Miracle-dz/UniFAR-FTUs huggingface dataset:
Pitfalls and Related Improvements of In Vivo Gas Uptake Pharmacokinetic Experimental Systems

Gas uptake chamber studies have been widely used to study inhalation pharmacokinetics (PKs) in rodents, often for the ultimate purpose of developing physiologically-based pharmacokinetic (PBPK) models that can be used to describe human PKs and to support risk assessment for the chemical. In the course of our studies of gasoline PKs, we revisited several important issues heretofore not thoroughly addressed. Here, we report several refinements which will significantly improve future studies with this type of system, relating to the understanding of loss rates, the importance of carbon dioxide removal, and sampling of blood and chamber air at the same time. Losses of chemicals in gas uptake systems consist of leakage, adsorption to system components, and adsorption to the hair and skin (fur) of experimental animals. The loss rates were experimentally determined for a series of chemicals and mixtures including n-hexane, benzene, toluene, ethylbenzene, o-xylene, gasoline, and other gasoline components. The rate of loss to the animals' fur was similar to loss rates to system components and involved absorption to both hair and skin. Most of the absorption to fur was reversible when the chamber concentration was low enough. The amount of chemical that desorbed from the animal after an experiment was significant when compared to the amount of chemical in the chamber at the end of a gas uptake experiment, indicating that the rate of decline in concentrations can be influenced by a decrease in the fur absorption rate or desorption of chemicals. A modified gas uptake system design is described in which a steel ring improved the connections to an autosampler and allowed insertion of probes to monitor gases, such as carbon dioxide (CO2), in the chamber. When CO2 absorbent efficiency was inadequate, CO2 concentrations rose to levels that significantly affected the animals' ventilation rate. Using a real-time CO2 probe, an absorbent system was developed that adequately controlled CO2 levels in the chamber. Attention to details of absorptive loss and CO2 scrubbing can improve the reliability of kinetic constants inferred from closed chamber studies. We then describe a method for extending gas uptake experiments by simultaneously collecting blood to be analyzed for chemicals and/or metabolites.
Screening for prostate cancer with prostate-specific antigen testing: American Society of Clinical Oncology Provisional Clinical Opinion.

PURPOSE An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) offers timely clinical direction to the ASCO membership after publication or presentation of potentially practice-changing data from major studies. This PCO addresses the role of prostate-specific antigen (PSA) testing in the screening of men for prostate cancer. CLINICAL CONTEXT Prostate cancer is the second leading cause of cancer deaths among men in the United States. The rationale for screening men for prostate cancer is the potential to reduce the risk of death through early detection. RECENT DATA Evidence from a 2011 Agency for Healthcare Research and Quality systematic review primarily informs this PCO on the benefits and harms of PSA-based screening. An update search was conducted to March 16, 2012, for additional evidence related to the topic. RESULTS In one randomized trial, PSA testing in men who would not otherwise have been screened resulted in reduced death rates from prostate cancer, but it is uncertain whether the size of the effect was worth the harms associated with screening and subsequent unnecessary treatment. Although there are limitations to the existing data, there is evidence to suggest that men with longer life expectancy may benefit from PSA testing. Adverse events associated with prostate biopsy are low for the majority of men; however, several population-based studies have shown increasing rates of infectious complications after prostate biopsy, which is a concern.
Awareness of Respiratory Failure Can Predict Early Postoperative Pulmonary Complications in Liver Transplant Recipients.

OBJECTIVES Cardiovascular and respiratory system complications are the most common causes of early mortality after liver transplant. We evaluated the causes of respiratory failure as an early postoperative pulmonary complication in liver transplant recipients. MATERIALS AND METHODS Patients who underwent orthotropic liver transplant between 2001 and 2014 were retrospectively evaluated. Clinical and demographic variables and pulmonary complications at the first and second visit after transplant were noted. The first visit was within the first week and the second was between 1 and 4 weeks after transplant. An arterial oxygen saturation value below 90% in room air for at least 1 day was considered a medically significant respiratory failure. RESULTS Our study included 204 (148 men and 56 women; mean age 43.0.4 ± 13.06 y) adult liver transplant recipients (46 from deceased and 158 from living donors). At the first visit after transplant, 161 patients (79%) had postoperative pulmonary complications, including pleural effusion accompanied by atelectasis (47.1%), only atelectasis (17.2%), and only pleural effusion (10.3%). At the second visit, complications included atelectasis associated with pleural effusion (12.3%) and pneumonia (12.3%). All patients had documented respiratory failure at the first visit, and 92 patients (45.1%) had respiratory failure at the second visit. Causes of respiratory failure at the first visit included atelectasis in 35 patients (17.2%) and atelectasis accompanied by pleural effusion in 96 patients (47.1%). At the second visit, 25 of 161 patients (25.3%) had respiratory failure due to pneumonia. Other causes included atelectasis accompanied by pleural effusion (24.2%) and pleural effusion (23.2%). Ninety-seven patients had no pulmonary complications. The mortality rate was 6.4% within the first visit and 8.7% within the second visit. CONCLUSIONS Pneumonia, atelectasis, and pleural effusion can cause respiratory failure within the first month after liver transplant. Early pulmonary examination, diagnosis, and treatment can improve patient survival.
Promising Practices for the Prevention and Control of Obesity in the Worksite

Purpose. To identify worksite practices that show promise for promoting employee weight loss. Data Source. The following electronic databases were searched from January 1, 1966, through December 31, 2005: CARL Uncover (via Ingenta), CDP, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Library, CRISP, Dissertation Abstracts, EMBASE, ERIC, Health Canada, INFORM (part of ABI/INFORM Proquest), LocatorPlus, New York Academy of Medicine, Ovid MEDLINE, SPORTDiscus, PapersFirst, PsycINFO, PubMed, and TRIP. Study Inclusion and Exclusion Criteria. Included studies were published in English, conducted at a worksite, designed for adults (aged ≥18 years), and reported weight-related outcomes. Data Extraction. Data were extracted using an online abstraction form. Data Synthesis. Studies were evaluated on the basis of study design suitability quality of execution, sample size, and effect size. Changes in weight-related outcomes were used to assess effectiveness. Results. The following six promising practices were identified: enhanced access to opportunities for physical activity combined with health education, exercise prescriptions alone, multicomponent educational practices, weight loss competitions and incentives, behavioral practices with incentives, and behavioral practices without incentives. Conclusions. These practices will help employers and employees select programs that show promise for controlling and preventing obesity. (Am J Health Promot 2011;25[3]:e12–e26.)
Lone noncompaction in Leber’s hereditary optic neuropathy

The association of Leber’s hereditary optic neuropathy (LHON) and left ventricular non-compaction in the absence of other neurologic or cardiac abnormalities has not been reported. In a 19-year-old man with deteriorating visual acuity, first in the right and two weeks later also in the left eye, LHON was diagnosed, based upon reduced visual acuity, abnormal visually evoked potentials, hyperaemia of the papilla, hyperaemia of the peripapillary capillaries, peripapillary teleangiectasias, congested peripapillary veins, complete central scotoma and spotted partial defects of the remaining visual field. No other ophthalmologic abnormalities were detected. Because of frequent cardiac involvement in LHON a thorough cardiologic investigation was carried out. The cardiovascular history was uneventful. Clinical cardiologic examination and ECG were normal.Transthoracic echocardiography, however, revealed left ventricular noncompaction in the apex and the lateral wall. No other cardiac abnormalities were found. In conclusion, LHON without other neurological abnormalities may be associated with lone left ventricular noncompaction. Patients with LHON should undergo a cardiologic investigation.
Towards Sustainability in Resource Sharing: A Game Theory Approach

Over-exploitation of present renewable resources has an impact on future generations unlike in traditional community relationship. Present generations maximize their pay-off by exhausting the resources. However, this minimizes the total pay-off of all generations as a whole. The failure to cooperate with future generations is mainly championed by a few. What policies can aid sustainable inter-generational resource usage? How can this few be deterred from over-exploitation of the present resources? How can those willing to cooperate be encouraged by guaranteeing sustainability? And can all these be achieved without a central authority? Some researchers proposed voting to solve these problems. However, this has a clear limitation in that it must be binding on all for it to work thereby necessitating the need for central authority. In this study, a reputation based model is proposed instead of voting. The model evaluates the reputation of agents based on their willingness to cooperate with the future. The agent's reputation defines other agents it interacts with in the society. Hence, cooperators tend to relate with fellow cooperators and are better off while defectors are worse off. It is shown that reputation is a viable alternative in the attainment of a sustainable society. However, this is only applicable for sustained interactions between the agents.
Exposure to CB-153 and p,p'-DDE and male reproductive function.

BACKGROUND During the last decades, there has been concern that exposure to endocrine disruptors, such as persistent organochlorine pollutants (POPs), may contribute to an impairment of male reproductive function. To investigate whether exposure to 2,2'4,4'5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) affects semen quantity and quality and reproductive hormones, 195 Swedish fishermen, aged 24-65 years, were investigated. METHODS The men provided semen samples which were analysed in a mobile laboratory unit. Blood samples and information relating to lifestyle, medical and reproductive history were obtained. RESULTS The subjects had a median CB-153 serum level of 193 ng/g lipid (range 39-1460) and a median p,p'-DDE serum level of 240 ng/g lipid (range 334-2251). When CB-153 was categorized into quintiles, the subjects in the quintile with the highest concentration (> 328 ng/g lipid), tended to have decreased sperm motility compared with the subjects in the lowest quintile (< 113 ng/g lipid). The age-adjusted mean difference was 9.9% (95% confidence interval -1.0 to 21% P = 0.08). We found no significant associations between p,p'-DDE and semen characteristics or reproductive hormones. CONCLUSION The association between CB-153 and sperm motility, although not formally significant, is of interest considering the possible endocrine-disrupting effects of polychlorinated biphenyls (PCBs).
Perlecan is required for the chondrogenic differentiation of synovial mesenchymal cells through regulation of Sox9 gene expression

We previously reported that perlecan, a heparan‐sulfate proteoglycan (Hspg2), expressed in the synovium at the cartilage‐synovial junction, is required for osteophyte formation in knee osteoarthritis. To examine the mechanism underlying this process, we examined the role of perlecan in the proliferation and differentiation of synovial mesenchymal cells (SMCs), using a recently established mouse synovial cell culture method. Primary SMCs isolated from Hspg2−/−‐Tg (Hspg2−/−;Col2a1‐Hspg2Tg/−) mice, in which the perlecan‐knockout was rescued from perinatal lethality, lack perlecan. The chondrogenic‐, osteogenic‐, and adipogenic‐potentials were examined in the Hspg2−/−‐Tg SMCs compared to the control SMCs prepared from wild‐type Hspg2+/+‐Tg (Hspg2+/+;Col2a1‐Hspg2Tg/−) littermates. In a culture condition permitting proliferation, both control and Hspg2−/−‐Tg SMCs showed similar rates of proliferation and expression of cell surface markers. However, in micromass cultures, the cartilage matrix production and Sox9 and Col2a1 mRNA levels were significantly reduced in Hspg2−/−‐Tg SMCs, compared with control SMCs. The reduced level of Sox9 mRNA was restored by the supplementation with exogenous perlecan protein. There was no difference in osteogenic differentiation between the control and Hspg2−/−‐Tg SMCs, as measured by the levels of Runx2 and Col1a1 mRNA. The adipogenic induction and PPARγ mRNA levels were significantly reduced in Hspg2−/−‐Tg SMCs compared to control SMCs. The reduction of PPARγ mRNA levels in Hspg2−/−‐Tg SMCs was restored by supplementation of perlecan. Perlecan is required for the chondrogenic and adipogenic differentiation from SMCs via its regulation of the Sox9 and PPARγ gene expression, but not for osteogenic differentiation via Runx2. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:837–846, 2017.
Bactrocera invadens (Diptera: Tephritidae), a New Invasive Fruit Fly Pest for the Afrotropical Region: Host Plant Range and Distribution in West and Central Africa

ABSTRACT In 2003, the invasive fruit fly Bactrocera invadens Drew, Tsuruta & White (Diptera: Tephritidae) (Drew et al. 2005), of possible Sri Lankan origin, has been detected in the East and about 1 yr later in West Africa. In regular surveys in Benin and Cameroon covering 4 yr, samples from 117 plant species across 43 families have been obtained. Incubation of field-collected fruits demonstrate that in West and Central Africa (WCA) B. invadens is highly polyphagous, infesting wild and cultivated fruits of at least 46 species from 23 plant families with guava (Psidium spp.), mango (Mangifera spp.), and citrus (spp.), and the wild hosts tropical almond (Terminalia catappa L.), African wild mango (Irvingia gabonensis (Aubry-Lecomte) Baill. ), and sheanut (Vitellaria paradoxa C.F.Gaertn.) showing the highest infestation index. B. invadens occurs in 22 countries of WCA with new records for Angola, Central African Republic, the Congo, DR Congo, Equatorial Guinea, Gabon, Gambia, Guinea Bissau, Mali, Mauritania, Niger, and Sierra Leone. Overall, the pest has spread across a North-South distance of ≈5,000 km representing a contiguous area of >8.3 million km2 within WCA. B. invadens has adapted to a wide range of ecological and climatic conditions extending from low land rainforest to dry savanna. Because of its highly destructive and invasive potential, B. invadens poses a serious threat to horticulture in Africa if left uncontrolled. Moreover, the presence of this quarantine pest causes considerable restrictions on international trade of affected crops.
Changes of alpha-fetoprotein levels could predict recurrent hepatocellular carcinoma survival after trans-arterial chemoembolization

Background There is paucity of information concerning whether AFP change is a predictor of prognosis for recurrent hepatocellular carcinoma (RHCC) patients after trans-arterial chemoembolization (TACE). Methods A total of 177 RHCC patients who received TACE as first-line therapy were retrospectively analyzed. The patients were classified into three groups according to their pre-TACE and post-TACE AFP levels (group A: AFP decreased, group B: AFP consistent normal, and group C: AFP increased). The recurrence to death survival (RTDS) and overall survival (OS) were estimated by the Kaplan-Meier method, and compared by the log-rank test. Multivariate analyses were performed to identify prognostic factors for OS and RTDS. Results There was no significant difference among the three groups concerning the baseline characteristics. The median overall survival (OS) was 74.5 months in group A (95% confidence interval (CI): 63.5, 85.6), 64.0 months in group B (95% CI: 52.3, 75.7) and 29.0 months in group C (95% CI: 24.1, 33.9; P<0.001). The median recurrence to death survival (RTDS) was 66.5 months (95% CI: 53.4, 79.6) in group A, 50.4 months (95% CI: 39.5, 61.4) in group B and 17.7 months (95% CI: 13.4, 22.1; P<0.001) in group C. Multivariate analysis revealed that tumor size at resection stage, tumor number at recurrent stage, cycles of TACE, mRECIST response and AFP change after TACE were significant independent risk factors for RTDS and OS. Conclusions AFP change could predict the prognoses of patients with RHCC who received trans-arterial chemoembolization, which may help clinicians make subsequent treatment decision.
ModLoop: automated modeling of loops in protein structures

SUMMARY ModLoop is a web server for automated modeling of loops in protein structures. The input is the atomic coordinates of the protein structure in the Protein Data Bank format, and the specification of the starting and ending residues of one or more segments to be modeled, containing no more than 20 residues in total. The output is the coordinates of the non-hydrogen atoms in the modeled segments. A user provides the input to the server via a simple web interface, and receives the output by e-mail. The server relies on the loop modeling routine in MODELLER that predicts the loop conformations by satisfaction of spatial restraints, without relying on a database of known protein structures. For a rapid response, ModLoop runs on a cluster of Linux PC computers. AVAILABILITY The server is freely accessible to academic users at http://salilab.org/modloop
Physical insights into the blood–brain barrier translocation mechanisms

The number of individuals suffering from diseases of the central nervous system (CNS) is growing with an aging population. While candidate drugs for many of these diseases are available, most of these pharmaceutical agents cannot reach the brain rendering most of the drug therapies that target the CNS inefficient. The reason is the blood–brain barrier (BBB), a complex and dynamic interface that controls the influx and efflux of substances through a number of different translocation mechanisms. Here, we present these mechanisms providing, also, the necessary background related to the morphology and various characteristics of the BBB. Moreover, we discuss various numerical and simulation approaches used to study the BBB, and possible future directions based on multi-scale methods. We anticipate that this review will motivate multi-disciplinary research on the BBB aiming at the design of effective drug therapies.
Expanding the (kaleido)scope: exploring current literature trends for translating electroencephalography (EEG) based brain–computer interfaces for motor rehabilitation in children

Rehabilitation applications using brain–computer interfaces (BCI) have recently shown encouraging results for motor recovery. Effective BCI neurorehabilitation has been shown to exploit neuroplastic properties of the brain through mental imagery tasks. However, these applications and results are currently restricted to adults. A systematic search reveals there is essentially no literature describing motor rehabilitative BCI applications that use electroencephalograms (EEG) in children, despite advances in such applications with adults. Further inspection highlights limited literature pursuing research in the field, especially outside of neurofeedback paradigms. Then the question naturally arises, do current literature trends indicate that EEG based BCI motor rehabilitation applications could be translated to children? To provide further evidence beyond the available literature for this particular topic, we present an exploratory survey examining some of the indirect literature related to motor rehabilitation BCI in children. Our goal is to establish if evidence in the related literature supports research on this topic and if the related studies can help explain the dearth of current research in this area. The investigation found positive literature trends in the indirect studies which support translating these BCI applications to children and provide insight into potential pitfalls perhaps responsible for the limited literature. Careful consideration of these pitfalls in conjunction with support from the literature emphasize that fully realized motor rehabilitation BCI applications for children are feasible and would be beneficial. • BCI intervention has improved motor recovery in adult patients and offer supplementary rehabilitation options to patients. • A systematic literature search revealed that essentially no research has been conducted bringing motor rehabilitation BCI applications to children, despite advances in BCI. • Indirect studies discovered from the systematic literature search, i.e. neurorehabilitation in children via BCI for autism spectrum disorder, provide insight into translating motor rehabilitation BCI applications to children. • Translating BCI applications to children is a relevant, important area of research which is relatively barren.
The migraine postdrome.

PURPOSE OF REVIEW Migraine is a common, disabling neurological disorder that affects up to 12% of the world population. Its pathophysiology is incompletely described. Of the various phases of migraine, the migraine postdrome is the least studied and hence the least understood. RECENT FINDINGS Electronic diary studies show patients are left disabled with non-headache symptoms in the migraine postdrome. Hence, the importance of understanding the phase better and ensuring that more effective treatments become available in the future to cut down the morbidity associated with this phase. SUMMARY The disability related to migraine is not limited to the headache phase and pans out to include the postdrome phase. The migraine postdrome needs to be studied more as this may improve our overall understanding of migraine mechanisms and also treat the concurrent symptoms better.
The regulation of size and form in the assembly of collagen fibrils in vivo

A possible mechanism for regulating the lateral growth of collagen fibrils in vivo is considered. A growth inhibitor associated with a particular part of the long semiflexible collagen molecule restricts that part of the molecule to the surface of the growing assembly. Lateral accretion ceases when these inhibitors form a complete circumferential layer around the fibril surface. Cell‐mediated removal of the inhibitors allows lateral growth to proceed to a second limiting layer, and so on to subsequent limiting layers. In this way, cycles of inhibitor removal and limited lateral accretion permit growth to be synchronized over large populations of fibrils. Observed diameter distributions in bundles of embryonic and neonatal fibrils are those expected from a mechanism of this kind. The mechanism depends on the existence of axial order (D‐periodicity) in fibrils, but not on any specific lateral packing of molecules. Rather, contacts between newly assembled molecules are presumed to be partly fluid‐like in lateral directions (except where covalent cross‐links have formed). Some initial fluidity in lateral packing prior to cross‐linking does not preclude the subsequent emergence of quasi‐crystalline packing as cross‐links form. The cylindrical shape of fibrils in vivo may also be attributable in part to fluidity of intermolecular contacts at the growing surface.