bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of aminoglycosides in animals within the EU: development of resistance in animals and possible impact on human and animal health: a review
Authors: van Duijkeren Engeline , Schwarz Christine , Bouchard Damien , Catry Boudewijn , Pomba Constança , Baptiste Keith Edward , Moreno Miguel A , Rantala Merja , Ružauskas Modestas , Sanders Pascal , Teale Christopher , Wester Astrid L , Ignate Kristine , Kunsagi Zoltan , Jukes Helen 
Published: March 2019

AbstractAminoglycosides (AGs) are important antibacterial agents for the treatment of various infections in humans and animals. Following extensive use of AGs in humans, food-producing animals and companion animals, acquired resistance among human and animal pathogens and commensal bacteria has emerged. Acquired resistance occurs through several mechanisms, but enzymatic inactivation of AGs is the most common one. Resistance genes are often located on mobile genetic elements, facilitating their spread between different bacterial species and between animals and humans. AG resistance has been found in many different bacterial species, including those with zoonotic potential such as Salmonella spp., Campylobacter spp. and livestock-associated MRSA. The highest risk is anticipated from transfer of resistant enterococci or coliforms (Escherichia coli) since infections with these pathogens in humans would potentially be treated with AGs. There is evidence that the use of AGs in human and veterinary medicine is associated with the increased prevalence of resistance. The same resistance genes have been found in isolates from humans and animals. Evaluation of risk factors indicates that the probability of transmission of AG resistance from animals to humans through transfer of zoonotic or commensal foodborne bacteria and/or their mobile genetic elements can be regarded as high, although there are no quantitative data on the actual contribution of animals to AG resistance in human pathogens. Responsible use of AGs is of great importance in order to safeguard their clinical efficacy for human and veterinary medicine.
E3 ligase Herc4 regulates Hedgehog signalling through promoting Smoothened degradation
Authors: Jiang Weirong , Yao Xia , Shan Zhaoliang , Li Wenting , Gao Yuxue , Zhang Qing 
Published: March 2019

Abstract
Hedgehog (Hh) signalling plays conserved roles in controlling embryonic development; its dysregulation causes many diseases including cancers. The G protein-coupled receptor Smoothened (Smo) is the key signal transducer of the Hh pathway, whose posttranslational regulation has been shown to be critical for its accumulation and activation. Ubiquitination has been reported an essential posttranslational regulation of Smo. Here, we identify a novel E3 ligase of Smo, Herc4, which binds to Smo, and regulates Hh signalling by controlling Smo ubiquitination and degradation. Interestingly, our data suggest that Herc4-mediated Smo degradation is regulated by Hh in PKA-primed phosphorylation-dependent and independent manners.
Identification of Candidates for Longer Lung Cancer Screening Intervals Following a Negative Low-Dose Computed Tomography Result
Authors: Robbins Hilary A , Berg Christine D , Cheung Li C , Chaturvedi Anil K , Katki Hormuzd A 
Published: March 2019

Abstract
Lengthening the annual low-dose computed tomography (CT) screening interval for individuals at lowest risk of lung cancer could reduce harms and improve efficiency. We analyzed 23 328 participants in the National Lung Screening Trial who had a negative CT screen (no ≥4-mm nodules) to develop an individualized model for lung cancer risk after a negative CT. The Lung Cancer Risk Assessment Tool + CT (LCRAT+CT) updates “prescreening risk” (calculated using traditional risk factors) with selected CT features. At the next annual screen following a negative CT, risk of cancer detection was reduced among the 70% of participants with neither CT-detected emphysema nor consolidation (median risk = 0.2%, interquartile range [IQR] = 0.1%–0.3%). However, risk increased for the 30% with CT emphysema (median risk = 0.5%, IQR = 0.3%–0.8%) and the 0.6% with consolidation (median = 1.6%, IQR = 1.0%–2.5%). As one example, a threshold of next-screen risk lower than 0.3% would lengthen the interval for 57.8% of screen-negatives, thus averting 49.8% of next-screen false-positives among screen-negatives but delaying diagnosis for 23.9% of cancers. Our results support that many, but not all, screen-negatives might reasonably lengthen their CT screening interval.
Conditional Bias Robust Estimation of the Total of Curve Data by Sampling in a Finite Population: An Illustration on Electricity Load Curves
Authors: Cardot Hervé , De Moliner Anne , Goga Camelia 
Published: March 2019

AbstractFor marketing or power grid management purposes, many studies based on the analysis of total electricity consumption curves of groups of customers are now carried out by electricity companies. Aggregated totals or mean load curves are estimated using individual curves measured at fine time grid and collected according to some sampling design. Due to the skewness of the distribution of electricity consumptions, these samples often contain outlying curves which may have an important impact on the usual estimation procedures. We introduce several robust estimators of the total consumption curve which are not sensitive to such outlying curves. These estimators are based on the conditional bias approach and robust functional methods. We also derive mean square error estimators of these robust estimators, and finally, we evaluate and compare the performance of the suggested estimators on Irish electricity data.
Soft Law, Authoritative Advice and Non-binding Agreements
Authors: Marmor Andrei 
Published: March 2019

Abstract
One of the most fascinating developments in the domain of international law in the last few decades is the astonishing proliferation of non-binding legal instruments or soft law, namely, norms or directives explicitly avoiding the imposition of legal obligations on the relevant parties. From a philosophical perspective, this is rather puzzling: how can we explain the idea of a non-binding directive or a non-binding contract? In this article I aim to provide an account of the rationale of soft law from the perspective of the practical reasons in play. First, I analyse the idea of authoritative advice, suggesting that when authorities advise their putative subjects, they purport to give the subject presumptive reasons for action. I explain what presumptive reasons are. Secondly, I suggest the possibility that something very similar is at work in cases of non-binding agreements, coupled with special accountability relations that such agreements invariably constitute.
Gender aspects in food allergy
Authors: Pali-Schöll Isabella , Jensen-Jarolim Erika 
Published: March 2019

Purpose of review
The difference of food allergy prevalence between male and female individuals is well documented and should have more impact for personalized diagnosis and management. Although in younger age male sex dominates, in adults more women are affected by food allergies. This sex disparity diminishes again around menopause, underlining the influence of sex hormones, but in addition, also metabolic gender-specific factors and differences in microbiome composition might contribute to the different expression of food allergy in the two genders. The sex-dependent and gender-dependent influence on development of food allergy, disease severity, as well as on social, dietary and neuropsychological factors in studies mainly published within past 18 months are discussed in this review.

Recent findings
Sex and gender differences likely play a role in food allergy development, for instance via influence on immune cells and mediators, or on the composition of the microbiome, but only few controlled studies on this specific topic are available.

Summary
Future prospective studies need to clearly take into account the sex and gender difference in order to provide personalized diagnosis, management and treatment of food allergy.
The Effect of Otoacoustic Emission Stimulus Level on the Strength and Detectability of the Medial Olivocochlear Reflex
Authors: Lewis James D. 
Published: March 2019

Objectives:
Previous work demonstrates the importance of a high signal to noise ratio (SNR) when using transient evoked otoacoustic emissions (TEOAEs) to assay the medial olivocochlear reflex (MOCR). Increasing stimulus level provides one means to increase TEOAE SNR. However, this may come at the expense of a smaller MOCR effect. It is not clear whether the gain in SNR associated with the use of higher stimulus levels outweighs the disadvantage of a potentially smaller MOCR effect. The present study investigated the strength and detectability of the MOCR when assayed using TEOAEs at different stimulus levels. The hypothesis was that although the strength of the MOCR decreases with increasing stimulus level, the occurrence of statistically significant MOCR effects increases due to an increase in TEOAE SNR.

Design:
Twenty-five young adult females with normal hearing participated in the study. TEOAEs were measured in the right ear with and without broadband noise presented in the left ear. The strength of the MOCR was quantified as the percent difference in the TEOAE between the contralateral noise and quiet conditions. Statistical bootstrapping was used to detect significant MOCR effects in individual subjects across different frequency bands and stimulus levels. The relationship between a detectable MOCR (response variable) and frequency, stimulus level, TEOAE SNR, MOCR strength, and subject (predictor variables) was evaluated using generalized linear mixed-effect models.

Results:
The number of statistically significant MOCR effects increased with stimulus level at all frequencies. Occurrence was highest for the 2-kHz TEOAE frequency band and lowest for the 4-kHz frequency band. The strength of the MOCR decreased with increasing click level. TEOAE SNR, MOCR strength, and stimulus level were significant predictors of a detectable MOCR: The likelihood of a detectable MOCR increased with TEOAE SNR, MOCR strength, and stimulus level.

Conclusions:
Despite a reduction in the strength of the MOCR with increasing stimulus level, the detectability of the MOCR increased. This is due, in part, to an increase in TEOAE SNR with stimulus level. For clinical implementation of TEOAE-based MOCR assays, achieving a high SNR is necessary to permit the detection of the MOCR in individual patients.
Acute Kidney Injury in Critically Ill Patients After Noncardiac Major Surgery: Early Versus Late Onset
Authors: Li Shengnan , Wang Shu , Priyanka Priyanka , Kellum John A. 
Published: March 2019

Objectives:
Acute kidney injury is a common complication of major surgery. However, acute kidney injury occurring within the first 48 hours after surgery (early acute kidney injury) and therefore likely related to the surgery itself is possibly different from acute kidney injury occurring after 48 hours (late acute kidney injury). The aim of this study was to describe the epidemiology and identify differences in risk factors and outcomes between early and late acute kidney injury following major surgery.

Design:
Retrospective cohort study.

Setting:
Academic Medical Center.

Patients:
Patients admitted to ICU following noncardiac major surgery.

Interventions:
None.

Measurements and Main Results:
We analyzed data from 3,499 patients and defined acute kidney injury according to full Kidney Disease: Improving Global Outcomes criteria and classified as early (48 hr or less) or late (> 48 hr to 7 d) based on time from surgery. Separate multivariable logistic regression models were fit to identify risk factors of early acute kidney injury compared with no acute kidney injury and risk factors of late acute kidney injury compared with no acute kidney injury. Overall 41.7% (1,459/3,499) developed early acute kidney injury versus 14.4% (504/3,499) late acute kidney injury. Most acute kidney injury occurred within 48 hours following surgery and 12 hours was the peak interval. Risk factors for early acute kidney injury included increased age, body mass index, decreased estimated glomerular filtration rate, and anemia, whereas late acute kidney injury cases were closely associated with postoperative factors, like sepsis, mechanical ventilation, positive fluid balance, blood transfusions and exposure to diuretics, vasopressors, and nonsteroidal anti-inflammatory drugs. After adjusting for age, body mass index, estimated glomerular filtration rate, comorbidities, surgery type, both early acute kidney injury (odds ratio [95% CI], 1.84 [1.50–2.27]) and late acute kidney injury (odds ratio [95% CI], 1.42 [1.09–1.85]) were associated with higher 1-year mortality compared with patients without acute kidney injury. We found similar results in a validation cohort of 10,723 patients admitted between 2008 and 2014.

Conclusions:
Most surgery-related acute kidney injury occurred within 48 hours of surgery. Acute kidney injury occurring within the first 48 hours was associated with underlying health, whereas acute kidney injury occurring after 48 hours was related to postoperative complications or drugs. Design of clinical and experimental interventions for acute kidney injury in this population should consider these differences.
Evaluating the Effects of Injected Calcium Hydroxylapatite on Changes in Human Skin Elastin and Proteoglycan Formation
Authors: González Noelani , Goldberg David J. 
Published: March 2019

BACKGROUND
Previous studies have shown that calcium hydroxylapatite (CaHa) injected intradermally resulted in new collagen production at 6 months after injection, and a possible increase in elastin formation. In addition, a recent study showed the formation of new collagen, elastin, and angiogenesis after injection at 4 and 9 months.

OBJECTIVE
To evaluate any changes in the presence of elastic fibers, proteoglycans, and elastin in photodamaged skin after injections with CaHa.

METHODS AND MATERIALS:
Fifteen subjects underwent a punch biopsy of the right infra-auricular areas before and after injection of CaHa on day 180. Specimens were stained for elastic fibers, elastin, and proteoglycan presence.

RESULTS
Quantitative analysis demonstrated a percent change in elastic fibers varying between 29% and 179% at 6 months in comparison with baseline. Subjects showed an increase in elastin between 12% and 66%. Subjects had positive mean percentage change in proteoglycans of 76.27% (t-test of 0.198).

CONCLUSION
This is the first study to show that CaHa can increase proteoglycans and echoed previous studies showing it can also have an effect on elastin, which indicates it can induce remodeling of all aspects of the extracellular matrix. Much larger and longer studies are required to confirm its unique impact on collagen, elastin, and proteoglycans.
Effectiveness of Early Laser Treatment in Surgical Scar Minimization: A Systematic Review and Meta-analysis
Authors: Kent Rhett A. , Shupp Jeffrey , Fernandez Stephen , Prindeze Nick , DeKlotz Cynthia M.C. 
Published: March 2019

BACKGROUND
Studies investigating the efficacy of lasers to minimize early surgical scars are low powered and report variable results. To further examine the evidence, the authors performed a systemic review and meta-analysis.

OBJECTIVE
To present the evidence of randomized controlled trials investigating the efficacy of laser modalities in minimizing surgical scars when applied <1 month after operation.

MATERIALS AND METHODS
A literature search of PubMed, EMBASE, Northern Light Life Sciences Conference Abstracts, and Cochrane Library was performed between November 6, 2015, and November 20, 2015. After assessing for inclusion, data extraction used the PRISMA checklist. Assessment for quality, validity, and risk of bias applied a scale devised by Jadad and colleagues, the Oxford Pain Validity Scale, and the RevMan risk of bias assessment tool, respectively. The GRADEpro application graded overall quality, and statistical analysis was performed with RevMan.

RESULTS
Approximately 4,373/4,397 abstracts and 16/24 full articles were excluded using predefined criteria, leaving 8 articles in the systematic review and 4 in the meta-analysis. The primary outcome reached statistical significance favoring the intervention group with standardized mean difference 0.39 (95% confidence interval, 0.05–0.74) and p = .03.

CONCLUSION
The outcome supports the efficacy of lasers in minimizing primarily closed surgical scars when treated <1 month after surgery.
Thread-Lifts: A Double-Edged Suture? A Comprehensive Review of the Literature
Authors: Tong Lana X. , Rieder Evan A. 
Published: March 2019

BACKGROUND
Thread-lifting has experienced a recent surge in popularity as interest in minimally invasive techniques for facial rejuvenation continues to grow. By placing barbed sutures along specific trajectories to lift the superficial musculoaponeurotic system to address facial ptosis, thread-lifting carries several advantages over the traditional facelift. Over the past few decades, there have been ongoing advances in the implementation of thread-lifting using barbed sutures.

OBJECTIVE
To review the current evidence regarding the safety and efficacy of thread-lifting for facial rejuvenation.

MATERIALS AND METHODS
An analysis was conducted of PubMed indexed English language literature regarding thread-lifting using barbed sutures.

RESULTS
Early studies using nonabsorbable barbed sutures described high revision and complication rates. Newer techniques implementing absorbable sutures have fewer adverse events, although the long-term efficacy of these procedures remains unclear.

CONCLUSION
Thread-lifts play a substantial role in minimally invasive techniques for facial rejuvenation. Additional studies are needed to better evaluate the safety and long-term efficacy of this quick, in-office procedure.
Skin Quality Improvement With VYC-12, a New Injectable Hyaluronic Acid: Objective Results Using Digital Analysis
Authors: Cavallini Maurizio , Papagni Marco , Ryder Timothy J. , Patalano Mariagrazia 
Published: March 2019

BACKGROUND
VYC-12 is a novel hyaluronic acid–based dermal filler designed to treat fine lines and improve skin quality. A specialist digital camera and proprietary Digital Analysis of the Cutaneous Surface (DACS) software have previously been used to objectively measure changes in skin features.

OBJECTIVE
To assess the effect of facial treatment with VYC-12 on skin texture using the specialist camera.

MATERIALS AND METHODS
This was a prospective, open-label, 2-center study of 40 women aged 35 to 60 years treated with multiple, microdepot intradermal injections of VYC-12 (2 mL in the face; 1 mL in the neck if required). Eight patients (20.0%) required a touch-up at Day 45. Images were acquired using the specialist camera at baseline and 45 days and 6 months after treatment, and were analyzed by DACS. Clinical improvements were also assessed subjectively using the Global Aesthetic Improvement Scale (GAIS).

RESULTS
VYC-12 improved skin texture from baseline after 45 days (mean improvement: 25.9% ± 9.2%) and 6 months (mean improvement: 30.7% ± 18.2%). Improvements were also evident using the GAIS. There were no major adverse events.

CONCLUSIONS
VYC-12 improves skin quality, as measured using an objective, fast, and reproducible measuring tool. VYC-12 represents a valuable addition to the treatment armamentarium.
A Latent Spatial Factor Approach for Synthesizing Opioid-Associated Deaths and Treatment Admissions in Ohio Counties
Authors: Hepler Staci , McKnight Erin , Bonny Andrea , Kline David 
Published: March 2019

Background:Opioid misuse is a major public health issue in the United States and in particular the state of Ohio. However, the burden of the epidemic is challenging to quantify as public health surveillance measures capture different aspects of the problem. Here, we synthesize county-level death and treatment counts to compare the relative burden across counties and assess associations with social environmental covariates.Methods:We construct a generalized spatial factor model to jointly model death and treatment rates for each county. For each outcome, we specify a spatial rates parameterization for a Poisson regression model with spatially varying factor loadings. We use a conditional autoregressive model to account for spatial dependence within a Bayesian framework.Results:The estimated spatial factor was highest in the southern and southwestern counties of the state, representing a higher burden of the opioid epidemic. We found that relatively high rates of treatment contributed to the factor in the southern part of the state, whereas relatively higher rates of death contributed in the southwest. The estimated factor was also positively associated with the proportion of residents 18–64 years of age on disability and negatively associated with the proportion of residents reporting white race.Conclusions:We synthesized the information in the opioid-associated death and treatment counts through a spatial factor model to estimate a latent factor representing the consensus between the two surveillance measures. We believe this framework provides a coherent approach to describe the epidemic while leveraging information from multiple surveillance measures.
The association between assisted reproductive technologies and low birth weight
Authors: Reig Andres , Seli Emre 
Published: March 2019

Purpose of review
To examine the existing literature in regards to the relationship between assisted reproductive technologies (ART) and low birth weight (LBW).

Recent findings
In 2017, Martin et al. reported on the incidence of low birth weight in relation to the number of embryos transferred, and showed that incidence of low birth weight in singletons correlates with number of embryos transferred. Meanwhile, several studies have shown increased weight of singletons born after frozen embryo transfers compared with fresh embryo transfers. A recent study published by Sekhon et al., among others, disputes these findings, and claims that frozen and fresh embryo transfers result in comparable birth weights. It is also noteworthy that Mass et al., in 2016, analyzed how birth weight as a result of assisted reproductive technologies has evolved over the years, and concluded that birth weight has not changed significantly over a long period of time.

Summary
Newborns conceived via assisted reproductive technologies are three times more likely to have low birth weight. Although multiple gestation and its associated prematurity are the main risk factors for low birth weight in ART-conceived pregnancies, some of the other processes specific to assisted reproduction also impact perinatal outcomes. Options, such as fresh or frozen embryo transfers, the number of embryos transferred, or endometrial preparation may all importantly affect birth weight and prematurity of ART-conceived newborns.