Case report: Effectiveness of sirolimus in a de novo FAS mutation leading to autoimmune lymphoproliferative syndrome-FAS and elevated DNT/Treg ratio

BackgroundThe autoimmune lymphoproliferative syndrome (ALPS) is a rare disease characterized by defective function of the FAS death receptor, which results in chronic, non-malignant lymphoproliferation and autoimmunity accompanied by elevated numbers of double-negative (DN) T cells (T-cell receptor α/β + CD4–CD8–) and an increased risk of developing malignancies later in life.Case descriptionHere, we report a patient with a de novo FAS mutation with a severe phenotype of ALPS-FAS. The FAS gene identified as a novel spontaneous germline heterozygous missense mutation (c.857G > A, p.G286E) in exon 9, causing an amino acid exchange and difference in hydrogen bond formation. Consequently, the treatment with sirolimus was initiated. Subsequently, the patient’s clinical condition improved rapidly. Moreover, DNT ratio continuously decreased during sirolimus application.ConclusionWe described a novel germline FAS mutation (c.857G > A, p.G286E) associated with a severe clinical phenotype of ALPS-FAS. Sirolimus effectively improved the patient clinical manifestations with obvious reduction of the DNT ratio

Potassium levels and the risk of all-cause and cardiovascular mortality among patients with cardiovascular diseases: a meta-analysis of cohort studies

Background: Abnormal blood potassium levels are associated with an increased risk of cardiometabolic diseases and mortality in the general population; however, evidence regarding the association between dyskalemia and mortality among patients with cardiovascular disease (CVD) remains inconclusive. This study aimed to evaluate the association of potassium levels with all-cause and cardiovascular mortality among patients with CVD. Methods: PubMed, Embase, Web of Science, and Cochrane Library databases were searched up to August 2023 to identify relevant cohort studies among patients with CVD, such as myocardial infarction, stroke, and heart failure. Abnormal potassium levels were considered as hypokalemia or hyperkalemia. The primary outcomes were all-cause mortality based on follow-up length (including in-hospital, short-term and long-term mortality) and cardiovascular mortality. The methodological quality of included studies was assessed by using the Newcastle-Ottawa Scale. The pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. Restricted cubic splines were applied to explore the dose-response relationship. Results: Thirty-one cohort studies involving 227,645 participants with an average age of 68.3 years were included in the meta-analysis, all of which achieved moderate to high quality. Hyperkalemia was significantly associated with an approximately 3.0-fold increased risk of all-cause in-hospital mortality (RR:2.78,95CI%:1.92,4.03), 1.8-fold of all-cause short-term mortality (RR:1.80, 95CI%:1.44,2.27), 1.3-fold of all-cause long-term mortality (RR:1.33, 95CI%:1.19,1.48) and 1.2-fold of cardiovascular mortality (RR:1.19, 95CI%:1.04,1.36). Similar positive associations were also observed between hypokalemia and risk of all-cause mortality and cardiovascular mortality. The RRs of all-cause in-hospital, short-term, long-term mortality and cardiovascular mortality with hyperkalemia were attenuated to 2.21 (95CI%:1.60,3.06), 1.46(95CI%:1.25,1.71), 1.23 (95CI%:1.09,1.39) and 1.13 (95CI%:1.00,1.27) when treating hypokalemia together with normokalemia as the reference group. A U-shaped association was observed between potassium levels and mortality, with the lowest risk at around 4.2 mmol/L. Conclusions: Both hypokalemia and hyperkalemia were positively associated with the risk of mortality in patients with CVD. Our results support the importance of potassium homeostasis for improving the CVD management. Registration: PROSPERO, CRD42022324337

Clinical Analysis of Pediatric Systemic Juvenile Xanthogranulomas: A Retrospective Single-Center Study

Objective: To investigate the clinical characteristics, treatment, and prognosis of children with systemic juvenile xanthogranuloma (JXG).Methods: Clinical data of children with JXG who were hospitalized in Beijing Children's Hospital, Capital Medical University, from January 2012 to December 2019 were retrospectively analyzed, including clinical manifestations, laboratory determinations, treatment, and prognosis of the children. Patients were treated with vindesine + prednisone as the first-line treatment and cytarabine + vindesine + dexamethasone ± cladribine as the second-line treatment.Results: Ten patients, including 8 males and 2 females, with a median of onset age of 1.95 (0.80–7.30) years, exhibited multi-system dysfunction. The median age of diagnosis was 2.45 (1.30–12.10) years. The most common location of extracutaneous lesions was the central nervous system (6 cases), followed by the lung (5 cases) and bone (4 cases). Nine patients underwent first-line chemotherapy, and 6 patients underwent second-line chemotherapy, including 5 patients with poorly controlled disease after first-line treatment. The median observation time was 29 (3–115) months. Nine patients survived, whereas one patient died of respiratory failure caused by pulmonary infection. At the end of follow-up, 7 patients were in active disease (AD)/regression state (AD-better), and 2 patients were in an AD/stable state (AD-stable). Three patients had permanent sequelae, mainly central diabetes insipidus. The rates of response to the first-line treatment and the second-line treatment were 40.0 and 66.7% respectively.Conclusion: The chemotherapy protocol for Langerhans cell histiocytosis (LCH) may be effective for patients with systemic JXG. Central nervous system involvement may not impact overall survival, but serious permanent sequelae may occur

Evaluating Temporal Factors in Combined Interventions of Workforce Shift and School Closure for Mitigating the Spread of Influenza

10.1371/journal.pone.0032203PLoS ONE7

Analysis of segregation solute redistribution and centerline in continuously cast thin slab

A model has been built to calculate the solute redistribution in continuously cast thin slab and the effect of the fluid flow in mush on the centerline segregation was analyzed. The corresponding simulation program was developed by applying the SIMPLER algorithm. The momentum, energy and species conservation equations were solved simultaneously. The macro-segregation of a 3-D thin slab with 900 mm x 50 mm cross section was simulated. The obtained results show that negative segregation forms near the slab surface and severe centerline segregation forms in the mid-thickness plane. The species concentration in the centerline of the slab increases obviously at the final solidification stage

Dynamic measurement of temperature field and deformation in hydraulic turbine blade at cooling stage of heat treatment

The hydraulic turbine blade is a kind of large, complex and curved casting. It is susceptible to significant warping deformation in the heat treatment process because of no-uniform cooling and phase transformation, which is a serious problem for the dimension control of the blade. A non-contact temperature field and dynamic displacement measurement system is established with the infrared thermal imaging system used for temperature measurement and special devices for the deformation measurement. It is adopted to investigate the temperature distribution and deformation behavior of a blade at the cooling stages of normalizing and tempering in production. The results reveal the temperature evolutions and dynamic deformation of the blade in heat treatment. The deformations of the blade mainly occur at the cooling stage of normalizing owing to the effect of uneven cooling and phase transformation. While, it is small during tempering in which only uneven cooling effect exists. This research and the results are of great significance to the exploration and study of the deformation behavior of hydraulic turbine blades. And the established system is useful for temperature fields and deformation measurement for parts during heat treatment

An Automatic Extraction Method of Rebar Processing Information Based on Digital Image

Reinforced steel is one of the most important building materials in civil engineering and improving the intelligence of steel reinforcement engineering can greatly promote the intelligent development of the construction industry. This research addressed the problems of the slow speed and poor accuracy of manually extracting rebar processing information, which leads to a low degree of rebar processing intelligence. Firstly, based on digital image processing technology, image preprocessing methods such as binarization and grayscale were used to eliminate redundant information in a detail drawing of a rebar. An image segmentation method based on pixel statistics was proposed to store the geometric and non-geometric information of the detail drawing of the rebar separately. Next, the bending angle was extracted by line thinning and corner detection, and the bending direction of the steel bar was determined based on the mathematical characteristics of the vector product. Finally, the non-geometric information was extracted by combining the morphological algorithm and the Optical Character Recognition (OCR) engine. According to the characteristics of the information sequence, an information mapping method was proposed to realize the integration of geometric and non-geometric information. The applicability and accuracy of this method for extracting the steel bar’s information were tested by experiments, and it was shown that the method also provides a theoretical basis for realizing the intelligentization and informatization of steel bar processing

Behavioral response to promotion-based public transport demand management: Longitudinal analysis and implications for optimal promotion design

Increasing ridership in the urban rail systems in major cities is outpacing their designed capacity. Promotion based demand management can facilitate better utilization of the available capacity of the existing system when the investment and opportunity to expand the system are limited. While several studies address short-term behavioral responses to such promotions using before and after analysis, how behavioral changes are sustained in the long run is also very important as well as differences in response among different user groups. Using an extensive smart card dataset over two years from Hong Kong’s urban heavy railway system, this paper explores the longitudinal behavior of passengers in response to a promotion aiming at changing passengers’ travel period from peak to the pre-peak. The approach uses customer segmentation to understand the heterogeneous response of different groups. Users who have high flexibility in schedule and familiarity with the system and travel long distances tend to be more likely to change their travel periods to take advantage of the discount. The longitudinal promotion analysis reveals that 35–40% of passengers who initially adopted the promotion will eventually revert to their previous travel time periods. The results suggest that the promotion designs should be adjusted/renewed over time to sustain the initial response given the attrition of early adopters. Based on the behavioral analysis, an ‘optimal’ promotion design approach is applied to examine the effectiveness of promotion strategies given different behavioral responses over time, heterogeneous group behavior, and constraints on the investment budgets and performance requirements. The promotion design using group-specific response can better target price-sensitive users, hence improves its effectiveness over time, while the design based on the average response shows a significant performance decrease. However, the optimal design schemes using different behavioral responses are relatively consistent in terms of the selected stations for promotion, though some differences exist in the discount levels and time periods for the areas where there can be more early morning travelers. From a design perspective, there is not much difference in the promotion effectiveness regardless of the behavioral response assumed for the design