bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal associations of gross motor development, motor milestone achievement and weight-for-length z score in a racially diverse cohort of US infants
Authors: Shoaibi Azza , Neelon Brian , Østbye Truls , Benjamin-Neelon Sara E 
Published: January 2019

ObjectivesTo investigate longitudinal associations between gross motor development, motor milestone achievement and weight-for-length z scores in a sample of infants. In a secondary aim, we explored potential bidirectional relationships, as higher weight-for-length z scores may impede motor development, and poor motor development may lead to obesity.DesignThe design was an observational birth cohort.SettingWe used data from the Nurture study, a birth cohort of predominately black women and their infants residing in the Southeastern USA.Participants666 women enrolled their infants in Nurture. We excluded infants with missing data on exposure, outcome or main covariates, leaving a total analytic sample of 425 infants.Primary outcomeThe outcome was weight-for-length z score, measured when infants were 3, 6, 9 12 months.ResultsAmong infants, 64.7% were black, 18.8% were white and 16.9% were other/multiple race. Mean (SD) breastfeeding duration was 17.6 (19.7) weeks. Just over one-third (38.5%) had an annual household income of < $20 000. After adjusting for potential confounders, higher motor development score was associated with lower weight-for-length z score (−0.004; 95% CI −0.001 to –0.007; p=0.01), mainly driven by associations among boys (−0.007; 95% CI −0.014 to –0.001; p=0.03) and not girls (0.001; 95% CI −0.005 to 0.008; p=0.62). Earlier crawling was the only milestone associated with a lower weight-for-length z score at 12 months (−0.328; 95% CI −0.585 to 0.072; p=0.012). However, this association appeared to be driven by male infants only (−0.461; 95% CI −0.825 to −0.096; p=0.01). Weight-for-length z score was unrelated to subsequent motor development score and was thus not bidirectional in our sample.ConclusionsHigher motor development score and earlier crawling were associated with lower subsequent weight-for-length z score. However, this was primary true for male infants only. These findings contribute to the growing body of evidence suggesting that delayed motor development may be associated with later obesity.
Prevalence and correlates of ‘sexual competence’ at first heterosexual intercourse among young people in Britain
Authors: Palmer Melissa J , Clarke Lynda , Ploubidis George B , Wellings Kaye 
Published: January 2019

BackgroundA greater understanding of the circumstances of first sexual intercourse, as opposed to an exclusive focus on age at occurrence, is required in order that sexual health and well-being can be promoted from the onset of sexual activity.MethodsWe used data from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) conducted in Britain. Participants were categorised as ‘sexually competent’ at first heterosexual intercourse if the following self-reported criteria applied to the event: contraceptive use, autonomy of decision, both partners ‘equally willing’, and occurrence at the perceived ‘right time’. We examined the prevalence of ‘sexual competence’, and its component parts, by age at first intercourse among 17–24-year-olds. Using multivariable logistic regression, we explored associations between sexual competence and potential explanatory factors.ResultsVariation in ‘sexual competence’ and its component parts was associated with, but not fully explained by, age at first sex: 22.4% and 36.2% of men and women who had first sex at age 13–14 years were categorised as ‘sexually competent’, rising to 63.7% and 60.4% among those aged ≥18 years at first intercourse. Lack of sexual competence was independently associated with: first intercourse before the age of 16 years, area-level deprivation (men only), lower educational level, black ethnicity (women only), reporting ‘friends’ as main source of learning about sex (women only), non-’steady’ relationship at first sex, and uncertainty of first partner’s virginity status.ConclusionsA substantial proportion of young people in Britain transition into sexual activity under circumstances incompatible with positive sexual health. Social inequalities in sexual health are reflected in the context of first intercourse.
Compact, Programmable, Two-Stage Configuration for Implantable Biopotential Recording Amplifiers
Authors: Maghami Mohammad Hossein , Sodagar Amir Masoud 
Published: January 2019

This paper proposes an area-efficient CMOS amplifier for neural recording applications. The proposed neural amplifier takes advantage of indirect negative feedback to realize a rather low upper [Formula: see text]3-dB cutoff frequency. As a result, the capacitance needed to realize the cutoff frequency is so small that can be easily implemented on-chip. Moreover, the proposed circuit also employs attenuators in the same feedback loop in order to further reduce the silicon area consumed by the capacitors and at the same time to increase the input impedance of the circuit. Designed based on a two-stage configuration, the amplifier provides tunable lower cutoff frequency and digitally-programmable upper cutoff frequency and voltage gain. The circuit is designed in a 0.18-[Formula: see text]m technology, and consumes 0.022[Formula: see text]mm2 and 0.27[Formula: see text]mm2 of chip areas for single- and eight-channel designs, respectively. Operated with a supply voltage of 1.8[Formula: see text]V, power consumption of the proposed amplifier is 36.7[Formula: see text][Formula: see text]W with the simulated input-referred noise of 4[Formula: see text][Formula: see text] over 1[Formula: see text]Hz–10[Formula: see text]kHz for each channel. The amplifier also provides an output swing of 0.95 Vpp with a total harmonic distortion of [Formula: see text]50[Formula: see text]dB at the frequency of 1[Formula: see text]kHz.
The Next Wave of Stroma-Targeting Therapy in Pancreatic Cancer
Authors: Huang Huocong , Brekken Rolf A. 
Published: January 2019

Abstract
The stroma of pancreatic ductal adenocarcinoma (PDA) forms a major barrier to therapy and immune surveillance. Elahi-Gedwillo and colleagues demonstrate that halofuginone has potent antifibrotic activity in PDA by directly inhibiting the activation of pancreatic stellate cells, thereby reducing the deposition of extracellular matrix components, including collagen and hyaluronic acid. As a result, halofuginone improves drug delivery and the infiltration of favorable immune cells such as immune-stimulatory myeloid cells and cytotoxic T cells. Despite recent controversies regarding targeting stroma in PDA, this study highlights that modifying the stroma of PDA remains an attractive strategy to improve the efficacy of therapy.
See related article by Elahi-Gedwillo et al., p. 372
Fucosylation Enhances the Efficacy of Adoptively Transferred Antigen-Specific Cytotoxic T Lymphocytes
Authors: Alatrash Gheath , Qiao Na , Zhang Mao , Zope Madhushree , Perakis Alexander A. , Sukhumalchandra Pariya , Philips Anne V. , Garber Haven R. , Kerros Celine , St. John Lisa S. , Khouri Maria R. , Khong Hiep , Clise-Dwyer Karen , Miller Leonard P. , Wolpe Steve , Overwijk Willem W. , Molldrem Jeffrey J. , Ma Qing , Shpall Elizabeth J. , Mittendorf Elizabeth A. 
Published: January 2019

AbstractPurpose:Inefficient homing of adoptively transferred cytotoxic T lymphocytes (CTLs) to tumors is a major limitation to the efficacy of adoptive cellular therapy (ACT) for cancer. However, through fucosylation, a process whereby fucosyltransferases (FT) add fucose groups to cell surface glycoproteins, this challenge may be overcome. Endogenously fucosylated CTLs and ex vivo fucosylated cord blood stem cells and regulatory T cells were shown to preferentially home to inflamed tissues and marrow. Here, we show a novel approach to enhance CTL homing to leukemic marrow and tumor tissue.Experimental Design:Using the enzyme FT-VII, we fucosylated CTLs that target the HLA-A2–restricted leukemia antigens CG1 and PR1, the HER2-derived breast cancer antigen E75, and the melanoma antigen gp-100. We performed in vitro homing assays to study the effects of fucosylation on CTL homing and target killing. We used in vivo mouse models to demonstrate the effects of ex vivo fucosylation on CTL antitumor activities against leukemia, breast cancer, and melanoma.Results:Our data show that fucosylation increases in vitro homing and cytotoxicity of antigen-specific CTLs. Furthermore, fucosylation enhances in vivo CTL homing to leukemic bone marrow, breast cancer, and melanoma tissue in NOD/SCID gamma (NSG) and immunocompetent mice, ultimately boosting the antitumor activity of the antigen-specific CTLs. Importantly, our work demonstrates that fucosylation does not interfere with CTL specificity.Conclusions:Together, our data establish ex vivo CTL fucosylation as a novel approach to improving the efficacy of ACT, which may be of great value for the future of ACT for cancer.
Utility of Diffusion-weighted Imaging to Decrease Unnecessary Biopsies Prompted by Breast MRI: A Trial of the ECOG-ACRIN Cancer Research Group (A6702)
Authors: Rahbar Habib , Zhang Zheng , Chenevert Thomas L. , Romanoff Justin , Kitsch Averi E. , Hanna Lucy G. , Harvey Sara M. , Moy Linda , DeMartini Wendy B. , Dogan Basak , Yang Wei T. , Wang Lilian C. , Joe Bonnie N. , Oh Karen Y. , Neal Colleen H. , McDonald Elizabeth S. , Schnall Mitchell D. , Lehman Constance D. , Comstock Christopher E. , Partridge Savannah C. 
Published: January 2019

Abstract

Purpose:
Conventional breast MRI is highly sensitive for cancer detection but prompts some false positives. We performed a prospective, multicenter study to determine whether apparent diffusion coefficients (ADCs) from diffusion-weighted imaging (DWI) can decrease MRI false positives.
Experimental Design: A total of 107 women with MRI-detected BI-RADS 3, 4, or 5 lesions were enrolled from March 2014 to April 2015. ADCs were measured both centrally and at participating sites. ROC analysis was employed to assess diagnostic performance of centrally measured ADCs and identify optimal ADC thresholds to reduce unnecessary biopsies. Lesion reference standard was based on either definitive biopsy result or at least 337 days of follow-up after the initial MRI procedure.

Results:
Of 107 women enrolled, 67 patients (median age 49, range 24–75 years) with 81 lesions with confirmed reference standard (28 malignant, 53 benign) and evaluable DWI were analyzed. Sixty-seven of 81 lesions were BI-RADS 4 (n = 63) or 5 (n = 4) and recommended for biopsy. Malignancies exhibited lower mean in centrally measured ADCs (mm2/s) than benign lesions [1.21 × 10−3 vs.1.47 × 10−3; P &lt; 0.0001; area under ROC curve = 0.75; 95% confidence interval (CI) 0.65–0.84]. In centralized analysis, application of an ADC threshold (1.53 × 10−3 mm2/s) lowered the biopsy rate by 20.9% (14/67; 95% CI, 11.2%–31.2%) without affecting sensitivity. Application of a more conservative threshold (1.68 × 10−3 mm2/s) to site-measured ADCs reduced the biopsy rate by 26.2% (16/61) but missed three cancers.

Conclusions:
DWI can reclassify a substantial fraction of suspicious breast MRI findings as benign and thereby decrease unnecessary biopsies. ADC thresholds identified in this trial should be validated in future phase III studies.
Nietzsche e Villa-Lobos: da música dionisíaca à canção folclórica
Authors: Lima Márcio José Silveira 
Published: January 2019

O artigo expõe aspectos da concepção de Nietzsche sobre a música dionisíaca, tentando apontar para possíveis convergências com a estética do compositor Villa-Lobos, cujas composições foram marcadas pela utilização de temáticas e escalas folclóricas. Trata-se de compreender a música dionisíaca em sua relação com a mitologia, defendendo que a noção de cultura trágica que decorre dessa relação significa para Nietzsche uma possibilidade de superação dos valores cristalizados há séculos no Ocidente, tanto em termos morais, quanto musicais. De igual maneira, ao enfatizar a importância da canção folclórica para a linguagem musical, Villa-Lobos se insere num contexto de superação da linguagem musical dominada pela escala tonal, ao mesmo tempo em que utiliza de seus procedimentos estéticos para uma intensa inserção no debate cultural de sua época em torno da identidade nacional brasileira.
Palavras-chaveNietzsche; Villa-Lobos; Música; Canção Dionisíaca; Música Folclórica.
Genetic Assessment of Potential Long-Term On-Target Side Effects of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Inhibitors
Authors: Nelson Christopher P. , Lai Florence Y. , Nath Mintu , Ye Shu , Webb Thomas R. , Schunkert Heribert , Samani Nilesh J. 
Published: January 2019

Background:

Although short-term trials have suggested that PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors are safe and reduce risk of cardiovascular diseases, their long-term safety is unclear. Genetic variants associated with lower activity of a gene can act as proxies to identify potential long-term side effects of drugs as recently exemplified by association of LDL (low-density lipoprotein)-lowering variants in the
HMGCR
(target for statins) and
PCSK9
genes with increased risk of type 2 diabetes mellitus (T2DM). However, analyses of the full spectrum of potential side effects of PCSK9 inhibition using a genetic approach have not been undertaken.

Methods:

We examined the association of an LDL-lowering variant in the
PCSK9
gene (T allele of rs1159147), as well as 2 LDL-lowering
HGCMR
variants (G allele of rs17238484 and T allele of rs12916) with 80 diseases and traits in up to 479 522 individuals in UK Biobank.

Results:

The
PCSK9
T allele was significantly (Bonferroni
P
<6.25×10
−4
) associated with risk of T2DM, increased body mass index, waist circumference, waist-hip ratio, diastolic blood pressure, type 1 diabetes mellitus, and insulin use. The
HMGCR
variants were also associated with risk of T2DM, although their previously reported associations with anthropometric traits were found to be confounded. Mediation analysis suggested that the association of the
PCSK9 T
allele with risk of T2DM but not diastolic blood pressure was largely independent of its association with body mass index and central obesity. Nominally significant associations of the
PCSK9 T
allele were also seen with peptic ulcer disease, depression, asthma, chronic kidney disease, and venous thromboembolism.

Conclusions:
Our findings support previous genetic analyses suggesting that long-term use of PCSK9 inhibitors, like statins, may be associated with increased risk of T2DM. Some other potential side effects need to be looked for in future studies of PCSK9 inhibitors, although we did not find signals that raise substantial concerns about their long-term safety.
Stability and Sea State as Limiting Conditions for TKE Dissipation and Dissipative Heating
Authors: Smith Andrew W. , Haus Brian K. , Zhang Jun A. 
Published: January 2019

Abstract
This study analyzes high-resolution ship data collected in the Gulf of Mexico during the Lagrangian Submesoscale Experiment (LASER) from January to February 2016 to produce the first reported measurements of dissipative heating in the explicitly nonhurricane atmospheric surface layer. Although typically computed from theory as a function of wind speed cubed, the dissipative heating directly estimated via the turbulent kinetic energy (TKE) dissipation rate is also presented. The dissipative heating magnitude agreed with a previous study that estimated the dissipative heating in the hurricane boundary layer using in situ aircraft data. Our observations that the 10-m neutral drag coefficient parameterized using TKE dissipation rate approaches zero slope as wind increases suggests that TKE dissipation and dissipative heating are constrained to a physical limit. Both surface-layer stability and sea state were observed to be important conditions influencing dissipative heating, with the stability determined via TKE budget terms and the sea state determined via wave steepness and age using direct shipboard measurements. Momentum and enthalpy fluxes used in the TKE budget are determined using the eddy-correlation method. It is found that the TKE dissipation rate and the dissipative heating are largest in a nonneutral atmospheric surface layer with a sea surface comprising steep wind sea and slow swell waves at a given surface wind speed, whereas the ratio of dissipative heating to enthalpy fluxes is largest in near-neutral stability where the turbulent vertical velocities are near zero.
The Impact of the Amazon–Orinoco River Plume on Enthalpy Flux and Air–Sea Interaction within Caribbean Sea Tropical Cyclones
Authors: Rudzin Johna E. , Shay Lynn K. , Jaimes de la Cruz Benjamin 
Published: January 2019

Abstract
The influence of the Amazon–Orinoco River plume in the Caribbean Sea on latent and sensible heat flux (enthalpy flux) and tropical cyclone (TC) intensity is investigated for Hurricanes Ivan (2004), Emily (2005), Dean (2007), and Felix (2007) using dropwindsonde data, satellite sea surface temperature (SST), and the SMARTS climatology. Relationships among enthalpy fluxes, ocean heat content relative to the 26°C isotherm depth (OHC), and SST during storm passage are diagnosed. Results indicate that sea surface cooling in the river plume, a low-OHC region, is comparable to that in the warm eddy region, which has high OHC. An isothermal layer heat budget shows that upper-ocean cooling in the river plume can be explained predominantly by sea-to-air heat flux, rather than by entrainment flux from the thermocline. The latter two findings suggest that relatively large upper-ocean stratification in the plume regime limited entrainment cooling, sustaining SST and enthalpy flux. Inspection of atmospheric variables indicates that deep moderate wind shear is prevalent, and equivalent potential temperature is enhanced over the river plume region for most of these storms. Thus, sustained surface fluxes in this region may have provided warm, moist boundary layer conditions, which may have helped these storms to rapidly intensify even over relatively low-OHC waters and moderate shear. These findings are important because several Caribbean Sea TCs, including these cases, have been underforecast with respect to intensity and/or rapid intensifications, yet minimal upper-ocean observations exist to understand air–sea interaction during TCs in the salinity-stratified Amazon–Orinoco plume regime.
3-Furan-2-yl-N-p-tolyl-acrylamide, a highly selective positive allosteric modulator of α7 nicotinic receptors, produces anxiolytic-like activity in mice
Authors: Targowska-Duda Katarzyna M , Budzynska Barbara , Michalak Agnieszka , Jozwiak Krzysztof , Biala Grazyna , Arias Hugo R 
Published: January 2019

Background: Several lines of investigations support the idea that nicotinic acetylcholine receptors modulate neuronal pathways involved in anxiety and depression. Aims: The purpose of this study was to determine whether 3-furan-2-yl-N-p-tolyl-acrylamide, a highly selective positive allosteric modulator of α7 nicotinic acetylcholine receptors, influences anxiety-like behaviour in mice, and to determine the modulatory activity of 3-furan-2-yl-N-p-tolyl-acrylamide on mice pretreated with either nicotine or selective α7-agonists (i.e. PNU-282987 or (2.4)-dimethoxybenzylidene anabaseine dihydrochloride). Methods: The elevated plus maze and novelty suppressed feeding tests were selected to evaluate 3-furan-2-yl-N-p-tolyl-acrylamide and other nicotinic ligands on anxiety-like behaviour in mice. Results: The results indicated that: (a) 3-furan-2-yl-N-p-tolyl-acrylamide induces anxiolytic-like activity at 0.5 (elevated plus maze) and 1.0 (novelty suppressed feeding) mg/kg, respectively, after acute treatment, whereas its efficacy is increased after chronic treatments (i.e. active at 0.1 mg/kg; elevated plus maze). This is the first time showing anxiolytic-like activity elicited by 3-furan-2-yl-N-p-tolyl-acrylamide, contrary to the lack of activity for PNU-120596 (0.1 mg/kg); (b) the anxiolytic-like activity of 0.5 mg/kg 3-furan-2-yl-N-p-tolyl-acrylamide is inhibited by methyllycaconitine, a selective α7-antagonist, suggesting that α7 nicotinic acetylcholine receptors are involved in this process; (c) 0.5 mg/kg 3-furan-2-yl-N-p-tolyl-acrylamide reverses the anxiogenic effects induced by 0.1 mg/kg nicotine but not by 10.0 mg/kg PNU-282987; and (d) inactive doses of both 3-furan-2-yl-N-p-tolyl-acrylamide (0.1 mg/kg) and (2.4)-dimethoxybenzylidene anabaseine dihydrochloride (1.0 mg/kg) produce anxiolytic-like effects, suggesting drug interactions, probably synergistic. Conclusions: Our findings indicated that anxiolytic-like activity is mediated by α7 nicotinic acetylcholine receptors, supporting the concept that these receptors modulate anxiety processes. The results indicating that the chronic treatment with 3-furan-2-yl-N-p-tolyl-acrylamide is more efficient than the acute treatment in eliciting anxiolytic-like activity, and that 3-furan-2-yl-N-p-tolyl-acrylamide reverses the anxiogenic effects induced by nicotine, might be of therapeutic importance during smoking cessation.
Alternation in dopamine D2-like and metabotropic glutamate type 5 receptor density caused by differing housing conditions during abstinence from cocaine self-administration in rats
Authors: Frankowska Małgorzata , Miszkiel Joanna , Pomierny-Chamioło Lucyna , Pomierny Bartosz , Giannotti Giuseppe , Suder Agata , Filip Małgorzata 
Published: January 2019

Background: Environmental conditions have an important function in substance use disorder, increasing or decreasing the risks of relapse. Several studies strongly support the role of the dopamine D2-like and metabotropic glutamate type 5 receptors in maladaptive neurobiological responses to cocaine reward and relapse. Aims: The present study employed cocaine self-administration with yoked-triad procedure in rats to explore whether drug abstinence in different housing conditions affects the drug-seeking behaviour and the dopamine D2-like and metabotropic glutamate type 5 receptor density and affinity in several regions of the animal brain. Methods: Rats were trained to self-administer cocaine and later they were forced to abstain either in: (a) enriched environment or (b) isolation cage conditions to evaluate the effect of housing conditions on the drug-seeking behaviour and to assess changes concerning receptors in animals brain. Results: Our results show that exposure to enriched environment conditions strongly reduced active lever presses during cue-induced drug-seeking. At the neurochemical level, we demonstrated a significant increase in the dopamine D2-like receptor density in the prefrontal cortex in animals following drug abstinence in isolation cage or enriched environment conditions, and the reduction in their density in the dorsal striatum provoked by isolation cage conditions. The metabotropic glutamate type 5 receptor density decreased only in the prefrontal cortex after isolation cage and enriched environment abstinence. Conclusions: This study shows the different impacts caused by the type of housing conditions during abstinence from cocaine self-administration on drug-seeking behaviour in rats. The observed changes in the dopamine D2-like and metabotropic glutamate type 5 receptor Bmax and/or Kd values were brain-region specific and related to either pharmacological and/or motivational features of cocaine.