Re ≤ 60, diameter ratio of two particles 0.125 ≤ β ≤ 2.4, and power-law index of the fluid 0.4 ≤ n ≤ 1.2. Some results are validated by comparing with other available results. The effects of Re, β, and n on the steady state of motion of two particles are discussed. The results show that, for two particles of the same diameter, the particle spacing l in the steady state is independent of n. In shear-thinning fluid, l increases rapidly at first and then slowly, finally approaching a constant for different Re. In shear-thickening fluid, although l tends to be stable in the end, the values of l after stabilization are different. For two particles of different sizes, l does not always reach a stable state, and whether it reaches a stable state depends on n. When the small particle is downstream, l increases rapidly at first and then slowly in shear-thickening fluid, but increases rapidly at first and then decreases slowly, finally approaching a constant in a shear-thinning fluid. In shear-thinning fluid, the larger n is, the smaller l is. In shear-thickening fluid, β has no effect on l in steady-state. When the large particle is downstream, l increases rapidly at first and then slowly in shear-thinning fluid but increases rapidly at first and then decreases in a shear-thickening fluid. The effect of n on l in the steady state is obvious. In shear-thinning fluid, l increases rapidly at first and then slowly, the larger Re is, the smaller l is. In shear- thickening fluid, l will reach a stable state.The steady state of motion of two particles in Poiseuille flow of power-law fluid is numerically studied using the lattice Boltzmann method in the range of Reynolds number 20 ≤  Just like the application of electronic robust control in the field of computing and communication, the precise and programmable control of the equilibrium position of microdroplets or particles in a channel or pipe has been applied to the field of biomedicine, materials synthesis, and so on . MasteriDue to its fundamental and practical significance, there have been a large number of theoretical, experimental, and numerical studies on the migration of rigid particles in a confined flow. About the migration of particles in a Newtonian fluid, we can get some intuitions or results from available experimental and numerical results ,4,5,6,7,Most of the previous studies focused on the flows with low Reynolds numbers, and the inertia can be ignored in such flows ,15,16. ATo better understand the interactions between particles, and between particles and fluid, as well as the formation mechanism of a stable particle train, we first studied the motion of two particles in the Poiseuille flow at a finite Reynolds number and provided a preliminary understanding of the mechanism through the interaction of two particles. It is possible to obtain predictions of the attractive or repulsive interaction of particles. For two particles, the results are different when the particles are initially on or not on the same horizontal line. Schaaf et al.  studied It can be seen from the above studies that there is still a lack of research on the formation of the stable relative position of two particles with different sizes in power-law fluid, and the effects of fluid characteristics, particle size, and flow conditions on the stable relative position of two particles have not been reported. Exploring the steady state of particles migrating in the flow has practical significance for particle detection, separation, focusing, and counting in an application. Therefore, the aim of this study is to assess the steady state of motion of two particles in the Poiseuille flow of power-law fluid and explore the effects of the power-law index of the fluid, Reynolds number, diameter ratio of two particles on the steady state of motion of two particles. We focus on the Poiseuille flow because it is very common in practical applications .if is the distribution function for the microscopic velocity ei in theith direction; τ is the dimensionless relaxation time τ = τ0/∆t(τ0 is collision time); ieqfis the equilibrium distribution function; Δt is the unit time step; Fp is the external force term.The lattice Boltzmann method (LBM) is used to numerically simulate the neutral suspended particles in the Poiseuille flow of power-law fluid. The LBM is a new type of hydrodynamic numerical method based on the molecular dynamics theory at the mesoscopic scale and has proven to be an effective method in the simulation of two-phase flow . Its maisc is the speed of sound; iw is the weight factor; ρ and u represent the fluid density and velocity, respectively.The equilibrium distribution function following the D3Q19 model proposed by Qian et al.  is: (2)fThe speed configuration of the D3Q19 model is as follows:bF is the body force. The fluid density  and velocity satisfy:The external force term with good stability proposed by He et al.  is:(4)Fpp = s2ρc.The macroscopic pressure is given directly by the equation of state by u is the velocity; ρ is the fluid density; p is the pressure; f is the body force; τ is the shear stress and given by μ the dynamic viscosity and By performing a Chapman–Enskog expansion, the macroscopic mass and momentum equations in the low Mach number limit can be recovered and have second-order accuracy in both time and space:m is the flow consistency coefficient; n is the power-law index, n = 1 corresponds to Newtonian fluid, and n < 1 and n > 1 correspond to shear-thinning and shear-thickening fluids, respectively; The effective viscosity is related to the shearing rate of the fluid by:ν =(2fτ−1)c2Δt/6, where fτ is the instantaneous local relaxation time for each fluid lattice point and c is the ratio of grid step to time step.The instantaneous local relaxation time for each fluid lattice point can be obtained by For shear-thinning fluids, at the zero-shear rate fluid lattice point, its apparent viscosity tends to infinity and diverges. For shear-thickening fluids, at the zero-shear rate fluid lattice point, its apparent viscosity will be equal to zero. Both of these cases can lead to unstable or low computational accuracy of the LBM. Therefore, the upper and lower limits of apparent viscosity can be set, respectively :(14):Combining Equations (18)–(21), the total force and torque on the particle are given by Equations (21) and (22) during the time period [For a moving boundary, a stepped zigzag boundary for particle calculation is formed using the bounce scheme proposed and perfected by Ladd  and AiduFinally, the velocity and position of the particle are obtained through Newton’s second law.The above method of calculating force or density reconstruction will fail if the distances between particles or between particles and walls are too small. Therefore, a short-range repulsion model should be introduced, i.e., the distances between particles or between particle and wall are not less than 1–2 lattice cells, thus the overlapping and collision of particles are also avoided.mC =MU2/a, M is the particle mass, U is the velocity and a is the particle radius; ε = 10−4 is a positive coefficient; d is the distance between the centers of two particles or the distance between the center of particle and wall; er is the direction vector; dmin = 2a; Δr = 2Δx represents two lattice cells when the repulsive force exists in the simulation.The repulsive force is introduced :(23)fr={x-y plane under the combined action of inertial force, viscoelasticity, and lift induced by the walls . In the simulation, L/H = 14:1 (L = 2000Δx) for balancing the computational efficiency and precision; a = 18 × lattice units; H/W ≤ 0.5 for ensuring that the number of equilibrium positions along the y-direction is only two sittings [Dl = 18~45Δx (Dl is the diameter of a large particle); blockage ratio k = Dl/H = 0.125~0.3, which reflects the influence of the walls on particle migration; the Reynolds number Re = ρUmaxn2−nH/m [ρ and Umax are the fluid density and maximum velocity, m is the power-law consistency, the range of Reynolds numbers is 20 ≤ Re ≤60 because the inertial migration of particles has a certain limit on Re [β = 0.125~2.4; the power-law index of the fluid n = 0.4~1.2. A periodic constraint is enforced in the x-direction to replicate an infinite domain in the flow direction. In the computation, the calculated time steps are 12 × 106 and 6 × 106 when the particles move to x/H = 500 and x/H = 250, respectively, along the flow direction (each step is the time taken for particles to migrate one grid).Two rigid particles, initially on the same horizontal line, migrate in a Poiseuille flow of power-law fluid as shown in sittings ; particlx2−nHn/m , where ρit on Re ; the diaFor the Poiseuille flow of power-law fluid, there exist analytical solutions for the velocity given by Bird et al. :(24)ux=UThe numerical results of fluid velocity are given in l are placed on the center-line of the flow.The trajectories of two particles in a simple shear flow are shown in H and D are shown in D = 18.75Δx and H = 150Δx in the following simulation for balancing the computational efficiency and precision.The moving boundary is at the midpoint of the solid interior lattice and the fluid exterior lattice, which makes the boundary appear jagged and the calculation results oscillate, so a sufficient number of grids are required to ensure the stability of the calculation. To validate that the calculation results do not depend on the number of grids, the numerical results of particle trajectories for different L are shown in L, so we select L = 2100Δx (14H) in the following simulation.In order to verify that the selected length of the flow does not affect the calculation results, the numerical results of particle trajectories for different length β = 1) are located initially on the same horizontal line with spacing l = 2D (D is the diameter of the large particle), the changes of the spacing of one of two particles along the flow direction for different power-law index n are shown in l/D approaches 10 for three kinds of n, i.e., l/D will eventually stabilize at 10 regardless of whether it is in a Newtonian fluid, shear-thinning fluid, or shear-thickening fluid, the particle spacing in the steady-state is independent of fluid properties. In addition, it can be seen that thel/D increases rapidly at the initial stage (0 < x/H < 10), and then slowly.Two particles of the same diameter  as shown in l/D increases rapidly at first, and then slowly and linearly in Newtonian fluid (n = 1).The case is the same as Newtonian fluid in shear-thickening fluid (n = 1.2), but the growth rate is greater for the latter. For shear-thinning fluid (n = 0.8), the case is completely different, l/D increases rapidly at first and then decreases slowly, finally approaching a constant, indicating that the particle spacing can reach a stable state finally.For the case of β = 1.2  as shown in l/D increases rapidly at first, then slowly and linearly in shear-thinning fluid, but l/D increases rapidly at first and then decreases in the shear-thickening fluid. In a Newtonian fluid, l/D increases rapidly at first and then decreases slowly, finally approaching a constant, and the particle spacing can reach a stable state finally. Therefore, the effect of fluid property on the particle spacing in the steady state is obvious.For the case of l/D along the flow direction for different Re are shown in l/D approaches 10 for three kinds of Re, i.e., the particle spacing in the steady-state is independent of Re in a Newtonian fluid. In addition, the time for particles to reach a steady-state is the shortest for Re = 20, followed by Re = 40 and Re = 60, the smaller Re is, the shorter the time for the particles to reach the steady-state is.The changes of l/D along the flow direction for different Re. For the case of shear-thinning fluid, as shown in l/D increases rapidly at first and then slowly, finally approaching ten for three kinds of Re, which is similar to the previous results [l/D after stabilization are different. l/D is the largest for Re = 20, followed by Re = 40 and Re = 60. results ,32,41. Hl/D of two particles with different sizes along the flow direction for different Re. For the case of β = 0.5, as shown in l/D increases rapidly at first and then slowly and linearly, but the growth rate is different for different Re. The larger Re is, the greater the growth rate is, and the larger the particle spacing is. The curves for Re = 60 Re = 40 are very close, so the change of l/D along the flow direction is not affected by Re at large Re. When a large particle is upstream, the wake area behind the large particle is relatively large, which directly affects the migration of small particle downstream, thus affecting the particle spacing. The characteristics of wake are related to Re, so there are different particle spacing at different Re.β = 2, as shown in l/D finally approaches a constant for different Re. When a small particle is upstream, the wake area behind the small particle is relatively small and has little effect on the migration of a large particle downstream, thus l/D approaches approximately the same constant for different Re.For the case of l/D along the flow direction at different Re in the shear-thinning fluid are shown in β = 0.5 as shown in l/D approaches approximately the same constant for different Re. However, for the case of β = 2 as shown in l/D increases rapidly at first and then slowly, the larger Re is, the smaller the particle spacing is.The changes of l/D along the flow direction at different Re in the shear-thickening fluid. It can be seen that l/D increases rapidly at first and then slowly, and the particle spacing cannot reach a stable state when a large particle is upstream as shown in l/D approaches approximately the constant five for the case of two particles of different sizes, while approaching approximately the constant ten for the case of two particles of the same size as shown in From Re in the present study but has a small effect on the value of particle spacing when a steady-state is reached. Therefore, only the stability characteristics of particle spacing at Re = 20 are analyzed here. The phase diagram for the stability properties of particle spacing under different β and n is shown in β and n.In the simulation, it is found that the Reynolds number does not affect the stability characteristics of particle spacing within the range of n on the particle spacing, we give the relationship between l/D and n as shown in In l/D and β is shown in β. The situation is the same when the small particle is upstream in shear-thickening fluid as shown in The relationship between Re ≤ 60, 0.125 ≤ β ≤ 2.4, and 0.4 ≤ n ≤ 1.2. Some results are validated by comparing the present results with available other results. The effects of Re, β, and n on the steady state of motion of two particles are discussed. The main conclusions are summarized as follows:(1)Re. The smaller Re is, the shorter the time for particles to reach the steady state. In shear-thinning fluid, the particle spacing increases rapidly at first and then slowly, finally approaching 10 for different Re. In shear-thickening fluid, although the particle spacing tends to be stable in the end, the values of particle spacing after stabilization are different, the smaller Re is, the larger particle spacing is.For two particles of the same diameter, the particle spacing increases rapidly at the initial stage, and then slowly, and the particle spacing in the steady state is independent of the power-law index of fluid. In a Newtonian fluid, the particle spacing in the steady state is independent of (2)Re is, the greater the growth rate is, and the larger the particle spacing is. In shear-thinning fluid, the particle spacing approaches approximately the same constant for different Re. The stronger the shear-thinning degree is, the smaller the particle spacing is. In shear-thickening fluid, particle spacing increases rapidly at first and then slowly, and cannot reach a stable state. The diameter ratio of two particles has no effect on the particle spacing in a steady state.For two particles of different sizes, the particle spacing does not always reach a stable state, and whether it reaches a stable state depends on the power-law index of the fluid. When the small particle is downstream, the particle spacing increases rapidly at first, then slowly and linearly in Newtonian fluid and shear-thickening fluid, but increases rapidly at first and then decreases slowly, finally approaching a constant in the shear-thinning fluid. In a Newtonian fluid, the particle spacing increases rapidly at first and then slowly and linearly, the larger The steady state of motion of two particles in the Poiseuille flow of power-law fluid is numerically studied using the LBM in the range of 20 ≤ Re. In a shear-thinning fluid, the particle spacing increases rapidly at first and then slowly; the larger Re is, the smaller the particle spacing is. In shear-thickening fluid, the particle spacing will reach a stable state.When the large particle is downstream, the particle spacing increases rapidly at first and then slowly and linearly in shear-thinning fluid, but increases rapidly at first and then decreases in the shear-thickening fluid. In a Newtonian fluid, the particle spacing increases rapidly at first, and then decreases slowly, finally approaching a constant. The effect of the power-law index on the particle spacing in the steady state is obvious. In a Newtonian fluid, the particle spacing finally approaches a constant for different


II or AuIII). Gelation proceeded by addition of an HPMC solution in N-methyl-2-pyrrolidone (NMP) to a metal ion aqueous solution. An increase in the composition ratio of the metal-coordination units from 10 mol% to 34 mol% (HPMC-34) increased the cross-linking rate with AuIII. Cross-linking immediately occurred after dropwise addition of an HPMC-34 solution to the AuIII solution, generating the separation between the phases of HPMC-34 and AuIII. The cross-linking of AuIII proceeded from the surface to the inside of the HPMC-34 droplets, affording spherical gels. In contrast, a decrease in the ratio of metal-coordination units from 10 mol% to 4 mol% (HPMC-4) decreased the PdII cross-linking rate. The cross-linking occurred gradually and the gels extended to the bottom of the vessel, forming fibrous gels. On the basis of the mechanism for the formation of gels with different morphologies, the gelation of HPMC-34 and AuIII provided nanosheets via gelation at the interface between the AuIII solution and the HPMC-34 solution. The gelation of HPMC-4 and PdII afforded nanofibers by a facile method, i.e., dropwise addition of the HPMC-4 solution to the PdII solution. These results demonstrated that changing the composition ratio of the metal-coordination units in HPMC can control the gelation behavior, resulting in different types of nanomaterials.We investigated the gelation of a hydrophilic polymer with metal-coordination units (HPMC) and metal ions (Pd Organic–inorganic hybrid materials, which consist of organic polymers containing inorganic metals dispersed at the nanometer scale, have generated a great deal of interest due to their unique properties such as flexibility, high transparency, high reactivity, and mechanical and thermal stabilities ,2,3,4,5.II or AuIII) upon addition of a dispersed aqueous solution of HPMC-8 to an aqueous solution of metal ions [II or AuIII afforded spherical and fibrous gels, respectively  with metal ions  solutions of HPMC-10 or HPMC-34  were added to 4.0 mM NaAuCl4 aqueous solutions (5 mL). In the gelation of HPMC-10, AuIII ions gradually cross-linked from the surface to the inside phase of HPMC-10 and the gels extended to the bottom of the container, forming fibrous gels  observations were conducted. Similar to the gel shapes in the photographs  at equilibrium and at t, and k is the pseudo-first-order rate constant (min−1). In the case of cross-linking reaction of HPMC-34, k was estimated to be 10.8 × 10−2 min−1 (R2 = 0.9712), which was faster than that for HPMC-10 . The gel fraction indicates the cross-linking density of the gels determined by removing soluble parts using Soxhlet extraction. Gel fractions of the gels from HPMC-34 and HPMC-10 were 0.76 and 0.14, respectively, indicating that the cross-linking density of HPMC-34-Au was higher than that of HPMC-10-Au.A kinetic study and the gel fraction were examined to explain the mechanism for the formation of the different shaped gels. Cross-linking rates of HPMC-34 and HPMC-10 with AuIII was faster than that of HPMC-10. In the cross-linking of HPMC-34, gelation with AuIII occurred immediately at the surface of the droplets after the dropwise addition of the HPMC solution to the AuIII solution. Gelation proceeded by immersing AuIII inside of the droplets, forming the higher cross-linking density and spherical gels. Contrastingly, due to the slower cross-linking rate of HPMC-10, the cross-linking occurred gradually with the diffusion of AuIII from the surface to the inside of the HPMC-10 phase, resulting in the formation of the lower cross-linking density and fibrous gels.On the basis of the results, a mechanism for the formation of the different morphologies was proposed. The cross-linking rate of HPMC-34 and AuII was compared to that of HPMC-10 with PdII. NMP solutions of HPMC-10 or HPMC-4  were added to 4.0 mM Na2PdCl4 aqueous solutions (5 mL). In the gelation of HPMC-10, immediate separation occurred between the HPMC-10 and PdII phases  and 8.62 × 10−2 min−1 (R2 = 0.9712), respectively. The gel fractions of the gels from HPMC-4 and HPMC-10 were 0.01 and 0.17, respectively, indicating that the cross-linking density of HPMC-4 was lower than that of HPMC-10. Consequently, the cross-linking reaction of HPMC-4 gradually proceeded with the diffusion of PdII from the surface to the inside of the HPMC phase due to the slower cross-linking rate, providing lower cross-linking density and fibrous gels as opposed to the gelation of HPMC-10 .As shown in III aqueous solution allowed instant separation of the HPMC-34 and AuIII phases  to an NMP solution of HPMC-34 with a higher specific gravity (1.63 g/cm3)). When the AuIII aqueous solutions  were gently added to the NMP solutions of HPMC-34 with different concentrations , the upper AuIII solution was miscible with the lower HPMC-34 concentration due to the slow cross-linking rate. In contrast, the increase in the concentration of HPMC-34 to 31, 35, and 37 wt% allowed instant cross-linking leading to the liquid/liquid separation, resulting in the formation of film-shaped gels at the interface  were added to the HPMC-34 solutions (35 wt%). In every case, liquid/liquid separations were observed (III (20 mmol) and HPMC (35 wt%) phases was transferred onto a Petri dish using tweezers, followed by washing with NMP and drying under reduced pressure. SEM and transmission electron microscope (TEM) images revealed the formation of a sheet structure  were added to a NaAuCl4 aqueous solution (4 mM) in a test tube. In all cases, elongated gels were obtained  and sodium tetrachloroaurate (III) dehydrate  were commercially available and used as received. Dimethylsulfoxide  was distilled under CaH2. N-Methylpyrrolidone  was used as received.Polyvinyl alcohol   was used as received. Methyl isothiocyanate  was distilled prior to use. Sodium tetrachloropalladate (II) (Na1H NMR spectra were measured with a JEOL JNM ECA-500 using tetramethylsilane (TMS) as an internal standard; δ values are given in parts per million (ppm). IR spectra were measured with a SHIMADZU FTIR IRPrestige-21 spectrometer, and the values are provided in cm−1. Flame atomic absorption spectrometry was conducted with a Hitachi Z-2310 polarized Zeeman atomic absorption spectrometer (AAS). X-ray photoelectron spectroscopy (XPS) was performed with a Kratos AXIS-NOVA instrument. Scanning electron microscopy (SEM) was performed using a HITACHI S-2500 instrument at an acceleration voltage of 1.5 kV. Energy-dispersive X-ray analysis (EDX/SEM) was conducted using a HITACHI S-3400N/BRUKER Quantax 200 System. Transmission electron microscopy (TEM) was conducted using a HITACHI HT-7700 instrument at an acceleration voltage of 20 kV. Samples for TEM analysis were deposited onto a Cu grid. Atomic force microscopy (AFM) was conducted with a KEYENCE VN-8010 instrument using a silicon substrate in the high amplitude mode (tapping mode) under an ambient condition.2PdCl4 (10.0 mL) or NaAuCl4 (10.0 mL). Gelation was conducted at room temperature for 2 min, and the obtained gel was dried to constant weight at 60 °C in vacuo.NMP solutions of HPMC  were added to 4.00 mM aqueous solutions of NaWdry is the weight of the dried gel before Soxhlet extraction and Wwash—dry is the weight of the dried gel after Soxhlet extraction.The gel fraction of the cross-linked HPMC was determined gravimetrically. The dry gels were washed with refluxed distilled water in a Soxhlet extraction to remove the soluble parts. The washed gels were dried to constant weight at 80 °C in vacuo. The gel fraction was calculated from the following equation:III ions  was carefully added to an NMP solution of HPMC-34  in a vial bottle. After 3 s, the obtained nanosheets were transferred from the interface between the AuIII ion layer and HPMC-34 layer onto a Petri dish. The nanosheets were washed with NMP, followed by drying under vacuum.An aqueous solution of Au2PdCl4 aqueous solution (20.0 mL), and the mixture was allowed to stand at room temperature for 4 min. The resulting gels were handled using tweezers and placed in a Petri dish. The gels were washed with NMP, followed by drying to obtain the fibrous gels.An NMP solution of HPMC-4  was added to a 25.0 mL test tube containing 4.00 mM Na


Dendrobium moschatum (Buch.-Ham.) Sw. 1805 is very distinctive among Dendrobium Sw. 1799, and it has high medicinal and ornamental values. Here, we reported the first complete chloroplast genome of D. moschatum. The complete genome of D. moschatum was 159,701 bp in length with 130 genes, including 38 tRNA, 8 rRNA, and 84 protein-coding genes. Phylogenetic analysis showed that D. moschatum was strongly allied with D. denneanum Kerr. 1933.The morphological characteristic of  Dendrobium Sw. 1799 (Orchidaceae) is one of the largest genera in angiosperms, over 1500 species that are mainly distributed in Asia and Oceania  Sw. 1805 has a very distinctive morphological characteristic among Dendrobium species featured with the length of erect stem to 1 m, inflorescences 20 cm, lip slipperlike  of the Red List of China Higher Plants based on IUCN Red List Categories and Criteria . Voucher specimens were deposited in the Dendrological Herbarium in Guizhou Academy of Forestry  and were identified as D. moschatum by Professor Lian-Hui Wang. The plant sample is cultivated and collection was permitted by the Institute of Forestry Biotechnology, Guizhou Academy of Forestry. Total DNA was extracted from fresh leaves using modified CTAB method (Doyle and Doyle http://www.1kmpg.cn/cpgview/) (The leave samples of pgview/) .D. moschatum (GenBank accession OM161978) is 15,9701 bp in length, which presented a typical quadripartite structure, containing a large single-copy  region, a small single-copy  region, and two inverted repeat regions   . Furthers 37.26% .D. moschatum, other 30 Dendrobium plastid genomes were selected to carry out analyses with Paphiopedilum micranthum T. Tang et F. T. Wang 1951 and P. armeniacum S. C. Chen et F. Y. Liu 1982 (Orchidaceae) as outgroups. Sequences were aligned using MAFFT 7.409 (Katoh and Standley http://www.phylo.org/) (Miller et al. D. comatum is phylogenetically related to D. denneanum Kerr 1933 (D. moschatum is of great benefit to further investigation on its phylogeny and conservation in Dendrobium.To infer phylogenetic position of err 1933 . This ne


The bold dashed line that appeared slightly to the right of the 2 value on the x-axis should have appeared in the position indicating “1.98.” This article has been corrected.1In the Original Investigation titled “Association of Intravenous Potassium and Magnesium Administration With Spontaneous Conversion of Atrial Fibrillation and Atrial Flutter in the Emergency Department,”


Endometrial carcinoma is the most common gynaecological cancer in developed countries. Most cases are low-volume/low-grade tumour at presentation; however, high-grade subtypes may present with locally advanced disease with higher propensity for spread outside of the pelvis. MRI has a role in local staging of the tumour and helping the clinicians in treatment decision making. This pictorial essay gives examples of endometrial carcinoma at different stages with histological correlation. It also explores the potential limitations and pitfalls of imaging in this context. MRI plays an important role in staging endometrial carcinoma particularly in the evaluation of depth of invasion into the myometrium.Factors such as large intracavitary tumour, cornual tumour location, variable tumour appearance, adenomyosis and fibroid can affect the MRI accuracy in assessing the depth of myometrial invasion.Measurement of depth of invasion is best performed on oblique axial post-contrast sequence—paralleling the pathologists’ histological assessment.Endometrial cancer is the most common gynaecological cancer in developed countries , 2. It pEndometrial cancer can be broadly divided into two types: Type I and Type II Fig. . The mosThe specific histology subtype of the endometrial carcinoma can influence the prognosis as well as the pattern of extra-uterine spread. Endometrioid subtype tends to spread by direct extension and nodal disease initially. In contrast, serous and clear-cell endometrial carcinoma is more aggressive with increased lymphovascular invasion, peritoneal and extra-abdominal spread .The prognosis of endometrial cancer is dependent on histological subtype, histological grade, lymphovascular invasion and FIGO staging , 5. TumoFIGO staging was last updated in 2009  Table 11. The maThe MRI protocol for the imaging of endometrial carcinoma as well as the value of the individual sequences is detailed in Table Endometrial carcinoma is intermediate in signal intensity on T2-weighted imaging and hyperintense compared to the myometrium. The tumour is hypoenhancing relative to the background myometrium on the contrast-enhanced sequences—a useful feature in evaluating the depth of myometrium invasion. Normal endometrium, in contrast, shows delayed enhancement similar to the myometrium. The tumour has signal restriction on diffusion weighted imaging (DWI) due to the increased cellularity. DWI findings help to identify the tumour when small. The tumour can be quite variable in its growth pattern. It may have a large polypoidal intracavitary component, diffuse thickening of the endometrium or minimal intracavitary component with bulk of the tumour growing into the myometrium.Most of the endometrial carcinoma presents at Stage 1. Stage IA and stage IB are differentiated by invasion greater than 50% of the myometrium Figs. , 3. WhilThe measurement on histology is based on low-field microscopy and is defined as tumour invasion into myometrial smooth muscle, relative to the estimated depth of the entire myometrium at that point Fig.  11, 12], 1211, 1The endometrium/myometrium interface is an important landmark, but it can be irregular or distorted due to fibroids or background adenomyosis. Identifying normal physiological enhancement of the subendometrial myometrium (junction zone) on the early DCE sequences is important to exclude myometrial invasion. However, it is not always present due to either timing of the scan or tumour involvement. It can also occasionally be mimicked by the early enhancement at the pushing front of the tumour. The latter tends to be irregular, thick and associated with large tumours.Large tumour volume may also distend the endometrial cavity. The intracavitary component of the large tumour may be erroneously included as part of the tumour depth into the myometrium leading to overestimation of the depth of invasion.Atypical appearance of the tumour can be seen particularly in relation to T2 signal. Occasionally, tumour may be isointense to the myometrium or contain T2 hyperintense mucinous components. In those cases, the contrast-enhanced sequences are more reliable in marking out the extent of the tumour.The invasion of the cervical stroma denotes stage II Fig. . CervicaInvolvement of the serosa (stage IIIA) on MRI is characterised by full thickness tumour signal replacement of the myometrium with irregularity at the uterine outer surface Fig. . This coOvarian involvement (stage IIIA) can occur with contiguous spread of the primary tumour with engulfment of the normal ovarian tissue Fig. . It can Vaginal involvement at time of initial diagnosis is rare. Vaginal involvement commonly is due to drop metastasis Fig.  and is sRadiologically, parametrial involvement occurs in the context of tumour involvement of the cervix. The involvement of the parametrium can be identified on MRI as loss of the full thickness low T2 cervical stroma signal with irregular interface at the adjacent parametrial fat or frank tumour extension into the fat Fig. . On histThe evaluation of the para-aortic nodes is easier on CT unless additional large field of view sequences are obtained through the abdomen. The evaluation of the pelvic nodes on MRI is still based on the short-axis dimension with a short-axis diameter cut-off of > 8 mm for pelvic lymph nodes and > 10 mm for para-aortic lymph nodes , 13. WhiWhilst rare, endometrial cancer can invade adjacent pelvic organs such as bladder and bowel Fig. . This woThe high-resolution T2 sequences are optimal for the assessing the relationship of the tumour to the adjacent organs. The local invasion on MRI shows tumour signal that disrupts the adjacent organs such as bowel or bladder. Bladder involvement requires extension to the bladder urothelium. Isolated detrusor muscle involvement is not considered to be stage IV disease. Often, involvement of the urinary bladder detrusor muscle leads to an oedematous mucosa (bullous oedema) in the bladder which can be seen on MRI or cystoscopy. Protuberant tumour in the bladder lumen with acute angle relative to the bladder inner layer would be highly concerning for urothelial involvement. The finding of a utero-vesical fistula also invariably infers the presence of bladder involvement.Endometrial carcinoma is the most common gynaecological cancer. Whilst most cases are low grade with low-volume disease, it can also present with higher grade and more advanced disease with higher risk of nodal spread. MRI can assist in the local staging of the endometrial carcinoma preoperatively and guide the surgical and management decisions. MRI can assess the depth of myometrial invasion and distinguish between stage 1A and stage 1B disease. Its accuracy can, however, be affected by factors such as fibroids, adenomyosis, atrophic myometrium, bulky tumour, indistinct or variegated endometrium/myometrium junction and atypical tumour appearance on MRI. Understanding these potential pitfalls would help the reporter to improve the accuracy in detection of deep myometrial invasion. MRI with its higher tissue contrast resolution also has a role in identifying the extra-uterine pelvic disease. The extra-uterine disease can be due to different patterns of spread including contiguous, drop metastases, transcoelomic and lymphatic nodal spread. We present in this paper the radiology–pathology correlation at the different FIGO stages to help reporting radiologists to have a better understanding of the local spread of endometrial carcinoma and its imaging appearance.


Tibialis Anterior (TA), not routinely tested muscle. Jitter measurement was taken using the intramuscular microaxonal stimulation technique in 32 healthy subjects. The mean MCD and the mean MCD of the 27th value from the 32 subjects had a normal distribution and were 19.79 ± 2.72 μs and 26.88 ± 3.56 μs, respectively. The suggested limit for the mean MCD is ≥ 26 μs and for the individual values is > 34 μs.Calculating the reference values for jitter parameters utilizing a disposable concentric needle have been already done for the most often tested muscles. Jitter, expressed as the mean consecutive difference (MCD), was measured in the  Extensor Digitorum (ED). Still, it could be affected by C7 radiculopathy presenting active denervation or chronic reinnervation, which increases the jitter values  muscle using intramuscular microaxonal stimulation and by recording with disposable CNE.Neuromuscular jitter, assessed by single-fiber electromyography (SFEMG), is the variation in time intervals between pairs of single fiber action potentials (SFAP) acquired with voluntary activation or the variation in time observed between stimulus and evoked SFAPs in response to nerve stimulation (s-jitter). Jitter is a sensitive indicator of neuromuscular junction (NMJ) function, and it is handy in examining individuals with suspected NMJ dysfunction, as in myasthenia gravis (MG). Because of the great concern over infection transmission, disposable concentric needle electrodes (CNE) are being used for jitter analysis –9 instear values . Jitter r values . This stThis study was in accord with the Helsinki Declaration of 1975 and approved by the ethics committee of the Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil, where the SFEMG studies were performed.Thirty-two adult patients of both sexes were recruited and invited to participate in the study. They were selected from the State Medical School (FAMERP). None had been diagnosed with a neuromuscular disorder, diabetes, injury affecting L5 root, sciatic or fibular nerves or were taking verapamil or amlodipine - calcium channel blockers medications that could increase jitter . The tem® display  was used in all subjects. The recordings were performed using a CNE 25 mm × 30 G with a recording area of 0.020 mm2 . The CNE used was approved by the Brazilian Agency for Health Surveillance (ANVISA). An amplitude detection algorithm was used to record and analyze time variations. In all cases, qualitative needle electromyography (EMG) was done in the TA muscle before starting the jitter measurement to exclude active denervation  or chronic reinnervation based on the motor unit action potentials (MUAP) with increased amplitude and duration, which is well-known to increase the jitter (The SFEMG test was done at the Neuromuscular Investigation Laboratory (LIN) at the FAMERP by the first author (JAK). The electrical activation technique measured jitter parameters in the TA muscle (details below). A Natus electrodiagnostic machine with UltraPro™ S100 Elite software in VikingAmbu®, Neuroline, Malaysia) inserted near the endplate motor zone (motor point) and positioned at a right angle to the course of the muscle fibers , 25 × 36 mm, and with 28 G  or 100% representing the perfect linear association and r = 0 (R-Sq. = 0) representing no association between the variables. The R-Sq was calculated between the mean MCD values and age, MUAP amplitude, and mean interpotential interval values. The software Minitab® was used for statistical evaluations.The Kolmogorov-Smirnov (KS), Anderson-Darling (AD), and Shapiro-Wilk (SW) normality tests were used for the mean MCD , the mean of the 27th highest MCD , and the individual MCD . The mean and standard deviation (SD) values were calculated for data with normal distribution, and the upper limit of normality was calculated as the mean plus 2 SDs. The median and percentiles values were calculated for data with the non-Gaussian distribution, and the upper limit of normality was calculated for the 97.5% highest value. To measure the linear association between two variables, a correlation of r (R-Sq.) was used, with Of the 32 patients, 16 were men and 16 were women. The mean, SD, and range of age are shown in R2) between the 32 mean MCD values and the mean interpotential interval is shown in The mean, SD, and range of the MCD (latencies) are shown in We found a reference limit for the MCD value as ≥26 μs and the individual MCD values as >34 μs. We used the 27th MCD value to calculate the upper limit of normality  of the individual values (outliers), as done in the CNE multicenter study . InsteadFrontalis, and Orbicularis Oculi. Tested facial muscles near the BoNT injections are the most affected in the percent of patients with increased jitter (up to 40%). The amount of jitter could rise to 56.6% above the reference upper limit and persist even after 11 months from the last injection , and 33.3% sensitivity and 92.3% specificity (area) for abnormal decrement (≥10%) between the fourth and the first response in all forms of the disease. In the same cases, SFEMG for any muscle was abnormal in 39.2%  in the segment fibular nerve to in 39.2% . Oh et ain 39.2%  describeFrontalis, and Orbicularis Oculi muscles for both voluntary and electrical activation . The CNE has already been a well-established method to measure jitter with the same sensitivity and specificity as the single fiber electrode, which is safe, well-supported, and reliable.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.This study was in accordance with the Helsinki Declaration of 1975 and approved by the Ethics Committee of the Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil, where the SFEMG studies were performed. The patients/participants provided their written informed consent to participate in this study.JK designed the study, prepared the protocol, and carried on the single-fiber electromyography exams. CG selected the subjects, tabulated data, and helped in manuscript revision. All authors participated in interpreting data and read and approved the final manuscript.This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Brazil (grant number 2022/02291-1).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.


Experiment 1). The profile of paired ascites and plasma was also compared in 17 cirrhotic patients (Experiment 2). Gas chromatography–mass spectrometry-based metabolomics identified 29 metabolites that significantly characterized ascites fluid, whether postoperative drainage fluid or plasma were used as controls. Ten elevated amino acids  and seven diminished lipids  largely comprised the cirrhotic ascites metabolomic phenotype that differed significantly (adjusted p < 0.002 to 0.03) from peritoneal drainage fluid or plasma. The pattern of upregulated amino acids in cirrhotic ascites did not indicate albumin proteolysis by peritoneal bacteria. Bidirectional clustering showed that the more severe the cirrhosis, the lower the lipid concentration in ascitic fluid. The metabolomic compartment of ascites in patients with decompensated cirrhosis is characterized by increased amino acids and decreased lipids. These novel findings have potential relevance for diagnostic purposes.Ascites is a common complication of decompensated liver cirrhosis, and yet relatively little is known about its biochemical composition. We conducted two metabolomic investigations, comparing the profile of ascites from 33 cirrhotic patients and postoperative peritoneal drainage fluid from 33 surgical patients ( Liver disease is responsible for about two million deaths per year worldwide. Up to half of these deaths are due to complications of liver cirrhosis (LC), the 11th most common cause of death globally . Approxi1H NMR [There are several reports on the background of metabolomics  and its 1H NMR . This sa1H NMR . A study1H NMR .Experiment 1). Additionally, we made a metabolomic comparison between paired plasma and ascites fluid in 17 of these cirrhotic patients (Experiment 2). The study is both of clinical and scientific significance because it demonstrates, in two separate investigational arms, how the peritoneal fluid compartment is metabolically altered in cirrhotic ascites. The elevation of amino acids and diminution of fatty acids in ascites may reveal new insights into the formation of ascites and have potential relevance for diagnostic purposes.The limited and heterogeneous reports involving cirrhotic ascites teach us little about the biochemical composition of ascites and in relation to clinical variables. Nor do these studies identify potential mechanisms for how small organic molecules enter ascitic fluid. We therefore conducted a metabolomic investigation of ascites fluid from 33 cirrhotic patients and of peritoneal drainage fluid from 33 postoperative patients as controls  model, the separation between ascites fluid samples and controls was much improved compared to the PCA  between ascites and control peritoneal drainage fluid. These metabolites are listed in Analysis by gas chromatography–mass spectrometry (GC-MS) of cirrhotic ascites fluid versus postoperative peritoneal fluid confirmed the presence of 58 metabolites, identified according to matching mass spectra with a spectral database and in direct comparison with an in-house library of authentic standards. Multivariate data analysis revealed a partial separation with little clustering for the 33 ascites patients vs. the 33 control postoperative peritoneal drainage patients in the principal components analysis (PCA) scores plot a. The to the PCA b. The OP the PCA c revealemyo-inositol, scyllo-inositol and fructose were all elevated in ascites. Diminished in ascites were the lipids lauric, myristic, palmitic, linoleic, oleic and stearic acids, together with cholesterol. These lipids also appeared as a tight cluster in the OPLS-DA loadings S-plot (p < 0.01). No other metabolite differed between these two etiological groups.Of particular note were elevated amino acids and lowered lipids in ascites. Further details of these metabolites are given in s S-plot c, again p values < 0.002 to 0.007) in ascites compared to peritoneal drainage. The generalized pattern that emerged from Experiment 1 was one of elevated amino acids and diminished lipids in cirrhotic ascites fluid. This was further validated using ROC analysis (p < 0.0001) ROC curve with an AUC of 0.74. Moreover, the combination of diminished lipid species lauric, myristic, palmitic, linoleic, oleic and stearic acids, together with cholesterol, also yielded a significant (p < 0.0001) ROC curve with an AUC of 0.90.Two general features of this analysis are of note. Firstly, the separation of ascites and surgical drainage samples in the PCA and OPLS-DA scores plots a,b is inanalysis , wherebyanalysis  yielded −33. In the OPLS-DA model, the scores plot  between cirrhotic ascites and controls (postoperative drainage fluid or cirrhotic ascites patient plasma) and details of these are given in For 17 of the ascites patients, the plasma metabolome was also investigated using GC-MS and compared with the ascites fluid metabolome. res plot b showed res plot c shows pExperiment 1 and Experiment 2 produced remarkably similar findings despite the vastly different study designs that used diverse controls. The metabolic phenotype of cirrhotic ascites has therefore been defined from two differential experimental perspectives.Accordingly, X and Y axes, respectively. Two cluster maps were derived from data generated in Experiment 1  with plasma creatinine concentration (D) and therefore, not unexpectedly, negatively (cyan/blue) with the estimated glomerular filtration rate (A). The cluster map for ascites fluid from Experiment 1 contained considerably more associations between clinical variables and metabolite levels  with stearic (9) and palmitic acids (8) and a positive correlation with all three BCAAs  was expressed in a cluster map with clinical covariates  was significantly different  between these two groups. The fundamental metabolic phenotype of cirrhotic ascites was elevated amino acids and diminished lipids. In Experiment 2, where cirrhotic ascites fluid was compared with plasma from the same patients, the concentration of 19 metabolites (7 not previously described in cirrhotic ascites fluid) was significantly different  between paired ascites fluid and plasma. Interestingly, the metabolic phenotype of cirrhotic ascites in both investigations was elevated amino acids and diminished lipids.Two investigations have been conducted with the aim of defining the metabolomic phenotype of cirrhotic ascites fluid. In Regarding the diminution of fatty acids and cholesterol in cirrhotic ascites relative to either postoperative drainage fluid or plasma, it is proposed that these observations can in part be interpreted in terms of the concentration and physicochemical properties of albumin. Cirrhotic ascites fluid is a transudative ascites due to portal hypertension with a serum–ascites albumin gradient (SAAG) ≥ 11 g/L . The meap < 0.0001) is currently unknown but is unlikely to be due to bacterial degradation of albumin or the transport into ascites bound to albumin. Notably, the two amino acids most strongly correlated between plasma and mesenteric lymph, threonine and methionine [Regarding the increased concentration of α-amino acids in ascites relative to both postoperative peritoneal drainage fluid and plasma, the observations cannot be attributed directly to the difference in albumin concentrations. Plasma concentrations of amino acids are not only subject to homeostatic control, but are also affected by many variables, including habitual diet , metabolthionine  were amoR,3S)-dihydroxybutanoic acid diastereomer, a metabolite of threonine and a putative oncometabolite in acute myeloid leukemia [S)-3,4-dihydroxybutanoic acid (2-deoxytetronic acid), an endogenous metabolite, dietary constituent and a metabolite of xylose produced by E.coli [The use of bidirectional clustering of demographic/clinical variables and metabolite concentrations provided novel insights into cirrhotic ascites. Firstly, the hotspots for serum creatinine concentration (crtn) with 2,3-dihydroxybutanoic acid  in both postoperative drainage fluid and ascites fluid may be related to their respective renal handling. This latter compound is the  and cirrhotic ascites (n = 47), groups that had SAAG values of 12 and 18 g/L (p < 0.01), respectively [p < 0.001) mean serum tyrosine concentration (124 ± 73 μM) than the malignant ascites patients (44 ± 17 μM). These findings are consistent with the cluster map observation that serum albumin and tyrosine concentrations are correlated.Secondly, the strong correlation (hotspot) between plasma albumin and tyrosine concentrations in the logFC cluster map is of interest. A ectively . This inZ), palmitic (16:0) and vaccenic (18:1 11E) acids. These data can be interpreted as meaning that the more severe the cirrhosis, the lower the concentration of these fatty acids in ascitic fluid relative to plasma.Thirdly, another logFC feature of significance was the negative correlation (cold spot) between Child–Pugh score and myristic (14:0), oleic (18:1 9Xiaozhang Tie (XT) [Animal models of ascites have furnished new knowledge regarding the mechanisms of ascites development. Intraperitoneal injection of carbon tetrachloride to rats induces decompensated liver cirrhosis with ascites . The appTie (XT) ,51. XT aTie (XT) . A generBetter understanding of the pathophysiology of ascites formation and the metabolic parameters associated with it through metabolomic investigations may lead to the identification of novel drug targets for its treatment and/or prevention. Future work will need to address how the presence of diseases other than cirrhosis—for example, hepatocellular carcinoma or cholangiocarcinoma—influences the molecular composition of ascites fluid. The metabolite profile of ascites might therefore be used as an aid to determine the presence of malignancies within the liver.Experiment 1, peritoneal fluid was collected either via abdominal paracentesis in patients with decompensated cirrhosis (n = 33) and from patients recovering from abdominal surgical interventions through peritoneal drain tubes (n = 33). In Experiment 2, plasma  was prepared from 17 of the patients with decompensated cirrhosis around the time of paracentesis. Samples were aliquoted, a sample sent for analysis and the remainder stored at −20 °C until analyzed. The etiology of cirrhosis (no. of cases) was HCV (2), alcohol (13), HCV plus alcohol (2), alcohol plus Laennec’s (3), HBV (2), HBV plus alcohol (1), NASH (3), HBV plus NASH (1), HBV plus HCV plus alcohol (1), autoimmune (1), hemochromatosis (1), HBV plus autoimmune (1), primary biliary cholangitis (1) and Budd Chiari syndrome (1). The ascites and postoperative patients did not differ by age  or by gender . The cirrhotic patients were Child–Pugh (CP) class A , B  and C  and the postoperative drainage patients had passive drainage (n = 18), Easy Flow drain (n = 10), Pigtail drain (n = 1) and Jackson Pratt drain (n = 1), with one drain not recorded. Several postoperative drainage patients had carcinoma, including colorectal carcinoma (n = 6), pancreatic carcinoma (n = 3), gastric carcinoma (n = 1), metastatic melanoma (n = 1) and hepatobiliary carcinomas (n = 3). The body mass indices, serum biochemistry and hematology and liver function tests of the two patient groups are displayed and compared (mean ± standard deviation) in p < 0.05), serum potassium (p < 0.05), estimated glomerular filtration rate (p < 0.05), leukocytes (p < 0.05), thrombocytes (p < 0.001) and Quick prothrombin test (p < 0.0001) and significantly higher serum sodium (p < 0.0001), total bilirubin (p < 0.001), hemoglobin (p < 0.0001) and INR (p < 0.001). Differences in liver enzymes ALT, AST, ALP and GGT were all non-significant, as were serum creatinine, glucose, total protein and albumin.All patients gave their written informed consent to the study, which was conducted according to the World Medical Association Declaration of Helsinki and complied with the provisions of the Good Clinical Practice guidelines and local laws. The study was approved by the ethics committee of Canton Bern . Exclusion criteria were age >80 or <18, insufficient biological samples or clinical and laboratory data and no informed consent. In Aliquots of samples (50 µL) were subjected to GC-MS analysis with 4-chlorophenylacetic acid  as internal standard using a slight modification of our published methods ,19,20. Sp values are all two sided. For the demographic data and clinical measurements, an unpaired t test was used. For the metabolomic data, group differences were analyzed nonparametrically using Mann–Whitney U test and then subjected to Bonferroni correction to eliminate false discovery due to multiple comparisons [p values and adjusted for multiple comparisons using the Bonferroni correction. Receiver operating characteristic (ROC) curves were generated using GraphPad Prism 9.3.1.Multivariate data analysis conducted using SIMCA. Univariate statistics were performed using GraphPad Prism 9.3.1 . Means are expressed ± S.D. and parisons . For paiClustering analysis was performed as follows: each metabolite was tested for statistical association with each of the clinical covariates. For discrete or binary covariates, a two-sided Student’s t-test was used. For numerical covariates, a t statistic was calculated from the Pearson correlation coefficient. The values used for the metabolites were either the log-transformed intensities or the log-fold change (logFC) values between ascites and blood plasma. Next, a matrix was constructed with all the obtained t values for each pair of metabolites (rows) and covariates (columns). Rows and columns where all t values were less than 3.5 were considered non-informative and discarded. The rows and columns of the resulting matrix were clustered using hierarchical clustering using correlation distance as a distance metric. The results were visualized on a cluster map.The investigation of cirrhotic ascites using GC-MS-based metabolomics identified 29 metabolites that significantly characterized ascites fluid compared with postoperative drainage fluid from surgical patients or from the cirrhotic patients’ own plasma. The metabolomic phenotype of cirrhotic ascites fluid principally comprised elevated amino acids and diminished fatty acids and cholesterol. The clustering of the amino acids, and also of the fatty acids, in the multivariate data analysis is suggestive of a single mechanism that facilitates entry of amino acids into ascites and a second common mechanism that constrains the entry of lipids into ascites. These novel findings have potential applicability to diagnostic determinations.


Internalizing, externalizing, and somatoform disorders are the most common and disabling forms of psychopathology. Our understanding of these clinical problems is limited by a reliance on self-report along with research using small samples. Social media has emerged as an exciting channel for collecting a large sample of longitudinal data from individuals to study psychopathology.This study reported the results of 2 large ongoing studies in which we collected data from Twitter and self-reported clinical screening scales, the Studies of Online Cohorts for Internalizing Symptoms and Language (SOCIAL) I and II.invalid), those who denied being Twitter users , Twitter users who gave their handles but whose accounts had high bot scores (bot-like), and Twitter users who provided their handles and had low bot scores . We explored whether there were significant differences among these groups in terms of their sociodemographic features, clinical symptoms, and aspects of social media use .The participants were a sample of Twitter-using adults (SOCIAL I: N=1123) targeted to be nationally representative in terms of age, sex assigned at birth, race, and ethnicity, as well as a sample of college students in the Midwest (SOCIAL II: N=1988), of which 61.78% (1228/1988) were Twitter users. For all participants who were Twitter users, we asked for access to their Twitter handle, which we analyzed using Botometer, which rates the likelihood of an account belonging to a bot. We divided participants into 4 groups: Twitter users who did not give us their handle or gave us invalid handles , and a few were deemed bot-like . A total of 31.43% (353/1123) gave no handle or gave an invalid handle . In SOCIAL II, many individuals were not Twitter users . Of the Twitter users in SOCIAL II , most were classified as either invalid  or valid , with a smaller fraction deemed bot-like . Participants reported high rates of mental health diagnoses as well as high levels of symptoms, especially in SOCIAL II. In general, the differences between individuals who provided or did not provide their social media handles were small and not statistically significant.Triangulating passively acquired social media data and self-reported questionnaires offers new possibilities for large-scale assessment and evaluation of vulnerability to mental disorders. The propensity of participants to share social media handles is likely not a source of sample bias in subsequent social media analytics. Research implicates various mechanisms in the etiology and maintenance of mental disorder symptoms, including sustained negative affect, disturbances in positive affect, disrupted social processes, disturbances in arousal and regulatory processes, sensorimotor problems, and cognitive dysfunction [So-called mental disorders, including depression, anxiety, substance use, and pain-related conditions, account for a substantial proportion of disabilities attributed to illness worldwide . Accordifunction . Howeverfunction , they arfunction . In addifunction .Characterizing heterogeneity in psychopathology requires large samples, which, as a result, have become a staple of modern clinical research, that is, clinical trials such as STAR*D (Sequenced Treatment Alternatives to Relieve Depression) , epidemiWe had used Twitter previously to study vulnerability to mental health symptoms. For example, in a study, we reported that individuals who had disclosed that they were diagnosed with depression in their tweets  had different circadian patterns of Twitter activity than a random sample of Twitter users . SpecifiIn spite of the potential offered by social media data for research into the mechanisms involved in the development and maintenance of mental disorders, there are limitations to passively acquired social media data. A limitation is that social media users are not representative of the general population ,20. TherIt has also been hypothesized that differences in variables such as need for self-disclosure  may biasTo address these limitations of social media research, namely the lack of sample representativeness and inability to verify health status, we conducted the Studies of Online Cohorts for Internalizing Symptoms and Language (SOCIAL). SOCIAL are cohort-based studies in which we triangulated self-reported disorder screening questionnaires with data acquired from social media. Participants in SOCIAL I and II completed a series of disorder screening questionnaires focused on internalizing symptoms that are meant to capture psychopathology more broadly. They were also asked to provide their Twitter handles which we subsequently verified for validity, including how closely they resembled the behavior of bots. SOCIAL I is a sample of Twitter users (Methods section) targeted to be nationally representative in terms of age, sex assigned at birth, race, and ethnicity, and SOCIAL II is a large sample of college students.valid Twitter handles pointing to their own social media content and those who did not or refused. The latter group can be separated into three subgroups: (1) users who refused to provide a valid Twitter handle , (2) users who denied being Twitter users (not a Twitter user), and (3) users who did provide an existing Twitter handle, but the accounts were deemed to be bot-like as defined by a machine learning classifier [Here, we describe the baseline sociodemographic characteristics, social media use data, and mental health characteristics of individuals in SOCIAL I and II. Because we asked individuals to self-report whether they used Twitter and to give us access to their Twitter accounts, we could compare sociodemographic characteristics, social media use data, and mental health differences between groups of individuals depending on their willingness to share their social media data. We distinguished approximately 2 groups of participants: those who provided assifier .Both SOCIAL samples answered self-reported questionnaires probing internalizing, externalizing, somatoform, and thought disorder symptoms . We alsoSOCIAL I purposefully sampled individuals via Qualtrics panels. We aimed to recruit approximately 1000 Twitter users, given the budgetary constraints for this study. Individuals were recruited from July 2020 to March 2021 for a study on “social media and mental health.” The sample was selected to represent the United States at the intersections of age, gender, race and ethnicity.All individuals in SOCIAL I were Twitter users. Accordingly, we could not ascertain the role that being a Twitter user in itself has on potential differences between individuals in baseline sociodemographic characteristics, social media use, and mental health symptoms. To have a sample of individuals who did not use Twitter as well as to have an additional sample with which to assess the transportability of results from SOCIAL I, we began the SOCIAL II study. SOCIAL II recruited college students from a predominantly White and Asian university in the Midwest. Individuals were compensated with credits in an introductory psychology course. Individuals were recruited from September 2020 to the present date.For individuals in SOCIAL I and SOCIAL II, we collected information on characteristics described in the following sections.parents’ annual household income. We present both of these as the same variable . In addition, in SOCIAL I, we asked participants to indicate their race by using a single category from a list . In SOCIAL II, we allowed participants to select multiple racial and ethnic identities, including all the possibilities in SOCIAL I along with Middle Eastern or North African. We recoded the categories in SOCIAL II to fit a version of the race variable in SOCIAL I that identified whether individuals were non-Hispanic White, non-Hispanic Black, Hispanic, Asian, or other .Specifically, we collected age, political orientation on a 10-point Likert scale , race, ethnicity, sex assigned at birth , gender identity , and sexual orientation . In SOCIAL I, we asked participants for their annual household income. In SOCIAL II, we asked participants to estimate their Individuals who were Twitter users  were queried about how much time they spent on Twitter  a week; a few days (3-5) a week; about once a day; or several times a day). This item was selected on the basis that it was used by the Pew Research Center in a previous study on social media use in the United States. In addition, all individuals were queried about their use of Twitter as well as other social media platforms on a binary scale . We asked for a Twitter handle for all individuals in the study who identified that they were Twitter users. Individuals could choose to enter a valid Twitter handle or to enter text to bypass the question (eg “I don’t want to give my Twitter handle”).DSM severity measures -9 and PHQ-15 for depression and somatic symptoms, respectively). Given that all these measures have different response types and number of items, and accordingly different ranges, we standardized them all as percentage of maximum point (POMP) scores [We compiled a battery of self-report disorder screening questionnaires for psychopathology . These m) scores . The POMWe conducted preliminary analyses to describe the samples, including the ranges represented in the different variables. The results of these analyses suggested that individuals gave relatively high ratings of self-reported manic symptoms, a problem that has been previously reported in the literature assessing hypomanic symptoms via self-report. Zimmerman  suggestebot from its web-based behavior and content . As per recommendations of the Botometer developers, we explored the distribution of bot scores and created a cutoff of 0.42 to classify individuals as bot-like or valid users.All individuals who reported that they were Twitter users were asked to provide their Twitter handles, which identify the individual on Twitter. The Twitter application programming interface, a free and public interface provided by Twitter, provides access to an individual’s past tweets (timelines) via their individual handle (provided the tweets were public). Hence, for individuals who provided a Twitter handle, we retrieved individual timelines (a time-sorted record of their past tweets). We assessed whether the corresponding Twitter accounts were valid and belonged to real users using the Botometer application programming interface, an algorithm that uses machine learning to predict whether a given account belongs to a invalid handles if they refused to provide their handle, answered the question about handles with a response that was not a syntactically valid Twitter account , or if Botometer failed to access the Twitter account. In addition to these 3 groups , in SOCIAL II, we included individuals who denied being Twitter users (not a Twitter user). We focused on the differences between these 3-4 subgroups using Twitter users who did not provide handles or who provided handles that were not syntactically valid account names .Individuals were classified as providing All analyses were conducted using the R programming language (version 4.1.2)  in R StuP values from a Kruskal-Wallis rank-sum test. For categorical variables, we reported the P values from a chi-square test to assess whether Twitter group membership is significantly related to specific baseline characteristics  or the P values from Fisher exact test when a cell size is <5. To characterize the magnitude of these associations , for binary variables, we report odds ratios (ORs) with 95% CIs when using individuals who provided invalid user names as the reference group. For nominal variables , we report a Cramer V. For continuous variables, we report the standardized β values and 95% CIs, representing the differences in SD units of each variable in question.To assess statistically significant differences between the sociodemographic factors, social media use, and mental health variables, we tested the association of each of these variables  with group membership . For continuous variables, we reported the Both studies were approved by the Indiana University Institutional Review Board (2002549202 and 2005948214).bot-like. Most of those who used Twitter reported using the platform at least “several times a day.” Individuals were approximately split along the political spectrum and there appeared to be variability in sexual orientation, gender identity, and socioeconomic status. Hispanic and Asian individuals appeared to be underrepresented relative to the population from the United States.In SOCIAL I (N=1123), the average participant was in their mid-30s, although there was variability in the ages represented . ApproxiThere were various statistically significant demographic differences among individuals in SOCIAL I based on Twitter status . In geneIn SOCIAL I, all individuals were recruited to be Twitter users. Other social media platforms used by most of the sample were Facebook, Instagram, and YouTube . There aThe POMP scores for the various measures of psychopathology as well as the reported diagnoses are presented in In SOCIAL II (N=1988), age was more restricted to the range 18 to 22 years, as would be expected of undergraduate students . Second, there were differences in reported race and ethnicity by Twitter user status . Specifically, individuals who provided valid Twitter handles were less likely to be Hispanic than individuals who were Twitter users but did not provide their handles .In SOCIAL II, Instagram and Snapchat were the most popular platforms and were used by almost all individuals . TwitterThe POMP scores for the various measures of psychopathology as well as the reported diagnoses are presented in Our results suggest that it is feasible to collect social media data from individuals who also provide information about a breadth of mental health symptoms. We found no evidence that individuals who provide valid Twitter accounts are a biased sample when compared with individuals who provide invalid handles, do not provide their handles, do not use Twitter, or are classified as bot-like. The widespread availability of social media  has faciWe conducted the SOCIAL I and SOCIAL II studies to triangulate data and meta-data obtained from social media with a range of validated clinical self-reports of symptoms of distress , fear , substance use , somatoform problems , and potential thought disorder symptoms . However, a concern about studies triangulating clinical data and social media data remains that individuals who volunteer their social media accounts in such studies are not representative of individuals on social media in general . In thisSome limitations inherent in our data are worth considering. First, social media use, especially frequent social media use, is not a random and normally distributed variable. Evidence suggests, for example, that a small portion of users are responsible for a large number of tweets. Thus, future analyses of the SOCIAL I and II data sets and related data sets should consider the frequency of social media activity as well as the nature of that activity. In addition, the decision to enter a study focused on social media may in itself introduce a selection bias that we cannot guard against. Although our samples allow us to study mental health and social media across units of analysis , we lack more objective data including biomarkers or even observer reports of mental health symptoms. Importantly, although we did not conduct semistructured interviews about mental disorder diagnoses, the diagnosis of mental disorders is largely influenced by the severity of symptoms . For manDespite the fact that social media samples are not representative of the entire population, social media users represent 20%-70% of all individuals in the United States , therebyWith these data sets, we can triangulate self-reported clinical data and data collected from social media. In both samples, mental health symptoms were relatively well represented, making them good, large-scale samples for studying psychopathology. Our current analyses suggest that individuals in these data sets who volunteered to give their Twitter handle, and provided a valid handle, were not different from other individuals in terms of their demographic characteristics, social media use, and mental health. A future direction for this line of work is to use self-reported mental health to replicate findings in which mental health is inferred through social media activity. Another direction is to extend the data collection to include ecological momentary assessments to triangulate to what extent social media behavior is a valid window into individuals’ mental health.


The development of pharmaceutical dosage forms that are tailored to specific populations according to their preferences and acceptability could improve medication adherence, which could lead to effective pharmacotherapy. This study evaluated the preference for and perceptions of fluid gels as a potential age-appropriate dosage form for older adults with dysphagia. The palatability and swallowability of the developed fluid gels were also assessed to determine the consumer acceptability of this formulation. A cross-sectional survey was conducted through the electronic distribution of a self-administered questionnaire among adults in Malaysia between April and December 2021. A randomized and double-blinded clinical study was conducted to evaluate the palatability and swallowability of the fluid gels in 30 healthy participants. A cross-sectional study involving 673 respondents revealed that the fluid gels were perceived positively by consumers (64.4%), were easily swallowed (50.8%), were safe to be consumed (45.3%), and were suitable as a new pharmaceutical formulation (43.8%). The clinical study shows that moderately thickened fluid gels masked the bitterness of the medication and were easily swallowed. The newly developed fluid gels were also positively perceived by the participants. Taken together, fluid gels have shown great potential as an innovative oral formulation that is suitable for consumption by elderly patients with dysphagia. Patient acceptance of medicines is a fundamental aspect in the development of pharmaceutical dosage forms, and it is essential for pharmacotherapy adherence and effectiveness. Patient acceptability is defined as the willingness and capability of the end users and their caregivers to administer and use the medicine as intended . It is iLiquid formulations are crucial for specific populations, such as pediatrics, geriatrics, and patients with dysphagia who commonly have difficulties in swallowing, as they are easy to swallow and offer a flexible dosage . HoweverDysphagia is a major geriatric syndrome with high prevalence among elderly patients. Owing to the difficulty in swallowing, older patients with dysphagia require an appropriate oral dosage form, or a modification of the dosage form, for safer administration of the oral medication. In general, increasing the bolus viscosity is widely practiced as a strategy for the management of dysphagia ,11. HighA fluid gel is a suspension of microgel particles that is produced by applying shear force during the gelation of a biopolymer solution . Fluid gIn total, 673 participants completed the questionnaire. The participants included 324 men (48.1%), with a mean (±SD) age of 36.2 (±12.7) years. A total of 437 respondents were working, while the remaining 236 were unemployed , with 31.2% (n = 210) of the respondents having monthly incomes of more than RM 5001 (USD 1186.76). The demographic information of the respondents is presented in p = 0.949), gender (p = 0.253), occupation (p = 0.246), and monthly income (p = 0.417) in terms of the preference toward liquid formulations. The preferences, according to the respondents’ social demography, are listed in Flavored liquid formulations (74.1%) with smooth textures (69.1%) and an absence of solid materials (65%) were the preferred formulations. Natural flavors, such as bee honey, were preferred over synthetic (78.1%) flavors. The formulations were also preferred if reconstitution was not required (81.4%) and if they could be taken in small doses (70.8%). However, almost half of the respondents preferred to take solid medicines, such as tablets or capsules, compared to liquid medicines (46.9%), particularly while travelling (71.1%). The preferred characteristics of the liquid formulation are shown in p < 0.001) in the age group >45 years , pensioners , and people with monthly incomes of more than RM 5001 , as shown in Most of the respondents did not have any difficulties or problems in administering liquid oral medications. The rejection factors for liquid formulations are listed in p = 0.006) and self-employed individuals .The perceived benefits and risks of fluid gels are illustrated in p = 0.021). Moreover, there was a significant positive and weak correlation between the subject’s preference for liquid formulation and the subject’s perceived benefit of fluid gels , and a nonsignificant negative and very weak correlation between the subject’s negative perception and the perceived benefit of fluid gels .There was a significant negative and very weak correlation between the subject’s preference for liquid formulation and the subject’s negative perception (rejection) toward liquid formulation , and Wilcoxon’s signed rank test comparing each pair showed a significant difference between Samples A and B (p < 0.001) and Samples B and C (p = 0.013).A thicker fluid gel of 0.5% gellan gum (VAS score = 51.23) was able to mask the intensity of medication bitterness better than a thinner fluid gel of 0% gellan gum (VAS score = 64.73) a. Howevep < 0.001). Wilcoxon’s signed rank test comparing each pair showed a significant difference between Samples D and E and Samples D and F, both with p < 0.001. However, no significant difference was observed between the thickened fluid gel (Samples E and F (p = 0.106)).All of the fluid gels were easy to swallow, with mean VAS scores of 17.27, 44.87, and 55.03 for Samples D, E, and F, respectively b. A thinp < 0.001), as shown in The results of the sensory assessment are summarized in Novel pharmaceutical formulations that minimize toxicity and improve drug efficacy offer many benefits to consumers and new avenues for pharmaceutical companies. As patients are the end users of medicines, the prescribers and pharmaceutical industries need to understand their preferences and their acceptability of medicines in order to nurture adherence to cost-effective therapies. Adherence to pharmaceutical formulations is affected by multidimensional aspects, including the palatability and swallowability of the formulation, as well as consumer preferences and perceptions toward the formulation. This study explored the preference toward and acceptability of a novel fluid gel so that it can be used as an alternative formulation to deliver medicine effectively and safely, particularly in the younger generation, the elderly, and in patients with dysphagia.The fluid gels were perceived to be easily swallowed and safe for consumption. This finding is in agreement with that of previous studies that report that a fluid with sufficient viscosity can be easily swallowed without causing any discomfort ,16,17. AThis study discovered that flavored medications were preferred by consumers, which is in agreement with other studies ,18. MediUnlike solid dosage forms, masking the bitterness of liquid formulations is difficult and leads to a high rejection rate among patients . MaskingThis study found that all the fluid gels were easily swallowed, probably because of the smooth texture of the formulation. Thin liquids are the easiest to swallow by healthy individuals, compared to thickened liquids, as they require less effort in swallowing ,23. ThinThe thickened fluid gels also had a low positive overall likeness as compared to the thin fluid gels among the healthy volunteers in this study. Low positive ratings toward thickened fluid gels may result from neophobia, which is a predisposition to reject formulations from a lack of experience with new products ,25. VariA majority of the respondents agreed that fluid gels and liquid formulations are more suitable for the young and the elderly than solid medicines, mainly because these groups cannot easily swallow solid medicines . Liquid This study has a few limitations. First, we recruited participants who self-assessed as healthy and who were able to self-administer online questionnaires, which excluded dysphagic patients or people diagnosed with swallowing difficulties. Therefore, studies that focus on these populations should be conducted to further investigate their acceptance toward fluid gels. Second, the perceptions of the respondents from an online questionnaire toward fluid gels were merely based on presumption, as most of the respondents had never had any experience in consuming a fluid gel. However, a clear illustration of the fluid gel was provided before the respondents answered the survey. This study provides preliminary data on fluid gels, upon which further investigation should be conducted. Further research is needed to formulate fluid gels in a pharmaceutical dosage form and to determine the ease of swallowing by patients to ensure their safety. The findings of this study strongly suggest that the pharmaceutical industry should consider manufacturing liquid gel formulations, as they are preferred by consumers and could benefit young children, the elderly, and patients with dysphagia.In summary, fluid gels were perceived positively by the healthy volunteers and the general population, and they can be formulated as an oral dosage form. Several formulation characteristics are important to increase the consumers’ preferences for liquid dosage forms, such as pleasant flavor, and ease of swallowing and measurement. Fluid gel that was thickened to a medium consistency (0.5% gellan gum) was able to mask medicine bitterness and could be swallowed easily. Thus, a novel pharmaceutical formulation that addresses problems that are associated with specific populations, and that is formulated with the most preferred characteristics, is expected to increase consumer medication acceptability and adherence, which is highly vital in elderly patients that are dependent on their pharmacotherapy.A cross-sectional survey and a clinical trial were conducted to enhance patient adherence by comprehending their preferences toward and acceptability of fluid gels. The survey assessed the patients’ preferences, the rejection factors, and the perceived benefits and risks with regard to fluid gels. A clinical study was conducted by evaluating the palatability and swallowability of fluid gels in 30 healthy participants. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee  (PPI/111/8/JEP-2021-596), and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.A cross-sectional survey was conducted through the electronic distribution of a self-administered questionnaire to the general adult population in Malaysia between April and December 2021, through an online survey form that used a five-point Likert scale. Social media networks were used to obtain suitable responses. Those who did not complete the survey were excluded from the study. The first section of the questionnaire consisted of the respondents’ demographic information, including age, sex, ethnicity, occupation, and monthly income. The second section outlined their preferences toward two oral liquid medicines . The definitions of the conventional and novel fluid gel formulations were provided at the beginning of the questionnaire. All key pharmaceutical characteristics of an ideal oral formulation, such as the texture, stability, flavor, administration, and storage, were included and were based on a five-point Likert scale (from 1 = strongly disagree to 5 = strongly agree). Questions that were negatively worded were reverse scored before summing the scores for each question. High scores signify positive preferences for liquid formulations, whereas low scores indicate negative preferences. The third section of the questionnaire focused on the factors that influence the preferences toward liquid formulations for medicine, using yes or no answers. Finally, the fourth section of the questionnaire asked about the perceived benefits and risks of the newly developed fluid gels on the basis of a five-point Likert scale (from 1 = strongly disagree to 5 = strongly agree). The scores were taken from the sum of the answers to all the items. As all the statements were positively worded, except for the risk-related questions ), low scores signified the negatively perceived benefits and risks of the fluid gel, whereas high scores indicated the positively perceived benefits and risks. All questions were developed and/or adapted from previous studies ,6,8.The development, pretesting, and piloting of the research questionnaire was accomplished on the basis of the principles of patient and public involvement (PPI) in research. A small-scale informal pilot of the questionnaire was conducted with 10 participants to ensure the face validity, to assess the comprehension of the questionnaire, and to improve the study by considering the feedback of the respondents. Following the pilot phase, minor changes were made to the questionnaire to improve the clarity. The total Cronbach’s alpha score was in the range of 0.963–0.988, which indicates good reliability and internal consistency. Paracetamol, low-acetylated gellan gum (Gelzan), poly(ethylene glycol), and sodium citrate were purchased from Sigma-Aldrich . Propylene glycol and citric acid were obtained from Nacalai Tesque, Inc., Kyoto, Japan. Methyl paraben (sc-218815) was obtained from Santa Cruz Biotechnology. Food-grade xylitol powder , honey powder (A&T Ingredients Sdn. Bhd.), and sucralose  were purchased from local suppliers.Fasiliti Loji Pandu Makanan), at the Faculty of Science and Technology, the Universiti Kebangsaan Malaysia. Fluid gels with viscosities suitable for different levels of dysphagia, as recommended by the International Dysphagia Diet Standardization Initiative [The fluid gels were prepared in a good manufacturing practice (GMP)-compliant facility for food processing  and the power of the study (80%), respectively. α is the estimated standard deviation, and Δ is the estimated effect size  [This single-center randomized double-blinded study was conducted at the Hospital Canselor Tuanku Muhriz UKM in Kuala Lumpur, Malaysia, in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki). All the participants in this study were recruited through advertisements on social media platforms. Eligible healthy adults aged 18–35 years were included in the study. We excluded from this study individuals with illnesses such as cough and flu; those who were using prescribed medication during the study period; those who had allergies, or the history of an allergy, to any component in the formulations; smokers; pregnant women; and nursing mothers. The sample size was calculated as follows :n = 2 × control) . TherefoThe participants underwent four sessions within a single visit: (1) Training for the bitterness evaluation; (2) Palatability testing; (3) Swallowability testing; and (4) Preference and perception evaluations of fluid gels. The participants were trained in the first session using three different concentrations of the paracetamol solution  in order to standardize the participant bitterness. Participants first tasted 5 mL of each solution by holding it in their mouth for 60 s and spitting it out without swallowing. They were informed of the numerical value and taste description of the solution . Taste masking was evaluated in the second session, in which all participants gargled 5 mL of Samples A, B, and C in their mouth for 60 s and then spat it out. For the third session, the participants swallowed 5 mL samples of the blank fluid gels ) in their usual manner to evaluate the ease of swallowing. In the sensory evaluation, the participants were blinded to minimize the bias. The participants were assisted by an unblinded assistant who was responsible for the sample preparation. The samples were given in a randomized order to prevent sequential bias. The sample sequence assignment was determined by using blocked randomization (block size = 6) to ensure balance across the study recruitment period . A 10 miData were entered and analyzed using the Statistical Package for Social Science (SPSS) Version 19 . Descriptive results were presented as frequencies, percentages, means (±SD), and medians. Nonparametric tests, such as two-independent sample tests and tests for several independent samples, and statistical analyses were used to determine significant associations between each variable. Correlation, the Mann–Whitney U test, and the Kruskal–Wallis H test were used in the cross-sectional study. Pearson correlations were used to examine the relationships between the preference and negative perception toward liquid formulations, and the perceived benefits of fluid gels.p-value less than 0.05 for all analyses, except for the pairwise comparison of the fluid gel samples .For the sensory analysis, Friedman’s ANOVA (nonparametric test for related samples) was used to screen for differences between samples, and Wilcoxon’s signed-rank test was used to determine differences between individual sample pairs. A significant level was accepted at a


People with HIV (PWH) who are initiated on guidelines-recommended first-line INSTI-based antiretroviral therapy routinely achieve rapid virologic suppression; however, those with a high baseline (BL) HIV-1 RNA and/or low CD4 count may be more challenging to manage in the short- and long-term. To further characterize long-term outcomes over 5 years in select subgroups, we analyzed results from two studies examining B/F/TAF as initial treatment stratified by BL HIV-1 RNA and/or CD4 count.Adults with HIV were randomized to receive blinded initial treatment with B/F/TAF versus dolutegravir [DTG]/abacavir/lamivudine (Study 1489) or DTG+F/TAF (1490) for 144 weeks (W) of blinded treatment followed by an optional switch to open-label B/F/TAF for 96W. We present virologic response  and study drug-related adverse events (DRAE) from a pooled analysis of participants originally randomized to B/F/TAF who had BL HIV-1 RNA 100,00-400,000 copies(c)/mL, HIV-1 RNA >400,000 c/mL and/or CD4 count < 200 cells/µL through W240.634 adults  originally randomized to B/F/TAF were included for analysis. At BL, 80 participants had a BL CD4 count < 200 cells/µL and 119 participants had HIV-1 RNA >100,000 c/mL, of whom, 20 had HIV-1 RNA >400,000 c/mL. At W240, virologic suppression was high for the low CD4 count and/or high HIV-1 RNA subgroups (Table). No participant in the final resistance analysis developed virologic resistance to any component of B/F/TAF. Across the subgroups, the most common DRAEs were nausea, headache and diarrhea and there were no serious DRAEs. There was only one discontinuation due to a DRAE in the low CD4 count subgroup, and none in the high HIV-1 RNA subgroup.Initial treatment with B/F/TAF was safe and efficacious over 5 years of follow-up in people with a high BL HIV-1 RNA and/or low CD4 count. These outcomes provide additional evidence that B/F/TAF is an effective and durable regimen for a broad range of PWH, including those with advanced disease.Moti Ramgopal, MD, FACP, FIDSA, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Speakers Bureau|Janssen: Advisor/Consultant|Janssen: Speakers Bureau|Merck: Advisor/Consultant|Merck: Speakers Bureau|ViiV: Advisor/Consultant|ViiV: Speakers Bureau Axel Baumgarten, MD, AbbVie: Honoraria|Gilead Sciences: Honoraria|Janssen: Honoraria|MSD: Honoraria|ViiV: Honoraria Anton Pozniak, MD, FRCP, Gilead: Grant/Research Support|Gilead: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|Merck: Honoraria|theratec: Honoraria|ViiV: Grant/Research Support|ViiV: Honoraria Chloe Orkin, MBChB, FRCP, MD, Gilead Sciences: Honoraria|GSK: Honoraria|Janssen: Honoraria|MSD: Honoraria Juan Manuel Tiraboschi, PhD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|MSD: Advisor/Consultant|MSD: Grant/Research Support|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support Debbie P. Hagins, MD, FAPCR, AAHIVS, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Speakers Bureau|Janssen: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|ViiV: Advisor/Consultant|ViiV: Grant/Research Support Hailin Huang, PhD, Gilead Sciences, Inc.: Employer|Gilead Sciences, Inc.: Stocks/Bonds Kristin Andreatta, MSc, Gilead Sciences, Inc: Employee of Gilead Sciences|Gilead Sciences, Inc: Stocks/Bonds Nathan Unger, PharmD, AAHIVP, Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds Jason Hindman, PharmD, MBA, Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds Hal Martin, MD, Gilead Sciences: employee|Gilead Sciences: Stocks/Bonds Jared Baeten, MD, PhD, Gilead Sciences: Employee|Gilead Sciences: Stocks/Bonds Olayemi Osiyemi, MD, Gilead: Advisor/Consultant|gsk: Advisor/Consultant|viiv: Advisor/Consultant.