Current status of hepatocellular carcinoma detection: screening strategies and novel biomarkers.

Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide. Delayed diagnosis is a major factor responsible for the poor prognosis of HCC. Several advances have been made in the field of liver imaging with the use of novel imaging contrasts, improving current imaging techniques with contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI), introduction of new technologies such as contrast liver ultrasound, and development of novel biomarkers with the goal of early detection of HCC and improving outcomes of patients with HCC. This review focuses on current surveillance strategies and development of biomarkers with the goal of early detection of HCC

Differences in receipt of opioid agonist treatment and time to enter treatment for opioid use disorder among specialty addiction programs in the United States, 2014-17.

BACKGROUND: Access to adequate treatment for opioid use disorder (OUD) has been a high priority among American policymakers. Elucidation of the sociodemographic and institutional differences associated with the use, or lack thereof, of opioid agonist therapy (OAT) provides greater clarity on who receives OAT. Timely access to care is a further consideration and bears scrutiny as well. METHODS: We draw upon data from the Treatment Episode Data Set-Admissions (TEDS-A) to analyse the relationship between sociodemographic and institutional characteristics and the receipt of opioid agonist treatments and time waiting to enter treatment. RESULTS: Estimates from logistic regression models highlight certain groups which show lower odds of receipt of OAT, including those in precarious housing arrangements, those unemployed or not otherwise in the labor force, and those referred by drug abuse care providers, educational institutions, employers, and the criminal justice system. Groups which showed higher odds of waiting over a week to enter treatment included those who were separated, divorced, or widowed, those working part-time, and those referred by drug abuse care providers, employers, and the criminal justice system. CONCLUSION: Given the efficacy of OAT and the adverse outcomes associated with long waiting times, coordinated effort is needed to understand why these differences persist and how they may be addressed through appropriate policy responses

Responses among substance abuse treatment providers to the opioid epidemic in the USA: Variations in buprenorphine and methadone treatment by geography, operational, and payment characteristics, 2007-16.

OBJECTIVE: To identify the geographic, organisational, and payment correlates of buprenorphine and methadone treatment among substance abuse treatment (SAT) providers. METHODS: Secondary analyses of the National Survey of Substance Abuse Treatment Services (NSSATS) from 2007-16 were conducted. We provide bivariate descriptive statistics regarding substance abuse treatment services which offered buprenorphine and methadone treatment from 2007-16. Using multiple logistic regression, we regressed geographic, organisational, and payment correlates on buprenorphine and methadone treatment. RESULTS: Buprenorphine is increasingly offered at SAT facilities though uptake remains comparatively low outside of the northeast. SAT facilities run by tribal governments or Indian Health Service which offer buprenorphine remain low compared to privately operated SAT facilities (AOR = 0.528). The odds of offering buprenorphine among facilities offering free or no charge treatment (AOR = 0.838) or a sliding fee scale (AOR = 0.464) was lower. SAT facilities accepting Medicaid payments showed higher odds of offering methadone treatment (AOR = 2.035). CONCLUSIONS: Greater attention towards the disparities in provision of opioid agonist therapies is warranted, especially towards the reasons why uptake has been moderate among civilian providers. Additionally, the care needs of Native Americans facing opioid-related use disorders bears further scrutiny

Health financing for universal health coverage in Sub-Saharan Africa: a systematic review.

BACKGROUND: Universal health coverage (UHC) embedded within the United Nations Sustainable Development Goals, is defined by the World Health Organization as all individuals having access to required health services, of sufficient quality, without suffering financial hardship. Effective strategies for financing healthcare are critical in achieving this goal yet remain a challenge in Sub-Saharan Africa (SSA). This systematic review aims to determine reported health financing mechanisms in SSA within the published literature and summarize potential learnings. METHODS: A systematic review was conducted aligned with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. On 19 to 30 July 2019, MEDLINE, EMBASE, Web of Science, Global Health Database, the Cochrane Library, Scopus and JSTOR were searched for literature published from 2005. Studies describing health financing approaches for UHC in SSA were included. Evidence was synthesised in form of a table and thematic analysis. RESULTS: Of all records, 39 papers were selected for inclusion. Among the included studies, most studies were conducted in Kenya (n = 7), followed by SSA as a whole (n = 6) and Nigeria (n = 5). More than two thirds of the selected studies reported the importance of equitable national health insurance schemes for UHC. The results indicate that a majority of health care revenue in SSA is from direct out-of-pocket payments. Another common financing mechanism was donor funding, which was reported by most of the studies. The average quality score of all studies was 81.6%, indicating a high appraisal score. The interrater reliability Cohen's kappa score, κ=0.43 (p = 0.002), which showed a moderate level of agreement. CONCLUSIONS: Appropriate health financing strategies that safeguard financial risk protection underpin sustainable health services and the attainment of UHC. It is evident from the review that innovative health financing strategies in SSA are needed. Some limitations of this review include potentially skewed interpretations due to publication bias and a higher frequency of publications included from two countries in SSA. Establishing evidence-based and multi-sectoral strategies tailored to country contexts remains imperative.Non

Health financing for universal health coverage in Sub-Saharan Africa: a systematic review.

BACKGROUND: Universal health coverage (UHC) embedded within the United Nations Sustainable Development Goals, is defined by the World Health Organization as all individuals having access to required health services, of sufficient quality, without suffering financial hardship. Effective strategies for financing healthcare are critical in achieving this goal yet remain a challenge in Sub-Saharan Africa (SSA). This systematic review aims to determine reported health financing mechanisms in SSA within the published literature and summarize potential learnings. METHODS: A systematic review was conducted aligned with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. On 19 to 30 July 2019, MEDLINE, EMBASE, Web of Science, Global Health Database, the Cochrane Library, Scopus and JSTOR were searched for literature published from 2005. Studies describing health financing approaches for UHC in SSA were included. Evidence was synthesised in form of a table and thematic analysis. RESULTS: Of all records, 39 papers were selected for inclusion. Among the included studies, most studies were conducted in Kenya (n = 7), followed by SSA as a whole (n = 6) and Nigeria (n = 5). More than two thirds of the selected studies reported the importance of equitable national health insurance schemes for UHC. The results indicate that a majority of health care revenue in SSA is from direct out-of-pocket payments. Another common financing mechanism was donor funding, which was reported by most of the studies. The average quality score of all studies was 81.6%, indicating a high appraisal score. The interrater reliability Cohen's kappa score, κ=0.43 (p = 0.002), which showed a moderate level of agreement. CONCLUSIONS: Appropriate health financing strategies that safeguard financial risk protection underpin sustainable health services and the attainment of UHC. It is evident from the review that innovative health financing strategies in SSA are needed. Some limitations of this review include potentially skewed interpretations due to publication bias and a higher frequency of publications included from two countries in SSA. Establishing evidence-based and multi-sectoral strategies tailored to country contexts remains imperative.Non

Tackling MARCKS-PIP3 circuit attenuates fibroblast activation and fibrosis progression.

Targeting activated fibroblasts, including myofibroblast differentiation, has emerged as a key therapeutic strategy in patients with idiopathic pulmonary fibrosis (IPF). However, there is no available therapy capable of selectively eradicating myofibroblasts or limiting their genesis. Through an integrative analysis of the regulator genes that are responsible for the activation of IPF fibroblasts, we noticed the phosphatidylinositol 4,5-bisphosphate (PIP2)-binding protein, myristoylated alanine-rich C-kinase substrate (MARCKS), as a potential target molecule for IPF. Herein, we have employed a 25-mer novel peptide, MARCKS phosphorylation site domain sequence (MPS), to determine if MARCKS inhibition reduces pulmonary fibrosis through the inactivation of PI3K/protein kinase B (AKT) signaling in fibroblast cells. We first observed that higher levels of MARCKS phosphorylation and the myofibroblast marker α-smooth muscle actin (α-SMA) were notably overexpressed in all tested IPF lung tissues and fibroblast cells. Treatment with the MPS peptide suppressed levels of MARCKS phosphorylation in primary IPF fibroblasts. A kinetic assay confirmed that this peptide binds to phospholipids, particularly PIP2, with a dissociation constant of 17.64 nM. As expected, a decrease of phosphatidylinositol (3,4,5)-trisphosphate pools and AKT activity occurred in MPS-treated IPF fibroblast cells. MPS peptide was demonstrated to impair cell proliferation, invasion, and migration in multiple IPF fibroblast cells in vitro as well as to reduce pulmonary fibrosis in bleomycin-treated mice in vivo. Surprisingly, we found that MPS peptide decreases α-SMA expression and synergistically interacts with nintedanib treatment in IPF fibroblasts. Our data suggest MARCKS as a druggable target in pulmonary fibrosis and also provide a promising antifibrotic agent that may lead to effective IPF treatments.-Yang, D. C., Li, J.-M., Xu, J., Oldham, J., Phan, S. H., Last, J. A., Wu, R., Chen, C.-H. Tackling MARCKS-PIP3 circuit attenuates fibroblast activation and fibrosis progression

Optimization of treatment planning workflow and tumor coverage during daily adaptive magnetic resonance image guided radiation therapy (MR-IGRT) of pancreatic cancer

Abstract Background To simplify the adaptive treatment planning workflow while achieving the optimal tumor-dose coverage in pancreatic cancer patients undergoing daily adaptive magnetic resonance image guided radiation therapy (MR-IGRT). Methods In daily adaptive MR-IGRT, the plan objective function constructed during simulation is used for plan re-optimization throughout the course of treatment. In this study, we have constructed the initial objective functions using two methods for 16 pancreatic cancer patients treated with the ViewRay™ MR-IGRT system: 1) the conventional method that handles the stomach, duodenum, small bowel, and large bowel as separate organs at risk (OARs) and 2) the OAR grouping method. Using OAR grouping, a combined OAR structure that encompasses the portions of these four primary OARs within 3 cm of the planning target volume (PTV) is created. OAR grouping simulation plans were optimized such that the target coverage was comparable to the clinical simulation plan constructed in the conventional manner. In both cases, the initial objective function was then applied to each successive treatment fraction and the plan was re-optimized based on the patient’s daily anatomy. OAR grouping plans were compared to conventional plans at each fraction in terms of coverage of the PTV and the optimized PTV (PTV OPT), which is the result of the subtraction of overlapping OAR volumes with an additional margin from the PTV. Results Plan performance was enhanced across a majority of fractions using OAR grouping. The percentage of the volume of the PTV covered by 95% of the prescribed dose (D95) was improved by an average of 3.87 ± 4.29% while D95 coverage of the PTV OPT increased by 3.98 ± 4.97%. Finally, D100 coverage of the PTV demonstrated an average increase of 6.47 ± 7.16% and a maximum improvement of 20.19%. Conclusions In this study, our proposed OAR grouping plans generally outperformed conventional plans, especially when the conventional simulation plan favored or disregarded an OAR through the assignment of distinct weighting parameters relative to the other critical structures. OAR grouping simplifies the MR-IGRT adaptive treatment planning workflow at simulation while demonstrating improved coverage compared to delivered pancreatic cancer treatment plans in daily adaptive radiation therapy

Ultrafast Spin-To-Charge Conversion at the Surface of Topological Insulator Thin Films

Strong spin-orbit coupling, resulting in the formation of spin-momentum-locked surface states, endows topological insulators with superior spin-to-charge conversion characteristics, though the dynamics that govern it have remained elusive. Here, we present an all-optical method that enables unprecedented tracking of the ultrafast dynamics of spin-to-charge conversion in a prototypical topological insulator Bi$_2$Se$_3$/ferromagnetic Co heterostructure, down to the sub-picosecond timescale. Compared to pure Bi$_2$Se$_3$ or Co, we observe a giant terahertz emission in the heterostructure than originates from spin-to-charge conversion, in which the topological surface states play a crucial role. We identify a 0.12-picosecond timescale that sets a technological speed limit of spin-to-charge conversion processes in topological insulators. In addition, we show that the spin-to-charge conversion efficiency is temperature independent in Bi$_2$Se$_3$ as expected from the nature of the surface states, paving the way for designing next-generation high-speed opto-spintronic devices based on topological insulators at room temperature.Comment: 19 pages, 4 figure