Miracle-dz/UniFAR-FTUs huggingface dataset:
LAG-3 confers poor prognosis and its blockade reshapes antitumor response in head and neck squamous cell carcinoma

ABSTRACT Immunotherapy with immune checkpoint molecule-specific monoclonal antibody have obtained encouraging results from preclinical studies and clinical trials, which promoted us to explore whether this kind of immunotherapy could be applicable to head and neck squamous cell carcinoma (HNSCC). Lymphocyte activation gene-3 (LAG-3) is an immune checkpoint control protein that negatively regulates T cells and immune response. Here, using the human tissue samples, we report these findings that LAG-3 is overexpressed on tumor-infiltrating lymphocytes (TILs; p < 0.001) and its overexpression correlates with the high pathological grades, lager tumor size and positive lymph node status in human primary HNSCC. Survival analysis identifies LAG-3 as a prognostic factor independent of tumor size and pathological grades for primary HNSCC patients with negative lymph node status (p = 0.014). Study in immunocompetent genetically defined HNSCC mouse model reports that LAG-3 is upregulated on CD4+ T cells, CD8+ T cells and CD4+Foxp3+ regulatory T cells (Tregs). In vivo study, administration of LAG-3-specific antibody retards tumor growth in a way associated with enhanced systemic antitumor response by potentiating the antitumor response of CD8+ T cells and decreasing the population of immunosuppressive cells. Taken together, our results offer a preclinical proof supporting the immunomodulatory effects of LAG-3 and suggest a potential therapeutic target of immunotherapy for HNSCC.
Novel gene expression mechanism in a fission yeast retroelement: Tf1 proteins are derived from a single primary translation product.

In sharp contrast to the single ORF of the Schizosaccharomyces pombe retrotransposon Tf1, retroviruses and most retrotransposons employ two different ORFs to separately encode the Gag and Pol proteins. The different ORFs are thought to allow for overexpression of the Gag protein relative to Pol protein presumed necessary for the assembly of functional retrovirus particles and virus‐like particles (VLPs). The results of in vivo experiments designed to detect the transposition of Tf1 show that Tf1 is indeed active and can insert itself into the host genome via a true retrotransposition process. Thus, a paradox emerged between the lack of any obvious means of overexpressing Tf1 Gag protein and the demonstrated functionality of the element. Epitope tagging experiments described here confirm that the Tf1 large ORF is intact and that there is no translational or transcriptional mechanism used to overexpress the Tf1 Gag protein. In addition, we used sucrose gradients and antisera specific for Tf1 capsid (CA) and integrase (IN) to show that the Tf1 proteins do assemble into uniform populations of macromolecular particles that also cosediment with Tf1 reverse transcription products. This evidence suggests that Tf1 proteins form VLPs without using the previously described mechanisms that retroviruses and retrotransposons require to overexpress Gag proteins.
Antibodies to macrophage stimulating protein (MSP): specificity, epitope interactions, and immunoassay of MSP in human serum

Abstract: Macrophage stimulating protein (MSP) is a member of a family of proteins characterized by a triple disulfide loop structure (kringle). We developed antibodies to human MSP for detection in Western blots, quantification in biological fluids, and neutralization of activity. Immunogens included native MSP, reduced and alkylated α and β chains, and peptides of MSP regions with minimal sequence similarity to other kringle proteins. We found three antibody categories based on interaction with the following types of epitope: primary sequence, discontinuous (dependent on disulfide bonds), and cryptic (not exposed in native MSP). None of the antibodies reacted with related kringle proteins. A specific sandwich ELISA was developed for measuring human MSP. The mean serum concentration was 4 nM. Serum MSP did not increase over a 24‐h period in response to intravenous lipopolysaccharide, indicating that MSP is not an acute phase protein. These findings are consistent with the hypothesis that regulation of MSP activity is by conversion of pro‐MSP to MSP rather than by rapid changes in rates of synthesis.
Income Inequality and Willingness to Pay for Environmental Public Goods

We study how the distribution of income among members of society, and income inequality in particular, affects social willingness to pay (WTP) for environmental public goods. We find that social WTP for environmental goods increases with mean income, and decreases (increases) with income inequality if and only if environmental goods and manufactured goods are substitutes (complements). Furthermore, social WTP for environmental normally changes more elastically with mean income than with income inequality. We derive adjustment factors for benefit transfer to control for differences in income distributions between a study site and a policy site. For illustration, we quantify how social WTP for environmental public goods depends on the respective income distribution for empirical case studies in Sweden, China and the World. We find that the effects of adjusting for income inequality can be substantial.
Tricaesium tris(pyridine-2,6-dicarboxylato-κ3 O 2,N,O 6)lutetium(III) octahydrate

Colourless block crystals of the title compound, Cs3[Lu(dipic)3]·8H2O [dipic is dipicolinate or pyridine-2,6-dicarboxylate, C7H3NO4] were synthesized by slow evaporation of the solvent. The crystal structure of this LuIII-complex, isostructural with the DyIII and EuIII complexes, was determined from a crystal twinned by inversion and consists of discrete [Lu(dipic)3]3− anions, Cs+ cations and water molecules involving hydrogen bonding. The Lu atom lies on a twofold rotation axis and is coordinated by six O atoms and three N atoms of three dipicolinate ligands. One Cs atom is also on a twofold axis. The unit cell can be regarded as successive layers along the crystallographic c-axis formed by [Lu(dipic)3]3− anionic planes and [Cs+, H2O] cationic planes. In the crystal structure, although the H atoms attached to water molecules could not be located, short O—O contacts clearly indicate the occurrence of an intricate hydrogen-bonded network through contacts with other water molecules, Cs cations or with the O atoms of the dipicolinate ligands.
Adalimumab for Crohn's disease in clinical practice at Mayo clinic: The first 118 patients

Background: We sought to assess the effectiveness and safety of adalimumab for the treatment of Crohn's disease (CD) in clinical practice. Methods: Demographic, clinical, and treatment data were abstracted from the medical record. The primary outcome was clinical response to induction therapy with adalimumab for CD (complete, partial, or nonresponse). Results: In all, 118 patients were prescribed adalimumab for CD between January 2003 and June 2007. All but five subjects (96%) had received prior infliximab and 50 were on systemic corticosteroids at the time of initial adalimumab dose (44%). A complete response was achieved in 53 patients and 20 patients had no response. The cumulative probability of any response (complete or partial) was 81.3% at 1 year. Dose escalation was required in 59 patients (1‐year cumulative probability, 54.0%). Among patients with complete response, 18 lost response during follow‐up (1‐year cumulative probability, 21.4%). Among 50 patients on corticosteroids at baseline the median daily dose was 20 mg, which decreased to a median of 0 mg during treatment. Sixty‐four patients (54%) experienced a total of 117 adverse events. Thirteen patients (11%) experienced 15 serious adverse events. Sixteen patients (14%) discontinued adalimumab due to an adverse event. Conclusions: Adalimumab was both effective and well tolerated for the treatment of CD in this tertiary practice with a high prevalence of past infliximab exposure. This experience largely predates FDA approval of adalimumab for CD. (Inflamm Bowel Dis 2010)
Bleeding Risk Associated with Resection of the Middle Turbinate during Functional Endoscopic Sinus Surgery

Background The decision to resect the middle turbinate (MT) during functional endoscopic sinus surgery is controversial. Although there have been a variety of studies that examined the functional outcome related to this maneuver, very few studies evaluated the potential for complications, in particular, epistaxis. Objective We sought to determine ifresection of the MT during functional endoscopic sinus surgery leads to an increased risk for postoperative bleeding. Methods Patients who underwent functional endoscopic sinus surgery for chronic sinusitis or nasal polyposis between 2004 and 2014 at a single institution were analyzed for bleeding and other complications after resection of the MT. Results Between 2004 and 2014,1185 sinus surgeries were performed by 18 surgeons. A propensity matched set of 228 patients who underwent turbinate resection, and 228 controls were selected based on predicted probabilities from a logistic regression that predicted turbinate resection and that was adjusted for age, sex, and procedure. There were 89 patients with bilateral turbinates removed and 139 with unilateral turbinates removed. There was no significant difference in major bleeding or other complication rates between the two groups. Patients who underwent resection of at least one MT were 3.95 times more likely to have minor bleeding compared with those who did not; this risk increased with the number of turbinates resected (trend p = 0.008). Patients on anticoagulation medications were at a significant risk of bleeding if their MT was removed (p = 0.007), whereas patients on aspirin or antiplatelet therapy were not at a significant risk. Conclusion There was no increased risk of major bleeding or other complication associated with resection of the MT. However, there was a significantly increased minor bleeding rate associated with MT resection, particularly ifthe patient was on anticoagulants.
Impact of Accounting Data on Stock Prices: The Case of Vietnam

This research is conducted for evaluating the impact of accounting numbers on stock prices of listed firms on Vietnam Stock Exchange. Data were collected from 416 listed firms for the period from 2012 to 2016. By using models of OLS, FEM, REM and GLS for evaluating the relationship between earnings per share (EPS), book value of stock (BV) and stock prices, the results show that EPS, BV have positive relationships with stock prices with the level of 48.13% basing on the model of Ohlson (1995) and on the model of Ohlson adjusted to Aboody et al. (2002). Based on the findings, some implications for investors and stakeholders have been given in the context of Vietnam.
Using snowball sampling method with nurses to understand medication administration errors.

AIMS AND OBJECTIVES We aimed to encourage nurses to release information about drug administration errors to increase understanding of error-related circumstances and to identify high-alert situations. BACKGROUND Drug administration errors represent the majority of medication errors, but errors are underreported. Effective ways are lacking to encourage nurses to actively report errors. METHODS Snowball sampling was conducted to recruit participants. A semi-structured questionnaire was used to record types of error, hospital and nurse backgrounds, patient consequences, error discovery mechanisms and reporting rates. RESULTS Eighty-five nurses participated, reporting 328 administration errors (259 actual, 69 near misses). Most errors occurred in medical surgical wards of teaching hospitals, during day shifts, committed by nurses working fewer than two years. Leading errors were wrong drugs and doses, each accounting for about one-third of total errors. Among 259 actual errors, 83.8% resulted in no adverse effects; among remaining 16.2%, 6.6% had mild consequences and 9.6% had serious consequences (severe reaction, coma, death). Actual errors and near misses were discovered mainly through double-check procedures by colleagues and nurses responsible for errors; reporting rates were 62.5% (162/259) vs. 50.7% (35/69) and only 3.5% (9/259) vs. 0% (0/69) were disclosed to patients and families. High-alert situations included administration of 15% KCl, insulin and Pitocin; using intravenous pumps; and implementation of cardiopulmonary resuscitation (CPR). CONCLUSIONS Snowball sampling proved to be an effective way to encourage nurses to release details concerning medication errors. Using empirical data, we identified high-alert situations. Strategies for reducing drug administration errors by nurses are suggested. RELEVANCE TO CLINICAL PRACTICE Survey results suggest that nurses should double check medication administration in known high-alert situations. Nursing management can use snowball sampling to gather error details from nurses in a non-reprimanding atmosphere, helping to establish standard operational procedures for known high-alert situations.
Health Care Utilisation and Transitions between Health Care Settings in the Last 6 Months of Life in Switzerland

Background Many efforts are undertaken in Switzerland to enable older and/or chronically ill patients to stay home longer at the end-of-life. One of the consequences might be an increased need for hospitalisations at the end-of-life, which goes along with burdensome transitions for patients and higher health care costs for the society. Aim We aimed to examine the health care utilisation in the last six months of life, including transitions between health care settings, in a Swiss adult population. Methods The study population consisted of 11'310 decedents of 2014 who were insured at the Helsana Group, the leading health insurance in Switzerland. Descriptive statistics were used to analyse the health care utilisation by age group, taking into account individual and regional factors. Zero-inflated Poisson regression model was used to predict the number of transitions. Results Mean age was 78.1 in men and 83.8 in women. In the last six months of life, 94.7% of the decedents had at least one consultation; 61.6% were hospitalised at least once, with a mean length of stay of 28.3 days; and nursing home stays were seen in 47.4% of the decedents. Over the same time period, 64.5% were transferred at least once, and 12.9% experienced at least one burdensome transition. Main predictors for transitions were age, sex and chronic conditions. A high density of home care nurses was associated with a decrease, whereas a high density of ambulatory care physicians was associated with an increase in the number of transitions. Conclusions Health care utilisation was high in the last six months of life and a considerable number of decedents were being transferred. Advance care planning might prevent patients from numerous and particularly from burdensome transitions.
Behavioural and cognitive abnormalities in an imprinting centre deletion mouse model for Prader–Willi syndrome

The genes in the imprinted cluster on human chromosome 15q11–q13 are known to contribute to psychiatric conditions such as schizophrenia and autism. Major disruptions of this interval leading to a lack of paternal allele expression give rise to Prader–Willi syndrome (PWS), a neurodevelopmental disorder with core symptoms of a failure to thrive in infancy and, on emergence from infancy, learning disabilities and over‐eating. Individuals with PWS also display a number of behavioural problems and an increased incidence of neuropsychiatric abnormalities, which recent work indicates involve aspects of frontal dysfunction. To begin to examine the contribution of genes in this interval to relevant psychological and behavioural phenotypes, we exploited the imprinting centre (IC) deletion mouse model for PWS (PWS‐IC+/−) and the five‐choice serial reaction time task (5‐CSRTT), which is primarily an assay of visuospatial attention and response control that is highly sensitive to frontal manipulations. Locomotor activity, open‐field behaviour and sensorimotor gating were also assessed. PWS‐IC+/− mice displayed reduced locomotor activity, increased acoustic startle responses and decreased prepulse inhibition of startle responses. In the 5‐CSRTT, the PWS‐IC+/− mice showed deficits in discriminative response accuracy, increased correct reaction times and increased omissions. Task manipulations confirmed that these differences were likely to be due to impaired attention. Our data recapitulate several aspects of the PWS clinical condition, including findings consistent with frontal abnormalities, and may indicate novel contributions of the imprinted genes found in 15q11–q13 to behavioural and cognitive function generally.
Postnatal development of cholinergic markers in the rat olfactory bulb: A histochemical and immunocytochemical study

The present study has defined the developmental time course and the distribution patterns of neuronal fibers and cell bodies displaying acetylcholinesterase (AChE) activity or choline acetyltransferase (ChAT) immunoreactivity in the rat olfactory bulb. The results indicate that the deployment of centrifugal AChE‐containing fibers is essentially postnatal. The subset of atypical glomeruli, including the modified glomerular complex, is innervated as early as the first postnatal day while the normal ones are not reached by this type of afferent before postnatal day 6. The comparison of AChE labelling with ChAT immunoreactivity strongly supports the assumption that AChE‐containing fibers represent mainly, if not exclusively, the cholinergic bulbopetal innervation emanating from the basal forebrain. A quantitative study has confirmed that the density of labelled fibers increases gradually in the postnatal period and spreads heterogeneously among the bulbar layers. The selective precocious innervation of atypical glomeruli is in favor of their involvement in the early processing of olfactory information in the olfactory bulb. Acetylcholinesterase is also expressed within a subset of ChAT‐negative interneurons of the developing olfactory bulb. The number of neurons expressing AChE increases from birth to postnatal day 15 and then decreases to reach the adult value on about postnatal day 30. This neuronal population could constitute a cholinoceptive subset mediating the effects of cholinergic afferents on the bulbar neuronal network.
The Role of Intellectual Capital To Economic Value Added (Empirical Study on Manufacturing Companies of Consumption Goods Sector)

The purpose of this study to analyze the influence of Intellectual Capital to Economic Value Added. The samples are 90 manufacture companies as the item of observations that were taken from annual reports listed of Indonesian Stock Exchange in 2011-2015. The model that used to measure intellectual capital was using Modified Value Added Intellectual Capital Coefficient (M-VAIC). M-VAIC component consist of Human Capital Efficiency (HCE), Structural Capital Efficiency (SCE), Capital Employed Efficiency (CEE) and Relational Capital Efficiency (RCE). This research is quantitative research and using panel data regression on balanced data of fixed effect for data analysis. The results showed that Human Capital Efficiency (HCE) and Structural Capital Efficiency (SCE) has no positive impact on Economy Value Added (EVA) but in this research has a positive impact on the Capital Employed Efficiency (CEE) and Relational Capital Efficiency (RCE) to Economic Value Added (EVA).
Development of a single coil coupled force VCM actuator for high TPI magnetic recording

A novel high bandwidth actuator assembly is developed for the applications of high TPI recording in hard disk drives. The novel design in VCM construction, with flat moving-coil, is as simple as a conventional one. The VCM generates orthogonal force or pure torque. A 3D FEA is conducted in the electromagnetic design to optimize some critical electromagnetic parameters and the main dimensions. A 3D FEA is also carried out to predict the dynamic performance. The study shows that the quasi-rigid body vibration mode has been substantially suppressed. Measurement of the characteristics of a prototype is carried out and the result is discussed.
Human S‐adenosylhomocysteine hydrolase: common gene sequence variation and functional genomic characterization

S‐Adenosylhomocysteine hydrolase (AHCY) is the only mammalian enzyme known to catalyze the hydrolysis of S‐adenosylhomocysteine. We have used a genotype‐to‐phenotype strategy to study this important enzyme by resequencing AHCY in 240 DNA samples from four ethnic groups. Thirty‐nine polymorphisms were identified – 28 of which were novel. Functional genomic studies for wild type AHCY and the three variant allozymes identified showed that two variant allozymes had slight, but significant decreases in enzyme activity, but with no significant differences in levels of immunoreactive protein. Luciferase reporter gene assays for common 5′‐flanking region haplotypes revealed that one haplotype with a frequency of ∼2% in Caucasian‐American subjects displayed a decreased ability to drive transcription. The variant nucleotide at 5′‐flanking region single nucleotide polymorphism (SNP) (−34) in that haplotype altered the DNA‐protein binding pattern during electrophoresis mobility shift assay. Finally, an AHCY genotype‐phenotype association study for expression in lymphoblastoid cells identified four SNPs that were associated with decreased expression. For the IVS6 (intervening sequence 6, i.e., intron 6) G56 > C SNP among those four, electrophoresis mobility shift assay showed that a C > G nucleotide change resulted in an additional shifted band. These results represent a step toward understanding the functional consequences of common genetic variation in AHCY for the regulation of neurotransmitter, drug and macromolecule methylation.
External and internal gelation of pectin solutions: microscopic dynamics versus macroscopic rheology

Pectin is a natural biopolymer that forms, in the presence of divalent cations, ionic-bound gels typifying a large class of biological gels stabilized by non-covalent cross-links. We investigate and compare the kinetics of formation and aging of pectin gels obtained either through external gelation via perfusion of free Ca2+ ions, or by internal gelation due to the supply of the same ions from the dissolution of CaCO3 nanoparticles. The microscopic dynamics obtained with photon correlation imaging, a novel optical technique that allows obtaining the microscopic dynamics of the sample while retaining the spatial resolution of imaging techniques, is contrasted with macroscopic rheological measurements at constant strain. Pectin gelation is found to display peculiar two-stage kinetics, highlighted by non-monotonic growth in time of both microscopic correlations and gel mechanical strength. These results are compared to those found for alginate, another biopolymer extensively used in food formulation.