bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of a dominant‐negative AtNEET‐H89C protein disrupts iron–sulfur metabolism and iron homeostasis in Arabidopsis
Authors: Zandalinas Sara I. , Song Luhua , Sengupta Soham , McInturf Samuel A. , Grant DeAna G. , Marjault Henri‐Baptiste , Castro‐Guerrero Norma A. , Burks David , Azad Rajeev K. , Mendoza‐Cozatl David G. , Nechushtai Rachel , Mittler Ron 
Published: October 2019

SummaryIron–sulfur (Fe–S) clusters play an essential role in plants as protein cofactors mediating diverse electron transfer reactions. Because they can react with oxygen to form reactive oxygen species (ROS) and inflict cellular damage, the biogenesis of Fe–S clusters is highly regulated. A recently discovered group of 2Fe–2S proteins, termed NEET proteins, was proposed to coordinate Fe–S, Fe and ROS homeostasis in mammalian cells. Here we report that disrupting the function of AtNEET, the sole member of the NEET protein family in Arabidopsis thaliana, triggers leaf‐associated Fe–S‐ and Fe‐deficiency responses, elevated Fe content in chloroplasts (1.2–1.5‐fold), chlorosis, structural damage to chloroplasts and a high seedling mortality rate. Our findings suggest that disrupting AtNEET function disrupts the transfer of 2Fe–2S clusters from the chloroplastic 2Fe–2S biogenesis pathway to different cytosolic and chloroplastic Fe–S proteins, as well as to the cytosolic Fe–S biogenesis system, and that uncoupling this process triggers leaf‐associated Fe–S‐ and Fe‐deficiency responses that result in Fe over‐accumulation in chloroplasts and enhanced ROS accumulation. We further show that AtNEET transfers its 2Fe–2S clusters to DRE2, a key protein of the cytosolic Fe–S biogenesis system, and propose that the availability of 2Fe–2S clusters in the chloroplast and cytosol is linked to Fe homeostasis in plants.
Successful treatment of a severe cannabinoid toxicity using extracorporeal therapy in a dog
Authors: Culler Christine A. , Vigani Alessio 
Published: October 2019

AbstractObjectiveTo describe the use of extracorporeal therapy (ECT) to treat severe cannabinoid intoxication in a dog with severe hyperlipidemia.Case SummaryA 7‐month‐old female intact Labrador Retriever presented with seizures and severe hyperesthesia that were refractory to multiple anticonvulsant medications and required induction of general anesthesia with propofol and mechanical ventilation. The dog's urine yielded a strong positive signal for delta‐9‐tetrahydrocannabinol (THC) on urine drug test and exposure to THC oil was confirmed by the owner. Bloodwork revealed severe hyperlipidemia such that IV lipid emulsion was considered contraindicated. The dog was treated with a 3‐hour ECT session, using charcoal hemoperfusion and hemodialysis in series. Neurologic signs improved during the session and mechanical ventilation was discontinued. Immediately after the session, the dog's mentation was significantly improved and seizures and hyperesthesia had ceased, although the dog remained moderately ataxic. The dog was hospitalized for 36 hours following the ECT session for continued monitoring. The dog fully recovered and was successfully discharged.New or Unique Information ProvidedTo the authors’ knowledge, this is the first published report to document ECT to treat THC intoxication in veterinary medicine. ECT may be considered as a treatment option for severe THC intoxication that is refractory to standard therapy or where severe hyperlipidemia precludes use of IV lipid emulsions.
Blood donation and donors: insights from a large German teaching hospital (2008–2017)
Authors: Chandler Torsten , Hiller Jens , Peine Sven , Stargardt Tom 
Published: October 2019

Background and objectivesThe availability of blood and blood products is crucial for the provision of high‐quality hospital services. We analyse changes in whole blood donations, donors and their behaviour over 9 years at a large German teaching hospital.Materials and methodsA descriptive analysis using data from over 34 000 donors and 265 000 donations from a large university hospital’s blood centre was conducted using data from July 2008 to December 2017. The analysis focussed on (a) whole blood donations and (b) donor characteristics and how they changed over time. We categorized donors into four categories according to their donation activity (First‐Time, Highly Active, Active and Reactivated).ResultsWe observed falling donations over time and that donors donated less frequently. Consequently, we show a downward trend in the number of Highly Active donors, whilst First‐Time donors remained stable. We also provide evidence that donors donated well below their capacity and that the blood type of donors appeared to be in line with the wider German donor population. Lastly, we show a sharp drop in the return rates of First‐Time donors over time.ConclusionWe recommend that Highly Active donors and former Highly Active donors are more carefully considered when planning donor engagement strategies and effort made in (at the very least) maintaining their donation activity. Our results in the context of the literature highlight the need for further research into the changing attitudes towards blood donation and prosocial activities.
Thermoacoustic Spectrum of a Swirled Premixed Combustor With Partially Reflecting Boundaries
Authors: Yong Kah Joon , Meindl Maximilian , Polifke Wolfgang , Silva Camilo F. 
Published: October 2019

Abstract
This study investigates the effect of partial acoustic reflection at inlet or outlet of a combustor on thermoacoustic stability. Parametric maps of the thermoacoustic spectrum are utilized for this purpose, which represent frequencies and growth rates of eigenmodes for a wide range of model parameters. It is found that a decrease of the acoustic reflection at the boundaries does not always imply an increase in the stability margin of the thermoacoustic system. As a matter of fact, a reduction in the acoustic reflection may sometimes destabilize a thermoacoustic mode. Additionally, we show that perturbed passive thermoacoustic modes may become intrinsic thermoacoustic (ITA) modes in the fully anechoic case. We briefly discuss the mode definitions “acoustic” and “intrinsic” commonly found in the literature. The computational analysis is based on a state-space formulation of the linearized Navier–Stokes equations (LNSEs) with discontinuous Galerkin discretization. This approach allows to describe the thermoacoustic system as a linear combination of internal acoustics, flame dynamics, and acoustic boundaries. Such a segregation grants a clear analysis of the respective effects of the individual subsystems on the general stability of the system, expressed in terms of adjoint-based eigenvalue sensitivity. The state-space formulation of the LNSE proposed in this paper offers a powerful and flexible framework to carry out thermoacoustic studies of combustors with arbitrary geometry and acoustic boundary conditions.
Personalise antidepressant treatment for unipolar depression combining individual choices, risks and big data (PETRUSHKA): rationale and protocol
Authors: Tomlinson Anneka , Furukawa Toshi A , Efthimiou Orestis , Salanti Georgia , De Crescenzo Franco , Singh Ilina , Cipriani Andrea 
Published: October 2019

IntroductionMatching treatment to specific patients is too often a matter of trial and error, while treatment efficacy should be optimised by limiting risks and costs and by incorporating patients’ preferences. Factors influencing an individual’s drug response in major depressive disorder may include a number of clinical variables (such as previous treatments, severity of illness, concomitant anxiety etc) as well demographics (for instance, age, weight, social support and family history). Our project, funded by the National Institute of Health Research, is aimed at developing and subsequently testing a precision medicine approach to the pharmacological treatment of major depressive disorder in adults, which can be used in everyday clinical settings.Methods and analysisWe will jointly synthesise data from patients with major depressive disorder, obtained from diverse datasets, including randomised trials as well as observational, real-world studies. We will summarise the highest quality and most up-to-date scientific evidence about comparative effectiveness and tolerability (adverse effects) of antidepressants for major depressive disorder, develop and externally validate prediction models to produce stratified treatment recommendations. Results from this analysis will subsequently inform a web-based platform and build a decision support tool combining the stratified recommendations with clinicians and patients’ preferences, to adapt the tool, increase its’ reliability and tailor treatment indications to the individual-patient level. We will then test whether use of the tool relative to treatment as usual in real-world clinical settings leads to enhanced treatment adherence and response, is acceptable to clinicians and patients, and is economically viable in the UK National Health Service.DiscussionThis is a clinically oriented study, coordinated by an international team of experts, with important implications for patients treated in real-world setting. This project will form a test-case that, if effective, will be extended to non-pharmacological treatments (either face-to-face or internet-delivered), to other populations and disorders in psychiatry (for instance, children and adolescents, or schizophrenia and treatment-resistant depression) and to other fields of medicine.
Coronary wave intensity patterns in stable coronary artery disease: influence of stenosis severity and collateral circulation
Authors: deMarchi Stefano F , Gassmann Christian , Traupe Tobias , Gloekler Steffen , Cook Stéphane , Vogel Rolf , Gysi Kurt , Seiler Christian 
Published: October 2019

ObjectiveWave intensity analysis is a method that allows separating pulse waves into components generated proximally and in the periphery of arterial trees, as well as characterising them as accelerating or decelerating. The early diastolic suction wave (eaDSW) is one of the most prominent wave events in the coronaries. The aim of this study was to determine whether (1) microvascular dilatation directly influences its energy, (2) stenosis severity can be assessed proximal to stenoses, (3) distal pulse wave entrapment exists in the presence of stenoses and (4) coronary collaterals influence wave entrapment.MethodsIn 43 coronary artery disease patients, Doppler flow velocity and pressure measurements were performed in a proximal coronary segment at rest, in a distal segment at rest, during adenosine-induced hyperaemia and during balloon occlusion. Wave energies were calculated as the area under the wave intensity curves.ResultsThe eaDSW energy showed a significant increase during hyperaemia, but did not differ between proximal and distal segments. There was no significant correlation between eaDSW energy and coronary stenosis severity. Pulse wave entrapment could not be observed consistently in the distal segments. Consequently, the effect of coronary collaterals on pulse wave entrapment could not be studied.ConclusionsMicrovascular dilation in the coronary circulation increases distal eaDSW energy. However, it does not show any diagnostically useful variation between measurement sites, various stenosis degrees and amount of collateral flow. The assessment eaDSW and its reflections were not useful for the quantification of coronary stenosis severity or the collateral circulation in clinical practice.
Pauli–Villars regularization elucidated in Bopp–Podolsky’s generalized electrodynamics
Authors: Ji Chueng-Ryong , Takashi Suzuki Alfredo , Henrique Sales Jorge , Thibes Ronaldo 
Published: October 2019

Abstract
We discuss an inherent Pauli–Villars regularization in Bopp–Podolsky’s generalized electrodynamics. Introducing gauge-fixing terms for Bopp–Podolsky’s generalized electrodynamic action, we realize a unique feature for the corresponding photon propagator with a built-in Pauli–Villars regularization independent of the gauge choice made in Maxwell’s usual electromagnetism. According to our realization, the length dimensional parameter a associated with Bopp–Podolsky’s higher order derivatives corresponds to the inverse of the Pauli–Villars regularization mass scale $$\Lambda $$Λ, i.e. $$a = 1/\Lambda $$a=1/Λ. Solving explicitly the classical static Bopp–Podolsky’s equations of motion for a specific charge distribution, we explore the physical meaning of the parameter a in terms of the size of the charge distribution. As an offspring of the generalized photon propagator analysis, we also discuss our findings regarding on the issue of the two-term vs. three-term photon propagator in light-front dynamics.
An improved test of the general relativistic effect of frame-dragging using the LARES and LAGEOS satellites
Authors: Ciufolini Ignazio , Paolozzi Antonio , Pavlis Erricos C. , Sindoni Giampiero , Ries John , Matzner Richard , Koenig Rolf , Paris Claudio , Gurzadyan Vahe , Penrose Roger 
Published: October 2019

Abstract
We report the improved test of frame-dragging, an intriguing phenomenon predicted by Einstein’s General Relativity, obtained using 7 years of Satellite Laser Ranging (SLR) data of the satellite LARES (ASI, 2012) and 26 years of SLR data of LAGEOS (NASA, 1976) and LAGEOS 2 (ASI and NASA, 1992). We used the static part and temporal variations of the Earth gravity field obtained by the space geodesy mission GRACE (NASA and DLR) and in particular the static Earth’s gravity field model GGM05S augmented by a model for the 7-day temporal variations of the lowest degree Earth spherical harmonics. We used the orbital estimator GEODYN (NASA). We measured frame-dragging to be equal to $$0.9910 \pm 0.02$$0.9910±0.02, where 1 is the theoretical prediction of General Relativity normalized to its frame-dragging value and $$\pm 0.02$$±0.02 is the estimated systematic error due to modelling errors in the orbital perturbations, mainly due to the errors in the Earth’s gravity field determination. Therefore, our measurement confirms the prediction of General Relativity for frame-dragging with a few percent uncertainty.
Efferent modulation of spontaneous lateral line activity during and after zebrafish motor commands
Authors: Lunsford Elias T. , Skandalis Dimitri A. , Liao James C. 
Published: October 2019

Accurate sensory processing during movement requires the animal to distinguish between external (exafferent) and self-generated (reafferent) stimuli to maintain sensitivity to biologically relevant cues. The lateral line system in fishes is a mechanosensory organ that experiences reafferent sensory feedback, via detection of fluid motion relative to the body generated during behaviors such as swimming. For the first time in larval zebrafish ( Danio rerio), we employed simultaneous recordings of lateral line and motor activity to reveal the activity of afferent neurons arising from endogenous feedback from hindbrain efferent neurons during locomotion. Frequency of spontaneous spiking in posterior lateral line afferent neurons decreased during motor activity and was absent for more than half of swimming trials. Targeted photoablation of efferent neurons abolished the afferent inhibition that was correlated to swimming, indicating that inhibitory efferent neurons are necessary for modulating lateral line sensitivity during locomotion. We monitored calcium activity with Tg(elav13:GCaMP6s) fish and found synchronous activity between putative cholinergic efferent neurons and motor neurons. We examined correlates of motor activity to determine which may best predict the attenuation of afferent activity and therefore what components of the motor signal are translated through the corollary discharge. Swim duration was most strongly correlated to the change in afferent spike frequency. Attenuated spike frequency persisted past the end of the fictive swim bout, suggesting that corollary discharge also affects the glide phase of burst and glide locomotion. The duration of the glide in which spike frequency was attenuated increased with swim duration but decreased with motor frequency. Our results detail a neuromodulatory mechanism in larval zebrafish that adaptively filters self-generated flow stimuli during both the active and passive phases of locomotion.NEW & NOTEWORTHY For the first time in vivo, we quantify the endogenous effect of efferent activity on afferent gain control in a vertebrate hair cell system during and after locomotion. We believe that this pervasive effect has been underestimated when afferent activity of octavolateralis systems is characterized in the current literature. We further identify a refractory period out of phase with efferent control and place this gain mechanism in the context of gliding behavior of freely moving animals.
Neoadjuvant PD-1 Immune Checkpoint Blockade Reverses Functional Immunodominance among Tumor Antigen–Specific T Cells
Authors: Friedman Jay , Moore Ellen C. , Zolkind Paul , Robbins Yvette , Clavijo Paul E. , Sun Lilian , Greene Sarah , Morisada Megan V. , Mydlarz Wojciech K. , Schmitt Nicole , Hodge James W. , Schreiber Hans , Van Waes Carter , Uppaluri Ravindra , Allen Clint 
Published: October 2019

AbstractPurpose:Surgical resection of primary tumor with regional lymphadenectomy remains the treatment of choice for patients with advanced human papillomavirus–negative head and neck squamous cell carcinoma. However, even when pathologic disease-free margins can be achieved, locoregional and/or distant disease relapse remains high. Perioperative immunotherapy may improve outcomes, but mechanistic data supporting the use of neoadjuvant or adjuvant treatment clinically are sparse.Experimental Design:Two syngeneic models of oral cavity carcinoma with defined T-cell antigens were treated with programmed death receptor 1 (PD-1) mAb before or after surgical resection of primary tumors, and antigen-specific T-cell responses were explored with functional and in vivo challenge assays.Results:We demonstrated that functional immunodominance developed among T cells targeting multiple independent tumor antigens. T cells specific for subdominant antigens expressed greater levels of PD-1. Neoadjuvant, but not adjuvant, PD-1 immune checkpoint blockade broke immunodominance and induced T-cell responses to dominant and subdominant antigens. Using tumors lacking the immunodominant antigen as a model of antigen escape, neoadjuvant PD-1 immune checkpoint blockade induced effector T-cell immunity against tumor cells lacking immunodominant but retaining subdominant antigen. When combined with complete surgical excision, neoadjuvant PD-1 immune checkpoint blockade led to formation of immunologic memory capable of preventing engraftment of tumors lacking the immunodominant but retaining subdominant antigen.Conclusions:Together, these results implicate PD-1 expression by T cells in the mechanism of functional immunodominance among independent T-cell clones within a progressing tumor and support the use of neoadjuvant PD-1 immune checkpoint blockade in patients with surgically resectable carcinomas.
ОЦІНКА ДІЯЛЬНОСТІ ГАСТРОЕНТЕРОЛОГІЧНОЇ СЛУЖБИ У ВІННИЦЬКІЙ ОБЛАСТІ ЗА 2016–2018 рр.
Authors: Komar O. M. , Kizlova N. M. 
Published: October 2019

Мета: оцінити діяльність гастроентерологічної служби у Вінницькій області за 2016–2018 рр. шляхом вивчення регіональних трендів поширеності, захворюваності, госпіталізації й летальності від хвороб органів травлення (ХОТ).
Матеріали і методи. Для оцінки діяльності гастроентерологічної служби у Вінницькій області обрано такі тренди: поширеність, захворюваність, рівень госпіталізації та летальності від хвороб органів травлення з поглибленим їх аналізом за нозологічними формами. Віковим контингентом для дослідження виокремлено доросле населення регіону. Аналізу та статистичній обробці підлягали дані, взяті з національної електронної медичної інформаційної системи eHealth. Методи дослідження – епідеміологічний, медико-статистичний.
Результати. Оцінка регіональних трендів поширеності й захворюваності хвороб органів травлення на 10 000 до­рослого населення виявила щорічне їх зниження, особливо вперше виявлених захворювань, показник наочності якого склав (-) 16,9 % (з 233,0 у 2016 р. до 193,7 у 2018 р.), поширеність ХОТ – (-) 8,93 % (з 2261,1 до 2059,2 відповідно).
Відзначено зростання частоти госпіталізації ХОТ за п’ятьма нозологічними формами (за показником наочності): диспепсія – (+) 30,28 %, проривна виразка шлунка та дванадцятипалої кишки – (+) 19,38 %, гастроезофагеальний рефлюкс – (+) 18,12 %, жовчнокам’яна хвороба, холецистит, холангіт – (+) 10,8 %, цироз печінки – (+) 8,95 %.
з’ясовано, що темп росту рівня летальності від ХОТ у 2018 р. до попереднього склав (+) 101,6 % (з 1,25 до 1,27), у тому числі за нозологічними формами: жовчнокам’яна хвороба, холецистит, холангіт – (+) 110,5 %, виразка шлунка та дванадцятипалої кишки – (+) 103,8 %, цироз печінки – (+) 102,5 %.
Висновки. Досліджені тренди поширеності, захворюваності, госпіталізації та летальності від хвороб органів травлення довели накопичення обтяженої ресурсомісткої хронічної патології шлунково-кишкового тракту та гепатобіліарної системи, вартість медичних процедур яких є найвищою. Причиною існуючої тенденції у розповсюдженні ХОТ є поєднаний вплив несприятливих чинників державного, системного й індивідуального характеру, які призводять до щорічного погіршення стану здоров’я населення України.
ВИКОРИСТАННЯ БІОСЕНСОРІВ ДЛЯ МОНІТОРИНГУ НАВКОЛИШНЬОГО СЕРЕДОВИЩА
Authors: Martsenyuk V. P. , Zhulkevych I. V. , Sverstiuk A. S. , Melnyk N. A. , Kozodii N. V. , Berezovska I. B. 
Published: October 2019

Мета: розглянути класифікацію біосенсорів (за типом перетворювача), принцип їх роботи, галузі застосування біосенсорів залежно від виду забруднювачів навколишнього середовища та основні напрямки подальшого розвитку біосенсорних технологій.
Матеріали і методи. У дослідженні застосовано бібліосемантичний та аналітичний методи.
Результати. Біосенсор є портативним аналітичним пристроєм, що складається з чутливого елемента біологічного походження та фізико-хімічного перетворювача. Його устаткування має такі компоненти: біорецептор, перетворювач, процесор сигналу на виході. Біосенсори класифікуються відповідно до біорецептора (ферменти, імуноафінність, ДНК і цілі мікробні клітини) чи перетворювача (електрохімічний, оптичний, п’єзоелектричний, електрохімічний та тепловий біосенсори). Як біосенсори, так і біологічні прилади можна використовувати як інструменти контролю параметрів навколишнього середовища – для оцінки фізичного, хімічного та біологічного моніторингу забруднювальних речовин у довкіллі. Основні програми біосенсорів призначено для виявлення та контролю різних забруднювальних речовин, включно солі важких металів, органічні та неорганічні забруднювачі, токсини, антибіотики і мікроорганізми.
Висновки. Застосування сучасних нанотехнологічних біосенсорів має великий потенціал для екологічного моніторингу та для виявлення забруднювальних речовин, оскільки дані біологічні пристрої є портативними і дають змогу проводити вимірювання в режимі реального часу. Принцип роботи біосенсора ґрунтується на здатності фіксування біологічного матеріалу, відбувається за допомогою фізичного або мембранного захоплення, нековалентних або ковалентних зв’язків.