Kramerashworth0008
3 that regulated expression of CTLA4. In addition, variants near STAT1/STAT4 (rs11889341 OR =1.24; p=1.34×10
), LINC00392 (rs9564997 OR =0.81; p=2.53×10
), IRF8 (rs11117432 OR =0.72; p=6.10×10
), and LILRA4/LILRA5 (rs11084330 OR =0.65; p=5.19×10
) had suggestive association signals with AIH.
Our study identifies two novel loci (CD28/CTLA4/ICOS and SYNPR) exceeding genome-wide significance and suggests four loci as potential risk factors. These findings highlight the importance of costimulatory signaling and neuro-immune interaction in the pathogenesis of AIH.
Our study identifies two novel loci (CD28/CTLA4/ICOS and SYNPR) exceeding genome-wide significance and suggests four loci as potential risk factors. These findings highlight the importance of costimulatory signaling and neuro-immune interaction in the pathogenesis of AIH.
The goal of this work is to provide temperature and concentration calibration of water diffusivity in polyvinylpyrrolidone (PVP) solutions used in phantoms to assess system bias and linearity in apparent diffusion coefficient (ADC) measurements.
ADC measurements were performed for 40 kDa (K40) PVP of six concentrations (0%, 10%, 20%, 30%, 40%, and 50% by weight) at three temperatures (19.5°C, 22.5°C, and 26.4°C), with internal phantom temperature monitored by optical thermometer (±0.2°C). To achieve ADC measurement and fit accuracy of better than 0.5%, three orthogonal diffusion gradients were calibrated using known water diffusivity at 0°C and system gradient nonlinearity maps. Noise-floor fit bias was also controlled by limiting the maximum b-value used for ADC calculation of each sample. The ADC temperature dependence was modeled by Arrhenius functions of each PVP concentration. The concentration dependence was modeled by quadratic function for ADC normalized by the theoretical water diffusion values. the reported calibration can be used for quality control and standardization of measured ADC values of PVP at different concentrations and temperatures.
The study provides ground-truth ADC values for K40 PVP solutions commonly used in diffusion phantoms for scanning at ambient room temperature. The described procedures and the reported calibration can be used for quality control and standardization of measured ADC values of PVP at different concentrations and temperatures.
Although statins are the cornerstone of lipid management, hardly any of the existing studies on statin treatment of dyslipidemia in nephrotic syndrome (NS) addressed patient-centered outcomes of cardiovascular events.
To evaluate whether statin treatment impacts the outcomes of cardiovascular events in patients with NS.
A single-center, retrospective, nested case-control study analyzed data from the First Affiliated Hospital of Army Medical University.
Patients diagnosed with NS from January 1, 1999, to November 30, 2014, were selected and followed up for 5years.
A total of 2706 patients with NS were enrolled in this study cohort. Among these, 115 patients diagnosed with cardiovascular disease (CVD) at the end of the observational period and 235 CVD-free controls enrolled by 12matching with gender, age, and index time were included in the study. Propensity score matching was used to match (11) the baseline characteristics of the cases and controls. The chi-square test was performed based on whether the patient used a statin as an exposure factor, and binary logistic regression analysis of the association between cardiovascular events and statin therapy duration was conducted. Subgroup analyses for relevant variables were also performed. The chi-square test showed that statin therapy was significantly associated with a reduction in CVD risk in patients with NS (p=0.002). Furthermore, the risk of cardiovascular events in patients with NS decreased as the length of statin treatment increased (OR=0.82 [95% CI 0.73-0.89], p<0.001).
For NS patients with dyslipidemia, statin therapy may be used to decrease CVD risk, and extended treatment was associated with more significant risk reduction.
For NS patients with dyslipidemia, statin therapy may be used to decrease CVD risk, and extended treatment was associated with more significant risk reduction.Ionizing radiation is a mainstay of high-grade glioma therapy. The current standard radiotherapeutic schedule involves a total 60 Gy split in 2.0 Gy fractions delivered on weekdays for six weeks. Thereafter, almost invariably the tumor relapses and progresses. In vitro studies have demonstrated that the therapeutic effectiveness of ionizing radiation towards high-grade glioma cells is greatly increased by splitting the total dose in fractions ten times smaller [0.1-0.5 Gy instead of standard 2.0 Gy-ultra-hyper-fractionated radiotherapy (ultra-hyper-FRT)]. Recently, it became possible to consistently translate this therapeutic effect to the animal setting, by using glioma-initiating cell-driven faithful animal modeling. A re-analysis of the literature reporting radiotherapeutic clinical trials also suggests that the lower the average fraction size, the higher is the achievable overall survival of patients. However, average fraction sizes ≤ 0.5 Gy have never been thoroughly investigated in the clinics. We propose to study in the clinical setting the therapeutic effect of an ultra-hyper-FRT schedule promptly extending the conventional radiation component of the current guidelines ("Stupp") therapeutic protocol.
To evaluate maternal and perinatal outcomes of late open fetal repair for open spina bifida (OSB) between 26
-27
weeks.
A cohort of fetuses with OSB who underwent open surgery in two fetal surgery centers (Argentina and Mexico). Two groups were defined based on the gestational age (GA) at intervention Management of Myelomeningocele Study (MOMS) time window group GA 19
-25
, and late intervention group GA 26
-27
.
Intrauterine OSB repair was successfully performed in 140 cases, either before (n=57) or after (n=83) 26weeks, at on average 25
(22
-25
) and 26
(26
-27
) weeks + days, respectively. There were no significant differences in the rate of premature rupture of membranes, chorioamnionitis, oligohydramnios, preterm delivery, perinatal death and maternal complications. The late intervention group showed a significantly lower surgical times (112.6 vs. 124.2min, p=0.01), lower interval between fetal surgery and delivery (7.9 vs. 9.2weeks, p<0.01) and similar rate of hydrocephalus requiring treatment (30.6% vs. 23.3%, p=0.44) than the MOMS time window group.
Late fetal surgery for OSB repair between 26
-27
weeks is feasible and was associated with similar outcomes than that performed before 26weeks. These findings may allow an extension of the proposed time window for cases with late diagnosis or referral.
Late fetal surgery for OSB repair between 26+0 -27+6 weeks is feasible and was associated with similar outcomes than that performed before 26 weeks. These findings may allow an extension of the proposed time window for cases with late diagnosis or referral.
Bridge to transplantation (BTT) with a SynCardia Total Artificial Heart (TAH) has been gaining momentum as a therapy for patients with biventricular heart failure. Recent transplant waitlist and posttransplant outcomes with this strategy have not been comprehensively characterized. We reviewed the United Network for Organ Sharing (UNOS) database to examine BTT outcomes for the TAH system since approval.
Adult patients listed for heart transplantation in the UNOS system between 2004 and 2020 who underwent BTT therapy with a TAH were included in the study. Trends in utilization of TAH compared with other durable mechanical support strategies were examined. The primary outcome was 1-year survival following heart transplantation following BTT with TAH. Secondary outcomes included waitlist deterioration and risk factors for waitlist or posttransplant mortality.
During the study 433 total patients underwent TAH implant as BTT therapy; 236 (54.4%) were listed with the TAH, while the remaining patients were upggation to determine the ideal population for this therapy.
Novel radiotherapy techniques like synchrotron X-ray microbeam radiation therapy (MRT) require fast dose distribution predictions that are accurate at the sub-mm level, especially close to tissue/bone/air interfaces. Tivantinib Monte Carlo (MC) physics simulations are recognized to be one of the most accurate tools to predict the dose delivered in a target tissue but can be very time consuming and therefore prohibitive for treatment planning. Faster dose prediction algorithms are usually developed for clinically deployed treatments only. In this work, we explore a new approach for fast and accurate dose estimations suitable for novel treatments using digital phantoms used in preclinical development and modern machine learning techniques. We develop a generative adversarial network (GAN) model, which is able to emulate the equivalent Geant4 MC simulation with adequate accuracy and use it to predict the radiation dose delivered by a broad synchrotron beam to various phantoms.
The energy depositions used for the trainie in MRT treatment planning, which requires fast and accurate predictions with sub-mm resolutions.
The proposed GAN model predicts dose distributions inside unknown phantoms with only small deviations from the full MC simulation with computations times of less than a second. It demonstrates good interpolation ability to unseen but similar phantom geometries and is flexible enough to be trained on data with different radiation scenarios without the need for optimization of the model parameter. This proof-of-concept encourages to apply and further develop the model for the use in MRT treatment planning, which requires fast and accurate predictions with sub-mm resolutions.Access to healthcare in developing countries remains a challenge. As a result, task-shifting to community health workers (CHWs) is increasingly used to mitigate healthcare worker shortages. Although there is solid evidence of CHW program effectiveness, less is known about CHWs' experiences of becoming and then working daily as CHWs-information that should play an important role in the design of CHW programs. We examined the experiences of a group of CHWs working in a government-run CHW program in South Africa's rural Eastern Cape Province. Semistructured qualitative interviews (N = 9) and focus groups (N = 2) focusing on motivations for becoming a CHW and experiences of working as CHWs were conducted and thematically analyzed. Three themes were identified (1) becoming a CHW, (2) facing challenges in the field, and (3) gaining community acceptance through respect and legitimacy. In this study, CHWs were motivated by altruism and a desire to help their community. They faced a range of challenges such as limited training, lack of supervision, equipment shortages, logistical issues, and clinics with limited services. Respect and legitimacy through community acceptance and trust is crucial for effective CHW work. CHWs in this study described how confidentiality and their own persistence facilitated the process of gaining respect and legitimacy. CHWs have a unique knowledge of contexts and requirements for successful programs and greater efforts are needed to include their perspectives to improve and develop programs. Recognition is needed to acknowledge the significant personal input required by CHWs for programs to be successful.
