The present work examines the analytical solutions of the double duffusive magneto free convective flow of Oldroyd-B fluid model of an inclined plate saturated in a porous media, either fixed or moving oscillated with existence of slanted externally magnetic field. The phenomenon has been expressed in terms of partial differential equations, then transformed the governing equations in non-dimensional form. On the fluid velocity, the influence of different angles that plate make with vertical is studied as well as slanted angles of the electro magnetic lines with the porous layered inclined plate are also discussed, associated with thermal conductivity and constant concentration. For seeking exact solutions in terms of special functions namely Mittag–Leffler functions, G-function etc., for Oldroyd-B fluid velocity, concentration and Oldroyd-B fluid temperature, Laplace integral transformation method is used to solve the non-dimensional model. The contribution of different velocity components are considered as thermal, mass and mechanical, and analyse the impacts of these components on the fluid dynamics. For several physical significance of various fluidic parameters on Oldroyd-B fluid velocity, concentration and Oldroyd-B fluid temperature distributions are demonstrated through various graphs. Furthermore, for being validated the acquired solutions, some limiting models such as Newtonian fluid in the absence of different fluidic parameters. Moreover, the graphical representations of the analytical solutions illustrated the main results of the present work and studied various cases regarding the movement of plate. Systematic analysis of such fluid flow models have significantly important for theoretical studies and practical implementations in modernistic mechanization. Among several proposed mathematical models for such fluids (non-Newtonian), Maxwell fluid attracted special attention because of its simplicity, also that can be predicted stress relaxation, which is the commonest non-Newtonian fluid due to its more extensive applications and substantial role in different fields serving as mechanical as well as chemical applications, bio engineering operations, metallurgy and especially in food processing industries. In 1867, James Clerk was first proposed the Maxwell fluid model, and James G. Oldroyd popularized the idea, a few years later9, with an aim to predict the visco elastic behavior of air10. Multiple products such as honey, soup, jelly, china clay, tomato sauce, artificial fibers, synthetic lubricants, concentrated fruit juices, pharmaceutical chemicals, paints and coal, etc. are some applied illustrations of such fluid. The study of Oldroyd-B fluid movement in the context of fluid mechanics, was explored by several mathematicians, scientists, researchers and engineers that depends upon various situations because of its naturalness. Some interesting features regarding different fluid models on flow, mass and energy transfer characteristics are mentioned in12.The process of heat and mass transfer has a great importance from the industrial point of view. Many researchers and scientists concentrate on this area. In modern technologies and various industrial fields, the non-Newtonian fluid theory has extensive impact because Newtonian fluid model can not express many flow characteristics. A non-Newtonian fluid that obeys the nonlinear relationships between the rate of shear strain and the shear stress. The non-Newtonian fluid theory has significant utilization in modern engineering, especially in petroleum industry used to extract crudeoil from different petroleum productions. The properties of Newtonian fluid in most of the cases are not valid but scientists desire to model the complex models for non-Newtonian fluid. The importance of non-Newtonian fluid has been enlarged from the last few decades, specifically in the research field. The non-Newtonian fluids have numerous ever-increasing applications in industrial sectors, but some specific are mentioned here, such as at large-scales reducing and enhancing heating/cooling systems, biochemical and process engineering, extrusion of molten plastic in industry, reducing oil pipe line friction, polymer processing, reducing fluid friction, well drilling, flow tracers, biological materials, biomedical flow analysis, plastic foam processing, lubrication processes, food processing industries, chemical processing, all emulsions, handling of muds, slurries and complex mixtures. Many researchers and scientists focused on non-Newtonian fluid while considering different fluid geometries. Therefore, simulating and modelling the flow phenomena of non-Newtonian fluid that is facilitated and play the important role in human life. Researchers investigated different non-Newtonian fluid models regarding physical and computational characteristics such as second grade model, viscoplastic model, power law model, Bingham plastic model, Jeffery model, Oldroyd-B fluid model, Brinkman type model, Casson model, Walters-B fluid model and Maxwell model13 provided a review on essential advances in double diffusive convection. Hughes et al.14 examined double diffusive convection taking two stabilizing gradients into account and analyzed the weird results of magnetic buoyancy. Ehrenstein et al.15 studied a Chebyshev collocation method aimed at Navier–Stokes equations considering application to double-diffusive convection. Srinivasacharya et al.16 investigated double diffusive natural convection with respect to power-law fluid saturated porous medium under Soret and Dufour Effects. Asha et al.17 examined double diffusion on peristaltic flow of nanofluid under the influences of magnetic field, porous medium, and thermal radiation. Krishna et al.18 analysed the hall and ion slip effects on unsteady MHD free convective rotating flow through a saturated porous medium over an exponential accelerated plate. Hall and ion slip effects on MHD rotating boundary layer flow of nanofluid past an infinite vertical plate embedded in a porous medium are studied by Krishna et al.19. Chamkha20 investegated the non-Darcy fully developed mixed convection in a porous medium channel under the influence of heat generation/absorption and hydromagnetic effects. Heat and mass transfer analysis of unsteady hybrid nanofluid flow over a stretching sheet with thermal radiation is examined by Sreedevi et al.21. Chamkha et al.22 discussed the effect of heat generation or absorption on thermophoretic free convection boundary layer from a vertical flat plate embedded in a porous medium. Murthy et al.23 examined the heat and mass transfer in a two-dimensional magnetohydrodynamic free convection boundary layer flow along a vertical semi-infinite flat surface immersed in a thermal and mass stratified Darcy porous medium under the influence of the Soret and Dufour effect. Two cases for MHD free convection flow are investigated by Narahari and Debnath24 such as: magnetic field is fixed regarding fluid (MFFRF) and other case is magnetic field is fixed regarding plate (MFFRP). Later on, both cases for MFFRF and MFFRP along with a chemical reaction and varying wall temperature, the results are extended by Shah et al.25. The parabolic partial differential equations governing the flow in the presence of a magnetic field, Hall currents and the free stream velocity has been studied by Takhar et al.26. Modather et al.27 presented the analytical solution of the problem related to MHD mass and heat transfer of an oscillatory two-dimensional viscous fluid that is electrically conducting over an infinite vertical permeable moving plate which is embedded in a porous medium along with a chemical reaction and transverse magnetic field. Prabhakar et al.28 investigated the impact of viscous dissipation numerically on MHD fluid flow over an oscillating vertical plate that is embedded in porous medium, in the presence of chemical reaction and thermal radiation with variable surface conditions. Ali29 investigated free convection flow of an electrically conducting fluid along a vertical plate embedded in a thermally stratified porous medium in the presence of a uniform normal magnetic field. MHD mixed convection from a semi-infinite, isothermal, vertical and permeable surface immersed in a uniform porous medium in the presence of thermal radiation and Dufour and Soret effects are studied by Ali30. Sparrow et al.31 analysed the natural convective flow othrough inclined plates along with generation of longitudinal. vortices. Free convective flow passing through an inclined flat plate together with variable viscosity and internal heat generation are studied by Siddiqa et al.32. Bhuvaneswari et al.33 examined natural convection flow of an inclined plate with variable thermal conductivity by scaling group transformations. Some relevant investigations related to inclined plates regarding different fluid models are mentioned in these studies38.Herbert et al.39 discussed the flow of Maxwell fluid over an inclined plate with heat and mass flux and computed solution by using the Laplace transformation method, because it has efficient applications for non-uniform boundary conditions and computed the exact solution for the presented model. But in the literature Oldroyd-B fluid model for inclined plate are not investigated yet nor published. To fill this gape a new Oldroyd-B model developed. For seeking exact solutions in terms of special functions namely Mittag–Leffler functions, G-function etc., for Oldroyd-B fluid velocity, concentration and Oldroyd-B fluid temperature, Laplace integral transformation method is used to solve the non-dimensional model. The contribution of different velocity components are considered as thermal, mass and mechanical, and analyse the impacts of these components on the fluid dynamics. For several physical significance of various fluidic parameters on Oldroyd-B fluid velocity, concentration and Oldroyd-B fluid temperature distributions are demonstrated through various graphs. Furthermore, for being validated the acquired solutions, some limiting models such as Newtonian fluid in the absence of different fluidic parameters. Moreover, the graphical representations of the analytical solutions illustrated the main results of the present work and studied various cases regarding the movement of plate.In the previous investigation, Zafar et al.34:Consider the unsteady, incompressible MHD Oldroyd-B fluid flow through inclined plate, having length infinite, that is embedded in a porous media. The plate is considered at y = 0 and the fluid flow is restrained to y > 0, in the direction that is along to the plate. Also, assumed that x-axis is taken along vertical, and an angle mentclass2pt{minimAlso equations for heat and mass are taken as:To reduce the number of involving parameters, introducing the following new set of unit-free quantitiesAfter employing this substitution, the transformed non-dimensional model, ignoring Here, In this section solution of the proposed model will be computed. To find the velocity field solution, first we acquired the temperature and concentration solution. In contemplation of, finding the exact expresssions for the temperature and concentration from Eqs. , 10), w, w10), wEmploying Laplace transformation to Eq.  with theWith the stated conditions for temperature asThe solution is written asUsing the conditions as given in Eq. , then thEmploying the Laplace inverse transformation on Eq. 18\documeFurther, the rate of heat transfer known as Nusselt number, it is denoted by (Nu) and can be calculated mathematically as:Using Laplace transformation technique on Eq.  with corThe solution is written asApplying the conditions as given in Eq. , its solTo find n on Eq. , to acquMoreover, the rate of masstransfer is known as Sherwood number, it is denoted by (Sh) and mathematically it is defined as:Solving Eqs.  and 27)27), we oTo derive the solution for velocity field Eq.  with appfrom Eq.  and the from Eq.  into , it is observed that the fluid does not remain at static position when it far away from the plate.It is perceived that the movement of the fluid are effected through the transfer of heat and mass in various engineering applications. So, different cases regarding fluid motion when the influence of some fluidic parameters are ignored, discussed in the next section for physical properties of computed results.In the present section, different cases regarding the modes of heating plate are discussed and the corresponding solutions are calculated for each case.Replacing ) in Eq. , we obtaNow, replacing , in Eq. , we haveNow, substituting into Eq. , we obtaAdditionally, the case when Further, by taking limit  for Eq. , yields425.the solutions for moving vertical plate in case of viscous fluidSubstituting, into Eq. , then so25, written asAgain limit It is depicted that, Eqs.  and  4545 that rhen Eqs.  and   in Eq. . Then rethe Eqs.  and 51)\document25, Eqs. (37), (38) and (39)] obtained for Newtonian fluid case. Moreover, when we are taking 24, Eq. (11-a) taking 40, Eqs. (12)] for thecase without considering the effects of porous, thermal and concentration distribution. Further, it is remarkable to mention that we get the same expression for differnt components of velocity like momentum, thermal, concentration and relations for various cases discussed in section "39.To validate the current acquried results, for  in Eqs. –36), th, th\docurelation , the cor25, as followAgain, for 0 in Eq. , then reThe work in the present article examines the analytical solutions of the magneto-free convective flow of Oldroyd-B fluid model that flow through porous inclined plate, saturated in porous media. The problem is formulated and represented in non-dimensional form with suitable new non-dimensional variables, as the free convection for general motions and oscillating movement over an inclined plate which lies in the porous material. For seeking exactsolution expressions in terms of G-function, for Oldroyd-B fluid velocity, concentration and temperature distribution, Laplace integral transformation method is used to solve the presented fluid model. For physical significance of various parameters involved in the problem and exploring the accomplished analytically solutions, various cases for theoretical interest having applications in engineering field are considered, and also parleyed some established results as limiting cases that has been existed in the literature. Results are demonstrated graphically, inorder to keenly analyse the effects of fluidic parameters Figure .for both cases aiding Figure Figure Figure Figures Figure Finally, the fluid velocity components  that contribute in the movement of the fluid, are displayed in Fig. entclass1pt{minimaIt is noticed that the value of fluid velocity does not become zero when it is far away from the plate in case of MFFRP.MFFRP (magnetic field is fixed relative to the plate), the velocity graphs are significantly larger than MFFRF(magnetic field is fixed relative to fluid).An increase in the values of relaxation time causes to decline velocity, but reverse impact noticed in case of retardation time.The increasing variation of buoyancy forces ratio parameter It is depicted that decay in fluid velocity is observed against the raising values of parameters It is observed that the three velocity components which play significant role and contributions of these components cannot be ignored.In this article, the analytical solutions of the magneto-free convective flow of Oldroyd-B fluid model that flow through porous inclined plate, saturated in porous media. The problem is formulated and represented in non-dimensional form with suitable new non-dimensional variables, as the freeconvection for general motions and oscillating movement over an inclined plate which lies in the porous material. For seeking exact solution expressions in terms of G-function and Mittag–Leffler function, for Oldroyd-B fluid velocity, concentration and temperature distribution, Laplace integral transformation method is used to solve the presented fluid model. For physical significance of various parameters involved in the problem and exploring the accomplished analytically solutions, various cases for theoretical interest having applications in engineering field are considered, and also parleyed some established results as limiting cases that has been existed in the literature. Results are demonstrated graphically, inorder to examine the effects ofsystem parameters for the inclined plate  and slanted external magnetic flux on the fluid motion, also discussed for a motion of slowly accelerating plate. Some main results are concluded as follow:


N-carboxystearamido methanesulfonic acid (MSA) was designed and synthesized. The rheological properties of the MSA/CTAB mixed system prepared using seawater were evaluated, and the variation laws of the related rheological parameters were discussed. The relevant fracturing technical parameters of the MSA/CTAB mixed system were comprehensively evaluated. The wormlike micelles formed by the non-covalent binding of MSA and CTAB molecules can resist the electrostatic effect of inorganic salts in the seawater. Meanwhile, the MSA/CTAB mixed system has an excellent pH response and revealed that the change from wormlike micelles to spherical micelles leads to the decrease of the apparent viscosity and the transition from Maxwell fluid to Newton-type fluid. Furthermore, the MSA/CTAB mixed system has excellent cyclic fracturing performance, which can meet the dual requirements of fracturing fluid cost and performance of offshore oilfield, and has a good application prospect.In this article, a novel salt-resistant pH-sensitive surfactant  Hydraulic fracturing technology is the preferred stimulation method for developing offshore low-permeability reservoirs . Convent2, and temperature; pH switches are time-controlled, thoroughly regulated and cost-effective, with good biocompatibility and high surface activity, so pH-sensitive surfactant is suitable as thickeners for clean fracturing fluids  was designed and synthesized. The molecular structure of MSA is shown in In this article, a novel salt-resistant pH-sensitive surfactant DL-cystetic acid was purchased from Hubei Jusheng Technology Co., Ltd., China. Stearic acid was purchased from Sinopharm Chemical Reagent Co., Ltd., China. The synthesis steps of MSA have been described in detail in our published paper . The 1H −1 was used as mother liquor, which was diluted with Bohai seawater to obtain the MSA/CTAB mixed solution with different concentrations. The pH value of the sample was adjusted by adding concentrated HCl solution and NaOH solid. All samples of viscoelastic fluid were placed in a constant temperature water bath at 25°C for 24 h before being tested.All samples were prepared with Bohai seawater. The mole ratio of MSA/CTAB was fixed at 1:1. The mixed solution with a total concentration of 200 mmol L−1. Before the dynamic rheological test, the dynamic stress-sweep test is needed to determine the linear viscoelastic region. The temperature of the sample should be maintained at about 25°C during the testing process.The steady-state and dynamic rheological properties were measured with the Physica MCR 302 rotational rheometer made by Anton Paar Company of Austria. The upper plate was a standard Searle-type concentric cylinder with a radius of 40 mm and a cone angle of 1.5. Before the test, the parameters of the rheometer are calibrated, and then the cone plate is cleaned and zeroed. When testing, make sure that the solution fills the gap between the upper and lower plates. The shear rate range of the steady-state rheological test is 0.01–100 sThe solution sample of 4 μL was transferred by the pipette gun and dropped on the 3.02-mm copper mesh with 200 meshes, and the excess sample was absorbed by the blotting paper. Then the copper mesh was put into liquid nitrogen to freeze quickly, and then the sample was cut off by vacuum spraying apparatus. Secondly, platinum was sprayed on the microstructure of the exposed sample, and then carbon was sprayed so that the micromorphology of the aggregate was printed on the platinum carbon film. Finally, the organic components of the replica films were corroded off, and the micromorphology of the samples was observed and photographed by a transmission electron microscope.The 10-ml quartz sample bottle was first treated with an acetone washing machine for 30 min, and then the dust particles were removed from the MSA/CTAB mixed solution by 0.22 μm syringe filter. Malvern Zetasizer Nano ZS90 laser light scattering instrument  was used in this experiment.The experimental methods of the evaluation indexes of fracturing fluid in this article were tested strictly according to China’s “General specification for fracturing fluids-SY/T6376—2008”, so they are not repeated here. In this article, the laboratory equipment for evaluating the cyclic utilization performance of fracturing fluid was designed and built. Therefore, the fracturing property of the MSA/CTAB mixed solution after several times of pH adjustments can be investigated whether it still meets the requirement of the fracturing standard. The schematic diagram of the experimental apparatus is shown in δ = 0.87, 1.25, 1.52, 2.33, 3.81, 4.51, 8.12, 8.33, and 12.44. The mass spectrum of MSA  . In thissolution . When the system .−1. All viscoelastic fluids exhibit similar characteristics in the low angular frequency region. The storage modulus G′ is less than the loss modulus G″, the fluid mainly shows the viscous characteristics. When the angular frequency (ω) is larger than a certain critical value (ωc) and enters the high angular frequency region, the storage modulus G′ begins to be larger than the loss modulus G". The change of G′ is smooth and tends to a certain value, which is defined as the platform modulus G0. The transition from viscosity to elasticity indicates the formation of wormlike micelles in the fluid, which is consistent with the steady-state rheological results  under different pH conditions, which accords with the dynamic rheological characteristics of the wormlike micelles. It should be noted that, as the pH value of the mixed solution decreases, the solution undergoes a transition from elastic to viscous dominance. The intersection point of the viscosity modulus and the elastic modulus of the solution gradually moves toward the high angular frequency, which demonstrates the decrease of the relaxation time τR. In general, the longer the relaxation time, the longer the wormlike micelles are, and vice versa (ce versa .Rh) of the dynamic light scattering can reflect changes in the aggregate structure in solution . The proppant was added into the mixed solution with a 30% mass fraction to test the proppant decreasing speed under different temperature conditions. The sand carrying capacity of fracturing fluid is an important index to evaluate whether proppant can be dispersed in fracturing fluid and keep non-subsidence for a certain time . At pres−1. As can be seen from The fracturing fluid is affected by mechanical shear and high temperature during construction, which leads to the micellar separation of wormlike micelles in clean fracturing fluid, and the performance of the fracturing fluid is decreased. Therefore, the temperature resistance and shear ability of fracturing fluid is an important index for evaluation . The tesThe gel-breaking property of fracturing fluid is the most crucial factor affecting the production of oil and gas well after fracturing operation. The fracturing fluid system with low residue content and low viscosity after gel breaking should be preferred . In thisThe mixed system concentration retention rate was measured using laboratory equipment to evaluate the fracturing fluid recycling performance. The related experimental results are shown in This article confirmed that the wormlike micelles formed by the non-covalent binding of MSA and CTAB molecules could resist the electrostatic effect of inorganic salts in the seawater. The excellent pH rheological responsiveness of the MSA/CTAB mixed system is due to the change of the self-assembled structure from wormlike micelles to spherical micelles. The results of the recycling performance evaluation show that the MSA/CTAB mixed system still meets the fracturing fluid performance requirements after three simulated recycling. It is hoped that the findings of this article will promote the application of clean fracturing fluid in oil fields.


Pineal gland tumours are reported rarely in Malayasia and early diagnosis and intervention promise a better prognosis for patients. We report a rare case of pineal gland tumour with drop metastases in the fourth ventricle in a 20-year-old young male with Parinaud syndrome. The patient, who had no underlying medical illnesses, presented with neurological symptoms and limb weakness associated with tremors and blurring of vision which worsened over a span of four months. The patient was having difficulty in ambulating with reduced power over the lower limbs with tremors as well as Parinaud syndrome indicated through the limitation of upward gaze, light-near dissociation of the pupils and convergence nystagmus. An MRI showed the presence of a pineal gland tumour with drop metastases in the fourth ventricle with calcification. The patient underwent an endoscopic third ventriculostomy and tumour biopsy. The biopsy indicated a pineal gland tumour with a germinoma subset and the patient was subjected to radiotherapy. Latency of diagnosis is an important prognostic factor as it reduces the survival rate for these patients hence the following discussion on the pineal gland tumour and its diagnostic dilemma. The pineal gland is located in the midbrain in close proximity to the superior colliculus, situated in between both the cerebral hemisphere . It is nThe presentation of pineal gland tumours can vary; their development can be as early as a few months to a few years and the symptoms presented depends largely on the location and the extension of the tumour. Clinical symptoms can also differ according to the age of presentation. Pineal gland lesions in children can also present as abnormal pubertal development specifically in accelerated stages of puberty in both males and females. Due to lesions in the hypothalamic-pituitary axis, these patients can also present with vasopressin deficiency. Pineal gland-specific lesions are not pathognomonic of the gland. As the symptoms are not specific, patients do not present with sleeping problems; however, there have been reported cases where sleep dysfunction such as narcolepsy occurs . Common The aim of this case report is to discuss the pineal gland tumour which is reported rarely in Malaysia as well as its presentation and the associated diagnostic dilemmas for treatment and prognostic factors.A 20-year-old Malay gentleman, with no underlying medical illness presented with a history of right upper limb unintentional tremors and motor weakness of four months duration prior to the first presentation. This was associated with gait imbalance and movement assistance. He also complained of diplopia more on the upward gaze which was intermittent and the patient could not quantify whether there was a presence of vertical or horizontal diplopia. There was also associated blurring of vision, generalized with no scotoma. There were no associated trauma and no eye pain or redness noted by the patient. He also denied the presence of any floaters, flashes, halos or any gaze provoked headaches.He was first seen in a peripheral hospital, where computer tomography (CT) of the brain and magnetic resonance imaging (MRI) of the brain and spine was done showing the presence of a pineal gland tumour with no metastases to the spine. He was then referred to Hospital Universiti Sains Malaysia (HUSM) Neurosurgical Ophthalmology team for surgical intervention.On examination, the visual acuity of the right eye (RE) was 6/6 and the left eye (LE) was 6/6. Regarding optic nerve function, light brightness was 100% over the bilateral eye; red desaturation was not affected in both eyes and there was no relative afferent pupillary defect (RAPD). Colour vision was done using the Standard Ishihara chart, which was highest for both eyes scoring 15/15 showing no compromise of the optic nerve function.There was obvious right eye hypotropia and limited extraocular muscle movement of bilateral eyes. Both eyes had a limitation of movement of the upward gaze of -2. Other movements of abduction, adduction and downward gazes of both eyes were not affected. Diplopia was noted in all gazes except downward gaze. There was the presence of positive convergence retraction. The pupillary reflex in light was poor but constricted well during accommodation. There was a presence of light-near dissociation. Otherwise, the anterior segment examination was normal with intraocular pressure of 12 mmHg for both eyes. The bilateral eyes’ fundus revealed a pink optic disc with a clear disc margin and good vessel calibre. The foveal reflex was good with a flat macula and normal surrounding retina. Systemic examination was normal, with all cranial nerves intact. Neurological examination showed normal tone for all upper and lower limbs with a full power of 5/5; however, there was hyperreflexia in all major joints for both upper and lower limbs. The sensation was intact for all limbs. There were no associated cerebellar signs.The baseline visual field examination was done and there was no visual field defect seen. Hess test for objective assessment of the extraocular muscle mobility was done, as seen in Figure Baseline blood investigation of tumour markers such as cancer antigen (CA) 125, alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin (b-HCG) was found to be normal. The carcinoembryonic antigen (CEA) was slightly elevated to 3.5 compared to the normal value of less than 3. CT brain and MRI brain and spine Figures  were donThe patient underwent an endoscopic third ventriculostomy and tumour biopsy. The tissue biopsy showed a pineal gland tumour of the germinoma subset. Tumour cells were positive for tumour marker CD117. The patient was then subsequently referred to the oncology team for radiotherapy. The patient responded well to chemotherapy and radiotherapy and is now currently on a six-monthly follow-up schedule to monitor his general status and ocular condition.Pineal gland tumours are rare tumours comprising about 0.5% of all central nervous system tumours in adults and less than 3% in children . In MalaPineal gland tumours can be classified according to the appearance of solidity with the presence of calcification or cystic lesions. It can also be further subdivided according to its histology, based on the World Health Organization Classification. The pineal gland tumour can be divided into four major groups with germinal tumour accounting for 50% of pineal gland tumours. Listed according to increasing malignancy potential are mature or benign teratoma, germinoma, immature or malignant teratoma, embryonic carcinoma, yolk sac tumour and choriocarcinoma. Pineal parenchymal tumours comprising 30% of all pineal gland tumours can be histologically seen as pineocytoma, pineoblastoma and pineal parenchymal tumours of intermediate differentiation. Glial and other tumours from supporting stroma comprise 25% of the tumours, papillary tumour of the pineal gland being its subtype and pineal cyst accounting for less than 3%, usually presenting as asymptomatic lesions and coincidental findings -10. In AGerm cell tumour has a male-to-female predominance with a ratio of 11:8, and the common age of occurrence is around 16 years old . Common Ophthalmological symptoms that are commonly associated with pineal gland tumours are known as Parinaud syndrome. This was first described in 1800 by French ophthalmologist, Henri Parinaud. It was initially speculated that the eye findings are due to lesions in the quadrigeminal area. Other terms used for this condition were Sylvian aqueduct syndrome, dorsal midbrain syndrome, pretectal syndrome, and Koerber-Salus-Elschnig syndrome.Parinaud syndrome is characterised by a triad of paralysis of conjugate up gaze, light-near dissociation of the pupils and convergence-retraction nystagmus during upward saccades. Lid retraction in the primary gaze (Collier’s sign) can also be observed . LimitatDiagnosis of pineal gland tumours depends on three major parameters: clinical presentation, imaging modalities, and histopathology with serum marker and cerebral-spinal fluid marker as adjuncts to the main parameters . In termAs mentioned earlier, biochemical serum and cerebrospinal fluid markers act as adjuncts to the diagnostic parameters. In pineal gland tumours, for embryonal and immature teratomas, there can be an increase of AFP in both serum and in the cerebro-spinal fluid. In choriocarcinoma and germinoma, there are increased levels of the b-HCG, lactate dehydrogenase and placenta alkaline phosphatase ,13. In oPatients with pineal gland tumours can present with various presentations and early diagnosis and management can help with the prognosis of the tumour. As clinical presentations can be vague, other adjuncts such as tumour markers, liver markers, cerebral spinal fluid markers, MRI imaging to look for tissue involvement and extension and tissue biopsy are needed for a definite diagnosis. As pineal gland tumours comprise a small number of cases in our current population, this has to be given some importance as it affects the younger age group and their quality of life in the long run. As shown in our case, the development of the tumour at the time of presentation was of a short duration of four months with acute deterioration, the initial presentation was vague and the patient presented with motor symptoms rather than typical pineal gland tumour symptoms. A high index of suspicion is needed to diagnose these cases early as prompt intervention promises a better outcome.


Rapid innovations in 3-D printing technology have created a demand for multifunctional composites. Advanced polymers like amorphous thermoplastic polyetherimide (PEI) can create robust, lightweight, and efficient structures while providing high-temperature stability. This work manufactured ULTEM, a PEI-based polymer, and carbon-fiber-infused ULTEM multi-material composites with varying layering patterns  using fused filament fabrication (FFF). The microstructure of fractured surfaces and polished cross-sections determined that the print quality of layers printed closer to the heated bed was higher than layers closer to the top surface, primarily due to the thermal insulating properties of the material itself. Mechanical properties of the multi-material parts were between those of the single-material parts: an ultimate tensile strength and elastic modulus of 59 MPa and 3.005 GPa, respectively. Multi-material parts from the same filaments but with different layering patterns showed different mechanical responses. Prints were of higher quality and demonstrated a higher elastic modulus (3.080 GPa) when consecutive layers were printed from the same filament (AAABBB) versus parts with printed layers of alternating filaments (ABABAB), which showed a higher ultimate strength (62.04 MPa). These results demonstrate the potential for creatively designing multi-material printed parts that may enhance mechanical properties. The accessibility and affordability of sizeable 3-D printing systems have opened the field of materials and manufacturing to many new possibilities. Polymer matrix composites with metal additives are being used to introduce multi-functionality to parts with complex geometries. Carbon additives are being used to enhance the durability of 3-D printed parts without adding significant weight. These, among others, are examples of 3-D printed materials being investigated for their potential to provide manufacturing materials and methods for aerospace applications. The future of aviation is limited by the weight of an aircraft’s many complicated components, and additive manufacturing aims to address that challenge.Fused filament fabrication (FFF), alternately known as fused deposition modeling (FDM), is an additive manufacturing (AM) process described as “a material extrusion process used to make thermoplastic parts through heated extrusion and deposition of materials layer by layer” . FFF is Multi-material extrusion does, however, present limitations and challenges. The possibility of weak bond strength between layers of different materials presents a significant challenge that needs to be addressed. The bonding in a multi-material part can be influenced by a variety of variables, such as the many different printing parameters  or the properties of the materials themselves  .Traditionally, most of the multi-material AM research is limited to a few materials: acrylonitrile butadiene styrene (ABS), polylactic acid (PLA), and high-impact polystyrene (HIPS). These three materials are easily accessible, biodegradable, partially biocompatible, and have high impact resistance, heat resistance, and toughness ,15,16,17A specific direction aviation research is currently taking is that of an electric aircraft with lighter, cooler, and more efficient motors and energy storage systems. While motors currently can reach the 95% efficiency range, motors and batteries have struggled with a heat management problem and a weight problem due to the required heavy safety systems. Potential mitigation of these problems can be addressed by replacing metals with lightweight yet strong polymers that can be 3-D printed to allow for new shapes and designs that help move heat away from sources by active or passive systems. New shapes from additive manufacturing can allow water cooling or forced air cooling of motor stators and battery cores, helping to keep systems lighter and running more efficiently at higher altitudes. PLA, ABS, and HIPS should be further investigated, but other polymers can prove more useful.g) of 186 °C [A thermoplastic material that offers the potential for applications in many engineering fields is ULTEM 9085, due to its high strength, low weight, flame retardancy, chemical resistance, and low toxicity. ULTEM 9085 can be acquired as a filament from various vendors for use in FFF. In this filament form, it exhibits a glass transition temperature  to study any effects the patterns may have on the mechanical properties. This research aimed to determine the effectiveness of using FFF to print multi-material ULTEM 9085 parts through careful observation of microstructure evolution and mechanical testing. Polymers like ULTEM 9085 show the potential to create strong, lightweight, and efficient structures to advance innovations in aviation.A HyRel Hydra 645  was used in this work to print ASTM D638  tensile Thermogravimetric analysis (TGA) was performed with a TGA Q500 thermogravimetric analyzer  for bulk filament pieces to estimate the wt.% addition of reinforcement and observe differences in impurities present in the filaments. The instrument was calibrated for temperature, heat flow, and weight according to the manufacturer’s suggestions. Specimens were cut from the filament spool and tested. TGA scans were run under air from room temperature (25 °C) to 600 °C at the heating rate of 10 °C/min. The sample purge was 60 cc/min, and the balance purge was 40 cc/min under the flowing nitrogen gas of 20 psi. Samples in the weight range of 3–5 mg were placed in a high-temperature platinum pan and degraded as a function of temperature; their mass loss was recorded by the TGA Universal Software .All parts were printed at 390 °C with an MK1-450 (HyRel) head. ULTEM 9085 and ULTEM 9085CF filaments were printed with a 1.0 mm nozzle. Parts were printed with three outer perimeters, 100% infill, and a layer height half the nozzle’s width. Perimeters are used to create a well-defined part exterior to ensure the part is made accurate to the specific dimensions of the design, and the rest of the part is printed within this outline. The bed was preheated to 200 °C for ULTEM 9085 materials. A coating of PVA was applied to the print bed to increase bed adhesion. Tensile samples were 3 mm thick with six 0.5 mm layers. Parts were printed at alternating raster angles of 0° and 45°. The use of more print layers was investigated, but the final parts were printed with only 6 layers at 0.5 mm for two reasons: 3 mm provides a typical coupon thickness for mechanical testing, and the print quality diminishes with increased number of layers because the part is built up further from the heated bed. The final shapes of the parts were made according to the ASTM standards for tensile testing. Samples cut from printed coupons of ULTEM 9085, ULTEM 9085CF, and ULTEM 9085 + ULTEM 9085CF were mounted in epoxy and polished for microstructural analysis of the cross-sections with an optical microscope. Measurements of % area porosity of the polished cross-sections were conducted on the optical micrographs using ImageJ . A Keyence VR-3200 profilometer  was used to develop 3-D scans of the fracture surfaces of the tensile specimens.For tensile testing, the strains were determined with an ARAMIS  photogrammetry system using Digital Image Correlation (DIC). DIC is a non-contact optical method used to measure deformation and strain in the specimens during the tensile tests. A visualization of the test setup and an example of the DIC analysis is shown in The thermal stability of the filaments used in this study was investigated to characterize the high-temperature capabilities of the printed parts. ULTEM 9085 and ULTEM 9085CF exhibit a two-step thermal degradation which the two points of inflection can note at 570 °C and 580 °C, respectively. The two-step degradation can be explained by the compositional makeup of ULTEM 9085 materials, which is a blend of PEI and polycarbonate. According to a previous study by Feng et al., polycarbonate exhibits a single-step degradation completed at approximately 510 °C . The firULTEM 9085CF maintains a higher remaining wt% by the end of the TGA test at 600 °C, specifically, there is 78 wt% remaining compared to 64 wt% for ULTEM 9085. The matrix of the ULTEM 9085CF materials should be functionally the same as the ULTEM 9085 material, as ULTEM 9085 is a material trademarked by SABIC. Therefore, the matrix of each material should behave the same during a TGA run. The higher 12 wt% present in the ULTEM 9085CF material can be attributed to the chopped carbon fibers added during the processing of the filament. ULTEM 9085CF, compared to ULTEM 9085, is not necessarily more stable at higher temperatures.A micrograph of an entire through-thickness cross-section of an ULTEM 9085 part is shown in Micrographs of the cross-section of the multi-material ULTEM 9085 + ULTEM 9085CF parts are shown in Using ImageJ, a similar porosity analysis was done, and the area % porosities of In all parts , the adhSome of the single and multi-material specimens after fracture are displayed in The rough fracture surface is also expected of brittle materials, whereas materials with a lower elastic modulus exhibit necking before fracture. Very ductile fractures usually form in a cone shape associated with the necking of a material, as is evident in the ULTEM 9085 part in Stress-strain curves of the single material specimens are shown in Two specimens of ULTEM 9085CF b underweStress–strain curves of the multi-material specimens are shown in The average elastic moduli and ultimate strengths of the singular-material ULTEM 9085 and the ULTEM 9085 + ULTEM 9085CF multi-material parts are shown in The ultimate strengths and elastic moduli observed in the ULTEM 9085 parts of this study are within the range of strengths observed in multiple studies ,35,36,37Interestingly, ABABAB patterned parts exhibit a lower elastic modulus but a higher ultimate strength than AAABBB patterned parts. AAABBB parts have three consecutive layers of a plastic material (ULTEM 9085) followed by three of a ductile-brittle material (ULTEM 9085CF). The three consecutive, porous ductile-brittle layers could allow crack propagation before necking begins with less resistance than the plastic ULTEM 9085 layers, which may cause the earlier failure. In comparison, the ABABAB parts show more plastic strain because the stiffer carbon-fiber-infused layers are interrupted by plastic ULTEM 9085 layers and prevent early tensile failure.In order to compare the three material types, In this study, multi-material parts were printed with ULTEM 9085 and ULTEM 9085CF. Upon studying the microstructure and the interface between consecutive layers, there is a clear difference in print quality between the first and last layers printed. ULTEM 9085 is appealing for its high thermal resistance. However, that same property is why heat does not efficiently conduct from the print bed to the highest print layers, resulting in poor application and adhesion of the material. A high-temperature material, such as ULTEM 9085, is problematic to easily 3-D print with the FFF process, and introducing a second material only complicates the optimization process.Furthermore, ULTEM 9085CF has a large amount of apparent porosity: approximately 31% area compared to 2% area for pure ULTEM 9085 layers. This extensive porosity results in poor adhesion, independent of the consecutive layers’ likeness or difference in materials, whereas successive layers of ULTEM 9085 adhere reasonably well until the printed layers are approximately 1.5 mm from the print bed. Print parameters can affect the quality of prints, but in this study, the print settings are reasonably chosen, as is shown by the high print quality of the pure ULTEM 9085 layers. However, the print chamber should be maintained at a high enough temperature to not allow significant cooling of the part during the printing process.However, even with the print difficulties, it is evident that the order in which a multi-material part is printed, AAABBB vs. ABABAB, has a pronounced effect on the resulting mechanical properties. This work has provided insight into how carbon-fiber-infused layers prevent necking in printed ULTEM 9085 parts while also inducing a higher ultimate tensile strength. The toughness of the different materials plays a role in the fracture behavior of the tensile coupons. While a ULTEM 9085 part would experience prolonged plastic strain or necking at the fracture surface due to its high plasticity, the introduction of the brittle carbon-fiber-infused ULTEM 9085 layers prevents this necking. Instead, it exhibits behavior more consistent with a brittle fracture. The mechanical response is explained by the individual mechanical characteristics of the two different ULTEM 9085 materials. The mechanical behavior can be predicted with a strong understanding of how the different brittle and ductile materials behave under tensile stress. Multi-material parts with alternating ULTEM 9085 and ULTEM 9085 CF layers exhibit more strain before failure than those with consecutive ULTEM 9085 layers (0.033 vs. 0.025 mm/mm), most likely due to the toughness of the ULTEM 9085 layers allowing continued elongation. Less plastic strain is observed in AAABBB parts, presumably due to the brittle ULTEM 9085 CF layers causing an early brittle fracture in half of the specimen or the micro-cracks formed from the large porosity.Further studies into multi-material printing, particularly with a high-temperature polymer such as polyetherimide, may add to the vast potential of additive manufacturing in the aeronautical and space industries. This study shows the potential for introducing multifunctionality, enhancing the already superb mechanical or thermal properties, and optimizing the printing parameters of promising part designs.


The study evaluated prognostic factors associated with varicella-zoster virus (VZV) infection and mortality in children with acute lymphoblastic leukemia (ALL) using data from the multicenter Chinese Children’s Cancer Group ALL-2015 trial.E2A/PBX1 fusion gene (11.6%) compared to those aged < 10 years  or with other fusion genes . Of the 10 deaths in children with ALL and VZV infection, 4 resulted from VZV complications. The differences between groups in the 5-year overall survival, event-free survival, cumulative recurrence, and death in remission were not statistically significant. The proportion of complex infection was higher in children with a history of exposure to someone with VZV infection .In total, 7,640 patients were recruited, and 138 cases of VZV infection were identified. The incidence of VZV infection was higher in patients aged ≥ 10 years (22.5%) and in patients with the VZV exposure was associated with an increased incidence of complex VZV infection and contributed to VZV-associated death in children with ALL. Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. The 5-year survival rate for childhood ALL in developed countries exceeds 90% . In patiVaricella-zoster virus (VZV) causes both varicella (chickenpox) and herpes zoster (HZ), also known as shingles. Varicella is a disease and does not reactivate, whilst VZV reactivates and causes HZ. In healthy children, varicella is a benign, self-limiting disease, whereas in immunocompromised children, VZV infection can be life-threatening. ALL suppresses the immune system, and chemotherapeutic agents such as steroids, methotrexate, and 6-mercaptopurine, can further reduce the B lymphocyte, T lymphocyte, and total immunoglobulin levels in children with ALL , making The CCCG-ALL-2015 trial was conducted in 20 major hospitals and medical centers in China, located in 18 provinces and municipalities, covering three-quarters of the country. This trial included Han Chinese and ethnic minorities such as Miao, Bai, Yi, and Tibetans. The rate of VZV vaccination and treatments administered to patients with varicella varied by region. Therefore, the study of VZV infection in children treated according to the CCCG-ALL-2015 protocol and impact of VZV infection on the prognosis of children with ALL is instructive in assessing its effectiveness, safety, and generalizability.This study was conducted in accordance with the Declaration of Helsinki and national and institutional ethics standards. This study was approved by the institutional review board of each participating center following the Central Institutional Review Board . Informed consent was obtained from parents, guardians, or patients, as appropriate.The information of each patient was required to be record in the case report form (CRF). Information on all cases of VZV infection was recorded as a part of adverse events and severe adverse events reporting, and detailed information related to VZV infection was collected, as specified in the protocol (ChiCTRIPR-14005706). Data on VZV infection was collected using a CRF.Diagnosis and classification of ALL were based on the morphology, cytogenetics, immunology, and molecular biology of leukemia cells. The fusion genes were identified by multiplex RT-PCR. The risk criteria were noted in the trial and all patients were treated according to the risk classification . VZV infInvestigating VZV infection and its prognostic relevance in children with ALL was one of the main purposes of the CCCG-ALL 2015 trial. In the trial protocol, VZV infection was well-defined, and treatment procedures were standardized. This study aimed to investigate the incidence and clinical characteristics of children with ALL and VZV infection, and its impact on disease prognosis and outcome.The primary endpoint was the occurrence of varicella/HZ. The secondary endpoints were event-free survival (EFS), overall survival (OS), and recurrence-free survival (RFS). OS refers to the time from disease diagnosis to death or the last follow-up. EFS refers to the time from diagnosis to induction failure, relapse, death, drop out, off-protocol treatment at the discretion of the treating physician, or the development of a second malignancy. The cumulative recurrence rate (CRR) refers to the cumulative incidence of local recurrence or metastases in all patients since initial remission. RFS refers to the survival time from initial remission to local recurrence or tumor metastasis. Outcome data reported here were updated on June 30, 2021.Patients received multi-agent chemotherapy at the following treatment phases: induction (weeks 1–7), consolidation (weeks 8–15), continuation therapy and reinduction (weeks 16–34), and maintenance phase (weeks 35–125) . Treatmehttps://www.r-project.org/). Other data were analyzed using SPSS Statistics for Windows, version 20.0 . Count data were presented as frequencies with percentages (%). Pearson’s Chi-squared (χ2) test was used to compare differences between groups when the total number of patients was > 40 and the expected frequency was T ≥ 5, whereas Yates continuity correction of χ2 was used when the total was > 40 and 1 ≤ T < 5. Fisher’s exact test was used when the total was < 40, the minimal expected frequency was < 1, or the P value was close to the inspection level (α = 0.05). In the case-control study, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. Variables with P < 0.20 at the univariate level were entered into a multivariable logistic regression model.Survival and competing risk statistical analyses were conducted using the R statistical software package, version 3.4.4 . Additionally, E2A/PBX1 positivity was more prevalent in the patients with VZV infection (4.2%) than in those without VZV infection . Sex, immune type, other subtypes classified based on other fusion genes, and risk classification did not differ significantly between the 2 groups , accounting for 2.9% (4/138) of the total cases of VZV infection, and 0.05% (4/7640) of newly ALL cases. The characteristics of the children in the ALL cohort, with and without VZV infection, are described in 2 groups Table 1.Of the 7640 ALL patients, 3818 patients (49.9%) received one dose of the vaccine before being diagnosed with ALL, and 92 of the 138 patients with VZV infection were vaccinated. Twenty-two patients (15.9%) were in induced remission, 14 (10.1%) were in the consolidation stage, 38 (27.5%) were undergoing continuation therapy 1, 63 (45.7%) were undergoing continuation therapy 2, and 1 (0.7%) was at the end of treatment Table 2.VZV infections were classified as simple type  in 110 patients (79.7%) and complex type (skin lesions with various infections or other organs affected) in 28 patients (20.3%). The subgroup with complex type VZV infection included 17 cases (60.7%) of cutaneous varicella with skin infection, 6 cases (21.4%) of cutaneous varicella combined with pneumonia, one case (1.9%) of cutaneous varicella combined with encephalitis, one (1.9%) of cutaneous varicella combined with respiratory and urinary tract involvement, one case (1.9%) of cutaneous varicella combined with skin infection and central nervous system involvement, one case (1.9%) of cutaneous varicella combined with septicemia, and one case (1.9%) with complications but no specific organ affected Table 2.Children with VZV exposure history were significantly more likely to develop complex VZV infections. The mortality rate was higher among children with complex VZV infection (14.3%) with all death cases being VZV-related, whereas that of simple VZV infection was only 5.45%, including 5 cases of ALL relapses and one of hemophagocytic lymphohistiocytosis. None of the patients died of simple VZV infection.P = 0.001). However, the 5-year OS and RFS rates were similar between children with varicella and those with HZ  of the 138 patients with VZV infection died during the follow-up period, of whom 7 (70%) were male; 9 had B-cell ALL, and 1 had T-cell ALL. Four patients died of complications of VZV infection, 5 patients died of relapse, and 1 died of treatment-related toxicity. Two relapses occurred after completion of chemotherapy and 3 relapsed during continuation stage 1 or 2. One patient infected with VZV who died was in the consolidation stage of ALL treatment, 2 were infected during induction therapy, and 7 were infected during the continuation stage. Four patients were classified as low-risk, 5 as intermediate-risk, and 1 as high-risk. Among the low-risk patients, only one patient died of an ALL relapse. Four patients died of severe infections secondary to complicated VZV infection with a confirmed history of VZV exposure, one died of hemophagocytic lymphohistiocytosis (as simple VZV infection had been under control for 15 months), and the other 5 patients with simple VZV died of ALL relapse Table 4.BCR/ABL1 gene fusion were prognostic for EFS . Patients with T-ALL, WBC ≥ 50×109/L, intermediate/high risk, and BCR/ABL1 gene fusion had lower EFS (P = 0.029) . The 5-year EFS rates of patients with and without VZV infection were 78.8% (95% CI: 69.5–89.3%) and 74.9% (95% CI: 73.7–76.1%), respectively (P = 0.09). The 5-year CRRs for patients with and without VZV infection were 15.8% ± 9.2% and 15.0% ± 1.0%, respectively (P = 0.71). The 5-year rates of death in remission for patients with and without VZV infection were 3.0% ± 2.9% and 2.3% ± 0.3%, respectively (P = 0.65). There were no significant differences between the groups  of relapse, 3 patients lost to follow-up (12%), 4 deaths (15%), and 3 (12%) active withdrawals from treatment. In contrast, among the patients without VZV infection, 1,697 patients accounted for 22.2% of events, including 851 (50.1%) cases of relapse, 120 (7.1%) patients lost to follow-up, 169 (10.0%) deaths, 279 (16.4%) active withdrawals from treatment, 50 (2.9%) cases of resistance to treatment, 12 (0.71%) cases of second tumors, 92 (5.4%) passive withdrawals from treatment, and 124 (7.3%) transfers to other medical institutes. Among the patients with and without VZV infection, the 5-year OS rates were 89.8% (95% CI: 84.4–95.6%) and 90.8% (95% CI: 90.0–91.6%), respectively  died from VZV infection. Caniza MA et al.  retrospenfection . Caniza nfection . Their rnfection  were simAmong 138 patients with VZV infection, the incidence of simple VZV infection was 79.7%, and the incidence of complex VZV infection was 20.3%. The incidence of complex VZV infection was significantly higher (55.6%) in children with exposure history. The 4 children who died of VZV infection had complex VZV infection, indicating that the risk of environmental exposure to VZV is greater for immunocompromised children and isolation should be enforced. In our cohort, VZV infection did not affect OS or ALL recurrence. Children with ALL and VZV infection had similar 5-year OS, EFS, and CRR to those without VZV infection. The Polish National ALL Cooperative Group reported that, although the incidence of VZV infection was higher in children with ALL than in the general population, none of the patients with ALL with VZV infection died . Their rE2A/PBX1 gene fusion, and environmental exposure to VZV predisposed patients to developing complex VZV infection, which directly increased their mortality rates. Protective measures, such as avoiding contact with individuals with VZV infection are suggested for immunocompromised children with ALL, even after vaccination.In conclusion, we found a significantly higher incidence of VZV infection in children with ALL than in the general population. Age ≥10 years, The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/This study was approved by the institutional review board of each participating center. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.SH, SS, and JT conceptualized and designed the study. WG and SH performed the literature review. PFX, JG, XMG, AWL, YYH, YZ, JHC, XWZ, BQQ, AGL, LCY, JSZ, ZL, XT, YX, LH, XDW, FZ, and LZW acquired the data. WG and JC performed the statistical analyses. WG and SH drafted the manuscript. JC created the figures. All authors were involved in data interpretation, and provided critical revision of the manuscript for important intellectual content.This work was supported by the grants from National Science Foundation of China (81970163 and 82170218); Jiangsu Key project (BE2021654); Suzhou Key Project (GSWS2020039); and National Clinical Research Center for Hematological Disorders (2020ZKPB02).We are grateful for the support from VIVA-China Children’s Cancer Foundation. The manuscript was edited for language by Editage.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.


Orthoreoviruses are non-pathogenic human viruses with a preference of lytic replication in human tumour cells. In this study, we evaluated the oncolytic efficacy of the bioselected oncolytic reovirus mutant jin-3 in multiple human prostate cancer models. The jin-3 reovirus displayed efficient infection, replication, and anti-cancer responses in 2D and 3D prostate cancer models, as well as in ex vivo cultured human tumour slices. In addition, the jin-3 reovirus markedly reduced the viability and growth of human cancer cell lines and patient-derived xenografts. The infection induced the expression of mediators of immunogenic cell death, interferon-stimulated genes, and inflammatory cytokines. Taken together, our data demonstrate that the reovirus mutant jin-3 displays tumour tropism, and induces potent oncolytic and immunomodulatory responses in human prostate cancer models. Therefore, jin-3 reovirus represents an attractive candidate for further development as oncolytic agent for treatment of patients with aggressive localised or advanced prostate cancer.Treatment of castration-resistant prostate cancer remains a challenging clinical problem. Despite the promising effects of immunotherapy in other solid cancers, prostate cancer has remained largely unresponsive. Oncolytic viruses represent a promising therapeutic avenue, as oncolytic virus treatment combines tumour cell lysis with activation of the immune system and mounting of effective anti-tumour responses. Mammalian  Prostate carcinoma is the second most common cancer and the fifth leading cause of cancer-related death in men worldwide . The devImmunotherapy has emerged as a viable and attractive strategy for the treatment of different solid cancers . DespiteOrthoreoviruses can be enhanced by natural selection and genetic modification . H&. H&19]. GAPDH expression. The sequences of the PCR primers used for the quantitation of cellular transcripts, viral RNA, and the detection of mycoplasma contamination can be found in Table Cells were seeded in six-well plates and exposed to oncolytic reovirus for 6, 24, and 48 h. Total RNA was isolated according to the manufacturer’s protocol . cDNA was generated by using random primers  and RT-qPCR was performed with GoTaq Mastermix , according to the manufacturer’s protocol in technical duplicates and biological triplicates . Gene expression was normalised to Cells were exposed to oncolytic reovirus with a MOI of 10. At 48 h post exposure, conditioned medium was collected. HMBG1 release was measured by performing an ELISA, according to the manufacturer’s protocol .3, intra-tumoural administration with 108 p.f.u. jin-3 reovirus in 10 μl PBS was initiated twice a week (n = 6 per group). For sample size calculations and in/exclusion criteria, see 3, mice were randomised based on body weight, tumour burden, and/or tumour size. Subsequently, tumours were treated by intra-tumoural injections of 108 p.f.u. jin-3 reovirus (n = 10 per group). Tumour growth was assessed by calliper measurements.Subcutaneous PC-3M-Pro4luc2 tumours were generated in male NSG mice (AVD1160020173725 and AVD1160020187004) . When tut tests were performed on data from in vivo experiments. *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.Statistical analyses were performed by using GraphPad Prism 8.0. One-way ANOVA was performed for viability experiments. All in vitro experiments were repeated at least twice. Data are represented as mean ± standard error of the mean (SEM). Two-way ANOVA and two-sided jin-3 reoviruses, and viral infection was monitored by RT-qPCR and confocal microscopy. Dose-dependent and time-dependent reoviral infection was observed upon exposure to R124 and jin-3 reovirus  after 7 and 10 days  and diminished tumour volume  and tumour weight . Expression of DDX58 that encodes for the cytosolic RNA sensor RIG-I, was also found to be significantly upregulated upon jin-3 reovirus administration  are of crucial importance in oncolytic virotherapy, as expression of ISGs associated with the sensitivity to oncolytic virotherapy , 25 Fig. Exposur8 h Fig. . Compare124 Fig. . Furtherion Fig. . In addireovirus   to determine the total tumour burden, changes in tumour volume, tumour weight, and reduction of pan-cytokeratin. In prolonged in vivo experiments and in a clinical setting, it will also be worthwhile to assess the effect of jin-3 Reovirus exposure on additional tumour markers in circulation, e.g., serum PSA. In this study, we observed that jin-3 reovirus administration induces several ISGs and inflammatory cytokines. The jin-3 reovirus-induced gene expression of key immunomodulators (activators of the adaptive and innate immune system) is further substantiated by the release of HMGB1 as one of the key DAMPs.We previously described the isolation of reoviruses with an expanded tropism . These sor JAM-A . The potjin-3 that displays strong oncolytic and immunomodulatory properties in state-of-the-art preclinical prostate cancer models, including patient-derived tumour slice models. Our findings support the notion that jin-3 reovirus can be potentially exploited in strategic treatment combinations to with otherwise less efficacious immuno-oncological or chemotherapeutical approaches to achieve improved and durable anti-tumour responses.In conclusion, we describe the evaluation as an oncolytic agent of the mutant reovirus Supplementary info


In this research article the heat transfer of generalized second grade fluid is investigated with heat generation. The fluid flow is analyzed under the effects of Magneto hydrodynamics over an infinite vertical flat plate. The Newtonian heating phenomenon has been adopted at the boundary. For this purpose the problem is divided into two compartments i.e. momentum equation and energy equations. Some specific dimensionless parameters are defined to convert the model equations into dimensionless system of equations. The solutions for dimensionless energy and momentum equations are obtained by using the Laplace transform technique. From obtained results by neglecting magneto hydrodynamic effects and heat source some special case are achieved which are already published in literature. The case for which the fractional parameter approaches to the classical order is also discussed and it has been observed that it is convergent. Finally, the influences of different physical parameters are sketched graphically. It has been observed that for increasing values of Prandtl number the velocity and temperature decreases, for increasing values of Grashof number the velocity of the fluid increases. Also it has been investigated that for increasing values of fractional parameter the velocity and temperature of the fluid increases. Subsequently, this framework was used for the analysis of different problems whose construction is relatively simple. The second-order Rivlin–Erickson equations has been applied to explain the pattern of a non-Newtonian fluid flowing unsteadily upon a flat surface as like the Couette flow and Poiseuille flux2. Many authors have been studied some of the unsteady flows of the second grade fluid4. Derivatives are mostly used to formulate the real world problems into mathematical models. In particular, fractional derivatives are more suitable for some well-known problems than regular derivative. In recent past the application of fractional order derivatives has been expanded in distinct fields. Especially, in dynamics of fluid, viscoelasticity, bioengineering, electrochemistry, finance, fluent currents tracers and in signal processing. Particularly, fractional derivatives are more suitable for some major problems than regular derivatives7. The fractional derivative models are used widely in different directions like, polymers for glass transition and glass state referable that the fractional derivative models can easily explains the complex behavior of a viscoelastic fluid11. Free convection flow of generalized viscous fluid upon a vertical plate with chemical and Newtonian heating is investigated in12. The fractional second grade fluid investigated by using the Caputo fractional derivatives13. In the near past Caputo and Fabrizio have presented a new fractional operator know as Caputo–Fabrizio operator, which has been used in many theoretical real word phenomena14. The generalized second grade fluid is investigated with Caputo–Fabrizio differential operation by adopting the Laplace transformation technique, and obtained the exact solutions to the problem15. Exact analytical for viscous fluid with non-singular kernal differential operator is gained16. Due to the rising concern of fractional derivative modeling many fractional models have been modeled using the existing models of fluid19. The convection heat-mass transfer of generalized grade second fluid is analyzed, and results achieved by Caputo–Fabrizio is compared Atangana Baleanu fractional operator20. The author analyzed heat transfer in convective flow of second grade fluid subjected to Newtonian heating using Atangana Baleanu fractional and Caputo Fabrizio fractional derivative. They also carried out the comparison of the two approaches21. The heat transfer in MHD flow of generalized second grade fluid with porosity in the medium by adopting Caputo Fabrizio derivative22. Heat transfer during the unsteady magneto hydrodynamic flow of a differential-type fluid in Forchhiemer medium was analyzed numerically23. The unsteady magneto hydrodynamic flow of viscoelastic fluid flowing in a porous medium24. Heat transfer during the incompressible time-dependent flow of Maxwell viscoelastic fluid by some stretching surface with chemical reaction and radiation source was investigated in25. The analysis of rate type anomalous Nano-fluid with Caputo non-integer order derivative flowing unsteadily was studied in26. The two-dimensional and two-directional MHD flow of fractional viscoelastic fluid was analyzed in27. The authors studied the unequal diffusivities of chemical species in a Forchhiemer medium by using Scott Blair model of viscoelastic fluid with unsteady convection in28. The author studied the effects of mixed convection with thermal radiation and chemical by using the space–time coupled Cattaneo–Friedrich Maxwell Model with Caputo fractional derivatives in a porous medium29. The authors used the fractional calculus to analyzed the thermo-diffusion phenomenon numerically in a Darcy medium30. Khan and Rasheed studied the numerical implementation and error analysis with variable heat flux of coupled non-linear fractional viscoelastic fluid in31. Mumtaz et al.32 studied the computational simulation of viscoelastic model of Scott Blair to the hybrid fractional Nanofluid in a porous Darcy medium.Basically the non-Newtonian fluids are divided into three main groups according to their actions with shear stress i.e. integral type, differential type and rate-type. (1) The integral type fluids are those fluids, whose shear stress is hardly dependent upon the shear rate. (2) the fluids whose shear strain and shear rate are related to each other are called differential type. (3) those fluids which have the properties of viscosity and elasticity are known as rate type. Grade Second fluids belongs to differential type which is more famous among the various popular models of the non-Newtonian fluids. The pioneers who designed the second grade fluid model were Coleman and NollThe main aim of this article is to extend the application of Caputo Fabrizio fractional derivative to the second grade fluid with magneto hydrodynamic effects in addition to the heat generation. Also the considered Newtonian heating is adopted at the boundary. The exact analytical solution has been achieved by using Laplace transformation on the dimensionless equations of the problem with suitable initial and boundary conditions. From obtained results by neglecting magneto hydrodynamic and heat source some special case are achieved which are published in literature. The case for which the fractional parameter approaches to the classical order also discussed and it has been observed that it is convergent. The exact solution of the problem is represented graphically to visualize the effects of physical parameters like time fractional, Magneto hydrodynamic, Prandtl number, Eta and Grashof Number etc.16. the unsteady flow is governed by the following set of partial differential equations. The flow of the fluid is represented by the following governing equations. The schematic diagram used in fluid flow problem is represented geometrically by Fig. Consider the second grade fluid of unsteady flow over in an infinite upright plate with Newtonian heating at the boundary, flow direction is x-axis and y-axis is perpendicular to the flat plate. When mentclass2pt{minimThe initial (ICs) and boundary (BCs) conditions areThe following dimensionless variables are utilized to gain a system of dimensionless governing equations from the set of dimensional governing equations.Using these dimensionless variables given in Eq.  in Eqs. To find a time-fractional order derivative model just interchange the time derivative of classical order with the time derivative of order The appropriate non-dimensional initial and boundary conditions areThe fractional operator used in this problem is Caputo–Fabrizio which is defined as under in (14) for In the above model, the solution of Eqs.  and 10)10) with With the help of Laplace technique we derived the differential equationLet The solution of the Eq.  with theUsing appendices (A_1) and (A_2) we getBy using the Laplace transform method to Eq.  and keepBy using the above conditions in Eq. , the genOrUsing appendix (A_1) and (A_3) we getFor Special Case When 1 = 0Special Cases(i)w condition of fluid temperature in place of 16 .The result given  is unifoIn the absence of heat generation (ii)In the absence of MHD effect and considering 16.The result given  is unifo16. Figure 16. The case for which the fractional parameter approaches to the classical order also discussed and it has been observed that it is convergent.By using Mathcad software different physical parameters were drawn to analyze the effects of fluid velocity and temperature. The parameter Alpha entclass1pt{minimaentclass1pt{minima16. The exact solution of the problem achieved by using Laplace transform technique are represented graphically to visualize the effects of physical parameters like time fractional, Magneto hydrodynamic, Prandtl number, heat source and Grashof Number. From graphical results it is concluded that;The increasing values of the Prandtl number and heat source reduce the temperature of the fluid.The increasing values of the fractional parameter alpha increases the temperature of the fluid.The increasing values of Prandtl number, heat source and MHD reduces the velocity of the fluid.The increasing values of the fractional parameter alpha and Grashof number increases the velocity of the fluid.16.By neglecting the heat source temperature equation and MHD in velocity equation we obtained a published which is given inThe considered study is about analyze the unsteady natural convection flow of generalized second grade fluid with magneto hydro dynamic effects and Newtonian heating in addition to heat generation. Some special cases of the obtained solution are discussed from which some well-known results are found in the published literature which are similar to published inSupplementary Information.


In “Development and Application of a Metaverse-Based Social Skills Training Program for Children with Autism Spectrum Disorder to Improve Social Interaction: Protocol for a Randomized Controlled Trial” :e35960) the authors made one addition.In the originally published article, the Acknowledgments section appeared as follows:This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant HI19C1015) and Institute of Information & communications Technology Planning & Evaluation (IITP) grant funded by the Korea government (MSIT).The Acknowledgments section has been corrected to:This work was supported by Institute of Information & communications Technology Planning & Evaluation (IITP) grant funded by the Korea government(MSIT)  on social interaction skills of patients with Autism Spectrum Disorder)The correction will appear in the online version of the paper on the JMIR Publications website on November 14, 2022, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article has also been resubmitted to those repositories.


As his symptoms resolved after lumbar puncture alone, he was discharged on the seventh day of hospitalization without receiving any specific medication. Serum VZV-IgG titer was found to be substantially elevated after two weeks. VZV infection and reactivations associated with vaccination, as well as past infections, should be included in the differential diagnoses of pediatric aseptic meningitis, even in the absence of skin rash in the entire course. Polymerase chain reaction (PCR) testing for VZV DNA in CSF should be performed in all cases, if available.Varicella-zoster virus (VZV) may cause aseptic meningitis in the pediatric age group. We describe a pediatric case of aseptic meningitis with a substantial increase of the paired serum antibody to VZV in which the child did not have skin rash during the course of illness. The patient was a 13-year-old boy without any history of exposure to VZV who was admitted with headache, vomiting, and low-grade fever. He had received one dose of varicella vaccine derived from the Oka/Biken strain (vOka) at the age of one year. Cerebrospinal fluid (CSF) analysis on admission revealed an elevated white blood cell count at 609/mm The diagnosis of pediatric aseptic meningitis can be challenging. Most cases are self-limiting and do not require any specific treatment. However, some patients may develop prolonged fever, headache, and vomiting with substantial pain and suffering. Varicella-zoster virus (VZV) may represent an etiology of aseptic meningitis or encephalitis in children, usually presenting with a vesicular rash that follows a dermatome . In clinA 13-year-old boy with a history of migraine and asthma presented to the emergency department (ED) with a headache, vomiting, and low-grade fever that had started three days prior. He had received one dose of varicella vaccine derived from the Oka/Biken strain (vOka) at one year of age. He had no history of VZV infection, and no epidemic or contact history of VZV infection. He had visited the ED one day before the current admission, complaining of headache accompanied by nausea, vomiting, and low-grade fever. However, he had been discharged with analgesics as his physical examination and CT findings had been unremarkable. Nevertheless, with no improvement in his symptoms, he revisited the ED the next day. He had no respiratory symptoms, abdominal pain, diarrhea, altered consciousness, abnormal behavior, or paralysis of the face and limbs. Physical examination revealed a temperature of 37.1 °C, heart rate of 65 beats/minute, blood pressure of 113/60 mmHg, respiratory rate of 16 breaths/minute, and oxygen saturation of 98% on room air. His face was pallid; he showed neck stiffness but there was no body rash.3 and a C-reactive protein level of 0.02 mg/dL. Urinalysis revealed an elevated ketone level, and a quantitative antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) returned negative. Brain MRI was unremarkable , glucose of 45 mg/dL  with a blood glucose of 91 mg/dL at the time of lumbar puncture, protein of 136.7 mg/dL , WBC count of 609/mm3  with 99.6% mononuclear cells and 0.4% polymorphonuclear neutrophils, chloride of 123 mEq/L , pneumococcal antigen negative, and Gram-stain negative for organisms, with slightly turbid appearance. Hence, he was diagnosed with aseptic meningitis.Blood examination Table  revealede Figure . CSF anaAfter the lumbar puncture, the patient's headache resolved quickly, and his general appearance became normal. He exhibited several fever spikes (maximum temperature of 38.5 °C), but the fever gradually resolved without any specific treatment, which might be attributed to the natural course of viral meningitis. Acetaminophen was given for occasional headaches and fever during his treatment. He was discharged on the seventh day of hospitalization with complete resolution of fever and no recurrent symptoms. Serum VZV-IgG titer measured by enzyme-immunoassay was substantially elevated from 4.3 (reference: <2.0) on admission to 73.3 after two weeks.We reported a case of aseptic meningitis with a substantial increase in serum VZV-IgG antibody titer. The patient was eventually managed without antivirals; no skin rash developed throughout the treatment course. As polymerase chain reaction (PCR) testing for VZV DNA in CSF was not performed due to the absence of rash and epidemic or contact history of VZV infection; we could prove neither VZV infection nor vOka reactivation in our case. Kawamura et al.  have recNotably, our patient’s condition resolved after lumbar puncture alone, indicating that antivirals may not always be required for VZV meningitis, which may have a self-limiting course. In our case, we did not suspect VZV meningitis owing to the lack of skin eruption, and nor did we suspect herpes simplex virus encephalitis because of the negative MRI findings; accordingly, no antivirals were administered. The role of antiviral therapy in VZV meningitis management has not yet been established , but mosAlthough the biggest limitation in the current case was that VZV was not proven via CSF PCR, and compatibility with the vaccine strain was not confirmed, it was clinically undeniable that it was a case of varicella vaccine meningitis without rash. VZV meningitis without encephalitis may improve with lumbar puncture alone and may resolve spontaneously without any medication, as in our case; therefore, some similar cases may have been overlooked. However, this issue of a possible underdiagnosis requires further validation from future studies. Although there have been substantial cases of varicella vaccine meningitis in the literature ,6,7, ourWe discussed a pediatric case of aseptic meningitis without rash, possibly associated with the varicella vaccine. Primary VZV infection and reactivations associated with vaccination, as well as the past infection, should be included in the differential diagnoses of pediatric aseptic meningitis without skin rash in the entire course. Paired serology findings can be used as a reference, but VZV PCR with CSF samples may be warranted for determining the etiology.


The pure pregnancy epulis is mostly vascular, and generally shrinks or disappears with the drop in estrogen levels following delivery. However, the fibrous epulis or granulomatous epulis may enlarge rapidly in the early stages of pregnancy, necessitating surgical resection after pregnancy. This report described a 25-year-old patient with a post-term pregnancy. She had a lump on the buccal side of left mandibular molar region that was associated with intermittent hemorrhage and eating difficulty. Since the patient feared the conventional surgery, the 980-nm diode laser excision was performed to remove the epulis two weeks after delivery, with the involved teeth preserved. The new technique of 980-nm diode semiconductor laser may be a potential good option to treat pregnancy epulis, with less discomfort and involved teeth preserved. Epulis is derived from the connective tissues of periodontal ligament and jaw alveolar process, and is considered to be a reactive proliferation caused by mechanical stimulation and chronic inflammatory stimuli.At present, the surgery is still the primary choice, and it includes resection of epulis and, to reduce relapse, removal of the affected teeth as well.A 25-year-old patient with a post-term pregnancy visited our hospital due to hemorrhage of epulis in the left lower posterior tooth region. The epulis was only at the size of a soybean before pregnancy, and it gradually increased during pregnancy, especially in the last month. Since the epulisrepeatedly bled and affected eating in the past weeks, it was necessary to be treated. A tumor-like mass was found on the buccal side of the left mandibular molar region between the lower left second premolar and the second molar on physical examination; the mass was irregular in appearance and measured 1×2.5×0.8 cm, and tended to bleedon its distal surface. Her oral hygiene was poor. The lower left mandibular second molar showed the first degree loosening, while the first molar second degree loosening. Since the date of delivery was close, no other special measure than mouth rinse with chlorhexidine was administered for anti-infection. The patient returned two weeks after a spontaneous delivery, complaining of increased tumor bleeding and discomfort due to swelling . Oral pamax = 14 W. Parameters we selected at the treatment were 5-15 J/cm2, 20-60 ms of the pulse width, and 1 mm of the spot diameter. We completed the resection at one time, with laser resection time of five minutes and the cumulative energy of 120 J. Under local infiltration anesthesia, the excision was made using 300 μm fiber, with power of 6 W and ratio of 50%, frequency of 10 Hz, average power of 3 W, and pulse mode of 4 W. No postoperative medication was prescribed (After fully informed of the benefits and complications of the optional measures to manage the epulis, the patient preferred to the 980-nm semiconductor laser surgery, with the preservation of the involved teeth. We used SIRO Laser Advance semiconductor laser equipment that was produced in Bentheim, Germany. Equipment parameters were λ = 980±15 nm and Pescribed . The surescribed .The occurrence and development of epulis is closely related to endocrine activity. Women at pregnancy are especially prone to recurrence of epulis.Diode lasers have the widest range of application in dentistry. They are used in endodontics and periodontics for their ability to reduce bacterial load, and also in surgery, as well as soft tissue and peri-implantitis treatment.Compared with the traditional surgical methods, the semiconductor laser surgery does not require suturing of wound and causes less postoperative discomfort, which has unparalleled advantages in oral soft tissue surgery. The new technique of 980-nm diode semiconductor laser may be a potential good option to treat pregnancy epulis, causing less discomfort and preserving the involved teeth. However, more clinical cases are required to confirm its reliability.