Summary
Background
Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti‐viral therapy affects ...survival after HCC diagnosis.
Methods
This was an international multicentre cohort study of 2518 HBV‐related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti‐viral therapy and cirrhosis on patients' risk of death.
Results
Approximately, 48% of patients received anti‐viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti‐viral therapy would have been indicated for >60% of the patients not on anti‐viral therapy based on American criteria. Patients with cirrhosis had lower 5‐year survival (34% vs 46%; P < 0.001) while patients receiving anti‐viral therapy had increased 5‐year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti‐viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001).
Conclusions
Anti‐viral therapy improved overall survival in patients with HBV‐related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti‐viral therapy in HBV‐related HCC and better linkage‐to‐care for HBV patients are needed.
Biomarkers that predict disease progression might assist the development of better therapeutic strategies for aggressive cancers, such as ovarian cancer. Here, we investigated the role of collagen ...type XI alpha 1 (COL11A1) in cell invasiveness and tumor formation and the prognostic impact of COL11A1 expression in ovarian cancer. Microarray analysis suggested that COL11A1 is a disease progression-associated gene that is linked to ovarian cancer recurrence and poor survival. Small interference RNA-mediated specific reduction in COL11A1 protein levels suppressed the invasive ability and oncogenic potential of ovarian cancer cells and decreased tumor formation and lung colonization in mouse xenografts. A combination of experimental approaches, including real-time RT-PCR, casein zymography and chromatin immunoprecipitation (ChIP) assays, showed that COL11A1 knockdown attenuated MMP3 expression and suppressed binding of Ets-1 to its putative MMP3 promoter-binding site, suggesting that the Ets-1-MMP3 axis is upregulated by COL11A1. Transforming growth factor (TGF)-beta (TGF-β1) treatment triggers the activation of smad2 signaling cascades, leading to activation of COL11A1 and MMP3. Pharmacological inhibition of MMP3 abrogated the TGF-β1-triggered, COL11A1-dependent cell invasiveness. Furthermore, the NF-YA-binding site on the COL11A1 promoter was identified as the major determinant of TGF-β1-dependent COL11A1 activation. Analysis of 88 ovarian cancer patients indicated that high COL11A1 mRNA levels are associated with advanced disease stage. The 5-year recurrence-free and overall survival rates were significantly lower (P=0.006 and P=0.018, respectively) among patients with high expression levels of tissue COL11A1 mRNA compared with those with low expression. We conclude that COL11A1 may promote tumor aggressiveness via the TGF-β1-MMP3 axis and that COL11A1 expression can predict clinical outcome in ovarian cancer patients.
The analysis aimed to identify the treatment gaps in current fracture liaison services (FLS) and to provide recommendations for best practice establishment of future FLS across the Asia-Pacific ...region. The findings emphasize the unmet need for the implementation of new programs and provide recommendations for the refinement of existing ones. The study’s objectives were to evaluate fracture liaison service (FLS) programs in the Asia-Pacific region and provide recommendations for establishment of future FLS programs. A systematic literature review (SLR) of Medline, PubMed, EMBASE, and Cochrane Library (2000–2017 inclusive) was performed using the following keywords: osteoporosis, fractures, liaison, and service. Inclusion criteria included the following: patients ≥ 50 years with osteoporosis-related fractures; randomized controlled trials or observational studies with control groups (prospective or retrospective), pre–post, cross-sectional and economic evaluation studies. Success of direct or indirect interventions was assessed based on patients’ understanding of risk, bone mineral density assessment, calcium intake, osteoporosis treatment, re-fracture rates, adherence, and mortality, in addition to cost-effectiveness. Overall, 5663 unique citations were identified and the SLR identified 159 publications, reporting 37 studies in Asia-Pacific. These studies revealed the unmet need for public health education, adequate funding, and staff resourcing, along with greater cooperation between departments and physicians. These actions can help to overcome therapeutic inertia with sufficient follow-up to ensure adherence to recommendations and compliance with treatment. The findings also emphasize the importance of primary care physicians continuing to prescribe treatment and ensure service remains convenient. These findings highlight the limited evidence supporting FLS across the Asia-Pacific region, emphasizing the unmet need for new programs and/or refinement of existing ones to improve outcomes. With the continued increase in burden of fractures in Asia-Pacific, establishment of new FLS and assessment of existing services are warranted to determine the impact of FLS for healthcare professionals, patients, family/caregivers, and society.
The strong spectral dependence of light absorption of brown carbon (BrC) aerosol is regarded to influence aerosol's radiative forcing significantly. The Absorption Angstrom Exponent (AAE) method has ...been widely used in previous studies to attribute light absorption of BrC at shorter wavelengths for ambient aerosols, with a theoretical assumption that the AAE of "pure" black carbon (BC) aerosol equals to 1.0. In this study, the AAE method was applied to both urban and rural environments in the Pearl River Delta (PRD) region of China, with an improvement of constraining the realistic AAE of "pure" BC through statistical analysis of on-line measurement data. A three-wavelength photo-acoustic soot spectrometer (PASS-3) and aerosol mass spectrometers (AMS) were used to explore the relationship between the measured AAE and the relative abundance of organic aerosol to BC. The regression and extrapolation analysis revealed that more realistic AAE values for "pure" BC aerosol (AAEBC) were 0.86, 0.82, and 1.02 between 405 and 781 nm, and 0.70, 0.71, and 0.86 between 532 and 781 nm, in the campaigns of urbanwinter, urbanfall, and ruralfall, respectively. Roadway tunnel experiments were conducted and the results further confirmed the representativeness of the obtained AAEBC values for the urban environment. Finally, the average light absorption contributions of BrC ( relative uncertainties) at 405 nm were quantified to be 11.7 % ( 5 %), 6.3 % ( 4 %), and 12.1 % ( 7 %) in the campaigns of urbanwinter, urbanfall, and ruralfall, respectively, and those at 532 nm were 10.0 % ( 2 %), 4.1 % ( 3 %), and 5.5 % ( 5 %), respectively. The relatively higher BrC absorption contribution at 405 nm in the ruralfall campaign could be reasonably attributed to the biomass burning events nearby, which was then directly supported by the biomass burning simulation experiments performed in this study. This paper indicates that the BrC contribution to total aerosol light absorption at shorter wavelengths is not negligible in the highly urbanized and industrialized PRD region.
Abstract
In two-dimensional (2D) NbSe
2
crystal, which lacks inversion symmetry, strong spin-orbit coupling aligns the spins of Cooper pairs to the orbital valleys, forming Ising Cooper pairs (ICPs). ...The unusual spin texture of ICPs can be further modulated by introducing magnetic exchange. Here, we report unconventional supercurrent phase in van der Waals heterostructure Josephson junctions (JJs) that couples NbSe
2
ICPs across an atomically thin magnetic insulator (MI) Cr
2
Ge
2
Te
6
. By constructing a superconducting quantum interference device (SQUID), we measure the phase of the transferred Cooper pairs in the MI JJ. We demonstrate a doubly degenerate nontrivial JJ phase (
ϕ
), formed by momentum-conserving tunneling of ICPs across magnetic domains in the barrier. The doubly degenerate ground states in MI JJs provide a two-level quantum system that can be utilized as a new dissipationless component for superconducting quantum devices. Our work boosts the study of various superconducting states with spin-orbit coupling, opening up an avenue to designing new superconducting phase-controlled quantum electronic devices.
Austenite steel, Nb-bearing alloy steel, and high-Cr alloy cast iron surfacing layers (SL) were grown on 45 steel base metal (SBM) by using the arc surfacing method with self-shielded flux-cored ...welding wire and fusion electrode, and the composition and microstructure of these SLs were analyzed. The criss-cross push-off (CCPO) specimens for each type were processed, and the bonding property between SLs and 45 SBM was measured using a customized CCPO test. The fracture path and fractograph characteristics were also investigated using a metallographic and scanning electron microscope. The experimental results indicated that the bonding strength (BS) of austenite steel SLs and 45 SBM was the highest (465 MPa); the fracturing sites were near the fusion line, and the fracture exhibited cleavage fracturing features. The BS of niobium-bearing alloy steel and 45 SBM was 310 MPa, and the fracture was at the bottom of the SLs and exhibited quasi-cleavage fracturing features. The BS of the alloy cast iron SLs and 45 SBM was 175 MPa, and the fracture was at the bottom of the SLs and showed brittle fracturing features.
Background
The Child–Pugh (CP) score is used widely to assess liver function and predict postoperative outcomes in patients with hepatocellular carcinoma (HCC). Recently, the albumin–bilirubin (ALBI) ...score has been validated as a predictor of overall survival in these patients. This study aimed to compare the ability of the ALBI and CP scores to predict outcomes in patients with HCC after liver resection with curative intent.
Methods
Consecutive patients who underwent liver resection with curative intent for HCC between January 2007 and July 2013 were included in this retrospective study. The performance of the ALBI score in predicting postoperative liver failure (PHLF) and long‐term survival was compared with that of the CP score.
Results
A total of 1242 patients were enrolled. Of these, 166 (13·4 per cent) experienced PHLF. The area under the receiver operating characteristic (ROC) curve of the ALBI score for predicting PHLF was greater than that of the CP score (0·723 versus 0·607; P < 0·001). Similar to findings for CP grade, the incidence and severity of PHLF increased with increasing ALBI grade. The ALBI grade stratified patients into at least two distinct overall survival cohorts (P < 0·001), whereas the CP grade did not. The ALBI grade also classified patients with CP grade A disease into two distinct overall survival cohorts (P < 0·001), and overall survival rates in the group with poorer survival were similar to those in the majority of patients with CP grade B disease. Both CP and ALBI scores had low power in predicting disease‐free survival.
Conclusion
The ALBI grade predicted PHLF and overall survival in patients with HCC undergoing liver resection with curative intent more accurately than the CP grade.
ALBI score may be better
Changes in two novel HBV serological markers, linearized hepatitis B surface antigen (HQ-HBsAg) and hepatitis B core-related antigen (HBcrAg), in the natural history of chronic hepatitis B (CHB) have ...not been well characterized. Serum HQ-HBsAg and HBcrAg levels of 404 Asian treatment-naïve CHB patients were analysed in a cross-sectional manner. Patients were categorized into five groups: immune tolerant (IT group, n = 52), immune clearance (IC group, n = 105), hepatitis B e antigen (HBeAg)-negative hepatitis (ENH group, n = 97), HBeAg-negative quiescent group (ENQ group, n = 95) and CHB with hepatitis B surface antigen (HBsAg) seroclearance (SC group, n = 55). HQ-HBsAg and HBcrAg were measured and correlated with HBV DNA, HBsAg, HBV genotype and clinical parameters. HQ-HBsAg showed good correlation with HBsAg, especially in the ENQ group (r = 0.874, p <0.001). Correlation of HQ-HBsAg with HBV DNA was less prominent and weakest in the ENH group (r = 0.268, p 0.008). HBcrAg correlated best with HBV DNA in the ENQ group (r = 0.537, p <0.001). In the ENQ group, 42.1% of patients had undetectable HBcrAg; this subgroup of patients, when compared with those with detectable HBcrAg, had significantly lower median HBV DNA (3.17/4.48 log IU/mL, p <0.001) and HBsAg (5.05/5.96 log mIU/mL, p <0.001) levels. Forty per cent of the SC group patients had detectable HQ-HBsAg and/or HBcrAg up to 42 months after HBsAg seroclearance. When comparing anti-HBs positivity and median time after HBsAg seroclearance in the SC group with and without detectable HQ-HBsAg/HBcrAg, there was no significant difference (22.7% and 36.4%, respectively, p 0.284, and 76.5 and 93.2 months, respectively, p 0.245). HQ-HBsAg and HBcrAg showed unique patterns of distribution throughout the five disease phases of CHB, including high detectability rates after HBsAg seroclearance, opening up different possibilities for their applicability.
Aim
Food allergy is common in children and adults, and could be potentially fatal in minor groups. It is important for physicians to identify the prevalence of food allergies and to recognise common ...food allergens to make precise diagnosis and choose correct therapeutic approaches.
Methods
We used a nationwide, cross‐sectional, random questionnaire‐based survey to estimate the self‐reported and expert‐screened prevalence of food allergies and to identify the common food allergens in Taiwan. In this study, the perceptional diagnosis of food allergies was screened by physicians according to descriptions of convincing symptoms and medical recordings; in the meantime, non‐allergic adverse reactions to foods, including food intolerance or food avoidance, were clarified.
Results
A total of 30 018 individuals who met the inclusion criteria was evaluated, and 6.95% of them were diagnosed as victims of food allergies. The prevalence was 3.44% in children under 3 years of age, 7.65% in children aged 4–18 years and 6.40% in adults respectively. About 77.33% of the food allergy population had experienced recurrent allergic attacks. Systemic reactions happened about 4.89% in food allergies group. The most commonly reported food allergen in Taiwan is seafood, including shrimp, crab, fish and mollusc. In addition, mango, milk, peanuts and eggs were also important food allergens in the general population; while milk, shellfish, peanuts and eggs were common in children.
Conclusions
Less than 10% of the Taiwan population suffers from food allergy with different allergic symptoms to variable food allergens in different age groups.
Open-shell radicals are usually thermodynamically and kinetically unstable due to their incompletely satisfied valency. However, the rapid development of radical chemistry in the past 100 years has ...demonstrated the possibility to prepare persistent and even stable radicals through rational design and appropriated chemical constructions. The existence of unpaired electrons of open-shell materials endows them with some unique physicochemical properties, which are difficult to be achieved in well-studied, closed-shell materials. This critical review summarizes some typical persistent and stable organic radicals, together with the presentations of their chemical synthesis and physicochemical properties. Furthermore, the up-to-date practical applications in magnetic, electronic, optoelectronic, and biologic fields based on functional organic radicals are presented. Finally, we carefully revise the critical limitations and challenges in radical chemistry and material functionalization, covering some core issues, including stability and commercialization perspectives, that need to be systematically considered in future.
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Open-shell organic radicals are attractive in material science and various areas due to their fundamental structures and unique physicochemical properties. However, the intrinsic instability arising from their incompletely satisfied valency hinders further development. In these decades, in-depth studies on structure-stability relationships proved the possibility to prepare persistent and even stable organic radicals, which have been successfully applied in various functional devices. In this review, we present a comprehensive overview on the design and synthesis of the recently reported persistent and stable radicals. We highlight their functionality and applications in magnetic, electronic, optoelectronic, biologic, and other emerging fields. Further efforts should be devoted to unraveling the novel and rational design paradigms, the underlying mechanisms and theories, and the evolution of physicochemical properties toward (multi)functionality and relevant technologies.
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