bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness and safety of meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB
Authors: Tiberi Simon , Payen Marie-Christine , Sotgiu Giovanni , D'Ambrosio Lia , Alarcon Guizado Valentina , Alffenaar Jan Willem , Abdo Arbex Marcos , Caminero Jose A. , Centis Rosella , De Lorenzo Saverio , Gaga Mina , Gualano Gina , Roby Arias Aurora Jazmín , Scardigli Anna , Skrahina Alena , Solovic Ivan , Sulis Giorgia , Tadolini Marina , Akkerman Onno W. , Alarcon Arrascue Edith , Aleska Alena , Avchinko Vera , Bonini Eduardo Henrique , Chong Marín Félix Antonio , Collahuazo López Lorena , de Vries Gerard , Dore Simone , Kunst Heinke , Matteelli Alberto , Moschos Charalampos , Palmieri Fabrizio , Papavasileiou Apostolos , Spanevello Antonio , Vargas Vasquez Dante , Viggiani Pietro , White Veronica , Zumla Alimuddin , Migliori Giovanni Battista 
Published: March 2016

No large study has ever evaluated the efficacy, safety and tolerability of meropenem/clavulanate to treat multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB). The aim of this observational study was to evaluate the therapeutic contribution, effectiveness, safety and tolerability profile of meropenem/clavulanate added to a background regimen when treating MDR- and XDR-TB cases.Patients treated with a meropenem/clavulanate-containing regimen (n=96) showed a greater drug resistance profile than those exposed to a meropenem/clavulanate-sparing regimen (n=168): in the former group XDR-TB was more frequent (49%versus6.0%, p<0.0001) and the median (interquartile range (IQR)) number of antibiotic resistances was higher (8 (6–9)versus5 (4–6)). Patients were treated with a meropenem/clavulanate-containing regimen for a median (IQR) of 85 (49–156) days.No statistically significant differences were observed in the overall MDR-TB cohort and in the subgroups with and without the XDR-TB patients; in particular, sputum smear and culture conversion rates were similar in XDR-TB patients exposed to meropenem/clavulanate-containing regimens (88.0%versus100.0%, p=1.00 and 88.0%versus100.0%, p=1.00, respectively). Only six cases reported adverse events attributable to meropenem/clavulanate (four of them then restarting treatment).The nondifferent outcomes and bacteriological conversion rate observed in cases who were more severe than controls might imply that meropenem/clavulanate could be active in treating MDR- and XDR-TB cases.
GOexpress: an R/Bioconductor package for the identification and visualisation of robust gene ontology signatures through supervised learning of gene expression data
Authors: Rue-Albrecht Kévin , McGettigan Paul A. , Hernández Belinda , Nalpas Nicolas C. , Magee David A. , Parnell Andrew C. , Gordon Stephen V. , MacHugh David E. 
Published: March 2016

Abstract
Background
Identification of gene expression profiles that differentiate experimental groups is critical for discovery and analysis of key molecular pathways and also for selection of robust diagnostic or prognostic biomarkers. While integration of differential expression statistics has been used to refine gene set enrichment analyses, such approaches are typically limited to single gene lists resulting from simple two-group comparisons or time-series analyses. In contrast, functional class scoring and machine learning approaches provide powerful alternative methods to leverage molecular measurements for pathway analyses, and to compare continuous and multi-level categorical factors.

Results
We introduce GOexpress, a software package for scoring and summarising the capacity of gene ontology features to simultaneously classify samples from multiple experimental groups. GOexpress integrates normalised gene expression data (e.g., from microarray and RNA-seq experiments) and phenotypic information of individual samples with gene ontology annotations to derive a ranking of genes and gene ontology terms using a supervised learning approach. The default random forest algorithm allows interactions between all experimental factors, and competitive scoring of expressed genes to evaluate their relative importance in classifying predefined groups of samples.

Conclusions
GOexpress enables rapid identification and visualisation of ontology-related gene panels that robustly classify groups of samples and supports both categorical (e.g., infection status, treatment) and continuous (e.g., time-series, drug concentrations) experimental factors. The use of standard Bioconductor extension packages and publicly available gene ontology annotations facilitates straightforward integration of GOexpress within existing computational biology pipelines.
Bacurd1/Kctd13 and Bacurd2/Tnfaip1 are interacting partners to Rnd proteins which influence the long-term positioning and dendritic maturation of cerebral cortical neurons
Authors: Gladwyn-Ng Ivan , Huang Lieven , Ngo Linh , Li Shan Shan , Qu Zhengdong , Vanyai Hannah Kate , Cullen Hayley Daniella , Davis John Michael , Heng Julian Ik-Tsen 
Published: March 2016

Abstract

Background
The development of neural circuits within the embryonic cerebral cortex relies on the timely production of neurons, their positioning within the embryonic cerebral cortex as well as their terminal differentiation and dendritic spine connectivity. The RhoA GTPases Rnd2 and Rnd3 are important for neurogenesis and cell migration within the embryonic cortex (Nat Commun 4:1635, 2013), and we recently identified the BTB/POZ domain-containing Adaptor for Cul3-mediated RhoA Degradation family member Bacurd2 (also known as Tnfaip1) as an interacting partner to Rnd2 for the migration of embryonic mouse cortical neurons (Neural Dev 10:9, 2015).

Findings
We have extended this work and report that Bacurd1/Kctd13 and Bacurd2/Tnfaip1 are interacting partners to Rnd2 and Rnd3 in vitro. Given that these genes are expressed during cortical development, we performed a series of in utero electroporation studies in mice and found that disruptions to Bacurd1/Kctd13 or Bacurd2/Tnfaip1 expression impair the long-term positioning of E14.5-born cortical neurons within the postnatal (P17) mouse cerebral cortex. We also find that forced expression of Bacurd1/Kctd13 and Bacurd2/Tnfaip1 alters the branching and dendritic spine properties of layer II/III projection neurons.

Conclusions
We identify Bacurd1/Kctd13 and Bacurd2/Tnfaip1 as interacting partners to Rnd proteins which influence the development of cortical neurons. Their neurodevelopmental functions are likely to be relevant to human brain development and disease.
Variational inequality formulation of circular cone eigenvalue complementarity problems
Authors: Chi Xiaoni , Wei Hongjin , Feng Yuqiang , Chen Jiawei 
Published: March 2016

AbstractIn this paper, we study the circular cone eigenvalue complementarity problem (CCEiCP) by variational inequality technique, prove the existence of a solution to CCEiCP, and investigate different nonlinear programming formulations of the symmetric and asymmetric CCEiCP, respectively. We reduce CCEiCP to a variational inequality problem on a compact convex set, which guarantees that CCEiCP has at least one solution. Based on the variational inequality formulation of CCEiCP, the symmetric CCEiCP can be reformulated as a nonlinear programming problem NLP1, and solved by computing a stationary point of the Rayleigh quotient function on a compact set. We formulate the asymmetric CCEiCP as another nonlinear programming problem NLP2, and show that any global minimum of NLP2with an objective function value equal to zero is a solution of the asymmetric CCEiCP. Moreover, a stationary point of NLP2is a solution of the asymmetric CCEiCP, if and only if the Lagrange multipliers associated with the equalities in NLP2are equal to zero. The different formulations of CCEiCP provide alternative approaches for solving CCEiCP, which will play an important role in designing efficient algorithms to solve CCEiCP.
Best proximity point theorems via fixed point theorems for multivalued mappings
Authors: Ardsalee Pinya , Saejung Satit 
Published: March 2016

AbstractIt is well known that the concept of a best proximity point includes that of a fixed point as a special case. In this paper, we show that the best proximity point theorems of Basha and Shahzad (Fixed Point Theory Appl. 2012:42, 2012) and of Fernández-León (J. Nonlinear Convex Anal. 15(2):313-324, 2014) can be regarded as a fixed point theorem for multivalued mappings which is modified as regards the results of Mizoguchi and Takahashi (J. Math. Anal. Appl. 141(1):177-188, 1989) and of Kada et al. (Math. Jpn. 44(2):381-391, 1996).
Interleukin-7 promotes human regulatory T cell development at the CD4+CD8+ double-positive thymocyte stage
Authors: Tuulasvaara Anni , Vanhanen Reetta , Baldauf Hanna-Mari , Puntila Juha , Arstila T Petteri 
Published: March 2016

Abstract
Although mature human FOXP3+ regulatory T cells are CD127 (IL-7Rα) negative, CD4+CD8+ FOXP3+ thymocytes express relatively high levels of CD127 and are responsive to IL-7. However, the role of IL-7 in human regulatory T cell development is poorly known. We show that at the CD4+CD8+ stage, FOXP3+ thymocytes are highly susceptible to apoptosis, and IL-7 selectively rescues them from death, leading to an increased frequency of FOXP3+ cells. IL-7 also promotes the development of regulatory T cell phenotype by inducing up-regulation of FOXP3+ and CTLA-4 expression. In contrast, IL-7 does not enhance proliferation of FOXP3+thymocytes or induce demethylation of FOXP3+ regulatory T cell-specific demethylated region. After the CD4+CD8+ stage, the FOXP3+ thymocytes down-regulate CD127 expression but despite very low levels of CD127, remain responsive to IL-7. These results suggest that IL-7 affects human regulatory T cell development in the thymus by at least 2 distinct mechanisms: suppression of apoptosis and up-regulation of FOXP3+ expression.
Reduced TNF-α response in preterm neonates is associated with impaired nonclassic monocyte function
Authors: Wisgrill Lukas , Groschopf Alina , Herndl Elisabeth , Sadeghi Kambis , Spittler Andreas , Berger Angelika , Förster-Waldl Elisabeth 
Published: March 2016

Abstract
Premature infants are highly susceptible to severe bacterial infections. The impaired infection control related to the functional immaturity of the neonatal innate immune system is an important cause of infection. Different monocyte subpopulations have been described and functionally characterized. However, data from preterm infants are scarce. We analyzed constitutive monocyte TLR2, TLR4, CD163, and HLA-DR expression in preterm cord blood. We further investigated activation of the signaling proteins ERK1/2 and NF-κB in monocyte subpopulations after ex vivo stimulation with the bacterial TLR agonists LPS and lipoteichoic acid. The functional outcome of the stimulation was determined by the intracellular production of TNF. Furthermore, the phagocytic activity was measured via flow cytometry. TLR4 and HLA-DR showed a gestational age-dependent increase. However, activation of ERK1/2 and NF-κB was impaired in neonatal monocyte subpopulations after stimulation with TLR agonists. Accordingly, intracellular TNF was diminished in preterm monocytes, especially in nonclassic monocytes. Premature monocytes showed high phagocytic activity, with significantly lower acidification of the phagosome. The reduced functional response of nonclassic monocytes of preterm neonates appears to be part of the diminished early immune response to bacterial cell wall components and is likely to contribute to their susceptibility to bacterial infection.
Case finding and screening clinical utility of the Patient Health Questionnaire (PHQ-9 and PHQ-2) for depression in primary care: a diagnostic meta-analysis of 40 studies
Authors: Mitchell Alex J. , Yadegarfar Motahare , Gill John , Stubbs Brendon 
Published: March 2016

BackgroundThe Patient Health Questionnaire (PHQ) is the most commonly used measure to screen for depression in primary care but there is still lack of clarity about its accuracy and optimal scoring method.AimsTo determine via meta-analysis the diagnostic accuracy of the PHQ-9-linear, PHQ-9-algorithm and PHQ-2 questions to detect major depressive disorder (MDD) among adults.MethodWe systematically searched major electronic databases from inception until June 2015. Articles were included that reported the accuracy of PHQ-9 or PHQ-2 questions for diagnosing MDD in primary care defined according to standard classification systems. We carried out a meta-analysis, meta-regression, moderator and sensitivity analysis.ResultsOverall, 26 publications reporting on 40 individual studies were included representing 26 902 people (median 502, s.d.=693.7) including 14 760 unique adults of whom 14.3% had MDD. The methodological quality of the included articles was acceptable. The meta-analytic area under the receiver operating characteristic curve of the PHQ-9-linear and the PHQ-2 was significantly higher than the PHQ-9-algorithm, a difference that was maintained in head-to-head meta-analysis of studies. Our best estimates of sensitivity and specificity were 81.3% (95% CI 71.6–89.3) and 85.3% (95% CI 81.0–89.1), 56.8% (95% CI 41.2–71.8) and 93.3% (95% CI 87.5–97.3) and 89.3% (95% CI 81.5–95.1) and 75.9% (95% CI 70.1–81.3) for the PHQ-9-linear, PHQ-9-algorithm and PHQ-2 respectively. For case finding (ruling in a diagnosis), none of the methods were suitable but for screening (ruling out non-cases), all methods were encouraging with good clinical utility, although the cut-off threshold must be carefully chosen.ConclusionsThe PHQ can be used as an initial first step assessment in primary care and the PHQ-2 is adequate for this purpose with good acceptability. However, neither the PHQ-2 nor the PHQ-9 can be used to confirm a clinical diagnosis (case finding).
Minimum Effective Doses of Succinylcholine and Rocuronium During Electroconvulsive Therapy: A Prospective, Randomized, Crossover Trial
Authors: Mirzakhani Hooman , Guchelaar Henk-Jan , Welch Charles A. , Cusin Cristina , Doran Mary E. , MacDonald Teresa O. , Bittner Edward A. , Eikermann Matthias , Nozari Ala 
Published: March 2016

BACKGROUND:
Neuromuscular blockade is required to control excessive muscle contractions during electroconvulsive therapy (ECT). In a crossover, assessor-blinded, prospective randomized study, we studied the minimum effective dose (MED) of succinylcholine and rocuronium for ECT. The MED was the lowest dose to provide a predefined qualitative measure of acceptable control of muscle strength during induced convulsions.

METHODS:
Succinylcholine (0.8 mg kg−1) or rocuronium (0.4 mg kg−1) was randomly administered in 227 ECT sessions to 45 patients. The dose was incrementally increased or decreased by 10% based on 2 psychiatrists’ (blinded to treatment) assessment of “acceptable” or “not acceptable” control of evoked muscle contractions (sufficient versus insufficient or excessive paralysis). The neuromuscular transmission was monitored quantitatively until full recovery.

RESULTS:
In our study, the MEDs of succinylcholine and rocuronium to produce acceptable ECT conditions in 50% of patients (MED50ECT) were 0.85 mg kg−1 (95% confidence interval [CI], 0.77–0.94) and 0.41 mg kg−1 (95% CI, 0.36–0.46) and in 90% of patients (MED90ECT) were 1.06 mg kg−1 (95% CI, 1.0–1.27) and 0.57 mg kg−1 (95% CI, 0.5–0.6), respectively. Nadir twitch height for acceptable muscle activity was 0% (0–4) and 4% (0–30; P < 0.001), respectively, and the time to recovery of the neuromuscular transmission was 9.7 ± 3.5 and 19.5 ± 5.7 minutes, respectively.

CONCLUSIONS:
A twitch suppression of >90% is needed for control of motor contractions during ECT. The initial ECT dose of succinylcholine should be selected based on each patient’s preprocedural condition, ranging between 0.77 and 1.27 mg kg−1 to produce acceptable muscle blockade in 50% to 90% of patients. Rocuronium–neostigmine combination is a safe alternative if appropriately dosed (0.36–0.6 mg kg−1) and monitored.
ARMS/Kidins220 and synembryn-B levels regulate NGF-mediated secretion
Authors: López-Benito Saray , Lillo Concepción , Hernández-Hernández Ángel , Chao Moses V. , Arévalo Juan C. 
Published: March 2016

ABSTRACT
Proper development of the nervous system requires a temporally and spatially orchestrated set of events including differentiation, synapse formation and neurotransmission. Nerve growth factor (NGF) acting through the TrkA neurotrophin receptor (also known as NTRK1) regulates many of these events. However, the molecular mechanisms responsible for NGF-regulated secretion are not completely understood. Here, we describe a new signaling pathway involving TrkA, ARMS (also known as Kidins220), synembryn-B and Rac1 in NGF-mediated secretion in PC12 cells. Whereas overexpression of ARMS blocked NGF-mediated secretion, without affecting basal secretion, a decrease in ARMS resulted in potentiation. Similar effects were observed with synembryn-B, a protein that interacts directly with ARMS. Downstream of ARMS and synembryn-B are Gαq and Trio proteins, which modulate the activity of Rac1 in response to NGF. Expression of dominant-negative Rac1 rescued the secretion defects of cells overexpressing ARMS or synembryn-B. Thus, this neurotrophin pathway represents a new mechanism responsible for NGF-regulated secretion.
A curated transcriptome dataset collection to investigate the immunobiology of HIV infection
Authors: Blazkova Jana , Boughorbel Sabri , Presnell Scott , Quinn Charlie , Chaussabel Damien 
Published: March 2016

Compendia of large-scale datasets available in public repositories provide an opportunity to identify and fill current gaps in biomedical knowledge. But first, these data need to be readily accessible to research investigators for interpretation. Here, we make available a collection of transcriptome datasets relevant to HIV infection. A total of 2717 unique transcriptional profiles distributed among 34 datasets were identified, retrieved from the NCBI Gene Expression Omnibus (GEO), and loaded in a custom web application, the Gene Expression Browser (GXB), designed for interactive query and visualization of integrated large-scale data. Multiple sample groupings and rank lists were created to facilitate dataset query and interpretation via this interface. Web links to customized graphical views can be generated by users and subsequently inserted in manuscripts reporting novel findings, such as discovery notes. The tool also enables browsing of a single gene across projects, which can provide new perspectives on the role of a given molecule across biological systems. This curated dataset collection is available at:http://hiv.gxbsidra.org/dm3/geneBrowser/list.
On the Impact of Uncertain Cost Reduction When Selling to Strategic Customers
Authors: Shum Stephen , Tong Shilu , Xiao Tingting 
Published: March 2016

Many products undergo cost reductions over their product life cycles. However, strategic customers may have more incentive to wait if they expect a cost reduction to lead to a price drop. A firm that does not face any uncertainty can use pricing strategies such as price commitment and price matching to alleviate the strategic waiting of customers. However, these pricing strategies provide less flexibility than dynamic pricing for a firm facing uncertainty. In this paper, we examine the impact of cost reduction under dynamic pricing, price commitment, and price matching when cost reduction can come from production learning or from technology advancement. The firm makes pricing decisions when facing uncertainty in future cost, and strategic customers decide whether to wait when facing uncertainty in future price. We show that in general the firm’s profit is higher when future cost is more uncertain, but not necessarily when cost reduction is more significant. In addition, production learning and technology advancement can have opposite effects on the optimal pricing decisions and the choice of pricing strategy. This paper was accepted by Yossi Aviv, operations management.
Assessment of Patient Safety Culture in Primary Healthcare Services in Alexandria, Egypt
Authors: Mohamed Aida Mohey , Ali Mona Shawki , Gewaifel Gihan Ismail 
Published: March 2016

Background: Patient safety is a critical component of healthcare quality. This study aimed at assessing the perceptions of primary healthcare staff members about patient safety culture and explores the areas of deficiency and opportunities for improvement concerning this issue.
Methods: This descriptive cross sectional study surveyed 328 staff members in 28 primary healthcare facilities in Alexandria using an anonymous direct structured interview format of a modified “Hospital Survey on Patient Safety Culture” adopted questionnaire. The total number of respondents was 250 participants (response rate = 76.2%). The main outcome measures include patient safety culture score including sub scores on 12 dimensions and 42 items; patient safety grade, number of events reported and factors contributing to the adverse events.
Results: The overall median% score for perception of patient safety culture at the facility level was 68.6%. After controlling of the confounders; being female respondent, being physicians or nurses or midwives, having long experience in PHC service and receiving education and training about safety issues were positively associated with positive response on patient safety culture scale. The domains with the highest positive score and are thus considered areas of strength were teamwork within units (80.0%), management support for patient safety (80.0%), supervisor expectations and actions promoting patient safety (75.0%) and handoffs and transitions (75.0%). Dimensions scoring the lowest and as such can be considered areas requiring improvement were overall perceptions of patient safety, frequency of events reported and staffing (60% give positive response for each). More than two-fifths (43.6%) did not report any events in the 12 months preceding the survey. The difference between professions regarding the most common procedure that causes adverse event is statistically significant. Patients' related factors such as ignorance and socio cultural acceptance were reported to be the most common factors contributing to the adverse events (92.4% of the studied participants reported that).
Conclusions: Improving patient safety culture should be a priority among health center administrators. Healthcare staff should be encouraged to report errors
Blow-up techniques and regularity near the boundary for free discontinuity problems
Authors: Maddalena Francesco , Solimini Sergio 
Published: March 2016

Abstract
In this paper we exploit some compactness properties of the set of quasiminimizers of a functional with free discontinuities with the aim of obtaining blow-up techniques. These techniques are finally applied to show regularity near the boundary of the minimizers of the Mumford-Shah functional.
Bifurcation From Infinity Induced by a Degeneracy in Semilinear Equations
Authors: Du Yihong , Ouyang Tiancheng 
Published: March 2016

Abstract
We show that for a class of semilinear elliptic eigenvalue problems, including the model case
-Δu = λu - h(x) - h(x)|u|p-1u, u|∂Ω = 0,
where p > 1 and the nonnegative function h(x) vanishes on a proper subset of Ω, global bifurcation branches from higher eigenvalues are unbounded and blow up at parameter values determined by the vanishing set Ω0 of h(x). In particular, we prove that bifurcation from infinity is possible only at λ ∈ {λk(Ω0) : k ≥ 1}. Moreover, when Ω is an interval, for each k ≥ 1, there is a pair of continuous solution curves that bifurcate out of (λk(Ω0), ∞). For various cases, we demonstrate that there is a global bifurcation branch connecting (λk(Ω), 0) and(λk(Ω0), ∞). Most of our results do not require the nonlinear term to be odd.