Search

Immune cells harboring somatic mutations reportedly infiltrate cancer tissues in patients with solid cancers and accompanying clonal hematopoiesis. Loss‐of‐function TET2 mutations are frequently observed in clonal hematopoiesis in solid cancers. Here, using a mouse lung cancer model, we evaluated the activity of Tet2‐deficient immune cells in tumor tissues. Myeloid‐specific Tet2 deficiency enhanced tumor growth in mice relative to that seen in controls. Single‐cell sequencing analysis of immune cells infiltrating tumors showed relatively high expression of S100a8/S100a9 in Tet2‐deficient myeloid subclusters. In turn, treatment with S100a8/S100a9 promoted Vegfa production by cancer cells, leading to a marked increase in the tumor vasculature in Tet2‐deficient mice relative to controls. Finally, treatment of Tet2‐deficient mice with an antibody against Emmprin, a known S100a8/S100a9 receptor, suppressed tumor growth. These data suggest that immune cells derived from TET2‐mutated clonal hematopoiesis exacerbate lung cancer progression by promoting tumor angiogenesis and may provide a novel therapeutic target for lung cancer patients with TET2‐mutated clonal hematopoiesis., Our study suggests that immune cells derived from TET2‐mutated clonal hematopoiesis exacerbate lung cancer progression by promoting tumor angiogenesis. We present evidence that signaling through the S100a8/S100a9‐Emmprin‐Vegfa axis is essential for progression of a lung cancer model established in a microenvironment of Tet2‐deficient immune cells. Furthermore, we provide a novel target for lung cancer patients with accompanying TET2‐mutated clonal hematopoiesis.

BACKGROUND In the population-based HIV impact assessment surveys, early infant diagnosis (EID) was provided to infants

BACKGROUND Conducting HIV surveys in resource-limited settings is challenging because of logistics, limited availability of trained personnel, and complexity of testing. We described the procedures and systems deemed critical to ensure high-quality laboratory data in the population-based HIV impact assessments and large-scale household surveys. METHODS Laboratory professionals were engaged in every stage of the surveys, including protocol development, site assessments, procurement, training, quality assurance, monitoring, analysis, and reporting writing. A tiered network of household, satellite laboratories, and central laboratories, accompanied with trainings, optimized process for blood specimen collection, storage, transport, and real-time monitoring of specimen quality, and test results at each level proved critical in maintaining specimen integrity and high-quality testing. A plausibility review of aggregate merged data was conducted to confirm associations between key variables as a final quality check for quality of laboratory results. RESULTS Overall, we conducted a hands-on training for 3355 survey staff across 13 surveys, with 160-387 personnel trained per survey on biomarker processes. Extensive training and monitoring demonstrated that overall, 99% of specimens had adequate volume and 99.8% had no hemolysis, indicating high quality. We implemented quality control and proficiency testing for testing, resolved discrepancies, verified >300 Pima CD4 instruments, and monitored user errors. Aggregate data review for plausibility further confirmed the high quality of testing. CONCLUSIONS Ongoing engagement of laboratory personnel to oversee processes at all levels of the surveys is critical for successful national surveys. High-quality population-based HIV impact assessments laboratory data ensured reliable results and demonstrated the impact of HIV programs in 13 countries.

International audience; OBJECTIVE: To systematically review evidence of rehabilitation interventions for improving outcomes in systemic sclerosis (SSc) and to evaluate evidence quality. METHODS: Several electronic databases were searched to identify studies in which rehabilitation professionals delivered, supervised, or participated in interventions for individuals with SSc. Randomized (RCTs) or non-randomized trials, one-arm trials, and prospective quasi-experimental studies with interventions were included if they had ≥ 10 participants. Quality appraisal was done by two independent raters using the Physiotherapy Evidence Database (PEDro) Scale. RESULTS: Sixteen good or excellent quality studies (15 RCTs, 1 prospective quasi-experimental study) were included. Most rehabilitation interventions focused on hands/upper extremities, followed by multicomponent, orofacial, and directed self-management. Sample sizes varied between 20 - 267 participants (median = 38). In 50% of studies, participants in intervention groups significantly improved compared to controls. Most studies demonstrated within-group improvements in intervention groups. Interventions varied in content, delivery, length, and dose and outcome measures collected. CONCLUSION: Existing evidence provides some support for rehabilitation in SSc, such as interventions that focus on hand and upper extremity outcomes or are multicomponent, although there is high study heterogeneity. The evidence base would benefit from interventions testing similar replicable components, use of common outcome measures, and incorporation of delivery modes that enable larger sample sizes. There are challenges in recruiting participants due to SSc’s rarity and involving participants in rehabilitation studies that require active participation over time due to high disease burden. Intervention studies designed to reduce participation barriers may facilitate translation of effective interventions into practice.

Single-use plastic waste is gradually considered a potential material for circular economy. Ion exchange resin obtained from polystyrene waste by sulfonating with H

Background: This study first efficiently applies the previous result Chen Electrical Unifying Approach (CEUA) utilized in the basic circuit theory to construct the control system matrix equation of the complicated block diagram. Methods: Based on the simple matrix operations proposed in this study, we can easily derive the transfer function without using the traditional Mason rule and the reduced techniques of the block diagram. We have successfully proposed a unifying approach to improve the disadvantages of the Mason rule, in which all loops must be found out and only the transfer function between the input node and the output node is evaluated, and the shortcoming of the reduced techniques for the block diagram is that the calculating process is too complex to be accepted. Results: The salient features of the proposed method are that the transfer function of the complicated block diagram can be easily obtained without using traditional Mason rule and the transfer function of any two nodes is immediately derived within only one calculation. Conclusion: We compared some demonstrated examples with some traditional approaches. Moreover, to demonstrate the practical applicability, the study has investigated one practical example.

Purpose To describe the methods used in the development of an intravenous chemotherapy workload and productivity dashboard and its impact on symptoms of burnout and technician turnover. Summary In February 2017, chemotherapy sterile preparation pharmacy technicians reported symptoms of burnout as a result of perceived increase in workload. In response, an i.v. chemotherapy workload and productivity dashboard was developed at an academic medical center to validate workload in comparison to the reported job stress of pharmacy technicians. The dashboard provided pharmacy leadership objective data to validate staff concerns and leveraged lean principles to level-load the work prior to requesting additional full-time equivalents (FTEs) to senior leadership. The rate of turnover of i.v. chemotherapy technicians was assessed before (December 2016–June 2017) and after (July 2017–January 2018) dashboard implementation and approval of an additional i.v. chemotherapy technician FTE. The addition of the new FTE resulted in a decrease in productivity from an average of 106% (range 67%–151%) to 84% (range 65%–110%). The interventions allowed for the ability to leverage a staffing-to-demand model, resulting in the observed improvement in technician symptoms of burnout and a notable decrease in the overall turnover rate of i.v. chemotherapy technicians. Conclusion The i.v. chemotherapy workload and productivity dashboard confirmed frontline staff perception and provided data to support the addition of labor resource and an opportunity to leverage a staffing-to-demand model to decrease symptoms of burnout and technician turnover.

Many women do not engage in regular physical activity and women's physical activity declines over the life cycle. The present study examines the association of regular leisure-time physical activity with affective experience among 881 middle-aged and older women from the National Survey of Midlife Development in the United States. In multiple linear regression and structural equation analyses, a higher level of leisure-time physical activity was related to more high-arousal and low-arousal positive affect and less high-arousal and low-arousal negative affect. Appreciating positive affective responses associated with physical activity can help to motivate women to engage in regular leisure-time physical activity.

The effect of K substitutions on the structural and superconducting properties of Bi–Pb–Sr–Ca–Cu–O (BPSCCO) system has been investigated. Polycrystalline samples with stoichiometry of Bi1.6Pb0.4Sr2−xKxCa2Cu3O10+δ, where x = (0.00, 0.02, 0.04, 0.06, 0.08, and 0.1), were prepared by using the conventional solid state reaction technique. The X-ray diffraction (XRD) and scanning electron microscopy (SEM) data showed that all samples consisted of high Tc (Bi-2223) and low Tc (Bi-2212) phases, and their volume fractions were found to vary with K content (x). The zero critical temperature was found to decrease from ~ (104.5 to 94.6) K, which was attributed to the decreases in hole carrier concentration. At 65 K, the magnetization critical current density (Jc) of the K-substituted samples was enhanced in comparison with that of the pure one. The Jc enhancement might be attributed to the formation of point defects resulting from the partial substitutions of K into Sr site in the BPSCCO system. In addition, the dominant pinning mechanism was found to be point-like pinning, as described using the Dew-Hughes model.

This research identifies factors that explain the liquidity of commercial banks in the Vietnam banking system from 2010 to 2015. Using the OLS regression method for analysis, it was found that: the interbank market helps commercial banks improve their liquidity; the larger the loan size, the higher the liquidity risk; good credit risk management has a positive impact on liquidity risk management; and long-term interest rate is negatively related to the liquidity of commercial banks. The research also makes recommendations on liquidity risk management policies to banks and policy-makers from the Government and the State Bank of Vietnam.

Huntington disease (HD) is a neurodegenerative disorder caused by a CAG expansion in the HTT gene that codes for an elongated polyglutamine tract in the huntingtin (HTT) protein. HTT is subject to multiple post-translational modifications (PTMs) that regulate its cellular function. Mutating specific PTM sites within mutant HTT (mHTT) in HD mouse models can modulate disease phenotypes, highlighting the key role of HTT PTMs in the pathogenesis of HD. These findings have led to increased interest in developing small molecules to modulate HTT PTMs in order to decrease mHTT toxicity. However, the therapeutic efficacy of pharmacological modulation of HTT PTMs in preclinical HD models remains largely unknown. HTT is palmitoylated at cysteine 214 by the huntingtin-interacting protein 14 (HIP14 or ZDHHC17) and 14-like (HIP14L or ZDHHC13) acyltransferases. Here, we assessed if HTT palmitoylation should be regarded as a therapeutic target to treat HD by (1) investigating palmitoylation dysregulation in rodent and human HD model systems, (2) measuring the impact of mHTT-lowering therapy on brain palmitoylation, and (3) evaluating if HTT palmitoylation can be pharmacologically modulate. We show that palmitoylation of mHTT and some HIP14/HIP14L-substrates is decreased early in multiple HD mouse models, and that aging further reduces HTT palmitoylation. Lowering mHTT in the brain of YAC128 mice is not sufficient to rescue aberrant palmitoylation. However, we demonstrate that mHTT palmitoylation can be normalized in COS-7 cells, in YAC128 cortico-striatal primary neurons and HD patient-derived lymphoblasts using an acyl-protein thioesterase (APT) inhibitor. Moreover, we show that modulating palmitoylation reduces mHTT aggregation and mHTT-induced cytotoxicity in COS-7 cells and YAC128 neurons.HighlightsPalmitoylation of mHTT is reduced in multiple transgenic HD mouse modelsHTT palmitoylation decreases with increasing polyQ length in HD patient cellsmHTT-lowering in mouse brains does not rescue aberrant palmitoylationmHTT palmitoylation in HD patient-derived cells can be rescued via APT inhibitionPromoting palmitoylation reduces mHTT aggregation and cytotoxicity in vitro