bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactobacillus bulgaricus improves antioxidant capacity of black garlic in the prevention of gestational diabetes mellitus: a randomized control trial
Authors: Si Lihui , Lin Ruixin , Jia Yan , Jian Wenwen , Yu Qing , Wang Min , Yang Shuli
Published: July 2019

Objectives: Lactobacillus bulgaricus may improve antioxidant capacity of black garlic in the prevention of gestational diabetes mellitus (GDM).

Methods: Black garlic was prepared with or without L. bulgaricus. Volatile and polysaccharides were analyzed by using LC-MS, Fourier Transform infrared (FTIR) and 13C nuclear magnetic resonance (NMR). The study design was parallel randomized controlled trial and 226 GDM patients were randomly assigned into BG (black garlic and L. bulgaricus) and CG (black garlic) groups, and allocation ratio was 1:1. The treatment duration was 40 weeks. Fasting blood glucose (FBG) and 1- and 2-h blood glucose (1hBG and 2hBG) after oral glucose tolerance test (OGTT) were detected. Antioxidant function of black garlic was determined by measuring plasma malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and total antioxidant capacity (T-AOC) in GDM patients. The comparison between two groups was made using two independent samples t test.

Results: The intake of nutrients was similar between two groups (P>0.05). L. bulgaricus promoted the transformation of the glucopyranoside to glucofuranoside. L. bulgaricus increased the abilities of black garlic for scavenging hydroxyl radicals, 2,2′-azino-bis (3-ethylbenzenthiazoline-6-sulfonic) acid (ABTS) and DPPH free radicals. L. bulgaricus reduced the levels of FBG, 1hBG and 2hBG, and incidence of perinatal complications (P<0.01). Plasma MDA level in the BG group was lower than in the CG group, whereas the levels of SOD, GSH-PX and T-AOC in the BG group were higher than in the CG group (P<0.01).

Conclusions: L. bulgaricus improves antioxidant capacity of black garlic in the prevention of GDM.
Neural network‐based quickprop control algorithm for grid connected solar PV‐DSTATCOM system
Authors: Shukl Pavitra , Singh Bhim
Published: July 2019

For the optimal operation of grid interfaced solar photovoltaic (PV) system, a neural network‐based Quickprop control algorithm is presented in this study. The solar PV array supplies maximum power by utilising an incremental conductance‐based maximum power point tracking technique to the grid and the load. When the solar power is not present, during cloudy days or at night, the distribution static compensator (DSTATCOM) operation is performed by harmonics mitigation and reactive power compensation of the loads connected at the point of intersection. The proposed system improves power quality when solar PV power is present, along with active power transfer from solar PV array to grid/load. Thus, a smooth transition is provided between these modes with neural network‐based Quickprop control algorithm. Moreover, the neural network‐based control technique offers enhanced accuracy due to the combinational neural structure in the estimation process. A laboratory prototype is developed for validation and experimental results corroborate reliable operation for modes of operation as DSTATCOM and grid interfaced PV system at varying load and solar insolation condition.
High‐strength concrete containing RHA and nano‐CaCO3
Authors: Rahbar Yahya , Mousavi Seyed Yasin , Nasserabadi Heydar Dashti
Published: July 2019

The properties of high‐strength concrete (HSC) containing rice‐husk ash (RHA) and nanocalcium carbonate (nano‐CaCO3) is evaluated. For this purpose, various HSC samples containing 0–20% RHA and 0–1.5% nano‐CaCO3 were prepared and investigated for the slump, compressive strength, absorption, electrical resistivity, chloride penetration depth and sulphuric acid (H2SO4) attack resistance. Results indicated that by a ternary combination of Portland cement (PC) + 10% RHA + 0.5% nano‐CaCO3, it is able to produce HSC with 28 days compressive strength of 101.7 MPa, which was 15% higher than that of estimated for plain HSC. Additionally, substituting optimum level of nano‐CaCO3 in HSC containing RHA could improve the electrical resistivity and reduce the water absorption and chloride ion penetration depth compared with binary use of PC + RHA. A lower mass loss has been determined for the ternary combination of PC + RHA + nano‐CaCO3 at all immersion times in 5% H2SO4 solution as compared with plain HSC. Moreover, considering HSC samples exposed to H2SO4 solution at the age of 84 days, it can be seen that the presence of nano‐CaCO3 in HSC containing RHA did not necessarily contribute to a significant reduction in the crushing load loss percentage compared with the binary use of PC + RHA.
Discovery of a giant and luminous Lyα+C IV+He II nebula at z = 3.326 with extreme emission line ratios
Authors: Marques-Chaves R. , Pérez-Fournon I. , Villar-Martín M. , Gavazzi R. , Riechers D. , Rigopoulou D. , Wardlow J. , Cabrera-Lavers A. , Clements D. L. , Colina L. , Cooray A. , Farrah D. , Ivison R. J. , Jiménez-Ángel C. , Martínez-Navajas P. , Nayyeri H. , Oliver S. , Omont A. , Scott D. , Shu Y.
Published: July 2019

We present the discovery of HLock01-LAB, a luminous and large Lyα nebula at z = 3.326. Medium-band imaging and long-slit spectroscopic observations with the Gran Telescopio Canarias reveal extended emission in the Lyα 1215 Å, C IV 1550 Å, and He II 1640 Å lines over ∼100 kpc, and a total luminosity LLyα = (6.4 ± 0.1)×1044 erg s−1. HLock01-LAB presents an elongated morphology aligned with two faint radio sources contained within the central ∼8 kpc of the nebula. The radio structures are consistent with faint radio jets or lobes of a central galaxy, whose spectrum shows nebular emission characteristic of a type-II active galactic nucleus (AGN). The continuum emission of the AGN at short wavelengths is however likely dominated by stellar emission of the host galaxy, for which we derive a stellar mass M* ≃ 2.3 × 1011 M⊙. Our kinematic analysis shows that the ionized gas is perturbed almost exclusively in the inner region between the radio structures, probably as a consequence of jet–gas interactions, whereas in the outer regions the ionized gas appears more quiescent. The detection of extended emission in C IV and C III] indicates that the gas within the nebula is not primordial. Feedback may have enriched the halo at at least 50 kpc from the nuclear region. Using rest-frame UV emission-line diagnostics, we find that the gas in the nebula is likely heated by the AGN. Nevertheless, at the center of the nebula we find extreme emission line ratios of Lyα/C IV ∼60 and Lyα/He II ∼80, one of the highest values measured to date, and well above the standard values of photoionization models (Lyα/He II ∼30 for case B photoionization). Our data suggest that jet-induced shocks are likely responsible for the increase of the electron temperature and, thus, the observed Lyα enhancement in the center of the nebula. This scenario is further supported by the presence of radio structures and perturbed kinematics in this region. The large Lyα luminosity in HLock01-LAB is likely due to a combination of AGN photoionization and jet-induced shocks, highlighting the diversity of sources of energy powering Lyα nebulae. Future follow-up observations of HLock01-LAB will help to reveal the finer details of the excitation conditions of the gas induced by jets and to investigate the underlying cooling and feedback processes in this unique object.
Aktuelle Standards und Ausblicke in der Behandlung des Ösophaguskarzinoms
Authors: Graf Dirk , Häussinger Dieter
Published: July 2019

Was ist neu?

Endoskopische Behandlung des mukosalen Frühkarzinoms (Tis und T1a) Die Mukosa-beschränkten Adeno- oder Plattenepithelkarzinome ohne Hinweis auf eine Gefäß- oder Lymphgefäßinfiltration mit guter oder mäßiger Differenzierung (G1–G2) sollten einer endoskopischen Resektion unterzogen werden.

Lokal begrenzte Stadien: T1b- und T2N0M0-Tumoren Für diese Patienten stellt die primäre komplette chirurgische Resektion inklusive Lymphadenektomie die Therapie der Wahl dar.

Lokal fortgeschrittene Stadien: cT3 / cT4-Tumoren oder cN1- bis cN3-Tumoren Im Falle von Adenokarzinomen sollten diese entweder perioperativ mit Chemotherapie (Goldstandard FLOT) oder wie Plattenepithelkarzinome neoadjuvant mit einer Radiochemotherapie behandelt werden. Chirurgischerseits geht der Trend zunehmend zum Einsatz von Hybridverfahren (Laparoskopie und offene Thorakotomie bzw. offene Laparotomie und Thorakoskopie) oder zu komplett minimalinvasiven Verfahren.

Palliative Chemotherapie Eine palliative Chemotherapie kann bei Patienten mit metastasiertem Adenokarzinom des Ösophagus das mediane Gesamtüberleben verbessern.
Vitamin D im Alter: Ist der Hype definitiv vorüber?
Authors: Bischoff-Ferrari Heike A.
Published: July 2019

Was ist neu?

Metaanalysen zur Wirkung von Vitamin D In den Jahren 2016 bis 2018 wurden 4 Metaanalysen publiziert, um den Nutzen von Vitamin D für die Frakturprävention zu untersuchen. 2 dieser Metaanalysen konzentrierten sich auf die Primärprävention von Frakturen bei Erwachsenen ab 50 Jahren, bei denen kein Risiko für Frakturen und kein Vitamin-D-Mangel bestand. Eine weitere Metaanalyse konzentrierte sich auf die Kombination von Vitamin D plus Kalzium und die zuletzt publizierte Metaanalyse auf die individuelle Wirkung von Vitamin D ohne Kalzium. Bezogen auf die heutigen Richtlinien ist wichtig, dass sich nur 1 der 3 jüngsten Metaanalysen vorwiegend an Erwachsene ab 65 Jahren mit erhöhtem Risiko bezüglich Stürze, Frakturen und Vitamin-D-Mangel richtete.

Was können wir nun empfehlen? In Anbetracht und nach kritischer Prüfung der Metaanalysen zu Vitamin D und Frakturprävention ist eine Vitamin-D-Supplementation mit oder ohne Kalzium bei älteren Erwachsenen ab 65 Jahren mit einem erhöhten Risiko für Vitamin-D-Mangel und einem erhöhten Risiko für Frakturen weiterhin sinnvoll.
Kristallarthritiden
Authors: Tausche Anne-Kathrin , Reuss-Borst Monika
Published: July 2019

Was ist neu?

Kristallarthritiden – Mikroskopie für die Diagnose essenziell Für die Diagnosesicherung der Kristallarthritiden ist für den Rheumatologen der mikroskopische Nachweis von Harnsäure- und/oder Kalziumpyrophosphat-Kristallen rasch bettseitig durchführbar. Ist eine Punktion nicht möglich, kann die Dual-Energy-Computertomografie helfen, Harnsäurekristalle sichtbar zu machen.

Gemeinsame Pathophysiologie der Kristall-vermittelten Entzündung Kristalle stellen „Gefahrensignale“ für das angeborene Immunsystem dar. Die unmittelbare Freisetzung von Interleukin 1β erklärt die anfallsartige Klinik, die allen Kristallarthritiden gemeinsam ist.

Antientzündliche Therapie der Kristallarthritiden Neben unspezifisch wirkenden antientzündlichen Therapien erklärt die gemeinsame Pathophysiologie (Aktivierung des Inflammasom-Komplexes und Interleukin-1β-Freisetzung) die Wirksamkeit von IL-1β-Antikörper-Therapien. Niedrig dosiertes Colchicin ist zur Anfallstherapie und in der Prophylaxe von entzündlichen Schüben eine wertvolle Therapieoption.

Kausale Therapie mit guter Evidenz bisher nur für die Gicht Nur durch eine langfristige konsequente Harnsäuresenkung unter den Harnsäurezielwert < 360 µmol/l (< 6 mg/dl) kann eine dauerhafte Remission der Gicht erreicht werden. Patienten mit dekompensierter Herzinsuffizienz und instabiler KHK sollten nicht primär Febuxostat erhalten. Die neue Kombinationsmöglichkeit von Allopurinol mit dem Urikosurikum Lesinurad wäre gerade für diese Patienten eine Alternative; aktuell ist Lesinurad in Deutschland (noch) nicht erstattungsfähig.
Aromapflege: Das riecht aber gut!
Authors: Mazurek Christian
Published: July 2019

Aromapflege stimuliert nicht nur unseren Geruchsinn – in der Versorgung von
psychisch erkrankten Menschen leistet sie noch viel mehr: Sie lindert belastende
psychische Symptome, steigert die Lebensqualität und kann dazu beitragen, dass
Patienten mehr Verantwortung für sich selbst übernehmen.
Pseudoaneurysm of Internal Carotid Artery following Endoscopic Endonasal Pituitary Surgery requiring Endovascular Treatment in an Acromegalic Patient with a Difficult Airway
Authors: Rodrigues Joanna S. , Gupta Ankit , Parakh Anil
Published: July 2019

A pituitary tumor scheduled for surgical excision can eventuate with a myriad of challenges. A 49-year-old acromegalic patient was admitted to our hospital for trans-nasal trans-sphenoidal pituitary surgery. Magnetic resonance imaging (MRI) of his brain revealed a well-defined lesion involving right half of the anterior lobe of pituitary. In the operating room, we encountered difficulty in management of the airway. The trachea could be intubated using fiberoptic bronchoscope via a proseal laryngeal mask airway after five attempts of failed intubation. Intraoperatively, the right internal carotid artery (ICA) was injured during excision of lateral part of the tumor with a blood loss of 3.5 L. Adenosine use to aid hemostasis was unsuccessful. Endovascular coil embolization was done to treat the pseudoaneurysm developed in the right ICA, to restore the blood flow. During this process, the patient developed medial rectus palsy and ptosis in the right eye, which improved gradually. The above amalgamation of maladies commanded an integrated and well-coordinated team approach to manage the catastrophic complications.
Tranexamic Acid in Neuroanesthesia and Neurocritical Care: Time for Its Critical Appraisal
Authors: Hooda Bhavna , Muthuchellappan Radhakrishnan
Published: July 2019

There is a renewed interest in the use of antifibrinolytics, especially tranexamic acid (TxA), in varied clinical settings such as trauma, perioperative bleeding, cardiac surgery, and multilevel spine instrumentation procedures. Because of its prothrombotic potential, the use of TxA in neurosurgical disorders has not gained popularity since this subset of the population is more prone to developing thromboembolic complications. However, recent studies have shown that TxA reduces blood loss, reduces the need for allogeneic blood transfusion, and is associated with minimal side effects. In this narrative review, Google Scholar, PubMed, and EMBASE databases were searched to identify publications relevant to the current use of TxA in varied neurosurgical and critical care settings. These publications were analyzed, and a summary of the findings and the role of future research on this drug are presented in this review.
Audiological correlates of cone beam computed tomography (CBCT) in cochlear implant recipients
Authors: Abdel Rahman Tayseer Taha , Abdel Kader Hesham Abd El Aty , Abdel Aziz Tougan Taha
Published: July 2019

Objectives:

To evaluate the role of Cone beam CT (CBCT) regarding the intracochlear electrode position, the exact localization of the electrode in either the Scala tympani or Scala vestibuli and any accompanying inner ear trauma to the delicate intracochlear structures and furthermore correlate these findings with the hearing thresholds and speech tests in patients with unilateral cochlear implant (CI).

Method:

A total number of 20 subjects were examined in this study, 6 males and 14 females, their ages ranged from 3 to 10 years who underwent cochlear implantation. CBCT was done to the entire study group 3 months after surgery. After one year, audio logical evaluation was done in the form of aided warble tone response, aided speech reception threshold and early speech perception test (ESP) both in quiet and in noise. The study group was subdivided according to the degree of inner ear trauma into four groups: grade 0 trauma (9 subjects), grade I trauma (3 subjects), grade II trauma (3 subjects), grade III trauma (5 subjects).

Results:

There was a significant difference among no trauma patients and trauma patients regarding the insertion angle, aided threshold at 250 Hz, percentage of working electrodes and ESP in noise test. Moreover, significant inverse correlation was present between the grade of trauma and both ESP in noise and the percentage of working electrodes.

Conclusions:

The optimal image quality and the small radiation dose renders CBCT as an optimal and secure imaging tool for the assessment of the CI electrode location and evaluation of inner ear trauma as it affects postoperative programing and hearing perspectives.
Implementation of hyperlinks to medication management policies and guidelines in the electronic health record
Authors: Dwenger Andrew T , Fox Erin R , Macdonald Elyse A , Edvalson Bryan J
Published: July 2019

Purpose

The implementation and maintenance of a process for adding and removing hyperlinks to medication management policies and guidelines approved by a pharmacy and therapeutics (P&T) committee into the electronic health record (EHR) are described.

Medication management policies and guidelines approved by the P&T committee are published on the University of Utah Health intranet, making it possible to add hyperlinks to this information within the EHR. Adding these hyperlinks allows policy and guideline information to be available to clinicians on the medication ordering, verification, and administration screens without requiring a separate search of the intranet. In a quality-improvement project, all medication management policies and guidelines posted on the intranet were reviewed for relevance to the medication ordering, verification, and administration processes. Hyperlinks to relevant policies and guidelines were implemented into the EHR for specific medications. At the beginning of the review, 100 unique drugs associated with 1 or more hyperlinks were identified. The hyperlinks referenced a total of 33 Web documents: 8 policies and 25 guidelines. There are 74 medication management policies and 78 medication management guidelines approved by the P&T committee at University of Utah Health. After investigator review, 12 of 74 policies (16%) and 41 of 78 guidelines (53%) were deemed relevant during the medication ordering, verification, and administration processes. The review and hyperlink implementation process took a total of 101 hours. A continual review process was developed to enable addition and removal of hyperlinks as appropriate.

Conclusion

Providing direct access to relevant medication management policies and guidelines approved by the P&T committee during the medication ordering, verification, and administration processes via hyperlinks in the EHR makes formulary information readily accessible by appropriate staff. These hyperlinks may also improve adherence to formulary information, reduce medication expenditure, and improve safety and therapeutic outcomes of medication therapy.
Creating an immunization content database for knowledge management across clinical systems
Authors: Wen Hamilton , Mathe Janos L , Weinberg Stuart T , Weitkamp Asli Ozdas , Nelson Scott D
Published: July 2019

Purpose

A initiative at an academic medical center to create a single database of immunization-related content to inform the build and configuration of immunization-related knowledge assets across multiple clinical systems is described.

Methods

Semistructured expert interviews were conducted to ascertain the immunization information needs of the institution’s clinical systems. Based on those needs, an immunization domain model constructed with data available from the Centers for Disease Control and Prevention (CDC) website was developed and used to analyze and compare current immunization-related content from CDC data sources with the content of the institution’s clinical systems.

Results

Five identified clinical systems that used immunization-related content collectively required 22 unique information concepts, 11 of which were obtainable from CDC vaccine code sets. The proportion of vaccines designated by CDC as active products (i.e., currently available administrable vaccines) that were included in the 5 clinical systems ranged from 59% to 95%; in addition, some non–active-status vaccines were listed as active-status products in the various clinical systems. Upon further review, updates to immunization-related content in the 5 clinical systems were implemented.

Conclusion

Creating a single database for immunization-related content based on CDC data facilitated an explicit and tractable knowledge management process and helped ensure that clinical systems had correct and current content. The immunization domain model created has the potential to assist in the automated detection of updates and relaying those updates to the applicable clinical systems.
Does bat response to traffic noise support the misleading cue hypothesis?
Authors: Geipel Inga , Amin Bawan , Page Rachel A , Halfwerk Wouter
Published: July 2019

The world has become a noisier place due to the increase in urbanization. Noise is generally considered an impediment, altering an animal’s behavior through masking or distraction. But noise can also provide useful information about the environment. For animals that rely on natural environmental noise as an indicator of favorable foraging conditions, increasing levels of anthropogenic noise might mislead informed decision-making. Bats use rain noise, a natural environmental cue, to delay their emergence from the roost, presumably to avoid sensory and metabolic costs associated with foraging in heavy rain. Here we tested the “misleading cue hypothesis,” asking whether traffic noise is mistaken for rain noise by bats. Given the acoustic similarity between rain noise and traffic noise, we predicted that bats would confuse the two. We conducted a playback experiment using rain, traffic, and ambient noise at natural roosts of common big-eared bats (Micronycteris microtis, Phyllostomidae) and recorded bat emergence behavior. In contrast to their response to rain noise, the bats did not delay roost emergence in response to traffic noise. Thus, we found that bats were able to discriminate between traffic noise and rain noise and were not misled by similarity in acoustic parameters in the two noise types, when emerging from their roost. Emerging bats did show more exploration flights during traffic noise than during rain noise, but not during ambient noise, suggesting that they perceive traffic noise as a novel acoustic cue. Our data provide new insights into perception of traffic noise by bats.
Discovering protein drug targets using knowledge graph embeddings
Authors: Mohamed Sameh K , Nováček Vít , Nounu Aayah
Published: July 2019

Motivation

Computational approaches for predicting drug–target interactions (DTIs) can provide valuable insights into the drug mechanism of action. DTI predictions can help to quickly identify new promising (on-target) or unintended (off-target) effects of drugs. However, existing models face several challenges. Many can only process a limited number of drugs and/or have poor proteome coverage. The current approaches also often suffer from high false positive prediction rates.

Results

We propose a novel computational approach for predicting drug target proteins. The approach is based on formulating the problem as a link prediction in knowledge graphs (robust, machine-readable representations of networked knowledge). We use biomedical knowledge bases to create a knowledge graph of entities connected to both drugs and their potential targets. We propose a specific knowledge graph embedding model, TriModel, to learn vector representations (i.e. embeddings) for all drugs and targets in the created knowledge graph. These representations are consequently used to infer candidate drug target interactions based on their scores computed by the trained TriModel model. We have experimentally evaluated our method using computer simulations and compared it to five existing models. This has shown that our approach outperforms all previous ones in terms of both area under ROC and precision–recall curves in standard benchmark tests.

Availability and implementation

The data, predictions and models are available at: drugtargets.insight-centre.org.

Supplementary information

Supplementary data are available at Bioinformatics online.
Using three-dimensional printed models to test for aposematism in a carabid beetle
Authors: Fukuda Shinpei , Konuma Junji
Published: July 2019

Many studies have demonstrated that bright colours sometimes evolve as warning coloration on the bodies of distasteful prey. However, few studies have demonstrated that the bright structural colours of beetles function as such aposematic signals for predators in the wild. To determine whether body colour might act as an aposematic signal in the carabid beetle Damaster blaptoides, we generated beetle models and conducted camera-trap and field experiments. Elaborate beetle models produced using a three-dimensional printer were used to determine which animals attack them in the wild. Red and black models were placed in forests to test which of the two types was attacked the least frequently. The camera-trap experiments indicated that mammals and birds were the potential predators of D. blaptoides. The field experiments revealed that predators attacked the red models significantly less frequently than the black models in each of three sites where red Damaster subspecies were distributed. In three sites where black Damaster subspecies were distributed, predators attacked both red and black models at similar rates. These results might imply that the predators learned more easily to avoid distasteful red beetles rather than black ones.
Yes-associated protein 1 is required for proliferation and function of bovine granulosa cells in vitro†
Authors: Plewes Michele R , Hou Xiaoying , Zhang Pan , Liang Aixin , Hua Guohua , Wood Jennifer R , Cupp Andrea S , Lv Xiangmin , Wang Cheng , Davis John S
Published: July 2019

Yes-associated protein 1 (YAP1) is a major component of the Hippo signaling pathway. Although the exact extracellular signals that control the Hippo pathway are currently unknown, increasing evidence supports a critical role for the Hippo pathway in embryonic development, regulation of organ size, and carcinogenesis. Granulosa cells (GCs) within the ovarian follicle proliferate and produce steroids and growth factors, which facilitate the growth of follicle and maturation of the oocyte. We hypothesize that YAP1 plays a role in proliferation and estrogen secretion of GCs. In the current study, we examined the expression of the Hippo signaling pathway in bovine ovaries and determined whether it was important for GC proliferation and estrogen production. Mammalian STE20-like protein kinase 1 (MST1) and large tumor suppressor kinase 2 (LATS2) were identified as prominent upstream components of the Hippo pathway expressed in granulosa and theca cells of the follicle and large and small cells of the corpus luteum. Immunohistochemistry revealed that YAP1 was localized to the nucleus of growing follicles. In vitro, nuclear localization of the downstream Hippo signaling effector proteins YAP1 and transcriptional co-activator with PDZ-binding motif (TAZ) was inversely correlated with GC density, with greater nuclear localization under conditions of low cell density. Treatment with verteporfin and siRNA targeting YAP1 or TAZ revealed a critical role for these transcriptional co-activators in GC proliferation. Furthermore, knockdown of YAP1 in GCs inhibited follicle-stimulating hormone (FSH)-induced estradiol biosynthesis. The data indicate that Hippo pathway transcription co-activators YAP1/TAZ play an important role in GC proliferation and estradiol synthesis, two processes necessary for maintaining normal follicle development.
Simplified integrated nested Laplace approximation
Authors: Wood Simon N
Published: July 2019

Integrated nested Laplace approximation provides accurate and efficient approximations for marginal distributions in latent Gaussian random field models. Computational feasibility of the original Rue et al. (2009) methods relies on efficient approximation of Laplace approximations for the marginal distributions of the coefficients of the latent field, conditional on the data and hyperparameters. The computational efficiency of these approximations depends on the Gaussian field having a Markov structure. This note provides equivalent efficiency without requiring the Markov property, which allows for straightforward use of latent Gaussian fields without a sparse structure, such as reduced rank multi-dimensional smoothing splines. The method avoids the approximation for conditional modes used in Rue et al. (2009), and uses a log determinant approximation based on a simple quasi-Newton update. The latter has a desirable property not shared by the most commonly used variant of the original method.
Impaired D2 receptor-dependent dopaminergic transmission in prefrontal cortex of awake mouse model of Parkinson’s disease
Authors: Li Mingli , Xu Huadong , Chen Guoqing , Sun Suhua , Wang Qinglong , Liu Bing , Wu Xi , Zhou Li , Chai Zuying , Sun Xiaoxuan , Lu Yang , Younus Muhammad , Zheng Lianghong , Zhu Feipeng , Jia Hongbo , Chen Xiaowei , Wang Changhe , Zhou Zhuan
Published: July 2019

Anxiety is a major early-onset non-motor symptom in Parkinson’s disease, but the underlying mechanisms remain largely unknown. By imaging brain circuits in an awake parkinsonian mouse model, Li, Xu et al. provide evidence that Parkinson’s disease-associated anxiety is caused by impaired postsynaptic D2 receptor-dependent dopaminergic transmission in prefrontal cortex.
Unique miRNA profiling of squamous cell carcinoma arising from ovarian mature teratoma: comprehensive miRNA sequence analysis of its molecular background
Authors: Yoshida Kosuke , Yokoi Akira , Kagawa Takumi , Oda Shingo , Hattori Satomi , Tamauchi Satoshi , Ikeda Yoshiki , Yoshikawa Nobuhisa , Nishino Kimihiro , Utsumi Fumi , Niimi Kaoru , Suzuki Shiro , Shibata Kiyosumi , Kajiyama Hiroaki , Yokoi Tsuyoshi , Kikkawa Fumitaka
Published: July 2019

Owing to its rarity, the carcinogenesis and molecular biological characteristics of squamous cell carcinoma arising from mature teratoma remain unclear. This study aims to elucidate the molecular background of malignant transformation from the aspects of microRNA (miRNA) profiling. We examined 7 patients with squamous cell carcinoma and 20 patients with mature teratoma and extracted their total RNA from formalin-fixed paraffin-embedded tissues. Then we prepared small RNA libraries and performed comprehensive miRNA sequencing. Heatmap and principal component analysis revealed markedly different miRNA profiling in cancer, normal ovarian and mature teratoma tissues. Then we narrowed down cancer-related miRNAs, comparing paired-cancer and normal ovaries. Comparisons of cancer and mature teratoma identified two markedly upregulated miRNAs (miR-151a-3p and miR-378a-3p) and two markedly downregulated miRNAs (miR-26a-5p and miR-99a-5p). In addition, these findings were validated in fresh cancer tissues of patient-derived xenograft (PDX) models. Moreover, several miRNAs, including miR-151a-3p and miR-378a-3p, were elevated in the murine plasma when tumor tissues were enlarged although miR-26a-5p and miR-99a-5p were not elucidated in the murine plasma. Finally, we performed target prediction and functional annotation analysis in silico and indicated that targets genes of these miRNAs markedly correlated with cancer-related pathways, including ‘pathway in cancer’ and ‘cell cycle’. In conclusion, this is the first study on miRNA sequencing for squamous cell carcinoma arising from mature teratoma. The study identified four cancer-related miRNAs that were considered to be related to the feature of malignant transformation. Moreover, miRNAs circulating in the murine plasma of the PDX model could be novel diagnostic biomarkers.
An LC-MS/MS Validated Method for Quantification of Chlorzoxazone in Human Plasma and Its Application to a Bioequivalence Study
Authors: He Jiake , Li Ning , Xu Jiaqiu , Zhu Jing , Yu Yang , Chen Xijing , Lu Yang
Published: July 2019

A simple, sensitive, specific, accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for determination of chlorzoxazone in human plasma was developed and validated to evaluate the pharmacokinetic characteristics of chlorzoxazone test or reference formulation. Sample preparation was achieved by one step protein precipitation and dilution with acetontrile. The chromatographic separation was performed at 40°C with a gradient mobile phase (0.3 mL/min) and a Shimadzu VP-ODS C18 analytical column (column size: 150 × 2.0 mm). TSQ quantum access triple-quadrapole MS/MS detection was operated in a negative mode by multiple reaction monitoring. Ion transitions at m/z 168.0→132.1 for chlorzoxazone and m/z 451.3→379.3 for repaglinide (internal standard) were used for the LC-MS/MS analysis. The calibration was linear (r ≥ 0.995) over the tested concentration range of 0.2–20 μg/mL for chlorzoxazone in plasma. Precision, accuracy, recovery, matrix effect and stability for chlorzoxazone were evaluated and were excellent within the range of tested concentrations. This method was successfully applied to a bioequivalence study in 20 healthy Chinese volunteers. This method could also contribute to the personalized medication and therapeutic drug monitoring of chlorzoxazone.
Short-term riparian restoration success measured by territory density and reproductive success of three songbirds along the Trinity River, California
Authors: Stephens Jaime L , Rockwell Sarah M
Published: July 2019

Water crises and endangered salmon are pressing environmental concerns influencing restoration decisions in the western United States. When instream restoration necessitates initial loss of riparian cover to restore floodplain function, a short-term goal to minimize harm to riparian-associated wildlife is a worthwhile benchmark. From 2012 to 2015, we examined short-term restoration success, as measured by territory characteristics and reproductive success in restored and reference sites, for 3 riparian bird species (Song Sparrow [Melospiza melodia], Yellow-breasted Chat [Icteria virens], and Yellow Warbler [Setophaga petechia]) along a 64 km stretch of the Trinity River, California. Territory size had the highest relative variable importance in sets of candidate models explaining territory density for all 3 species, and was inversely related to territory density for each. The effect of site type (i.e. restored vs. reference) in explaining territory density was least for Song Sparrow, greater for Yellow Warbler (for which density was 1.4 times greater on reference sites), and greatest for Yellow-breasted Chat (which were more than twice as dense on reference sites). While territory density and mean territory size were inversely related, we found no relationship between territory density or site type and mean productivity per nest, and nest success did not differ between restored and reference sites for any species. In combination, these results suggest that restoration has achieved short-term success as measured by reproductive success, but has not yet been fully successful in supporting similar territory densities as reference sites. In order to determine whether long-term restoration goals are fully achieved, future research should continue to measure density of the 3 focal species as vegetation on the replanted floodplains matures.
Habitat productivity is a poor predictor of body size in rodents
Authors: Alhajeri Bader H , Porto Lucas M V , Maestri Renan
Published: July 2019

The “resource availability hypothesis” predicts occurrence of larger rodents in more productive habitats. This prediction was tested in a dataset of 1,301 rodent species. We used adult body mass as a measure of body size and normalized difference vegetation index (NDVI) as a measure of habitat productivity. We utilized a cross-species approach to investigate the association between these variables. This was done at both the order level (Rodentia) and at narrower taxonomic scales. We applied phylogenetic generalized least squares (PGLS) to correct for phylogenetic relationships. The relationship between body mas and NDVI was also investigated across rodent assemblages. We controlled for spatial autocorrelation using generalized least squares (GLS) analysis. The cross-species approach found extremely low support for the resource availability hypothesis. This was reflected by a weak positive association between body mass and NDVI at the order level. We find a positive association in only a minority of rodent subtaxa. The best fit GLS model detected no significant association between body mass and NDVI across assemblages. Thus, our results do not support the view that resource availability plays a major role in explaining geographic variation in rodent body size.
Assessment of technical efficiency of public hospitals in Turkey
Authors: Küçük Aziz , Özsoy Volkan Soner , Balkan Dursun
Published: July 2019

Background

Turkish public hospitals have been subjected to health care reform because of increasing cost pressure, inequities in access to health care, poor quality of care and limited patient responsiveness in the last three decades. This study investigates the impact of recent hospital reforms on the efficiency of public hospitals.

Methods

The study provides a comprehensive evaluation of the efficiency of Turkish hospitals by using Data Envelopment Analysis (DEA). The estimation of efficiency of 669 public hospitals of Turkey is performed by an output-oriented model of DEA under the assumption of variable return-to-scale by using data collected from the Ministry of Health (MoH) over the period 2013–17.

Results

The average efficiency score is equal to 0.83 for all MoH hospitals. Considering the hospital type, the efficiency scores of training and research hospitals are higher than those of the general and branch hospitals. In addition, considering the hospital size, huge-scale hospitals have the highest efficiency score in all years. Moreover, overcrowded regions such as Marmara and South-eastern Anatolia regions had higher efficiency scores than other geographical regions.

Conclusions

The results indicate that recent health reforms did not significantly enhance hospital efficiency. Thus, policymakers and managers should take the necessary precautions to increase hospital efficiency.
Kinderreicher familien or familles nombreuses? French pronatalism in interwar Alsace
Authors: Andersen Margaret
Published: July 2019

This article explores the introduction of family policy in Alsace following the Great War and the efforts of local pronatalist leaders to create a new moral order in the region. While French goals of promoting population growth have been well documented at the national level, relatively little attention has been accorded to the unique way in which the demographic question developed outside Paris. The interwar period in France was marked by shifting boundaries and population movements across borders, both of which shaped French pronatalism. Because such developments factored into understandings of both French identity and concerns about population growth, French demographic policy cannot be fully understood without considering how these questions developed in regions such as Alsace. As this article shows, the introduction of a pronatalist family policy and moral crusade intersected with concurrent efforts to minimize German influences and make the region more ‘French’.
Forcing the President's Hand: How the US Congress Shapes Foreign Policy through Sanctions Legislation
Authors: Tama Jordan
Published: July 2019

Given the US president's leading role in many areas of American foreign policy, one might expect the president to prevail in executive-legislative clashes over economic sanctions. In this paper, I show that, with surprising frequency, US legislators overcome presidential opposition to their sanctions proposals and induce the president to take foreign policy actions that he or she would not otherwise take. My argument explains why the president often signs and implements sanctions legislation despite considering it inadvisable, as well as how sanctions legislation can influence foreign policy actions, the behavior of foreign governments, or international diplomacy in other ways. I support the argument with descriptive statistics based on an original data set of over a hundred legislative sanctions proposals and a case study of the effects of legislative initiatives targeting Iran over a period of two decades. The paper's findings show that legislative activity is more important than some previous research on sanctions and US foreign policy suggests.
Systemic pharmacokinetics and safety of high doses of nebulized colistimethate sodium in critically ill patients with hospital-acquired and ventilator-associated pneumonia
Authors: Benítez-Cano Adela , de Antonio-Cuscó Marta , Luque Sonia , Sorlí Luisa , Carazo Jesús , Ramos Isabel , Bermejo Silvia , Campillo Nuria , Horcajada Juan P , Samsó Enric , Grau Santiago
Published: July 2019

Objectives

To assess the pharmacokinetics of formed colistin in plasma and the safety of two different high doses of colistimethate sodium administered via nebulization in critically ill surgical patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP).

Patients and methods

Formed colistin plasma concentrations were measured in critically ill surgical patients with pneumonia treated with two different doses of nebulized colistimethate sodium (3 MIU/8 h versus 5 MIU/8 h). Adverse events possibly related to nebulized colistimethate sodium were recorded.

Results

Twenty-seven patients (15 in the 3 MIU/8 h group and 12 in the 5 MIU/8 h group) were included. Colistin plasma concentrations were unquantifiable (<0.1 mg/L) in eight (53.3%) patients in the 3 MIU/8 h group and in seven patients (58.3%) in the 5 MIU/8 h group. Median (IQR) quantifiable colistin plasma concentrations before nebulization and at 1, 4 and 8 h were 0.17 (0.12–0.33), 0.20 (0.11–0.24), 0.17 (0.12–0.23) and 0.17 (0.11–0.32) mg/L, respectively, in the 3 MIU/8 h group and 0.20 (0.11–0.35), 0.24 (0.12–0.44), 0.24 (0.10–0.49) and 0.23 (0.11–0.44) mg/L, respectively, in the 5 MIU/8 h group, with no differences between the two groups at any time. Renal impairment during nebulized treatment was observed in three patients in each group, but was unlikely to be related to colistimethate sodium treatment. Nebulized colistimethate sodium therapy was well tolerated and no bronchospasms or neurotoxicity events were observed.

Conclusions

In this limited observational case series of critically ill patients with HAP or VAP treated with high doses of nebulized colistimethate sodium, systemic exposure was minimal and the treatment was well tolerated.
Phenotypic and genotypic characterization of linezolid-resistant Enterococcus faecium from the USA and Pakistan
Authors: Wardenburg Kate E , Potter Robert F , D’Souza Alaric W , Hussain Tahir , Wallace Meghan A , Andleeb Saadia , Burnham Carey-Ann D , Dantas Gautam
Published: July 2019

Objectives

Linezolid is an important therapeutic option for the treatment of infections caused by VRE. Linezolid is a synthetic antimicrobial and resistance to this antimicrobial agent remains relatively rare. As a result, data on the comparative genomics of linezolid resistance determinants in Enterococcus faecium are relatively sparse.

Methods

To address this knowledge gap in E. faecium, we deployed phenotypic antibiotic susceptibility testing and Illumina WGS on hospital surface (environmental) and clinical isolates from the USA and Pakistan.

Results

We found complete concordance between isolate source country and mechanism of linezolid resistance, with all the US isolates possessing a 23S rRNA gene mutation and the Pakistan isolates harbouring two to three acquired antibiotic resistance genes. These resistance genes include the recently elucidated efflux-pump genes optrA and poxtA and a novel cfr-like variant. Although there was no difference in the linezolid MIC between the US and Pakistan isolates, there was a significant difference in the geometric mean of the MIC between the Pakistan isolates that had two versus three of the acquired antibiotic resistance genes. In five of the Pakistan E. faecium that possessed all three of the resistance genes, we found no difference in the local genetic context of poxtA and the cfr-like gene, but we identified different genetic contexts surrounding optrA.

Conclusions

These results demonstrate that E. faecium from different geographical regions employ alternative strategies to counter selective pressure of increasing clinical linezolid use.
16 Digestawell® fiber improves in-vitro digestibility of alfalfa and coastal bermudagrass hay fed to horses
Authors: Perron Brittany S , Wagner-Wells Ashley , Boyd Jamie , Girard Ivan , Guiterrez Noheli , Burt Justin C , Splan Rebecca
Published: July 2019

Enhanced microbial activity in the equine hindgut increases nutrient availability, reduces fecal waste, and adds value to low quality forages. The dietary supplement DigestaWell® Fiber (DF; fibrolytic cofactors: methionine and B vitamins), designed to increase microbial efficiency, has been shown to improve in-vitro digestibility of alfalfa and tall fescue forages after 48-h incubation. The objective of this study was to determine if DF would improve in-vitro dry matter digestibility (DMD) and ADF digestibility (ADFD) of alfalfa and coastal bermudagrass hays incubated for 48h or 72h. Utilizing a crossover design, four mature Quarter Horse mares were fed 2% BW daily of alfalfa (AF; 32.8% NDF, 27.1% ADF) or coastal bermudagrass (CB; 63.2% NDF, 35.4% ADF) hay for 19-d periods. DMD and ADFD were determined after 48-h or 72-h incubation with or without treatment (320mg/L DF) at 37.5°C in an ANKOM Daisy II incubator inoculated with 200g fresh feces. Forage samples were run in triplicate. Data were transformed to approximate normality, then analyzed using a repeated measures mixed model in SAS with main effects of forage, treatment, incubation time, and feeding period, and statistically significant interactions. Across incubation times, DMD was higher for AF than CB (P < 0.01; 49.4% vs 42.1%). Across forages, DMD was higher at 72h than at 48h incubation (P < 0.01; 47.5% vs 43.9%). DF improved DMD across forages at 48h (P = 0.03), but not at 72h (P = 0.47). Across incubation times, DF improved DMD of CB (P < 0.01), but not AF (P = 0.79). Additionally, across both forages and both incubation times, DF improved ADFD (P < 0.01). In conclusion, DF may improve microbial fermentation in the equine hindgut. Future research should investigate in-vivo effects of oral supplementation of DF on forage digestibility measures.
80 Effectiveness of naturally sourced mixed tocopherols as an antioxidant when compared to Bha and Bht in fresh pork sausage
Authors: Venzor Leila G , Smith William B , Waddell Jolena N , Kinman Lea A
Published: July 2019

Fresh ground pork products are highly susceptible to deteriorative oxidation due to high fat content and increased surface area exposure of proteins. Recent trends and health concerns among consumers have sparked interest in finding alternatives for synthetic ingredients used for preservation of commercially manufactured processed meats. The objective of this study was to compare the effectiveness of naturally sourced mixed tocopherols to a mixture of butylated hydroxylanisole (BHA) and butylated hydroxytoluene (BHT) on prevention of lipid oxidation and color stability in fresh pork sausage patties. Duplicate batches of pork Boston butt trim and pork back fat were mixed 5:1, respectively, coarse ground, and combined with pork sausage seasoning. Pork mixture was then fine ground and 3175.5 g portions were assigned to one of three treatments: no antioxidants (CON), 0.01% of BHA and 0.01% BHT mixture (SYN), or 0.03% Decanox MTS30P (MTS). Patties (56.7 g) were hand pressed, placed on Styrofoam trays (S4), polyvinyl chloride film overwrapped and positioned in a retail display case. Patties (n = 45) were evaluated for instrumental color (L*, a*, and b*) and display discoloration (1 = very bright, to 8 = tan to brown) in 12-hr intervals for 252 hr. Fifteen patties from each treatment were collected for thiobarbituric acid reactive substance analysis. No differences between treatments (P > 0.05) were found for display discoloration or instrumental color. SYN patties had significantly lower malondialdehyde values (P = 0.047) than both CON and MTS patties at 252 hr. In conclusion, mixed tocopherols were not as effective as synthetic antioxidants in slowing lipid oxidation. However, it can be noted that mixed tocopherols can replace synthetic antioxidants in ground pork sausage and have the same effect on color stability.