bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary Integration and Modularity in the Archosaur Cranium
Authors: Felice Ryan N , Watanabe Akinobu , Cuff Andrew R , Noirault Eve , Pol Diego , Witmer Lawrence M , Norell Mark A , O'Connor Patrick M , Goswami Anjali
Published: May 2019

Complex structures, like the vertebrate skull, are composed of numerous elements or traits that must develop and evolve in a coordinated manner to achieve multiple functions. The strength of association among phenotypic traits (i.e., integration), and their organization into highly-correlated, semi-independent subunits termed modules, is a result of the pleiotropic and genetic correlations that generate traits. As such, patterns of integration and modularity are thought to be key factors constraining or facilitating the evolution of phenotypic disparity by influencing the patterns of variation upon which selection can act. It is often hypothesized that selection can reshape patterns of integration, parceling single structures into multiple modules or merging ancestrally semi-independent traits into a strongly correlated unit. However, evolutionary shifts in patterns of trait integration are seldom assessed in a unified quantitative framework. Here, we quantify patterns of evolutionary integration among regions of the archosaur skull to investigate whether patterns of cranial integration are conserved or variable across this diverse group. Using high-dimensional geometric morphometric data from 3D surface scans and computed tomography scans of modern birds (n = 352), fossil non-avian dinosaurs (n = 27), and modern and fossil mesoeucrocodylians (n = 38), we demonstrate that some aspects of cranial integration are conserved across these taxonomic groups, despite their major differences in cranial form, function, and development. All three groups are highly modular and consistently exhibit high integration within the occipital region. However, there are also substantial divergences in correlation patterns. Birds uniquely exhibit high correlation between the pterygoid and quadrate, components of the cranial kinesis apparatus, whereas the non-avian dinosaur quadrate is more closely associated with the jugal and quadratojugal. Mesoeucrocodylians exhibit a slightly more integrated facial skeleton overall than the other grades. Overall, patterns of trait integration are shown to be stable among archosaurs, which is surprising given the cranial diversity exhibited by the clade. At the same time, evolutionary innovations such as cranial kinesis that reorganize the structure and function of complex traits can result in modifications of trait correlations and modularity.
4-Hydroxyglutamate is a novel predictor of pre-eclampsia
Authors: Sovio Ulla , McBride Nancy , Wood Angela M , Masconi Katya L , Cook Emma , Gaccioli Francesca , Charnock-Jones D Stephen , Lawlor Debbie A , Smith Gordon C S
Published: May 2019

Background

Pre-term pre-eclampsia is a major cause of maternal and perinatal morbidity and mortality worldwide. A multi-centre randomized–controlled trial has shown that first-trimester screening followed by treatment of high-risk women with aspirin reduces the risk of pre-term pre-eclampsia. However, the biomarkers currently employed in risk prediction are only weakly associated with the outcome.

Methods

We conducted a case–cohort study within the Pregnancy Outcome Prediction study to analyse untargeted maternal serum metabolomics in samples from 12, 20, 28 and 36 weeks of gestational age (wkGA) in women with pre-eclampsia delivering at term (n = 165) and pre-term (n = 29), plus a random sample of the cohort (n = 325). We used longitudinal linear mixed models to identify candidate metabolites at 20/28 wkGA that differed by term pre-eclampsia status. Candidates were validated using measurements at 36 wkGA in the same women. We then tested the association between the 12-, 20- and 28-wkGA measurements and pre-term pre-eclampsia. We externally validated the association using 24- to 28-wkGA samples from the Born in Bradford study (25 cases and 953 controls).

Results

We identified 100 metabolites that differed most at 20/28 wkGA in term pre-eclampsia. Thirty-three of these were validated (P < 0.0005) at 36 wkGA. 4-Hydroxyglutamate and C-glycosyltryptophan were independently predictive at 36 wkGA of term pre-eclampsia. 4-Hydroxyglutamate was also predictive (area under the receiver operating characteristic curve, 95% confidence interval) of pre-term pre-eclampsia at 12 (0.673, 0.558–0.787), 20 (0.731, 0.657–0.806) and 28 wkGA (0.733, 0.627–0.839). The predictive ability of 4-hydroxyglutamate at 12 wkGA was stronger than two existing protein biomarkers, namely PAPP-A (0.567, 0.439–0.695) and placenta growth factor (0.589, 0.463–0.714). Finally, 4-hydroxyglutamate at 24–28 wkGA was positively associated with pre-eclampsia (term or pre-term) among women from the Born in Bradford study.

Conclusions

4-hydroxyglutamate is a novel biochemical predictor of pre-eclampsia that provides better first-trimester prediction of pre-term disease than currently employed protein biomarkers.
Maximum number of modes of Gaussian mixtures
Authors: Améndola Carlos , Engström Alexander , Haase Christian
Published: May 2019

Gaussian mixture models are widely used in Statistics. A fundamental aspect of these distributions is the study of the local maxima of the density or modes. In particular, it is not known how many modes a mixture of $k$ Gaussians in $d$ dimensions can have. We give a brief account of this problem’s history. Then, we give improved lower bounds and the first upper bound on the maximum number of modes, provided it is finite.
Identification and Quantification of 5-Fluoro ADB and the 5-Fluoro ADB Ester Hydrolysis Metabolite in Postmortem Blood Samples by LC–MS/MS
Authors: Seither Joshua Z , Reidy Lisa J , Boland Diane M
Published: May 2019

5-Fluoro ADB, also known as 5-fluoro MDMB-PINACA, is a potent synthetic cannabinoid that is an agonist to the human cannabinoid CB1 and CB2 receptors. Adverse physiological and psychological effects that have resulted in hospitalization and/or death have been associated with 5-Fluoro ADB use. In addition, analytical confirmation of 5-Fluoro ADB use has been reported in both forensic human performance toxicology and postmortem cases. An analytical method for the identification and quantification of 5-fluoro ADB and the 5-fluoro ADB ester hydrolysis metabolite in human blood samples by liquid chromatography–tandem mass spectrometry was created and validated. The linear range of this assay was determined to be 0.01–10 ng/mL for 5-fluoro ADB and 10–500 ng/mL for the 5-fluoro ADB ester hydrolysis metabolite. The method met both precision and accuracy requirements. Endogenous and exogenous interferences were not observed. Ion suppression exceeding 25% was observed for 5-fluoro ADB. However, additional experiments were performed to ensure that the observed suppression did not affect other method validation parameters such as limit of detection and accuracy. Blood samples from 36 postmortem cases were analyzed utilizing this methodology. The average blood concentration of 5-fluoro ADB was 0.29 ng/mL in central blood specimens and 0.05 ng/mL in peripheral blood specimens. The average blood concentration of the 5-fluoro ADB ester hydrolysis metabolite was 49 ng/mL in central blood specimens and 21 ng/mL in peripheral blood specimens. A serum sample was also analyzed and had a serum concentration of 0.12 ng/mL for 5-fluoro ADB and 42 ng/mL for the 5-fluoro ADB ester hydrolysis metabolite. As the concentration of the 5-fluoro ADB ester hydrolysis metabolite was found at a greater concentration than that of 5-fluoro ADB, this metabolite may be a useful marker to monitor in an attempt to confirm 5-fluoro ADB use in toxicological investigations.
Effects of larval Age at Grafting and Juvenile Hormone on Morphometry and Reproductive Quality Parameters of in Vitro Reared Honey Bees (Hymenoptera: Apidae)
Authors: De Souza Daiana A , Hartfelder Klaus H , Tarpy David R
Published: May 2019

The honey bee queen plays a central role in the Apis mellifera L. (Hymenoptera: Apidae) colony, and her high reproductive capacity is fundamental for building up the workforce of a colony. Caste development in honey bee females involves elaborate physiological pathways unleashed at the beginning of the first larval instars, with juvenile hormone (JH) playing a crucial role. Here we took advantage of established in vitro rearing techniques to conduct a 2 × 2 experimental design and test initial rearing age (young vs old) and JH treatment (JH III vs solvent control) to enlighten the role of nutrient quality and JH in shaping honey bee female fertility, morphological features related to queenliness, and key physiological parameters (hemolymph vitellogenin/Vg, sugar levels, and Vg transcript levels). Our results show that while the age at initial larval rearing had major impacts on external morphology development, where younger larvae exhibited a higher probability to develop into queen-like adults morphotypes, the JH application during the larval stage improved physiological pathways related to ovary development and metabolism during the ontogenic development. We detected that the supplementation of queen larvae with JH promoted important benefits regarding queen fertility as the increase of ovariole number and vg levels at hemolymph, both crucial factors at eggs production. The data presented here provide guidance in efforts to improve honey bee queen quality, especially in light of frequent episodes of queen failures in the beekeeping industry.
Geographical Variations in Life Histories of House Flies, Musca domestica (Diptera: Muscidae), in Punjab, Pakistan
Authors: Khan Hafiz Azhar Ali , Khan Muhammad Umer , Nasiba Amara , Riaz Saira , Altaf Maria
Published: May 2019

Musca domestica Linnaeus is an important public health pest with the ability to adapt to diverse climates. Assessment of variations in biology and life-history traits of insects along geographical gradients is important for a successful management plan in different regions. We investigated life-history traits and life table parameters of M. domestica from six different geographical regions of Punjab, Pakistan: Rahim Yar Khan (RYK), Bahawalpur (BWP), Multan (MTN), Lahore (LHR), Gujrat (GJT), and Murree (MRE). Overall, M. domestica from localities of lower latitude and elevations with higher mean temperatures completed their development faster than those from localities of higher latitude and elevations with lower mean temperatures. The immature developmental time was the longest for the MRE population that was collected from higher latitude and elevation with cooler climate, whereas the shortest for the RYK population from lower latitude with warmer climate. Pupal weights were heavier for the RYK, BWP, and MTN populations, all were from the lowest latitude and elevations with warmer climate, compared with rest of the field populations. Similarly, rate of adult eclosion, fecundity, egg hatching, longevity, and life table parameters such as intrinsic rate of population increase, mean relative growth rate, net reproductive rate, and biotic potential were significantly higher for the RYK, BWP, and MTN populations compared with the GJT, LHR, and MRE populations of M. domestica. The current results will probably be of importance when planning management of M. domestica in different geographical regions of Pakistan.
Undervalued potential of crassulacean acid metabolism for current and future agricultural production
Authors: Davis Sarah C , Simpson June , Gil-Vega Katia del Carmen , Niechayev Nicholas A , Tongerlo Evelien van , Castano Natalia Hurtado , Dever Louisa V , Búrquez Alberto
Published: May 2019

A review of the agricultural value of plants that use crassulacean acid metabolism, spanning traditional knowledge and uses, recent genomic discoveries, physiological adaptations, and known commercial values.
What the Future ‘Might’ Brings
Authors: Boylan David
Published: May 2019

This paper concerns a puzzle about the interaction of epistemic modals and future tense. In cases of predictable forgetfulness, speakers cannot describe their future states of mind with epistemic modals under future tense, but promising theories of epistemic modals do not predict this. In §1, I outline the puzzle. In §2, I argue that it undermines a very general approach to epistemic modals that draws a tight connection between epistemic modality and evidence. In §3, I defend the assumption that tense can indeed scope over epistemic modals. In §4, I outline a new way of determining the domain of quantification of epistemic modals: epistemic modals quantify over the worlds compatible with the information accumulated within a certain interval. Information loss can change which interval is relevant for determining the domain. In §5, I defend the view from some objections. In §6, I explore the connections between my view of epistemic modality and circumstantial modality.
Identification of Young Stellar Object candidates in the Gaia DR2 x AllWISE catalogue with machine learning methods
Authors: Marton G , Ábrahám P , Szegedi-Elek E , Varga J , Kun M , Kóspál Á , Varga-Verebélyi E , Hodgkin S , Szabados L , Beck R , Kiss Cs
Published: May 2019

The second Gaia Data Release (DR2) contains astrometric and photometric data for more than 1.6 billion objects with mean Gaia G magnitude <20.7, including many Young Stellar Objects (YSOs) in different evolutionary stages. In order to explore the YSO population of the Milky Way, we combined the Gaia DR2 data base with Wide-field Infrared Survey Explorer (WISE) and Planck measurements and made an all-sky probabilistic catalogue of YSOs using machine learning techniques, such as Support Vector Machines, Random Forests, or Neural Networks. Our input catalogue contains 103 million objects from the DR2xAllWISE cross-match table. We classified each object into four main classes: YSOs, extragalactic objects, main-sequence stars, and evolved stars. At a 90 per cent probability threshold, we identified 1 129 295 YSO candidates. To demonstrate the quality and potential of our YSO catalogue, here we present two applications of it. (1) We explore the 3D structure of the Orion A star-forming complex and show that the spatial distribution of the YSOs classified by our procedure is in agreement with recent results from the literature. (2) We use our catalogue to classify published Gaia Science Alerts. As Gaia measures the sources at multiple epochs, it can efficiently discover transient events, including sudden brightness changes of YSOs caused by dynamic processes of their circumstellar disc. However, in many cases the physical nature of the published alert sources are not known. A cross-check with our new catalogue shows that about 30 per cent more of the published Gaia alerts can most likely be attributed to YSO activity. The catalogue can be also useful to identify YSOs among future Gaia alerts.
Atomic and molecular gas in IllustrisTNG galaxies at low redshift
Authors: Diemer Benedikt , Stevens Adam R H , Lagos Claudia del P , Calette A R , Tacchella Sandro , Hernquist Lars , Marinacci Federico , Nelson Dylan , Pillepich Annalisa , Rodriguez-Gomez Vicente , Villaescusa-Navarro Francisco , Vogelsberger Mark
Published: May 2019

We have recently developed a post-processing framework to estimate the abundance of atomic and molecular hydrogen (H i and H2, respectively) in galaxies in large-volume cosmological simulations. Here we compare the H i and H2 content of IllustrisTNG galaxies to observations. We mostly restrict this comparison to z ≈ 0 and consider six observational metrics: the overall abundance of H i and H2, their mass functions, gas fractions as a function of stellar mass, the correlation between H2 and star formation rate, the spatial distribution of gas, and the correlation between gas content and morphology. We find generally good agreement between simulations and observations, particularly for the gas fractions and the H i mass–size relation. The H2 mass correlates with star formation rate as expected, revealing an almost constant depletion time that evolves up to z = 2 as observed. However, we also discover a number of tensions with varying degrees of significance, including an overestimate of the total neutral gas abundance at z = 0 by about a factor of 2 and a possible excess of satellites with no or very little neutral gas. These conclusions are robust to the modelling of the H i/H2 transition. In terms of their neutral gas properties, the IllustrisTNG simulations represent an enormous improvement over the original Illustris run. All data used in this paper are publicly available as part of the IllustrisTNG data release.
Phase 0 Clinical Trial Strategies for the Neurosurgical Oncologist
Authors: Sanai Nader
Published: May 2019

In an era of escalating drug discovery costs, shifting priorities within the pharmaceutical industry, and longstanding challenges in central nervous system drug delivery, surgical trials offer an avenue to identify promising agents with demonstrable tumor penetration and molecular effects. The rise of pharmacodynamic- and pharmacokinetic-driven clinical trials, including phase 0 study designs, creates an opportunity for the neurosurgical oncologist to engage drug development for brain tumor patients directly. Here, we review the phase 0 clinical trial mechanism as well as its current and future applications within neurosurgical oncology.
Cigarette Smoking Is Associated With Lower Quadriceps Cross-sectional Area and Attenuation in Older Adults
Authors: Marques Elisa A , Elbejjani Martine , Frank-Wilson Andrew W , Gudnason Vilmundur , Sigurdsson Gunnar , Lang Thomas F , Jonsson Palmi V , Sigurdsson Sigurdur , Aspelund Thor , Siggeirsdottir Kristin , Launer Lenore , Eiriksdottir Gudny , Harris Tamara B
Published: May 2019

Introduction

In addition to well-established links with cardiovascular and respiratory diseases, cigarette smoking may affect skeletal muscle; however, associations with quadriceps atrophy, density, and function are unknown. This study explored the associations of current and former smoking with quadriceps muscle area and attenuation as well as muscle force (assessed as knee extension peak torque) and rate of torque development—a measure of muscle power in older adults.

Methods

Data from 4469 older adults, aged 66–95 years at baseline in the Age, Gene/Environment Susceptibility-Reykjavik Study with measurements of thigh computed tomography, isometric knee extension testing, self-reported smoking history, and potential covariates were analyzed.

Results

Sex differences were observed in these data; therefore, our final analyses are stratified by sex. In men, both former smokers and current smokers had lower muscle area (with β= –0.10, 95% confidence interval [CI] = –0.17 to –0.03 and β = –0.19, 95% CI = –0.33 to –0.05, respectively) and lower muscle attenuation (ie, higher fat infiltration, β = –0.08, 95% CI = –0.16 to –0.01 and β = –0.17, 95% CI = –0.34 to –0.01, respectively) when compared with never smokers. Smoking status was not associated with male peak torque or rate of torque development. In women, current smoking was associated with lower muscle attenuation (β = –0.24, 95% CI = –0.34 to –0.13) compared to never smoking. Among female smokers (current and former), muscle attenuation and peak torque were lower with increasing pack-years.

Conclusions

Results suggest that cigarette smoking is related to multiple muscle properties at older age and that these relationships may be different among men and women.

Implications

This article presents novel data, as it examined for the first time the relationship between smoking and computed tomography-derived quadriceps muscle size (cross-sectional area) and attenuation. This study suggests that current cigarette smoking is related to higher muscle fat infiltration, which may have significant health implications for the older population, because of its known association with poor physical function, falls, and hip fractures.
Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism, Lower Extremity Strength, and Physical Performance in Older Adults
Authors: Shuler Kurt , Sucic Joseph F , Talley Susan Ann , Goldberg Allon
Published: May 2019

Background

Evidence for associations between the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and physical performance is conflicting. Furthermore, investigations of relationships between lower extremity strength and physical performance have usually not considered the role of the ACE genotype, and it is unclear whether there are variations in relationships between lower extremity strength and physical performance among ACE genotypes in older adults.

Objective

The objectives of this study were to investigate associations between the ACE I/D polymorphism and physical performance and to determine whether relationships between lower extremity strength and physical performance vary among ACE genotypes in older adults.

Design

This was a cross-sectional observational study.

Methods

Community-dwelling adults (N = 88) who were at least 60 years old completed physical performance and lower extremity strength tests. After DNA was extracted from saliva, ACE I/D polymorphism genotyping was done. The Spearman rank order correlation coefficient was used to examine associations between lower extremity strength and physical performance within ACE genotype subgroups. Analysis of covariance and linear regression were used to examine ACE genotype and ACE genotype × lower extremity strength interaction effects in relation to physical performance.

Results

Genotype-specific correlation coefficients exhibited substantial variation among ACE genotype subgroups; however, differences did not attain statistical significance. Statistically significant genotype × lower extremity strength interaction effects in relation to physical performance were detected.

Limitations

The cross-sectional design precludes inferring causal relationships between strength and performance. The small sample size contributed to limited power to detect additional interaction effects and to detect statistically significant differences between correlation coefficients among ACE genotype subgroups.

Conclusions

The ACE I/D polymorphism is, interactively with lower extremity strength, associated with physical performance. Genotype-specific correlation coefficients and ACE genotype × lower extremity strength interaction effects on physical performance are consistent with variations in relationships between lower extremity strength and performance among ACE genotype subgroups.
Treatment Effect of Low-Intensity Pulsed Ultrasound on Benzene- and Cyclophosphamide-Induced Aplastic Anemia in Rabbits
Authors: Liu Baoru , Chen Wenzhi , Jiang Jingwei , Zhou Weichen , Zhang Yu , He Ruixin , Wang Yong , Li Junshu , Liang Dandan , Chen Junlin , Wang Wei , Luo Dong , Wang Yan
Published: May 2019

Background

Transplantation and immunosuppressive therapies are the available treatments for aplastic anemia; however, each strategy has its advantages and disadvantages.

Objective

The aim of this study was to find a new strategy for aplastic anemia treatment.

Design

This was an experimental and comparative study.

Methods

The aplastic anemia model was established by injecting rabbits with benzene and cyclophosphamide. The rabbits with aplastic anemia were divided into low-intensity pulsed ultrasound (LIPUS) and control groups. The distal femoral metaphysis of rabbits in the LIPUS group was treated with ultrasound for 30 days (20 min/d), whereas the control group received a sham treatment. Diarrhea, mortality, and blood cell count were evaluated. The levels of forkhead box P3, interleukin 17, interleukin 4, and interferon gamma were measured using an enzyme-linked immunosorbent assay. Bone marrow hyperplasia was observed by hematoxylin-eosin staining and scanning electron microscopy.

Results

The numbers of red blood cells (RBCs), white blood cells (WBCs), and platelets (PLTs) were lower, the amount of hematopoietic tissue was lower, and the amount of adipose tissue was higher in the rabbit aplastic anemia model than in the normal rabbits. The numbers of RBCs, WBCs, and PLTs increased after LIPUS treatment. The interleukin 17 level decreased, whereas the forkhead box P3 level increased. The amount of hematopoietic tissue increased, whereas the amount of adipose tissue decreased.

Limitations

The number of hematopoietic stem cells could not be evaluated.

Conclusions

LIPUS improved the hematopoietic microenvironment, accelerated the reconstruction of bone marrow cells, and increased the quantity and quality of RBCs, WBCs, and PLTs in the peripheral blood. Hence, it can serve as a novel treatment strategy for aplastic anemia in the future.
Revisiting the Egyptian Uprising of 2011: Exploring the Role of Relational Networks within the Cairo-Based Political Opposition
Authors: Wackenhut Arne F
Published: May 2019

Revisiting the Egyptian Uprising of 2011, I argue that strong relational networks linking actors in the broader Cairo-based political opposition—a conglomerate of prodemocracy movement organizations—should be understood as a necessary, albeit insufficient, causal condition for the diffusion of protest. These networks fulfilled two essential functions. 1) They were critical in terms of professionally socializing a new generation of activists—many of whom would become early riser participants during the initial protests on January 25, 2011. 2) The networks allowed for critically important coordination of and mobilization for the protests as they cut across boundaries of individual social and protest movement organizations. Based on 55 semi-structured interviews, I trace the genesis of these relational networks during the first decade of the new millennium, showing how a coalition of actors sought to capitalize on a transnational demonstration effect triggered by the Tunisian Revolution. This group—linked by dense relational networks—then functioned as early risers during the initial stages of the uprising and encouraged other segments of Egyptian society to join the protests and to openly challenge a regime that had often been regarded as impenetrable to popular demands for socio-political change from below.
What the Radiologist Needs to Know About Sinonasal Masses
Authors: Keir Graham , Jay Ann K.
Published: May 2019

Although malignancies in the sinonasal cavity comprise only 3% of all head and neck cancers and 1% of all malignancies,1 they are important disease entities to consider because of their nonspecific clinical presentation. There is considerable overlap of symptoms of sinonasal tumors with symptoms of the much more common rhinosinusitis. CT for rhinosinusitis symptoms is common in clinical practice and often ordered by primary care physicians who do not have the instruments to perform thorough endoscopic nasal examinations. Thus, the first physician to suggest the presence of a sinonasal lesion often is the general radiologist, frequently one without neuroradiology subspecialty training. It is imperative that radiologists not only are aware of imaging findings of both benign and malignant sinonasal masses and mass-like lesions but also are able to recommend the next appropriate steps in patient management.
Unmet Menstrual Hygiene Needs Among Low-Income Women
Authors: Kuhlmann Anne Sebert , Bergquist Eleanor Peters , Danjoint Djenie , Wall L. Lewis
Published: May 2019

(Abstracted from Obstet Gynecol 2019;133:238–244)

Women with adequate menstrual hygiene have access to soap and water for washing, access to clean sanitary materials (that can be changed in private), and access to a place for the hygienic disposal of used sanitary materials or washing reusable pads. Inadequate menstrual hygiene is common among women in low-resource countries.
Intrapartum Test for Detection of Group B Streptococcus Colonization During Labor
Authors: Picchiassi Elena , Coata Giuliana , Babucci Giulia , Giardina Irene , Summa Valentina , Tarquini Federica , Centra Michela , Bini Vittorio , Cappuccini Benito , Di Renzo Gian Carlo
Published: May 2019

(Abstracted from J Matern Fetal Neonatal Med 2018;31(24):3293–3300)

Maternal colonization with group B streptococcus (GBS) leading to neonatal sepsis remains a predominant cause of neonatal morbidity and mortality in the world. Many countries have adopted screening strategies, such as the antepartum GBS screening culture at 35 to 37 weeks of pregnancy (antepartum culture), to identify women who need intrapartum antibiotic prophylaxis (IAP) in order to avoid the GBS peripartum transmission to the fetus.
Use of biologics in chronic sinusitis with nasal polyps
Authors: Wang Chengshuo , Zhang Luo
Published: May 2019

Purpose of review

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory condition with different endotypes between patients from eastern or western countries. Targeted biologics are currently used to treat CRSwNP, but the outcomes widely vary. This review focuses on the present use of biologics for treating CRSwNP.

Recent findings

Monoclonal biologics have been used as an innovative therapy for multiple allergic diseases and comorbid allergic conditions. Over the past several decades, numerous biomarkers have been investigated and were found to be closely correlated with CRSwNP, improving the understanding of inflammatory patterns and endotype classifications for CRSwNP and prompting discussion regarding the use of biologics in CRSwNP. Efficacies vary in reports of different research groups, but it has been found that patients with TH-2-driven inflammatory patterns respond better to the use of biologics than those with non-TH-2-driven CRSwNP. These findings suggest the importance and urgency of developing criteria for biologics in CRSwNP.

Precisely determining patient criteria, identifying treatment biomarkers based on endotyping for CRSwNP and determinations of contraindications for long-term utilization may be useful for optimizing treatment strategies and improving the therapeutic efficacy of biologics to achieve long-term control starting at early stages.
Bias in the Peer Review Process
Authors: Tvina Alina , Spellecy Ryan , Palatnik Anna
Published: May 2019

Peer review is the major method used by the scientific community to evaluate manuscripts and decide what is suitable for publication. However, this process in its current design is not bulletproof and is prone to reviewer and editorial bias. Its lack of objectivity and transparency raise concerns that manuscripts might be judged based on interests irrelevant to the content itself and not on merit alone. This commentary reviews some of the most common biases that could potentially affect objective evaluation of a manuscript and proposes alternatives to the current single-blind peer review process that is being used by most scientific journals, including Obstetrics & Gynecology. By rethinking and tackling the shortcomings of the current methodology for peer review, we hope to create a discussion that will eventually lead to improving research and, ultimately, patient care.
Cost Effectiveness of Neonatal Resuscitation at 22 Weeks of Gestation
Authors: Yieh Leah , Dukhovny Dmitry , Zhou Clarice G. , Gievers Ladawna , Caughey Aaron B.
Published: May 2019

OBJECTIVE:

To evaluate the cost effectiveness of three different approaches to the care of neonates born at 22 weeks of gestation: universal resuscitation, selective resuscitation, or no resuscitation.

METHODS:

We constructed a decision-analytic model using TreeAge to compare the outcomes of death and survival with and without neurodevelopmental impairment in a theoretical cohort of 5,176 neonates (an estimate of the annual number of deliveries that occur in the 22nd week of gestation in the United States). We took a societal perspective using a lifetime horizon, and all costs were expressed in 2017 U.S. dollars. Effectiveness was based on combined maternal and neonatal quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio was determined (cost/QALY) for each additional survivor. The willingness to pay threshold was set at $100,000/QALY. All model inputs were derived from the literature. Deterministic and probabilistic sensitivity analyses were performed to interrogate model assumptions.

RESULTS:

Universal resuscitation would result in 373 survivors, 123 of whom would have severe disability. Selective resuscitation would produce 78 survivors with 26 affected by severe impairments. No resuscitation would result in only eight survivors and three neonates with severe sequelae. Selective resuscitation was eliminated by extended dominance because this strategy had a higher incremental cost-effectiveness ratio than universal resuscitation, which was a more effective intervention. The incremental cost-effectiveness ratio of universal resuscitation compared with no resuscitation was not cost effective at $106,691/QALY. Monte Carlo simulations demonstrated that universal resuscitation is more effective but also more expensive compared with no resuscitation, with only 35% of simulations below the willingness to pay threshold.

CONCLUSION:

In our model, neither selective nor universal resuscitation of 22-week neonates is a cost-effective strategy compared with no resuscitation.
Pharmacist Provision of Hormonal Contraception in the Oregon Medicaid Population
Authors: Anderson Lorinda , Hartung Daniel M. , Middleton Luke , Rodriguez Maria I.
Published: May 2019

OBJECTIVE:

To describe early utilization of pharmacist prescription of contraception in Oregon's Medicaid program.

METHODS:

Using Oregon Medicaid claims data, we conducted a retrospective analysis and quantified overall and monthly trends in pharmacist-prescribed contraceptives from January 1, 2016, to December 31, 2017. Our population was restricted to patients obtaining a new prescription for oral and transdermal methods and who had continuous Medicaid coverage during the study period. We summarized demographic and utilization characteristics, including whether patients were continuing or switching methods or initiating contraception. New prescriptions were those written to patients who did not have one for hormonal contraception in the prior 30 days. To assess program safety, we examined rates of prescriptions to patients with medical contraindications to contraceptive use.

RESULTS:

Among the 3,614 patients receiving a new prescription for oral or transdermal contraceptives in the Oregon Medicaid program from all health care providers, 367 (10%) received their prescription from a pharmacist. Five months after implementation, pharmacists filled an average of 61 prescriptions per month as the prescriber. Most claims originated from retail chain pharmacies (94%) in urban locations (71%). The majority of patients who were prescribed contraception by pharmacists (73.8%) had no history of contraceptive prescriptions in the preceding 30 days (n=252). Ages ranged from 13 to 49 years, fewer patients lived in a rural location (35.7%), most received a combined hormonal pill (90.5%), and the average day's supply dispensed was 65 (range of 21–364 days). Fewer than 5% (12) of patients had a diagnostic code indicating a possible contraindicating comorbidity.

CONCLUSION:

Among Medicaid enrollees, we found that 10% of all new oral and transdermal contraceptive prescriptions were written by pharmacists.
Treating Myomatous Erythrocytosis Syndrome With Uterine Artery Embolization
Authors: Gordon Brian , Fischbeck Tucker , Salamo Russell , Schroff Stuart
Published: May 2019

BACKGROUND:

Myomatous erythrocytosis syndrome, a form of secondary polycythemia associated with uterine leiomyomas, increases the risk of thrombosis and traditionally has been treated with hysterectomy.

CASE:

The patient is a 68-year-old woman with 7-year history of polycythemia initially thought to be secondary to a gastrointestinal stromal tumor that persisted after resection. A subsequent search for an alternative etiology led to the discovery of an 11.2-cm submucosal leiomyoma and likelihood of myomatous erythrocytosis syndrome. The patient declined surgical management and continued to undergo recurrent phlebotomy to maintain a hematocrit of less than 45% until consultation with an interventional radiology specialist. She underwent uterine artery embolization in July 2017, and her hematocrit has remained within normal limits through 17 months of follow-up.

CONCLUSION:

Uterine artery embolization is an effective alternative treatment modality for myomatous erythrocytosis syndrome.
Softer Tissue Issues in Orthopaedic Trauma
Authors: Nauth Aaron , Egol Kenneth A. , Walden Timothy , Boyer Martin , Anglen Jeffrey , Broekhuyse Henry M.
Published: May 2019

There are number of significant issues outside of the bone and/or fracture that are important to consider in the treatment of orthopaedic trauma. Joint contractures, heterotopic bone formation, managing a traumatized soft-tissue envelope or substantial soft-tissue defects represent a few of these important issues. This article reviews these issues, including the best available evidence on how to manage them.
Previous Implant Fractures: A New Descriptive Classification System
Authors: Egol Kenneth A. , Carlock Kurtis D. , Kelly Erin A. , Seetharam Abhijit , Mullis Brian H. , Marcantonio Andrew J. , Bramlett Kasey J. , Nchako Corbyn M. , Watson J. Tracy , Cannada Lisa K. , Konda Sanjit R.
Published: May 2019

Objectives:

To propose a previous implant fractures (PIFs) classification system with good interobserver reliability.

Design:

Retrospective classification.

Setting:

Four academic medical centers.

Patients/Participants:

A retrospective review of PIFs treated at 4 academic medical centers over 10 years was performed. Data collected included initial implant and PIF radiographs. There were 103 PIFs in 96 patients during the study period. Seventy-three (70.9%) were about plate/screw (PS) constructs and 30 (29.1%) were about intramedullary (IM) devices.

Intervention:

Assignment of PIF classification.

Main Outcome Measurements:

PIFs were classified based on initial implant (PS or IM) and fracture location with respect to the initial implant (proximal or distal to the implant, at the tip of the construct, or within the construct). Reliability of this scheme was assessed among 5 observers using Fleiss' kappa tests.

Results:

Of PIFs about plate/screw constructs, 26.0% were proximal/distal to the implant (classification: PS1), 57.5% involved bone between the most proximal/distal screw and the same end of the plate (classification: PS2), and 16.4% involved only bone between the most proximal and distal screws (classification: PS3). Of PIFs about IM, 43.3% were distal to the device (classification: IM1), 46.7% involved bone between the most proximal/distal locking bolt and the same end of the device (classification: IM2), and 10.0% involved only bone between locking bolts (classification: IM3). Interobserver reliability for the classification system was excellent between observers, κ = 0.839, P < 0.0005.

Conclusions:

The proposed system offers a simple method to classify and describe fractures that occur about a previously implanted fracture device. Development of a classification system will allow for comparison of treatment modalities between injury types.
Erythropoietin Improves Cardiovascular Function in Adult Rats After Acute Hemorrhage
Authors: Puchulu María B. , Arreche Noelia , Zotta Elsa , Donato Martin , Ogonowski Natalia , Fellet Andrea , Balaszczuk Ana M.
Published: May 2019

Erythropoietin (EPO) has been linked to cardioprotective effects. However, its effects during the aging process are little known. We investigated the effect of EPO administration on hemodynamic parameters, cardiac function, oxidative damage, and erythropoietin receptor (EPOR) expression pattern in the hypovolemic state. EPO was administered (1000 IU/kg/3 days) and then acute hemorrhage (20% blood loss) was induced in young and adult rats. There was no difference in plasmatic EPO in either age group. The hemodynamic basal condition was similar, without alterations in renal function and hematocrit, in both age groups. After bleeding, both EPO-treated age groups had increased blood pressure at the end of the experimental protocol, being greater in adult animals. EPO attenuated the tachycardic effect. Ejection fraction and fractional shortening were higher in adult EPO-treated rats subjected to hemorrhage. In the left ventricle, young and adult EPO-treated rats subjected to bleeding showed an increased EPOR expression. A different EPOR expression pattern was observed in the adult right atrial tissue, compared with young animals. EPO treatment decreased oxidative damage to lipids in both age groups. EPO treatment before acute hemorrhage improves cardiovascular function during the aging process, which is mediated by different EPOR pattern expression in the heart tissue.
Quantification of the Plasma Concentration of Apatinib by 2-Dimensional Liquid Chromatography
Authors: Yu Yue , Shi Jing , Wang Feng , Tang Xiao-hui , Liu Yu-guo
Published: May 2019

Background:

Apatinib is a new oral micromolecular tyrosine kinase inhibitor, which is mainly used as a third-line treatment for chemotherapy-refractory advanced metastatic gastric cancer patients. However, apatinib has shown dose titration and severe adverse reactions in clinical practice. Quantification of plasma concentrations of apatinib may be an effective method to balance the clinical efficacy and adverse reactions. The purpose of this study was to develop and validate a 2-dimensional liquid chromatography method for the measurement of apatinib in plasma.

Methods:

The analysis of apatinib was performed using a 2-dimensional high-performance liquid chromatography system. We precipitated the proteins with acetonitrile. The mobile phases consisted of a first-dimensional mobile phase (acetonitrile:methanol:25 mmol·L−1 ammonium phosphate = 25:25:50, V/V/V, pH adjusted to 7.2 using phosphoric acid) and a second-dimensional mobile phase (acetonitrile:10 mmol·L−1 ammonium phosphate = 28:72, vol/vol, pH adjusted to 3.7 using phosphoric acid). The ultraviolet detection wavelength was set at 340 nm. The temperature of the detector cell was 40°C, and the injection volume was 500 μL.

Results:

The range of calibration curve was 15.27–1491.48 ng/mL. The accuracy and imprecision were within ±2.23% and less than 10.22%, respectively (intraday and interday). The range of recovery was 97.45%–108.92%. The intraday and interday relative SDs (reproducibility) of high-performance liquid chromatography retention times were less than 0.18% and 0.46%, respectively. In the clinical assessment, the dose range of apatinib mesylate for patients with gastric cancer was 250–500 mg every day (2–60 days), resulting in trough plasma concentrations between 272.7 and 727.8 ng/mL.

Conclusions:

A simple, convenient, accurate, and robust 2-dimensional liquid chromatography method was developed and verified, which successfully determined the plasma concentrations of apatinib in patients with gastric cancer.
Nonmicrosurgical Grafting for Facial Nerve Branches with Permanent Sensational Functional Outcome
Authors: Ali Yasser Helmy , Al Sheikh Abd El-Fattah
Published: May 2019

A 49-year-old man underwent intraoperatively modified procedure from superficial to radical parotidectomy with excision of the facial nerve 4 branches, temporal, zygomatic, buccal, and mandibular. We have dissected and harvested the branches of the great auricular nerve to repair the defects of the temporal, zygomatic, buccal, and mandibular nerves without microsurgery aid. The aims of the repair were just to mark the nerve endings, to try autologous grafting, and to avoid neuroma(s) formation, although neuroma(s) formations from motor nerves are rare. We did an immediate temporary nonmicrosurgical nerve grafting, and we have sutured each nerve anastomosis by 2–3 stitches of Prolene 6–0. We have observed facial nerve branches’ recovery on the second month, even with radiation therapy, and then gradually more improvements on the third month and then on the sixth month of the follow-up. Finally, the procedure results in permanent sensational functional outcome after 1 year. Because we did not plan a microsurgical repair, this case report does not support any intended nonmicrosurgical procedures for facial nerve repair, but it raises questions for laboratory and animal investigations about the size of Prolene we have used, grip repair taking the epineurium and fascicle in mass closure, and the positive fast functional results. In surgical environments where microscope or microinstruments are lacking, one can still perform primary nerve grafting.
Myasthenia gravis presentation and treatment variations: A case study approach
Authors: Deters Darlene , Patel Darpan I.
Published: May 2019

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder that can affect the ocular, bulbar, neck, proximal limb, and respiratory muscles. This case study presents two similar individuals diagnosed with MG that presented with varying symptomatology and also with a different response to therapy. These two patients represent a unique patient group that represents only 10% of patients diagnosed with MG.
Psychological affection in rheumatoid arthritis patients in relation to disease activity
Authors: Hassan Amal Ali , Nasr Mona Hamdy , Mohamed Ahmed Lotfi , Kamal Ahmed Mohmed , Elmoghazy Alyaa Diaa
Published: May 2019

Rheumatoid arthritis (RA) is a common, systemic autoimmune disease characterized by persistent symmetric polyarthritis (synovitis). Anxiety and depression are common among patients with RA, compared to the general population and have been associated with increased pain, fatigue, physical disability and health care costs, and an overall reduced health-related quality of life. The aim of the present study was to assess the relation between psychological factors (anxiety and depression) and disease activity (and severity) parameters in RA patients.

This national, single-center, cross-sectional study recruited over 6 months 25 patients with RA diagnosed according to the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria, and 25 healthy control individuals. All participants were subjected to the clinical and laboratory evaluation of disease activity and psychological assessment according to the International Classification of Mental and Behavioral Disorders tenth revision. Significance and regression analyses were performed to determine disease activity and severity predictors.

80% of RA patients had depression and 52% anxiety symptoms, while only 8% of healthy controls reported mild depression (P < .001). Data also found highly significant correlation between depressive symptoms and RA disease activity (P < .05).

Psychiatric manifestations are common in RA and they strongly correlate with severity of the disease.