue along any axes13. Many methods have been used to determine TV, but computer-assisted image analysis based volume measurement is considered as the most accurate14. Planimetric calculation includes the contouring of the lesion on each axial-slice which puts an additional time burden on the radiologist; therefore, this method is not routinely used in clinical practice and is limited to only in research settings14. A recent expert-consensus panel concluded insufficient evidence to recommend any optimal method for measuring TV with MRI1; however volumetric measurements allows accurate assessment of tumour by adding a third dimension and can measure the maximum-diameter in any plane15.A recent review by Eldred-Evans et al. has reported an increasing number of studies evaluating volumetric assessment of tumours against radical prostatectomy as the reference standard16. For these reasons, tumour-size and volume estimation with MRI should be considered with care in clinical practice since it may have implications for risk stratification12. PI-RADS v2.1 assessment uses a 2D approach for tumour measurement, and this assessment may be influenced by 3D measurement of diameter and volume of tumour, which has not been thoroughly investigated. The objectives of the current study were to (a) develop an automated method for 3D measurement of tumour using ellipsoid-fit model, (b) compare the TV and TMD measured with the ellipsoid-fit model against the current standard i.e. the manual-assessment with axial planes by the radiologist and (c) investigate the effect of 3D measurement of tumour in PI-RADS v2.1 assessment.PI-RADS v2.1 assessment has different decision rules for each score, and MRI derived TMD and TV were associated with csPCa2, reconstructed matrix = 320 × 320, voxel size = 0.49 × 0.49 × 3 mm2, slice thickness = 3 mm, slice gap = 3 mm and number of slices = 36. Diffusion-weighted imaging (DWI) was acquired using echo-planar imaging sequence with TR/TE = 6831/81 ms, FOV = 292 × 292 mm2, reconstructed matrix = 112 × 112, voxel size = 2.6 × 2.6 × 3 mm3, slice thickness = 3 mm, slice gap = 3 mm, number of slice = 36 with five b-values of 0, 500, 1000, 1500 and 2000 s/mm2. ADC values were calculated using the vendor-provided software at the clinical workstation. A mono-exponential model using all five b-values with the least-square optimisation was used for ADC calculation17.The current study protocol was conducted with approval from the Institutional review board (IRB), All India Institute of Medical Sciences (AIIMS), New Delhi  and informed consent was waived off by IRB for this study because of the retrospective nature of the study. This study was performed in accordance with institute guidelines and regulations. MRI dataset of 43 patients (age = 65 ± 8.5 years) with clinically proven PCa  were included in this retrospective study. MRI was acquired with a 1.5 T scanner  at the AIIMS, New Delhi with using a standard MRI protocol from August 2018 to October 2019. T2-weighted imaging (T2WI) were acquired using a turbo spin-echo sequence with TR/TE = 3330/90 ms, field of view (FOV) = 250 × 250 mm19. The pre-processing steps included manual segmentation of the prostate gland and peripheral zone (PZ) using DWI (b = 2000 s/mm2), performed with the help of a radiologist (> 20 years of experience in prostate MRI). The segmented prostate region consisted of approximately 5–8 slices for each subject. Data was interpolated to generate finer slices (1 mm) and to account for slice gap. Lesion scoring was performed according to PI-RADS v2.1 guideline by a radiologist9.MRI data were transferred to a workstation  in DICOM format. A modified in-built routine of MATLAB  was used for 3D measurements2) data; then the same ROIs were later applied on T2W images and ADC images of the respective subject. In this study, maximum diameter was measured using DWI and T2W lesion ROIs on the sequence that radiologist considered to best depicted the index lesion. The ROI-based volume was calculated by the summation of all lesion areas in each slice and multiplication by the factor of slice-profile (3 mm slice-thickness plus 3 mm gap). The analysis was performed using image processing software ImageJ .Initially, lesion region-of-interest (ROIs) (size range = 50–200 voxels) were drawn on PZ of DWI , shape and size9. In the current study, PI-RADS v2.1 score ≥ 3 was defined as a visible tumour on MRI. PI-RADS v2.1 scores were assessed independently based on manual-assessment by the radiologist and 3D tumour measurements using automated ellipsoid-fit method.MRI images were analysed and scored by the radiologist with PI-RADS v2.1 using a 5-point scalet-test, Pearson-correlation coefficient (r), Bland–Altman plots and violin-plots. The Kolmogorov–Smirnov test was used to test the normality of the data. All statistical analyses were performed using MedCalc statistical software for windows version-15.8.TMD and TV obtained from manual assessment were compared with ellipsoid-fit method findings using paired sample p < 0.05) for both TV and TMD than manual assessment by factor of approximately 1.31 for TV and 1.74 for TMD. There was good correlation (r = 0.85 and p < 0.05) for TV and moderate correlation (r = 0.55 and p < 0.05) for TMD between manual and ellipsoid-fit measurement method. A significant bias in the agreement between manual assessment and ellipsoid-fit based tumour measurements, graphically displayed by scatter and the Bland–Altman plots  were classified as score-5, and for score-4, 11 out of 18 (61%) patients were classified as score-5 compared to manual-assessment.Figure 5. Maximum-diameter and volume of tumour provide an important information in determining the clinically significant PCa3.Accurate non-invasive measurement of prostate TV could significantly improve the determination of tumour prognosis. MRI has become a standard method for patient selection and guiding biopsy and focal therapy11. Wolters et al. reported a positive relationship between TV of > 0.5 cc at radical prostatectomy, PCa staging and Gleason-score19. Another study found that in 2D measurement, TMD was a valuable parameter to differentiate between PI-RADS assessment score-4 and 5, and showed a significant correlation with higher Gleason scores2. At present, there are no other feasible non-invasive image-based alternatives, although developments in new methods can refine volume estimations. PI-RADS v2.1 aims to standardise the estimation of prostate gland volume by proposing either whole prostate segmentation or the use of the ellipsoid-fit method9. In some studies, ellipsoid-fit method was used to calculate prostate gland volume to assess the diagnostic accuracy of prostate-specific antigen density (PSAd) in predicting PCa, which provided greater reliability than the alternative methods21; it may be preferable to use the ellipsoid-fit method to determine the 3D measurement of prostate tumour to assess the PI-RADS v2.1 scores, as proposed in the current study.Several studies have evaluated the agreement between MRI based TV and histological TV based on radical prostatectomy specimens and found an underestimation of MRI based measurement, ranging from 4 to 97%22.In the current study, an automated ellipsoid-fit model was used for 3D measurement of TV and TMD and these quantitative parameters were compared with the manual assessment of the radiologist using the current standard axial slices. Along with this, the effect of 3D measurement of tumour in PI-RADS v2.1 assessment was also investigated. Maximum diameter and volume of the tumour in PZ were measured from DWI and T2WI, using the sequence that radiologist considered the best depicted the index lesion. Only biparametric MRI (T2WI and DWI) was used for this study but inclusion of additional sequences might improve the diagnosis, which need to be explored. There might be some variations in TV and size depending on the type of imaging technique as lesion contrast may vary in different sequenceThe current study found that ellipsoid-fit method showed higher TV and TMD values than manual-assessment with variability ranging from 17 to 26% and 34 to 46%, respectively. It was observed that ellipsoid-fit based TMD showed large variation than manual-assessment, which was expected as radiologist measurement are carried on axial slices showing largest lesion. However, during ellipsoid-fit, major axis is considered as TMD, which is expected to be higher than 2D measurement. Score-3 measurements were found to have higher variability than score-4 and score-5, due to intermediate density and heterogeneous tumour morphology which remains obscure on prostate MRI.23. In literature, studies have found an underestimation of TV (4 to 97%) by a radiologist based on 2D assessment with MRI against histopathological measurements, similarly in this study where manual-assessment by radiologist was found to underestimate TV by 17–26% and TMD by 34–46% compared to the ellipsoid-fit based measurements. From the results of the current study, it is implied that the measurements obtained with ellipsoid-fit method for PCa can be comparable with the literature histopathological analysis. Violin-plot was utilised in this study to visualise the distribution of TV and TMD across all patients as well as its probability density.Bland–Altman analysis showed a significant bias in the agreement between manual-assessment and ellipsoid-fit based measurements. The bias might occur due to the conservative approach of radiologist for tumour measurements and the inherent curvature bias in 3D ellipsoid-fittingAs found in the current study with the ellipsoid-fit method based measurements, 61% patients of score-4 and 40% patients of score-3 were changed as score-5 because of higher TMD (≥ 1.5 cm) as per updated PI-RADS v2.1. PI-RADS v2.1 scores were found to have a linear relationship with TV, which could be an important clinical parameter for PCa diagnosis. The current study only demonstrates that maximum diameter of tumour can be practically in any direction, not necessarily in axial plane only. Thus obvious hypothesis was whether measuring the maximum diameter in these specific cases, changes the PI-RADS score. The current study focuses on the development of 3D measurement tool using ellipsoid-fit approach and give only preliminary evidence for its impact on PI-RADS v2.1 score in small patient cohort. By observing the results, it is evident that ellipsoid-fit based measurements were higher than the conventional radiologist assessment in some cases, which has changed the PI-RADS scores. One of the major limitations of this study is the Gleason scores based on radical prostatectomy specimen were not available at our centre and biopsy proven Gleason scores were available but not for all the patients for building a conclusive evidence. There was also much variability in the Gleason scores that were found in patients under this study, even in patients whose PI-RADS scores were not changed by ellipsoid method. This is just an observational evidence. The bigger question to embark upon is for the PI-RADS community to evaluate this 3D tumour measurement with the larger studies to evaluate the clinical implications, which are beyond the scope of this study.24 and these tools have shown good diagnostic accuracy for PCa among all available AI-based tool25. However, there are some inherited problems these methods usually face, such as it is not always possible to get access to these trained models for larger clinical adoption, and often it is not simple for the end users to implement these. The larger question on bias in training dataset with respect to MRI machine, acquisition site and populations cohort etc., always requires a wider multi-centric and multi-geographical location dataset to be included in the training process, which is currently not available.There are few artificial intelligence (AI)-based automatic segmentation tool which can delineate lesions and calculate the lesion volume. A comprehensive overview of current commercial products/public tools is summarized by Sunoqrot et al.Our study focuses on demonstrating the development of a 3D measurement tool using a simple mathematical operation, an ellipsoid-fit approach and its impact on PI-RADS v2.1 score. The program is developed in-house for lesion measurement in the MATLAB , which gave us insightful information of whole fitting algorithm and PI-RADS assessment. It is easily scalable and require less computation power as compared to any AI-based approach.23, which need to be further investigated.There are other limitations to the current study. First, the data were acquired from a single institution and a small cohort; it may influence the outcomes. A large cohort and multicentre study can provide stronger evidence for larger clinical application. Second, the reference measurement was done by only one radiologist; inter-observer and intra-observer variability were not evaluated. Third, benign lesions (score-2) were not included in this study because these cases are not usually biopsied as per current standard of guidelines. It is also observed that, not all lesions fit well with the ellipsoid model, especially the PI-RADS 5. This could be possibly because the extra prostatic invasion of the lesion was not evaluated in this study and the inherent curvature bias in ellipsoid-fitting methodology3D measurement of tumour using automated ellipsoid-fit method has been developed and its impact on PI-RADS v2.1 scoring was assessed in a cohort of patients with prostate cancer. Ellipsoid-fit method led to find an increase in the TMD by 34–46% and TV by 17–26% and more than 40% of patients with PI-RADS v2.1 score-3 or 4 were changed to score-5. In future, a study on evaluating the potential clinical implications of proposed 3D ellipsoid fit based tumour measurements in PI-RADS scoring should be carried out.


The simulation data presented in this paper describes the interaction between a thin-walled aluminum cylinder and a gas bubble in a near-field underwater explosion. The simulation is performed using the AERO-F/S solvers. The finite element AERO-S solver is used to simulate the structural dynamics of the cylinder, including its yielding and collapse. The AERO-F solver is used to simulate the fluid dynamics of the explosion bubble, the surrounding liquid water, and the air inside the cylinder. The two solvers are coupled using an embedded boundary method and the FInite Volume method with Exact two-material Riemann problems (FIVER). The data presented in this paper corresponds to a representative case with initial pressure  The simulation accounts for large structural deformation, yielding, plastic deformation, and self-contact. It also accounts for the compressibility of the gas bubble and the surrounding liquid water.•The simulation predicts a counter-intuitive mode of collaspe, in which the closest point on the cylinder to the explosive charge moves towards the charge.•The data presented in this manuscript allows researchers to repeat the simulation, which is a representative case in the co-submitted paper •The simulation input files can be modified to study related problems involving cavitation bubbles, underwater explosion, and fluid-structure interaction.1This paper presents a set of data associated with the numerical simulation of the interactions between a high-pressure gas bubble and a thin-walled aluminum cylinder, in the context of near-field underwater explosion. The fluid dynamics is simulated using finite volume method implemented in the AERO-F solver Simulation folder. A sequence of 626 image files are placed in the Images folder, which shows the evolution of the structural deformation, bubble dynamics, and the fluid velocity and pressure fields. An animation created using these images is located in the Video folder. The screen outputs generated by the simulation are recorded in a file, and placed inside the Simulation folder.22.12.2changeset 2101:7f9049f89e19 in the AERO-F repository changeset 3152:f484d5c512c8 in the AERO-S repository The simulation was performed using 2.3input.st and fem.in. Detailed information about each parameter can be found in the manuals of AERO-F and AERO-S The fluid domain is divided into 639 subdomains, with each one assigned to one CPU core. The simulation parameters are specified in tinkercliffs_sbatch.sh.Before launching the simulation, the fluid mesh and partition files were converted into 639 binary files, each one containing the mesh information of one subdomain. This was done using the SOWER program The simulation was performed using 640 CPU cores. The time step size was 2.4Outputs of the simulation include, but are not limited to, the fluid pressure, velocity, and level-set (for liquid-gas interface tracking) fields and the structural displacement, velocity, stress, and strain fields. Additional data in the form of images and animation can be found in the uploaded folder. All the images were generated using ParaView, version 5.8.1.This work does not involve human subjects, animal experiments, or data collected from social media platforms.Wentao Ma: Conceptualization, Methodology, Investigation, Visualization, Software, Writing – original draft, Writing – review & editing. Xuning Zhao: Investigation, Visualization, Writing – review & editing. Christine Gilbert: Resources, Writing – review & editing. Kevin Wang: Conceptualization, Methodology, Software, Writing – original draft, Writing – review & editing, Project administration.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


Granular cell tumours are uncommon acquired benign tumours of nerve sheath origin that are usually seen in the head and neck region and upper aero-digestive tract. They usually present as solitary small sized nodules in middle age. The tumour is usually benign and composed of sheets of large sized cells with abundant granular cytoplasm containing lysosomal macro-inclusions known as pustulo-ovoid bodies of Milian (POB) that represent the heterogeneity of the lysosomes. No well-established criteria for malignancy have been described for this tumour. In this article, we have discussed a rare case of granular cell tumour of the penis with its characteristic histomorphology and immunohistochemistry and relevant differential diagnosis. Granular cell tumour is an uncommon, benign tumour of nerve sheath origin. Most are acquired and present as a solitary skin-coloured nodule, less than 2 cm in size . UsuallyA 49-year-old immunocompetent male presented with the complaint of a single, non-itchy nodule on the shaft of the penis for one month. On clinical evaluation, the nodule was on the shaft of the penis, 1.5 cm in diameter and firm with no ulceration. No definite punctum was visible. There was no discharge from the lesion or penile urethra. No inguinal lymph nodes were palpable. The patient did not have any history of sexual exposure. No comorbidities were present. Excision of the nodule was done with the clinical diagnosis of epidermal inclusion cyst and sent for histopathological examination. A clinical photograph of the lesion was not taken at that time as the clinical suspicion was that of an indurated epidermal inclusion cyst and a diagnosis of granular cell tumour was not considered prior to the excision of nodule.Microscopic examination of 5 um Hematoxylin and Eosin (H&E)-stained sections showed unremarkable mucosal epithelium. The subepithelial connective tissue showed an unencapsulated tumour comprised of sheets of large, polygonal cells with a central vesicular nucleus, variably conspicuous nucleoli, and abundant coarsely granular eosinophilic cytoplasm . Large cGranular cell tumour or Abrikossoff tumour is an uncommon, benign tumour of nerve sheath origin. Most tumours are acquired and present as solitary skin-coloured nodules, less than 2 cm in size . About 1Similar tumours called congenital epulis are seen on the anterior alveolar ridge in neonates .The overlying epithelium often shows pseudo-epithelioma-tous hyperplasia, which may be misdiagnosed as squamous cell carcinoma. Often, small nerves are seen in and around the tumour. Abundant granular cytoplasm is present. The cytoplasmic lysosomal macro-inclusions or pustulo-ovoid bodies of Milian (POB) are an easily recognizable component of granular cell tumour and they appear to represent the heterogeneity of the lysosomes, giving the appearance of large granules that have partially detached from the adjacent cytoplasm .No well-established criteria for malignancy have been described for this tumour. However, tumour size greater than 5 cm, vascular invasion, necrosis, increased mitosis, apoptotic cells, cell spindling and rapid growth have been reported in malignant lesions .Histologically, these tumours need to be differentiated from melanocytic neoplasms, leiomyosarcoma, atypical fibroxanthoma, dermatofibroma with granular cell change, and adult-type rhabdomyoma. Absence of melanin pigment or any epithelial component, and negative HMB45 helped to rule out melanocytic neoplasms. Leiomyosarcoma with an epithelioid morphology show necrosis, atypical mitosis, and epithelioid cell morphology, and stain on immunohistochemistry for SMA and Myogenin which are negative in granular cell tumours. Dermatofibroma usually have an admixture of fibroblastic, myofibroblastic, and histiocytic cells with a storiform pattern with inflammatory cells, foam cells, and giant cells. Some of them may demonstrate granular cell change. On immunohistochemistry, the dermatofibromas are negative for S100P.Adult-type rhabdomyoma has typical histological finding of large polyhedral cells with abundant eosinophilic and granular cytoplasm. Cross striations may be appreciated and these tumours are positive for SMA, Desmin, and Myogenin, and are negative for S100P on immunohistochemical stains.Immunohistochemical studies favour a Schwann cell origin. On immunohistochemical examination, granular cell tumours usually express S100 protein, CD68, microphthalmia transcription factor (MITF), inhibin-α, and NSE  with relevant immunohistochemistry help to diagnose these unusual neoplasms. These tumours are treated by surgical excision and rarely recur. The knowledge about the occurrence of this rare tumour at an unusual site should be borne in mind and confirmed by relevant immunohistochemical stains that help to establish the diagnosis and rule out other mimics.The authors declare no conflict of interest.


We present an atypical case of a patient with hepatic hemangiomas showing fluid-fluid levels on computed tomography (CT) and magnetic resonance imaging (MRI). None of the lesions showed contrast enhancement, mimicking complicated hepatic cysts or metastasis with hemorrhagic content. On contrast-enhanced ultrasound the lesions showed peripheral nodular enhancement with complete fill-in on late phases, suggestive of hepatic hemangioma.Teaching point: Contrast-enhanced ultrasound (CE-US) may be useful in diagnosing atypical hepatic hemangioma showing fluid-fluid levels on computed tomography (CT) or magnetic resonance imaging (MRI). Hemangioma is the most common benign hepatic tumor, usually diagnosed without difficulty due to typical imaging features. However, atypical features of hepatic hemangiomas including fluid-fluid level have been reported 23. When 21We present a case of hepatic hemangiomas with fluid-fluid levels on CT and MRI that was further evaluated with contrast-enhanced ultrasound (CE-US).A 57-year-old man was admitted for elevated liver enzymes and carbohydrate antigen 19–9. On contrast-enhanced CT, there were rounded, non-enhancing cystic lesions in liver segments four, five, and seven . Each leAccordingly, ultrasound-guided biopsy was planned. In contrast to CT or MRI findings, ultrasound revealed that all lesions appeared solid with homogenous hyperechogenicity. CE-US revealed very slow peripheral nodular enhancement and complete fill-in, and without washout on delayed-phase . These fFluid-fluid level may be detected when a lesion contains substances of different densities in a cystic or confined space. This feature, caused by the sedimentation effect, has been reported in several hepatic lesions, such as complicated cysts, mucinous cystic neoplasm, or metastases with cystic, hemorrhagic, or necrotic changes . Fluid-f123Several reports 23 propos22Ghai et al.  suggesteCE-US may contribute to the final diagnosis of an atypical hepatic hemangioma with fluid-fluid levels when the characteristic hemangioma enhancement pattern is not observed on CT or MRI, and further lesion characterization is relevant for further patient management.


R0 surgical resection is the preferred treatment for bone and soft tissue sarcoma. However, there is still a lack of precise technology that can visualize bone and soft tissue sarcoma during surgery to assist the surgeon in judging the tumor surgical boundary. Fluorescence imaging technology has been used in the diagnosis of cancer. It is a simple and essentially safe technique that takes no additional time during the operation. Intraoperative fluorescence imaging has potential application prospects in assisting the surgeons in judging the tumor boundary and improving the accuracy of surgical resection. This review mainly starts with clinical studies, animal experimentation, and newly designed probes of intraoperative fluorescence imaging of bone and soft tissue sarcoma, to appraise the application prospects of fluorescence imaging technology in bone and soft tissue sarcoma. Traditionally, surgeons mainly use preoperative CT(computed tomography) and MRI(magnetic resonance imaging) to assess the tumor boundary within the surgeons’ naked eyes to select the scope of resection during the surgery . CT and The essence of intraoperative tumor fluorescence imaging is to allow fluorescent dyes to accumulate in tumor tissue during the operation so that the surgeons can find the boundary of the tumor. Fluorescent probes have different principles, such as EPR effects (enhanced permeability and retention) and antigen-antibody reactions. To date, fluorescence imaging has exhibited promising advantages in various tumors, such as brain tumors , breast In recent years, intraoperative fluorescence imaging of bone and soft tissue sarcoma has been explored in clinical studies, animal experimentation, and these studies have led to the development of new probes.Based on the principle of fluorescent probes, we divide the current fluorescent probes into four types and summarize them in Most non-specific probes rely on a passive targeting strategy, which preferentially accumulates molecules in tumors. The passive targeting strategy attributes to the tumor microenvironment such as accumulation of acidity, anoxic habitat, and necrotic tissue . It is nThe principle fluorescent component of tetracycline is achelate formed upon combination with calcium ions ontrabecular bone . OWEN etCompared with fluorescent probes for fluorescence imaging in the visible region, the research direction in recent years has focused more on fluorescent probes with excitation wavelength in the near-infrared region NIR-1 (700-900nm). Near-infrared fluorescence with a wavelength of 700-900nm is rarely absorbed in tissues .via clathrin-mediated endocytosis (CME) . ICG has absorption and fluorescence spectra in the near-infrared (NIR) region. The excitation wavelength is 780nm, and it emits fluorescence in the range of 700-850nm. The red light is visible to the naked eye, but most of the light is not . Most reis (CME) . Indocyais (CME) . HoweverMany factors can influence the EPR effect, including tumor type, size, and vascular mediators. As a result, the intensity of the ICG signal is unpredictable . If the via some enzymes in the tumor and microenvironment, therefore this probe is activated.Some scientists have also designed activatable fluorescent probes that emit fluorescence only in tumor tissues. This probe contains a chemical group, which can be broken down Many activatable fluorescent probes have applications in other types of tumors, and could theoretically be used for intraoperative imaging of bone and soft tissue tumors. The activatable fluorescent probes for the tumor microenvironment are mainly activated by extracellular enzymes specifically emitted in the tumor microenvironment. In addition to cathepsin-activated fluorescent probes that have been used in soft tissue sarcoma animal experimentation, there are also fluorescent probes activated by matrix metalloproteinases . The actActivatable fluorescence probes reduce the fluorescence intensity of normal tissues and further increase the tumor-to-background ratio (TBR). But at the same time, the chemical synthesis of probes is complicated, and there is still a lack of further research on the adverse reactions of these probes.Unlike ICG with the EPR effect, specific probes do not rely on the tumor microenvironment but instead rely on a targeting moiety conjugated to a contrast agent with a high binding affinity. These probes have higher targeting properties than indocyanine green .The original design method is to combine monoclonal antibodies with fluorescent dyes to create fluorescent probes. Previously, monoclonal antibodies were used as targeted drugs to treat tumors. For example, Bevacizumab is a monoclonal antibody that binds to vascular endothelial growth factor-A(VEGF-A)which is highly expressed in tumor cells  and playIn recent years, with the development of chemical synthesis technology, moieties for active targeting have become available, such as nanoparticle scaffolds, peptides, ligands, and aptamers. Compared with antibodies, the moieties have similar binding characteristics but show better tumor penetration and more rapid clearance from non-targeted tissues . For exaSpecific fluorescent probes are based on active targeting, their synthesis is complicated. Tumors are heterogeneous, so we can’t find a tumor marker expressed in each tumor tissue. The majority of specific probes are still in the pre-clinical stage. It requires more feasibility and toxicity studies, particularly for small molecule probes before clinical trials.SPECT/CT, MRI, and NIR combined multimodal imaging technology have gained significant popularity. Scientists have designed fluorescent probes with SPECT/CT, MRI sensitive groups, and fluorescent dyes   and have produced several fluorescent probes for tumor imaging in the NIR-2 range . AccordiPresently the widely used non-specific fluorescent probe in tumor surgery is indocyanine green. Overall, these cases in the past five years support that bone and tissue sarcoma can fluoresce after injection, and the tumor boundary is consistent with the pathological section control.For example, Fourman (2018)  injectedAnother example of what is meant by Mahjoub , is thatIn addition to indocyanine green, non-specific fluorescent probes such as Alizarin Red and Tetracycline had been expected to have great potential for intraoperative imaging of bone and soft tissue sarcoma. However, the fluorescence excitation wavelengths are 465nm and 490nm, which are both in the visible light range, and the fluorescence area overlaps with normal tissues. There have been few related studies in recent years.According to the different characteristics of tumor cells and tumor microenvironments from normal tissues, scientists have designed activatable optical probes. In 2016, Bartholf Dewitt S  used theSome specific probes have been designed, and animal experimentation has proved their specificity and sensitivity. Most specific probes are created by combining fluorescent dyes with antibodies or ligands that precisely bind to tumor cells Table 1.Based on this probe design idea, our team designed a specific fluorescent probe CS2-N-E9R for Ewing’s sarcoma-specific fusion protein EWS-FLI1 (E/F) in 2021 . Our speFor example, Li et al.  combinedAnother example of what is designed by Zhou  is CH105This technology is further exemplified in animal experimentation using indocyanine green and ABY-029 combined fluorescence imaging in soft tissue sarcoma surgery. Sardar et al.  discoverXu’s experimentation study explored the feasibility of specific fluorescent probes used for intraoperative imaging after radiotherapy and chemotherapy . Xu desiAnother research compared several fluorescent probes on soft tissue sarcoma mice . The resIn addition to the fluorescent probes that have been assessed on bone and soft tissue sarcoma, many newly designed fluorescent probes may have the potential to be used in intraoperative imaging of bone and soft tissue sarcoma. Mahalingam et al.  designedFor a ligand or antibody that specifically binds to bone and soft tissue sarcoma, the ideal is to find a target not expressed in other tissues and expressed in all bone and soft tissue sarcoma, especially tissue cells surrounding the tumor. There are many studies on tumor-specific markers of bone and soft tissue tumor cells. CxCR4 (Cys-X-Cys receptor 4), PDGFR-β(Platelet-derived growth factor receptor-β), TEM1 , VEGFR-1, EGFR, VEGFR-2, IGF-1R, IGF-2R, CD40, et al. are high specific tumor markers –58. ScieIn the case of specific fluorescent probes, future research could focus on developing new probes specifically binding to bone and soft tissue sarcoma, determining whether existing fluorescent probes can be used for bone and soft tissue sarcoma, and evaluating the advantages, disadvantages, and effectiveness of the probes.Probes for multimodal visualization in MRI, SPECT/CT, and Near-Infrared Optical Imaging have gotten attention in the past five years. These probes have the potential for preoperative tumor imaging, surgical planning, and intraoperative tumor fluorescence imaging.It is exemplified in the animal experimentation undertaken by Xu with 99mTc-Gd@OVA-Cy nanoprobe . ResearcScientists designed many fluorescent probes for multimodal imaging in the past five years. But there are few animal experiments on whether these fluorescent probes can be applied to bone and soft tissue sarcoma. Lee et al.  designedResearchers also focus on probes for multimodal visualization in SPECT/CT and intraoperative near-infrared optical imaging. A notable example is the folate-ECG-ROX targeted folate receptor in the tumor . AnotherReports about intraoperative fluorescence imaging of bone and soft tissue sarcoma are limited Table 2.In a similar case in the UK, 11 patients with bone and soft tissue sarcoma were admitted for ICG intraoperative fluorescence imaging . ICG wasThis technology is further demonstrated in studies using Bevacizumab-IRDye800cw fluorescence imaging in 15 patients with soft tissue sarcoma during surgery . ResearcFurthermore, bone and soft tissue tumor metastasis are frequent. Fluorescence imaging can detect tumor metastasis in bone and soft tissue. These clinical trials reveal the need for fluorescence imaging among metastases. Patients subjected toI CG injection were assessed after 24 hours . Among 44 patients with soft tissue sarcoma lung metastases, 40 lung metastases showed fluorescence during Video-assisted thoracoscopic surgery(VATS). Among 40 cases of osteosarcoma lung metastases, 36 cases had fluorescence. The depth of all lung metastases without fluorescence imaging was more than 2 cm. According to Predina, fluorescence imaging during ICG surgery is better for detecting tumor metastasis with a depth smaller than 2 cm and a diameter greater than 5 mm .Scheichel  performePredina and colleagues studied a patient with osteosarcoma lung metastases undergoing surgery and showed that fluorescence imaging with OTL38 enabled the detection of Lung metastases. According to previous studies, FR-α is overexpressed in 80% of primary osteosarcoma. The lung metastases had strong fluorescence after intravenous injection of 0.025mg/kg OTL38. However, the researchers did not specify whether fluorescence was observed in the primary osteosarcoma .At present, intraoperative fluorescence imaging does not use quantitative norms to determine whether it is tumor tissue. There is no standard for how high the fluorescence contrast should be to indicate a tumor in intraoperative fluorescence imaging technology. To determine the standard, it is important to conduct clinical trials including large sample size and compare with pathological results. Futhermore, a technique combining biophysics-inspired modeling and artificial intelligence (AI) was envisioned to monitor intraoperative changes in NIR intensities over time in different tissue and provide clinically significant lesion identification . In addiThe manufacture and use of fluorescent probes for intraoperative fluorescence imaging of bone and soft tissue sarcoma have a potential future. Non-specific probes may additionally fluoresce in non-tumor areas, which can cause surgeons to misjudge. The main direction of new fluorescent probes will be specific fluorescent probes with high specificity to label tumors. With the further investigation of the mechanism of bone and soft tissue sarcoma, scientists will discover more specific tumor-expressed molecules. We can accordingly design specific fluorescent probes with high specificity and sensitivity.Simultaneously, we noticed that tumors are heterogeneous, and it is difficult for a probe to image all tumors of the same type. Experiments are currently underway to combine two fluorescent probes with different principles to increase accuracy and lower the negative rate. In the future, we can design fluorescent probes with multiple responses to tumors and the microenvironment to further reduce the false-negative rate of fluorescence during tumor surgery.ZC: writing-original draft. HH: visualization, formal analysis. SH: investigation. YW: supervision. LC: conceptualization. YX: writing—review and editing. All authors contributed to the article and approved the submitted version.This work was supported by National Natural Science Foundation of China (NO. 82103285), the Improvement Project for Theranostic ability on Difficulty miscellaneous disease(Tumor) (ZLYNXM202005), the Research Fund from Medical Sci-Tech Innovation Platform of Zhongnan Hospital, Wuhan University (PTXM2021003).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.


Several studies have suggested that anti-silencing function 1 B (ASF1B) can serve as a good potential marker for predicting tumor prognosis. But the values of ASF1B in gliomas have not been elucidated and further confirmation is needed.Transcriptomic and clinical data were downloaded from The Cancer Genome Atlas database (TCGA), genotypic tissue expression (GTEx), and the Chinese Gliomas Genome Atlas database (CGGA). Univariate and multivariate Cox regression analyses were used to investigate the link between clinical variables and ASF1B. Survival analysis was used to assess the association between ASF1B expression and overall survival (OS). The relationship between ASF1B expression and OS was studied using survival analysis. To investigate the probable function and immunological infiltration, researchers used gene ontology (GO) analysis, gene set enrichment analysis (GSEA), and single-sample GSEA (ssGSEA).In glioma tissues, ASF1B expression was considerably higher than in normal tissues. The survival analysis found that increased ASF1B expression was linked with a poor prognosis in glioma patients. ASF1B demonstrated a high diagnostic value in glioma patients, according to a Receiver Operating Characteristic (ROC) analysis. ASF1B was found to be an independent predictive factor for OS in a Cox regression study . GO, KEGG, and GSEA functional enrichment analysis revealed that ASF1B was associated with nuclear division, cell cycle, m-phase, and cell cycle checkpoints. Immuno-infiltration analysis revealed that ASF1B was positively related to Th2 cells, macrophages, and aDC and was negatively related to pDC, TFH, and NK CD56 bright cells.A high level of ASF1B mRNA expression was correlated with a poor prognosis in glioma patients in this study, implying that it could be a reliable prognostic biomarker for glioma patients. Gliomas are the most prevalent primary malignancy of the central nervous system (CNS), accounting for more than 30% of all primary brain tumors and over 80% of all malignancies. They are also the major cause of death in patients with primary CNS tumors , 2. The Through processes such as histone-modifying enzymes, histone chaperones, and chromatin remodeling proteins, chromatin can be abnormally activated or expressed, regulating proteins that are directly associated with the genesis and spread of cancer , 13. AntIn this study, we first used the Cancer Genome Atlas (TCGA) database to confirm the prognostic value of ASF1B expression in glioma patients, and then validated the value using the Chinese Glioma Genome Atlas (CGGA) database. We used enrichment analysis and GSEA analysis to learn more about the biological functions and pathways that ASF1B may participate in the development of gliomas. Furthermore, we studied immune infiltration to see whether there was a link between ASF1B and immune cell infiltration and to understand the potential role of ASF1B from multiple aspects Figure 1https://xenabrowser.net/datapages/) was used to download the TCGA glioma data and the equivalent normal tissue data of GTEx by toil processing evenly. The protein expression of ASF1B in normal and glioma tissues was investigated using the Human Protein Atlas (https://www.proteinatlas.org/) database. Glioma patients were separated into two groups based on the median expression value of ASF1B: low expression and high expression. As an external validation, we downloaded glioma data from the CGGA (http://www.cgga.org.cn/) (Dataset ID: mRNAseq 693).UCSCXENA (2(FC) >2.0 or log2(FC) <−2.0 and adj-p-value <0.05 was considered as the threshold for DEGs. The results of the DEGs are shown in the volcano and heat map.In this study, R package DESeq2 (1.26.0) was used to analyze low and high ASF1B mRNA expression to obtain DEGs . Log2 <0.05 and normalized enrichment score (NES) >1 were considered significant enrichment.The R package clusterProfiler package (3.14.3) is used for GO enrichment analysis. GSEA was performed using the R package clusterProfiler too, which performed 2,000 times of gene set permutations for each analysis . We chosWe quantified 24 types of immune cells associated with levels of glioma immune infiltration to evaluate the correlation between immune cells and ASF1B expression by using the ssGSEA  method from the GSVA package (1.34.0) in R . The Harrell consistency index and calibration plots were created to evaluate the dependability and correctness of the prognostic model strengths. According to ASF1B, glioma patients were divided into high- and low-risk categories. The Kaplan–Meier curve was created to indicate the difference in overall survival (OS) between the two groups. The prediction accuracy of ASF1B was evaluated using receiver operating characteristic (ROC) curves.The Wilcoxon signed-rank test was used to evaluate paired samples, while the Wilcoxon rank-sum test was used to assess unpaired samples. The Kruskal–Wallis test, the Wilcoxon signed-rank test, and logistic regression were used to determine the link between clinical features and ASF1B expression. The chi-square test or Fisher’s exact test was used to examine the connection between ASF1B expression and clinical features. To generate a nomogram, researchers used univariate and multivariate Cox regression analyses of clinical variables and ASF1B to uncover relevant predictive markers. Statistical significance was defined as a P-value of less than 0.05. R (version 3.6.3) was used to conduct statistical analysis.ASF1B exhibited different expression profiles in different tumors and was significantly upregulated in glioblastoma and low-grade glioma Table 1.Clinical data on 696 and 693 glioma patients were gathered from the TCGA and CGGA databases, respectively, for this investigation Table 2.Compared with the ASF1B low expression group, the ASF1B high expression group had worse OS ((HR = 5.03 (3.76–6.73), log-rank P <0.001) from the TCGA database , P <0.001), IDH mutant (HR = 2.02 (1.33–3.06), P = 0.001), and 1p/19q non-codeletion (HR = 4.32 (3.34–5.59), P <0.001). ASF1B expression was related to a poor prognosis   Table S1Additionally, we identified key pathways associated with ASF1B by GSEA analysis and found that 106 data sets met the adjusted criteria of P-value <0.05 and FDR <0.05.  (No. 81860225), the Key Research and Development Plan of Jiangxi Province (No. 20203BBG73060), The Natural Science Foundation of Jiangxi Province (No. 20212BAB206029), the Science and Technology Project of Jiangxi Provincial Health Care Commission (No.20195116), and the Young Talents Research and Cultivation Foundation of the First Affiliated Hospital of Nanchang University (No. YFYPY202038).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. 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The primary objective of the study is to explore the phenomena of dusty fluid flow through an inclined irregular channel under the impact of the transversely applied magnetic field of fixed strength. The density and viscosity of the working fluid are assumed to vary along with the height of the channel as it behaves as a replica of many real world mechanisms. Hence, a stratified dusty fluid through a channel that tilts to an angle  Thermal diffusion is a natural mechanism that occurs due to variation in temperature within the system. The phenomenon of heat transfer on dusty fluid flows is known to have abundant applications in many technological devices and industrial processes namely underground heat pump systems, grain storage, insulation materials, thermal design of buildings, commercial refrigeration, float glass production, etc. Initially, the mathematical model for the dusty fluid flows has been formulated by Saffman  to examiDuring the past few decades, the heat transfer effect on magnetohydrodynamic (MHD) fluid flows are attractive from both mathematical and physical standpoints as it attributes that liquid metals occur either in nature or industries are electrically conducting. Such flow analyzes have considerable applications in engineering and technological problems including MHD generators, power generation systems, high temperature plasma, etc. Ibrahim  has emplThe heat transfer analysis of MHD fluid flows through a porous medium is significant since the porous matrix amplifies the process of heating/cooling and prevents heat loss as in a heat exchanger. The fluid momentum can be reduced remarkably when the flow is through a porous matrix . The cloThe studies discussed above are focused mainly on flows with constant physical properties. However, the physical properties like density and viscosity of the dusty fluid may vary significantly due to changes in temperature. In recent years, understanding the instability phenomena that accompany the transportation of the fluid has been the area of interest in many real world problems. In the designs that purify the contaminated groundwater due to waste repositories have been major studies to reduce the health risks to humans. The viscosity and density of the underground fluid vary and depend on the temperature and porosity of the medium. Also, a major difference in the velocity of the fluid is noticed when the constant and variable viscosity is taken into account . Lai andTherefore, in view of the recent developments in various technological fields, this article is aimed to formulate the effects of variable pressure and variable viscosity of MHD dusty fluid flow over an inclined wavy channel through a porous medium. This model is studied under two different conditions, that is, convective and Navier slip boundaries which are found in various engineering problems. From the literature review, research on the fluid flow with variable pressure and viscosity is very narrow and this particular model is not studied before as per the authors’ knowledge. Therefore, the main objective of the article is concentrated on the examination of a tilted irregular channel under variable pressure and viscosity. The numerical solution is obtained and the influence of emerging parameters on velocity profiles and temperature distribution have been analyzed. In order to visualize the various phenomenon of the flow, the contours of velocity and temperature fields are plotted. Further, the variations of skin-friction coefficient and the local Nusselt number are tabulated in view of engineering applications.x-axis overlaps with the direction of the flow and the magnetic field of fixed strength The dust particles are distributed uniformly throughout the fluid flow.N) is fixed.The number density of dust particles , aft, aft4), i.when ii.when The dimensionless form of the boundary conditions  and 6)  6) are rwhere i.when ii.when where A numerical approach to the mathematical model is preferable to an analytical approach, as it conquers the difficulties of time consumption, solving techniques, etc. Hence, the prescribed flow is analyzed by a finite difference scheme. The approximations of coupled equations of fluid and dust velocities  and 9)  9) and ti.when ii.when The corresponding numerical approximation of boundary conditions (Case: 1)  arei.whand the numerical discretization of the boundary conditions (Case: 2)  arei.when ii.when wherex and y axes and it is based on the boundaries in which the flow is analyzed. In the current problem, the numerical algorithm was executed for different values of m and Here The analysis of shear stress and heat transfer rate near the wall have been researched for centuries. Over the last few decades, knowledge of these factors become more focal area, especially in aerospace sectors which bridges to improvise the quality while designing the equipment.The friction between a moving dusty fluid and the inclined channel i.e., wall shear stress is analyzed through skin-friction and is given byThe comparison of heat transfer rate between the conduction and convection of fluid can be analyzed by the Nusselt number. The dimensional heat transfer coefficientT distributions against a few physical parameters which have a strong influence on the dusty fluid flow subjected to two different boundary conditions mentioned above. Alike nature in the variation of T is noticed in both cases. However, the magnitude differs with respect to adopted boundary conditions. Hence the physical interpretations and consequences thus discussed below for the flow phenomena over distinct parameters are going well with cases 1 and 2. In the figures the case 1 and 2 figures are referred as (a) and (b) respectively. This section provides graphical solutions and descriptions for the same to study the behavior of dusty fluid flow and thermal diffusion under the impact of various parameters involved. It is apparent from Fluid and dust phase velocities strictly increase for rising Reynolds number (Inspection of The skin-friction coefficient (The dusty fluid flow approaches high velocity when the stratified decay parameter, Reynolds number, and permeability of porous medium increase, whereas the effect is contrary for Hartmann number.Noticeable enhancement in temperature profile is observed for raising values of Eckert number, Hartmann number and reducing the value of Prandtl number and Biot number.Velocity fields of dusty fluid phase in case 1 is comparatively higher than in case 2 irrespective of variation in flow pertinent parameters.Temperature distribution is found to be more in the case of convective boundary than in Navier slip boundary, i.e., case 2.Increment in stratified decay parameter, Reynold number, and permeability of porosity yield reduction in friction factor, and the opposite effect is experienced with increment in Hartmann number.The heat transfer rate is magnified by boosting the values of A numerical technique has been adopted to describe viscoelastic dusty fluid flow through an inclined channel for convective and Navier slip boundaries. Discussion on flow phenomena under the effect of various parameters has been provided. The impact of parameters on shear and heat transfer rates are also computed. Based on this study, the following conclusions are drawn:The current study totally focused on the stratified dusty fluid. This study has further scope if it will be modeled to a dusty nanofluid or with non-Newtonian fluid that has high real world applications.


The diagnosis of internal neoplasia in horses is challenging. Increased production of hormones physiologic for adult animals  or typical for the foetal phase  might aid in tumour diagnostics. Thymidine kinase‐1 and alkaline phosphatase are examples of intracellular enzymes, whose activity in the blood may increase in some neoplasia cases. Furthermore, inappropriate production of abnormal monoclonal or autologous antibodies can accompany lymphoma and multiple myeloma. Many of those tumour markers lead to clinical or laboratory changes, called paraneoplastic syndromes, such as hypercalcaemia and erythrocytosis.The interpretation of the results of the tumour marker measurements in horses is complicated due to many factors affecting the markers’ concentration or activity  and other diseases triggering the same changes. Moreover, the presence of paraneoplastic syndromes is inconsistent, which leads to low sensitivity of those substances as tumour markers.In conclusion, screening for neoplasia in horses is not recommended. The measurement of tumour markers should be performed only in risk groups with suspicious clinical or laboratory findings, and the results should be interpreted with caution. It is advisable to add inflammatory markers to the tumour profile or repeat the measurements. The measurement of tumour markers in horses should be performed only in risk groups or in patients with suspicious clinical/laboratory findings (paraneoplastic syndromes). The results should be interpreted with caution as many factors  affect their concentration or activity. It is advisable to add inflammatory markers to the tumour profile or repeat the measurements. Abbreviations: ACTH, adrenocorticotropin; AFP, alpha‐fetoprotein; AMH, anti‐Müllerian hormone; EPO, erythropoietin; NE, norepinephrine; PTHrP, parathyroid‐hormone‐related protein. Nevertheless, there is ongoing research on tests confirming the diagnosis in questionable cases or even predicting the development of some skin tumours, for example, a genetic test for a squamous cell carcinoma at the limbus in Haflingers  or pathologic cell production . Moreover, neoplastic cells can produce or induce the production of specific substances that cause secondary changes in blood work or clinical signs, which are called paraneoplastic syndromes. Measuring the level of those circulating substances can help to diagnose, determine the stage or prognosis, monitor treatment and control for the recurrence of neoplasia; thus, they are called tumour markers. Paraneoplastic syndromes reported in horses include pruritis and alopecia, hypertrophic osteopathy (Marie's disease), pemphigus, hypoglycaemia, hypercalcaemia, erythrocytosis, neuropathies, immune‐mediated haemolytic anaemia (IMHA) or thrombocytopenia (IMTP), and monoclonal gammopathy  is widely used as a marker of hormonally active adenoma or, less commonly, carcinoma of the pars intermedia of the pituitary gland in horses, which causes a clinical syndrome called pituitary pars intermedia dysfunction (PPID)  is a glycoprotein produced by the yolk sac and later by the liver of the mammalian fetus  and inhibin are protein hormones produced by Sertoli cells in the male fetus and play a role in sex differentiation  production . Paraneoplastic secondary erythrocytosis seems more common than the primary one in horses   plays a central role in calcium homeostasis and skeletal formation in the fetus, and its concentration drops considerably in adults  is produced by hepatocytes, biliary epithelial cells, the intestine and osteoblasts; thus, an increase in its activity in the blood can be indicative of cholestasis, intestinal pathology or bone remodelling  is an intracellular enzyme that is activated in the G1 and S phases of the cell cycle when DNA doubles before mitosis or meiosis  and hepatotropic viruses, are associated with the increased activity of serum TK1  were quite promising  or viral (equine infectious anaemia) infections   and antibodies . Unfortunately, none of the substances described is an ideal biomarker, and general screening for neoplasia in horses is not recommended. The results should be interpreted together with history, signalment, suspicious clinical signs or laboratory findings  and evaluated for consistency. Many factors increase the concentration/activity of the tumour markers reported Table , and theMore research needs to be undertaken to clarify the sensitivity and specificity of tumour markers in equine medicine.Writing‐Original Draft Preparation: Karolina Drozdzewska. Writing‐Review and Editing: Heidrun Gehlen.The authors state that they have no conflict of interest.The authors confirm that the ethical policies of the journal, as noted on the journal's author guidelines page, have been adhered to. No ethical approval was required as this is a review article with no original research data.https://publons.com/publon/10.1002/vms3.1042The peer review history for this article is available at


Sci., 2021, 12, 14167–14173, https://doi.org/10.1039/D1SC01850G.Correction for ‘Cooperative C–H activation of pyridine by PBP complexes of Rh and Ir can lead to bridging 2-pyridyls with different connectivity to the B–M unit’ by Yihan Cao  The authors regret that the incorrect US National Science Foundation grant number (grant CHE-2102095) was provided in the Acknowledgements section. The correct grant number is CHE-2102324.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.