bluuebunny/crossref_metadata_2025 huggingface dataset:
The hedgehog signaling pathway is expressed in the adult mouse hypothalamus and modulated by fasting
Authors: Antonellis Patrick J. , Engle Staci E. , Brewer Kathryn M. , Berbari Nicolas F.
Published: June 2021

The importance of the primary cilium was initially highlighted by the class of human genetic disorders known as ciliopathies. Patients with ciliopathies such as Bardet-Biedl and Alström syndrome exhibit hyperphagia-associated obesity as a core clinical phenotype. How primary cilia contribute to energy homeostasis and feeding behavior is complex and unclear, but cilia appear important in both developmental and homeostatic processes. Primary cilia are important signaling centers, required for hedgehog signaling and localization of specific G protein-coupled receptors (GPCRs) with known roles in feeding behavior in mammals. The hedgehog pathway is best known for its role in developmental patterning, but now has recognized roles in adult tissues as well. In the postnatal brain, cilia and hedgehog signaling are important for growth and maintenance of neural progenitors, however, the role of hedgehog signaling in the differentiated adult brain is less clear. Here, we provide a detailed analysis of the expression of core components of the hedgehog signaling pathway in the adult mouse hypothalamus with an emphasis on feeding centers. We show that hedgehog pathway genes continue to be expressed in differentiated neurons important for regulation of feeding behavior. Furthermore, we demonstrate for the first time that pathway activity is regulated at the transcriptional level by fasting. These data suggest that hedgehog signaling is involved in the proper functioning of brain regions which regulate feeding behavior and that hedgehog pathway dysfunction may play a role in the obesity observed in certain ciliopathies.

Significance Statement

Here we investigate the expression of hedgehog pathway components in the adult mouse hypothalamus. Using dual labeling in situ hybridization we show that core components of the signaling pathway are expressed in multiple neuronal cell types within the hypothalamic feeding centers. Our findings also support previous findings that astrocytes are responsive to hedgehog signaling, as determined byGli1andPtch1expression. Using qPCR analysis, we show that hypothalamic hedgehog pathway activity is upregulated in response to fasting and this response is nuclei specific. These data not only provide a more detailed understanding of hedgehog pathway expression in the adult mouse hypothalamus but also provide direct evidence of a novel role for hedgehog signaling in the physiological response to fasting.
Incorporation of unnatural amino acid for the tagging of cannabinoid receptors 1 and 2 reveals receptor roles in regulating cAMP levels
Authors: Thomas Alix , Schultz Carsten , Laguerre Aurélien
Published: June 2021

The role of CB1/CB2 co-expression in cell signaling remains elusive. We established a simplified mammalian cell model system in which expression of CB1 or CB2 can be easily monitored under a confocal microscope. For this, we applied amber codon suppression in live cells to incorporate a single trans-cyclooctene (TCO) bearing amino acid in one of the extracellular loops of CB1 or CB2, followed by fluorescent labeling via click chemistry. We employed genetically encoded biosensors to measure the roles of CB1 and/or CB2 in regulating intracellular calcium ([Ca2+]i) and cAMP ([cAMP]i) levels. We show that the agonist-mediated activation of tagged-CB1 or -CB2 can transiently elevate [Ca2+]i levels. However, when the two receptors were co-expressed in the same cell, CB2 no longer signaled through calcium although CB1-mediated transient elevation of [Ca2+]i levels was unaffected. Because of the existence of crosstalk between calcium and cAMP signaling, we measured the effects of CB1 and/or CB2 in regulating adenylate cyclase activity. We found that the expression of CB1 increased forskolin-induced [cAMP]i levels compared to non-transfected cells. Conversely, CB2 expression decreased stimulated [cAMP]i levels under the same conditions. Finally, co-expressed CB1 and CB2 receptors showed additive yet opposing effects on stimulated [cAMP]i levels. These observations suggest that co-expressed CB1/CB2 act locally as a pair in regulating cell excitability by modulating stimulated [cAMP]i levels.
Mutational bias in spermatogonia impacts the anatomy of regulatory sites in the human genome
Authors: Kaiser Vera B. , Talmane Lana , Kumar Yatendra , Semple Fiona , MacLennan Marie ,   Deciphering Developmental Disorders Study, FitzPatrick David R. , Taylor Martin S. , Semple Colin A.
Published: June 2021

Mutation in the germline is the ultimate source of genetic variation, but little is known about the influence of germline chromatin structure on mutational processes. Using ATAC-seq, we profile the open chromatin landscape of human spermatogonia, the most proliferative cell-type of the germline, identifying transcription factor binding sites (TFBSs) and PRDM9-binding sites, a subset of which will initiate meiotic recombination. We observe an increase in rare structural variant (SV) breakpoints at PRDM9-bound sites, implicating meiotic recombination in the generation of structural variation. Many germline TFBSs, such as NRF, are also associated with increased rates of SV breakpoints, apparently independent of recombination. Singleton short insertions (>=5 bp) are highly enriched at TFBSs, particularly at sites bound by testis active TFs, and their rates correlate with those of structural variant breakpoints. Short insertions often duplicate the TFBS motif, leading to clustering of motif sites near regulatory regions in this male-driven evolutionary process. Increased mutation loads at germline TFBSs disproportionately affect neural enhancers with activity in spermatogonia, potentially altering neurodevelopmental regulatory architecture. Local chromatin structure in spermatogonia is thus pervasive in shaping both evolution and disease.
A mixed-method approach to tailor the implementation of a participatory Total Worker Health® program
Authors: Nobrega Suzanne , Morocho Cesar , Robertson Michelle M. , Kurowski Alicia , Rice Serena , Henning Robert A. , Punnett Laura
Published: June 2021

Purpose

Total Worker Health® (TWH) programs, which represent a holistic approach for advancing worker safety, health and well-being, require an employer to adapt programmatic coordination and employee involvement in program design and delivery. Organizational readiness for such measures requires competencies in leadership, communication, subject expertise and worker participation. In the absence of documented methods for TWH readiness assessment, the authors developed a process to prospectively identify implementation facilitators and barriers that may be used to strengthen organizational competencies and optimize the organizational “fit” in advance.

Design/methodology/approach

The mixed-method baseline assessment instruments comprised an online organizational readiness survey and a key leader interview; these were administered with key organizational and labor leaders in five US healthcare facilities. Findings about organizational resources, skills available and potential implementation barriers were summarized in a stakeholder feedback report and used to strengthen readiness and tailor implementation to the organizational context.

Findings

The research team was able to leverage organizational strengths such as leaders' commitment and willingness to address nontraditional safety topics to establish new worker-led design teams. Information about program barriers (staff time and communication) enabled the research team to respond with proactive tailoring strategies such as training on participant roles, extending team recruitment time and providing program communication tools and coaching.

Originality/value

A new method has been developed for prospective organizational readiness assessment to implement a participatory TWH program. The authors illustrate its ability to identify relevant organizational features to guide institutional preparation and tailor program implementation.
Ancient saltern metagenomics: tracking changes in microbes and their viruses from the underground to the surface
Authors: Ramos‐Barbero Mª Dolores , Viver Tomeu , Zabaleta Ane , Senel Ece , Gomariz María , Antigüedad Iñaki , Santos Fernando , Martínez‐García Manuel , Rosselló‐Móra Ramon , Antón Josefa
Published: June 2021

Microbial communities in hypersaline underground waters derive from ancient organisms trapped within the evaporitic salt crystals and are part of the poorly known subterranean biosphere. Here, we characterized the viral and prokaryotic assemblages present in the hypersaline springs that dissolve Triassic‐Keuper evaporite rocks and feed the Añana Salt Valley (Araba/Alava, Basque Country, Spain). Four underground water samples (around 23% total salinity) with different levels of exposure to the open air were analysed by means of microscopy and metagenomics. Cells and viruses in the spring water had lower concentrations than what are normally found in hypersaline environments and seemed to be mostly inactive. Upon exposure to the open air, there was an increase in activity of both cells and viruses as well as a selection of phylotypes. The underground water was inhabited by a rich community harbouring a diverse set of genes coding for retinal binding proteins. A total of 35 viral contigs from 15 to 104 kb, representing partial or total viral genomes, were assembled and their evolutionary changes through the spring system were followed by SNP analysis and metagenomic island tracking. Overall, both the viral and the prokaryotic assemblages changed quickly upon exposure to the open air conditions.
Can Fiat‐backed Stablecoins Be Considered Cash or Cash Equivalents Under International Financial Reporting Standards Rules?
Authors: Hampl Filip , Gyönyörová Lucie
Published: June 2021

Stablecoins are a rapidly evolving subcategory of cryptocurrency that aim to reduce the price fluctuations of traditional cryptocurrencies and thus become a common digital payment instrument. This paper aims to assess the material substance of fiat‐backed stablecoins to determine whether fiat‐backed stablecoins could be considered, in accordance with IFRS, as cash or cash equivalents. We chose 11 fiat‐backed stablecoins representing 99.97% of the total market capitalisation of all fiat‐backed stablecoins. Using a three‐step approach, we performed an analysis of the legal and general terms and conditions of the selected stablecoins and of cryptocurrency exchanges, and quantitatively analysed their risk characteristics in comparison with fiat currency pairs, money market indexes and instruments, and traditional cryptocurrencies. The results show that nine of the 11 stablecoins met the objective requirements of cash equivalents according to their material substance and, using an extensive interpretation of IAS 7, could be reported as cash equivalents. This study enhances understanding of the material substance of fiat‐backed stablecoins for their financial reporting and can be used by entities when creating accounting policies under existing IFRS rules and by accounting standard setters as evidence when formulating new rules or officially interpreting existing ones to provide guidance on the financial reporting of fiat‐backed stablecoins.
CHD4 variants are associated with childhood idiopathic epilepsy with sinus arrhythmia
Authors: Liu Xiao‐Rong , Ye Ting‐Ting , Zhang Wen‐Jun , Guo Xuan , Wang Jie , Huang Shao‐Ping , Xie Long‐Shan , Song Xing‐Wang , Deng Wei‐Wen , Li Bing‐Mei , He Na , Wu Qian‐Yi , Zhuang Min‐Zhi , Xu Meng , Shi Yi‐Wu , Su Tao , Yi Yong‐Hong , Liao Wei‐Ping ,   For the China Epilepsy Gene 1.0 Project
Published: June 2021

Aims

CHD4 gene, encoding chromodomain helicase DNA‐binding protein 4, is a vital gene for fetal development. In this study, we aimed to explore the association between CHD4 variants and idiopathic epilepsy.

Methods

Trios‐based whole‐exome sequencing was performed in a cohort of 482 patients with childhood idiopathic epilepsy. The Clinical Validity Framework of ClinGen and an evaluating method from five clinical‐genetic aspects were used to determine the association between CHD4 variants and epilepsy.

Results

Four novel heterozygous missense mutations in CHD4, including two de novo mutations (c.1597A>G/p.K533E and c.4936G>A/p.E1646K) and two inherited mutations with co‐segregation (c.856C>G/p.P286A and c.4977C>G/p.D1659E), were identified in four unrelated families with eight individuals affected. Seven affected individuals had sinus arrhythmia. From the molecular sub‐regional point of view, the missense mutations located in the central regions from SNF2‐like region to DUF1087 domain were associated with multisystem developmental disorders, while idiopathic epilepsy‐related mutations were outside this region. Strong evidence from ClinGen Clinical Validity Framework and evidences from four of the five clinical‐genetic aspects suggested an association between CHD4 variants and epilepsy.

Conclusions

CHD4 was potentially a candidate pathogenic gene of childhood idiopathic epilepsy with arrhythmia. The molecular sub‐regional effect of CHD4 mutations helped explaining the mechanisms underlying phenotypic variations.
Resilience or Catastrophe? A possible state change for monarch butterflies in western North America
Authors: Crone Elizabeth E. , Schultz Cheryl B.
Published: June 2021

In the western United States, the population of migratory monarch butterflies is on the brink of collapse, having dropped from several million butterflies in the 1980s to ~2000 butterflies in the winter of 2020–2021. At the same time, a resident (non‐migratory) monarch butterfly population in urban gardens has been growing in abundance. The new resident population is not sufficient to make up for the loss of the migratory population; there are still orders of magnitude fewer butterflies now than in the recent past. The resident population also probably lacks the demographic capacity to expand its range inland during summer months. Nonetheless, the resident population may have the capacity to persist. This sudden change emphasises the extent to which environmental change can have unexpected consequences, and how quickly these changes can happen. We hope it will provoke discussion about how we define resilience and viability in changing environments.
Surgical colic caused by fibrous bands and adhesions in absence of previous abdominal surgery: 9 cases (2012–2019)
Authors: Giusto G. , Cerullo A. , Gandini M.
Published: June 2021

Background

Intestinal pathologies caused by adhesions or fibrous bands in the absence of previous abdominal surgery have been reported in humans but rarely in horses.

Objectives

To describe the clinical and surgical features of acute colic in horses caused by adhesions or fibrous bands in the absence of previous abdominal surgery.

Study design

Retrospective case series.

Methods

Records of horses that underwent exploratory laparotomy at the University of Turin VTH between 2012 and 2019 were reviewed. Clinical and surgical features of cases diagnosed with adhesions or fibrous bands as the primary cause of colic were retrieved, excluding those that had a history of previous abdominal surgery, either for gastrointestinal or urogenital problems.

Results

Nine out of 293 horses which underwent exploratory laparotomy between 2012 and 2019 met the inclusion criteria for the study. In three cases, the adhesion involved the omentum (and the caecal apex, mesojejunum or mesocolon). In one case, a fibrous band 3–4 cm long running across the mesojejunum parallel to the small intestine strangled a loop of small intestine. In the remaining cases, the adhesion involved the left colon. Of these, two were geldings and the adhesion involved the internal inguinal ring region. Both had funiculitis after castration. The others were mares, and in one of them the adhesion was at the level of a small hernia in the left lateral abdominal wall.

Main limitations

Small number of cases.

Conclusions

This is the first case series of surgical colic caused by adhesions in a virgin abdomen. In horses, abdominal adhesions in the absence of previous abdominal trauma may be a cause of colic. Parturition, colon displacement and castration may be predisposing factors for the formation of intra‐abdominal adhesions.
Symmetric dimethylarginine and renal function analysis in horses with dehydration
Authors: Lo Hsiao‐Chien , Winter Judith C. , Merle Roswitha , Gehlen Heidrun
Published: June 2021

Background

Acute dehydration caused by a variety of diseases in horses can lead to acute kidney injury. However, current renal biomarkers usually indicate renal damage late in the course of the disease. A novel biomarker would be helpful to diagnose renal disease earlier.

Objectives

(1) To estimate the correlation of serum symmetric dimethylarginine (SDMA) concentrations with the degree of dehydration, traditional renal biomarkers and renal function analysis, and (2) to determine the value of SDMA as a prognostic and early biomarker of renal injury in horses.

Study design

Prospective cohort.

Methods

Serum SDMA, creatinine and urea concentrations and renal function analysis were measured in 41 horses with dehydration at 4 time points until 48 h after admission. Horses were grouped according to their dehydration level into mildly, moderately and severely dehydrated groups.

Results

Serum SDMA concentrations at admission correlated with creatinine concentrations (r = .412, P < .001). Differences in SDMA concentrations at admission were detected among dehydration levels but not between survivors and nonsurvivors. Significant correlations of SDMA concentrations with other markers of renal function analysis and short‐term outcome were not observed.

Main limitations

Besides the small sample size and low statistical power, missing urine samples at specific time points were also 1 of the main limitations. Only 1 of the horses developed acute kidney injury, which made the evaluation of the predictive value of SDMA difficult.

Conclusions

SDMA concentrations correlated significantly with creatinine concentrations in dehydrated horses. Further research is needed to reveal the application of SDMA in horse.
Biological and environmental influences on the migration phenology of Atlantic salmon Salmo salar smolts in a chalk stream in southern England
Authors: Simmons Olivia M. , Gregory Stephen D. , Gillingham Phillipa K. , Riley William D. , Scott Luke J. , Britton J. Robert
Published: June 2021

Migration enables animals to access important resources throughout their lifetime but exists in a trade‐off with elevated mortality risk. In spring, juvenile Atlantic salmon (smolts) migrate from their natal rivers for marine feeding grounds, with the timing of their marine entry a potentially important determinant of their long‐term survival. However, there is relatively little known on how the interaction of biological and environmental factors affect smolt migration phenology at the individual level, and how these vary throughout the duration of the smolt seaward migration (run).

Using 15‐year tag, recapture, and detection datasets of individual smolts (marked with passive integrated transponder tags) from a chalk stream in southern England, the influences of a range of biological and environmental variables were tested on the run timing of individual smolts, measured as the timing of their arrival in a lower river reach.

The probability of smolts arriving earlier in the lower river reach was elevated following winters that were relatively warm, and when there were larger positive daily changes in water temperature and discharge during the run. Early migrants tended to be larger individuals and from sites lower in the catchment, from where the smolts had to migrate relatively shorter distances. Later migrants were more likely to migrate in schools, but with schooling behaviour also more likely to occur during daylight than at night.

The relative influence of some of these variables altered throughout the run. Relative changes in daily water temperature were not important during the middle period of the smolt run but were important at the start and end of the run. Relative changes in daily discharge were most influential towards the end of the run, when even relatively small changes in discharge had a strong influence on migration.

These results reveal the importance of a wide range of biological and environmental variables on the phenology of smolt migrations, and how their influence can alter throughout the run. With predictions of annually increasing river temperatures, more frequent and intense discharge events, and associated shifts to earlier migration, these results emphasise that such changes in climate are likely to have substantial consequences on the future success of smolt migrations and thereby future numbers of returning adult spawners.
Multicomponent oxide composites for carriers in catalytic applications
Authors: Vora Aliakbar M. , Yadav Ran Bahadur , Basrur Arun G.
Published: June 2021

Binary, ternary, and quaternary composite oxides of rare earths (La and Ce) with one or more of aluminum, magnesium, and zirconium, prepared by coprecipitation are studied. Potential use is carrier in steam or dry reforming of hydrocarbons and ethanol. Individual components influence specific surface area, porosity, acidity, hydrothermal stability, and oxygen storage capacity (OSC) differently. Interaction effects between components further influence these properties resulting in unexpected trends. Alumina and magnesia form solid solutions with zirconia until 650℃. Magnesia imparts better hydrothermal stability to zirconia. Aluminum and magnesium form MgAl2O4 spinel in ternary composites. Specific surface area varies linearly with alumina content. Alumina influences porosity, whereas magnesia influences pore diameter. The composites are mesoporous. Only binary composites present unimodal, pore size distribution. Composites containing alumina present type H2 isotherms while the remaining composites present H3 type isotherms. OSC increases over ZrO2/CeO2 5.7 to 15.3 molar. Magnesia and alumina affect microstructure and hydrothermal stability in contrasting ways. Thermogravimetry indicates that ternary composites of zirconia with alumina or magnesia form through oxolation. Surface hydroxyls with varying acidity are seen by FTIR in as synthesized samples. Magnesia and zirconia influence acidity in opposite ways, which impacts deactivation in the decomposition of 2‐methyl‐3‐butyn‐2‐ol.
Distracting activities in times of COVID‐19 pandemic and their relation to labor supply
Authors: Nilmar de Oliveira José , Orrillo Jaime , Gamboa Franklin
Published: June 2021

Under the hypothesis that workers become distracted and spend less time working during the COVID‐19 pandemic, we analyze, via a model of endogenous growth, the relationship between distracting activities and home office supply. We find a strong theoretical relation between the intertemporal elasticity of substitution of the time spent on distracting activities and the intertemporal elasticity of substitution of home office labor. We also analyze the effect that the intertemporal elasticity of substitution of home office labor has on the marginal productivity of effective labor and the growth rate of production.
Effect of recovery‐based interventions on recovery knowledge and attitudes of mental health professionals, regarding recovery‐oriented practice: A quantitative narrative review
Authors: Sreeram Anju , Cross Wendy , Townsin Louise
Published: June 2021

Mental health recovery is an enabling process encouraging consumers to live a productive life, notwithstanding the presence of debilitating symptoms of illness. The recovery model has been integrated into all areas of mental health. However, literature shows that mental health professionals are not equipped to provide recovery‐oriented care to consumers. Researchers have recommended recovery‐based interventions to develop knowledge, attitudes, and skills to promote recovery‐oriented practice in mental health, yet there is a paucity of research regarding the effect of recovery‐oriented interventions on the knowledge and attitudes of mental health professionals to improve recovery‐oriented practice. Therefore, the purpose of the current review is to understand the effectiveness of interventions on recovery knowledge and attitudes of mental health professionals regarding recovery‐oriented practice. The papers were identified through the Population Intervention Comparison and Outcome strategy. The heterogeneity of the selected papers led to a narrative review instead of a systematic review with meta‐analysis. The analysis suggested that recovery‐based interventions are effective in enhancing the recovery knowledge and attitudes of mental health professionals. Recovery‐based interventions have the potential to reduce the use of physical restraints and improve work satisfaction among mental health professionals. The limitations of the studies were the heterogeneity of the selected populations and the absence of strong methodologies to assess the effect of the interventions. Therefore, future investigations should be focused on the effect of interventions on a homogeneous group using randomized controlled trials.
Development of deep red–emitting CaBiVO5:Pr3+ phosphor for multifunctional optoelectronic applications
Authors: Kaur Harpreet , Jayasimhadri Mula
Published: June 2021

Orthorhombic Pr3+‐doped calcium bismuth vanadate (CBV: Pr3+) phosphors have been synthesized successfully via a citrate‐gel method. The single‐phase formation of CBV: Pr3+ phosphor has been endorsed by X‐ray diffraction (XRD) analysis. The scanning electron microscopy (SEM) image reveals dense‐particle packaging with the quasi‐spherical shape for the prepared CBV: Pr3+ phosphors. Under blue light excitation, CBV: Pr3+ phosphors exhibit intense red emission bands located at 608 and 656 nm wavelengths, overlapping with the absorption spectrum of PR phytochrome, which is present in plants. To achieve the maximum red intensity, the Pr3+ ion concentration is optimized to be 1.25 mol% in the CBV host, after which the emission intensity ceases due to concentration quenching. Dexter's theory disclosed the possibility of d‐d multipolar interaction among Pr3+ ions at higher concentrations of Pr3+ ions in the CBV host. The CIE coordinates are found to be positioned in the pure red region for CBV: Pr3+ phosphor and in the proximity of red‐emitting commercial phosphor. The temperature‐dependent spectral studies manifest substantial thermal stability of the as‐synthesized phosphor. All the studies mentioned above specify the tremendous potentiality of thermally stable CBV: Pr3+ phosphor in agricultural lighting and w‐LED applications.
Y3NbO7 transparent ceramic series for high refractive index optical lenses
Authors: Huang Muzhang , Li Lieyang , Feng Yingjie , Zhao Xiaohui , Pan Wei , Wan Chunlei
Published: June 2021

A2B2O7 and A3BO7 transparent ceramic families are potential materials for optical lenses because of their high refractive index. Although nonstoichiometry is widely present in these material families, its effect on refractive index and optical properties has not yet been fully studied. In this study, optical properties are reported for the Y3NbO7 transparent ceramic series, Y1−xNbxO1.5+x (x = 0.20, 0.22, 0.24, 0.25, 0.26), which were fabricated by a pressureless pre‐sintering and a hot isostatic pressing post‐sintering treatment. The refractive index increases from 2.04 to 2.10 (at 587.6 nm) as the Nb content x increases, which is mainly attributed to the variation in the oxygen ion/vacancy ratio. The Abbe number is larger than 40, showing a decreasing trend as the Nb content x increases. The specimen with x = 0.24 has the highest inline transmittance, which were 62% and 76% at 587.6 and 2000 nm, respectively, for a 1‐mm‐thick specimen. Through the approach of nonstoichiometry, Y1−xNbxO1.5+x series exhibit balanced properties of refractive index, Abbe number, and transmittance, which can be considered as a promising candidate for high refractive index optical lenses.
Is there a role for the p75 neurotrophin receptor in mediating degeneration during oxidative stress and after hypoxia?
Authors: Sankorrakul Kornraviya , Qian Lei , Thangnipon Wipawan , Coulson Elizabeth J.
Published: June 2021

Cholinergic basal forebrain (cBF) neurons are particularly vulnerable to degeneration following trauma and in neurodegenerative conditions. One reason for this is their characteristic expression of the p75 neurotrophin receptor (p75NTR), which is up‐regulated and mediates neuronal death in a range of neurological and neurodegenerative conditions, including dementia, stroke and ischaemia. The signalling pathway by which p75NTR signals cell death is incompletely characterised, but typically involves activation by neurotrophic ligands and signalling through c‐Jun kinase, resulting in caspase activation via mitochondrial apoptotic signalling pathways. Less well appreciated is the link between conditions of oxidative stress and p75NTR death signalling. Here, we review the literature describing what is currently known regarding p75NTR death signalling in environments of oxidative stress and hypoxia to highlight the overlap in signalling pathways and the implications for p75NTR signalling in cBF neurons. We propose that there is a causal relationship and define key questions to test this assertion.

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Muscle architecture and passive lengthening properties of the gastrocnemius medialis and Achilles tendon in children who idiopathically toe‐walk
Authors: Harkness‐Armstrong Carla , Maganaris Constantinos , Walton Roger , Wright David M. , Bass Alfie , Baltzopoulos Vasilios , O’Brien Thomas D.
Published: June 2021

Children who idiopathically toe‐walk (ITW) habitually operate at greater plantarflexion angles and thus, at shorter muscle‐tendon unit (MTU) lengths than typically developing (TD) children. Therefore, it is often assumed that habitual use of the gastrocnemius muscle in this way will cause remodelling of the muscle‐tendon architecture compared to TD children. However, the gastrocnemius muscle architecture of children who ITW has never been measured. It is essential that we gain a better understanding of these muscle‐tendon properties, to ensure that appropriate clinical interventions can be provided for these children. Five children who ITW (age 8 ± 2 years) and 14 TD children (age 10 ± 2 years) participated in this study. Ultrasound was combined with isokinetic dynamometry and surface electromyography, to measure muscle architecture at common positions and passive lengthening properties of the gastrocnemius muscle and tendon across full range of motion. Regardless of which common condition groups were compared under, both the absolute and normalised to MTU muscle belly and fascicle lengths were always longer, and the Achilles tendon length was always shorter in children who ITW than TD children (p < 0.05; large effect sizes). The passive lengthening properties of the muscle and tendon were not different between groups (p > 0.05); however, passive joint stiffness was greater in children who ITW at maximum dorsiflexion (p = 0.001) and at a joint moment common to all participants (p = 0.029). Consequently, the findings of this pilot study indicate a remodelling of the relative MTU that does not support the concept that children who ITW commonly experience muscle shortening. Therefore, greater consideration of the muscle and tendon properties are required when prescribing clinical interventions that aim to lengthen the MTU, and treatments may be better targeted at the Achilles tendon in children who ITW.
Analysis of discharge documentation for older adults living with dementia: A cohort study
Authors: Parker Kirsten J. , Phillips Jane L. , Luckett Tim , Agar Meera , Ferguson Caleb , Hickman Louise D.
Published: June 2021

Background

Older adults living with dementia frequently transition between healthcare settings. Care transitions increase vulnerability and risk of iatrogenic harm.

Aim and objective

To examine the quality of transitional care arrangements within discharge documentation for older people living with dementia.

Design

Secondary analysis of cohort study data.

Method

A secondary analysis of the IDEAL Study [ACTRN12612001164886] discharge documents, following the STROBE guidelines. Participants had a confirmed diagnosis of dementia and were discharged from hospital to a nursing home. An audit tool was used to extract the data. This was developed through a synthesis of existing tools and finalised by an expert panel. The analysis assessed the quality of discharge documentation, in the context of transitional care needs, and presented results using descriptive statistics. Functional ability; physical health; cognition and mental health; medications; and socio environmental factors were assessed.

Results

Sixty participants were included in analyses, and half were male (52%), with a total participant mean age of 83 (SD 8.7) years. There was wide variability in the quality of core discharge information, ranging from excellent (37%), adequate (43%) to poor (20%). A sub‐group of these core discharge documentation elements that detailed the participants transitional care needs were rated as follows: excellent (17%), adequate (46%) and poor (37%).

Conclusion

Discharge documentation fails to meet needs of people living with dementia. Improving the quality of discharge documentation for people living with dementia transitioning from hospital to nursing home is critical to provide safe and quality care.

Relevance to clinical practice

There is a need for safe, timely, accurate and comprehensive discharge information to ensure the safety of people living with dementia and prevent adverse harm.
Ovarian clear cell carcinoma with an immature teratoma component showing ARID1A deficiency and an identical PIK3CA mutation
Authors: Kihara Atsushi , Iizuka Toshihiko , Endo Shinichi , Horie Koji , Kanda Hiroaki , Niki Toshiro
Published: June 2021

We herein report a case of ovarian clear cell carcinoma with an immature teratoma component that exhibited aggressive behavior. A 47‐year‐old woman presented with abdominal distention, and computed tomography detected a cystic mass on the right ovary. The resected mass had mural nodules, most of which showed a pale‐yellow appearance; some nodules had a heterogeneous cut surface with bright yellow and white areas. Histologically, the former nodules were composed of clear cell carcinoma, while the latter contained teratomatous tissues, such as immature skeletal muscle, adipose tissue, and enteric glands. The tumor was staged as pT1c. Despite adjuvant chemotherapy and additional lymph node dissection, she had local recurrence and multiple liver metastasis 6 months after the first surgery. The disease rapidly progressed, and she died 9 months after the first surgery. Clear cell carcinoma and immature teratoma both showed ARID1A deficiency and an identical PIK3CA mutation, which suggested their clonal relationship.
Long non‐coding RNA IGF2‐AS promotes trophoblast cell proliferation, migration, and invasion by regulating miR‐520g/N‐cadherin axis
Authors: Li Mei , Zhang Hong , Kong Qingbi
Published: June 2021

Background

Recurrent miscarriage (RM) is a distressing reproductive issue worldwide. Dysfunction of trophoblasts can trigger numerous unfavorable pregnant outcomes such as RM, stillbirth, and fetal malformation.

Methods

In this text, the roles and molecular basis of long non‐coding RNA insulin growth factor 2 antisense (IGF2‐AS) in the development of trophoblast cells were further investigated. IGF2‐AS, microRNA‐520g (miR‐520g), and N‐cadherin levels were measured by RT‐qPCR assay. Cell viability, the number of colonies, cell apoptosis, migration, and invasion were measured by CCK‐8 assay, colony formation assay, flow cytometry, transwell migration, and invasion assays, respectively. The relative proteins expression was detected by western blot.

Results

The interaction between miR‐520g and IGF2‐AS or N‐cadherin was tested by bioinformatics prediction analysis, and confirmed by dual‐luciferase reporter assay, RNA pull‐down assay, and RNA immunoprecipitation (RIP) assay. Our data revealed that IGF2‐AS and N‐cadherin levels were notably decreased, and miR‐520g was strikingly increased in the placentas from RM patients. IGF2‐AS overexpression promoted cell proliferation, migration, invasion, epithelial‐mesenchymal transition (EMT), and hampered cell apoptosis in trophoblast cells, while IGF2‐AS deletion exhibited opposite results. Moreover, miR‐520g was a target gene of IGF2‐AS and negatively regulated by IGF2‐AS. MiR‐520g inhibitor enhanced the proliferation, migration, and invasion capability of trophoblast cells, suppressed cell apoptosis, and promoted the EMT process. Moreover, the effects of IGF2‐AS overexpression on trophoblast cells were reversed by miR‐520g upregulation.

Conclusions

These findings indicated that IGF2‐AS facilitated trophoblast cell proliferation, migration, invasion, EMT, and suppressed cell apoptosis by regulating miR‐520g/N‐cadherin axis, providing potential biomarkers for RM.
Cure with heart in mind!
Authors: Landgren O.
Published: June 2021

Linked to: S. Ekberg et al. J Intern Med 2021; https://doi.org/10.1111/joim.13303
Posteromedial Corner Release with the Knee in Figure‐of‐Four Position vs Conventional Position for Varus Knee Arthroplasty
Authors: Ji Quan‐bo , Li Jun‐cheng , Zheng Qing‐yuan , Geng Zong‐jie , Ni Ming , Sun Jing‐yang , Wang Yan , Zhang Guo‐qiang
Published: June 2021

Objective

To introduce posteromedial corner release with the knee in the figure‐of‐four position versus the conventional position for varus knee arthroplasty.

Methods

This is a retrospective study. From March 2015 to September 2019, a series of 123 patients (139 knees) with varus knee were randomly and blindly allocated to experimental group (60 patients; 68 knees) and control group (57 patients; 65 knees). Patients in experimental group underwent posteromedial corner release with the knee in the figure‐of‐four position; and patients in control group with the knee in the conventional position. If soft tissue balance was not completely achieved or the medial gap was still tight, an additional loosening technique were used to achieve symmetric medial and lateral space in both groups. Time for soft tissue balancing was defined as the time from the start of the spacer test to the end of the balance test. Length of release was defined as the distance from the osteotomy surface of the tibial plateau to the farthest structures released. The rating system of Hospital for Special Surgery (HSS) knee score was used to evaluate the clinical results. Quantitative variables were described as mean and standard deviation, and compared by one‐way analysis of variance.

Results

The mean age of experimental group and control group was 70.2 ± 8.7 years and 68.7 ± 6.2 years, respectively (P > 0.05). Preoperatively, the mean HSS score of the groups was 38.2 ± 11.3 and 39.1 ± 10.7, respectively (P > 0.05). The mean varus knee angle was 19.7° ± 9.3° and 19.3° ± 10.7°, respectively (P > 0.05). The mean time for soft tissue balancing was 8.4 ± 3.3 min and 11.3 ± 6.9 min in experimental and control group, respectively (P < 0.05). The mean length of releasing posteromedial corner structures was 35.5 ± 13.4 mm and 27.3 ± 9.7 mm in experimental and control group, respectively (P < 0.05). Additional special loosening techniques were performed in eight knees in experimental group and seven knees in control group. The HSS scores 5 years after surgery were 95.1 ± 16.9 and 94.8 ± 17.2 respectively (P > 0.05). No complications were found during the follow‐up time, and the clinical symptoms were observed to be significantly improved in the patients.

Conclusion

The posteromedial corner can be released more extensively and thoroughly when the knee is placed in the figure‐of‐four position during varus knee arthroplasty.
The parental magma composition, crustal contamination process, and metallogenesis of the Shitoukengde Ni‐Cu sulfide deposit in the Eastern Kunlun Orogenic Belt, NW China
Authors: Li Liang , Zhang Dexin , Tan Shucheng , Sun Fengyue , Wang Chao , Zhao Tuofei , Li Shijin , Yang Yanqian
Published: June 2021

Shitoukengde is an important magmatic Ni–Cu sulfide deposit in the Eastern Kunlun Orogenic Belt (EKOB). It comprises several mafic–ultramafic complexes and contains different kinds of mafic–ultramafic rocks. Lherzolite and olivine websterite are the most significant Ni–Cu‐hosted rocks. The No. I complex hosts six Ni–Cu ore bodies, and the depth of the intrusion has great exploration potential. Therefore, geochronology, geochemistry, and mineral chemistry of the Shitoukengde deposit were studied to constrain its mineralization time, parental magma composition, and crustal contamination process. Zircon U–Pb dating of olivine websterite shows the magmatic origin (Th/U = 0.40–1.05) and an age of 418.1 ± 8.7 Ma (MSWD = 0.01), which is coeval with the Xiarihamu, Akechukesai, and other Cu–Ni deposits in the EKOB. Geochemically, the mafic–ultramafic rocks are characterized by low SiO2, TiO2, and Na2O + K2O and high MgO (9.49–36.02%), with Mg# values of 80–87. They are relatively enriched in LREE and LILEs (e.g., K, Rb, and Th), with weakly positive Eu anomalies (δEu = 0.83–2.26), but depleted in HFSEs (e. g., Ta, Nb, Zr, and Ti). Based on the electron microprobe analyses, all of the olivines are chrysolite (Fo = 81–86), and the pyroxenes are dominated by clinoenstatite (En = 80–84) and augite (En = 49–55) in the mafic–ultramafic rocks. Therefore, the composition of parental magma is estimated to be picritic basaltic magma with SiO2 and MgO concentrations of 54.47 and 13.95%, respectively. The zircon εHf(t) values of olivine websterite vary from −0.8 to 4.6, with a TDM1 of 0.84–1.06 Ga, indicating that the parental magma was derived from relatively high degree partial melting (about 13.4%) of a depleted mantle source and experienced significant crustal contamination (about 12–16%). We propose that crustal assimilation, rather than fractional crystallization, played a key role in triggering the sulfide saturation of the Shitoukengde deposit, and the metallogenesis of “deep liquation–pulsing injection” is the key mechanism underlying its formation. The parental magma, before intruding, underwent liquation and partial crystallization at depth, partitioning into barren, ore‐bearing, and ore‐rich magma and ore pulp, and was then injected multiple times, resulting in the formation of the Shitoukengde Ni–Cu deposit.
Cramér‐von Mises tests for change points
Authors: Erlemann Rasmus , Lockhart Richard , Yao Rihan
Published: June 2021

We study two nonparametric tests of the hypothesis that a sequence of independent observations is identically distributed against the alternative that at a single change point the distribution changes. The tests are based on the Cramér–von Mises two‐sample test computed at every possible change point. One test uses the largest such test statistic over all possible change points; the other averages over all possible change points. Large sample theory for the average statistic is shown to provide useful p‐values much more quickly than bootstrapping, particularly in long sequences. Power is analyzed for contiguous alternatives. The average statistic is shown to have limiting power larger than its level for such alternative sequences. Evidence is presented that this is not true for the maximal statistic. Asymptotic methods and bootstrapping are used for constructing the test distribution. Performance of the tests is checked with a Monte Carlo power study for various alternative distributions.
Depression and its associated factors among people with multidrug‐resistant tuberculosis in Myanmar
Authors: Theingi Phyo , Kamiya Yasuhiko , Myat Moe Myat , Cho San Cho , Cox Sharon E.
Published: June 2021

Background

Depression is an important potential comorbidity in persons with tuberculosis (TB), yet data in many settings are scarce.

Objective

To estimate the prevalence and risk factors of depression in persons with multidrug‐resistant tuberculosis (MDR‐TB) in Myanmar.

Methods

A cross‐sectional survey among MDR‐TB participants at Aung San MDR‐TB treatment centre in Yangon during routine clinic follow‐up visits. Patients Health Questionnaire‐9 (PHQ‐9) in the local language was used to screen for depression and structured questionnaires conducted. Univariable and multivariable logistic regression models were performed to identify associations.

Results

Three‐hundred and twenty‐nine participants were enrolled between 19th December 2019 and 31st January 2020; 33% (111/329) in the intensive treatment phase. The prevalence of depressive symptoms (PHQ‐9 ≥ 10) was (34/329) 10.33%. Multivariable analysis indicated financial hardship as a result of MDR‐TB symptoms/treatment (aOR = 2.63, 95%CI: 1.12–6.67), suffering ≥1 respiratory symptoms (aOR = 6.72, 95%CI: 2.41–18.76), high education level (aOR = 4.26, 95%CI: 1.70–10.70), reported diabetes (aOR = 3.05, 95%CI: 1.16–7.99) as associated with depressive symptoms, with weak evidence of an association in females (aOR = 2.09, 95%CI: 0.94–4.65).

Conclusion

Depressive symptoms are more common in those with comorbidities/TB symptoms. Further research is required to determine the effects of interventions to support persons with depressive symptoms identified using simple, standardised validated tools like PHQ‐9.
Turbulence in Small Air Jets at Exit Velocities Up to 705 Feet per Second
Authors: Lassiter L. W.
Published: June 2021

Turbulence intensity, scale, and spectrum measurements were made on model jets of 1 in. and 2-in. diam at various mean velocities. The indications are that only in the fully developed flow is turbulence intensity invariant with mean velocity; intensity in the core, in the turbulent annulus, and in the transition region decreases in varying degrees with mean velocity increase. Longitudinal and radial scales of turbulence were found to increase in the annulus in proportion to about the square root of axial distance, and longitudinal scale is about 65 per cent greater than radial scale. Both radial and longitudinal scales seem to be essentially constant with mean velocity. Turbulence spectra were found to consist of a sharply peaked band of frequencies in the core, degenerating to a slightly peaked broad band at points in the mixing regions.
A Direct Method for Determining Airy Polynomial Stress Functions
Authors: Neou Ching-Yuan
Published: June 2021

Simplified procedures are developed for systematically reducing Airy stress functions expressed as doubly infinite power series to desired polynomial forms on the bases of compatibility and boundary conditions only, without resort to patching or guessing, as is necessary in the conventional superposition and “semi-inverse” methods.
The Mobility of Levers Having Uniformly Distributed Mass
Authors: Creech M. D.
Published: June 2021

This paper shows how the mobility of a uniform rigid lever of mass M with m arbitrary mobilities connected along its length can be analyzed. The mass of the lever is divided into n equal mobilities connected to a rigid weightless lever together with the m other mobilities. It is shown that the infinite-series expansion representing this case is convergent to a finite value.
Response of Nonlinearly Supported Spherical Boundaries to Shock Waves
Authors: Baron M. L.
Published: June 2021

An integral transform technique is used to solve a boundary-value problem in which the partial differential equation is linear but the associated boundary condition is nonlinear. A spherical cavity in an infinite acoustic medium has an elastically supported boundary such that the pressure-displacement relation on the boundary is nonlinear. The response of the boundary to a plane shock wave which progresses across the cavity and envelops it is obtained by solving two auxiliary boundary-value problems with linear boundary conditions. Using influence coefficients obtained from these solutions, a nonlinear integral equation for the response of the actual boundary is obtained. The integral equation is solved numerically for a set of parameters, and curves for the pressure-time and displacement-time responses of the boundary are presented.