Miracle-dz/UniFAR-FTUs huggingface dataset:
From alcohol initiation to tolerance to problems: Discordant twin modeling of a developmental process

Abstract The current study examined a stage-based alcohol use trajectory model to test for potential causal effects of earlier drinking milestones on later drinking milestones in a combined sample of two cohorts of Australian monozygotic and same-sex dizygotic twins (N = 7,398, age M = 30.46, SD = 2.61, 61% male, 56% monozygotic twins). Ages of drinking, drunkenness, regular drinking, tolerance, first nontolerance alcohol use disorder symptom, and alcohol use disorder symptom onsets were assessed retrospectively. Ages of milestone attainment (i.e., age-of-onset) and time between milestones (i.e., time-to-event) were examined via frailty models within a multilevel discordant twin design. For age-of-onset models, earlier ages of onset of antecedent drinking milestones increased hazards for earlier ages of onset for more proximal subsequent drinking milestones. For the time-to-event models, however, earlier ages of onset for the “starting” milestone decreased risk for a shorter time period between the starting and the “ending” milestone. Earlier age of onset of intermediate milestones between starting and ending drinking milestones had the opposite effect, increasing risk for a shorter time period between the starting and ending milestones. These results are consistent with a causal effect of an earlier age of drinking milestone onset on temporally proximal subsequent drinking milestones.
Translational Advances of Hydrofection by Hydrodynamic Injection

Hydrodynamic gene delivery has proven to be a safe and efficient procedure for gene transfer, able to mediate, in murine model, therapeutic levels of proteins encoded by the transfected gene. In different disease models and targeting distinct organs, it has been demonstrated to revert the pathologic symptoms and signs. The therapeutic potential of hydrofection led different groups to work on the clinical translation of the procedure. In order to prevent the hemodynamic side effects derived from the rapid injection of a large volume, the conditions had to be moderated to make them compatible with its use in mid-size animal models such as rat, hamster and rabbit and large animals as dog, pig and primates. Despite the different approaches performed to adapt the conditions of gene delivery, the results obtained in any of these mid-size and large animals have been poorer than those obtained in murine model. Among these different strategies to reduce the volume employed, the most effective one has been to exclude the vasculature of the target organ and inject the solution directly. This procedure has permitted, by catheterization and surgical procedures in large animals, achieving protein expression levels in tissue close to those achieved in gold standard models. These promising results and the possibility of employing these strategies to transfer gene constructs able to edit genes, such as CRISPR, have renewed the clinical interest of this procedure of gene transfer. In order to translate the hydrodynamic gene delivery to human use, it is demanding the standardization of the procedure conditions and the molecular parameters of evaluation in order to be able to compare the results and establish a homogeneous manner of expressing the data obtained, as ‘classic’ drugs.
Facial emotion expression recognition by children at familial risk for depression: high-risk boys are oversensitive to sadness.

BACKGROUND Offspring of depressed parents are at greatly increased risk for mood disorders. Among potential mechanisms of risk, recent studies have focused on information processing anomalies, such as attention and memory biases, in the offspring of depressed parents. In this study we examined another information processing domain, perceptual sensitivity to emotion cues in facial expressions, as a potential mechanism of risk that characterizes the offspring of depressed parents. METHODS The study included 64 children at familial-risk for depression and 40 low-risk peers between the ages 7 and 13(Mage = 9.51; SD = 2.27). Participants were presented with pictures of facial expressions that varied in emotional intensity from neutral to full-intensity sadness or anger (i.e., emotion recognition), or pictures of faces morphing from anger to sadness (emotion discrimination). After each picture was presented, children indicated whether the face showed a specific emotion (i.e., sadness, anger) or no emotion at all (neutral) using a forced choice paradigm. We examined group differences in the intensity of emotion that suggested greater sensitivity to specific emotions. RESULTS In the emotion recognition task, boys (but not girls) at familial-risk for depression identified sadness at significantly lower levels of emotional intensity than did their low-risk peers. The high and low-risk groups did not differ with regard to identification of anger. In the emotion discrimination task, both groups displayed over-identification of sadness in ambiguous mixed faces but high-risk youth were less likely to show this labeling bias than their peers. CONCLUSION Our findings are consistent with the hypothesis that enhanced perceptual sensitivity to subtle traces of sadness in facial expressions may be a potential mechanism of risk among boys at familial-risk for depression. This enhanced perceptual sensitivity does not appear to be due to biases in the labeling of ambiguous faces.
On the bending characteristics of damaged composite conoidal shells - a finite element approach

A finite element analysis of composite conoidal shells with delamination damage is carried out to explore the bending characteristics of such shell configurations. Civil and structural engineers have always preferred conoidal shell configuration, which is a ruled and aesthetically pleasant shape. The introduction of laminated composite as the structural material has provided the impetus to explore the different behavioral aspects of composite conoids. The laminated composites are susceptible to delamination damage, occurring due to manufacturing defects or over loadings. Keeping the above points in mind, a finite element analysis using isoparametric shell bending element is presented here, incorporating a multipoint constraint algorithm to take care of compatibility of deformation and equilibrium of forces and moments at the delamination crack front. The formulation is validated through solution of benchmark problems, and a number of delaminated conoidal shells with different boundary conditions are solved for different extents of delamination damage and stacking sequences under uniformly distributed load. The truncation ratio, and hence curvature values, are also varied keeping in mind the industrial requirements of both full and truncated conoids. Results are carefully analyzed to arrive at a set of meaningful conclusions.
Emerging Fusarium and Alternaria Mycotoxins: Occurrence, Toxicity and Toxicokinetics

Emerging Fusarium and Alternaria mycotoxins gain more and more interest due to their frequent contamination of food and feed, although in vivo toxicity and toxicokinetic data are limited. Whereas the Fusarium mycotoxins beauvericin, moniliformin and enniatins particularly contaminate grain and grain-based products, Alternaria mycotoxins are also detected in fruits, vegetables and wines. Although contamination levels are usually low (µg/kg range), higher contamination levels of enniatins and tenuazonic acid may occasionally occur. In vitro studies suggest genotoxic effects of enniatins A, A1 and B1, beauvericin, moniliformin, alternariol, alternariol monomethyl ether, altertoxins and stemphyltoxin-III. Furthermore, in vitro studies suggest immunomodulating effects of most emerging toxins and a reproductive health hazard of alternariol, beauvericin and enniatin B. More in vivo toxicity data on the individual and combined effects of these contaminants on reproductive and immune system in both humans and animals is needed to update the risk evaluation by the European Food Safety Authority. Taking into account new occurrence data for tenuazonic acid, the complete oral bioavailability, the low total body clearance in pigs and broiler chickens and the limited toxicity data, a health risk cannot be completely excluded. Besides, some less known Alternaria toxins, especially the genotoxic altertoxins and stemphyltoxin III, should be incorporated in risk evaluation as well.
Role of Δ133p53 isoform in NF-κB inhibitor PDTC-mediated growth inhibition of MKN45 gastric cancer cells

AIM To investigate the role of Δ133p53 isoform in nuclear factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC)-mediated growth inhibition of MKN45 gastric cancer cells. METHODS The growth rate of MKN45 cells after treatment with different concentrations of only PDTC or PTDC in combination with cisplatin was detected by the CCK-8 assay. mRNA expression levels of Δ133p53, p53β, and the NF-κB p65 subunit and p65 protein levels were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence, respectively. Growth of MKN45 cells was significantly inhibited by PDTC alone in a dose-dependent manner (P < 0.01). Moreover, the inhibitory effect of cisplatin was remarkably enhanced in a dose-dependent manner by co-treatment with PDTC (P < 0.01). RESULTS RT-PCR analysis revealed that mRNA expression of p65 was curbed significantly in a dose-dependent manner by treatment with only PDTC (P < 0.01), and this suppressive effect was further enhanced when co-treated with cisplatin (P < 0.01). With respect to the other p53 isoforms, mRNA level of Δ133p53 was significantly reduced in a dose-dependent manner by treatment with only PDTC or PTDC in combination with cisplatin (P < 0.01), whereas p53β mRNA expression was not altered by PDTC treatment (P > 0.05). A similar tendency of change in p65 protein expression, as observed for the corresponding mRNA, was detected by immunofluorescence analysis (P < 0.01). Pearson correlation analysis demonstrated that Δ133p53 and p65 mRNA expression levels were positively related, while no significant relationship was observed between those of p65 and p53β (r = 0.076, P > 0.01). CONCLUSION Δ133p53 isoform (not p53β) is required in PDTC-induced inhibition of MKN45 gastric cancer cells, indicating that disturbance in the cross-talk between p53 and NF-κB pathways is a promising target in pharmaceutical research for the development of treatment strategies for gastric cancer.
Effects of prior authorization on medication discontinuation among Medicaid beneficiaries with bipolar disorder.

OBJECTIVE Few data exist on the cost and quality effects of increased use of prior-authorization policies to control psychoactive drug spending among persons with serious mental illness. This study examined the impact of a prior-authorization policy in Maine on second-generation antipsychotic and anticonvulsant utilization, discontinuations in therapy, and pharmacy costs among Medicaid beneficiaries with bipolar disorder. METHODS Using Medicaid and Medicare utilization data for 2001-2004, the authors identified 5,336 patients with bipolar disorder in Maine (study state) and 1,376 in New Hampshire (comparison state). With an interrupted time-series and comparison group design, longitudinal changes were measured in second-generation antipsychotic and anticonvulsant use; survival analysis was used to examine treatment discontinuations and rates of switching medications. RESULTS The prior-authorization policy resulted in an 8-percentage point reduction in the prevalence of use of nonpreferred second-generation antipsychotic and anticonvulsant medications (those requiring prior authorization) but did not increase use of preferred agents (no prior authorization) or rates of switching. The prior-authorization policy reduced total pharmacy reimbursements for bipolar disorder by $27 per patient during the eight-month policy period. However, the hazard rate of treatment discontinuation (all bipolar drugs) while the policy was in effect was 2.28 (95% confidence interval=1.36-4.33) higher than during the prepolicy period, with adjustment for trends in the comparison state. CONCLUSIONS The small reduction in pharmacy spending for bipolar treatment after the policy was implemented may have resulted from higher rates of medication discontinuation rather than switching. The findings indicate that the prior-authorization policy in Maine may have increased patient risk without appreciable cost savings to the state.
Feelings Thermometer: An Early Intervention Scale for Seclusion/Restraint Reduction Among Children and Adolescents in Residential Psychiatric Care.

PROBLEM Restraints and/or seclusions (R/S) are events that have the potential to cause patient injury, staff injury, re-traumatization, and even death. There is a gap in available data regarding alternative strategies for reducing R/S. METHOD A 140-bed children and adolescent residential treatment hospital implemented a "Feelings Thermometer Scale" on each unit. The "Feelings Thermometer" allowed the resident to point to a face on the scale to rate how they were feeling from "Cool" to "On Fire! " Once the resident identified with a feeling and rating, options were offered for alternative cool down locations corresponding to each level of escalation. Data were analyzed 6 weeks before and 6 weeks after implementation of the "Feelings Thermometer. " FINDINGS There were 129 R/S during the 6-week period prior to the implementation of the "Feelings Thermometer. " There were a total of 91 R/S during the 6-week period postimplementation of the "Feelings Thermometer. " Overall, a 29.1% decrease in R/S was experienced throughout the hospital. CONCLUSION The findings of this study suggest that further investigation may be warranted to promote alternative R/S reduction strategies.
Current guidelines for chemoembolization for hepatocellular carcinoma: Room for improvement?

Transarterial chemoembolization (TACE) is the most common oncologic therapy used according to the American Association for the Study of Liver Diseases (AASLD) guidelines established in 2005, revised in 2011. The purpose of this study was to determine how AASLD criteria for the management of hepatocellular carcinoma (HCC) have impacted TACE practice in the community. Clinical, demographic, and cause of death information were collected for patients diagnosed with HCC in the 2012 linkage of the Surveillance, Epidemiology, and End Results Medicare database. Propensity score survival analysis was used to compare survival outcomes in patients whose HCC tumor characteristics were less than, met, or were beyond AASLD criteria. The proportion of patients with HCC receiving TACE who met the AASLD‐recommended criteria increased after the 2005 guidelines were published. Up to 17% of patients treated with TACE had tumor characteristics less than the AASLD criteria and were not offered potentially curative therapies. Propensity score matching demonstrated the largest survival advantage in patients with HCC whose tumor characteristics met the AASLD criteria (hazard ratio, 0.42; 95% confidence interval, 0.38‐0.47). A significant survival advantage was also observed in patients with HCC whose tumor characteristics exceeded the AASLD criteria. Conclusion: The AASLD criteria successfully identify a population of patients with HCC that maximally benefit from TACE therapy. However, patients with HCC with tumor characteristics beyond the AASLD criteria also appear to receive a significant survival advantage with TACE. Further studies are necessary to improve referral patterns and appropriate use of chemoembolization in the management of unresectable HCC. (Hepatology Communications 2017;1:338–346)
Bottom–up and top–down effects on plant communities: nutrients limit productivity, but insects determine diversity and composition

Top–down effects of herbivores and bottom–up effects of nutrients shape productivity and diversity across ecosystems, yet their single and combined effects on spatial and temporal beta diversity is unknown. We established a field experiment in which the abundance of insect herbivores (top–down) and soil nitrogen (bottom–up) were manipulated over six years in an existing old-field community. We tracked plant α and β diversity – within plot richness and among plot biodiversity- and aboveground net primary productivity (ANPP) over the course of the experiment. We found that bottom–up factors affected ANPP while top–down factors influenced plant community structure. Across years, while N reduction lowered ANPP by 10%, N reduction did not alter ANPP relative to control plots. Further, N reduction lowered ANPP by 20% relative to N addition plots. On the other hand, the reduction of insect herbivores did not alter plant richness (α diversity) yet consistently promoted Shannon's evenness, relative to plots where insect herbivores were present. Further, insect herbivores promoted spatial-temporal β diversity. Overall, we found that the relative importance of top–down and bottom–up controls of plant ANPP, plant α diversity, and composition (β diversity) can vary significantly in magnitude and direction. In addition, their effects varied through time, with bottom–up effects influencing ANPP quickly while the effects of top–down factors emerging only late in the experiment to influence plant community composition via shifts in plant dominance.
Utility of the BRAF p.V600E immunoperoxidase stain in FNA direct smears and cell block preparations from patients with thyroid carcinoma

The identification of BRAF mutations in thyroid cancer has prognostic and therapeutic implications. Although the gold standard for identifying BRAF mutations is molecular testing, the ability to perform BRAF p.V600E immunostaining on fine‐needle aspiration (FNA) samples can facilitate the rapid triaging of patients to treatment options.
Multi-level Factorisation Net for Person Re-identification

Key to effective person re-identification (Re-ID) is modelling discriminative and view-invariant factors of person appearance at both high and low semantic levels. Recently developed deep Re-ID models either learn a holistic single semantic level feature representation and/or require laborious human annotation of these factors as attributes. We propose Multi-Level Factorisation Net (MLFN), a novel network architecture that factorises the visual appearance of a person into latent discriminative factors at multiple semantic levels without manual annotation. MLFN is composed of multiple stacked blocks. Each block contains multiple factor modules to model latent factors at a specific level, and factor selection modules that dynamically select the factor modules to interpret the content of each input image. The outputs of the factor selection modules also provide a compact latent factor descriptor that is complementary to the conventional deeply learned features. MLFN achieves state-of-the-art results on three Re-ID datasets, as well as compelling results on the general object categorisation CIFAR-100 dataset.
Carvacrol‐rich oregano oil and thymol‐rich thyme red oil inhibit biofilm formation and the virulence of uropathogenic Escherichia coli

Urinary tract infections are caused primarily by uropathogenic Escherichia coli (UPEC), and indwelling catheters are usually colonized by UPEC biofilms tolerant to common antibiotics. Hence, UPEC biofilms pose a substantial challenge, and there is an urgent need for effective control strategies.
Cycling efficiency and energy cost of walking in young and older adults.

To determine whether age affects cycling efficiency and the energy cost of walking (Cw), 190 healthy adults, ages 18-81 yr, cycled on an ergometer at 50 W and walked on a treadmill at 1.34 m/s. Ventilation and gas exchange at rest and during exercise were used to calculate net Cw and net efficiency of cycling. Compared with the 18-40 yr age group (2.17 ± 0.33 J·kg-1·m-1), net Cw was not different in the 60-64 yr (2.20 ± 0.40 J·kg-1·m-1) and 65-69 yr (2.20 ± 0.28 J·kg-1·m-1) age groups, but was significantly ( P < 0.03) higher in the ≥70 yr (2.37 ± 0.33 J·kg-1·m-1) age group. For subjects >60 yr, net Cw was significantly correlated with age ( R2 = 0.123; P = 0.002). Cycling net efficiency was not different between 18-40 yr (23.5 ± 2.9%), 60-64 yr (24.5 ± 3.6%), 65-69 yr (23.3 ± 3.6%) and ≥70 yr (24.7 ± 2.7%) age groups. Repeat tests on a subset of subjects (walking, n = 43; cycling, n = 37) demonstrated high test-retest reliability [intraclass correlation coefficients (ICC), 0.74-0.86] for all energy outcome measures except cycling net energy expenditure (ICC = 0.54) and net efficiency (ICC = 0.50). Coefficients of variation for all variables ranged from 3.1 to 7.7%. Considerable individual variation in Cw and efficiency was evident, with a ~2-fold difference between the least and most economical/efficient subjects. We conclude that, between 18 and 81 yr, net Cw was only higher for ages ≥70 yr, and that cycling net efficiency was not different across age groups. NEW & NOTEWORTHY This study illustrates that the higher energy cost of walking in older adults is only evident for ages ≥70 yr. For older adults ages 60-69 yr, the energy cost of walking is similar to that of young adults. Cycling efficiency, by contrast, is not different across age groups. Considerable individual variation (∼2-fold) in cycling efficiency and energy cost of walking is observed in young and older adults.
Silver nanoparticles induced reactive oxygen species via photosynthetic energy transport imbalance in an aquatic plant

Abstract The rapid growth in silver nanoparticles (AgNPs) commercialization has increased environmental exposure, including aquatic ecosystem. It has been reported that the AgNPs have damaging effects on photosynthesis and induce oxidative stress, but the toxic mechanism of AgNPs is still a matter of debate. In the present study, on the model aquatic higher plant Spirodela polyrhiza, we found that AgNPs affect photosynthesis and significantly inhibit Photosystem II (PSII) maximum quantum yield (Fv/Fm) and effective quantum yield (ΦPSII). The changes of non-photochemical fluorescence quenching (NPQ), light-induced non-photochemical fluorescence quenching [Y(NPQ)] and non-light-induced non-photochemical fluorescence quenching [Y(NO)] showed that AgNPs inhibit the photo-protective capacity of PSII. AgNPs induce reactive oxygen species (ROS) that are mainly produced in the chloroplast. The activity of ribulose-1, 5-bisphosphate carboxylase–oxygenase (Rubisco) was also very sensitive to AgNPs. The internalized Ag, regardless of whether the exposure was Ag+ or AgNPs had the same capacity to generate ROS. Our results support the hypothesis that intra-cellular AgNP dissociate into high toxic Ag+. Rubisco inhibition leads to slowing down of CO2 assimilation. Consequently, the solar energy consumption decreases and then the excess excitation energy promotes ROS generation in chloroplast.