Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of interindividual differences in hepatic functions and drug sensitivity by using human iPS-derived hepatocytes

Significance We found that individual cytochrome P450 (CYP) metabolism capacity and drug sensitivity could be predicted by examining them in the primary human hepatocytes–human induced pluripotent stem cells–hepatocyte-like cells (PHH-iPS-HLCs). We also confirmed that interindividual differences of CYP metabolism capacity and drug responsiveness that are due to the diversity of individual single nucleotide polymorphisms in the CYP gene could also be reproduced in the PHH-iPS-HLCs. These findings suggest that interindividual differences in drug metabolism capacity and drug response could be predicted by using HLCs differentiated from human iPS cells. We believe that iPS-HLCs would be a powerful technology not only for accurate and efficient drug development, but also for personalized drug therapy. Interindividual differences in hepatic metabolism, which are mainly due to genetic polymorphism in its gene, have a large influence on individual drug efficacy and adverse reaction. Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem (iPS) cells have the potential to predict interindividual differences in drug metabolism capacity and drug response. However, it remains uncertain whether human iPSC-derived HLCs can reproduce the interindividual difference in hepatic metabolism and drug response. We found that cytochrome P450 (CYP) metabolism capacity and drug responsiveness of the primary human hepatocytes (PHH)-iPS-HLCs were highly correlated with those of PHHs, suggesting that the PHH-iPS-HLCs retained donor-specific CYP metabolism capacity and drug responsiveness. We also demonstrated that the interindividual differences, which are due to the diversity of individual SNPs in the CYP gene, could also be reproduced in PHH-iPS-HLCs. We succeeded in establishing, to our knowledge, the first PHH-iPS-HLC panel that reflects the interindividual differences of hepatic drug-metabolizing capacity and drug responsiveness.
Transient role of the rat prelimbic cortex in goal‐directed behaviour

Lesion studies show that goal‐directed actions mediated by action‐outcome (A‐O) associations and habits mediated by stimulus‐response (S‐R) associations can be dissociated during instrumental training, with the prelimbic region of the medial prefrontal cortex being involved in the former and the infralimbic region in the latter. The present work further investigates the role of the prelimbic region in acquisition vs. expression of goal‐directed instrumental behaviour, using reversible neuronal inactivation and outcome devaluation procedures. In a first experiment, inactivating the prelimbic cortex at the time of testing did not alter the sensitivity to devaluation, indicating that this region was not essential for the expression of A‐O associations. In a second experiment, the prelimbic cortex was inactivated throughout the training phase. At the time of testing the performance was insensitive to devaluation, indicating that the acquired response was not goal‐directed but mediated by an S‐R association. These data challenge the view that the habit system replaces the goal‐directed system as training progresses. They show that the prelimbic cortex plays a transient but crucial role in the acquisition of goal‐directed responding and that the A‐O and S‐R systems can operate in a competitive fashion early in training.
Cortical Movement Preparation and Conscious Decisions: Averaging Artifacts and Timing Biases

The main goal of our article (Trevena & Miller, 2002a) was to elucidate the smearing artifact that arises in event-related potential (ERP) research and the consequences of this artifact for studies examining the relative timing of brain activity and conscious awareness. We believe that our article substantiates four main conclusions, and we consider the implications of various points raised by the commentators with respect to each of these conclusions. (1) A smearing artifact can make the onset of an ERP component appear much earlier in average ERP than it actually occurs, on average, in individual trials. For example, smearing makes the readiness potential (RP) and lateralized readiness potential (LRP) appear to start earlier than they actually do. Thus, smearing could potentially explain the finding that these types of brain activity appear to precede conscious decisions to move (e.g., Libet, Gleason, Wright, & Pearl, 1983). That is, conscious decisions might always precede RP and LRP onset in individual trials, even if the onsets of these smeared components of brain activity start before the average time of the conscious decision. A proper interpretation of Libet et al.’s (1983) effect thus requires consideration of the effects of smearing. (2) One plausible way to correct for the smearing artifact is to compare the onsets of RP and LRP against the earliest times at which conscious decisions to move are made. If these onsets precede even the earliest conscious decisions, then the smearing artifact is not wholely responsible for their early onsets. (3) After using this correction in the paradigm of Libet et al. (1983), the onset of RP precedes conscious decisions by too large an amount to be explained solely by the smearing artifact. On the other hand, RP onset also precedes conscious decisions and motor responses by such a long time that it is unlikely to represent subconscious motor preparation for the spontaneous response. It could instead represent a general preparation to ‘‘do something in the not-too-distant future,’’ an intention that the participant must consciously hold given the instructions of the experimenter. (4) After using this same correction, the onset of the LRP does not precede conscious decisions. Thus, the conscious decision may always precede LRP onset.
Changes in the relationships between dogs, owners and veterinarians in Norway and Iceland

Norwegian and Icelandic dog owners were interviewed about aspects of their dog keeping and their attitudes to the veterinary profession. Dogs were found to play an important role in the lives of their owners, who had high expectations of their veterinarians, not only with respect to the treatment of their dogs but also with respect to themselves as clients. About one-third of owners reported problems related to a lack of trust and poor communications in encounters with their veterinarians.
Behavioral Model of IEEE 802.15.4 Beacon-Enabled Mode Based on Colored Petri Net

The IEEE 802.15. 4 standard is widely employed in power-constrained scenarios, such as Wireless Sensor Networks deployments. Therefore, modeling this standard is useful to predict network performance and fine-tune parameter settings. Previous work rely on determining all reachable network states, usually by a Markov chain, which is often complex and error prone. In contrast, we provide a novel behavioral approach to the IEEE 802.15. 4 modeling, which covers the literature gap in assessing all metrics of interest, modeling asymmetric traffic condition and fully comprising the beacon-enabled mode. In addition, it is possible to test different values for the parameters of the standard, such as aMaxFrameRetries, macMaxCSMABackoffs, initialCW, and aUnitBackoffPeriod. The model was validated by NS2 simulations and by a testbed composed of telosB motes.
The Impact of the Massachusetts Health Care Reform on Unpaid Medical Bills

The Massachusetts health care reform was expected to reduce the financial burden of medical care, but literature exploring this effect is limited. In this study, we use hospital financial information and a panel data difference-in-difference model to assess the impact of the Massachusetts health care reform on unpaid medical bills. We find that the reform reduced the financial burden for patients, reflected by a 26percent decrease in hospital bad debt. The effect was more pronounced among safety-net hospitals, indicating a larger benefit for the most vulnerable population.
Effects of Cold Exposure on Rat Adrenal Tyrosine Hydroxylase: An Analysis of RNA, Protein, Enzyme Activity, and Cofactor Levels

Abstract: Long‐term cold exposure (5–7 days) is known to induce concomitant increases in the levels of adrenomedullary tyrosine hydroxylase (TH) RNA, protein, and enzyme activity. In this report, we compare the time courses of these changes and investigate the effects of cold exposure on the levels of biopterin, the cofactor required for tyrosine hydroxylation. After only 1 h of cold exposure, TH mRNA abundance increased 71% compared with nonstressed controls. Increases in total cellular TH RNA levels were maximal (threefold over control values) within 3–6 h of cold exposure and remained elevated throughout the duration of the experiment (72 h). TH protein levels increased rapidly after 24 h of cold exposure and reached a maximal value threefold above that of controls at 48–72 h. Despite the relatively rapid and large elevations in TH RNA and protein content, only modest increases in TH activity were detected during the initial 48 h of cold exposure. Adrenomedullary biopterin increased rapidly after the onset of cold exposure, rising to a level approximately twofold that of the nonstressed controls at 24 h, and remained at this level throughout the duration of the stress period. Taken together, the results of this time course study indicate that cold‐induced alterations in adrenal TH activity are mediated by multiple cellular control mechanisms, which may include pre‐ and posttranslational regulation. Our findings also suggest that cold stress‐induced increases in the levels of the TH cofactor may represent another key event in the sympathoadrenal system's response to cold stress.
[Protective effect of fructose-1,6-diphosphate against ultrastructural damage in the hippocampus of rats with repeated febrile seizures].

OBJECTIVE Fructose-1, 6-diphosphate (FDP), serving as a cellular energy substance, has shown its roles in the treatment of hypoxic-ischemic encephalopathy and myocardial damage. The present study aimed at exploring the potentiality of the protective effect of FDP against ultrastructural damage of the hippocampus caused by febrile seizures (FS) in rats. METHODS Thirty-six 21-day-old male Sprague-Dawley rats were randomly divided into three groups: untreated FS (control), high-dose FDP-treated FS and low-dose FDP-treated FS. FS were induced by hyperthermal bath. Thirty minutes before FS induction, rats in the high-dose and low-dose FDP-treated groups received a peritoneal injection of FDP at a dosage of 50 and 25 mg per 100 g of body weight respectively, whereas the same volume of 0.9% sodium chloride solution were injected to the rats in the control group. Transmission electron microscopy was used to examine the ultrastructural pathologic changes of neurons and organelles as well as the features of synaptic morphological parameters in the hippocampal CA1 area. RESULTS Neuronal degeneration and necrosis, mitochondria swelling, polyribosomes disaggregation from endoplasmic reticula, and golgiosomes dilation in the hippocampal CA1 area in the two FDP intervention groups were less severe compared with the control group. FDP treatment resulted in significant increases in postsynaptic density thickness (F=12.47, P<0.01), synaptic active zone length (F=14.75, P<0.01) and synaptic interface curvature (F=3.77, P<0.05), as well as a shorter interspace of neural synapses (F=7.29, P<0.01) when compared with the control group. There were no significant differences in the ultrastructural changes between the two FDP treatment groups. CONCLUSIONS FDP can ameliorate ultrastructural damage in the hippocampus caused by FS in rats. However, further research is warranted for a reasonable and effective dosage of FDP.
Correlation of mucocutaneous manifestations of HIV/AIDS infection with CD4 counts and disease progression

Background As the search for reliable clinical indicators for management of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) in resource‐poor settings continues, mucocutaneous disorders of HIV should be considered among key clinical indicators for prediction of underlying immune status, disease progression, and possible complications of highly active antiretroviral therapy in Africa.
AN INDUSTRIAL-SCALE STUDY ON THE IMPACT OF VACCINATION UPON RAINBOW TROUT PERFORMANCE

The effect of intraperitoneal (ip) vaccination upon the performance of rainbow trout (n = 1611), maintained under commercial production conditions (aerated spring water, 9.8 oC, 150 L/min), was evaluated over a 7week period. Vaccine impact was examined with reference to control (n = 1683) and injected control (sterile filtered water; n = 1537) animals. All groups were run in triplicate (i. e., n ≥ 500 fish per gorup). Animals were fed to satiation twice daily. Vaccination suppressed (P <0.05) growth in weight over the entire period of study when compared to control treatments. A corresponding decline in specific growth rates (P < 0.05), over the first 29 d of the trial, was also observed for vaccinated fish. Feed conversion efficiencies and feed ratio were similarly negatively affected in vaccinated animals for 29 d postvaccination (P <0.05). The vaccine caused abdominal adhesions although no differences were observed in body composition.
The pharmacological management of NAFLD in children and adolescents

ABSTRACT Introduction: Non-alcoholic fatty liver disease (NAFLD) represents a spectrum, including ‘simple’ steatosis, non-alcoholic steatohepatitis (NASH), and fibrosis. Increasing prevalence of NAFLD has followed the international rise in obesity and lifestyle modification is the mainstay therapy for children. To date, pharmacological trials have had varying efficacy but a large number of new agents are in early phase trials for adults. Areas covered: This review explores the effect of current and potential future paediatric NAFLD treatments in terms of histological and biochemical endpoints. The potential for the extension of adult treatments to children is discussed, as well as what limits the use of certain agents in children. Expert commentary: No drugs have yet to be licenced for NAFLD. Trial heterogeneity makes comparison of drugs between studies challenging. FXR agonists are yet to be trialled in children but may represent a safe and potentially efficacious therapy. Future treatments would likely encompass a multimodal approach that may include bariatric surgery.
Risk Factors for Intracranial Hemorrhage in Acute Ischemic Stroke Patients Treated With Recombinant Tissue Plasminogen Activator: A Systematic Review and Meta-Analysis of 55 Studies

Background and Purpose— Recombinant tissue plasminogen activator (rtPA) is an effective treatment for acute ischemic stroke but is associated with an increased risk of intracranial hemorrhage (ICH). We sought to identify the risk factors for ICH with a systematic review of the published literature. Methods— We searched for studies of rtPA-treated stroke patients that reported an association between a variable measured before rtPA infusion and clinically important ICH (parenchymal ICH or ICH associated with clinical deterioration). We calculated associations between baseline variables and ICH with random-effect meta-analyses. Results— We identified 55 studies that measured 43 baseline variables in 65 264 acute ischemic stroke patients. Post-rtPA ICH was associated with higher age (odds ratio, 1.03 per year; 95% confidence interval, 1.01–1.04), higher stroke severity (odds ratio, 1.08 per National Institutes of Health Stroke Scale point; 95% confidence interval, 1.06–1.11), and higher glucose (odds ratio, 1.10 per mmol/L; 95% confidence interval, 1.05–1.14). There was approximately a doubling of the odds of ICH with the presence of atrial fibrillation, congestive heart failure, renal impairment, previous antiplatelet agents, leukoaraiosis, and a visible acute cerebral ischemic lesion on pretreatment brain imaging. Little of the variation in the sizes of the associations among different studies was explained by the source of the cohort, definition of ICH, or degree of adjustment for confounding variables. Conclusions— Individual baseline variables were modestly associated with post-rtPA ICH. Prediction of post-rtPA ICH therefore is likely to be difficult if based on single clinical or imaging factors alone. These observational data do not provide a reliable method for the individualization of treatment according to predicted ICH risk.
The growth of northeastern Tibet and its relevance to large‐scale continental geodynamics: A review of recent studies

Recent studies of the northeastern part of the Tibetan Plateau have called attention to two emerging views of how the Tibetan Plateau has grown. First, deformation in northern Tibet began essentially at the time of collision with India, not 10–20 Myr later as might be expected if the locus of activity migrated northward as India penetrated the rest of Eurasia. Thus, the north‐south dimensions of the Tibetan Plateau were set mainly by differences in lithospheric strength, with strong lithosphere beneath India and the Tarim and Qaidam basins steadily encroaching on one another as the region between them, the present‐day Tibetan Plateau, deformed, and its north‐south dimension became narrower. Second, abundant evidence calls for acceleration of deformation, including the formation of new faults, in northeastern Tibet since ~15 Ma and a less precisely dated change in orientation of crustal shortening since ~20 Ma. This reorientation of crustal shortening and roughly concurrent outward growth of high terrain, which swings from NNE‐SSW in northern Tibet to more NE‐SW and even ENE‐WSW in the easternmost part of northeastern Tibet, are likely to be, in part, a consequence of crustal thickening within the high Tibetan Plateau reaching a limit, and the locus of continued shortening then migrating to the northeastern and eastern flanks. These changes in rates and orientation also could result from removal of some or all mantle lithosphere and increased gravitational potential energy per unit area and from a weakening of crustal material so that it could flow in response to pressure gradients set by evolving differences in elevation.
Use of M-CHAT for a multinational screening of young children with autism in the Arab countries

There has been a decline in the mortality rate among infants and children under five years of age in the last decade in many developing countries. This has led to a shift in focus to look beyond survival to the prevention or reduction of impairment and promotion of children's health. With the apparent rise in the prevalence of autism spectrum disorders (ASD) in the Arab countries the development of an Arabic tool for early diagnosis and intervention was sought as part of an effort to better understand the prevalence of this disorder. The Modified Checklist for Autism in Toddlers (M-CHAT) was chosen. The study was conducted in nine Arabic speaking countries. The final analysis included 228 children (122 screened positive for ASD). The sensitivity (0.86), the specificity (0.80) and positive predictive value (0.88) were very similar to Robins et al. study (2001). Maternal health problems during pregnancy and labour were found to be more significant for ASD mothers than their control. In addition, child health problems were more evident among ASD subjects as reported by their parents with significant differences from controls. The limitation of the study is that the sample size is not large enough to generalize the results to all countries of the region. The strength of the study is that it is the first known study where Arab countries undertook a collaborative mental health study using the same tool for screening for a specific disorder.
Tracking the intermediate stages of epithelial-mesenchymal transition in epithelial stem cells and cancer

Epithelial-mesenchymal transition (EMT) is an essential developmental program that becomes reactivated in adult tissues to promote the progression of cancer. EMT has been largely studied by examining the beginning epithelial state or the ending mesenchymal state without studying the intermediate stages. Recent studies using trophoblast stem (TS) cells paused in EMT have defined the molecular and epigenetic mechanisms responsible for modulating the intermediate "metastable" stages of EMT. Targeted inactivation of MAP3K4, knockdown of CBP, or overexpression of SNAI1 in TS cells induced similar metastable phenotypes. These TS cells exhibited epigenetic changes in the histone acetylation landscape that cause loss of epithelial maintenance while preserving self-renewal and multipotency. A similar phenotype was found in claudin-low breast cancer cells with properties of EMT and stemness. This intersection between EMT and stemness in TS cells and claudin-low metastatic breast cancer demonstrates the usefulness of developmental EMT systems to understand EMT in cancer.
Do we get it right? Radiation oncology outpatients' perceptions of the patient centredness of life expectancy disclosure

A patient‐centred approach to discussing life expectancy with cancer patients is recommended in Western countries. However, this approach to eliciting and meeting patient preferences can be challenging for clinicians. The aims of this study were the following: (i) to examine cancer patients' preferences for life expectancy disclosure; and (ii) to explore agreement between cancer patients’ preferences for, and perceived experiences of, life expectancy disclosure.
Refractory Venous Leg Ulcers: A Study of Risk Factors

BACKGROUND Although certain risk factors for poor healing of leg ulcers have been identified, data concerning the characteristics of refractory ulcers have not been specifically studied in the literature. OBJECTIVE To study the characteristics of refractory venous leg ulcers. METHODS We retrospectively studied prognostic factors for healing in patients with refractory venous leg ulcers followed and treated in our dermatology department between January 1993 and January 2000. Each patient included in this study was compared with two patients matched for age and gender and presenting leg ulcers with normal healing, followed during the same period. RESULTS Thirty-two of 571 patients with leg ulcers were included. The study population consisted of 20 females and 12 males with a mean age 73.5 years. The control population comprised 64 patients, 40 females and 24 males, with a mean age of 73 years. Univariate analysis demonstrated the negative prognostic impact of several previously identified factors (including surface area and history of the ulcer). In particular, multivariate analysis identified four main risk factors for refractory ulcer that are often associated in these patients: associated arterial disease, presence of post-thrombotic popliteal sequelae, recurrence of the ulcer, and disability. CONCLUSION Four main risk factors that are often associated were identified, indicating the multifactorial nature of these refractory ulcers.