Virus-derived circular RNAs populate hepatitis C virus-infected cells.

It is known that pre-mRNAs in eukaryotic cells can be processed to circular RNAs by a backsplicing mechanism. Circular RNAs have great stability and can sequester proteins or small RNAs to exert functions on cellular pathways. Because viruses often exploit host pathways, we explored whether the RNA genome of the cytoplasmic hepatitis C virus is processed to yield virus-derived circRNAs (vcircRNAs). Computational analyses of RNA-seq experiments predicted that the viral RNA genome is fragmented to generate hundreds of vcircRNAs. More than a dozen of them were experimentally verified by rolling-circle amplification. VcircRNAs that contained the viral internal ribosome entry site were found to be translated into proteins that displayed proviral functions. Furthermore, two highly abundant, nontranslated vcircRNAs were shown to enhance viral RNA abundance. These findings argue that novel vcircRNA molecules modulate viral amplification in cells infected by a cytoplasmic RNA virus.

Computerized Cognitive Training in Mild Cognitive Impairment: Findings in African Americans and Caucasians.

BACKGROUND: African Americans with MCI may be at increased risk for dementia compared to Caucasians. The effect of race on the efficacy of cognitive training in MCI is unclear. METHODS: We used data from a two-site, 78-week randomized trial of MCI comparing intensive, home-based, computerized training with Web-based cognitive games or Web-based crossword puzzles to examine the effect of race on outcomes. The study outcomes were changes from baseline in cognitive and functional scales as well as MRI-measured changes in hippocampal volume and cortical thickness. Analyses used linear models adjusted for baseline scores. This was an exploratory study. RESULTS: A total of 105 subjects were included comprising 81 whites (77.1%) and 24 African Americans (22.8%). The effect of race on the change from baseline in ADAS-Cog-11 was not significant. The effect of race on change from baseline to week 78 in the Functional Activities Questionnaire (FAQ) was significant with African American participants' FAQ scores showing greater improvements at weeks 52 and 78 (P = 0.009, P = 0.0002, respectively) than white subjects. Within the CCT cohort, FAQ scores for African American participants showed greater improvement between baseline and week 78, compared to white participants randomized to CCT (P = 0.006). There was no effect of race on the UPSA. There was no effect of race on hippocampal or cortical thickness outcomes. CONCLUSIONS: Our preliminary findings suggest that web-based cognitive training programs may benefit African Americans with MCI at least as much as Caucasians, and highlight the need to further study underrepresented minorities in AD prevention trials. (Supported by the National Institutes of Health, National Institute on Aging; ClinicalTrials.gov number, NCT03205709.).

Expectancy Does Not Predict 18-month Treatment Outcomes with Cognitive Training in Mild Cognitive Impairment.

BACKGROUND: Computerized cognitive training (CCT) has emerged as a potential treatment option for mild cognitive impairment (MCI). It remains unclear whether CCT's effect is driven in part by expectancy of improvement. OBJECTIVES: This study aimed to determine factors associated with therapeutic expectancy and the influence of therapeutic expectancy on treatment effects in a randomized clinical trial of CCT versus crossword puzzle training (CPT) for older adults with MCI. DESIGN: Randomized clinical trial of CCT vs CPT with 78-week follow-up. SETTING: Two-site study - New York State Psychiatric Institute and Duke University Medical Center. PARTICIPANTS: 107 patients with MCI. INTERVENTION: 12 weeks of intensive training with CCT or CPT with follow-up booster training over 78 weeks. MEASUREMENTS: Patients rated their expectancies for CCT and CPT prior to randomization. RESULTS: Patients reported greater expectancy for CCT than CPT. Lower patient expectancy was associated with lower global cognition at baseline and older age. Expectancy did not differ by sex or race. There was no association between expectancy and measures of everyday functioning, hippocampus volume, or apolipoprotein E genotype. Expectancy was not associated with change in measures of global cognition, everyday functioning, and hippocampus volume from baseline to week 78, nor did expectancy interact with treatment condition. CONCLUSIONS: While greater cognitive impairment and increased age was associated with low expectancy of improvement, expectancy was not associated with the likelihood of response to treatment with CPT or CCT.

Withdrawn as duplicate: Post-yield softening of bending-dominated metal metamaterials.

This article has been withdrawn due to a publisher error that caused the article to be duplicated. The definitive version of this article is published under DOI https://doi.org/10.1210/pnasnexus/pgad075.

Post-yield softening of bending-dominated metal metamaterials.

Post-yield softening (PYS) plays an important role in guiding the design of high-performance energy-absorbing lattice materials. PYS is usually restricted to lattice materials that are stretching dominated according to the Gibson-Ashby model. Contrary to this long-held assumption, this work shows that PYS can also occur in various bending-dominated Ti-6Al-4V lattices with increasing relative density. The underlying mechanism for this unusual property is elucidated using the Timoshenko beam theory. It is attributed to the increase in stretching and shear deformation with increasing relative density, thereby increasing the tendency towards PYS. The finding of this work extends perspectives on PYS for the design of high-performance energy-absorbing lattice materials.

New weighting methods when cases are only a subset of events in a nested case-control study.

Nested case control (NCC) is a sampling method widely used for developing and evaluating risk models with expensive biomarkers on large prospective cohort studies. In a typical NCC design, biomarker values are obtained on a subcohort, where cases consist of all the events (subjects who experience the event during the follow-up). However, when the number of events is not small, due to the cost and limited availability of biospecimen, one may select only a subset of events as cases. We refer to such a variation as the untypical NCC. Unfortunately, existing inverse probability weighted (IPW) estimators for the untypical NCC are biased, and they only focus on relative risk parameters under the proportional hazards (PH) model. In this manuscript, we propose new weighting methods that produce consistent IPW estimators for not only relative risk parameters but also several metrics that evaluate a risk model's predictive performance. We also provide the inference procedure via perturbation resampling, which captures all the variance and between-subject covariance induced by the sampling processes for both case and control selections. In addition, our methods are not limited to the PH model, and they can be applied to the time-specific generalized linear model. Under the typical NCC design, our new weights are equivalent to the weight proposed by Samuelsen; under the untypical NCC, the IPW estimators using our weights have smaller bias and variance than the existing methods. We will demonstrate this improved performance via both analytical and numerical investigations.

[Rapid determination of 30 volatile organic compounds in workplace air by gas chromatography].

Objective: To establish a method for rapid detection of DB-WAX capillary column and determination of the workplace air in 30 kinds of volatile organic pollutants. Methods: In August 2020, N-pentane, n-hexane, methylcyclohexane, octane, Acetone, ethyl acetate, butanone, benzene, 3-pentanone, trichloroethylene, tetrachloroethylene, toluene, butyl acetate, 2-hexanone, Isoamyl acetate, ethylbenzene, p-xylene, m-xylene, amyl acetate, o-xylene, chlorobenzene, styrene, cyclohexanone, P-chlorotoluene, bromobenzene, M-dichlorobenzene, p-dichlorobenzene, O-dichlorobenzene, o-Chlorotoluene, 1, 2 , 4-trichlorobenzene of 30 kinds of substances in air were collected by activated carbon tube. After analysis by carbon disulfide, the analytical solution was analyzed by DB-WAX column and determined by FID detector. Results: The above 30 kinds of volatile organic pollutants had good separation effect, the correlation coefficient of the standard curve was above 0.999, the relative standard deviation was 0.1%-3.2%, the desorption efficiency was 77.0%-117.1% , the lower limit of quantitation was 0.33-5.33 µg/ml, and the lowest quantitation concentration was 0.22-3.55 mg/m(3), the recoveries ranged was 95.4%-104.9%. Conclusion: The method can effectively separate and accurately determine 30 volatile organic compounds in these workplaces, and the method is simple and quick.

Robust bulk micro-nano hierarchical copper structures possessing exceptional bactericidal efficacy.

Conventional copper (Cu) metal surfaces are well recognized for their bactericidal properties. However, their slow bacteria-killing potency has historically excluded them as a rapid bactericidal material. We report the development of a robust bulk superhydrophilic micro-nano hierarchical Cu structure that possesses exceptional bactericidal efficacy. It resulted in a 4.41 log10 reduction (>99.99%) of the deadly Staphylococcus aureus (S. aureus) bacteria within 2 min vs. a 1.49 log10 reduction (96.75%) after 240 min on common Cu surfaces. The adhered cells exhibited extensive blebbing, loss of structural integrity and leakage of vital intracellular material, demonstrating the rapid efficacy of the micro-nano Cu structure in destructing bacteria membrane integrity. The mechanism was attributed to the synergistic degradation of the cell envelope through enhanced release and therefore uptake of the cytotoxic Cu ions and the adhesion-driven mechanical strain due to its rapid ultimate superhydrophilicity (contact angle drops to 0° in 0.18 s). The scalable fabrication of this micro-nano Cu structure was enabled by integrating bespoke precursor alloy design with microstructure preconditioning for dealloying and demonstrated on 2000 mm2 Cu surfaces. This development paves the way to the practical exploitation of Cu as a low-cost antibiotic-free fast bactericidal material.

[Establishment of a nomogram model for predicting hematoma expansion in intracerebral hemorrhage and its multidimensional evaluation].

Objective: To establish a nomogram model for hematoma expansion (HE) prediction after intracerebral hemorrhage (ICH) and evaluate its performance in a multidimensionally way. Methods: A total of 348 ICH patients who were firstly diagnosed and hospitalized in the Second Affiliated Hospital of Soochow University from January 2017 to December 2019 were collected retrospectively. There were 236 males and 112 females, and their age ranged from 18 to 94 (62.0±14.6) years. All patients were divided into HE group (n=121) or non-HE group (n=227) according to the presence or absence of HE. The clinical and imaging features were compared between the two groups. Multivariate logistic regression analysis was performed for determining the independent predicting factors for HE prediction and a Nomogram model was established by using these factors. Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the prediction effectiveness, accuracy and clinical practicability of the model, respectively. Bootstrap method was used for internal validation. Results: There were significant differences in onset time, swirl sign, history of anticoagulants administrations, systolic blood pressure when admission, Glasgow coma scale (GCS) scores and RBC distribution width between the two groups[(1.77(1.0, 2.5) h vs 2(1, 3) h, 72 cases (59.5%) vs 94 cases (41.4%), 17 cases (14.0%) vs 15 cases (6.6%), (170.69±29.19) mmHg(1 mmHg=0.133 kPa) vs (163.84±26.07) mmHg, 11(8, 14) scores vs 14(10, 15) scores, 44.3% (41.2%, 46.8%) vs 42.4% (40.1%, 45.3%);respectively, all P<0.05]. Multivariate logistic regression analysis demonstrated that onset time (OR=0.809, 95%CI: 0.682-1.961, P=0.015), swirl sign (OR=0.562, 95%CI:0.349-0.905, P=0.018), history of anticoagulants administrations (OR=0.394, 95%CI: 0.180-1.861, P=0.020), and GCS (OR=0.881, 95%CI: 0.815-1.952, P=0.001) were the predicting factors for HE. The area under the curve (AUC) of the Nomogram model was 0.735(95%CI: 0.687-0.805), which demonstrated that the model has an ideal prediction effectiveness. The calibration curve showed that the prediction probability of HE of the model fits well with the actual probability, and with high calibration. DCA showed relatively wide range of optional threshold probability of the model (ranging from 14% to 72%), the clinical practicability of this model was high. The internal validation results showed a C-index of 0.703, indicated a good discrimination power. Conclusion: The established Nomogram model can predict the HE of ICH with good prediction effectiveness, discrimination power and with good clinical practicability, which can be capable of providing an intuitive and visual guidance tool for timely identifying ICH patients who may have HE.

A relationship between the incremental values of area under the ROC curve and of area under the precision-recall curve.

BACKGROUND: Incremental value (IncV) evaluates the performance change between an existing risk model and a new model. Different IncV metrics do not always agree with each other. For example, compared with a prescribed-dose model, an ovarian-dose model for predicting acute ovarian failure has a slightly lower area under the receiver operating characteristic curve (AUC) but increases the area under the precision-recall curve (AP) by 48%. This phenomenon of disagreement is not uncommon, and can create confusion when assessing whether the added information improves the model prediction accuracy. METHODS: In this article, we examine the analytical connections and differences between the AUC IncV (ΔAUC) and AP IncV (ΔAP). We also compare the true values of these two IncV metrics in a numerical study. Additionally, as both are semi-proper scoring rules, we compare them with a strictly proper scoring rule: the IncV of the scaled Brier score (ΔsBrS) in the numerical study. RESULTS: We demonstrate that ΔAUC and ΔAP are both weighted averages of the changes (from the existing model to the new one) in separating the risk score distributions between events and non-events. However, ΔAP assigns heavier weights to the changes in higher-risk regions, whereas ΔAUC weights the changes equally. Due to this difference, the two IncV metrics can disagree, and the numerical study shows that their disagreement becomes more pronounced as the event rate decreases. In the numerical study, we also find that ΔAP has a wide range, from negative to positive, but the range of ΔAUC is much smaller. In addition, ΔAP and ΔsBrS are highly consistent, but ΔAUC is negatively correlated with ΔsBrS and ΔAP when the event rate is low. CONCLUSIONS: ΔAUC treats the wins and losses of a new risk model equally across different risk regions. When neither the existing or new model is the true model, this equality could attenuate a superior performance of the new model for a sub-region. In contrast, ΔAP accentuates the change in the prediction accuracy for higher-risk regions.

Serum calprotectin correlates with risk and disease severity in psoriasis patients and the decrease of calprotectin predicts better response to tumor necrosis factor inhibitors.

The article "Serum calprotectin correlates with risk and disease severity in psoriasis patients and the decrease of calprotectin predicts better response to tumor necrosis factor inhibitors, by M. Qian, N.-J. Song, published in Eur Rev Med Pharmacol Sci 2018; 22 (13): 4299-4309-DOI: 10.26355/eurrev_201807_15426-PMID: 30024620" has been withdrawn from the authors since the conclusions of the paper had some shortcomings and the authors decided to improve them further. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/15426.

[Study on the hospitalization cost and its influencing factors of imported malaria patients in Guangxi Zhuang Autonomous Region and Yunnan Province].

OBJECTIVE: To analyze the hospitalization cost and its influencing factors of imported malaria patients in Guangxi Zhuang Autonomous Region and Yunnan Province, so as to provide insights into the evaluation of the economic burden due to imported malaria, and the guiding of malaria control and the rational allocation of medical resources. METHODS: The data pertaining to the hospitalization costs of imported malaria patients admitted to Shanglin County People's Hospital in Guangxi Zhuang Autonomous Region during the period from January 1 through December 31, 2019, and Tengchong Municipal People's Hospital in Yunnan Province from January 1, 2015 to December 31, 2019, were collected, and the epidemiological data of these imported malaria patients were extracted from the Information Management System for Parasitic Diseases Control and Prevention, China. The composition of the hospitalization expenses was analyzed using a descriptive method. In addition, the factors affecting the hospitalization expenses of imported malaria patients were identified using a univariate analysis and a recursive system model. RESULTS: A total of 206 imported malaria patients were included in this study, including 194 men (94.17%) and 12 women (5.83%). The mean length of hospital stay was 5.00 days per patient and the median hospitalization expenses were 2 813.07 Yuan per time, in which the expenses for laboratory examinations were the highest (45.31%, 1 274.62/2 813.07). Univariate analysis showed that hospital (z = 5.43, P < 0.01), type of malaria (χ2 = 34.86, P < 0.01) and type of payment (χ2 = 7.72, P < 0.05) were factors affecting the hospitalization expenses of imported malaria patients. Recursion system modeling revealed that the total effects on hospitalization expenses of imported malaria patients included length of hospital stay (0.78), selection of hospital (0.34), basic medical insurance for urban and rural residents (0.19), new rural cooperative medical care (0.17), Plasmodium falciparum malaria (0.15), gender (0.11) and P. vivax malaria (0.09). CONCLUSIONS: The hospitalization expenses of imported malaria patients are affected by multiple factors in Guangxi Zhuang Autonomous Region and Yunnan Province, in which the length of hospital stay is the most predominant influencing factor. A reduction in the length of hospital stay is effective to decrease the hospitalization expenses of imported malaria patients.

[The 486th case: chronic diarrhea and orthostatic hypotension].

A 57-year-old man was admitted to hospital with diarrhea for 10 months and dizziness for 4 months. The patient had 1-2 liters watery stool per day, without pyogenic blood or abnormality in gastroenteroscopy examination. The level of hemoglobin and albumin was generally normal, and fasting test was positive. At the same time, he was accompanied with hyperalgesia of lower limbs and orthostatic hypotension. After the discussion of multiple disciplinary teams, the patient was diagnosed with amyloidosis by sural nerve biopsy, myocardial MRI, and the assays of urine immunoelectrophoresis and serum free light chain. Light chain amyloidosis was confirmed after excluded the diagnosis of familial amyloidosis. The patient was improved after courses of chemotherapy with melphalan and dexamethasone.

Intravenous administration of bone marrow mesenchymal stem cells alleviates renal failure in diabetic mice.

OBJECTIVE: To study the protective effect and mechanism of intravenously administered bone marrow mesenchymal stem cells (BMSCs) on renal failure in diabetic mice. PATIENTS AND METHODS: BMSCs were obtained from the bone marrow of mice, identified by flow cytometry and tri-line differentiation test. Diabetic model (DM) mice were established using STZ and infused with mice BMSCs intravenously, followed by the analysis of fasting blood glucose and proteinuria levels, renal tissue damage by optical microscope and electron microscope, and PI3K/AKT signaling protein expression in kidney by Western blot and endocrine function by immunofluorescence staining. RESULTS: DM mice exhibited gradually increased albumin excretion rate with time, and the MSC-treated diabetic mice presented significantly reduced proteinuria levels. HE staining indicated that MSC administration mitigated renal damage as proved by smaller tubular dilatation, reduced glomerulosclerosis and trace protein cylinders, and recovered kidney ultrastructure as shown by improved mesangial dilatation and podocyte loss. Further, BMSCs treatment activated PI3K/AKT signaling, which was downregulated in diabetic mice. However, MSC administration failed to improve pancreatic endocrine function in DM mice. CONCLUSIONS: Intravenous administration of MSCs can effectively prevent renal failure in diabetic mice by activating PI3K/AKT signaling pathway.