Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Recurrence Surveillance on Recurrence Patterns After Resection of Hepatocellular Carcinoma.

OBJECTIVE This study aims to validate a previously reported recurrence clinical risk score (CRS). SUMMARY OF BACKGROUND DATA Salvage transplantation after hepatocellular carcinoma (HCC) resection is limited to patients who recur within Milan criteria (MC). Predicting recurrence patterns may guide treatment recommendations. METHODS An international, multicenter cohort of R0 resected HCC patients were categorized by MC status at presentation. CRS was calculated by assigning 1 point each for initial disease beyond MC, multinodularity, and microvascular invasion. Recurrence incidences were estimated using competing risks methodology, and conditional recurrence probabilities were estimated using the Bayes theorem. RESULTS From 1992 to 2015, 1023 patients were identified, of whom 613 (60%) recurred at a median follow-up of 50 months. CRS was well validated in that all 3 factors remained independent predictors of recurrence beyond MC (hazard ratio 1.5-2.1, all P < 0.001) and accurately stratified recurrence risk beyond MC, ranging from 19% (CRS 0) to 67% (CRS 3) at 5 years. Among patients with CRS 0, no other factors were significantly associated with recurrence beyond MC. The majority recurred within 2 years. After 2 years of recurrence-free survival, the cumulative risk of recurrence beyond MC within the next 5 years for all patients was 14%. This risk was 12% for patients with initial disease within MC and 17% for patients with initial disease beyond MC. CONCLUSIONS CRS accurately predicted HCC recurrence beyond MC in this international validation. Although the risk of recurrence beyond MC decreased over time, it never reached zero.
Constrained mutational sampling of amino acids in HIV-1 protease evolution

HIV-1 samples a large number of sequence variants that help the virus to evade the immune system and escape from antiviral drugs. However, it is unclear how amino acid changes that require multiple nucleotide mutations contribute to the evolution of HIV-1. In a large database of HIV-1 protease sequences from circulating viruses we find that the most frequently observed amino acids are disproportionately accessible by single-base mutations from the consensus amino acid. Multiple-base mutations at a codon may be rarely sampled and/or exhibit fitness defects. To investigate the impact of fitness effects on mutant frequency, we quantified the experimental impacts of all individual amino acid changes in protease on the expansion of HIV-1 in tissue culture. Many amino acid changes requiring multiple nucleotide mutations that efficiently supported viral replication were observed rarely, or not at all, in the sequence database. Frequently observed amino acid changes that require multiple nucleotide mutations were accessible by single nucleotide mutational intermediates with higher fitness, on average, compared to the intermediates for unobserved amino acid changes. An additive quasispecies model that combined different mutational barriers for single- and multiple-base mutations with the experimental fitness effects showed an improved correspondence with clinical observations of mutant frequencies compared to fitness alone. Our results indicate that mutational sampling provides a larger barrier than fitness effects to amino acid changes requiring multiple base mutations in HIV-1 protease.
Integrative Physiology/Experimental Medicine Chylomicronemia Elicits Atherosclerosis in Mice—Brief Report

Objective—The risk of atherosclerosis in the setting of chylomicronemia has been a topic of debate. In this study, we examined susceptibility to atherosclerosis in Gpihbp1-deficient mice (Gpihbp1 / ), which manifest severe chylomicronemia as a result of defective lipolysis. Methods and Results—Gpihbp1 / mice on a chow diet have plasma triglyceride and cholesterol levels of 2812 209 and 319 27 mg/dL, respectively. Even though nearly all of the lipids were contained in large lipoproteins (50 to 135 nm), the mice developed progressive aortic atherosclerosis. In other experiments, we found that both Gpihbp1-deficient “apo-B48–only” mice and Gpihbp1-deficient “apo-B100–only” mice manifest severe chylomicronemia. Thus, GPIHBP1 is required for the processing of both apo-B48– and apo-B100–containing lipoproteins. Conclusions—Chylomicronemia causes atherosclerosis in mice. Also, we found that GPIHBP1 is required for the lipolytic processing of both apo-B48 – and apo-B100 – containing lipoproteins. (Arterioscler Thromb Vasc Biol. 2010;30:20-23.)
The effects of five days of intensive preoperative inspiratory muscle training on postoperative complications and outcome in patients having cardiac surgery: a randomized controlled trial

Objective: To determine the prophylactic efficacy of short-term intensive preoperative inspiratory muscle training on the incidence of postoperative pulmonary complications in patients scheduled for cardiac surgery. Design: Single-blind, randomized controlled pilot study. Setting: TEDA International Cardiovascular Hospital, China. Subjects: In total, 197 subjects aged ⩾50 years scheduled for cardiac surgery were selected. Intervention: The intervention group (n = 98) received five days of preoperative inspiratory muscle training on top of the usual care received by the patients in the control group (n = 99). Main measures: The primary outcome variable was the occurrence of postoperative pulmonary complications. The secondary outcome variables were inspiratory muscle strength, lung function and length of hospitalization. Results: After cardiac surgery, a total of 10 (10.2%) of the 98 patients in the intervention group and 27 (27.3%) of 99 patients in the control group had postoperative pulmonary complications (risk ratio, 0.23; 95% confidence interval (CI), 0.09–0.58, P = 0.002). The study revealed that, compared with the control group, the intervention group had a significant increase in inspiratory muscle strength (by 10.48 cm H2O, P < 0.001), forced expiratory volume in the first second of expiration (FEV1) %predicted (by 3.75%, P = 0.030), forced vital capacity (FVC) %predicted (by 4.15%, P = 0.008) and maximal voluntary ventilation (MVV) %predicted (by 6.44%, P = 0.034). Length of hospital stay was 7.51 (2.83) days in the intervention group and 9.38 (3.10) days in the control group (P = 0.039). Conclusion: A five-day intensive pattern of preoperative inspiratory muscle training reduced the incidence of postoperative pulmonary complications and duration of postoperative hospitalization in patients undergoing cardiac surgery.
The Simple Pediatric Activity Ultrasound Score (SPAUSS) for the Accurate Detection of Pediatric Inflammatory Bowel Disease.

OBJECTIVE To identify the most significant ultrasound (US) parameters that predict inflammatory activity and develop a simple US activity score. METHODS Patients were identified through retrospective evaluation of an established database of children with inflammatory bowel disease (IBD). Patients with endoscopy and US within 60 days were included (N = 75). US parameters evaluated included: bowel wall thickness (BWT), mesenteric inflammatory fat, lymphadenopathy and hyperemia. The weighted kappa statistic was calculated to assess agreement between sonographic and endoscopically identified disease location. Using a proportional odds model and ordinal logistic regression, statistically significant (p < 0.05) parameters were used to generate a score. Variables were weighted to classify individuals into severity classes. Receiver operating characteristic curves (ROC) were plotted to demonstrate the score's discriminative and predictive capacity. RESULTS There was substantial agreement between US and endoscopy for all disease locations (weighted kappa = 0.85) and substantial agreement for ileocolonic disease (weighted kappa = 0.96). Two sonographic parameters were identified as contributing significantly to disease activity: BWT and mesenteric inflammatory fat (p < 0.05). A predictive score was developed incorporating BWT, hyperemia and inflammatory fat and ROC curves demonstrated good predictive capacity to distinguish between the absence of disease (normal) and active disease with an AUC of 82.1%. CONCLUSIONS The most important sonographic parameters for predicting disease activity were BWT and mesenteric inflammatory fat. When combined with hyperemia into a simple score, there was accurate detection of inflammatory activity in children with IBD. This score may facilitate non-invasive, bedside detection of inflammation and standardize the use of US in children.
Timing Variability during Gait Initiation Is Increased in People with Alzheimer’s Disease Compared to Controls

Background/Aims: Variability of constant speed walking is closely related to falls risk in people with Alzheimer’s disease (AD) who fall at 3 times the rate of normal elders. Falls are likely to be provoked during gait initiation, so this study aimed to determine if people with mild-moderate AD have greater variability of gait at initiation. Methods: Measures of step and stride length and time, step width and double support time were recorded during gait initiation for 10 males and 10 females with AD and 20 age- and gender-matched controls. Variability was calculated using the coefficient of variation (CV). Effect size was calculated using Cohen’s d. Results: During gait initiation AD participants had greater variability than controls in stride timing (AD CV = 4.65, Control CV = 3.64; p < 0.05, d = 0.71) and double support proportion (AD CV = 9.40, Control CV = 7.62; p < 0.05, d = 0.8). Conclusion: Increased timing variability in people with AD occurs during gait initiation as well as during constant speed walking and is evident in the early disease stages.
Peptide‐based building blocks as structural elements for supramolecular Gd‐containing MRI contrast agents

Magnetic resonance imaging (MRI) is one of the most important clinic diagnostic tool used to obtain high‐quality body images. The administration of low‐molecular‐weight Gd complex–based MRI contrast agents (CAs) permits to increase the 1H relaxation rate of nearby water molecules, thus modulating signal intensity and contrast enhancement. Even if highly accurate, MRI modality suffers from its low sensitivity. Moreover, low‐molecular‐weight CAs rapidly equilibrate between the intravascular and extravascular spaces after their administration. In order to improve their sensitivity and limit the extravasation phenomenon, several macromolecular and supramolecular multimeric gadolinium complexes (dendrimers, polymers, carbon nanostructures, micelles, and liposomes) have been designed until now. Because of their biocompatibility, low immunogenicity, low cost, and easy synthetic modification, peptides are attractive building blocks for the fabbrication of novel materials for biomedical applications. We report on the state of the art of supramolecular CAs obtained by self‐assembly of three different classes of building blocks containing a peptide sequence, a gadolinium complex, and, if necessary, a third functional portion achieving the organization process.
Weak premating isolation between Clitarchus stick insect species despite divergent male and female genital morphology

Documenting natural hybrid systems builds our understanding of mate choice, reproductive isolation and speciation. The stick insect species Clitarchus hookeri and C. tepaki differ in their genital morphology and hybridize along a narrow peninsula in northern New Zealand. We utilize three lines of evidence to understand the role of premating isolation and species boundaries: (a) genetic differentiation using microsatellites and mitochondrial DNA; (b) variation in 3D surface topology of male claspers and 2D morphometrics of female opercular organs; and (c) behavioural reproductive isolation among parental and hybrid populations through mating crosses. The genetic data show introgression between the parental species and formation of a genetically variable hybrid swarm. Similarly, the male and female morphometric data show genital divergence between the parental species as well as increased variation within the hybrid populations. This genital divergence has not resulted in reproductive isolation between species, instead weak perimating isolation has enabled the formation of a hybrid swarm. Behavioural analysis demonstrates that the entire mating process influences the degree of reproductive isolation between species undergoing secondary contact. Mechanical isolation may appear strong, whereas perimating isolation is weak.
Perspectives on trace chemical safety and chemophobia: risk communication and risk management

ABSTRACT Safety issues regarding consumer products contaminated with trace amounts of chemicals are of great concern to consumers, with the degree of concern occasionally escalating to the psychological syndrome, chemophobia (i.e., the fear of chemicals). Hazardous substances frequently implicated in safety concerns include heavy metals (arsenic, mercury, cadmium, and lead), volatile organic compounds (VOC) such as benzene and o-toluidine, pesticides, carcinogens, radioactive substances, and endocrine disrupting chemicals (EDC) such as bisphenol A and phthalates. To improve communication of risk to society, members of academia, government, consumer organizations, and industry participated in this workshop to discuss and exchange perspectives on trace chemical safety. From the perspective of academia, integrated risk assessments need to be implemented to encompass various exposure sources and routes. The identification and investigation of new exposure-related biomarkers are also recommended to verify direct causal relationships between specific chemical exposure and effects on human health. As for regulation, governments need to establish and maintain acceptable limits for trace chemicals in products. In addition, harmonized efforts need to be undertaken among government agencies to share regulatory limits and effectively control trace chemicals in consumer products. Manufacturers need to faithfully abide by Good Manufacturing Practice (GMP) guidelines, monitor sources of contamination, and minimize these for consumer safety. To effectively resolve safety issues arising from trace chemicals exposure, collaborative efforts are needed involving academia, government, consumer organizations, and industry. Further, scientific evidence-based risk assessment is a critical approach to effectively manage trace chemical safety issues.
Complete mitochondrial genome of the marine polychaete, Marphysa sanguinea (Polychaeta, Eunicida)

Abstract The complete mitochondrial genome of Marphysa sanguinea from northern China was determined. This entire sequence was 15,159 bp in length, containing 13 protein-coding genes (PCGs), 2 rRNA genes, 22 tRNA genes and a putative control region (D-loop). The base composition of the genome was 30.7% A, 30.3% T, 26.5% C and 12.6% G. Some PCGs shared nucleotides with neighboring genes, and all 13 PCGs had ATG as a start codon. Two complete stop codons (TAA, TAG) were used by the PCGs. Compared to other marine polychaetes and oligophaetes, most of the PCGS were without any rearrangement, except for ND2 and ND3, in which the order was reversed.
Avoiding Alzheimer’s disease: The important causative role of divalent copper ingestion

In this review, we point out that developed countries are undergoing an epidemic of Alzheimer’s disease, not shared by undeveloped countries. We also point out that this epidemic is new, developing during the 20th century. This suggests that an environmental change occurring in the 20th century in developed countries is causing the epidemic. The author hypothesizes that the environmental change causing the epidemic of Alzheimer’s disease is ingestion of divalent copper. The hypothesis is based on data indicating that food copper is primarily monovalent copper, and humans evolved safe ways of channeling monovalent copper, but not divalent copper. Humans were not exposed to divalent copper until the 20th century, due to the use of copper plumbing and supplement pills containing copper, and that exposure, which occurs in developed countries, does not occur in undeveloped countries. Data in support of the hypothesis show that tiny amounts of divalent copper added to drinking water of Alzheimer’s disease animal models greatly enhance Alzheimer’s disease, and ingestion of copper (which is always divalent copper)-containing supplement pills by humans is quite toxic to cognition. Impact statement The work described in this review is very important to scientists working on Alzheimer’s disease (AD) because it reveals a cause for the explosive epidemic of this disease. It is also important to the public because it provides a method to avoid this newly revealed cause, and thereby avoid AD. The field is advanced because this review reveals new information about the mechanism of AD pathogenesis, namely copper, and specifically divalent copper, toxicity is important. New information about divalent copper toxicity in the brain affecting cognition is revealed. The field is impacted strongly because, in view of the frustrations that have occurred in treatment developed, now most AD can be prevented. This means the suffering of the patient, the prolonged and difficult care required by caregivers, and the enormous expenditures for this one disease, can now be avoided.
Neural Mechanisms Involved in the Noxious Physical Stress‐Induced Inhibition of Ovarian Estradiol Secretion

Stress is known to change the secretion of ovarian steroid hormones via the hypothalamic–pituitary–ovarian (HPO) axis. Noxious physical stress can cause reflex responses in visceral function via autonomic nerves. This article reviews our recent animal studies on neural mechanisms involved in ovarian estradiol secretion induced by noxious physical stress stimulation. In anesthetized rats, noxious physical stress (pinching the hindpaw or electrical stimulation of the tibial nerve) decreased ovarian estradiol secretion. These noxious stress‐induced ovarian hormonal responses were observed after decerebration but were abolished after spinal transection. Electrical stimulation of the ovarian sympathetic nerves (superior ovarian nerves: SON) decreased ovarian estradiol secretion. The reduced secretion of ovarian estradiol induced by hindpaw pinching was abolished by bilateral severance of the SON. Efferent activity of the SON was increased following hindpaw pinching. Thus, the inhibition of ovarian estradiol secretion during noxious physical stress was mainly integrated in the brainstem, and this inhibitory response was due to reflex activation of sympathetic nerves to the ovary. In rats, the sympathetic inhibitory regulation of ovarian estradiol secretion was pronounced when the HPO axis was inhibited by chronic estradiol treatment. Considering the female life cycle, extensive physical stress may inhibit ovarian function, especially before puberty and during old ages when the HPO axis is inactive. Anat Rec, 302:904–911, 2019. © 2019 Wiley Periodicals, Inc.
Detection of Intracoronary Thrombus by Magnetic Resonance Imaging in Patients With Acute Myocardial Infarction

Background— Persistent intracoronary thrombus after plaque rupture is associated with an increased risk of subsequent myocardial infarction and mortality. Coronary thrombus is usually visualized invasively by x-ray coronary angiography. Non–contrast-enhanced T1-weighted magnetic resonance (MR) imaging has been useful for direct imaging of carotid thrombus and intraplaque hemorrhage by taking advantage of the short T1 of methemoglobin present in acute thrombus and intraplaque hemorrhage. The aim of this study was to investigate the use of non–contrast–enhanced MR for direct thrombus imaging (MRDTI) in patients with acute myocardial infarction. Methods and Results— Eighteen patients (14 men; age, 61±9 years) underwent MRDTI within 24 to 72 hours of presenting with an acute coronary syndrome before invasive x-ray coronary angiography; MRDTI was performed with a T1-weighted, 3-dimensional, inversion-recovery black-blood gradient-echo sequence without contrast administration. Ten patients were found to have intracoronary thrombus on x-ray coronary angiography (left anterior descending, 4; left circumflex, 2; right coronary artery, 4; and right coronary artery–posterior descending artery, 1), and 8 had no visible thrombus. We found that MRDTI correctly identified thrombus in 9 of 10 patients (sensitivity, 91%; posterior descending artery thrombus not detected) and correctly classified the control group in 7 of 8 patients without thrombus formation (specificity, 88%). The contrast-to-noise ratio was significantly greater in coronary segments containing thrombus (n=10) compared with those without visible thrombus (n=131; mean contrast-to-noise ratio, 15.9 versus 2.6; P<0.001). Conclusion— Use of MRDTI allows selective visualization of coronary thrombus in a patient population with a high probability of intracoronary thrombosis.
Improvements in Radiographic Progression-Free Survival Stratified by ERG Gene Status in Metastatic Castration-Resistant Prostate Cancer Patients Treated with Abiraterone Acetate

Purpose: Gene fusions leading to androgen receptor–modulated ERG overexpression occur in up to 70% of metastatic castration-resistant prostate cancers (mCRPC). We assessed the association between ERG rearrangement status and clinical benefit from abiraterone acetate. Experimental Design: COU-AA-302 is a phase III trial comparing abiraterone acetate and prednisone versus prednisone in chemotherapy-naïve mCRPC. ERG status was evaluated by FISH on archival tumors. End points included radiographic progression-free survival (rPFS), time to PSA progression (TTPP), rate of ≥50% PSA decline from baseline, and overall survival (OS). Cox regression was used to evaluate association with time-to-event measures and Cochran–Mantel–Haenszel for PSA response. Results: ERG status was defined for 348 of 1,088 intention-to-treat patients. ERG was rearranged in 121 of 348 patients with confirmed ERG status (35%). Cancers with an ERG fusion secondary to deletion of 21q22 and increased copy number of fusion sequences (class 2+ Edel) had a greater improvement in rPFS after abiraterone acetate and prednisone [22 vs. 5.4 months; HR (95% confidence interval, CI), 0.31 (0.15–0.68); P = 0.0033] than cancers with no ERG fusion [16.7 vs. 8.3 months; 0.53 (0.38–0.74); P = 0.0002] or other classes of ERG rearrangement. There was also greater benefit in this subgroup for TTPP. Conclusions: Both ERG-rearranged and wild-type cancers had a significant improvement in rPFS with abiraterone acetate and prednisone in the COU-AA-302 trial. However, our data suggest that 2+ Edel cancers, accounting for 15% of all mCRPC patients and previously associated with a worse outcome, derived the greatest benefit. Clin Cancer Res; 21(7); 1621–7. ©2015 AACR.
Coefficient Matrix Decomposition Method and BIBO Stabilization of Stochastic Systems with Time Delays

The mean square BIBO stabilization is investigated for the stochastic control systems with time delays and nonlinear perturbations. A class of suitable Lyapunov functional is constructed, combined with the descriptor model transformation and the decomposition technique of coefficient matrix; thus some novel delay-dependent mean square BIBO stabilization conditions are derived. These conditions are expressed in the forms of linear matrix inequalities (LMIs), whose feasibility can be easily checked by using Matlab LMI Toolbox. Finally, three numerical examples are given to demonstrate that the derived conditions are effective and much less conservative than those given in the literature.