bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of inflammatory pain and cough by a novel charged sodium channel blocker
Authors: Tochitsky Ivan , Jo Sooyeon , Andrews Nick , Kotoda Masakazu , Doyle Benjamin , Shim Jaehoon , Talbot Sebastien , Roberson David , Lee Jinbo , Haste Louise , Jordan Stephen M. , Levy Bruce D. , Bean Bruce P. , Woolf Clifford J.
Published: May 2021

Background and Purpose

Many pain‐triggering nociceptor neurons express TRPV1 or TRPA1, cation‐selective channels with large pores that enable permeation of QX‐314, a cationic analogue of lidocaine. Co‐application of QX‐314 with TRPV1 or TRPA1 activators can silence nociceptors. In this study, we describe BW‐031, a novel more potent cationic sodium channel inhibitor, and test whether its application alone can inhibit pain associated with tissue inflammation and whether this strategy can also inhibit cough.

Experimental Approach

We tested the ability of BW‐031 to inhibit pain in three models of tissue inflammation:‐ inflammation in rat paws produced by complete Freund's adjuvant or by surgical incision and a mouse ultraviolet (UV) burn model. We tested the ability of BW‐031 to inhibit cough induced by inhalation of dilute citric acid in guinea pigs.

Key Results

BW‐031 inhibited Nav1.7 and Nav1.1 channels with approximately sixfold greater potency than QX‐314 when introduced inside cells. BW‐031 inhibited inflammatory pain in all three models tested, producing more effective and longer‐lasting inhibition of pain than QX‐314 in the mouse UV burn model. BW‐031 was effective in reducing cough counts by 78%–90% when applied intratracheally under isoflurane anaesthesia or by aerosol inhalation in guinea pigs with airway inflammation produced by ovalbumin sensitization.

Conclusion and Implications

BW‐031 is a novel cationic sodium channel inhibitor that can be applied locally as a single agent to inhibit inflammatory pain. BW‐031 can also effectively inhibit cough in a guinea pig model of citric acid‐induced cough, suggesting a new clinical approach to treating cough.
Neogene basin infilling from cosmogenic nuclides (10Be and21Ne) in Atacama, Chile: Implications for palaeoclimate and supergene copper mineralization
Authors: Sanchez Caroline , Regard Vincent , Carretier Sébastien , Riquelme Rodrigo , Blard Pierre‐Henri , Campos Eduardo , Brichau Stéphanie , Lupker Maarten , Hérail Gérard
Published: May 2021

Increasing evidence suggests that supergene exotic copper deposits were emplaced during periods of geomorphic quiescence and pulses of humidity in arid environments. We tested this idea in the Centinela Mining District in the Atacama Desert (northern Chile). We collected 14 sand samples at depth (up to 110 m) in two open‐pit mines (Central Tesoro and Mirador) exposing Miocene sediment, and located in the El Tesoro Basin, which hosts two exotic copper‐rich orebodies. We inverted the10Be and21Ne concentrations by using a two‐box model (IMIS, inversion of multi‐isotopes in a sedimentary basin) composed of an eroding source of sediment and a depositional sedimentary basin, and by selecting denudation and sedimentation rate histories that can explain our data. The ages found demonstrate that the two exotic orebodies were deposited during a narrow period between 14 Ma (10 Ma younger than previously thought) and 9.5 Ma, when an ignimbrite covered the sedimentary sequence. The dated lower exotic copper orebody was deposited during or just before a sharp decrease in the sedimentation rates (from >100 to 0.5–5 m/Ma), which is consistent with published sedimentological and carbonate isotopic data in this district. This confirms the idea that exotic deposits form during a quiescence of the geomorphic activity. Nevertheless, our model suggests that the back‐ground denudation rate providing sediment to these basins between ca. 14 Ma and ca. 9.5 Ma was surprisingly high (>250 m/Ma) for such an arid environment. These denudation rates can be explained by a relatively rapid local back‐scarp retreat providing most of the sediment to these basins and possibly a wetter climate compared to the present. Then, during the period 10–7 Ma, the denudation rates decreased to >50 m/Ma. This decrease may correspond to a local progressive decrease in the slope of the surrounding hills, or to a progressive aridification, or a combination of both phenomena.
Pathogenic variants of ATG4D in infertile men with non‐obstructive azoospermia identified using whole‐exome sequencing
Authors: Sha Yanwei , Liu Wensheng , Wei Xiaoli , Zhu Xingshen , Tang Bowen , Zhang Xiaoya , Yang Xiaoyu , Wang Yifeng , Wang Xiong
Published: May 2021

Non‐obstructive azoospermia (NOA) is the most severe form of male infertility, and it is primarily associated with genetic defects. We performed whole‐exome sequencing of 236 patients with NOA and identified a homozygous pathogenic variant of autophagy‐related 4D cysteine peptidase (ATG4D) in two siblings from a consanguineous family and compound heterozygous pathogenic variants of ATG4D in two sporadic cases. The expression of LC3B, a regulator of autophagic activity, was significantly decreased, and the apoptosis rate of spermatogenic cells in testicular tissues was increased. Transfection of GC‐2spd cells with a ATG4D mutant plasmid (Flag‐Atg4dmut) significantly decreased the expression level of Lc3b and increased the rate of apoptosis. Moreover, a pathogenic variant in X‐linked ATG4A and compound heterozygous pathogenic variants of ATG4B were identified in one patient each. All novel variants were segregated by disease phenotype and were predicted to be pathogenic. Our findings revealed that autophagy‐related cysteine peptidase family genes may play crucial roles in human spermatogenesis and identified ATG4D as a novel candidate gene for male infertility due to NOA.
Neurological development of children who are HIV‐exposed and uninfected
Authors: Toledo Gabriela , Côté Hélène C F , Adler Catherine , Thorne Claire , Goetghebuer Tessa
Published: May 2021

Widespread use of antiretroviral drugs for pregnant/breastfeeding females with human immunodeficiency virus (HIV) has led to declining vertical transmission. Despite being HIV‐uninfected, the increasing number of children who are HIV‐exposed and uninfected (CHEU) often present with developmental alterations. We review seminal and recent evidence on the neurological development of CHEU and associations with early life HIV/antiretroviral exposure. Our conceptual model highlights the numerous exposures and universal risk factors for CHEU developmental disorders. Early studies suggest a significant association between HIV exposure and neurological abnormalities, varying according to the burden of HIV‐specific exposures and other risk factors. More recent observations from the modern era are inconsistent, although some studies suggest specific antiretrovirals may adversely affect neurological development of CHEU. As the CHEU population continues to grow, alongside simultaneous increases in types and combinations of antiretrovirals used in pregnancy, long‐term monitoring of CHEU is necessary for understanding the effects of HIV/antiretroviral exposure on CHEU developmental outcomes.

What this paper adds

Evidence on the neurological development of children who are human immunodeficiency virus (HIV)‐exposed and uninfected (CHEU) is synthesized.

Comparisons are made to children who are HIV‐unexposed, across treatment eras and settings, and by antiretroviral drug regimens and drug classes.

CHEU exposures are complex and include HIV‐specific and universal risk factors which may affect development during the early years of life.
A broadscale analysis of host‐symbiont cophylogeny reveals the drivers of phylogenetic congruence
Authors: Hayward Alexander , Poulin Robert , Nakagawa Shinichi
Published: May 2021

Symbioses exert substantial biological influence, with great evolutionary and ecological relevance for disease, major evolutionary transitions, and the structure and function of ecological communities. Yet, much remains unknown about the patterns and processes that characterise symbioses. A major unanswered question is the extent to which symbiont phylogenies mirror those of their hosts and if patterns differ for parasites and mutualists. Addressing this question offers fundamental insights into evolutionary processes, such as whether symbionts typically codiverge with their hosts or if diversity is generated via host switches. Here, we perform a meta‐analysis of host‐symbiont phylogenetic congruence, encompassing 212 host‐symbiont cophylogenetic studies that include ~10,000 species. Our analysis supersedes previous qualitative assessments by utilising a quantitative framework. We show that symbiont phylogeny broadly reflects host phylogeny across biodiversity and life‐history, demonstrating a general pattern of phylogenetic congruence in host‐symbiont interactions. We reveal two key aspects of symbiont life‐history that promote closer ties between hosts and symbionts: vertical transmission and mutualism. Mode of symbiosis and mode of transmission are intimately interlinked, but vertical transmission is the dominant factor. Given the pervasiveness of symbioses, these findings provide important insights into the processes responsible for generating and maintaining the Earth's rich biodiversity.
Cross‐sectional study on patients' understanding and views of the informed consent procedure of a secondary stroke prevention trial
Authors: Eichner Felizitas A. , Reis Joschua M. , Dores Joaquim , Pavlovic Vladimir , Kreß Luisa , Daneshkhah Naeimeh , Weinhardt Renate , Grau Armin , Mühler Johannes , Soda Hassan , Schwarzbach Christopher J. , Schuler Michael , Häusler Karl Georg , Heuschmann Peter U.
Published: May 2021

Background and purpose

Improving understanding of study contents and procedures might enhance recruitment into studies and retention during follow‐up. However, data in stroke patients on understanding of the informed consent (IC) procedure are sparse.

Methods

We conducted a cross‐sectional study among ischemic stroke patients taking part in the IC procedure of an ongoing cluster‐randomized secondary prevention trial. All aspects of the IC procedure were assessed in an interview using a standardized 20‐item questionnaire. Responses were collected within 72 h after the IC procedure and analyzed quantitatively and qualitatively. Participants were also asked their main reasons for participation.

Results

A total of 146 stroke patients (65 ± 12 years old, 38% female) were enrolled. On average, patients recalled 66.4% (95% confidence interval = 65.2%–67.5%) of the content of the IC procedure. Most patients understood that participation was voluntary (99.3%) and that they had the right to withdraw consent (97.1%); 79.1% of the patients recalled the study duration and 56.1% the goal. Only 40.3% could clearly state a benefit of participation, and 28.8% knew their group allocation. Younger age, higher graduation, and allocation to the intervention group were associated with better understanding. Of all patients, 53% exclusively stated a personal and 22% an altruistic reason for participation.

Conclusions

Whereas understanding of patient rights was high, many patients were unable to recall other important aspects of study content and procedures. Increased attention to older and less educated patients may help to enhance understanding in this patient population. Actual recruitment and retention benefit of an improved IC procedure remains to be tested in a randomized trial.
Artificial selection for nonreproductive host killing in a native parasitoid on the invasive pest, Drosophila suzukii
Authors: Kruitwagen Astrid , Wertheim Bregje , Beukeboom Leo W.
Published: May 2021

Establishment and spread of invasive species can be facilitated by lack of natural enemies in the invaded area. Host‐range evolution of natural enemies augments their ability to reduce the impact of the invader and could enhance their value for biological control. We assessed the potential of the Drosophila parasitoid, Leptopilina heterotoma (Hymenoptera: Figitidae), to exploit the invasive pest Drosophila suzukii by focusing on three performance indices: (i) attack rate; (ii) host killing, consisting of killing rate and lethal attack rate (killing efficiency); and (iii) successful offspring development (reproductive success). We found significant intraspecific variation in attack rate and killing rate and lethal attack rate among seven European populations, but offspring generally failed to successfully develop from the D. suzukii host. We crossed these European lines to create a genetically variable source population and performed a half‐sib analysis to quantify genetic variation. Using a Bayesian animal model, we found that attack rate and killing rate had a heritability of , lethal attack rate , and offspring development . We then artificially selected wasps with the highest killing rate of D. suzukii for seven generations to test whether host‐killing could be improved. There was a small and inconsistent response to selection in the three selection lines. Realized heritability () after four generations of selection was 0.17 but near zero after seven generations of selection. The genetic response might have been masked by an increased D. suzukii fitness resulting from adaptation to laboratory conditions. Our study reveals that native, European, L. heterotoma can attack the invasive pest, D. suzukii and significantly reduce fly survival and that different steps of the parasitization process need to be considered in the evolution of host‐range. It highlights how evolutionary principles can be applied to optimize performance of native species for biological control.
Optoacoustic imaging of the skin
Authors: Deán‐Ben Xosé Luís , Razansky Daniel
Published: May 2021

Optoacoustic (OA, photoacoustic) imaging capitalizes on the synergistic combination of light excitation and ultrasound detection to empower biological and clinical investigations with rich optical contrast while effectively bridging the gap between micro and macroscopic imaging realms. State‐of‐the‐art OA embodiments consistently provide images at micron‐scale resolution through superficial tissue layers by means of focused illumination that can be smoothly exchanged for acoustic‐resolution images at diffuse light depths of several millimetres to centimetres via ultrasound beamforming or tomographic reconstruction. Taken together, this unique multi‐scale imaging capacity opens unprecedented capabilities for high‐resolution in vivo interrogations of the skin at scalable depths. Moreover, diverse anatomical and functional information is retrieved via dynamic mapping of endogenous chromophores such as haemoglobin, melanin, lipids, collagen, water and others. This, along with the use of non‐ionizing radiation, facilitates a clinical translation of the OA modalities. We review recent progress in OA imaging of the skin in preclinical and clinical studies exploiting the rich contrast provided by endogenous substances in tissues. The imaging capabilities of existing approaches are discussed in the context of initial translational studies on skin cancer, inflammatory skin diseases, wounds and other conditions.
Inter‐domain horizontal gene transfer of nickel‐binding superoxide dismutase
Authors: Sutherland K. M. , Ward L. M. , Colombero C.‐R. , Johnston D. T.
Published: May 2021

The ability of aerobic microorganisms to regulate internal and external concentrations of the reactive oxygen species (ROS) superoxide directly influences the health and viability of cells. Superoxide dismutases (SODs) are the primary regulatory enzymes that are used by microorganisms to degrade superoxide. SOD is not one, but three separate, non‐homologous enzymes that perform the same function. Thus, the evolutionary history of genes encoding for different SOD enzymes is one of convergent evolution, which reflects environmental selection brought about by an oxygenated atmosphere, changes in metal availability, and opportunistic horizontal gene transfer (HGT). In this study, we examine the phylogenetic history of the protein sequence encoding for the nickel‐binding metalloform of the SOD enzyme (SodN). The genomic potential to produce SodN is widespread among bacteria, including Actinobacteriota (Actinobacteria), Chloroflexota (Chloroflexi), Cyanobacteria, Proteobacteria, Patescibacteria, and others. The gene is also present in many archaea, with Thermoplasmatota and Nanoarchaeota representing the vast majority of archaeal sodN diversity. A comparison of organismal and SodN protein phylogenetic trees reveals several instances of HGT, including multiple inter‐domain transfers of the sodN gene from the bacterial domain to the archaeal domain. Nearly half of the archaeal members with sodN live in the photic zone of the marine water column. The sodN gene is widespread and characterized by apparent vertical gene transfer in some sediment‐ or soil‐associated lineages within the Actinobacteriota and Chloroflexota phyla, suggesting the ancestral sodN likely originated in one of these clades before expanding its taxonomic and biogeographic distribution to additional microbial groups in the surface ocean in response to decreasing iron availability. In addition to decreasing iron quotas, nickel‐binding SOD has the added benefit of withstanding high reactant and product ROS concentrations without damaging the enzyme, making it particularly well suited for the modern surface ocean.
Grassland soil organic carbon stocks along management intensity and warming gradients
Authors: Poeplau Christopher
Published: May 2021

Grasslands are a major terrestrial ecosystem type and store large amounts of soil organic carbon (SOC) per unit area. Quantitative and mechanistic knowledge on the effects of management on SOC stocks in grasslands is limited. Also, climate change can be seen as an indirect anthropogenic threat to SOC stocks, with warming effects on grassland SOC being currently understudied. Here, several studies investigating the effects of management and warming on SOC stocks are summarised, with a central to northern European focus. SOC sequestration increased with management intensity, i.e. cutting frequency and mineral fertilisation, even without external C inputs. This was partly explicable by increased productivity in more intensively managed grasslands. In addition, the availability of nutrients was found to foster microbial anabolism, leading to a more efficient build‐up of SOC in fertilised as compared to unfertilised soils. Interestingly, the addition of 1 kg nitrogen as NPK fertiliser consistently led to approximately 1 kg of additional SOC. Sequestration of SOC might thus compensate for a major part of the increased greenhouse gas emissions associated with highly intensive grassland management. Including perennial grasses in agricultural crop rotations is multi‐beneficial and proved to be a very efficient measure to increase SOC stocks. At the same time, soil warming depleted SOC, both in natural subarctic as well as in managed temperate grasslands. Climate change can thus be expected to counterbalance efforts of SOC build‐up to some extent. Future research should focus on the interactive effects of climate change and management, which will be important for future management decisions.
Transcriptome analysis of gene expression changes upon enzymatic dissociation in skeletal myoblasts
Authors: Miyawaki‐Kuwakado Atsuko , Wu Qianmei , Harada Akihito , Tomimatsu Kosuke , Fujii Takeru , Maehara Kazumitsu , Ohkawa Yasuyuki
Published: May 2021

Single‐cell RNA‐sequencing analysis is one of the most effective tools for understanding specific cellular states. The use of single cells or pooled cells in RNA‐seq analysis requires the isolation of cells from a tissue or culture. Although trypsin or more recently cold‐active protease (CAP) has been used for cell dissociation, the extent to which the gene expression changes are suppressed has not been clarified. To this end, we conducted detailed profiling of the enzyme‐dependent gene expression changes in mouse skeletal muscle progenitor cells, focusing on the enzyme treatment time, amount and temperature. We found that the genes whose expression was changed by the enzyme treatment could be classified in a time‐dependent manner and that there were genes whose expression was changed independently of the enzyme treatment time, amount and temperature. This study will be useful as reference data for genes that should be excluded or considered for RNA‐seq analysis using enzyme isolation methods.
Bioactive phytocompound mulberroside C and endophytes of Morus alba as potential inhibitors of HIV‐1 replication: a mechanistic evaluation
Authors: Vora J , Velhal S , Sinha S , Patel V , Shrivastava N
Published: May 2021

Objectives

Despite considerable advancement in antiretroviral therapy, development of safe, effective, and multi‐targeted drugs for HIV still remains a big challenge. Endophytes are untouched and, hence, an important and novel sources in drug discovery endeavours. The present study was conducted to identify the anti‐HIV compounds from Morus alba and endophytes isolated from it.

Methods

The extracts of isolated endophytes were screened using high‐performance liquid chromatography (HPLC). Further, all samples were analysed for their cytotoxicity using a thiazolyl blue tetrazolium bromide assay. Subsequently, anti‐HIV activity was performed using cell‐based and cell‐free assay. At the end, potential endophytes were identified using gene sequencing.

Results

A total of 27 endophytes were isolated from the eight stem bark samples of M. alba. Of the 27 endophytes, extracts of total of four endophytes showed a profile similar to the M. alba plant when analysed by HPLC. Further experimentation with extracts of these four endophytes, along with an extract of M. alba stem bark and its bioactive molecule, mulberroside C, revealed that all these six samples have good inhibitory potential for HIV. Among them, mulberroside C and two endophytic fungal extracts showed very potent anti‐HIV activity. Subsequently, mechanistic studies at the molecular level showed that out of six test samples, three acted as protease inhibitors. Further, all four potential endophytes were identified using gene sequencing.

Conclusions

The overall findings of these studies can help in the development of a novel anti‐HIV candidate from mulberroside C, an extract of stem bark of M. alba and extracts of these endophytes. However, further validation and clinical studies are required to develop an anti‐HIV drug.
The link between trait and state professional skepticism: A review of the literature and a meta‐regression analysis
Authors: Khan Mohammad Jahanzeb , Oczkowski Eddie
Published: May 2021

Motivated by the need to better understand the trait–state skepticism relationship, and also building upon prior literature syntheses, this study examines the literature that empirically investigates the trait–state skepticism relationship using experimental methodology. A meta‐regression analysis is conducted on Pearson correlations between trait skepticism and state skepticism to identify the overall effect and key drivers of this relationship. On average, there is no noticeable effect size for the relation between trait and state skepticisim across the studies; however, there are three key determinants of the correlation across studies mainly (1) the use of the Inverse Rotter trait measure compared to other measures reduces the correlation, (2) the use of graduate auditor samples compared to seasoned professionals intensifies the correlation and (3) the use of a low risk environment in the research design reduces correlation. The review and analysis are timely as the literature re‐examines how professional skepticism is conceptualized and operationalized moving forward.
The emerging role of microRNA in regulating the mTOR signaling pathway in immune and inflammatory responses
Authors: Nazari Nazanin , Jafari Farzaneh , Ghalamfarsa Ghasem , Hadinia Abolghasem , Atapour Amir , Ahmadi Majid , Dolati Sanam , Rostamzadeh Davood
Published: May 2021

The mechanistic/mammalian target of rapamycin (mTOR) is considered to be an atypical protein kinase that plays a critical role in integrating different cellular and environmental inputs in the form of growth factors, nutrients and energy and, subsequently, in regulating different cellular events, including cell metabolism, survival, homeostasis, growth and cellular differentiation. Immunologically, mTOR is a critical regulator of immune function through integrating numerous signals from the immune microenvironment, which coordinates the functions of immune cells and T cell fate decisions. The crucial role of mTOR in immune responses has been lately even more appreciated. MicroRNAs (miRNAs) are endogenous, small, noncoding single‐stranded RNAs that act as molecular regulators involved in multiple processes during immune cells development, homeostasis, activation and effector polarization. Several studies have recently indicated that a range of miRNAs are involved in regulating the phosphoinositide 3‐kinase/protein kinase B/mTOR (PI3K/AKT/mTOR) signaling pathway by targeting multiple components of this signaling pathway and modulating the expression and function of these targets. Current evidence has revealed the interplay between miRNAs and the mTOR pathway circuits in various immune cell types. The expression of individual miRNA can affect the function of mTOR signaling to determine the cell fate decisions in immune responses through coordinating immune signaling and cell metabolism. Dysregulation of the mTOR pathway/miRNAs crosstalk has been reported in cancers and various immune‐related diseases. Thus, expression profiles of dysregulated miRNAs could influence the mTOR pathway, resulting in the promotion of aberrant immunity. This review summarizes the latest information regarding the reciprocal role of the mTOR signaling pathway and miRNAs in orchestrating immune responses.
Gm40600 promotes CD4+ T‐cell responses by interacting with Ahnak
Authors: He Youdi , Fang Ying , Zhai Bing , Liu Xiaoling , Zhu Gaizhi , Zhou Shan , Xu Yaqi , Wang Xiaoqian , Su Wenting , Wang Renxi
Published: May 2021

It is important to characterize novel proteins involved in T‐ and B‐cell responses. Our previous study demonstrated that a novel protein, Mus musculus Gm40600, reduced the proliferation of Mus musculus plasmablast (PB)‐like SP 2/0 cells and B‐cell responses induced in vitro by LPS. In the present study, we revealed that Gm40600 directly promoted CD4+ T‐cell responses to indirectly up‐regulate B‐cell responses. Importantly, we found that CD4+ T‐cell responses, including T‐cell activation and differentiation and cytokine production, were increased in Gm40600 transgenic (Tg) mice and were reduced in Gm40600 knockout (KO) mice. Finally, we demonstrated that Gm40600 promoted the Ahnak‐mediated calcium signalling pathway by interacting with Ahnak to maintain a cytoplasmic lateral location of Ahnak in CD4+ T cells. Collectively, our data suggest that Gm40600 promotes CD4+ T‐cell activation to up‐regulate the B‐cell response via interacting with Ahnak to promote the calcium signalling pathway. The results suggest that targeting Gm40600 may be a means to control CD4+ T‐cell‐related diseases.
Language familiarity influences own‐race face recognition in 9‐ and 12‐month‐old infants
Authors: Hillairet de Boisferon Anne , Kubicek Claudia , Gervain Judit , Schwarzer Gudrun , Loevenbruck Hélène , Vilain Anne , Fort Mathilde , Méary David , Pascalis Olivier
Published: May 2021

During their first year, infants attune to the faces and language(s) that are frequent in their environment. The present study investigates the impact of language familiarity on how French‐learning 9‐ and 12‐month‐olds recognize own‐race faces. In Experiment 1, infants were familiarized with the talking face of a Caucasian bilingual German‐French speaker reciting a nursery rhyme in French (native condition) or in German (non‐native condition). In the test phase, infants’ face recognition was tested by presenting a picture of the speaker's face they were familiarized with, side by side with a novel face. At 9 and 12 months, neither infants in the native condition nor the ones in the non‐native condition clearly recognized the speaker's face. In Experiment 2, we familiarized infants with the still picture of the speaker's face, along with the auditory speech stream. This time, both 9‐ and 12‐month‐olds recognized the face of the speaker they had been familiarized with, but only if she spoke in their native language. This study shows that at least from 9 months of age, language modulates the way faces are recognized.
A novel autophagy‐related lncRNA survival model for lung adenocarcinoma
Authors: Wu Liwei , Wen Zilu , Song Yanzheng , Wang Lin
Published: May 2021

Long non‐coding RNA (lncRNA) is an important regulatory factor in the development of lung adenocarcinoma, which is related to the control of autophagy. LncRNA can also be used as a biomarker of prognosis in patients with lung adenocarcinoma. Therefore, it is important to determine the prognostic value of autophagy‐related lncRNA in lung adenocarcinoma. In this study, autophagy‐related mRNAs‐lncRNAs were screened from lung adenocarcinoma and a co‐expression network of autophagy‐related mRNAs‐lncRNAs was constructed by using The Cancer Genome Atlas (TCGA). The univariate and multivariate Cox proportional hazard analyses were used to evaluate the prognostic value of the autophagy‐related lncRNAs and finally obtained a survival model composed of 11 autophagy‐related lncRNAs. Through Kaplan‐Meier analysis, univariate and multivariate Cox regression analysis and time‐dependent receiver operating characteristic (ROC) curve analysis, it was further verified that the survival model was a new independent prognostic factor for patients with lung adenocarcinoma. In addition, based on the survival model, gene set enrichment analysis (GSEA) was used to illustrate the function of genes in low‐risk and high‐risk groups. These 11 lncRNAs were GAS6‐AS1, AC106047.1, AC010980.2, AL034397.3, NKILA, AL606489.1, HLA‐DQB1‐AS1, LINC01116, LINC01806, FAM83A‐AS1 and AC090559.1. The hazard ratio (HR) of the risk score was 1.256 (1.196‐1.320) (P < .001) in univariate Cox regression analysis and 1.215 (1.149‐1.286) (P < .001) in multivariate Cox regression analysis. And the AUC value of the risk score was 0.809. The 11 autophagy‐related lncRNA survival models had important predictive value for the prognosis of lung adenocarcinoma and may become clinical autophagy‐related therapeutic targets.
Interobserver variability in the classification of childhood maculopapular cutaneous mastocytosis
Authors: Torrelo A. , Vergara‐de‐la‐Campa L. , Azaña J.M. , Greenberger S. , Lam J.M. , Lawley L.P. , Morren M.‐A. , Schaffer J.V. , García‐Doval I. , Matito A. , Alvarez‐Twose I.
Published: May 2021

Background

Maculopapular cutaneous mastocytosis (MPCM) in children is classified in two variants: (i) monomorphic variant, presenting with the small macules or papules typically seen in adult patients; and (ii) polymorphic variant with larger lesions of variable size and shape, typically seen in children. The definition of polymorphic and monomorphic variants is mostly intuitive, and a validation of this classification has not been done.

Objective

To study interobserver variability in the classification of MPCM in two groups of observers: mastocytosis experts and general dermatologists.

Materials and methods

Nineteen cases of childhood MPCM were shown blindly, for classification as monomorphic or polymorphic type, to 10 independent observers (eight dermatologists, one allergist and one haematologist) from Europe and North America with a vast experience in the management of paediatric mastocytosis. Also, the same cases were shown on a screen to 129 general dermatologists attending a meeting; their votes were registered by remote controls. The interobserver variability kappa coefficient (with 95% confidence interval) was calculated to measure the reliability of the correlation.

Results

The value of kappa interobserver variability coefficient for the group of 10 experts (95% confidence interval) was 0.39 (0.18–0.63), which is considered as ‘fair’. The value of kappa interobserver variability coefficient for the group of 129 general dermatologists (95% confidence interval) was 0.17 (0.06–0.39), which is considered as ‘slight’. A complete agreement of all 10 experts was achieved in only four of 19 cases (21.1%) The most voted choice was concordant between the two groups in only 11 of the 19 cases.

Conclusions

We failed to validate the classification system of childhood MPCM in monomorphic and polymorphic types. While the rate of agreement was low for mastocytosis experts, it was nearly the agreement expected by chance in general dermatologists.
Isolated autosomal recessive woolly hair/hypotrichosis: genetics, pathogenesis and therapies
Authors: Akiyama M.
Published: May 2021

Isolated autosomal recessive woolly hair/hypotrichosis (ARWH) is a rare hereditary hair disease characterized by tightly curled sparse hair at birth or in early infancy. Patients with ARWH consist of genetically heterogeneous groups. Woolly hair autosomal recessive 1 (ARWH1) (MIM #278150), woolly hair autosomal recessive 2 (ARWH2) (MIM #604379) and woolly hair autosomal recessive 3 (ARWH3) (MIM #616760) are caused by mutations in LPAR6, LIPH and KRT25, respectively. In addition, nonsense variants in C3ORF52 (*611956) were identified in ARWH patients. The frequencies of the mutations in the causative genes in ARWH patients are thought to differ by ethnicity and country/geographical area. Large numbers of ARWH families with LIPH mutations have been described only in populations from Japan, Pakistan and the Volga–Ural region of Russia. In that region of Russia, most ARWH families have an extremely prevalent founder mutation, the deletion of exon 4, in LIPH. In the Pakistani population, 47.2% of ARWH families had the disease due to LIPH mutations and 52.8% of them carried LPAR6 mutations. The prevalent, recurrent LIPH mutation c.659_660delTA (p.Ile220Argfs*29) was found in more than half of Pakistani ARWH families with LIPH mutations. Most Japanese ARWH families (98.7%) harbour LIPH mutations, including the two highly prevalent, recurrent LIPH mutations c.736T>A (p.Cys246Ser) and c.742C>A (p.His248Asn). In ARWH patients whose disease was due to LIPH, LPAR6 or C3ORF52 mutations, the loss of function of LIPH, LPAR6 or C3ORF52 leads to reduced LIPH‐LPA‐LPAR6 signalling, resulting in the decreased transactivation of EGFR signalling and the phenotype of underdeveloped hairs. Our recent prospective interventional study suggests that topical minoxidil might be a promising treatment for ARWH due to LIPH mutations, although sufficiently effective treatments have not been established for ARWH yet.
Product selection in online marketplaces
Authors: Etro Federico
Published: May 2021

A marketplace such as Amazon hosts many products by third party sellers and acts as a first party or private label retailer. Assuming an advantage of Amazon in logistics and of sellers in marketing, we investigate whether entry by Amazon is excessive from the point of view of consumers. With competitive sellers, entry may be either overprovided or underprovided, but the incentives of Amazon and consumers are correctly aligned for a family of power surplus functions (generating for instance linear, isoelastic, and loglinear demands). Competition for customers with other retailers reduces commissions and prices preserving the efficiency result. Market power by sellers increases (reduces) the incentives to retail private label (first party) products, and generates a bias toward underprovision of entry. We extend the analysis to delivery fulfillment by the marketplace, product differentiation with price competition on the platform, and a dynamic analysis of the incentives of sellers to enter and the marketplace to launch copycat products.
Physician survey regarding updated PCV13 vaccine recommendations for adults ≥65 years
Authors: Hurley Laura P. , O'Leary Sean T. , Kobayashi Miwako , Crane Lori A. , Cataldi Jessica , Brtnikova Michaela , Beaty Brenda L. , Gorman Carol , Lindley Megan C. , Kempe Allison
Published: May 2021

Background

In June 2019, the Advisory Committee on Immunization Practices recommended discontinuing the routine use of the pneumococcal conjugate vaccine (PCV13) among adults aged ≥65 years and instead recommended PCV13 be used based on shared clinical decision making (SCDM).

Objectives

We wanted to assess among primary care physicians (1) knowledge and attitudes regarding the new SCDM PCV13 recommendation and (2) how the new recommendation will affect their likelihood of recommending PCV13 to adults aged ≥65 years.

Design

This was done by mail and internet‐based survey, which was conducted October 2019 through January 2020. The study was carried out on a nationally representative sample of general internists (GIMs) and family physicians (FPs).

Results

The response rate was 64% (617/968, GIM 57%, FP 71%). Only 41% of respondents were aware of the SCDM PCV13 recommendation in adults aged ≥65 years; 76% agreed (37% “Strongly,” 39% “Somewhat”) that their patients aged ≥65 years will get confused by having a SCDM recommendation for PCV13 and a routine recommendation for the pneumococcal polysaccharide vaccine (PPSV23); 60% agreed (18% “Strongly,” 42% “Somewhat”) that they were unsure of what points to emphasize when having a SCDM conversation with an adult aged ≥65 years about receiving PCV13. Just over 50% reported they would be less likely to recommend PCV13 for adults aged ≥65 years as a result of the new recommendation, but 42% reported that their recommendation for PCV13 would not change.

Conclusions

Word of the new ACIP recommendation for PCV13 for adults aged ≥65 years needs to be further disseminated. Investigation into why some physicians do not plan to change their recommendations is warranted.
Social cognition and executive functioning in multiple sclerosis: A cluster‐analytic approach
Authors: Henry Audrey , Lannoy Séverine , Chaunu Marie‐Pierre , Tourbah Ayman , Montreuil Michèle
Published: May 2021

Multiple sclerosis (MS) is associated with deficits in social cognition, the process underlying social interaction and cognitive function. However, the relationships between executive impairment and social cognition remain unclear in MS. Previous studies exclusively focused on group comparisons between healthy controls and patients with MS, treating the latter as a homogeneous population. The variability of socio‐ and neurocognitive profiles in this pathology therefore remains underexplored. In the present study, we used a cluster analytic approach to explore the heterogeneity of executive and social cognition skills in MS. A total of 106 patients with MS were compared with 53 healthy matched controls on executive (e.g., working memory) and social cognition (facial emotion recognition and theory of mind) performances. A cluster analysis was then performed, focusing on the MS sample, to explore the presence of differential patterns of interaction between executive and social cognition difficulties and their links to sociodemographic, clinical and cognitive variables. We identified three distinct functional profiles: patients with no executive or social cognition deficits (Cluster 1); patients with difficulties in facial emotion recognition and theory of mind and, to a lesser extent, executive functioning (Cluster 2); and patients with executive functioning difficulties only (Cluster 3). Clinical characteristics (disease duration, disability, fatigue) did not differ between clusters.

Conclusions

These results suggest that there are qualitative differences in the social cognition and executive difficulties that are commonly found among patients with MS. If replicated, the identification of these profiles in clinical practice could allow for more individualized rehabilitation.
Proximal weakness involvement in the first Italian case of Charcot‐Marie‐Tooth 2CC harboring a novel frameshift variant in NEFH
Authors: Aruta Francesco , Severi Daniele , Iovino Aniello , Spina Emanuele , Barghigiani Melissa , Ruggiero Lucia , Iodice Rosa , Santorelli Filippo Maria , Manganelli Fiore , Tozza Stefano
Published: May 2021

Charcot‐Marie‐Tooth (CMT) diseases are a clinically and genetically heterogeneous group of disorders. Different variants in the neurofilament heavy chain (NEFH) gene have been described to cause the CMT2CC subtype. Here we report the first Italian patient affected by CMT2CC, harboring a novel variant in NEFH. In describing our patient, we also reviewed previously CMT2CC individuals, and suggested to consider NEFH variant if patients have an axonal sensory‐motor neuropathy with a prominent proximal muscles involvement with early requirement of walking aids or wheelchair, remembering a motor neuron disorder.
Digitally Fabricated Removable Complete Denture Clinical Workflows using Additive Manufacturing Techniques
Authors: Wagner Stephen A. , Kreyer Robert
Published: May 2021

The use of computer aided design and computer aided manufacturing in the fabrication of complete removable dentures has demonstrated that the prostheses produced are superior in many ways to removable dentures produced using analog techniques. A variety of clinical workflows that take advantage of digital technology have been shown to shorten the number of appointments required to produce high quality prostheses. This paper presents an overview of additive manufacturing in contemporary removable complete denture workflows and describes effective three appointment clinical techniques using additive manufacturing to produce a clinical trial denture and definitive prosthesis.
Public investment criteria under optimal nonlinear income taxation without commitment
Authors: Morita Shigeo , Obara Takuya
Published: May 2021

In this study, we highlight that the incredibility of the government's commitment to a certain tax policy is a determinant of production inefficiency. We show that if the government cannot commit to a certain tax policy and if the types of taxpayers are completely separated, then the production efficiency theorem could be violated in an optimal solution. In this case, an incremental unit of public or private capital affects taxpayers' labor supply through wage rates. In a situation where public capital is more (less) complementary to labor than private capital, public investment tightens (relaxes) the incentive compatibility constraint more than private investment.
Outcomes, complications and risk factors following fluoroscopically guided transcondylar screw placement for humeral intracondylar fissure
Authors: Carwardine D. , Burton N. J. , Knowles T. G. , Barthelemy N. , Parsons K. J.
Published: May 2021

Objectives

To describe the surgical technique and complications for fluoroscopically guided transcondylar screw placement for humeral intracondylar fissure in dogs.

Materials and Methods

A retrospective review was undertaken of cases from two hospitals where identical surgical technique was employed. Factors were analysed for any association with postoperative complications.

Results

Sixty‐two dogs (82 elbows) were reviewed for which the postoperative complication rate was 45%; a total of 15% of cases required revision surgery. Complications were more likely in cases operated on earlier in the case series and with increasing dog bodyweight. Both increasing surgical time and being a neutered female were protective against postoperative complications.

Clinical Significance

Fluoroscopically guided transcondylar screw placement for humeral intracondylar fissure is associated with a high postoperative complication rate (45%) with 15% of cases requiring revision surgery.
Leveraging water, sanitation and hygiene for nutrition in low‐ and middle‐income countries: A conceptual framework
Authors: Zavala Eleonor , King Shannon E. , Sawadogo‐Lewis Talata , Roberton Timothy
Published: May 2021

In low‐ and middle‐income countries (LMICs), access to water, sanitation and hygiene (WASH) is associated with nutritional status including stunting, which affects 144 million children under 5 globally. Despite the consistent epidemiological association between WASH indicators and nutritional status, the provision of WASH interventions alone has not been found to improve child growth in recent randomized control trials. We conducted a literature review to develop a new conceptual framework that highlights what is known about the WASH to nutrition pathways, the limitations of certain interventions and how future WASH could be leveraged to benefit nutritional status in populations. This new conceptual framework will provide policy makers, program implementors and researchers with a visual tool to bring into perspective multiple levels of WASH and how it may effectively influence nutrition while identifying existing gaps in implementation and research.
Putting self‐regulated learning in context: Integrating self‐, co‐, and socially shared regulation of learning
Authors: Bransen Derk , Govaerts Marjan J. B. , Panadero Ernesto , Sluijsmans Dominique M. A. , Driessen Erik W.
Published: May 2021

Processes involved in the regulation of learning have been researched for decades, because of its impact on academic and workplace performance. In fact, self‐regulated learning is the focus of countless studies in health professions education and higher education in general. While we will always need competent individuals who are able to regulate their own learning, developments in healthcare require a shift from a focus on the individual to the collective: collaboration within and between healthcare teams is at the heart of high‐quality patient care. Concepts of collaborative learning and collective competence challenge commonly held conceptualisations of regulatory learning and call for a focus on the social embeddedness of regulatory learning and processes regulating the learning of the collective. Therefore, this article questions the alignment of current conceptualisations of regulation of learning with demands for collaboration in current healthcare. We explore different conceptualisations of regulation of learning (self‐, co‐, and socially shared regulation of learning), and elaborate on how the integration of these conceptualisations adds to our understanding of regulatory learning in healthcare settings. Building on these insights, we furthermore suggest ways forward for research and educational practice.
CO2‐responsive CCT protein interacts with 14‐3‐3 proteins and controls the expression of starch synthesis–related genes
Authors: Fukayama Hiroshi , Miyagawa Fumihiro , Shibatani Naoki , Koudou Aiko , Sasayama Daisuke , Hatanaka Tomoko , Azuma Tetsushi , Yamauchi Yasuo , Matsuoka Daisuke , Morita Ryutaro
Published: May 2021

CO2‐responsive CCT protein (CRCT) is a positive regulator of starch synthesis–related genes such as ADP‐glucose pyrophosphorylase large subunit 1 and starch branching enzyme I particularly in the leaf sheath of rice (Oryza sativa L.). The promoter GUS analysis revealed that CRCT expressed exclusively in the vascular bundle, whereas starch synthesis–related genes were expressed in different sites such as mesophyll cell and starch storage parenchyma cell. However, the chromatin immunoprecipitation (ChIP) using a FLAG‐CRCT overexpression line and subsequent qPCR analyses showed that the 5′‐flanking regions of these starch synthesis–related genes tended to be enriched by ChIP, suggesting that CRCT can bind to the promoter regions of these genes. The monomer of CRCT is 34.2 kDa; however, CRCT was detected at 270 kDa via gel filtration chromatography, suggesting that CRCT forms a complex in vivo. Immunoprecipitation and subsequent MS analysis pulled down several 14‐3‐3‐like proteins. A yeast two‐hybrid analysis and bimolecular fluorescence complementation assays confirmed the interaction between CRCT and 14‐3‐3‐like proteins. Although there is an inconsistency in the place of expression, this study provides important findings regarding the molecular function of CRCT to control the expression of key starch synthesis–related genes.