We aimed to determine the surveillance performance of alpha‐fetoprotein (AFP), lectin‐reactive AFP (AFP‐L3), des‐gamma‐carboxy prothrombin (DCP), and their combinations for the early detection of ...hepatocellular carcinoma (HCC) by using prospectively collected longitudinal samples in patients at risk. Among 689 patients with cirrhosis and/or chronic hepatitis B who participated in four prospective studies, 42 HCC cases were diagnosed, selected, and matched with 168 controls for age, sex, etiology, cirrhosis, and duration of follow‐up in a 1:4 ratio. Levels of AFP, AFP‐L3, and DCP at the time of HCC diagnosis, month −6, and month −12 were compared between cases and controls. Of 42 HCC cases, 39 (93%) had cirrhosis, 36 (85.7%) had normal alanine aminotransferase levels, and 31 (73.8%) had very early‐stage HCC (single <2 cm). AFP and AFP‐L3 began to increase from 6 months before diagnosis of HCC in cases (P < 0.05), while they remained unchanged in controls. At HCC diagnosis, the area under the receiver operator characteristic curves (AUROCs) for AFP, AFP‐L3, and DCP were 0.77, 0.73, and 0.71, respectively. Combining AFP and AFP‐L3 showed a higher AUROC (0.83), while adding DCP did not further improve the AUROC (0.86). With the optimal cutoff values (AFP, 5 ng/mL; AFP‐L3, 4%), the sensitivity and specificity of AFP and AFP‐L3 combination were 79% and 87%, respectively. The sensitivity of ultrasonography was 48.6%, which was increased to 88.6% and 94.3% by adding AFP and AFP + AFP‐L3, respectively. Conclusion: Among three biomarkers, AFP showed the best performance in discriminating HCC cases from controls; the AFP and AFP‐L3 combination, adopting cutoff values (5 ng/mL and 4%, respectively), significantly improved the sensitivity for detecting HCC at a very early stage.
Reading skills are foundational for daily lives, academic achievement, and careers. In this study, we systematically reviewed literacy interventions in low‐ and middle‐income countries, and estimated ...their effects on children's reading skills using a meta‐analytic approach. A total of 67 studies (N = 213,464) from 32 countries found in various databases (e.g., PsycINFO, ERIC) and sources (e.g., United States Agency for International Development) met our inclusion criteria. The results revealed an overall effect of .30 across various literacy outcomes. Effects varied for different outcomes, such that largest effects were found in emergent literacy skills (e.g., .40) and the smallest effects in reading comprehension (.25) and oral language skills (.20). Effects also varied as a function of other features such as teacher training support.
Microporous polyvinylidene difluoride (PVDF) hollow fiber membranes were fabricated via a thermally-induced phase separation (TIPS) method using an environmental-friendly hydrophobic solvent, acetyl ...tributyl citrate (ATBC, tradename Citroflex® A4). To maximize membrane tensile strength, the TIPS method was fully utilized by spinning fibers with high polymer content. It was observed that the fiber quality was significantly affected by the dope and bore flow rates and compositions, and an appropriate spinning range was established. The prepared membranes were subsequently stretched to tune the porosity, mean pore size, permeability, tensile strength, and fiber strain. A design of experiment (DOE) analysis was conducted using a 3-factor quadratic model to optimize the stretching conditions and to understand the effects of the parameters and interactions thereof. The permeability of the stretched membranes improved by a factor of 35 (15.1–538Lm−2h−1bar−1), and the tensile strength increased from 7.2MPa to 8.4MPa at the expense of the fiber strain. The DOE analysis revealed that the stretching ratio positively affects the permeability and porosity but decreases the fiber strain. On the other hand, it was determined that the stretching temperature positively influences the permeability and fiber strength. The stretched membranes exceeded the PVDF performance upper bound prepared by the TIPS method. The membranes were primarily in the α-phase polymorph, and stretching the fibers up to 40% at 90°C did not induce any detectable β-phase crystals. The proposed preparation method offers a feasible and sustainable alternative to fabricate hollow fibers membranes with high tensile strength and high permeability.
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•Microporous PVDF membranes were prepared via TIPS using a green hydrophobic solvent.•A stretching step was applied using a Design of Experiment (DOE).•Stretched membranes showed strong tensile strength and permeability improvement.
RNA tails play integral roles in the regulation of messenger RNA (mRNA) translation and decay. Guanylation of the poly(A) tail was discovered recently, yet the enzymology and function remain obscure. ...Here we identify TENT4A (PAPD7) and TENT4B (PAPD5) as the enzymes responsible for mRNA guanylation. Purified TENT4 proteins generate a mixed poly(A) tail with intermittent non-adenosine residues, the most common of which is guanosine. A single guanosine residue is sufficient to impede the deadenylase CCR4-NOT complex, which trims the tail and exposes guanosine at the 3' end. Consistently, depletion of TENT4A and TENT4B leads to a decrease in mRNA half-life and abundance in cells. Thus, TENT4A and TENT4B produce a mixed tail that shields mRNA from rapid deadenylation. Our study unveils the role of mixed tailing and expands the complexity of posttranscriptional gene regulation.
Tributyl O-acetyl citrate, also called acetyl tributyl citrate (ATBC), a new, environmental friendly diluent was introduced to prepare flat sheet and hollow fiber poly(vinylidene fluoride) (PVDF) ...membranes via thermally induced phase separation (TIPS). A phase diagram of PVDF/diluent is presented and the effect of different parameters such as polymer concentration, quenching temperature, air gap, and bore fluid temperature on the morphologies, properties, and water permeability of the PVDF membranes were investigated. The prepared PVDF membranes exhibited α form, and the mechanical properties and pure water flux are promising.
•An environmental diluent ATBC was introduced to prepare PVDF membranes for the first time.•Phase diagram of PVDF and this environmental diluent was measured for the first time.•Both flat sheet and hollow fiber PVDF membranes were prepared using this new diluent for the first time.•Bicontinuous structure was formed using this new environmental diluent.
There is a paucity of data regarding the differentiating characteristics of patients with laboratory-confirmed and those negative for Middle East respiratory syndrome coronavirus (MERS-CoV) in South ...Korea. This hospital-based retrospective study compared MERS-CoV-positive and MERS-CoV-negative patients. A total of seven positive patients and 55 negative patients with a median age of 43 years (P = 0.845) were included. No statistical differences were observed with respect to their sex and the presence of comorbidities. At the time of admission, headache (28.6% vs. 3.6%; odds ratio OR, 10.60; 95% confidence interval CI, 1.22–92.27), myalgia (57.1% vs. 9.1%; OR, 13.33; 95% CI, 2.30–77.24), and diarrhea (57.1% vs. 14.5%; OR, 7.83; 95% CI, 1.47–41.79) were common among MERS-CoV-positive patients. MERS-CoV-positive patients were more likely to have a low platelet count (164 ± 76.57 vs. 240 ± 79.87) and eosinophil (0.27 ± 0.43 vs. 2.13 ± 2.01; P = 0.003). Chest radiography with diffuse bronchopneumonia was more frequent in MERS-CoV-positive patients than in negative patients (100% vs. 62.5%; P = 0.491). The symptoms of headache, myalgia, and diarrhea, as well as laboratory characteristics, including low platelet counts and eosinophil, and chest X-ray showing diffuse bronchopneumonia might enhance the ability to detect patients in South Korea infected with MERS-CoV.
Ultrasonography (US) is generally recommended for the surveillance of hepatocellular carcinoma (HCC) in patients at risk. However, in patients with cirrhosis who have sufficiently high HCC incidence, ...surveillance using magnetic resonance imaging (MRI) with liver‐specific contrast showed markedly higher sensitivity in detecting early‐stage HCC than US. This study aimed to compare the cost‐effectiveness of semiannual surveillance using MRI versus US in patients with compensated cirrhosis and to identify the population that would gain optimal cost‐effectiveness through MRI surveillance. We designed a Markov model to compare the expected costs and quality‐adjusted life‐years (QALYs), between MRI and US, with a 20‐year time horizon, from the health care system perspective. The starting age of the cohort was 50 years, and 71% had hepatitis B virus–associated cirrhosis. The cycle length was 6 months. Transition probabilities and costs were obtained mainly from a prospective cohort study (the PRIUS study, NCT01446666). Cost and effectiveness were discounted at 5%. An incremental cost‐effectiveness ratio (ICER) was calculated and tested using sensitivity analyses. The cost‐effectiveness analysis indicated that the use of MRI incurred $5,562 incremental costs, 0.384 incremental life‐years (LYs), and 0.221 incremental QALYs compared to US. The annual HCC incidence was the most influential factor on the ICER. The ICERs were $14,474/LY and $25,202/QALY at an annual HCC incidence of 3%. When the HCC incidence rate was >1.81%, the ICER was below $50,000/QALY. With increased HCC incidence, MRI surveillance was acceptable as a cost‐effective option, even with an increased MRI/US cost ratio. Conclusion: Semiannual surveillance using MRI with liver‐specific contrast may be more cost‐effective than US in patients with virus‐associated compensated cirrhosis at sufficiently high HCC risk despite the higher test cost of MRI.
To develop clinical predictive nomograms generating per-patient numerical probabilities of postoperative recurrence-free and overall survival at specific times.
The prognosis after surgical resection ...is diverse in patients with early-stage hepatocellular carcinoma (HCC).
In a retrospective review, we evaluated data from 1085 mostly early-stage patients newly diagnosed with HCC who were subsequently treated by curative resection. We randomly divided the subjects into derivation (n = 760) and validation (n = 325) samples. Multivariate Cox proportional hazards models were developed and separately validated on the basis of pre- and postoperative clinical and pathological covariates assessed for association with 2-year recurrence and 5-year HCC-specific death. The discriminatory accuracy of the models was compared with traditional tools by analyzing receiver operating characteristic curves.
The statistical nomograms built on the basis of sex, serum albumin, platelet count, microvascular invasion, and calculated tumor volume had good calibration and discriminatory abilities, with c-indices of 0.69 (2-year recurrence) and 0.66 (5-year survival), respectively. These models showed satisfactory goodness-of-fit and discrimination abilities in the independent validation cohort (c-index, 0.66 for 2-year recurrence; and 0.67 for 5-year survival). The areas under the receiver operating characteristic curve using our methods were greater than those of conventional staging systems in the validation patients, indicating better discriminatory capability (corresponding c-indices, 0.55-0.56; and 0.55-0.61, respectively).
Our simple user-friendly calculators, which present graphically postsurgical prognostic models for recurrence and survival outcomes in patients with curatively resectable HCC, offer useful guidance to clinicians and patients for individually planning recurrence surveillance and adjuvant therapy.
Management of endometrial cancer, an adenocarcinoma of the endometrium which occupies most uterine corpus neoplasms, including uterine sarcomas, has been more relevant due to its increasing ...incidence. Extensive research on tumorigenesis molecular mechanisms and molecular characterization across cancers has brought paradigm shifts in the treatment of various malignant tumors. Endometrial cancer treatment has been traditionally guided according to the disease extent or histology types, while recent studies on molecular features have led to the introduction of targeted agents into clinical use, along with conventional chemotherapeutic agents in patients with recurrent or metastatic disease. Considering the proven efficacy and relatively tolerable toxicities of targeted therapies across malignant tumors, improvement of treatment outcomes is also expected in endometrial cancer by adopting an individualized therapy depending on the specific molecular features. Efficacy assessment of new biological agents is still ongoing based on previous preclinical data on endometrial cancer molecular features. Here, endometrial cancer molecular characterization will be reviewed, and then, we will introduce preclinical data, directing the adoption of new biological agents.
Background
Current major guidelines for diagnosis of hepatocellular carcinoma (HCC) based on imaging findings are different from each other and do not include clinical risk factors as a diagnostic ...criteria.
Purpose
To developed and validated a new diagnostic score system using MRI and clinical features as applied in chronic hepatitis B patients.
Study Type
Retrospective observational study.
Subject
A total of 418 treatment‐naïve patients (out of 902 patients) with chronic hepatitis B having 556 lesions suspected for HCC which were eligible for curative treatment.
Field Strength/sequence
T1W GRE in‐ and opposed‐phase, T2W FSE, DWI, and T1W 3D‐GRE dynamic contrast‐enhanced sequences at 1.5 T and 3 T.
Assessment
Six radiologists with 7–22 years of experience independently evaluated MR images based on Liver Imaging Reporting and Data System (LI‐RADS) version 2018.
Statistical Tests
Based on logistic regression analysis of MRI features and clinical factors, a risk score system was devised in derivation cohorts (268 patients, 352 lesions) and externally validated (150 patients, 204 lesions). The performance of the new score system was assessed by Harell's c‐index. Using cutoff value of 12, maintaining positive predictive value ≥95%, the diagnostic performances of the score system were compared with those of LR‐5.
Results
The 15‐point diagnostic scoring system used MRI features (lesion size, nonrim arterial phase hyperenhancement, portal venous phase hypointensity, hepatobiliary phase hypointensity, and diffusion restriction) and clinical factors (alpha‐fetoprotein and platelet). It showed good discrimination in the derivation (c‐index, 0.946) and validation cohorts (c‐index, 0.907). Using a risk score of 12 as a cut‐off, this system yielded higher sensitivity than LR‐5 (derivation cohort, 76.8% vs. 52.1%; validation cohort, 73.4% vs. 49.5%) without significant decrease in specificity (derivation cohort, 93.1% vs. 97.2%, P = 0.074; validation cohort, 91.7% vs. 96.1%, P = 0.299).
Data Conclusion
A new score system showed improved sensitivity in chronic hepatitis B patients compared to LI‐RADS without significant compromise in specificity.
Evidence Level
3
Technical Efficacy
Stage 2.
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