Miracle-dz/UniFAR-FTUs huggingface dataset:
pH Dependence of Organic Anion-Transporting Polypeptide 2B1 in Caco-2 Cells: Potential Role in Antiretroviral Drug Oral Bioavailability and Drug–Drug Interactions

Human intestinal epithelium expresses a number of drug efflux and influx transporters that can restrict and/or facilitate intestinal drug uptake during absorption. Organic anion-transporting polypeptide 2B1 (OATP2B1), a multispecific organic anion uptake transporter localized at the brush-border membrane of intestinal epithelial cells, is known to transport many endogenous substrates (e.g., steroid conjugates) and xenobiotics (e.g., statins). At present, limited information is available on the mechanism of HIV protease inhibitor (PIs) intestinal uptake. In this study, we examined the interaction of PIs with the OATP2B1 transport system in Caco-2 cells, an in vitro model of human intestinal epithelium, and Madin-Darby canine kidney II cells stably transfected with OATP2B1. The expression of OATP2B1 transcript and protein was confirmed by reverse transcription-polymerase chain reaction and immunoblot analysis, respectively. Estrone-3-sulfate (E3S) uptake demonstrated biphasic saturation kinetics in Caco-2 cells, with dissociation constants (KM) of 6 ± 2 μM and 1.5 ± 0.2 mM. Several PIs potently inhibited OATP2B1-mediated transport in Caco-2 cells at clinically relevant IC50 concentrations for ritonavir (0.93 μM), atazanavir (2.2 μM), lopinavir (1.7 μM), tipranavir (0.77 μM), and nelfinavir (2.2 μM). An inwardly directed proton gradient was identified as the driving force of E3S uptake through NH4Cl intracellular acidification studies with a H+:E3S stoichiometry for OATP2B1 of 1:1. In contrast, although atazanavir and ritonavir uptake by Caco-2 cells was stimulated by low extracellular pH, this process was not mediated by OATP2B1 and was not affected by an outwardly directed H+ gradient. Because OATP2B1 exhibits an increasing number of drug substrates, including several statins, alterations of its function by PIs could result in clinically significant drug–drug interactions in the intestine.
SAVE: an algorithm for smoothed adaptive video over explicit rate networks

Supporting compressed video efficiently on networks is a challenge because of its burstiness. Although a large number of applications using compressed video are rate adaptive, it is also important to preserve quality as much as possible. We propose a smoothing and rate adaptation algorithm, called SAVE, that the compressed video source uses in conjunction with explicit rate based control in the network. SAVE smoothes the demand from the source to the network, thus helping achieve good multiplexing gains. SAVE maintains the quality of the video and ensures that the delay at the source buffer does not exceed a bound. We examine the effectiveness of SAVE across 28 different traces (entertainment and teleconferencing videos) using different compression algorithms.
Developing mHealth Remote Monitoring Technology for Attention Deficit Hyperactivity Disorder: A Qualitative Study Eliciting User Priorities and Needs

Background Guidelines in the United Kingdom recommend that medication titration for attention deficit hyperactivity disorder (ADHD) should be completed within 4-6 weeks and include regular reviews. However, most clinicians think that weekly clinic contact is infeasible, and audits have shown that this timeline is rarely achieved. Thus, a more effective monitoring and review system is needed; remote monitoring technology (RMT) may be one way to improve current practice. However, little is known about whether patients with ADHD, their families, and clinicians would be interested in using RMT. Objective To explore patients’, parents’, and health care professionals’ views and attitudes toward using digital technology for remote monitoring during titration for ADHD. Methods This was a qualitative study, and data were collected through 11 focus groups with adults and young people with ADHD, parents of children with ADHD, and health care professionals (N=59). Results All participant groups were positive about using RMT in the treatment of ADHD, but they were also aware of barriers to its use, especially around access to technology and integrating RMT into clinical care. They identified that RMT had the most potential for use in the ongoing management and support of ADHD, rather than during the distinct titration period. Participants identified features of RMT that could improve the quality of consultations and support greater self-management. Conclusions RMT has the potential to augment support and care for ADHD, but it needs to go beyond the titration period and offer more to patients and families than monitoring through outcome measures. Developing and evaluating an mHealth app that incorporates the key features identified by end users is required.
An Improved Algorithm for Finding Tree Decompositions of Small Width

We present a modification of Bodlaender's linear time algorithm that, for constant k, determines whether an input graph G = (V, E) has treewidth k and, if so, constructs a tree decomposition of G of width at most k. Our algorithm has the following additional feature: if G has treewidth greater than k then a subgraph G′ of G of treewidth greater than k is returned along with a tree decomposition of G′ of width at most 2k. A consequence is that the fundamental disjoint rooted paths problem can now be solved in O(n2) time. This is the primary motivation for this paper.
Loss of Siglec expression on T lymphocytes during human evolution

We report here that human T cells give much stronger proliferative responses to specific activation via the T cell receptor (TCR) than those from chimpanzees, our closest evolutionary relatives. Nonspecific activation using phytohemagglutinin was robust in chimpanzee T cells, indicating that the much lower response to TCR simulation is not due to any intrinsic inability to respond to an activating stimulus. CD33-related Siglecs are inhibitory signaling molecules expressed on most immune cells and are thought to down-regulate cellular activation pathways via cytosolic immunoreceptor tyrosine-based inhibitory motifs. Among human immune cells, T lymphocytes are a striking exception, expressing little to none of these molecules. In stark contrast, we find that T lymphocytes from chimpanzees as well as the other closely related “great apes” (bonobos, gorillas, and orangutans) express several CD33-related Siglecs on their surfaces. Thus, human-specific loss of T cell Siglec expression occurred after our last common ancestor with great apes, potentially resulting in an evolutionary difference with regard to inhibitory signaling. We confirmed this by studying Siglec-5, which is prominently expressed on chimpanzee lymphocytes, including CD4 T cells. Ab-mediated clearance of Siglec-5 from chimpanzee T cells enhanced TCR-mediated activation. Conversely, primary human T cells and Jurkat cells transfected with Siglec-5 become less responsive; i.e., they behave more like chimpanzee T cells. This human-specific loss of T cell Siglec expression associated with T cell hyperactivity may help explain the strikingly disparate prevalence and severity of T cell-mediated diseases such as AIDS and chronic active hepatitis between humans and chimpanzees.
Characterising the reproducibility and reliability of dietary patterns among Yup'ik Alaska Native people

FFQ data can be used to characterise dietary patterns for diet–disease association studies. In the present study, we evaluated three previously defined dietary patterns – ‘subsistence foods’, market-based ‘processed foods’ and ‘fruits and vegetables’ – among a sample of Yup'ik people from Southwest Alaska. We tested the reproducibility and reliability of the dietary patterns, as well as the associations of these patterns with dietary biomarkers and participant characteristics. We analysed data from adult study participants who completed at least one FFQ with the Center for Alaska Native Health Research 9/2009–5/2013. To test the reproducibility of the dietary patterns, we conducted a confirmatory factor analysis (CFA) of a hypothesised model using eighteen food items to measure the dietary patterns (n 272). To test the reliability of the dietary patterns, we used the CFA to measure composite reliability (n 272) and intra-class correlation coefficients for test–retest reliability (n 113). Finally, to test the associations, we used linear regression (n 637). All factor loadings, except one, in CFA indicated acceptable correlations between foods and dietary patterns (r>0·40), and model-fit criteria were >0·90. Composite and test–retest reliability of the dietary patterns were, respectively, 0·56 and 0·34 for ‘subsistence foods’, 0·73 and 0·66 for ‘processed foods’, and 0·72 and 0·54 for ‘fruits and vegetables’. In the multi-predictor analysis, the dietary patterns were significantly associated with dietary biomarkers, community location, age, sex and self-reported lifestyle. This analysis confirmed the reproducibility and reliability of the dietary patterns in the present study population. These dietary patterns can be used for future research and development of dietary interventions in this underserved population.
Implications of Laparoscopic Cholecystectomy for Surgical Residency Training

Background: Widespread adoption of minimal access techniques forced a generation of abdominal surgeons to re-learn many standard abdominal procedures. This threatened to reduce the pool of suitable “training” operations for surgical residents. Methods: Operator grade, duration of operation, acute/elective operation, conversion rate, complications, and postoperative stay were recorded prospectively on all laparoscopic cholecystectomies (LC) since 1992. This data was evaluated to determine how the introduction of LC affected residents' training. Results: The percentage of LCs performed by residents increased progressively to reach 58%. Operating time was longer for trainee surgeons, particularly for acute cases (145 ± 50 minutes vs 111 ± 54 minutes, p<0.05); however, conversion rate, incidence of complications, and postoperative stay were no different. Conclusions: LC can be performed by surgical trainees with similar complication rates and outcomes as those of qualified surgeons. Once institutional experience has accumulated, this procedure can be integrated into residency training.
[Comparison of ROI-C and traditional cage with anterior plating for anterior cervical discectomy and fusion].

OBJECTIVE To study clinical outcomes following anterior cervical discectomy and fusion (ACDF) using ROI-C compared to traditional cage with anterior plating in treating the cervical spondylotic myelopathy. METHODS A total of 66 patients with the cervical spondylotic myelopathy were treated with ACDF between April 2011 and October 2012. Twenty-three patients underwent ACDF using the ROI-C device were classified as the ROI-C group and 43 patients received traditional cage with anterior plating served as the titanium plate group. Related indicators, such as operation time, intraoperative blood loss, intraoperative fluoroscopy times, incidence of postoperative dysphagia and ratio of bone graft fusion were recorded and compared between two groups. The clinical outcomes were evaluated by Japanese Orthopaedic Association (JOA) scores and visual analog scale (VAS) scores. The pre- and postoperative results were compared with a paired sample t-test. The results between groups were compared utilizing the grouped t-test or χ² test. RESULTS All cases were followed up. The follow-up period was 12 to 38 months and 14 to 39 months in ROI-C group and titanium plate group respectively. For the age, gender, the JOA scores, VAS scores of neck pain and arm pain during preoperative, the surgical level constituent ratio and the follow-up time, there were no significant differences between two groups. In ROI-C group, the operation time was (123 ± 38) minutes, intraoperative blood loss was (84 ± 37)ml, exposure times to the X-ray C-arm machine was (3.5 ± 0.7) times, which were all significantly lower than titanium plate group ((165 ± 60) minutes, (128 ± 66) ml, (5.9 ± 1.2) times respectively, t = -3.27, -3.25, - 9.45, P = 0.02, 0.02, 0.00). The mean JOA scores increased significantly from pre-surgery to 1 month postoperatively, 3 months postoperatively, and last follow-up in ROI-C group (t = 11.94, 11.32, 10.60, all P = 0.00) and titanium plate group(t = 15.07, 19.51, 17.55, all P = 0.00). The mean VAS scores of neck pain and arm pain decreased significantly from pre-surgery to 1 month postoperatively, 3 months postoperatively, and last follow-up in ROI-C group (t = -16.64-- 9.68, all P = 0.00) and titanium group(t = -16.56--12.38, all P = 0.00). There was no significant difference on JOA scores and VAS scores of neck pain and arm pain between the two groups at the same time (P > 0.05). However, significant difference was observed in incidence of postoperative dysphagia (χ² = 6.79, P = 0.01). In addition, bony fusion was obtained in all cases at the last follow-up postoperatively. There was no significant difference on ratio of bone graft fusion between two groups. CONCLUSION The ROI-C leads to similar clinical outcomes compared to traditional cage combined with anterior plating for the treatment of the cervical spondylotic myelopathy, while the ROI-C carries a simpler operation, shorter operation time, less intraoperative blood loss, less exposure times to the X-ray and a lower risk of postoperative dysphagia.
A call-by-need lambda calculus with locally bottom-avoiding choice: context lemma and correctness of transformations

We present a higher-order call-by-need lambda calculus enriched with constructors, case expressions, recursive letrec expressions, a seq operator for sequential evaluation and a non-deterministic operator amb that is locally bottom-avoiding. We use a small-step operational semantics in the form of a single-step rewriting system that defines a (non-deterministic) normal-order reduction. This strategy can be made fair by adding resources for book-keeping. As equational theory, we use contextual equivalence (that is, terms are equal if, when plugged into any program context, their termination behaviour is the same), in which we use a combination of may- and must-convergence, which is appropriate for non-deterministic computations. We show that we can drop the fairness condition for equational reasoning, since the valid equations with respect to normal-order reduction are the same as for fair normal-order reduction. We develop a number of proof tools for proving correctness of program transformations. In particular, we prove a context lemma for both may- and must- convergence that restricts the number of contexts that need to be examined for proving contextual equivalence. Combining this with so-called complete sets of commuting and forking diagrams, we show that all the deterministic reduction rules and some additional transformations preserve contextual equivalence. We also prove a standardisation theorem for fair normal-order reduction. The structure of the ordering ≤c is also analysed, and we show that Ω is not a least element and ≤c already implies contextual equivalence with respect to may-convergence.
The growth factor receptors HER-2/neu and EGFR, their relationship, and their effects on the prognosis in early stage (FIGO I-II) epithelial ovarian carcinoma

Epithelial ovarian cancer is a heterogeneous disease and many biologic and molecular factors are important for its development and progression, including growth rate, metastatic potential, chemo- and radiosensitivity, and prognosis. Even in the early stages (FIGO I–II), many questions persist about the biologic behavior, optimal treatment, and prognosis. In a series of 106 patients with epithelial ovarian cancers in FIGO stages IA-IIC, a number of known prognostic factors (age, FIGO stage, histopathologic type, and tumor grade) were studied in relation to two important growth factor receptors for oncogenesis (HER-2/neu and EGFR). Immunohistochemical techniques were used. All patients received adjuvant radiotherapy 4–6 weeks after the primary surgery. In a univariate analysis, the expression of the HER-2/neu receptor was not associated with any of the clinicopathologic factors studied or survival status. Positive EGFR staining was associated with poor survival in a univariate analysis. Co-expression of HER-2/neu and EGFR was most frequently seen in serous tumors and positive staining for HER-2/neu alone was associated with mucinous tumors. Both endometrioid and clear cell tumors belonged to the largest subgroup with concomitant negativity for both HER-2/neu and EGFR. In a multivariate Cox analysis, the tumor grade and EGFR status of the tumors were independent and significant prognostic factors. A therapeutic strategy for epithelial ovarian cancer might be to decrease EGFR expression by gene therapy in combination with adjuvant radiotherapy or chemotherapy.
Mental Status as a Common Factor for Masticatory Muscle Pain: A Systematic Review

Masticatory muscle pain (MMP) is the primary reason for chronic non-odontogenic orofacial pain in the human population. MMP has become a considerable social problem, which affects about 12–14% of the adult population and is 1.5–2 times more frequent in women than in men. This term defines a pain which has its origins in the masticatory muscles. Although MMP is typically felt in the face, jaws, and preauricular area, MMP can radiate to the ear, teeth, head, and neck. This systematic review explains the relationship between MMP and common mental states, such as anxiety, depression, mood and stress-related disorders, and is reported in accordance with PRISMA guidelines. We performed a search in the PubMed database for peer-reviewed articles published after November 1st 2006 in the context of MMP and mental states. According to the defined criteria, 38 studies were finally included into the systematic review, of which prospective cohort studies were found to be the most common. We investigated four primary outcomes (anxiety, depression, mood disorders, and stress-related disorders) and several secondary outcomes of search. Seventy-nine percent of studies concerned depression, 42% anxiety, 29% mood disorders, and 21% stress-related disorders. Most of the studies showed a relationship between MMP and alterations in mental status. Nonetheless, the researchers usually evidenced only the co-occurrence of psychiatric disorders and dysfunctions of the masticatory muscles among the group of patients, in large part in women. Moreover, some studies were marked with limited generalizability of the reported results, quality flaws and heterogeneity. In the light of the analyzed literature, the causal relationship between mental states and MMP is still not clearly established.
A database of thermodynamic properties of the reactions of glycolysis, the tricarboxylic acid cycle, and the pentose phosphate pathway

A database of thermodynamic properties is developed, which extends a previous database of glycolysis and tricarboxylic acid cycle by adding the reactions of the pentose phosphate pathway. The raw data and documented estimations of solution properties are made electronically available. The database is determined by estimation of a set of parameters representing species-level free energies of formation. The resulting calculations provide thermodynamic and network-based estimates of thermodynamic properties for six reactions of the pentose phosphate pathway for which estimates are not available in the preexisting literature. Optimized results are made available in ThermoML format. Because calculations depend on estimated hydrogen and metal cation dissociation constants, an uncertainty and sensitivity analysis is performed, revealing 23 critical dissociation constants to which the computed thermodynamic properties are particularly sensitive. Database URL: http://www.biocoda. org/thermo
Effects of ooplasm transfer on paternal genome function in mice.

BACKGROUND The ooplasm plays a central role in forming the paternal pronucleus, and subsequently in regulating the expression of paternally inherited chromosomes. Previous studies in mice have revealed genetic differences in paternal genome processing by ooplasm of different genotypes. Ooplasm donation coupled to intracytoplasmic sperm injection (ICSI) has been used in human assisted reproductive technology (ART). This procedure exposes the developing paternal pronucleus to 'foreign' ooplasm, which may direct aberrant epigenetic processing. The potential effects of the foreign ooplasm on epigenetic information in the paternal pronucleus are unknown; however, some human progeny from ooplasm donation procedures display abnormalities. METHODS In this study, we employed inter-genotype ooplasm transfer followed by ICSI using two mouse strains, C57BL/6 and DBA/2, to explore the influence of foreign ooplasm on paternal pronucleus function. In order to assay for effects on the paternal genome without masking effects of the maternal genome, we examined ooplasm effects in diploid androgenones, which are produced by pronuclear transfer to contain exclusively two paternal sets of chromosomes, in combination with ICSI. RESULTS There was no significant effect of intra-strain ooplasm transfer among androgenones made with either C57BL/6 or DBA/2 oocytes. There was a significant negative effect on androgenone blastocyst development with inter-genotype transfer (10% volume) of DBA/2 ooplasm to C57BL/6 oocytes (P < 0.05). The reciprocal inter-genotype ooplasm transfer had no significant effect. CONCLUSIONS Thus, inter-genotype ooplasm transfer in conjunction with ICSI can alter the function of the paternal genome. However, the effect of foreign ooplasm is restricted to a negative effect, with no evidence of a positive effect. This study provides important new information about the possible consequences of ooplasm donation in human ART.
High density lipoprotein cholesterol increases with living altitude.

BACKGROUND The relationship between high density lipoprotein cholesterol (HDL) serum level and the altitude at which people live is controversial. METHODS A cross-sectional study was carried out in the adult population (30-64 years) of the Island of El Hierro (Canary Islands, Spain). In all, 594 individuals representative of the El Hierro population for gender, age, district and the altitude at which they lived were included. The factors measured included HDL, living altitude, body mass index (BMI), smoking habits, alcohol consumption, diabetes, menopause in women, and physical activity and dietary habits. RESULTS The HDL showed a correlation with living altitude (r = 0.14, P < 0.01) and with BMI (r = -0.19, P < 0.01). Smokers had lower HDL levels than ex-smokers and non-smokers (P < 0.05). Men who were moderate drinkers had higher HDL levels than heavy or mild drinkers and non-drinkers (P < 0.01). Physical activity was only related to HDL in men with levels >1.52 mmol/l, who walked on the average more than the rest (P < 0.05). Variables not showing the expected relationship with HDL were diabetes and the menopause in women (probably due to a low statistical power of their subsamples). Regression analysis, with HDL as dependent variable showed that the association between HDL and altitude persists when taking altitude as a categorical or a continuous variable. CONCLUSIONS High density lipoprotein cholesterol levels are linearly and significantly increased when living at a higher altitude. This fact should be taken into account when comparing cardiovascular risk in populations living at different altitudes.
Consensus problem of second-order multi-agent systems with input delay and communication delay

Asynchronously-coupled consensus algorithm is adopted to solve the consensus problem of the second-order multi-agent systems with both input delay and communication delay. Sufficient conditions, which depend on the input delay and the communication delay, are obtained for the agents converging to a stationary consensus asymptotically by using the frequency domain analysis. Simulation illustrates the correctness of the results.