bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction between the MtDELLA–MtGAF1 Complex and MtARF3 Mediates Transcriptional Control of MtGA3ox1 to Elaborate Leaf Margin Formation in Medicago truncatula
Authors: Wen Lizhu , Kong Yiming , Wang Hongfeng , Xu Yiteng , Lu Zhichao , Zhang Jing , Wang Minmin , Wang Xiao , Han Lu , Zhou Chuanen 
Published: December 2020

Abstract
The molecular mechanisms underlying the diversity of leaf shapes have been of great interest to researchers. Leaf shape depends on the pattern of serrations and the degree of indentation of leaf margins. Multiple transcription factors and hormone signaling pathways are involved in this process. In this study, we characterized the developmental roles of SMALL AND SERRATED LEAF (SSL) by analyzing a recessive mutant in the model legume Medicago truncatula. An ortholog of Arabidopsis thaliana GA3-oxidase 1 (GA3ox1), MtGA3ox1/SSL, is required for GA biosynthesis. Loss of function in MtGA3ox1 results in the small plant and lateral organs. The prominent phenotype of the mtga3ox1 mutant is a more pronounced leaf margin, indicating the critical role of GA level in leaf margin formation. Moreover, 35S:MtDELLA2ΔDELLA and 35S:MtARF3 transgenic plants display leaves with a deeply wavy margin, which resembles those of mtga3ox1. Further investigations show that MtGA3ox1 is under the control of MtDELLA1/2/3–MtGAF1 complex-dependent feedback regulation. Further, MtARF3 behaves as a competitive inhibitor of MtDELLA2/3–MtGAF1 complexes to repress the expression of MtGA3ox1 indirectly. These findings suggest that GA feedback regulatory circuits play a fundamental role in leaf margin formation, in which the posttranslational interaction between transcription factors functions as an additional feature.
Willingness to Share yet Maintain Influence: A Cross-Sectional Study on Attitudes in Sweden to the Use of Electronic Health Data
Authors: Belfrage Sara , Lynöe Niels , Helgesson Gert 
Published: December 2020

Abstract
We have investigated attitudes towards the use of health data among the Swedish population by analyzing data from a survey answered by 1645 persons. Health data are potentially useful for a variety of purposes. Yet information about health remains sensitive. A balance therefore has to be struck between these opposing considerations in a number of contexts. The attitudes among those whose data is concerned will influence the perceived legitimacy of policies regulating health data use. We aimed to investigate what views are held by the general public, and what aspects matter for the willingness to let one’s data be used not only for one’s own care but also for other purposes. We found that while there is a broad willingness to let one’s data be used, the possibility to influence that use is considered important. The study also indicated that when respondents are required to balance different interests, priority is typically given to compulsory schemes ensuring that data are available where needed, rather than voluntary participation and data protection. The policy implications to be drawn from this are not self-evident, however, since the fact that a majority has a certain attitude does not by itself determine the most adequate policy.
Quarantines: Between Precaution and Necessity. A Look at COVID-19
Authors: Raposo Vera Lúcia 
Published: December 2020

Abstract
The events surrounding COVID-19, combined with the mandatory quarantines widely imposed in Asia and Europe since the virus outbreak, have reignited discussion of the balance between individual rights and liberties and public health during epidemics and pandemics. This article analyses this issue from the perspectives of precaution and necessity. There is a difficult relationship between these two seemingly opposite principles, both of which are frequently invoked in this domain. Although the precautionary principle (PP) encourages the use of quarantines, including mandatory quarantines, and associated restrictive measures, the principle of necessity (PN) puts a break on such measures. The COVID-19 pandemic reveals once again the different interrelations between these two principles. However, the alleged conflict between the PN and the PP is based on a superficial analysis. The relation between these two principles is far more complex, as this article will demonstrate.
Pain Induced Changes in Brain Oxyhemoglobin: A Systematic Review and Meta-Analysis of Functional NIRS Studies
Authors: Hall MacGregor , Kidgell Dawson , Perraton Luke , Morrissey Jack , Jaberzadeh Shapour 
Published: December 2020

Abstract

Background
Neuroimaging studies show that nociceptive stimuli elicit responses in an extensive cortical network. Functional near-infrared spectroscopy (fNIRS) allows for functional assessment of changes in oxyhemoglobin (HbO), an indirect index for cortical activity. Unlike functional magnetic resonance imaging (fMRI), fNIRS is portable, relatively inexpensive, and allows subjects greater function. No systematic review or meta-analysis has drawn together the data from existing literature of fNIRS studies on the effects of experimental pain on oxyhemoglobin changes in the superficial areas of the brain.

Objectives
To investigate the effects of experimental pain on brain fNIRS measures in the prefrontal-cortex and the sensory-motor-area; to determine whether there is a difference in oxyhemodynamics between the prefrontal-cortex and sensory-motor-area during pain processing; to determine if there are differences in HbO between patients with centralized persistent pain and healthy controls.

Methods
Studies that used fNIRS to record changes in oxyhemodynamics in prefrontal-cortex or sensory-motor-cortex in noxious and innoxious conditions were included. In total, 13 studies were included in the meta-analysis.

Results
Pain has a significantly greater effect on pre-frontal-cortex and sensory-motor areas than nonpainful stimulation on oxyhemodynamics. The effect of pain on sensory-motor areas was greater than the effect of pain on the prefrontal-cortex. There was an effect of centralized pain in the CPP group on oxyhemodynamics from a noxious stimulus compared to control’s response to pain.

Conclusions
Pain affects the prefrontal and sensory-motor cortices of the brain and can be measured using fNIRS. Implications of this study may lead to a simple and readily accessible objective measure of pain.
PEDIATRIC REGIONAL DRL ASSESSMENT IN COMMON CT EXAMINATIONS FOR MEDICAL EXPOSURE OPTIMIZATION IN TEHRAN, IRAN
Authors: Tahmasebzadeh Atefeh , Paydar Reza , Soltani kermanshahi Mojtaba , Maziar Asghar , Rezaei Mehdi , Reiazi Reza 
Published: December 2020

Abstract
The main purpose of this pilot study was to assess the regional diagnostic reference level (RDRL) of computed tomography (CT) examinations to optimise medical exposure in five pediatric medical imaging centers in Tehran, Iran where the most frequent CT examinations were investigated. For each patient, CT volume dose indexes (CTDIvol) and dose length product (DLP) in each group were recorded and their third quartile was calculated and set as RDRL. Pediatrics were divided into four age groups (&lt;1; 1–5; 5–10 and 10–15 years). Then, the third quartile values for head, chest and abdomen-pelvic CTs were, respectively, calculated for each group in terms of CTDIvol: 21.3, 24.4, 24.2 and 36.3 mGy; 2.9, 3.2, 3.7 and 5.7 mGy; 3.7, 5.7, 6.3 and 6.8 mGy; and in terms of DLP: 322.2, 390.1, 424.9 and 694.1 mGy.cm; 53.1, 115.2, 145.3 and 167.6 mGy.cm and 128.7, 317.7, 460.2 and 813.8 mGy.cm. Finally, RDRLs were compared with other countries and preceding data in Iran. As a result, CTDIVOL values were lower than other national and international studies except for chest and abdomen-pelvic values obtained in Europe. Moreover, this matter applied to DLP so that other formerly reported values were higher than the present study but European values for chest and abdomen-pelvic scans and also Tehran studies conducted in 2012. Variation of scan parameters (tube voltage (kVp), tube current (mAs) and scan length), CTDIvol and DLP of different procedures among different age groups were statistically significant (P-value &lt; 0.05). The variations in dose between CT departments as well as between identical scanners suggest a large potential for optimization of examinations relative to which this study provides helpful data.
Phylogenomic Analysis of Ultraconserved Elements Resolves the Evolutionary and Biogeographic History of Segmented Trapdoor Spiders
Authors: Xu Xin , Su Yong-Chao , Ho Simon Y W , Kuntner Matjaž , Ono Hirotsugu , Liu Fengxiang , Chang Chia-Chen , Warrit Natapot , Sivayyapram Varat , Aung Khin Pyae Pyae , Pham Dinh Sac , Norma-Rashid Y , Li Daiqin 
Published: December 2020

Abstract
The segmented trapdoor spiders (Liphistiidae) are the sole surviving family of the suborder Mesothelae, which forms the sister lineage to all other living spiders. Liphistiids have retained a number of plesiomorphic traits and their present-day distribution is limited to East and Southeast Asia. Studying this group has the potential to shed light on the deep evolutionary history of spiders, but the phylogeny and divergence times of the family have not been resolved with confidence. We performed phylogenomic and molecular dating analyses of 2765 ultraconserved element loci from 185 liphistiid taxa. Our analyses show that the crown group of Liphistiidae appeared in the mid-Cretaceous at 102 Ma (95% credibility interval 92–113 Ma), but it was not until the Neogene that much of the diversification within the family occurred in mainland Southeast and East Asia. This diversification was coincident with tectonic events such as the extension of the East Asian continental margin, as well as geological upheavals in Indochina induced by the collision between India and Asia. Our study highlights the important role of major tectonic events in shaping the evolutionary history, present-day diversity, and geographical distribution of mesothele and liphistiid spiders. [biogeography; concatenation; Liphistiidae; molecular dating; summary coalescent; UCEs.]
A target safety assessment of the potential toxicological risks of targeting plasmepsin IX/X for the treatment of malaria
Authors: Barber Jane , Sikakana Phumzile , Sadler Claire , Baud Delphine , Valentin Jean-Pierre , Roberts Ruth 
Published: December 2020

Abstract
The aspartic proteases plasmepsin IX/X are important antimalarial drug targets due to their specificity to the malaria parasite and their vital role as mediators of disease progression. Focusing on parasite-specific targets where no human homologue exists reduces the possibility of on-target drug toxicity. However, there is a risk of toxicity driven by inadequate selectivity for plasmepsins IX/X in Plasmodium over related mammalian aspartic proteases. Of these, CatD/E may be of most toxicological relevance as CatD is a ubiquitous lysosomal enzyme present in most cell types and CatE is found in the gut and in erythrocytes, the clinically significant site of malarial infection. Based on mammalian aspartic protease physiology and adverse drug reactions (ADRs) to FDA-approved human immunodeficiency virus (HIV) aspartic protease inhibitors, we predicted several potential toxicities including β-cell and congenital abnormalities, hypotension, hypopigmentation, hyperlipidaemia, increased infection risk and respiratory, renal, gastrointestinal, dermatological, and other epithelial tissue toxicities. These ADRs to the HIV treatments are likely to be a result of host aspartic protease inhibition due a lack of specificity for the HIV protease; plasmepsins are much more closely related to human CatD than to HIV proteinase. Plasmepsin IX/X inhibition presents an opportunity to specifically target Plasmodium as an effective antimalarial treatment, providing adequate selectivity can be obtained. Potential plasmepsin IX/X inhibitors should be assayed for inhibitory activity against the main human aspartic proteases and particularly CatD/E. An investigative rodent study conducted early in drug discovery would serve as an initial risk assessment of the potential hazards identified.
Effects of chlorpyrifos exposure on liver inflammation and intestinal flora structure in mice
Authors: Zhang Yecui , Jia Qiang , Hu Chenyang , Han Mingming , Guo Qiming , Li Shumin , Bo Cunxiang , Zhang Yu , Qi Xuejie , Sai Linlin , Peng Cheng 
Published: December 2020

AbstractChlorpyrifos (CPF) is an organophosphate insecticide commonly used to treat fruit and vegetable crops. CPF can cause severe adverse effects on body organs including the liver and central nervous system. This study investigated the CPF-induced inflammation in mice and explored the role of intestinal flora changes in liver inflammation. Adult C57BL/6 male mice were exposed to a CPF of 0.01-, 0.1-, 1- and 10-mg/kg bodyweight for 12 weeks. The mice in experimental group given CPF solution dissolved in corn oil vehicle by gavage, was administered by intraoral gavage for 5 days per week for 12 weeks. Histopathological examination and inflammatory factor detection were performed on mice liver tissue. Faeces were used for 16S ribosomal RNA high-throughput sequencing to explore the impact of CPF on intestinal flora structure and diversity. The results showed that 1- and 10-mg/kg CPF caused different degrees of liver focal inflammation. The structure of intestinal flora changed significantly in mice including the decreased beneficial bacteria (Akkermansia, Prevotella and Butyricimonas) and increased pathogenic bacteria (Helicobacter and Desulfovibrio). Meanwhile, the results of Q-RT-PCR showed that there was more total bacterial DNA in the liver tissue of the mice treated with 10-mg/kg groups. In conclusion, the imbalance of intestinal flora, the decreased abundance of beneficial bacteria and the increased abundance of pathogenic bacteria, as well as the increase of total bacterial DNA in the liver tissues, maybe associated with the liver focal inflammation induced by CPF.
Choice of biologics in asthma endotypes
Authors: Wangberg Hannah , Woessner Katharine 
Published: December 2020

Purpose of review
The aim of this study was to highlight the phenotypes and endotypes of asthma as a tool for selection of the Food and Drug Administration approved biologic therapies.

Recent findings
An evolving concept of asthma has led to the identification of distinct phenotypes and endotypes in this disease. Asthma endotypes are defined as the biological mechanism and are often categorized as T2-high and T2-low based on the influence of T helper type 2 (T2) cells and type 2 cytokines, including interleukin (IL)-4, IL-5, IL-9 and IL-13. Biomarkers such as peripheral blood absolute eosinophil count, total IgE, specific IgE and fractional exhaled nitric oxide may be used as indicators of asthma endotypes and help predict response to biologic therapies. There are currently five biologic therapies approved as a treatment option for T2-high asthma: omalizumab, benralizumab, mepolizumab, reslizumab and dupilumab.

Summary
Here, we explore the current understandings of asthma endotypes and review their associated phenotypes. We provide practical and evidence-based guidance for clinicians considering a biologic for asthma add-on maintenance therapy.
Low- and Middle-Income Country Host Perceptions of Short-Term Experiences in Global Health: A Systematic Review
Authors: Lu Paul M. , Mansour Rania , Qiu Maylene K. , Biraro Irene A. , Rabin Tracy L. 
Published: December 2020

Purpose
Stakeholders have expressed concerns regarding the impact of visiting trainees and physicians from high-income countries (HICs) providing education and/or short-term clinical care in low- and middle-income countries (LMICs). This systematic review aimed to summarize LMIC host perceptions of visiting trainees and physicians from HICs during short-term experiences in global health (STEGH).

Method
In September 2018 then again in August 2020, the authors searched 7 databases (PubMed, Embase, Scopus, Web of Science, ERIC, Cochrane Library, Global Index Medicus) for peer-reviewed studies that described LMIC host perceptions of STEGH. They extracted information pertaining to study design, participant demographics, participant perceptions, representation of LMICs and HICs, and HIC visitors’ roles and used thematic synthesis to code the text, develop descriptive themes, and generate analytical themes.

Results
Of the 4,020 studies identified, 17 met the inclusion criteria. In total, the studies included 448 participants, of which 395 (88%) represented LMICs. The authors identified and organized 42 codes under 8 descriptive themes. They further organized these descriptive themes into 4 analytical themes related to STEGH: (1) sociocultural and contextual differences, (2) institutional and programmatic components, (3) impact on host institutions and individuals, and (4) visitor characteristics and conduct.

Conclusions
STEGH can have both beneficial and detrimental effects on LMIC host institutions and individuals. The authors translated these findings into a set of evidence-based best practices for STEGH that provide specific guidance for LMIC and HIC stakeholders. Moving forward, LMIC and HIC institutions must work together to focus on the quality of their relationships and create conditions in which all stakeholders feel empowered to openly communicate to ensure equity and mutual benefit for all parties.
Unique Variant of Cerebrotendinous Xanthomatosis Presenting With Eyelid Involvement Due to Heterozygous CYP7A1 and SLC10A1 Gene Mutations
Authors: Krbanjevic Aleksandar , Lekakh Olga , Kadkol Shrihari , Mohapatra Gayatry , Gushchin Anna 
Published: December 2020

Abstract:
We report a case of a novel phenotypic variant of cerebrotendinous xanthomatosis (CTX) with an adult onset, caused by 2 coexisting mutations involving the CYP7A1 and SLC10A1 genes. A 49-year-old male patient presented with eyelid xanthomatosis associated with dermatochalasis, nystagmus, right-sided paresis with hyperreflexia and atypical parkinsonism. Bilateral xanthomatous plaques involving both Achilles tendons were subsequently detected. Histopathology of the eyelids demonstrated marked diffuse stromal infiltrates of prominent foamy histiocytes. His lipid profile showed only a slightly elevated non-high density lipoprotein cholesterol level but with normal cholesterol and cholestanol levels. By contrast, classic CTX characteristically demonstrates a markedly elevated cholestanol and a mutation involving the CYP27A1 gene for enzyme cholesterol 27-hydroxylase. Unexpectedly, molecular studies on this patient revealed a heterozygous mutation involving 2 different genes, namely, CYP7A1 and SLC10A1 genes. The CYP7A1 gene encodes for the enzyme cholesterol 7α-hydroxylase, which is a rate-limiting enzyme in the cholesterol degradation. The SLC10A1 Na+/taurocholate cotransporter gene is involved in the enterohepatic circulation of bile acids and for the hepatocyte uptake of cholesterol. We are the first to report an unusual case of an adult-onset CTX manifesting with eyelid xanthomas associated with an uncharacteristic lipid profile and a detection of novel heterozygous mutations of CYP7A1 and SLC10A1 genes in this neurocutaneous syndrome.
Information tools for care coordination in patient handover: Is an electronic medical record enough to support nurses?
Authors: Ghosh Kaushik , Dohan Michael S. , Curl Eileen , Goodwin Mary , Morrell Patricia , Guidroz Paul 
Published: December 2020

Background
Effectiveness of end-of-shift patient handover between nurses may be impacted by poor communication. This can be improved with the use of information tools, either electronic or paper-based. Few studies have investigated the activities that support patient handover, and fewer have explored how several of these tools used together affects the handover process.

Purpose
The aim of this study was to understand coordination challenges in end-of-shift patient handover between nurses and the influence of multiple information tools used in that context.

Methodology
A qualitative methodology to investigate phenomena in an acute care hospital in the United States was used in this study. Semistructured interviews were used to elicit insights from 16 nurses. Data were analyzed by coding three types of task dependencies (prerequisite, simultaneous, and shared) and three information tools (electronic medical records [EMRs], Kardex, and printouts of EMR data).

Results
In preparation for a handover, nurses were burdened by ensuring that information in the EMR was correct and complete. A one-sheet Kardex was the tool nurses in the study preferred, because the essential information was at hand and it provided structure to the communication. Printouts of EMR data were often physically cumbersome and not useful in their current form, although they may be useful for communicating anomalous data.

Conclusion
This study provides insights regarding the challenges of care coordination in end-of-shift patient handover between nurses and the usages of a variety of information tools in preparation for handover, as well as the actual handover process.

Practice Implications
Multiple interrelated information tools may be used to support patient handover. Health leaders should focus efforts on further advancing protocols for end-of-shift nurse handovers. Health system designers should design information tools to align them with their defined purpose in the handover process. Future work should consider both the information needs of nurses and the goal of improving nurse workflows.
Extending the Limbus-to-Cannula Distance to 6.0 mm During Pars Plana Vitrectomy in Highly Myopic Eyes
Authors: Iwama Yasuaki , Ikeda Toshihide , Nakashima Hiroshi , Matsumoto Eri , Inoue Ryo , Emi Kazuyuki 
Published: December 2020

Purpose:
To evaluate the utility of extending the limbus-to-cannula distance to 6.0 mm during pars plana vitrectomy for highly myopic eyes.

Methods:
Four eyes with axial lengths exceeding 31.0 mm, that underwent 25-gauge pars plana vitrectomy were retrospectively evaluated. Assuming that cannulas were inserted 3.5 mm and 6.0 mm from the corneal limbus, the distance from the cannula to the fovea (CF distance) was preoperatively evaluated using anterior segmental optical coherence tomography. Surgical complications were also investigated.

Results:
The CF distance was shortened by 1.22 ± 0.05 mm and 1.22 ± 0.09 mm on the temporal and nasal sides, respectively, by inserting the cannula at 3.5 mm to 6.0 mm from the corneal limbus. As per the preoperatively measured CF distance, one of the cannulas was inserted 6.0 mm from the corneal limbus in three eyes. Their cannulas were confirmed to be inserted at the pars plana, and no surgical complications associated with this technique were observed.

Conclusion:
Extending the limbus-to-cannula distance to 6.0 mm during pars plana vitrectomy could be one of the options to reach the posterior pole in highly myopic eyes. A preoperatively measured CF distance can be a clinical criterion in determining the cannula position.