bluuebunny/crossref_metadata_2025 huggingface dataset:
A high-flux automated laboratory small-angle X-ray scattering instrument optimized for solution scattering
Authors: Lyngsø Jeppe , Pedersen Jan Skov
Published: January 2021

A commercially available small-angle X-ray scattering (SAXS) NanoSTAR instrument (Bruker AXS) with a liquid-metal-jet source (Excillum) has been optimized for solution scattering and installed at iNANO at Aarhus University. The instrument (named HyperSAXS) employs long high-quality parabolic Montel multilayer optics (Incoatec) and a novel compact scatterless pinhole slit with Ge edges, which was designed and built at Aarhus University. The combination of the powerful source and optimized geometry gives an integrated X-ray intensity close to 109 photons s−1 for a standard range of scattering vector moduli q = 0.0098–0.425 Å−1, where q = (4πsinθ)/λ and λ is the Ga Kα wavelength of 1.34 Å. The high intensity of the instrument makes it possible to measure dilute samples of, for example, protein or surfactant with concentrations of 1 mg ml−1 in a few minutes. A flow-through cell, built at Aarhus University, in combination with an automated sample handler has been installed on the instrument. The sample handler is based on the commercial Gilson GX-271 injection system (Biolab), which also allows samples to be stored under thermostatted conditions. The sample handler inserts and removes samples, and also cleans and dries the sample cell between measurements. The minimum volume of the flow-through capillary is about 20 µl. The high intensity additionally allows time-resolved measurements to be performed with a temporal resolution of seconds. For this purpose a stopped-flow apparatus, (SFM-3000, Bio-Logic) was connected to the flow-through cell by high-performance liquid chromatography tubing. This configuration was chosen as it allows vacuum around the sample cell and thus maintains a low background. The instrument can readily be converted into a low-q setup with a q range of 0.0049–0.34 Å−1 and an X-ray intensity of about 5 × 107 photons s−1.
catena-Poly[[(2,2′-bipyridine-κ2
N,N′)manganese(II)]-di-μ-bromido]
Authors: Ha Kwang
Published: January 2021

In the polymeric title complex, [MnBr2(C10H8N2)]
n
, the MnII ion, situated on a twofold axis of symmetry, is six-coordinated in a distorted octahedral coordination geometry defined by two N atoms from the chelating 2,2′-bipyridine ligand and four bridging Br− anions. The crystal reveals a one-dimensional Br-bridged chain along the c-axis direction with a zigzag topology. In the crystals, contacts between chains include π–π interactions between pyridyl rings [inter-centroid separation = 4.082 (1) Å]
Intraspecific variations in leaf traits, productivity and resource use efficiencies in the dominant species of subalpine evergreen coniferous and deciduous broad‐leaved forests along the altitudinal gradient
Authors: Hikosaka Kouki , Kurokawa Hiroko , Arai Takahisa , Takayanagi Sakino , Tanaka Hiroshi O. , Nagano Soichiro , Nakashizuka Tohru
Published: January 2021

Many studies have reported intraspecific variations in leaf functional traits, but their contribution to plant performance and ecosystem function are poorly understood. We studied altitudinal gradients of intraspecific variations in leaf traits, productivity and resource use efficiency in the dominant species of subalpine evergreen coniferous and deciduous broad‐leaved forests in Japan.

We addressed three hypotheses, which are exclusive to each other. (1) Leaf traits vary along the leaf economics spectrum (LES). Plants that grow at lower and higher altitudes have fast‐ and slow‐return strategies, respectively, which improve productivity or resource use efficiency in the respective habitat. (2) Leaf trait variations are not consistent with the LES, but they contribute to improving productivity or resource use efficiency in the respective habitat. (3) Leaf trait variations do not contribute to improving productivity or resource use efficiency at higher altitudes.

On the studied mountain range, Fagus crenata, a deciduous broad‐leaved tree, and Abies mariesii, an evergreen conifer, are the dominant species at lower and higher altitudes respectively. In F. crenata, leaf mass per area (LMA) and nitrogen concentrations were higher at higher altitudes. The net assimilation rate and light use efficiency during the growing season were greater at higher altitudes, which compensated for the shorter growing season in terms of annual productivity. In A. mariesii, the LMA was lower and the leaf life span was unchanged at higher altitudes. Productivity and resource use efficiency decreased with altitude.

Synthesis. We conclude that F. crenata improves its productivity and resource use efficiency at higher altitudes by altering its leaf functional traits (Hypothesis 2), whereas alterations to leaf traits in A. mariesii are not associated with any improvement at higher altitudes (Hypothesis 3), which may result from the negative impact of environmental stress. Hence, the ecological significance of altitudinal variations in leaf traits depends on species and environment.
Critical seed transfer distances for selected tree species in eastern North America
Authors: Pedlar John H. , McKenney Daniel W. , Lu Pengxin
Published: January 2021

Forest planting events present key opportunities to enhance forest adaptation and growth through the selection of appropriate growing materials (seeds and seedlings). Critical to such efforts is knowledge of the climatic distance that seed sources can be moved before significant growth forfeitures are incurred. These limits, referred to here as critical seed transfer distances (CSTD), can be used to identify a potential seed procurement region for any given planting site and can readily incorporate climate change projections.

We assembled provenance trial data from a variety of sources and employed transfer functions to derive CSTDs for five major tree species in eastern North America.

Optimal height growth at test sites was associated with modest warm‐to‐cold (i.e. northward) seed transfers of 1.6°C on average. Calculated transfer limits were large, indicating that seed sources could be moved significant climatic distances before height growth was less than 90% relative to that of the local seed source. These broad relationships, which were relatively consistent across species, would allow considerable flexibility in resulting seed transfer systems; however, given the significant uncertainty surrounding climate change—particularly in the location and timing of extreme weather events—prudent application of seed transfer limits may be appropriate.

Synthesis: We assembled and analysed a significant amount of provenance data to derive novel information on seed movement limits for five tree species in eastern North America. This information will support forest managers in ongoing efforts to incorporate climate change into forest regeneration operations.
Jihadism au rebours: Orientalism and Occidentalism for a Counter‐Hegemonic Liberation Theology
Authors: Demichelis Marco
Published: January 2021

Following its colonial project, Western Europe imposed a political and cultural understanding of state nationalism and religious homogeneity on the entire world in the nineteenth and twentieth centuries. In parallel with this twofold process, “Religious Nationalism” emerged during the Cold War, affecting the Middle East and framing an updated Abrahamic version of religious supremacism: Wahhabi Islam, the Iranian Revolution, and Israeli Orthodox Judaism were politically backed, becoming the frontrunners of a new Global‐Religious narrative of conflict. This article aims to critically analyse the Western‐Islamic manipulation of “Jihadism” as an artificial and fabricated product, starting from the “deconstruction” of Jihad–Jihadism as an anti‐hegemonic narrative. The anti‐colonial “Islamic” framework of resistance to the Empire (United States) has effectively adopted the same colonial methodology: using violence and sectarianism in trying to reach its goals. Is the Islamic Supremacist “narrative” more influenced by Western thought than by a real understanding of Islam? At the same time, this article aims to stress the historical reasons why the Arab world has been artificially affected by a peculiar form of “Religious Revanchism” which can be understood only if O. Roy's Holy Ignorance dialogues with Steve Biko's Consciousness in emphasising the need for an updated Islamic Liberation Theology.
Assessing the Effects of Seasonal Tariff‐rate Quotas on Vegetable Prices in Switzerland
Authors: Loginova Daria , Portmann Marco , Huber Martin
Published: January 2021

Causal estimation of the short‐term effects of tariff‐rate quotas (TRQs) on vegetable producer prices is hampered by the large variety and different growing seasons of vegetables and is therefore rarely performed. We quantify the effects of Swiss seasonal TRQs on domestic producer prices of a variety of vegetables based on a difference‐in‐differences estimation using a novel dataset of weekly producer prices for Switzerland and neighbouring countries. We find that TRQs increase prices of most vegetables by more than 20% above the prices in neighbouring countries during the main harvest time for most vegetables and even more than 50% for some vegetables. The effects are stronger for more perishable vegetables and for conventionally produced ones compared with organic vegetables. However, we do not find clear‐cut effects of TRQs on the week‐to‐week price volatility of vegetables although the overall lower price volatility in Switzerland compared with neighbouring countries might be a result of the TRQ system in place.
FAWMine: An integrated database and analysis platform for fall armyworm genomics
Authors: Yang Pengcheng , Wang Depin , Guo Wei , Kang Le
Published: January 2021

Fall armyworm (Spodoptera frugiperda), a native insect species in the Americas, is rapidly becoming a major agricultural pest worldwide and is causing great damage to corn, rice, soybeans, and other crops. To control this pest, scientists have accumulated a great deal of high‐throughput data of fall armyworm, and nine versions of its genomes and transcriptomes have been published. However, easily accessing and performing integrated analysis of these omics data sets is challenging. Here, we developed the Fall Armyworm Genome Database (FAWMine, http://159.226.67.243:8080/fawmine/) to maintain genome sequences, structural and functional annotations, transcriptomes, co‐expression, protein interactions, homologs, pathways, and single‐nucleotide variations. FAWMine provides a powerful framework that helps users to perform flexible and customized searching, present integrated data sets using diverse visualization methods, output results tables in a range of file formats, analyze candidate gene lists using multiple widgets, and query data available in other InterMine systems. Additionally, stand‐alone JBrowse and BLAST services are also established, allowing the users to visualize RNA‐Seq data and search genome and annotated gene sequences. Altogether, FAWMine is a useful tool for querying, visualizing, and analyzing compiled data sets rapidly and efficiently. FAWMine will be continually updated to function as a community resource for fall armyworm genomics and pest control research.
Oviposition preference and offspring performance of Apoderus dimidiatus (Coleoptera: Atelabidae) between Rosa multiflora and Rubus ichangensis
Authors: Xie Meng , Du Jinying , Yang Kunqi , Song Shaoting , Lv Zonghui , Xu Huailiang , Wen An Xiang , Wang Qin , Jiang Yanzhi , Zhu Guangxiang , Wu Jiayun , Yao Yongfang , Ni Qingyong
Published: January 2021

Leaf‐rolling weevils (Coleoptera: Atelabidae) are considered to be specialists that oviposit only on one or two plant species. However, Apoderus dimidiatus can oviposit on at least five species. We aimed to determine whether A. dimidiatus females have different preferences for oviposition substrates, and whether differences in physical factors, nutrition and parasitism affected their choices. We observed the number of cradles, hatched larvae, pupae, emerging adults and parasitism rate during one breeding season. Weevils were given access to two host plant species, Rosa multiflora and Rubus ichangensis, and the leaf size and nutrient contents of the two plant species were investigated. We found that nutritional content, especially soluble carbohydrate, correlated with oviposition preference of weevils, and the more nutritious plant species, R. multiflora, was the preferred host in our experiment. Weevils can also use Ru. ichangensis and other plant species as hosts, likely to relieve the high parasitic pressure when laying eggs on a single host species.
Predictors of mortality in a multiracial urban cohort of persons with type 2 diabetes and novel coronavirus 19
Authors: Myers Alyson K. , Kim Tara S. , Zhu Xu , Liu Yan , Qiu Michael , Pekmezaris Renee
Published: January 2021

Background

Diabetes has been identified as a risk factor for intubation and mortality in patients with coronavirus disease 2019 (COVID‐19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). We seek to examine the impact of clinical variables such as glycosylated hemoglobin (HbA1c) on mortality and need for intubation, as well as demographic variables such as age, sex, and race on persons with type 2 diabetes and COVID‐19.

Methods

Analyses were conducted on 4413 patients with an International Classification of Diseases and Related Health Problems (ICD‐10) diagnosis of type 2 diabetes and COVID‐19. Survival analysis was conducted using Kaplan‐Meier curves and the log‐rank test to compare subgroup analyses.

Results

In this multivariate analysis, male gender, older age, and hyperglycemia at admission were associated with increased mortality and intubation, but this was not seen for race, ethnicity, insurance type, or HbA1c. Based on Kaplan‐Meier analysis, having comorbid conditions such as hypertension, chronic kidney disease, and coronary artery disease was associated with a statistically significant increased risk of mortality.

Conclusions

Glycemic levels at admission have a greater impact on health outcomes than HbA1c. Older men and those with comorbid disease are also at greater risk for mortality. Further longitudinal studies need to be done to evaluate the impact of COVID‐19 on type 2 diabetes.
A chromosome‐level genome assembly for the tertiary relict plant Tetracentron sinense oliv. (trochodendraceae)
Authors: Li Minjie , Yang Yongzhi , Xu Renping , Mu Wenjie , Li Ying , Mao Xingxing , Zheng Zeyu , Bi Hao , Hao Guoqian , Li Xiaojie , Xu Xiaoting , Xi Zhenxiang , Shrestha Nawal , Liu Jianquan
Published: January 2021

Tetracentron sinense and Trochodendron aralioides are two Tertiary relict species of large trees in the family Trochodendraceae with narrow distributions on the mainland and islands of eastern Asia. They belong to the order Trochodendrales, which is one of the four early‐diverged eudicot lineages. These two relict species provide a good system in which to examine genomic changes that occurred as they survived during repeated climatic oscillations in the Quaternary. We sequenced the genome of Te. sinense and compared it with that of Tr. aralioides. We found that Te. sinense has a smaller genome size (986.3 Mb) than that of Tr. aralioides (1610 Mb). Repetitive elements made the major contribution to the contrasting genome sizes in the two species, with most bursts of repeats occurring within the past four million years when the climate oscillated greatly. These species share two rounds of whole‐genome duplications. The mainland species Te. sinense had a larger effective population size than the island species Tr. aralioides after the largest glaciation during the Quaternary climatic oscillation. However, soon after this recovery stage, the effective population sizes of both species continued to decrease, although the current effective population size of Te. sinense is still larger than that of Tr. aralioides. We recovered three distinctly diverged clades through resequencing the genomes of 50 individuals across the distributional range of Te. sinense in China. Our results provide an important genomic resource with which to examine early trait evolution in the core eudicots and assist efforts to conserve this relict tree species.
Prognostic impact of maximum standardized uptake value on 18F‐FDG PET/CT imaging of the primary lung lesion on survival in advanced non‐small cell lung cancer: A retrospective study
Authors: Qiu Xiaoling , Liang Hongge , Zhong Wei , Zhao Jing , Chen Minjiang , Zhu Zhaohui , Xu Yan , Wang Mengzhao
Published: January 2021

Background

Positron emission tomography/computed tomography (PET/CT) has been recognized for diagnosing and staging lung cancer, but the prognostic value of standardized uptake value (SUV) on 18F‐FDG PET/CT imaging in patients with advanced non‐small cell lung cancer (NSCLC) remains controversial.

Methods

We performed a retrospective analysis of patients with advanced NSCLC who had undergone 18F‐FDG PET/CT before systemic treatment between June 2012 and June 2016. The relationship between the maximum SUV (SUVmax) of the pulmonary lesion and lesion size was evaluated via Spearman's correlation analysis. We collected patients' clinical and pathological data. Univariate and multivariate analyses were performed to analyze the factors influencing survival.

Results

We included 157 patients with advanced NSCLC. Among these, 135 died, 13 survived, and nine were lost to follow‐up (median follow‐up period, 69 months). SUVmax was correlated with lesion size and was significantly greater for tumors ≥3 cm than for tumors <3 cm (10.2 ± 5.4 vs. 5.6 ± 3.3, t = −6.709, p = 0.000). Univariate analysis showed that survival was associated with gender, tumor size, epidermal growth factor receptor gene mutation or anaplastic lymphoma kinase rearrangement, SUVmax of the primary lung lesion, and treatment lines. Multivariate analysis showed a significant correlation between SUVmax of the primary lung lesion and survival. The mortality risk of patients with SUVmax ≤6 was 35% lower than that of patients with SUVmax >6 (HR = 0.651, 95% confidence interval, 0.436–0.972; Wald value, 4.400; p = 0.036).

Conclusions

The SUVmax of the primary lung lesion on PET/CT is significantly correlated with survival in treatment‐naive patients with advanced NSCLC.
Here to chair: Gender differences in the path to leadership
Authors: Sethuraman Kinjal N. , Lin Michelle , Rounds Kirsten , Fang Andrea , Lall Michelle D. , Parsons Melissa , Linden Judith A. , Gursahani Kamal , Raukar Neha , Perman Sarah M. , Dobiesz Valerie A.
Published: January 2021

Objective

Career paths leading to department chair positions are elusive. Women represent only 11% of academic emergency department (ED) chairs. It is unclear whether the pathway to chair is different for men and women; the characteristics, achievements, and qualifications among those who become ED chairs is unknown.

Methods

This study is a cross‐sectional analysis of curriculum vitae (CV) of current ED chairs in departments with Accreditation Council for Graduate Medical Education (ACGME)‐accredited residency programs. Former women chairs were included due to paucity of current women chairs. Statistics were calculated using bivariate and multivariate analysis.

Results

Of 163 eligible chairs, 88 CV (54%) were obtained, including six former women chairs. A majority (86.4%) self‐identified as White/Caucasian, 21.5% were women, 46% were chief residents, 28.4% completed additional postgraduate degrees, and 21.8% were fellowship trained. At time of chair appointment, 58% were professor rank, 53.5% held ED operations roles, and 32% served as vice chair. Women were more likely to be in educational (53% vs. 22%) versus operational (26% vs. 61%, p = 0.02) roles. Women obtained more advanced degrees (47% vs. 25%, p = 0.02), were awarded more nonfederal grants (median = 7 vs. 3, p = 0.04), and achieved more national committee leadership (median = 4 vs. 1, p = 0.02). There were no gender differences in fellowship training, awards, leadership training programs, publications, federal grants, or national/international lectures after adjusting for years in practice.

Conclusion

While the majority of chairs held prior leadership roles in ED operations, only one in five women chairs did, suggesting gender differences in the path to chair attainment. These differences in paths may contribute to persistent gender disparities in ED chairs and may be influenced by career path choices, implicit bias, and structural barriers.
Alterations in Insulin Levels in Adults with Prenatal Alcohol Exposure
Authors: Kable Julie A. , Mehta Puja K. , Coles Claire D.
Published: January 2021

Objective

Evidence suggests that prenatal alcohol exposure (PAE) may adversely impact insulin production and signaling but there is limited information on the range of these effects and their future health consequences.

Method

A prospective cohort of predominantly African‐American individuals identified while in utero and followed into adulthood were used to evaluate differences in various indicators of diabetes, including fasting plasma glucose, hemoglobin A1c (HbA1c), and insulin levels. The homeostatic model assessment of insulin resistance (HOMA‐IR) was also computed. Body mass index (BMI) was calculated and normal defined as < 25 kg/m2. Participants were categorized as having PAE (n = 39) if their mothers drank at least 1 ounce of absolute alcohol per week or more during the 1st trimester of pregnancy and as Controls (n = 22) if their mothers reported abstaining from alcohol consumption during pregnancy.

Results

Mean age of the sample was 36.0 ± 1.5 years. Indices of glucose metabolism, including fasting plasma glucose and hemoglobin A1c levels, did not vary by group status but insulin levels and HOMA‐IR values varied by group status and BMI level. PAE individuals with a normal BMI had lower insulin levels than Controls. However, in PAE subjects, there was a steeper increase in insulin levels relative to their BMI than in Control subjects. A cluster of 5 PAE cases had low levels of insulin and 4 of the 5 had severe cognitive impairment.

Conclusions

The bidirectional effects on insulin level and insulin resistance associated with PAE may indicate differential rates of diabetes disease impact or differential PAE impact in the brain and peripheral areas involved in insulin production and signaling. These alterations may contribute to the metabolic disease risk associated with PAE.
Coronectomy of mandibular third molars: a systematic literature review and case studies
Authors: Mann A , Scott JF
Published: January 2021

Background

Extraction of mandibular third molars (M3M) close to the inferior alveolar nerve (IAN) has a higher risk of neurological disturbance. This review aims to evaluate the evidence supporting the use of the coronectomy technique compared to complete extraction for such M3Ms. Case studies by a specialist oral and maxillofacial surgeon are included to illustrate clinical practice.

Methods

Three databases (Cochrane Library, Embase, PubMed) were searched (November 2020). Additional articles were sought by hand searching the reference list of included articles. All studies published in English comparing outcomes of coronectomy with complete extraction with at least 50 subjects and 6 months follow‐up were included.

Results

Of the six included studies, five reported a lower rate of IAN disturbance after coronectomy compared with complete extraction. There were no reported cases of lingual nerve disturbance. Other outcomes of coronectomy such as pain, infection, alveolar osteitis were either similar or lower compared to complete extraction. There were high rates of root migration but low rates of exposure and reoperation. Follow‐up protocols varied considerably.

Conclusions

There is medium quality evidence to support the option of coronectomy for high risk M3M cases. Further studies to develop follow‐up protocols to assist general dental practice is warranted.
Obstetric and perinatal outcomes for women with pre‐existing diabetes in rural compared to metropolitan settings in Victoria, Australia
Authors: Williamson Rebecca L. , McCarthy Elizabeth A. , Oats Jeremy J. , Churilov Leonid , Lappas Martha , Shub Alexis
Published: January 2021

Background

Pre‐existing diabetes in pregnancy is associated with an increased risk of complications. Likewise, living in rural, regional and remote Victoria, Australia, is also associated with poorer health outcomes. There is a gap in the literature with regard to whether Victorian women with pre‐existing diabetes experience a greater risk of adverse pregnancy outcomes compared to their metropolitan counterparts.

Aim

Our objective is to compare obstetric and perinatal outcomes for women with pre‐existing diabetes delivering in rural vs metropolitan hospitals in Victoria, Australia.

Materials and Methods

Retrospective population‐based study using routinely collected state‐based data of singleton births to women with type 1 and type 2 diabetes who delivered in metropolitan (n = 3233) and rural hospitals (n = 693) in Victoria, Australia, between 2006–2015. Pearson's χ2 test, Fisher’s exact test and MannWhitney U‐test were used to compare obstetric and perinatal outcomes between metropolitan and rural locations.

Results

Delivery in a rural hospital was associated with higher rates of stillbirth (2.3% vs 1.1%, P = 0.027), macrosomia (25.9% vs 16.9%, P < 0.001), shoulder dystocia (8.4% vs 3.5%, P < 0.001) and admission to the neonatal intensive care unit/special care nursery (73.2% vs 59.3%, P < 0.001). Smoking (18.0% vs 8.9%, P < 0.001), overweight/obesity (P = 0.047) and socioeconomic disadvantage (P < 0.001) were more common in rural women.

Conclusions

Women with pre‐existing diabetes who deliver in rural hospitals experience a greater risk of adverse perinatal outcomes and present with increased maternal risk factors. These results suggest a need to improve care for women with pre‐existing diabetes in rural Victoria.
Review highlights the latest research in Kingella kingae and stresses that molecular tests are required for diagnosis
Authors: Yagupsky Pablo
Published: January 2021

Aim

The aim of this study was to provide an update on paediatric Kingella kingae infections.

Methods

We used the PubMed database to identify studies published in English, French and Spanish up to 15 November 2020.

Results

Kingella kingae colonised the oropharynx after the age of 6 months, and the mucosal surface was the portal of entry of the organism to the bloodstream and the source of child‐to‐child spread. Attending day care centres was associated with increased carriage rate and transmission and disease outbreaks were detected in day care facilities. Skeletal system infections were usually characterised by mild symptoms and moderately elevated inflammation markers, requiring a high clinical suspicion index. The organism was difficult to recover in cultures and molecular tests significantly improve its detection. Kingella kingae was generally susceptible to beta‐lactam antibiotics, and skeletal diseases and bacteraemia responded to antimicrobial, leaving no long‐term sequelae. However, patients with endocarditis frequently experienced life‐threatening complications and the case fatality rate exceeded 10%.

Conclusion

Kingella kingae was the prime aetiology of skeletal system infections in children aged 6–48 months. Paediatricians should be aware of the peculiar features of this infection and the need to use molecular tests for diagnosis.
Impact of the COVID‐19 pandemic on children with and without risk for neurodevelopmental impairments
Authors: Ehrler Melanie , Werninger Isabelle , Schnider Barbara , Eichelberger Dominique A. , Naef Nadja , Disselhoff Vera , Kretschmar Oliver , Hagmann Cornelia F. , Latal Beatrice , Wehrle Flavia M.
Published: January 2021

Aim

To examine how the ongoing COVID‐19 pandemic impacts child well‐being and family functioning, particularly among children at risk for neurodevelopmental impairments.

Methods

Families of 73 typically developing children, 54 children born very preterm (VPT) and 73 children with congenital heart disease (CHD) from two prospective cohort studies were assessed prior to (mean age: 10.4 [SD: 1.2] years) and during (mean age: 12.8 [SD: 2.0] years) the pandemic, more specifically, in April/May 2020. Child well‐being and family functioning were assessed with validated, parent‐reported questionnaires and tested with linear mixed models. Group comparison of child distress and parental concerns related to medical implications of COVID‐19 and homeschooling, assessed with 5‐point Likert scales, was done with Mann–Whitney U tests.

Results

Children's psychological well‐being and family functioning (both, p < 0.001) decreased significantly during the pandemic, irrespective of group. Children with CHD were reported to be more concerned about becoming infected with SARS‐CoV‐2 than were others. Child distress due to homeschooling and parents' concerns about children's academic achievements were significantly higher in VPT and CHD children than in typically developing peers (all p < 0.001).

Conclusion

The COVID‐19 pandemic substantially impacts the whole family and leads to additional distress in families with children at risk for neurodevelopmental impairments. These families should receive individualised counselling and assistance from healthcare providers and schools during the pandemic.
Cognitive profiles of extremely preterm children: Full‐Scale IQ hides strengths and weaknesses
Authors: F. Kaul Ylva , Johansson Martin , Månsson Johanna , Stjernqvist Karin , Farooqi Aijaz , Serenius Fredrik , B. Thorell Lisa
Published: January 2021

Aim

To study whether a specific cognitive profile can be identified for children born extremely preterm (EPT) by investigating: 1) strengths and weaknesses not revealed by Full‐Scale IQ, 2) overlap between different cognitive deficits and 3) proportion of EPT children with multiple deficits.

Methods

We analysed data from the 4th version of Wechsler Intelligence Scales for Children in EPT children (n = 359) and matched controls (n = 367), collected within the 6.5‐year follow‐up of a population‐based prospective cohort study.

Results

Extremely preterm children performed worse than controls on all measures. Group differences were the largest in Perceptual Reasoning (PRI) and Working Memory (WMI), but differences between indices were small. However, when conducting categorical analyses, deficits in PRI and/or WMI were not more common than other combinations. Many EPT children had no or mild cognitive deficits, although often in multiple domains.

Conclusion

Extremely preterm children had greater weaknesses in working memory and perceptual abilities. However, detailed analyses of cognitive subscales showed large heterogeneity and provided no support for a specific cognitive profile. In conclusion, Full‐Scale IQ scores hide strengths and weaknesses and individual profiles for EPT children need to be considered in order to provide appropriate support.
Development and validation of a self‐report measure of practical barriers to medication adherence: The medication practical barriers to adherence questionnaire (MPRAQ)
Authors: Chan Amy Hai Yan , Vervloet Marcia , Lycett Helen , Brabers Anne , van Dijk Liset , Horne Rob
Published: January 2021

Aim

This study reports the development and validation of a new self‐report measure, the Medication Practical barriers to Adherence Questionnaire (MPRAQ), which assesses practical barriers to medication adherence.

Methods

The MPRAQ comprises 15 statements describing practical barriers. Responses are scored on a 5‐point Likert scale; higher scores indicate more practical barriers. Initial face validity was evaluated by cognitive testing with patients from a diabetes support group. Following refinement, internal reliability and construct validity were assessed in two samples: patients recruited via Amazon mTurk and the Nivel Dutch Healthcare Consumer Panel (COPA). Respondents completed the Beliefs about Medicines Questionnaire (BMQ‐General and BMQ‐Specific), and the Medication Adherence Report Scale (MARS‐5). The mTurk sample also completed the Perceived Sensitivity to Medicines questionnaire (PSM) and repeated the MPRAQ 2 weeks later to assess test‐retest reliability.

Results

Face validity was evaluated in 15 patients (46% female; mean (SD) age 64 (12) years). A total of 184 mTurk participants completed the questionnaire (in English) and 334 in COPA (in Dutch). Internal reliability was acceptable (mTurk α = 0.89; COPA α = 0.94). Construct validity was confirmed, with significant correlation between the MPRAQ and BMQ‐Specific Concerns (mTurk r = 0.546, P < .0001; COPA r = 0.370, P < .0001), BMQ‐General Harm (mTurk r = 0.504, P < 0.0001; COPA r = 0.219, P < .0001), BMQ‐General Overuse (mTurk r = 0.324, P < .0001; COPA r = 0.109, P = .047) and PSM (mTurk only r = 0.463, P < .0001), and a negative correlation with MARS‐5 (mTurk r = −0.450, P < .0001; COPA r = −0.260, P < .0001). MPRAQ did not correlate with BMQ‐Specific Necessity or BMQ‐General Benefit. Correlation between MPRAQ baseline and 2‐week follow‐up scores confirmed test‐retest reliability (r = 0.745, P < .0001; n = 52).

Conclusion

MPRAQ is a reliable and valid self‐report measure of practical adherence barriers.
High erythroferrone expression in CD71+ erythroid progenitors predicts superior survival in myelodysplastic syndromes
Authors: Riabov Vladimir , Mossner Maximilian , Stöhr Alexandra , Jann Johann‐Christoph , Streuer Alexander , Schmitt Nanni , Knaflic Antje , Nowak Verena , Weimer Nadine , Obländer Julia , Palme Iris , Schumann Christiane , Baldus Claudia D. , Schulze Torsten J. , Wuchter Patrick , Röhl Henning , Jawhar Ahmed , Weiss Christel , Boch Tobias , Metzgeroth Georgia , Neumann Martin , Hofmann Wolf‐Karsten , Nolte Florian , Nowak Daniel
Published: January 2021

Ineffective erythropoiesis and iron overload are common in myelodysplastic syndromes (MDS). Erythroferrone (ERFE) and growth/differentiation factor 15 (GDF15) are two regulators of iron homeostasis produced by erythroid progenitors. Elevated systemic levels of ERFE and GDF15 in MDS are associated with dysregulated iron metabolism and iron overload, which is especially pronounced in MDS with SF3B1 gene mutations. However, the role of ERFE and GDF15 in MDS pathogenesis and their influence on disease progression are largely unknown. Here, we analyzed the expression of ERFE and GDF15 in CD71+ erythroid progenitors of n = 111 MDS patients and assessed their effects on patient survival. The expression of ERFE and GDF15 in MDS was highly aberrant. Unexpectedly, ERFE expression in erythroprogenitors was highly relevant for MDS prognosis and independent of International Prognostic Scoring System (IPSS) stratification. Although ERFE expression was increased in patients with SF3B1 mutations, it predicted overall survival (OS) in both the SF3B1wt and SF3B1mut subgroups. Of note, ERFE overexpression predicted superior OS in the IPSS low/Int‐1 subgroup and in patients with normal karyotype. Similar observations were made for GDF15, albeit not reaching statistical significance. In summary, our results revealed a strong association between ERFE expression and MDS outcome, suggesting a possible involvement of ERFE in molecular MDS pathogenesis.
Non‐Hodgkin lymphoma after treatment for classical Hodgkin lymphoma: a report from the German Hodgkin Study Group
Authors: Eichenauer Dennis A. , Müller Horst , Elger Leonard , Goergen Helen , Fuchs Michael , Kreissl Stefanie , Böll Boris , Diehl Volker , von Tresckow Bastian , Borchmann Peter , Engert Andreas
Published: January 2021

Data on non‐Hodgkin lymphoma (NHL) after classical Hodgkin lymphoma (cHL) are scarce. We therefore performed a retrospective analysis comprising 11·841 cHL patients who had first‐line treatment within the randomized German Hodgkin Study Group (GHSG) HD7–HD15 studies. After a median follow‐up of 106 months, 175 patients (1·5%) had developed NHL. The median time to NHL was 44 months, the median age at NHL diagnosis was 54 years. The five‐year event‐free survival and overall survival estimates from the diagnosis of NHL were 36·9% and 44·2%, respectively. Thus, NHL after cHL is a rare event primarily affecting older individuals and often resulting in the patient´s death.
Therapeutic efficacy of the novel selective RNA polymerase I inhibitor CX‐5461 on pulmonary arterial hypertension and associated vascular remodelling
Authors: Xu Xia , Feng Hua , Dai Chaochao , Lu Weida , Zhang Jun , Guo Xiaosun , Yin Qihui , Wang Jianli , Cui Xiaopei , Jiang Fan
Published: January 2021

Background and Purpose

CX‐5461 is a novel selective RNA polymerase I (Pol I) inhibitor. Previously, we found that CX‐5461 could inhibit pathological arterial remodelling caused by angioplasty and transplantation. In the present study, we explored the pharmacological effects of CX‐5461 on experimental pulmonary arterial hypertension (PAH) and PAH‐associated vascular remodelling.

Experimental Approach

PAH was induced in Sprague–Dawley rats by monocrotaline or Sugen/hypoxia.

Key Results

We demonstrated that CX‐5461 was well tolerated for in vivo treatments. CX‐5461 prevented the development of pulmonary arterial remodelling, perivascular inflammation, pulmonary hypertension, and improved survival. More importantly, CX‐5461 partly reversed established pulmonary hypertension. In vitro, CX‐5461 induced cell cycle arrest in human pulmonary arterial smooth muscle cells. The beneficial effects of CX‐5461 in vivo and in vitro were associated with increased activation (phosphorylation) of p53.

Conclusion and Implications

Our results suggest that pharmacological inhibition of Pol I may be a novel therapeutic strategy to treat otherwise drug‐resistant PAH.
Targeting the CB2 receptor and other endocannabinoid elements to delay disease progression in amyotrophic lateral sclerosis
Authors: Rodríguez‐Cueto Carmen , García‐Toscano Laura , Santos‐García Irene , Gómez‐Almería Marta , Gonzalo‐Consuegra Claudia , Espejo‐Porras Francisco , Fernández‐Ruiz Javier , de Lago Eva
Published: January 2021

Cannabinoids form a singular group of plant‐derived compounds, endogenous lipids and synthetic derivatives with multiple therapeutic effects exerted by targeting different elements of the endocannabinoid system. One of their therapeutic applications is the preservation of neuronal integrity exerted by attenuating the multiple neurotoxic events that kill neurons in neurodegenerative disorders. In this review, we will address the potential of cannabinoids as neuroprotective agents in amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disorder characterized by muscle denervation, atrophy and paralysis, and progressive deterioration in upper and/or lower motor neurons. The emphasis will be paid on the cannabinoid type 2 (CB2) receptor, whose activation limits glial reactivity, but the potential of additional endocannabinoid‐related targets will be also addressed. The evidence accumulated so far at the preclinical level supports the need to soon move towards the patients and initiate clinical trials to confirm the potential of cannabinoid‐based medicines as disease modifiers in ALS.

LINKED ARTICLES

This article is part of a themed issue on Recent advances in ALS pathogenesis and therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.6/issuetoc
Impairment of platelet NO signalling in coronary artery spasm: role of hydrogen sulphide
Authors: Imam Hasan , Nguyen Thanh H. , Stafford Irene , Liu Saifei , Heresztyn Tamila , Chirkov Yuliy Y. , Horowitz John D.
Published: January 2021

Background and Purpose

The pathophysiology of coronary artery spasm (CAS), with its associated ischaemic crises, is currently poorly understood and treatment is frequently ineffective. In view of increasing evidence that platelet‐based defects may occur in CAS patients, we investigated platelet reactivity in CAS patients and whether symptomatic crises reflect activation of platelet–endothelial interactions.

Experimental Approach

CAS patients were evaluated during acute and/or chronic symptomatic phases and compared with healthy control subjects. Inhibition of ADP‐induced platelet aggregation by the NO donor sodium nitroprusside (SNP) and plasma concentrations of syndecan 1 (glycocalyx shedding marker), tryptase (mast cell activation marker) and platelet microparticles were measured.

Key Results

Inhibition of platelet aggregation by SNP was diminished in chronic CAS, with further (non‐significant) deterioration during symptomatic crises, whereas plasma concentrations of syndecan 1, tryptase and platelet microparticles increased. Treatment of patients with high‐dose N‐acetylcysteine (NAC) plus glyceryl trinitrate rapidly increased platelet responsiveness to SNP and decreased plasma syndecan 1 concentrations. The effect of NAC on platelet responsiveness to SNP was confirmed in vitro and mimicked by the H2S donor NaHS. Conversely, inhibition of enzymatic production of H2S attenuated NAC effect.

Conclusion and Implications

CAS is associated with substantial impairment of platelet NO signalling. During acute symptomatic exacerbations, platelet resistance to NO is aggravated, together with mast cell activation and damage to both vasculature and platelets. NAC, via release of H2S, reverses platelet resistance to NO and terminates glycocalyx shedding during symptomatic crises: This suggests that H2S donors may correct the pathophysiological anomalies underlying CAS.
Neurological risks and benefits of cytokine‐based treatments in coronavirus disease 2019: from preclinical to clinical evidence
Authors: Pignataro Giuseppe , Cataldi Mauro , Taglialatela Maurizio
Published: January 2021

Immunodeficiency and hyperinflammation are responsible for the most frequent and life‐threatening forms of coronavirus disease 2019 (COVID‐19). Therefore, cytokine‐based treatments targeting immuno‐inflammatory mechanisms are currently undergoing clinical scrutiny in COVID‐19‐affected patients. In addition, COVID‐19 patients also exhibit a wide range of neurological manifestations (neuro‐COVID), which may also benefit from cytokine‐based treatments. In fact, such drugs have shown some clinical efficacy also in neuroinflammatory diseases. On the other hand, anti‐cytokine drugs are endowed with significant neurological risks, mainly attributable to their immunodepressant effects. Therefore, the aim of the present manuscript is to briefly describe the role of specific cytokines in neuroinflammation, to summarize the efficacy in preclinical models of neuroinflammatory diseases of drugs targeting these cytokines and to review the clinical data regarding the neurological effects of these drugs currently being investigated against COVID‐19, in order to raise awareness about their potentially beneficial and/or detrimental neurological consequences.

LINKED ARTICLES

This article is part of a themed issue on The second wave: are we any closer to efficacious pharmacotherapy for COVID 19? (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.10/issuetoc
Beneficial effects of a combination of natural product activators of autophagy on endothelial cells and platelets
Authors: Carnevale Roberto , Nocella Cristina , Schiavon Sonia , Cammisotto Vittoria , Cotugno Maria , Forte Maurizio , Valenti Valentina , Marchitti Simona , Vecchio Daniele , Biondi Zoccai Giuseppe , Rubattu Speranza , Martinelli Ombretta , Pignatelli Pasquale , Violi Francesco , Volpe Massimo , Versaci Francesco , Frati Luigi , Frati Giacomo , Sciarretta Sebastiano
Published: January 2021

Background and Purpose

Oxidative stress and insufficient autophagy activity are associated with inflammatory processes and are common features of many cardiovascular diseases (CVDs). We investigated if a combination of natural activators of autophagy could modulate oxidative stress, platelet aggregation and endothelial cell survival and function in response to stress.

Experimental Approach

Ex vivo platelet aggregation and activation, H2O2 production and autophagy were measured in platelets of subjects at high cardiovascular risk, including smokers, patients with metabolic syndrome (MetS) and patients with atrial fibrillation (AF). In vitro, the effects of a mixture of natural pro‐autophagy molecules and antioxidants on platelets and human umbilical vein endothelial cells (HUVECs) were evaluated.

Key Result

Autophagy appeared to be inhibited, whereas aggregation was increased in platelets from AF and MetS patients and in smokers, as compared with healthy subjects. Treatment of platelets isolated from these patients with a mixture composed of trehalose, spermidine, catechin and epicatechin (Mix1) or with a mixture composed of trehalose, spermidine and nicotinamide (Mix2), significantly reduced platelet activation and oxidative stress, and increased autophagy, compared with the effect of each compound alone. Similarly, treatment of HUVECs with a combination of these compounds exhibited beneficial effects and increased endothelial cell survival, nitric oxide bioavailability and angiogenesis in response to stress in a potentiated manner.

Conclusion and Implications

A combination of natural activators of autophagy could inhibit platelet activity and oxidative stress and improve endothelial cell survival and function in a potentiated manner representing a useful strategy to reduce the effect of risk factors on CVD occurrence.

LINKED ARTICLES

This article is part of a themed issue on Cellular metabolism and diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.10/issuetoc
Toddlers Prefer Adults as Informants: 2‐ and 3‐Year‐Olds’ Use of and Attention to Pointing Gestures From Peer and Adult Partners
Authors: Kachel Gregor , Moore Richard , Hepach Robert , Tomasello Michael
Published: January 2021

Two‐ and 3‐year‐old children (N = 96) were tested in an object‐choice task with video presentations of peer and adult partners. An immersive, semi‐interactive procedure enabled both the close matching of adult and peer conditions and the combination of participants’ choice behavior with looking time measures. Children were more likely to use information provided by adults. As the effect was more pronounced in the younger age‐group, the observed bias may fade during toddlerhood. As there were no differences in children’s propensity to follow peer and adult gestures with their gaze, these findings provide some of the earliest evidence to date that young children take an interlocutor’s age into account when judging ostensively communicated testimony.