bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recommendations on dose level selection for repeat dose toxicity studies
Authors: Sewell Fiona , Corvaro Marco , Andrus Amanda , Burke Jonathan , Daston George , Delaney Bryan , Domoradzki Jeanne , Forlini Carole , Green Maia Louise , Hofmann Thomas , Jäckel Sven , Lee Moung Sook , Temerowski Michael , Whalley Paul , Lewis Richard 
Published: April 2022

AbstractPrior to registering and marketing any new pharmaceutical, (agro)chemical or food ingredient product manufacturers must, by law, generate data to ensure human safety. Safety testing requirements vary depending on sector, but generally repeat-dose testing in animals form the basis for human health risk assessments. Dose level selection is an important consideration when designing such studies, to ensure that exposure levels that lead to relevant hazards are identified. Advice on dose level selection is provided in test guidelines and allied guidance documents, but it is not well harmonised, particularly for selection of the highest dose tested. This paper further builds on concepts developed in a technical report by the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) which recommends pragmatic approaches to dose selection considering regulatory requirements, animal welfare and state of the art scientific approaches. Industry sectors have differing degrees of freedom to operate regarding dose level selection, depending on the purpose of the studies and the regulatory requirements/legislation, and this is reflected in the overall recommended approaches. An understanding of systemic exposure should be utilised where possible (e.g., through toxicokinetic approaches) and used together with apical endpoints from existing toxicity studies to guide more appropriate dose level selection. The highest dose should be limited to a reasonable level, causing minimal but evident toxicity to the test animals without significantly compromising their well-being. As the science of predictive human exposure further develops and matures, this will provide exciting and novel opportunities for more human-relevant approaches to dose level selection.
Tissue-resident immunity in the female and male reproductive tract
Authors: Yüzen Dennis , Arck Petra Clara , Thiele Kristin 
Published: April 2022

AbstractThe conception of how the immune system is organized has been significantly challenged over the last years. It became evident that not all lymphocytes are mobile and recirculate through secondary lymphoid organs. Instead, subsets of immune cells continuously reside in tissues until being reactivated, e.g., by a recurring pathogen or other stimuli. Consequently, the concept of tissue-resident immunity has emerged, and substantial evidence is now available to support its pivotal function in maintaining tissue homeostasis, sensing challenges and providing antimicrobial protection. Surprisingly, insights on tissue-resident immunity in the barrier tissues of the female reproductive tract are sparse and only slowly emerging. The need for protection from vaginal and amniotic infections, the uniqueness of periodic tissue shedding and renewal of the endometrial barrier tissue, and the demand for a tailored decidual immune adaptation during pregnancy highlight that tissue-resident immunity may play a crucial role in distinct compartments of the female reproductive tract. This review accentuates the characteristics of tissue-resident immune cells in the vagina, endometrium, and the decidua during pregnancy and discusses their functional role in modulating the risk for infertility, pregnancy complications, infections, or cancer. We here also review data published to date on tissue-resident immunity in the male reproductive organs, which is still a largely uncharted territory.
Intensity standardization of MRI prior to radiomic feature extraction for artificial intelligence research in glioma—a systematic review
Authors: Fatania Kavi , Mohamud Farah , Clark Anna , Nix Michael , Short Susan C. , O’Connor James , Scarsbrook Andrew F. , Currie Stuart 
Published: April 2022

Abstract
Objectives
Radiomics is a promising avenue in non-invasive characterisation of diffuse glioma. Clinical translation is hampered by lack of reproducibility across centres and difficulty in standardising image intensity in MRI datasets. The study aim was to perform a systematic review of different methods of MRI intensity standardisation prior to radiomic feature extraction.

Methods
MEDLINE, EMBASE, and SCOPUS were searched for articles meeting the following eligibility criteria: MRI radiomic studies where one method of intensity normalisation was compared with another or no normalisation, and original research concerning patients diagnosed with diffuse gliomas. Using PRISMA criteria, data were extracted from short-listed studies including number of patients, MRI sequences, validation status, radiomics software, method of segmentation, and intensity standardisation. QUADAS-2 was used for quality appraisal.

Results
After duplicate removal, 741 results were returned from database and reference searches and, from these, 12 papers were eligible. Due to a lack of common pre-processing and different analyses, a narrative synthesis was sought. Three different intensity standardisation techniques have been studied: histogram matching (5/12), limiting or rescaling signal intensity (8/12), and deep learning (1/12)—only two papers compared different methods. From these studies, histogram matching produced the more reliable features compared to other methods of altering MRI signal intensity.

Conclusion
Multiple methods of intensity standardisation have been described in the literature without clear consensus. Further research that directly compares different methods of intensity standardisation on glioma MRI datasets is required.

Key Points
• Intensity standardisation is a key pre-processing step in the development of robust radiomic signatures to evaluate diffuse glioma.
• A minority of studies compared the impact of two or more methods.
• Further research is required to directly compare multiple methods of MRI intensity standardisation on glioma datasets.
Application of PREVENA (Surgical Incision Protection System) in reducing surgical site infections following reversal of ileostomy or colostomy: the PRIC study protocol
Authors: Low Ernest Z. , Nugent Timothy S. , O’Sullivan Niall J. , Kavanagh Dara , Larkin John O. , McCormick Paul H. , Mehigan Brian J. , Kelly Michael E. 
Published: April 2022

Abstract
Aim
There is a current lack of evidence in the literature to support the routine use of negative pressure wound therapy (NPWT) to reduce the risk of surgical site infections (SSI) in the setting of ileostomy or colostomy reversal. The aim of this study is to examine whether routine NPWT confers a lower rate of SSI than conventional dressings following reversal of ileostomy or colostomy.

Methods
The PRIC study is a randomized, controlled, open-label, multi-centre superiority trial to assess whether routine NPWT following wound closure confers a lower rate of SSI following reversal of ileostomy or colostomy when compared to conventional dressings. Participants will be consecutively identified and recruited. Eligible participants will be randomized in a 1:1 allocation ratio, to receive either the NPWT (PREVENA) dressings or conventional dressings which will be applied immediately upon completion of surgery. PREVENA dressings will remain applied for a duration of 7 days. Surgical wounds will then be examined on post-operative day seven as well as during follow-up appointments in OPD for any evidence of SSI. In the interim, public health nurses (PHN) will provide out-patient support services incorporating wound assessment and care as part of a routine basis. Study investigators will liaise with PHN to gather the relevant data in relation to the time to wound healing. Our primary endpoint is the incidence of SSI within 30 days of stoma reversal. Secondary endpoints include measuring time to wound healing, evaluating wound healing and aesthetics and assessing patient satisfaction.

Conclusion
The PRIC study will assess whether routine NPWT following wound closure is superior to conventional dressings in the reduction of SSI following reversal of ileostomy or colostomy and ascertain whether routine NPWT should be considered the new standard of care.
Impact of early ablation of atrial fibrillation on long-term outcomes: results from phase II/III of the GLORIA-AF registry
Authors: Ding Wern Yew , Calvert Peter , Gupta Dhiraj , Huisman Menno V. , Lip Gregory Y. H. ,   the GLORIA-AF Investigators
Published: April 2022

Abstract
Background
First-line ablation for atrial fibrillation (AF) reduces the risk of recurrent atrial arrhythmias compared to medical therapy. However, the prognostic benefit of early AF ablation remains undetermined. Herein, we aimed to evaluate the effects of early AF ablation compared to medical therapy.

Methods
Using data from phase II/III of the GLORIA-AF registry, we studied patients who were consecutively enrolled with newly diagnosed AF (< 3 months before baseline visit) and an increased risk of stroke (CHA2DS2–VASc ≥ 1). At baseline visit, 445 (1.7%) patients were treated with early AF ablation and 25,518 (98.3%) with medical therapy. Outcomes of interest were the composite outcome of all-cause death, stroke and major bleeding, and pre-specified outcomes of all-cause death, cardiovascular (CV) death, non-CV death, stroke and major bleeding.

Results
A total of 25,963 patients (11733 [45.2%] females; median age 71 [IQR 64–78] years; 17424 [67.1%] taking non-vitamin K antagonist oral anticoagulants [NOACs]) were included. Over a follow-up period of 3.0 (IQR 2.3–3.1) years, after adjustment for confounders, early AF ablation was associated with a significant reduction in the composite outcome of all-cause death, stroke and major bleeding (HR 0.50 [95% CI 0.30–0.85]) and all-cause death (HR 0.45 [95% CI 0.23–0.91]). There were no statistical differences between the groups in terms of CV death, non-CV death, stroke and major bleeding. Similar results were obtained in a propensity-score matched analysis of patients with comparable baseline variables.

Conclusions
Early AF ablation in a contemporary prospective cohort of AF patients who were predominantly treated with NOACs was associated with a survival advantage compared to medical therapy alone.

Trial registration
Clinical trial registration: http://www.clinicaltrials.gov. Unique identifiers: NCT01468701, NCT01671007 and NCT01937377.

Graphical abstract

Created with BioRender.com.
Optogenetic manipulation of cardiac electrical dynamics using sub-threshold illumination: dissecting the role of cardiac alternans in terminating rapid rhythms
Authors: Biasci V. , Santini L. , Marchal G. A. , Hussaini S. , Ferrantini C. , Coppini R. , Loew L. M. , Luther S. , Campione M. , Poggesi C. , Pavone F. S. , Cerbai E. , Bub G. , Sacconi L. 
Published: April 2022

AbstractCardiac action potential (AP) shape and propagation are regulated by several key dynamic factors such as ion channel recovery and intracellular Ca2+ cycling. Experimental methods for manipulating AP electrical dynamics commonly use ion channel inhibitors that lack spatial and temporal specificity. In this work, we propose an approach based on optogenetics to manipulate cardiac electrical activity employing a light-modulated depolarizing current with intensities that are too low to elicit APs (sub-threshold illumination), but are sufficient to fine-tune AP electrical dynamics. We investigated the effects of sub-threshold illumination in isolated cardiomyocytes and whole hearts by using transgenic mice constitutively expressing a light-gated ion channel (channelrhodopsin-2, ChR2). We find that ChR2-mediated depolarizing current prolongs APs and reduces conduction velocity (CV) in a space-selective and reversible manner. Sub-threshold manipulation also affects the dynamics of cardiac electrical activity, increasing the magnitude of cardiac alternans. We used an optical system that uses real-time feedback control to generate re-entrant circuits with user-defined cycle lengths to explore the role of cardiac alternans in spontaneous termination of ventricular tachycardias (VTs). We demonstrate that VT stability significantly decreases during sub-threshold illumination primarily due to an increase in the amplitude of electrical oscillations, which implies that cardiac alternans may be beneficial in the context of self-termination of VT.
Opinion paper: gynecological surgery in local anesthesia?
Authors: Neis Felix , Wallwiener Diethelm , Henes Melanie , Krämer Bernhard , Brucker Sara 
Published: April 2022

Abstract
Purpuse
The paracervical block (PCB) is a local anesthesia procedure that can be used to perform gynecological surgeries without the need for further anesthesia. With the PCB, surgeries can be moved from the central operating room to outpatient operating rooms, where they can be performed without the presence of an anesthesia team.

Methods
In this paper, the indications, implementation and limitations of the procedure are discussed.

Conclusion
Especially in times of scarce staff and OR resources during the Corona pandemic, OR capacity can be expanded in this way.
Organelle-specific localization of glutathione in plants grown under different light intensities and spectra
Authors: Gasperl Anna , Zellnig Günther , Kocsy Gábor , Müller Maria 
Published: April 2022

AbstractPlant ascorbate and glutathione metabolism counteracts oxidative stress mediated, for example, by excess light. In this review, we discuss the properties of immunocytochemistry and transmission electron microscopy, redox-sensitive dyes or probes and bright-field microscopy, confocal microscopy or fluorescence microscopy for the visualization and quantification of glutathione at the cellular or subcellular level in plants and the quantification of glutathione from isolated organelles. In previous studies, we showed that subcellular ascorbate and glutathione levels in Arabidopsis are affected by high light stress. The use of light-emitting diodes (LEDs) is gaining increasing importance in growing indoor crops and ornamental plants. A combination of different LED types allows custom-made combinations of wavelengths and prevents damage related to high photon flux rates. In this review we provide an overview on how different light spectra and light intensities affect glutathione metabolism at the cellular and subcellular levels in plants. Findings obtained in our most recent study demonstrate that both light intensity and spectrum significantly affected glutathione metabolism in wheat at the transcriptional level and caused genotype-specific reactions in the investigated Arabidopsis lines.
T-shaped micromixers aligned in a row: characterization of the engulfment regime
Authors: Camarri Simone 
Published: April 2022

AbstractAccurate control of mixing between two fluids is a fundamental aspect in many applications and generally implies the use of small devices operating at low velocities. This is often achieved using micromixers which, due to the combination of small dimensions and low velocities, work in the laminar regime and generally process very limited flow rates. The flow rates can be increased using more mixers at the same time. In this respect it is appealing to use several micromixers connected in a unique device. In this paper we propose and characterize a simple strategy to connect several T-mixers together by aligning them in a row and feeding them by shared inlet channels. Since engulfment is the preferred flow regime for mixing, we investigate the proposed devices specifically focusing on the onset and on the properties of the engulfment regime. This investigation is carried out by a combined use of numerical simulation and linear stability analysis. The results reported here show that the proposed strategy can lead to compact devices in which the single mixers manifest engulfment, although some important differences in comparison with isolated T-mixers may exist depending on the spacing between the inlet/outlet channels in the device.
Das unerwartet kritisch kranke Kind in der Kindernotfallaufnahme: Sind wir vorbereitet?
Authors: Mohrmann Chris , Lange Matthias , Rosner Bastian , Heep Axel , Warnecke Tobias 
Published: April 2022

ZusammenfassungHintergrundDas unerwartete Eintreffen eines kritisch kranken Kindes, ohne vorherige rettungsdienstliche Versorgung oder Anmeldung, stellt in der Kindernotaufnahme eine seltene Fallkonstellation dar, wodurch entsprechende Routine bei der Versorgung fehlen kann. Eine Erhöhung der Handlungssicherheit kann durch Anwendung einer Prozessrisikoanalyse gelingen, welche als etablierte Methode des klinischen Risikomanagements Abläufe präventiv nach möglichen Risiken der bestehenden (Behandlungs‑)Prozesse untersucht und abwehrende Maßnahmen ableitbar macht.MethodeDie Prozessrisikoanalyse soll exemplarisch anhand des Beispiels „Unerwartete Versorgung eines kritisch kranken Kindes“ durchgeführt und vorgestellt werden. Eine kleinteilige Aufgliederung in Haupt- und Teilabschnitte erlaubt die Erstellung eines prozessbezogenen Risikoprofils, auf Grundlage dessen eine Priorisierung von Risiken nach Kriterien wie Eintrittswahrscheinlichkeit und potenziellem Schadensausmaß vorgenommen wird. Dadurch werden abwehrende Maßnahmen nach Dringlichkeit ableitbar, welche den hier untersuchten Patientenpfad optimieren können.SchlussfolgerungDurch Prozessrisikoanalysen von klinischen Abläufen können bestehende Risiken detektiert und potenzielle Maßnahmen zur Reduktion dargestellt werden. Für den exemplarisch beschriebenen Fall konnten vier prozessbezogene Hauptrisiken (Untertriagierung, Fehl‑/Nichtdiagnostik, Fehler in Medikation und Auswahl von Devices, unzureichende Infrastruktur und interdisziplinäre Abstimmung) aufgezeigt werden. Daraus folgend wurden potenziell abwehrende Maßnahmen beschrieben und die notwendigen Ressourcen abgeschätzt.
Plasma arylsulfatase A levels are associated with cognitive function in Parkinson’s disease
Authors: Li Mingjian , Shi Xiaoxue , Ma Jianjun , Sun Wenhua , Wang Zhidong , Li Dongsheng , Zheng Jinhua , Zhao Zhenxiang , Gu Qi , Chen Siyuan 
Published: April 2022

Abstract

Background
Arylsulfatase A (ARSA), a lysosomal enzyme, has been shown to inhibit the aggregation and propagation of α-synuclein (α-syn) through its molecular chaperone function. The relationship between ARSA levels and Parkinson’s disease (PD) in the Chinese Han population remains controversial, and few quantitative research studies have investigated the relationship between plasma ARSA levels and PD.

Objectives
The purpose of this study was to investigate the relationships between ARSA levels and cognitive function in PD patients and to evaluate the association of ARSA and α-syn levels with nonmotor symptoms.

Methods
Enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma ARSA and α-syn levels in 50 healthy controls, 120 PD patients (61 PD patients with no cognitive impairment (PD-NCI) and 59 PD patients with cognitive impairment (PD-CI)). Motor symptoms and nonmotor symptoms (cognitive function, Unified Parkinson’s Disease Rating Scale (UPDRS) score, depression, anxiety, constipation, olfactory dysfunction, sleep disruption, and other symptoms) were assessed with the relevant scales. The Kruskal–Wallis H test was used for comparison between groups, and Pearson/Spearman analysis was used for correlation analysis.

Results
The plasma ARSA concentrations were lower in the PD-CI group than in the PD-NCI group. The plasma α-syn levels in the PD-CI group were higher than those in the healthy control group, and the plasma ARSA levels were correlated with the Mini-Mental State Examination (MMSE scores) and Hoehn and Yahr (H-Y) stage.

Conclusion
We used a quantitative assessment method to show that low plasma ARSA levels and high α-syn levels are related to cognitive impairment in PD patients. Plasma ARSA levels gradually decrease with PD progression.
Redox-active ligands in artificial photosynthesis: a review
Authors: Benkó Tímea , Lukács Dávid , Li Mingtao , Pap József S. 
Published: April 2022

AbstractGiven the rising socioeconomic issues of fossil fuels, efficient artificial photosynthesis would be an important milestone toward a sustainable world. A key step of photosynthesis is the catalytic photooxidation of water by photosystem II, which has a mean lifetime of 30 min under full sunlight. Since the efficiency of photosystem II is controlled by redox-active tyrosine–histidine pairs that regulate the light-induced flow of charges, research has recently focused on the utilization of redox-active ligands in artificial systems. Here we review the molecular catalysis of water oxidation with emphasis on redox cooperation modes between ligands and metal centers. Molecular systems involving redox-active ligands could achieve up to 100% efficiency with respect to oxygen production, overpotential of 200–300 mV and turnover frequency above 100 s−1, which is comparable to the natural process. Nonetheless, molecular catalysts are often prone to degradation of the organic ligand. The oxidative activation of ligands can contribute to the water oxidation reactivity of a metal–ligand complex, or lead to controlled catalyst film formation. We discuss the design of functional analogs to the tyrosine–histidine pair that for the most part rely on abundant elements and exploit redox-active molecular moieties to assist the catalytic centers. We highlight analogies with the cooperation between the natural oxygen-evolving complex and the redox-active tyrosine–histidine pairs found in photosystem II.
A novel robust network data envelopment analysis approach for performance assessment of mutual funds under uncertainty
Authors: Peykani Pejman , Emrouznejad Ali , Mohammadi Emran , Gheidar-Kheljani Jafar 
Published: April 2022

AbstractMutual fund (MF) is one of the applicable and popular tools in investment market. The aim of this paper is to propose an approach for performance evaluation of mutual fund by considering internal structure and financial data uncertainty. To reach this goal, the robust network data envelopment analysis (RNDEA) is presented for extended two-stage structure. In the RNDEA method, leader–follower (non-cooperative game) and robust optimization approaches are applied in order to modeling network data envelopment analysis (NDEA) and dealing with uncertainty, respectively. The proposed RNDEA approach is implemented for performance assessment of 15 mutual funds. Illustrative results show that presented method is applicable and effective for performance evaluation and ranking of MFs in the presence of uncertain data. Also, the results reveal that the discriminatory power of robust NDEA approach is more than the discriminatory power of deterministic NDEA models.
Exploring Carceral Food Systems as Sites of Contestation and Possibility in Canadian Federal Prisons: The Food Services Modernization Initiative
Authors: Wilson Amanda 
Published: April 2022

AbstractCentering the perspectives and lived experiences of incarcerated persons, this article considers the ways food is used as a tool and site of contestation and possibility within federal prisons in Canada. Focusing specifically on the implementation of and resistance to the Food Services Modernization Initiative, I explore food as “contested terrain” within carceral systems, making visible a range of tactics of resistance employed by incarcerated persons, from testimonials and official complaints to direct collective action. In analyzing these actions and narratives, I reflect on the importance of both food justice and prisoner justice to transforming carceral food systems and call for greater acknowledgment of carceral food systems within food movement discourses and campaigns.