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Abstract Background and Aim High autoimmune hepatitis (AIH) and overlap syndrome (OS) prevalence have been previously documented among Alaska Native people. The purpose of this project is to report changes in AIH/OS prevalence over time, clinical characteristics, and factors associated with biochemical remission. Methods We reviewed medical records for Alaska Native/American Indian (AN/AI) patients diagnosed with AIH/OS between 1984 and 2021. Point prevalence was calculated based on AIH/OS patients alive at the end of 2021 and at 5‐year intervals from July 1, 2000, to July 1, 2020. Results We identified 189 AN/AI persons diagnosed with AIH or OS (157 AIH, 32 OS). Of these 189, 137 were alive at the end of 2021 for a point prevalence of 91.2 per 100 000 (95% confidence interval [CI]: 77.2–107.8)—75.9 (95% CI: 63.2–91.2) for AIH and 15.3 (95% CI: 10.2–23.0) for OS. Prevalence for both AIH and OS has risen steadily since 2000. Eighty‐nine consented participants (62.7%) achieved biochemical remission with a median time from diagnosis to start of remission of 1.9 years (IQR 0.5–5.0 years). Consented patients with fatty liver were less likely to achieve remission, but their time to remission was shorter than for patients without fatty liver. Conclusion The AN/AI population in Alaska continues to have the highest reported prevalence of AIH/OS in the world, with prevalence rising steadily since 2000. High reported AIH/OS prevalence is likely due in part to strong referral networks for liver disease. Detection and treatment can lead to biochemical remission and improved health outcomes.

In this work, we construct a new model of compact stars in the presence of anisotropic matter in the Rastall theory of gravity. For this, we considered the anisotropic matter content when formulating the Rastall field equations. Secondly, the Tolman–Oppenheimer–Volkoff (TOV) equation in the context of Rastall theory is formulated. We apply the Finch–Skea ansatz in the static and spherically symmetric geometry to obtain the analytic solution of the derived field equations in the Rastall theory of gravity. We match the internal solution to the corresponding external Schwarzschild space-time in order to determine the values of the unknown constants involved in the Rastall field equations due to the Finch–Skea ansatz. The resulting model is applied to a few prominent compact stars in order to verify its physical viability. Energy conditions, the TOV equation, stability analysis via sound speeds (radial and transverse in this case), equation of state parameters, mass function, compactness, and surface redshift are some of the analytical expressions that are examined in this inquiry. In order to verify the physical acceptance of the obtained results, we provided a graphical analysis of some necessary analytical expressions. Also, the numerical values of some physical parameters are calculated and are presented in the tabular form to observe the Buchdahl limit and some other important criterion. We note that our model is well consistent with the physical requirements.

The CD38-targeting antibody daratumumab has marked activity in multiple myeloma (MM). Natural killer (NK) cells play an important role during daratumumab therapy by mediating antibody-dependent cellular cytotoxicity via their FcγRIII receptor (CD16), but they are also rapidly decreased following initiation of daratumumab treatment. We characterized the NK cell phenotype at baseline and during daratumumab monotherapy by flow cytometry and cytometry by time of flight to assess its impact on response and development of resistance (DARA-ATRA study; NCT02751255). At baseline, nonresponding patients had a significantly lower proportion of CD16+ and granzyme B+ NK cells, and higher frequency of TIM-3+ and HLA-DR+ NK cells, consistent with a more activated/exhausted phenotype. These NK cell characteristics were also predictive of inferior progression-free survival and overall survival. Upon initiation of daratumumab treatment, NK cells were rapidly depleted. Persisting NK cells exhibited an activated and exhausted phenotype with reduced expression of CD16 and granzyme B, and increased expression of TIM-3 and HLA-DR. We observed that addition of healthy donor-derived purified NK cells to BM samples from patients with either primary or acquired daratumumab-resistance improved daratumumab-mediated MM cell killing. In conclusion, NK cell dysfunction plays a role in primary and acquired daratumumab resistance. This study supports the clinical evaluation of daratumumab combined with adoptive transfer of NK cells.

Abstract The occurrence of hematuria during a right heart catheterization can be a sign of renal perforation, a rare but life‐threatening complication that could be developed due to the misdirection of wire into the abdominopelvic venous plexus. We showed this complication could be managed with venoplasty of the common iliac vein.

Abstract Background and Aims In Myanmar, public sector treatment programs for hepatitis C virus (HCV) infection were nonexistent until June 2017. WHO highlights the importance of simplification of HCV service delivery through task‐shifting among health workers and decentralization to the primary health care level. Between November 2016 and November 2017, a study was conducted to describe the epidemiological data and real‐world outcomes of treating HIV/HCV coinfected patients with generic direct acting antiviral (DAA) based regimens in the three HIV clinics run by nonspecialist medical doctors in Myanmar. Methods HCV co‐infection among people living with HIV (PLHIV) from two clinics in Yangon city and one clinic in Dawei city was screened by rapid diagnostic tests and confirmed by testing for viral RNA. Nonspecialist medical doctors prescribed sofosbuvir and daclatasvir based regimens (with or without ribavirin) for 12 or 24 weeks based on the HCV genotype and liver fibrosis status. Sustained virologic response at 12 weeks after treatment (SVR12) was assessed to determine cure. Results About 6.5% (1417/21,777) of PLHIV were co‐infected with HCV. Of 864 patients enrolled in the study, 50.8% reported history of substance use, 27% history of invasive medical procedures and 25.6% history of incarceration. Data on treatment outcomes were collected from 267 patients of which 257 (96.3%) achieved SVR12, 7 (2.6%) failed treatment, 2 (0.7%) died and 1 (0.4%) became loss to follow‐up. Conclusion The study results support the integration of hepatitis C diagnosis and treatment with DAA‐based regimens into existing HIV clinics run by nonspecialist medical doctors in a resource‐limited setting. Epidemiological data on HIV/HCV co‐infection call for comprehensive HCV care services among key populations like drug users and prisoners in Yangon and Dawei.

In this investigation, the exact solutions of variable coefficients of generalized Zakharov-Kuznetsov (ZK) equation and the Gardner equation are studied with the help of an extended generalized G′/G expansion method. The main objective of this study is to establish the closed-form solutions and dynamics of analytical solutions to the generalized ZK equation and the Gardner equation. The generalized ZK equation and the Gardner equation govern the behavior of nonlinear wave phenomena in the presence of magnetic field in plasma dynamics, turbulence, bottom topography, and quantum field theory. We construct innovative solutions to the models under consideration using various computing tools and a recently developed extended generalized G′/G expansion technique. The extended generalized G′/G expansion technique is a well-defined and simple technique which is based on the initial assumed solutions of the polynomial of G′/G. The derived solutions for both the equations are the hyperbolic, trigonometric, and rational functions. The obtained solutions have shock/kink waves and multisoliton, which depict the dynamical representations of the acquired solutions through the three-dimensional surface plots and the contour plots.

Abstract Fluorescence‐guided surgery (FGS) aids surgeons with real‐time visualization of small cancer foci and borders, which improves surgical and prognostic efficacy of cancer. Despite the steady advances in imaging devices, there is a scarcity of fluorophores available to achieve optimal FGS. Here, 1) a pH‐sensitive near‐infrared fluorophore that exhibits rapid signal changes in acidic tumor microenvironments (TME) caused by the attenuation of intramolecular quenching, 2) the inherent targeting for cancer based on chemical structure (structure inherent targeting, SIT), and 3) mitochondrial and lysosomal retention are reported. After topical application of PH08 on peritoneal tumor regions in ovarian cancer‐bearing mice, a rapid fluorescence increase (< 10 min), and extended preservation of signals (> 4 h post‐topical application) are observed, which together allow for the visualization of submillimeter tumors with a high tumor‐to‐background ratio (TBR > 5.0). In addition, PH08 is preferentially transported to cancer cells via organic anion transporter peptides (OATPs) and colocalizes in the mitochondria and lysosomes due to the positive charges, enabling a long retention time during FGS. PH08 not only has a significant impact on surgical and diagnostic applications but also provides an effective and scalable strategy to design therapeutic agents for a wide array of cancers.

Abstract Deferoxamine (DFO) is an FDA‐approved iron‐chelating agent which shows good therapeutic efficacy, however, its short blood half‐life presents challenges such as the need for repeated injections or continuous infusions. Considering the lifelong need of chelating agents for iron overload patients, a sustained‐release formulation that can reduce the number of chelator administrations is essential. Here, injectable hydrogel formulations prepared by integrating crosslinked hyaluronic acid into Pluronic F127 for an extended release of DFO nanochelators are reported. The subcutaneously injected hydrogel shows a thermosensitive sol–gel transition at physiological body temperature and provides a prolonged release of renal clearable nanochelators over 2 weeks, resulting in a half‐life 47‐fold longer than that of the nanochelator alone. In addition, no chronic toxicity of the nanochelator‐loaded hydrogel is confirmed by biochemical and histological analyses. This injectable hydrogel formulation with DFO nanochelators has the potential to be a promising formulation for the treatment of iron overload disorders.

In this paper, we introduce new coincidence fixed point theorems for generalized ϕ,ψ-contractive mappings fulfilling kind of an admissibility provision in a Hausdorff b-rectangular metric space with the support of C-functions. We applied our results to establish the existence of a solution for some integralitions. Finally, an example is presented to clarify our theorem.

The Cattaneo-Christov model will be used to examine the significance of heat generation, viscous dissipation, and thermal radiation on a double-diffusive MHD flow in this study. In this study, it was discovered that heat and mass transfer can be affected by nonlinear buoyancy significance. The flow direction was subjected to a uniform magnetic field. A set of partial differential equations governs the current design (PDEs). In order to simplify these equations, they are converted into ordinary differential equations (ODEs). In order to numerically solve the nonlinear ODEs, the spectral relaxation method (SRM) is utilized. In order to decouple and linearize the equation sets, the SRM employs the Gauss-Seidel relaxation method. Geothermal power generation and underground storage systems are just a few examples where this research could be put to use. When compared to previous findings, the current outcomes were discovered to be closely related. Owing to an increase in Lorentz force, the imposed magnetic field slows down fluid motion. Viscosity dissipation and heat generation all contribute to the formation of an ever-thicker thermal boundary layer. When the Cattaneo-Christov models are used, the thermal and concentration boundary layers get a lot thicker.

Abstract Many processes throughout the heliosphere such as flares, coronal mass ejections (CMEs), storms and substorms have abrupt onsets. The waiting time between these onsets provides key insights as to the underlying dynamical processes. We explore the tail of these waiting time distributions (WTDs) in the context of random processes driven by the solar magnetic activity cycle, which we approximate by a sinusoidal driver. Analytically, we find that the distribution of large waiting times of such a process approaches a power law slope of −2.5, which is primarily controlled by the conditions when the driving is minimum. We find that the asymptotic behavior of WTDs of solar flares, CMEs, geomagnetic storms, and substorms exhibit power laws that are in reasonable agreement with a sinusoidally driven nonstationary Poisson process. However, the WTD of substorms during solar minimum may be more consistent with prolonged periods of weak driving followed by abrupt increase in the rate.

In this paper, authors prove new variants of Hermite–Jensen–Mercer type inequalities using ψ–Riemann–Liouville fractional integrals with respect to another function via convexity. We establish generalized identities involving ψ–Riemann–Liouville fractional integral pertaining first and twice differentiable convex function λ, and these will be used to derive novel estimates for some fractional Hermite–Jensen–Mercer type inequalities. Some known results are recaptured from our results as special cases. Finally, an application from our results using the modified Bessel function of the first kind is established as well.

In this paper, we present a new class of sextic trigonometric Bernstein (ST-Bernstein, for short) basis functions with two shape parameters along with their geometric properties which are similar to the classical Bernstein basis functions. A sextic trigonometric Bézier (ST-Bézier, for short) curve with two shape parameters and their geometric characteristics is also constructed. The continuity constraints for the connection of two adjacent ST-Bézier curves segments are discussed. Shape control parameters can provide an opportunity to modify the shape of curve as designer desired. Some open and closed curves are also part of this study.

This work presents the new cubic trigonometric Bézier-type functions with shape parameter. Basis functions and the curve satisfy all properties of classical Bézier curve-like partition of unity, symmetric property, linear independent, geometric invariance, and convex hull property and have been proved. The C3 and G3 continuity conditions between two curve segments have also been achieved. To check the applicability of proposed functions, different types of open and closed curves have been constructed. The effect of shape parameter and control points has been observed. It is observed that, by decreasing the value of shape parameter, the curve moves toward the control polygon and vice versa. The CT-Bézier curve is closer to the cubic Bézier curve for a fixed value of shape parameter. The proposed CT-Bézier curve can be used to represent ellipse. Using proposed basis functions, we have constructed the spiral segment which is very useful to construct fair curves and desirable to design trajectories of mobile robots, highway, and railway routes’ designing.

Various polymerase chain reaction- (PCR-) based methods with varying positivity rates were designed to detect the Helicobacter pylori babA2 gene. To compare different primer sets, babA2 prevalence was determined in 279 H. pylori-positive pediatric samples using the 832 bp, 139 bp, and 271 bp PCR primer sets, resulting in 34.0%, 51.3%, and 79.6% prevalence of the babA2 gene, respectively. The babA2 status determined using the 832 bp and 139 bp PCR primer sets significantly correlated with bacterial density and activity of inflammation, whereas no such correlations were found using the 271 bp PCR primer set. The 139 and 832 bp PCR primer sets concordantly detected the babA2 gene in 93 cases; however, in comparison to the 832 bp PCR primer set, the 139 bp PCR primer set detected additional 50 babA2 cases, whereas only two 832 bp positive cases were missed. The 271 bp PCR primer set missed 32 babA2 cases that were 832 bp and/or 139 bp PCR positive, but tested solely positive in 109 cases. Interestingly, cloning of a subset of 271 bp PCR positive samples revealed amplification of the babA/B gene chimera. Hence, in our opinion, the 271 bp PCR protocol is not a reliable diagnostic tool for detecting the babA2 gene in children. Our results reaffirm previous observations that the use of certain babA2 PCR primer sets can significantly impact estimation of the prevalence and clinical relevance of the H. pylori babA2 gene in children, suggesting babA2 detection methods should be carefully selected.

Abstract Introduction Reward and stress are important determinants of motivated behaviors. Striatal regions play a crucial role in both motivation and hedonic processes. So far, little is known on how cognitive effort interacts with stress to modulate reward processes. This study examines how cognitive effort (load) interacts with an unpredictable acute stressor (threat‐of‐shock) to modulate motivational and hedonic processes in healthy adults. Materials and Methods A reward task, involving stress with unpredictable mild electric shocks, was conducted in 23 healthy adults aged 20–37 (mean age: 24.7 ± 0.9; 14 females) during functional magnetic resonance imaging (fMRI). Manipulation included the use of (a) monetary reward for reinforcement, (b) threat‐of‐shock as the stressor, and (c) a spatial working memory task with two levels of difficulty (low and high load) for cognitive load. Reward‐related activation was investigated in a priori three regions of interest, the nucleus accumbens (NAcc), caudate nucleus, and putamen. Results During anticipation, threat‐of‐shock or cognitive load did not affect striatal responsiveness to reward. Anticipated reward increased activation in the ventral and dorsal striatum. During feedback delivery, both threat‐of‐shock and cognitive effort modulated striatal activation. Higher working memory load blunted NAcc responsiveness to reward delivery, while stress strengthened caudate nucleus reactivity regardless reinforcement or load. Conclusions These findings provide initial evidence that both stress and cognitive load modulate striatal responsiveness during feedback delivery but not during anticipation in healthy adults. Of clinical importance, sustained stress exposure might go along with dysregulated arousal, increasing therefore the risk for the development of maladaptive incentive‐triggered motivation. This study brings new insight that might help to build a framework to understand common stress‐related disorders, given that these psychiatric disorders involve disturbances of the reward system, cognitive deficits, and abnormal stress reactivity.

Despite the role of epidermal growth factor receptor (EGFR) signaling in head and neck squamous cell carcinoma (HNSCC) development and progression, clinical trials involving EGFR tyrosine kinase inhibitors (TKIs) have yielded poor results in HNSCC patients. Mechanisms of acquired resistance to the EGFR TKI erlotinib was investigated by developing erlotinib‐resistant HNSCC cell lines and comparing their gene expression profiles with their parental erlotinib‐sensitive HNSCC cell lines using microarray analyses and subsequent pathway and network analyses. Erlotinib‐resistant HNSCC cells displayed a significant upregulation in immune response and inflammatory pathways compared to parental cells. Interleukin‐6 (IL‐6) was one of thirteen genes that was significantly differentially expressed in all erlotinib‐resistant HNSCC cell lines, which was validated using RT‐PCR and ELISA. Blockade of IL‐6 signaling using the IL‐6 receptor antagonist tocilizumab, was able to overcome erlotinib‐resistance in erlotinib‐resistant SQ20B tumors in vivo. Overall, erlotinib‐resistant HNSCC cells display elevated IL‐6 expression levels compared to erlotinib‐sensitive HNSCC cells and blockade of the IL‐6 signaling pathway may be an effective strategy to overcome resistance to erlotinib and possibly other EGFR TKIs for HNSCC therapy.