bluuebunny/crossref_metadata_2025 huggingface dataset:
Detecting plant species in the field with deep learning and drone technology
Authors: James Katherine , Bradshaw Karen
Published: August 2020

Aerial drones are providing a new source of high‐resolution imagery for mapping of plant species of interest, amongst other applications. On‐board detection algorithms could open the door to allow for applications in which drones can intelligently interact with their environment. However, the majority of plant detection studies have focused on detection in post‐flight processed orthomosaics. Greater research into developing detection algorithms robust to real‐world variations in environmental conditions is necessary, such that they are suitable for deployment in the field under variable conditions.

We outline the steps necessary to develop such a system, show by example how real‐world considerations can be addressed during model training and briefly illustrate the performance of our best performing model in the field when integrated with an aerial drone.

Our results show that introducing variations in brightness as an additional augmentation strategy during training is beneficial when dealing with real‐life data. We achieved a 27% improvement in the F1‐score obtained on the unseen test set when using this approach. Further improvements to the model performance were obtained through the use of weight map‐based loss, accounting for uncertainty in the annotation masks due to the indistinct nature of the edges of the target plants using weighting. This resulted in a 15% improvement in precision for the best configuration of hyper‐parameters, yielding a final model with an F1‐score of 83% and accuracy of 96%. Finally, results computed on the fly show that such a system is deployable in the field.

This study shows that it is possible for a commercially available drone, integrated with a deep learning model, to detect invasive plants in the field and demonstrates methodology which could be applied to developing similar systems for other plant species of interest. The ability to perform detection on the fly is necessary for future applications in which intelligent interaction between a drone and its environment is required.
phyloregion: R package for biogeographical regionalization and macroecology
Authors: Daru Barnabas H. , Karunarathne Piyal , Schliep Klaus
Published: August 2020

Biogeographical regionalization is the classification of regions in terms of their biota and is key to our understanding of the ecological and historical drivers affecting species distribution in macroecological or large‐scale conservation studies. However, despite the mass production of species distributions and phylogenetic data, statistical and computational infrastructure to successfully incorporate, manipulate and analyse such massive amounts of data had not been fully developed.

Here, we present phyloregion, a statistical package for the analysis of biogeographical regionalization and macroecology in the R computing environment, tailored for mega phylogenies and macroecological datasets of ever‐increasing size and complexity.

Compared to available packages, phyloregion is several times faster and allocates less memory than other packages for analysis of alpha diversity (including phylogenetic diversity, phylogenetic endemism and evolutionary distinctiveness and global endangerment) and beta diversity (including cluster analysis, determining optimal number of clusters and evolutionary distinctiveness of regions).

We demonstrate the scalability of the package to large datasets with comprehensive phylogenies and global distribution maps of squamate reptiles (amphisbaenians, lizards and snakes), and show that different phyloregions differ strongly in evolutionary distinctiveness across scales. Visualization tools allow graphical exploration of the generated patterns of biogeographical regionalization and macroecology in geographical space.

Ultimately, phyloregion will facilitate rapid biogeographical analyses that will accommodate the ongoing mass production of species occurrence records and phylogenetic datasets at any scale and for any taxonomic group into completely reproducible R workflows.
Tensor decomposition for infectious disease incidence data
Authors: Korevaar Hannah , Metcalf C. Jessica , Grenfell Bryan T.
Published: August 2020

Many demographic and ecological processes generate seasonal and other periodicities. Seasonality in infectious disease transmission can result from climatic forces such as temperature and humidity; variation in contact rates as a result of migration or school calendar; or temporary surges in birth rates. Seasonal drivers of acute immunizing infections can also drive longer‐term fluctuations.

Tensor decomposition has been used in many disciplines to uncover dominant trends in multi‐dimensional data. We introduce tensors as a novel method for decomposing oscillatory infectious disease time series.

We illustrate the reliability of the method by applying it to simulated data. We then present decompositions of measles data from England and Wales. This paper leverages simulations as well as much‐studied data to illustrate the power of tensor decomposition to uncover dominant epidemic signals as well as variation in space and time. We then use tensor decomposition to uncover new findings and demonstrate the potential power of the method for disease incidence data. In particular, we are able to distinguish between annual and biennial signals across locations and shifts in these signals over time.

Tensor decomposition is able to isolate variation in disease seasonality as a result of variation in demographic rates. The method allows us to discern variation in the strength of such signals by space and population size. Tensors provide an opportunity for a concise approach to uncovering heterogeneity in disease transmission across space and time in large datasets.
Similar burden of pathogenic coding variants in exceptionally long‐lived individuals and individuals without exceptional longevity
Authors: Gutman Danielle , Lidzbarsky Gabriel , Milman Sofiya , Gao Tina , Sin-Chan Patrick , Gonzaga‐Jauregui Claudia ,   Regeneron Genetics Center, Deelen Joris , Shuldiner Alan R. , Barzilai Nir , Atzmon Gil
Published: August 2020

Centenarians (exceptionally long‐lived individuals—ELLI) are a unique segment of the population, exhibiting long human lifespan and healthspan, despite generally practicing similar lifestyle habits as their peers. We tested disease‐associated mutation burden in ELLI genomes by determining the burden of pathogenic variants reported in the ClinVar and HGMD databases using data from whole exome sequencing (WES) conducted in a cohort of ELLI, their offspring, and control individuals without antecedents of familial longevity (n = 1879), all descendent from the founder population of Ashkenazi Jews. The burden of pathogenic variants did not differ between the three groups. Additional analyses of variants subtypes and variant effect predictor (VEP) biotype frequencies did not reveal a decrease of pathogenic or loss‐of‐function (LoF) variants in ELLI and offspring compared to the control group. Case–control pathogenic variants enrichment analyses conducted in ELLI and controls also did not identify significant differences in any of the variants between the groups and polygenic risk scores failed to provide a predictive model. Interestingly, cancer and Alzheimer's disease‐associated variants were significantly depleted in ELLI compared to controls, suggesting slower accumulation of mutation. That said, polygenic risk score analysis failed to find any predictive variants among the functional variants tested. The high similarity in the burden of pathogenic variation between ELLI and individuals without familial longevity supports the notion that extension of lifespan and healthspan in ELLI is not a consequence of pathogenic variant depletion but rather a result of other genomic, epigenomic, or potentially nongenomic properties.
Cocaine treatment demands in 10 western European countries: observed trends between 2011 and 2018
Authors: Antoine Jérôme , Berndt Nadine , Astudillo Mariana , Cairns Donal , Jahr Stefan , Jones Andrew , Kuijpers Wil , Llorens Noelia , Lyons Suzi , Maffli Etienne , Magliocchetti Natalia , Molina Olivas Marta , Palle Christophe , Schwarzkopf Larissa , Wisselink Jeroen , Montanari Linda
Published: August 2020

Aims

To describe cocaine treatment demand in 10 western European countries and to examine the size, direction and temporality of recent trends in the proportion of cocaine users among all clients entering treatment.

Design

Aggregated data collected through the European Union standardized treatment demand monitoring system (TDI) between 2011 and 2018 were used.

Setting

Belgium, England, France, Germany, Ireland, Italy, Luxembourg, Spain, Switzerland and the Netherlands.

Participants

In total, more than 700 000 cocaine treatment records were analysed. Clients in treatment for cocaine as primary drug were predominantly male (85%), with an average age of 35 years.

Measurements

Number of treatment episodes for substance use and for cocaine as primary or secondary drug were collected year‐ and country‐wise. When available, powder cocaine and crack and patients with and without previous treatment were differentiated.

Findings

Among the participating countries the share of cocaine as primary drug in treatment demand ranged between 4.7% [95% confidence interval (CI) = 4.6–4.9%] in Germany and 43.1% in Spain (95% CI = 42.6–43.5%). The general trend analysis showed a decreasing proportion of cocaine‐related treatment entrants between 2011 and 2014 among all subgroups followed by a strong increase in 2015. The increase appeared stronger than for powder cocaine. Seven of 10 countries observed a recent significant increase in the proportion of treatment entrants reporting cocaine as the primary substance: Belgium [annual percentage change (APC) = 9.6%, P < 0.01], England (APC = 14.9%, P < 0.05), France (APC = 21.8%, P < 0.01), Ireland (APC = 28.2%, P < 0.01), Italy (APC = 7.8%, P < 0.01), Spain (APC = 7.0%, P < 0.05) and Switzerland (APC = 12.0%, P < 0.05). Trends were similar when looking at cocaine reported as primary or adjunctive substance.

Conclusions

Despite substantial country‐specific variation regarding cocaine prevalence and treatment demand, there has been an overall significant increase since 2015 in the share of cocaine‐related treatment demand in western Europe.
The landscape configuration and lethality of snare poaching of sympatric guilds of large carnivores and ungulates
Authors: Mudumba Tutilo , Jingo Sophia , Heit David , Montgomery Robert A.
Published: August 2020

Poaching of wildlife presents one of the biggest conservation challenges in the 21st century. Snaring is one of the primary means of capturing target animals. To prioritise interventions intending to reduce snaring, we describe an approach for quantifying the configuration and lethality of snares. We conducted transect surveys in Murchison Falls National Park. All the snares that we recovered were made of wire with the majority (81.0%, n = 546 of 674) deriving from vehicle tire wire. The density of snares ranged from 0.08 to 4.58 snares/km2, which is the highest known density in sub‐Saharan Africa. The majority (63%) of the animals caught in wire snares were unrecovered and wasted. We found that noose width, vertical drop, wire circumference, anchor height, proportion of un‐thicketed area, grass height, distance to river and village had a significant positive relationships to lethality, while snare thickness, charms, tree DBH, thicket diameter, distance to nearest road negatively affected lethality. We recommend adopting wholistic anti‐snare countermeasures such as the human heritage‐centred conservation to empower local people. Our method illustrates the opportunity to standardise temporal and spatial measurements of snare density and configuration necessary to stop illegal wildlife poaching.
Recurrent miscarriage is not associated with a higher prevalence of inherited and acquired thrombophilia
Authors: Vomstein Kilian , Herzog Anna , Voss Pauline , Feil Katharina , Goeggl Tamara , Strowitzki Thomas , Toth Bettina , Kuon Ruben‐Jeremias
Published: August 2020

Problem

Although not being recommended in guidelines, many physicians perform routine screening for thrombophilia in RM patients suspecting a higher prevalence in these patients. The aim of this study was to analyze the prevalence of inherited and acquired thrombophilia in a large cohort of RM patients.

Method of study

Within a multicenter case‐control study, n = 820 RM patients and n = 141 controls were included. The prevalence of inherited and acquired thrombophilia including deficiency of protein C/S and antithrombin, elevation of factor VIII activity, APC resistance including mutation in the factor V Leiden gene, mutation in the prothrombin gene and antiphospholipid antibodies were assessed. Further, we performed a meta‐analysis of the prevalence of thrombophilia in RM patients including studies between 01/2000 and 01/2020.

Results

An antiphospholipid syndrome (APLS) was only present in RM patients. Increased factor VIII concentration was significantly more prevalent in controls (RM vs controls: 5.8% vs 11.0%). None of the other thrombophilia did differ significantly between RM patients and controls. The meta‐analysis revealed no significant difference in the occurrence of these thrombophilia between RM patients and controls.

Conclusion

The prevalence of inherited thrombophilia does not differ between RM patients and controls. When analyzing rare events like thrombophilia, a high number of patients are needed to obtain reliable results, which might explain contradictory findings in previous studies analyzing small cohorts of RM patients. Despite being less prevalent than previously described, we still recommend screening for APLS as it is associated with severe pregnancy complications.
From Partisan Universal to Concrete Universal? The Pashtun Tahaffuz Movement in Pakistan
Authors: Mallick Ayyaz
Published: August 2020

This paper explores the question of universal‐particular through the anti‐war Pashtun Tahaffuz (Protection) Movement in Pakistan. With its demands couched in the language of pain, rights to life and “dignity”, the PTM mobilises popular Pashtun sentiments as a “partisan universal”: a political formulation which achieves the common good even as it attends to particular interests. However, within the re‐formulated urban question in post‐9/11 Pakistan, PTM also attempts to make common cause with other ethnic‐spatial communities through shared—but situated and differentiated—experiences of dispossession. Thus, the PTM’s “dialectic of experience” is a partisan universal in search of a “concrete universal”: a non‐totalising but encompassing and open universality, a universal politics which works through the particularity of specific groups’ experiences. It is in this terrain of political practice, and its attendant theoretical articulations, that we will find the—contingent and processual—resolution of the transition from particularity to universality.
Evaluation of analytical accuracy of HER2 status in patients with breast cancer
Authors: Jensen Steffen Grann , Thomas Peter Engel , Christensen Ib Jarle , Balslev Eva , Hansen Alastair , Høgdall Estrid
Published: August 2020

Human epidermal growth factor receptor 2 (HER2) gene status and overexpression, occurring in ~ 13.6% of primary breast cancers, is essential for identifying patients likely to benefit from biological treatment. In this method of evaluation study, we tested and compared the HER2 gene–protein assay (GPA) with routine HER2 immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). The GPA was evaluated using 67 formalin‐fixed paraffin‐embedded (FFPE) HER2 equivoval IHC (2+) breast cancer tissue samples. Overall, agreement between GPA silver in situ hybridization (SISH) and FISH was 91.9% (57/62). Regression analysis revealed slightly higher, but non‐significant difference in HER2/chromosome enumeration probe 17 (CEP17) ratio for GPA as compared to FISH (p = 0.074). Intraclass correlation coefficients (ICCs) of 0.94 and Spearman´s rank correlation coefficients of 0.93 (p < 0.0001) for FISH and GPA SISH suggested strong inter‐observer association for methods with one observer counting on average 0.23 significant higher for GPA SISH (p = 0.014). Intra‐observer IHC method reproducibility was 52.6% (κ = 0.3122, p = 0.004) and 79.7% (κ = 0.6428, p = 0.9197), suggesting fair significant and substantial non‐significant difference between tests for reviewers. Inter‐observer reproducibility for IHC methods was 53%. While inter‐observer reproducibility for experienced IHC interpretation suggested significant differences (κ = 0.3636, p = 0.0332), unexperienced interpretation of IHC GPA suggested fair non‐significant difference between reviewers (κ = 0.3101, p = 0.0747). Using FISH as reference, the diagnostic indices for GPA SISH were as follows: sensitivity 100%, specificity 95% and accuracy 92%. Inaccuracy between tests was in 80% of cases due to ISH categorization as equivocal by one of the methods. IHC results highlight that it may be beneficial with a method for simultaneously visualization of HER2 gene and protein status.
You Wouldn’t Like Me When I’m Angry: A Daily Diary Study of Displaced Online Aggression in Dual‐Earner Couples
Authors: Vranjes Ivana , Baillien Elfi , Erreygers Sara , Vandebosch Heidi , De Witte Hans
Published: August 2020

Modern technologies can aid working processes as well as provide individuals with an opportunity to connect and form interpersonal relationships. However, they can also create a context for displaced aggression. In this study, we examine whether people experiencing work stressors may engage in online antisocial behavioral as a means of venting their negative emotions. Specifically, we investigate whether experiencing stressors at work fuels anger in the private context and whether this anger triggers subsequent displaced aggression in the form of antisocial online behavior (AOB) throughout the evening. Additionally, we examine the crossover of anger to AOB in couples in their private context. We conducted a diary study amongst 95 dual‐earner couples, twice a day, during five consecutive working days. Results confirmed that men’s daily work stressors spilled over to their private context in the form of anger after work and AOB throughout the evening. No crossover effects were found from their partner. For women, a crossover effect was found of their partner’s work stressors and anger on their own AOB. These results demonstrate gender differences in displaced online aggression.
Developing an instrument to assess cancer patient preparedness for transition to survivorship care in Korea
Authors: Lim Jung‐won
Published: August 2020

Purpose

The current study specified the initial qualitative stage to develop an instrument that assesses whether patients with cancer in Korea are ready for the transition from hospital‐based to community‐based survivorship care, focusing on psychosocial and behavioral aspects.

Methods

Individual interviews with cancer survivors, family members, and healthcare professionals in South Korea were conducted. Subsequently, analyses of qualitative data for creating items and pilot testing were performed to develop an instrument for Korean cancer survivors.

Results

An item pool for an initial version of a new instrument called the “Preparedness for Transition to Survivorship Care Instrument (PTSCI)” was developed by creating 20 themes and 41 subthemes around each of the 401 codes. After assessing face validity, a set of 46 items was chosen. The 46 items were organized into 6 components: (1) physical, (2) cognitive, (3) psychological, (4) social, (5) health management, and (6) information. The Cronbach's alpha of the instrument in the pilot testing was 0.872.

Discussion

The PTSCI offers an opportunity to identify the psychosocial and behavioral status of patients with cancer in the survivorship phase. This new instrument can be used to test psychosocial and behavioral interventions for individuals who are not ready for the survivorship care phase.
Infant drug exposure via breast milk
Authors: Verstegen Ruud H.J. , Anderson Philip O. , Ito Shinya
Published: August 2020

More than half of women take medications during breastfeeding, predisposing their infants to medication exposure via breast milk. As a result, adverse drug reactions may emerge in the infant, although they are rarely reported. Disposition of maternal drugs in breast milk is described with several key parameters, which include relative infant dose (RID): infant drug intake via milk (weight‐ and time‐adjusted) expressed as a percentage of the similarly adjusted mother's dose. Most drugs show RID values of <10%, indicating that drug concentrations in infant serum do not reach a level known to be therapeutic in adults unless drug clearance is markedly lower than the adult level on a weight basis. RID is a function of milk‐to‐(maternal) plasma drug concentration ratio (MP ratio) and maternal drug clearance. Therefore, MP ratio between drugs must be interpreted not by itself but with maternal drug clearance of each drug. This is why some drugs such as phenobarbital show an MP ratio of <1 but an RID as high as 50–70%, while morphine shows an MP ratio of 2 but an RID in the range of 5%. Using RID, we interpreted case reports of infant adverse outcomes, and we observed cases with relatively low infant serum concentrations of drug, consistent with low RID, as well as those with near‐ or above‐adult therapeutic serum concentrations, with or without increased drug intake (i.e. high RID). It is important to consider both pharmacokinetic and pharmacodynamic factors in interpreting adverse outcomes in infants breastfed by a mother taking medications.
Antipsychotics inhibit the mitochondrial bioenergetics of pancreatic beta cells isolated from CD1 mice
Authors: Elmorsy Ekramy , Alelwani Walla , Kattan Shahad , Babteen Nouf , Alnajeebi Afnan , Ghulam Jihan , Mosad Soad
Published: August 2020

Antipsychotics (APs) are widely used medications with reported diabetogenic side effects. This study investigated the effect of commonly used APs, namely chlorpromazine (CPZ), haloperidol (HAL) and clozapine, on the bioenergetics of male CD1 mice isolated pancreatic beta cells as an underlying mechanism of their diabetogenic effects. The effect of APs on Alamar blue reduction, adenosine triphosphate (ATP) production and glucose‐stimulated insulin secretion (GSIS) of isolated beta cells was evaluated. Then, the effects of APs on the activities of mitochondrial complexes and their common coding genes expression, oxygen consumption rate (OCR), mitochondrial membrane potential (MMP) and lactate production were investigated. The effects of APs on the mitochondrial membrane fluidity (MMF) and mitochondrial membrane fatty acid composition were also examined. Results showed that the tested APs significantly decreased cellular ATP production and GSIS of the beta cells. The APs significantly inhibited the activities of mitochondrial complexes and their coding gene expression, MMP and OCR of the treated cells, with a parallel increase in lactate production to different extents with the different APs. CPZ and HAL showed increased MMF and mitochondrial membrane polyunsaturated fatty acid content. In conclusion, the tested APs‐induced mitochondrial disruption can play a role in their diabetogenic side effect.
The role of eosinophil morphology in distinguishing between reactive eosinophilia and eosinophilia as a feature of a myeloid neoplasm
Authors: Goasguen Jean E. , Bennett John M. , Bain Barbara J. , Brunning Richard , Zini Gina , Vallespi Maria‐Teresa , Tomonaga Masao , Locher Clara ,   The International Working Group on Morphology of MDS
Published: August 2020

Morphological features of eosinophils in patients with reactive eosinophilia (28 patients) and clonal eosinophilia (26 patients) have been compared with each other and with the eosinophil characteristics of healthy volunteers (three subjects) and of patients with the idiopathic hypereosinophilic syndrome (three patients). Morphological features, assessed in isolation from other haematological abnormalities, were found to have poor specificity for a myeloid neoplasm. The most useful feature was the presence of basophilic granules in mature eosinophils, which was associated particularly with acute myeloid leukaemia with inv(16). Marked reduction in granules occurred more often in some subsets of the myeloid neoplasm group but nevertheless was lacking in specificity since it was not infrequently seen in reactive eosinophilia. Although experienced morphologists more often considered that a myeloid neoplasm was likely in patients in whom this was the diagnosis (69%), myeloid neoplasia was also considered likely in a considerable proportion (39%) of patients with reactive eosinophilia. Morphological abnormalities of eosinophils therefore cannot be assessed in isolation in seeking to make a diagnosis of a myeloid neoplasm. Morphology is, however, needed and should be integrated with the results of other investigations.
Hydrogen sulfide signalling in the CNS ‐ Comparison with NO
Authors: Kimura Hideo
Published: August 2020

Hydrogen sulfide (H2S) together with polysulfides (H2Sn, n > 2) are signalling molecules like NO with various physiological roles including regulation of neuronal transmission, vascular tone, inflammation and oxygen sensing. H2S and H2Sn diffuse to the target proteins for S‐sulfurating their cysteine residues that induces the conformational changes to alter the activity. On the other hand, 3‐mercaptopyruvate sulfurtransferase transfers sulfur from a substrate 3‐mercaptopyruvate to the cysteine residues of acceptor proteins. A similar mechanism has also been identified in S‐nitrosylation. S‐sulfuration and S‐nitrosylation by enzymes proceed only inside the cell, while reactions induced by H2S, H2Sn and NO even extend to the surrounding cells. Disturbance of signalling by these molecules as well as S‐sulfuration and S‐nitrosylation causes many nervous system diseases. This review focuses on the signalling by H2S and H2Sn with S‐sulfuration comparing to that of NO with S‐nitrosylation and discusses on their roles in physiology and pathophysiology.
Anti‐tuberculosis effect of isoniazid scales accurately from zebrafish to humans
Authors: van Wijk Rob C. , Hu Wanbin , Dijkema Sharka M. , van den Berg Dirk‐Jan , Liu Jeremy , Bahi Rida , Verbeek Fons J. , Simonsson Ulrika S.H. , Spaink Herman P. , van der Graaf Piet H. , Krekels Elke H.J.
Published: August 2020

Background and Purpose

There is a clear need for innovation in anti‐tuberculosis drug development. The zebrafish larva is an attractive disease model in tuberculosis research. To translate pharmacological findings to higher vertebrates, including humans, the internal exposure of drugs needs to be quantified and linked to observed response.

Experimental Approach

In zebrafish studies, drugs are usually dissolved in the external water, posing a challenge to quantify internal exposure. We developed experimental methods to quantify internal exposure, including nanoscale blood sampling, and to quantify the bacterial burden, using automated fluorescence imaging analysis, with isoniazid as the test compound. We used pharmacokinetic–pharmacodynamic modelling to quantify the exposure–response relationship responsible for the antibiotic response. To translate isoniazid response to humans, quantitative exposure–response relationships in zebrafish were linked to simulated concentration–time profiles in humans, and two quantitative translational factors on sensitivity to isoniazid and stage of infection were included.

Key Results

Blood concentration was only 20% of the external drug concentration. The bacterial burden increased exponentially, and an isoniazid dose corresponding to 15 mg·L−1 internal concentration (minimum inhibitory concentration) leads to bacteriostasis of the mycobacterial infection in the zebrafish. The concentration–effect relationship was quantified, and based on that relationship and the translational factors, the isoniazid response was translated to humans, which correlated well with observed data.

Conclusions and Implications

This proof of concept study confirmed the potential of zebrafish larvae as tuberculosis disease models in translational pharmacology and contributes to innovative anti‐tuberculosis drug development, which is very clearly needed.
TASK‐1 channel blockade by AVE1231 increases vasocontractile responses and BP in 1‐ to 2‐week‐old but not adult rats
Authors: Shvetsova Anastasia A. , Gaynullina Dina K. , Schmidt Nadine , Bugert Peter , Lukoshkova Elena V. , Tarasova Olga S. , Schubert Rudolf
Published: August 2020

Background and Purpose

The vasomotor role of K2P potassium channels during early postnatal development has never been investigated. We tested the hypothesis that TASK‐1 channel (K2P family member) contribution to arterial vascular tone and BP is higher in the early postnatal period than in adulthood.

Experimental Approach

We studied 10‐ to 15‐day‐old (“young”) and 2‐ to 3‐month‐old (“adult”) male rats performing digital PCR (dPCR) (using endothelium‐intact saphenous arteries), isometric myography, sharp microelectrode technique, quantitative PCR (qPCR) and Western blotting (using endothelium‐denuded saphenous arteries), and arterial pressure measurements under urethane anaesthesia.

Key Results

We found mRNA of Kcnk1–Kcnk7, Kcnk12, and Kcnk13 genes to be expressed in rat saphenous artery, and Kcnk3 (TASK‐1) and Kcnk6 (TWIK‐2) were most abundant in both age groups. The TASK‐1 channel blocker AVE1231 (1 μmol·L−1) prominently depolarized arterial smooth muscle and increased basal tone level and contractile responses to methoxamine of arteries from young rats but had almost no effect in adult rats. The level of TASK‐1 mRNA and protein expression was higher in arteries from young compared with adult rats. Importantly, intravenous administration of AVE1231 (4 mg·kg−1) had no effect on mean arterial pressure in adult rats but prominently raised it in young rats.

Conclusion and Implications

We showed that TASK‐1 channels are important for negative feedback regulation of vasocontraction in young but not adult rats. The influence of TASK‐1 channels most likely contributes to low BP level at perinatal age.
Suppressor of Ty 16 promotes lung cancer malignancy and is negatively regulated by miR‐1227‐5p
Authors: Yang Lu , Wang Xing , Jiao Xinyan , Tian Bixia , Zhang Miao , Zhou Can , Wang Ruiqi , Chen He , Wang Bo , Li Juan , Liu Jie , Zhang Guanjun , Liu Peijun
Published: August 2020

Suppressor of Ty 16 (Spt16) is a component of the facilitates chromatin transcription (FACT) complex, which is a histone chaperone and involved in gene transcription, DNA replication, and DNA repair. Previous studies showed that FACT is highly expressed in cancer, and cancer cells are more reliant on FACT than normal cells. However, the relationship between Spt16 and lung cancer remains unclear. In this study, we explored the functions of Spt16 in lung cancer cells. The effects of Spt16 on lung cancer cell proliferation, cell cycle progression, apoptosis, migration, and invasion were examined. We found that knockdown of Spt16 led to obvious decreases of both Rb and MCM7, and further activated the DNA damage response (DDR) pathway. In addition, a novel micro‐RNA, miR‐1227‐5p, directly targeted the 3′‐UTR of Spt16 and regulated the mRNA levels of Spt16. Furthermore, we found that CBL0137, the functional inhibitor of FACT, showed similar effects as loss of Spt16. Together, our data indicated that Spt16 is likely to be an essential regulator for lung cancer malignancy and is negatively regulated by miR‐1227‐5p.
Chaperone‐mediated autophagy receptor modulates tumor growth and chemoresistance in non–small cell lung cancer
Authors: Ichikawa Akihiro , Fujita Yu , Hosaka Yusuke , Kadota Tsukasa , Ito Akihiko , Yagishita Shigehiro , Watanabe Naoaki , Fujimoto Shota , Kawamoto Hironori , Saito Nayuta , Yoshida Masahiro , Hashimoto Mitsuo , Minagawa Shunsuke , Hara Hiromichi , Motoi Noriko , Yamamoto Yusuke , Ochiya Takahiro , Araya Jun , Kuwano Kazuyoshi
Published: August 2020

Chaperone‐mediated autophagy (CMA) is a lysosomal degradation pathway of selective soluble proteins. Lysosome‐associated membrane protein type 2a (LAMP2A) is the key receptor protein of CMA; downregulation of LAMP2A leads to CMA blockade. Although CMA activation has been involved in cancer growth, CMA status and functions in non–small cell lung cancer (NSCLC) by focusing on the roles in regulating chemosensitivity remain to be clarified. In this study, we found that LAMP2A expression is elevated in NSCLC cell lines and patient's tumors, conferring poor survival and platinum resistance in NSCLC patients. LAMP2A knockdown in NSCLC cells suppressed cell proliferation and colony formation and increased the sensitivity to chemotherapeutic drugs in vitro. Furthermore, we found that intrinsic apoptosis signaling is the mechanism of cell death involved with CMA blockade. Remarkably, LAMP2A knockdown repressed tumorigenicity and sensitized the tumors to cisplatin treatment in NSCLC‐bearing mice. Our discoveries suggest that LAMP2A is involved in the regulation of cancer malignant phenotypes and represents a promising new target against chemoresistant NSCLC.
Prognostic impact of CRTC1/3‐MAML2 fusions in salivary gland mucoepidermoid carcinoma: A multiinstitutional retrospective study
Authors: Okumura Yoshihide , Nakano Satsuki , Murase Takayuki , Ueda Kaori , Kawakita Daisuke , Nagao Toshitaka , Kusafuka Kimihide , Urano Makoto , Yamamoto Hidetaka , Kano Satoshi , Tsukahara Kiyoaki , Okami Kenji , Nagao Toru , Hanai Nobuhiro , Iwai Hiroshi , Kawata Ryo , Tada Yuichiro , Nibu Ken‐Ichi , Inagaki Hiroshi
Published: August 2020

Mucoepidermoid carcinoma (MEC) is rare, but the most common primary malignancy of the salivary gland and not infrequent in young individuals. CRTC1/3‐MAML2 fusions are frequently detected in MEC and are useful as a diagnostic biomarker. However, there has been debate as to whether the fusions have prognostic significance. In this study, we retrospectively collected 153 salivary gland MEC cases from 11 tertiary hospitals in Japan. As inclusion criteria, the MEC patients in this study had curative surgery as the initial treatment, received no preoperative treatment, and had no distant metastasis at the time of the initial surgery. The MEC diagnosis was validated by a central pathology review by five expert salivary gland pathologists. The CRTC1/3‐MAML2 fusions were detected using FISH and RT‐PCR. In 153 MEC cases, 90 (58.8%) were positive for CRTC1/3‐MAML2 fusions. During the follow‐up period, 28 (18.3%) patients showed tumor recurrence and 12 (7.8%) patients died. The presence of the fusions was associated with favorable tumor features. Of note, none of the fusion‐positive patients died during the follow‐up period. Statistical analysis showed that the presence of the fusions was a prognostic indicator of a better overall survival in the total and advanced‐stage MEC cohorts, but not in the early‐stage MEC cohort. In conclusion, CRTC1/3‐MAML2 fusions are an excellent biomarker for favorable overall survival of patients with salivary gland MEC.
A ceRNA network and a potential regulatory axis in gastric cancer with different degrees of immune cell infiltration
Authors: Zhang Kai , Zhang Lei , Mi Yang , Tang YouCai , Ren FeiFei , Liu Bin , Zhang Yi , Zheng PengYuan
Published: August 2020

Immune cell infiltration is an important indicator of whether tumor patients will benefit from immunotherapy. Gastric cancer is one of the most common tumors in the world, and new indicators of immunotherapy are urgently needed. The aim of this study was to construct ceRNA networks in gastric cancer with different degrees of immune cell infiltration. We analyzed the expression profiles of different gastric cancer with different degrees of immune cell infiltration retrieved from The Cancer Genome Atlas (TCGA) database and found differentially expressed lncRNAs, mRNAs, and miRNAs. A ceRNA regulatory network of gastric cancer with different degrees of immune cell infiltration was constructed using functional annotation, RNA‐RNA interaction prediction, correlation analysis, survival analysis, and other comprehensive bioinformatics methods. The interaction and correlation between ceRNAs were verified using experiments on tumor tissues and cell lines. Cell line experiments showed a potential RP11‐1094M14.8/miR‐1269a/CXCL9 axis that was consistent with the ceRNA theory. qRT‐PCR results showed that RP11‐1094M14.8 knockdown significantly reduced the expression of CXCL9, and RP11‐1094M14.8 overexpression had the opposite effect. The results of clinical analysis of gastric cancer samples showed that RP11‐1094M14.8 and CXCL9 were highly expressed in hot tumors, and CXCL9 was positively correlated with a better prognosis for patients. The constructed novel ceRNA network and the potential regulatory axis may provide a comprehensive understanding of the potential mechanisms of development in gastric cancer with different degrees of immune cell infiltration. The RP11‐1094M14.8/miR‐1269a/CXCL9 axis may serve as a potential immune‐therapeutic target for gastric cancer with different degrees of immune cell infiltration.
Retinal microvasculature impairment in patients with congenital heart disease investigated by optical coherence tomography angiography
Authors: Li Cong , Zhong Pingting , Yuan Haiyun , Dong Xinran , Peng Qingsheng , Huang Manqing , Wu Qiaowei , Liu Baoyi , Xu Minghui , Kuang Yu , Zeng Xiaomin , Xiao Yu , Fang Ying , Yu Honghua , Yang Xiaohong
Published: August 2020

Importance

A high prevalence of retinal abnormalities have been reported in congenital heart disease (CHD), but quantitative analysis of retinal vasculature is scarce. Optical coherence tomography angiography (OCTA) is a noninvasive method to quantitatively assess the retinal microvasculature.

Background

To investigate the retinal microvasculature changes in CHD patients by using OCTA.

Design

Cross‐sectional study.

Participants

A total of 158 participants including 57 cyanotic CHD (CCHD) patients, 60 acyanotic CHD (ACHD) patients and 41 control subjects were included.

Methods

All participants underwent a comprehensive ophthalmologic examination, including refraction measurement, intraocular pressure measurement and OCTA.

Main Outcome Measures

Vessel density (VD) was measured within the radial peripapillary capillary (RPC), superficial capillary plexus (SCP) and deep capillary plexus (DCP) of the macula.

Results

CCHD patients had significantly lower VD in the RPC, SCP and DCP (all P < .01) compared to control subjects, and significantly lower VD in the RPC and DCP (both P < .05) compared to ACHD patients. Besides, among the CHD group, VD in the RPC was positively correlated with oxygen saturation (whole image, ρ = 0.45; peripapillary, ρ = 0.48) and negatively correlated with haematocrit (whole image, ρ = 0.55; peripapillary, ρ = 0.55) (all P < .001).

Conclusions and Relevance

Retinal VD might be a surrogate to reflect the effect of chronic systemic hypoxemia in CHD patients. OCTA could be a convenient and noninvasive tool to evaluate the retinal structure and function in CHD patients.
Sleep among youths in foster care: Associations with potentially traumatic events, PTSD and mental health
Authors: Lehmann Stine , Gärtner Askeland Kristin , Hysing Mari
Published: August 2020

Among maltreated youth in foster care, little is known about frequency of sleep problems and its association to potential traumatic events (PTEs) and mental health. Among youths in foster care, we examined: (1) sleep patterns, difficulties initiating and maintaining sleep (DIMS) and related functional impairment; (2) whether exposure to PTEs, symptoms of post‐traumatic stress disorder (PTSD) and general mental health problems are associated with DIMS and related functional impairment, controlling for age, gender and time in foster care; and (3) whether PTSD and general mental health problems mediate the association between PTEs and DIMS. Foster youths in Norway (n = 299) completed a survey on sleep behaviour, the Child and Adolescent Trauma Screen, and the Strengths and Difficulties Questionnaire. Overall, 53.2% reported DIMS. For 82.1%, these sleep problems had lasted 3 months plus. Increased PTEs, PTSD and general mental health problems were all associated with increased DIMS score. Increased rate of PTEs was associated with decreased sleep duration. PTSD and general mental health problems partially mediated the association between PTEs and DIMS. Youth in foster care are at high risk of sleep problems, related to traumatic experiences and mental health problems. Treatment of PTSD may improve sleep problems among maltreated youth.
Premature aging disorders: A clinical and genetic compendium
Authors: Schnabel Franziska , Kornak Uwe , Wollnik Bernd
Published: August 2020

Progeroid disorders make up a heterogeneous group of very rare hereditary diseases characterized by clinical signs that often mimic physiological aging in a premature manner. Apart from Hutchinson‐Gilford progeria syndrome, one of the best‐investigated progeroid disorders, a wide spectrum of other premature aging phenotypes exist, which differ significantly in their clinical presentation and molecular pathogenesis. Next‐generation sequencing (NGS)‐based approaches have made it feasible to determine the molecular diagnosis in the early stages of a disease. Nevertheless, a broad clinical knowledge on these disorders and their associated symptoms is still fundamental for a comprehensive patient management and for the interpretation of variants of unknown significance from NGS data sets. This review provides a detailed overview on characteristic clinical features and underlying molecular genetics of well‐known as well as only recently identified premature aging disorders and also highlights novel findings towards future therapeutic options.
Spectrum and frequencies of non GJB2 gene mutations in Czech patients with early non‐syndromic hearing loss detected by gene panel NGS and whole‐exome sequencing
Authors: Safka Brozkova Dana , Poisson Marková Simona , Mészárosová Anna Uhrová , Jenčík Ján , Čejnová Vlasta , Čada Zdeněk , Laštůvková Jana , Rašková Dagmar , Seeman Pavel
Published: August 2020

Non‐syndromic autosomal recessive hearing loss is an extremely heterogeneous disease caused by mutations in more than 80 genes. We examined Czech patients with early/prelingual non‐syndromic, presumably genetic hearing loss (NSHL) without known cause after GJB2 gene testing. Four hundred and twenty‐one unrelated patients were examined for STRC gene deletions with quantitative comparative fluorescent PCR (QCF PCR), 197 unrelated patients with next‐generation sequencing by custom‐designed NSHL gene panels and 19 patients with whole‐exome sequencing (WES). Combining all methods, we discovered the cause of the disease in 54 patients. The most frequent type of NSHL was DFNB16 (STRC), which was detected in 22 patients, almost half of the clarified patients. Other biallelic pathogenic mutations were detected in the genes: MYO15A, LOXHD1, TMPRSS3 (each gene was responsible for five clarified patients, CDH23 (four clarified patients), OTOG and OTOF (each gene was responsible for two clarified patients). Other genes (AIFM1, CABP2, DIAPH1, PTPRQ, RDX, SLC26A4, TBC1D24, TECTA, TMC1) that explained the cause of hearing impairment were further detected in only one patient for each gene. STRC gene mutations, mainly deletions remain the most frequent NSHL cause after mutations in the GJB2.
Vascular plant extinction in the continental United States and Canada
Authors: Knapp Wesley M. , Frances Anne , Noss Reed , Naczi Robert F. C. , Weakley Alan , Gann George D. , Baldwin Bruce G. , Miller James , McIntyre Patrick , Mishler Brent D. , Moore Gerry , Olmstead Richard G. , Strong Anna , Kennedy Kathryn , Heidel Bonnie , Gluesenkamp Daniel
Published: August 2020

Extinction rates are expected to increase during the Anthropocene. Current extinction rates of plants and many animals remain unknown. We quantified extinctions among the vascular flora of the continental United States and Canada since European settlement. We compiled data on apparently extinct species by querying plant conservation databases, searching the literature, and vetting the resulting list with botanical experts. Because taxonomic opinion varies widely, we developed an index of taxonomic uncertainty (ITU). The ITU ranges from A to F, with A indicating unanimous taxonomic recognition and F indicating taxonomic recognition by only a single author. The ITU allowed us to rigorously evaluate extinction rates. Our data suggest that 51 species and 14 infraspecific taxa, representing 33 families and 49 genera of vascular plants, have become extinct in our study area since European settlement. Seven of these taxa exist in cultivation but are extinct in the wild. Most extinctions occurred in the west, but this outcome may reflect the timing of botanical exploration relative to settlement. Sixty‐four percent of extinct plants were single‐site endemics, and many occurred outside recognized biodiversity hotspots. Given the paucity of plant surveys in many areas, particularly prior to European settlement, the actual extinction rate of vascular plants is undoubtedly much higher than indicated here.
Viability testing of discarded livers with normothermic machine perfusion: Alleviating the organ shortage outweighs the cost
Authors: Raigani Siavash , De Vries Reinier J. , Carroll Cailah , Chen Ya‐Wen , Chang David C. , Shroff Stuti G. , Uygun Korkut , Yeh Heidi
Published: August 2020

Background

Over 700 donor livers are discarded annually in the United States due to high risk of poor graft function. The objective of this study was to determine the impact of using normothermic machine perfusion to identify transplantable livers among those currently discarded.

Study Design

A series of 21 discarded human livers underwent viability assessment during normothermic machine perfusion. Cross‐sectional analysis of the Scientific Registry of Transplant Recipients database and cost analysis was performed to extrapolate the case series to national experience.

Results

21 discarded human livers were included in the perfusion cohort. 11 of 20 (55%) eligible grafts met viability criteria for transplantation. Grafts in the perfusion cohort had a similar donor risk index compared with discarded grafts (n = 1402) outside of New England in 2017 and 2018 (median [IQR]: 2.0 [1.5, 2.4] vs. 2.0 [1.7, 2.3],P = .40). 705 (IQR 677‐741) livers were discarded annually in the United States since 2005, translating to the potential for 398 additional transplants nationally. The median cost to identify a transplantable graft with machine perfusion was $28,099 USD.

Conclusions

Normothermic machine perfusion of discarded livers could identify a significant number of transplantable grafts, significantly improving access to liver transplantation.