bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome and Functions of Granulocytic Myeloid-Derived Suppressor Cells Determine their Association with Disease Severity of COVID-19
Authors: Dean Matthew J. , Ochoa Juan B. , Sanchez-Pino Maria , Zabaleta Jovanny , Garai Jone , Del Valle Luis , Wyczechowska Dorota , Buckner Lyndsey , Philbrook Phaethon , Majumder Rinku , Heide Richard Vander , Dunkenberger Logan , Thylur Ramesh , Nossaman Robert , Roberts W. Mark , Chapple Andrew , Collins Jack , Luke Brian , Johnson Randall , Koul Hari , Rees Christopher A. , Morris Claudia R. , Garcia-Diaz Julia , Ochoa Augusto C.
Published: March 2021

COVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19, that deplete arginine but are not associated with respiratory complications. Our data shows that differences in the type, function and transcriptome of Granulocytic-MDSC (G-MDSC) may in part explain the severity COVID-19, in particular the association with pulmonary complications. Large infiltrates by Arginase 1+ G-MDSC (Arg+G-MDSC), expressing NOX-1 and NOX-2 (important for production of reactive oxygen species) were found in the lungs of patients who died from COVID-19 complications. Increased circulating Arg+G-MDSC depleted arginine, which impaired T cell receptor and endothelial cell function. Transcriptomic signatures of G-MDSC from patients with different stages of COVID-19, revealed that asymptomatic patients had increased expression of pathways and genes associated with type I interferon (IFN), while patients with severe COVID-19 had increased expression of genes associated with arginase production, and granulocyte degranulation and function. These results suggest that asymptomatic patients develop a protective type I IFN response, while patients with severe COVID-19 have an increased inflammatory response that depletes arginine, impairs T cell and endothelial cell function, and causes extensive pulmonary damage. Therefore, inhibition of arginase-1 and/or replenishment of arginine may be important in preventing/treating severe COVID-19.
Adolescent ethanol exposure decreases cholinergic markers, blunts behaviorally-evoked acetylcholine and increases in apical dendritic branching within the orbital frontal cortex
Authors: Kipp BT , Nunes PT , Galaj E , Hitchcock B , Nasra T , Poynor KR , Heide SK , Reitz NL , Savage LM
Published: March 2021

During adolescence, heavy binge-like ethanol consumption can lead to frontocortical structural and functional impairments. These impairments are likely driven by adolescence being a critical time point for maturation of brain regions associated with higher-order cognitive functioning. Rodent models of heavy binge-like ethanol exposure show consistent disruptions to the typical development of the prefrontal cortex (PFC). All deep cortical layers receive cholinergic projections that originate from the Nucleus basalis of Meynert (NbM) complex. These cholinergic projections are highly involved in learning, memory, and attention. Adolescent intermittent ethanol exposure (AIE) induces cholinergic dysfunction as a result of an epigenetic suppression of the genes that drive the cholinergic phenotype. The current study used a model of AIE to assess structural and functional changes to the frontal cortex and NbM following binge-like ethanol exposure in adolescence. Western blot analysis revealed long-term disruptions of the cholinergic circuit following AIE: choline acetyltransferase (ChAT) was suppressed in the NbM and vesicular acetylcholine transporter (VAChT) was suppressed in the orbitofrontal cortex (OFC). In vivo microdialysis for acetylcholine efflux during a spatial memory task determined changes in cholinergic modulation within the PFC following AIE. However, AIE spared performance on the spatial memory task and on an operant reversal task. In a second study, Golgi-Cox staining determined that AIE increased apical dendritic complexity in the OFC, with sex influencing whether the increase in branching occurred near or away from the soma. Spine density or maturity was not affected, likely compensating for a disruption in neurotransmitter function following AIE.

Significance Statement

Adolescent ethanol exposure decreases cholinergic markers in the basal forebrain to orbital frontal cortical circuit, which lead to a massive suppression of behaviorally-activated tonic release acetylcholine and sex-dependent increases in dendritic branching. We concluded that cholinergic dysfunction is a contributor to cognitive impairments associated with heavy alcohol exposure during adolescence.

Data Sharing

The data that support the findings of this study are available from the corresponding author upon reasonable request.
Coordinating With a Robot Partner Affects Action Monitoring Related Neural Processing
Authors: Czeszumski Artur , Gert Anna L. , Keshava Ashima , Ghadirzadeh Ali , Kalthoff Tilman , Ehinger Benedikt V. , Tiessen Max , Björkman Mårten , Kragic Danica , König Peter
Published: March 2021

Robots start to play a role in our social landscape, and they are progressively becoming responsive, both physically and socially. It begs the question of how humans react to and interact with robots in a coordinated manner and what the neural underpinnings of such behavior are. This exploratory study aims to understand the differences in human-human and human-robot interactions at a behavioral level and from a neurophysiological perspective. For this purpose, we adapted a collaborative dynamical paradigm from Hwang et al. (1). All 16 participants held two corners of a tablet while collaboratively guiding a ball around a circular track either with another participant or a robot. In irregular intervals, the ball was perturbed outward creating an artificial error in the behavior, which required corrective measures to return to the circular track again. Concurrently, we recorded electroencephalography (EEG). In the behavioral data, we found an increased velocity and positional error of the ball from the track in the human-human condition vs. human-robot condition. For the EEG data, we computed event-related potentials. To explore the temporal and spatial differences in the two conditions, we used time-regression with overlap-control and corrected for multiple-comparisons using Threshold-Free-Cluster Enhancement. We found a significant difference between human and robot partners driven by significant clusters at fronto-central electrodes. The amplitudes were stronger with a robot partner, suggesting a different neural processing. All in all, our exploratory study suggests that coordinating with robots affects action monitoring related processing. In the investigated paradigm, human participants treat errors during human-robot interaction differently from those made during interactions with other humans.
ModPhred: an integrative toolkit for the analysis and storage of nanopore sequencing DNA and RNA modification data
Authors: Pryszcz Leszek P. , Novoa Eva Maria
Published: March 2021

Motivation

DNA and RNA modifications can now be identified using Nanopore sequencing. However, we currently lack a flexible software to efficiently encode, store, analyze and visualize DNA and RNA modification data.

Results

Here we presentModPhred, a versatile toolkit that facilitates DNA and RNA modification analysis from nanopore sequencing reads in a user-friendly manner.ModPhredintegrates probabilistic DNA and RNA modification information within the FASTQ and BAM file formats, can be used to encode multiple types of modifications simultaneously, and its output can be easily coupled to genomic track viewers, facilitating the visualization and analysis of DNA and RNA modification information in individual reads in a simple and computationally efficient manner.

Availability and Implementation

ModPhredis available athttps://github.com/novoalab/modPhred, is implemented in Python3, and is released under an MIT license.

Supplementary Data

Supplementary Data are available atBioinformaticsonline.
Identification of Blood Based Bio-Marker for Huntington’s disease using in-silico gene expression analysis
Authors: Chakraborty Souvik
Published: March 2021

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder with profound phenotypic characters. HD is at present incurable and there are several trials going on to find a cure. HD is caused when there is a mutation in the Huntingtin gene which is found to be associated with axonal transport. Diagnosis is based on the signs and symptoms of the patients but by that time the psychomotor problems have already reached the level from where reversing the disease is impossible. Blood based biomarkers can be used for the diagnosis of the disease at an early stage. In this study several gene expression study data were analyzed and there were 329 Differentially Expressed Genes (DEGs) in all the three chosen datasets. Protein protein interaction network was created using STRING and CytoHubba plug-in was used to identify top ten hub genes which are CXCL8, PSMC6, UBE2D1, UBE2D1, CD27, UBE2D3, SF3B1, CASP3, EIF4E, BIRC2 and PTEN. Online software Enrichr was used for Gene Ontology and KEGG pathway enrichment analysis to find out the biological process, molecular function, cellular component and the pathways that were enriched in HD. This study finds out that those genes which were present in all the three datasets namely FNDC3A, BCLAF1 and ALCAM were not the hub genes. So further studies are required for identifying a potential biomarker of HD.
Somatic DNA demethylation generates tissue-specific methylation states and impacts flowering time
Authors: Williams Ben P. , Bechen Lindsey A. , Pohlmann Deborah A. , Gehring Mary
Published: March 2021

Cytosine methylation is a reversible epigenetic modification to DNA. In plants, removal of cytosine methylation is accomplished by the four members of the DME family of 5-methylcytosine DNA glycosylases. Demethylation by DME is critical for seed development. Consequently, determining the function of the entire gene family in somatic tissues by mutant analysis has not been possible. Here, we bypassed the reproductive defects ofdmemutants to create somatic quadruple homozygous mutants of the entire DME family.dme; ros1; dml2; dml3(drdd) leaves exhibit hypermethylated genomes compared to both wild-type plants andrddtriple mutants, indicating functional redundancy among all four demethylases. Targets of demethylation include regions co-targeted by RNA-directed DNA methylation and, surprisingly, CG gene body methylation, indicating dynamic methylation at these little-understood sites. Additionally, many tissue-specific methylation differences are absent indrdd, suggesting a role for active demethylation in generating divergent epigenetic states across wild-type tissues. Furthermore,drddplants display a striking early flowering phenotype, which is associated with 5’ hypermethylation and transcriptional down-regulation ofFLOWERING LOCUS C. Active DNA demethylation is therefore required for proper methylation patterning across somatic tissues and defines the epigenetic landscape of both intergenic and coding regions.
Structural differences/similarities of diastereotopic groups in three new chiral phosphoramides
Authors: Lal Zakaria Negin , Pourayoubi Mehrdad , Eghbali Toularoud Mahsa , Dušek Michal , Skorepova Eliska
Published: March 2021

The crystal structures of two single-enantiomer amidophosphoesters with an (O)2P(O)(N) skeleton and one single-enantiomer phosphoric triamide with an (N)2P(O)(N) skeleton were studied. The compounds are diphenyl [(R)-(+)-α-4-dimethylbenzylamido]phosphate, (I), and diphenyl [(S)-(−)-α-4-dimethylbenzylamido]phosphate, (II), both C21H22NO3P, and N-(2,6-difluorobenzoyl)-N′,N′′-bis[(R)-(+)-α-ethylbenzyl]phosphoric triamide, C25H28F2N3O2P, (III). The asymmetric units contain two amidophosphoester molecules for (I) and (II), and one phosphoric triamide molecule for (III). In the crystal structures of (I) and (II), molecules are assembled in a similar one-dimensional chiral ribbon architecture, but with almost a mirror-image relationship with respect to each other through N—H...O(P) and C—H...O(P) hydrogen bonds along [010]. In the crystal structure of (III), the chiral tape architecture along [100] is mediated by N—H...O(P) and N—H...O(C) hydrogen bonds, and the tapes are connected into slabs by C—H...O interactions (along the ab plane). The differences/similarities of the two diastereotopic phenoxy groups in (I)/(II) and the two chiral amine fragments in (III) were studied on the grounds of geometry, conformation and contribution to the crystal packing, as well as 1H and 13C signals in a solution NMR study.
The too-much-of-a-good-thing effect of new ventures' opportunity development on innovation strategy under the Chinese context
Authors: Yin Miaomiao , Zhou Bingyu
Published: March 2021

Purpose

The purpose of this research is to reveal how to improve the quality of entrepreneurship by exploring the key factor, opportunity development, impacting the innovation strategy of new ventures. It also introduces political and business ties as moderating variables to reveal the uniqueness of entrepreneurial activities in the Chinese context.

Design/methodology/approach

Empirical data from 215 entrepreneurs and top executives in Chinese new ventures were gathered through a survey and the statistical method used is the regression model.

Findings

The empirical results indicate that: (1) new ventures' opportunity creation positively impacts innovation strategy, while opportunity discovery has a curvilinear (invertedU-shape) impact on innovation strategy; (2) the relationship between opportunity development and innovation strategy is moderated by political and business ties.

Originality/value

This research analyzes and compares the effect of opportunity discovery and opportunity creation on new ventures' innovation strategy. This research further offers an in-depth understanding of the influence mechanism between opportunity development and innovation strategy among Chinese new ventures. Further, the results provide practical guidance for new ventures to develop innovation strategies and for Chinese governments to make entrepreneurial policies.
Profiling gifters via a psychographic segmentation analysis: insights for retailers
Authors: Quach Xuan , Lee Seung Hwan (Mark)
Published: March 2021

Purpose

The aim of this study is to profile types of gifters via a set of psychographic consumption traits (frugality, gratitude, market mavenism and novelty seeking) and identify differences among the groups regarding their gift-purchasing behavior.

Design/methodology/approach

Based on the data from 193 participants, the authors seek to identify and profile unique consumer segments (gifters) generated from the four psychographic consumption traits. Second, once the segments are established, the authors analyze how the segments differ across 16 unique gift-purchasing behaviors.

Findings

The data generated four distinct consumer segments: experiential gifters, considerate gifters, convenience gifters and astute gifters. Across the segments, there were differences in their gift consumption behavior (e.g. time/effort spent, desire for customization, gift presentation, derived joy, purchasing frequency, eco-friendliness, seeking assistance, regifting and more).

Research limitations/implications

US-based sample was collected via an online panel in January; this may restrict the generalizability of the research, given that gift consumption customs may vary across different countries. Thus, future research should include participants from other geographic regions to increase the external validity of the research.

Practical implications

Retail managers can use this knowledge to devise marketing strategies focused on the gift-purchasing behaviors of each group.

Originality/value

Segmenting clusters based on differences in consumption traits provides insights to retailers looking to build a competitive advantage, particularly in a gift purchasing context.
Surviving the aftermaths of natural disasters: the earthen vessels of Kerala, India
Authors: Menon Devaki Vadakepat , Vadakepat Vanaja Menon
Published: March 2021

Purpose

Since 2018, the two floods and droughts that struck Kerala's economy have threatened the state's sustainable earthen vessel production. Current studies allocate focus to the pottery industry's techno-social impacts and ethnography of the potter community; hence, there is a gap in understanding consumers, who are responsible for environmentally conscious behaviors, and their switch from earthen vessels to other materials adaptable to modern kitchens. This study aims to bridge gaps in understanding the reasons behind their demand shift and the challenges of earthenware consumption and production after the disasters.

Design/methodology/approach

This quantitative research explored the perceptions of pottery producers and consumers in Kerala. The sample for the primary survey comprised 590 randomly selected consumers and one master artisan from each of Kerala's total of 44 registered pottery communities. Unpublished records provided the secondary data on production and sales.

Findings

An upward shift in the demand for earthen vessels after natural calamities is observed. Quality, availability and adaptability are consumer concerns. The Markov chain analysis predicts that future consumption of earthen vessels depends on improved marketing mix strategies. After natural disasters, persistent demand exists for earthen vessels, but sustainable production is challenged due to the deteriorating quality and shortage of clay along with the consequent increase in procurement costs of raw materials.

Originality/value

As the earthen vessel industry was affected by disasters very recently, this study contributes an immediate exploration of its sustainable production and consumption challenges.
Consumer attitude towards green products: revisiting the profile of green consumers using segmentation approach
Authors: Mehta Pooja , Chahal Harpreet Singh
Published: March 2021

Purpose

Over the last few decades, there has been a substantial increase in environmentally conscious consumers' willingness to switch their preferences from mainstream products to green products. Hence, it becomes essential for academicians and marketers to understand the notion, attributes and a comprehensive profile of green consumers. Since consumer attitude towards green products is not widely studied in developing countries, the present study aims at exploring the profile of green consumers in India (Punjab State) based on the same in the Indian context.

Design/methodology/approach

The study used the survey method, and a sample of 400 respondents was selected from the Punjab State of India. Initially, principal component analysis was employed to reduce the dimensions. Following this, cluster analysis was applied to segment consumer market in distinctive segments. Results of cluster analysis were validated with discriminant analysis and finally, differences amongst the segments of green and non-green consumers were examined to build on the profile of green consumers.

Findings

The study segmented the consumer market based on consumer attitude towards green products. Results of the study revealed four distinct segments. “Dynamic Green”, the largest cluster, presents truly green consumers who exhibit a positive attitude towards green products. Finally, the study highlighted the attitudinal profile of green and non-green consumers and differences amongst the segments were explained.

Research limitations/implications

Similar study should be conducted in other developing/developed countries. Furthermore, cross-cultural studies can be undertaken to contrast consumer attitude towards green products. The study may also be extended to probe the connection between consumers' attitude and actual behaviour towards green products.

Originality/value

The study examined the role of consumer attitude towards green products in identifying the distinct segment of green consumers and determining different configurations of consumer characteristics to build on the profile of green consumers.
Association of F11R polymorphisms and gene expression with primary Sjögren’s syndrome patients
Authors: Fang Tzu‐Jung , Li Ruei‐Nian , Lin Yuan‐Zhao , Lin Chia‐Hui , Tseng Chia‐Chun , Sung Wan‐Yu , Ou Tsan‐Teng , Wu Cheng‐Chin , Yen Jeng‐Hsien
Published: March 2021

Aims

F11R gene encodes junctional adhesion molecule‐A protein (JAM‐A), which is expressed in various types of cells and is involved in leukocyte extravasation during inflammation. Sjögren's syndrome (SS) is a chronic systemic inflammatory disease that involves lymphocytes invasion of exocrine glands. F11R has been studied in autoimmune diseases, but any association between F11R and SS has not yet been investigated. Therefore, experiments were undertaken to examine the relationships among F11R gene polymorphism, messenger RNA (mRNA) expression and SS patients.

Methods

Three hundred and twenty‐nine patients with SS, and 223 healthy controls were enrolled in their recruitment from the Kaohsiung Medical University Hospital. Genomic DNA was extracted from peripheral blood mononuclear cells and gene polymorphisms were genotyped by TaqMan real‐time polymerase chain reaction (PCR). F11R mRNA expression was quantitated by quantitative real‐time PCR with TaqMan Gene Expression Assay.

Results

Our study showed the genotype ‐688A/C (rs6695707) was not found in relation to SS patients. The odds ratio of ‐436A/G (rs12567886) genotype was notably associated with less susceptibility of SS in human leukocyte antigen (HLA)‐DR2 negative and HLA‐DR3 negative individuals. F11R mRNA expression was lower in SS patients than in the cells of healthy controls.

Conclusion

The result indicated that G allele of ‐436A/G genotype has the potential protective effect against SS disease condition. F11R mRNA was expressed significantly lower in SS patients.
Genome‐wide association study of fleece traits in Inner Mongolia Cashmere goats
Authors: Wang F. H. , Zhang L. , Gong G. , Yan X. C. , Zhang L. T. , Zhang F. T. , Liu H. F. , Lv Q. , Wang Z. Y. , Wang R. J. , Zhang Y. J. , Wang Z. X. , Liu Z. H. , He L. B. , Su R. , Zhao Y. H. , Li J. Q.
Published: March 2021

Inner Mongolia Cashmere goat is a well‐known local cashmere goat breed in China. It is famous for excellent fleece quality and a significant advantage in cashmere yield compared to other cashmere goat breeds. In this study, a genome‐wide association study was used to investigate fiber length, fiber diameter, and cashmere yield of 192 Inner Mongolia Cashmere goats using the Illumina GoatSNP52K Beadchip panel. We discovered that four single nucleotide polymorphisms (SNPs) reached genome‐wide significance levels. These SNPs were located in some genes, e.g. FGF12, SEMA3D, EVPL, and SOX5, possibly related to fleece traits in Inner Mongolia Cashmere goat. Gene ontology enrichment analysis revealed that these genes were enriched in several biological pathways that were involved in hair follicle development in cashmere goats. In summary, the identified significant SNPs and genes provide useful information to explore genetic mechanisms underlying the variation in fleece traits and genomic selection of Chinese cashmere goat.
Mining the 99 Lives Cat Genome Sequencing Consortium database implicates genes and variants for the Ticked locus in domestic cats (Felis catus)
Authors: Lyons L. A. , Buckley R. M. , Harvey R. J. ,   the 99 Lives Cat Genome Consortium
Published: March 2021

Tabby patterns of fur coats are defining characteristics in wild and domestic felids. Historically, three autosomal alleles at one locus (Tabby): Abyssinian (Ta; a.k.a. ticked), mackerel (Tm; a.k.a. striped) and blotched (tb; a.k.a. classic, blotched) were thought to control these patterns in domestic cats and their breeds. Currently, at least three loci influence cat tabby markings, two of which are designated Tabby and Ticked. The Tabby locus is laeverin (LVRN) and affects the mackerel and blotched patterns. The unidentified gene for the Ticked locus on cat chromosome B1 was suggested to control the presence or absence of the ticked pattern (Tabby – Abyssinian (Ta; a.k.a. ticked). The cat reference genome (Cinnamon, the Abyssinian) has the ticked phenotype and the variant dataset and coat phenotypes from the 99 Lives Cat Genome Consortium (195 cats) were used to identify candidate genes and variants associated with the Ticked locus. Two strategies were used to find the Ticked allele(s), one considered Cinnamon with the reference allele or heterozygous (Strategy A) and the other considered Cinnamon as having the variant allele or heterozygous (Strategy B). For Strategy A, two variants in Dickkopf Wnt Signaling Pathway Inhibitor 4 (DKK4), a p.Cys63Tyr (B1:41621481, c.188G>A) and a less common p.Ala18Val (B1:42620835, c.53C>T) variant are suggested as two alleles influencing the Ticked phenotype. Bioinformatic and molecular modeling analysis suggests that these changes disrupt a key disulfide bond in the Dkk4 cysteine‐rich domain 1 or Dkk4 signal peptide cleavage respectively. All coding variants were excluded as Ticked alleles using Strategy B.
Impact of a physician – critical care practitioner pre‐hospital service in Wales on trauma survival: a retrospective analysis of linked registry data
Authors: Lyons J. , Gabbe B. J. , Rawlinson D. , Lockey D. , Fry R. J. , Akbari A. , Lyons R. A.
Published: March 2021

The Emergency Medical Retrieval and Transfer Service for Wales launched in 2015. This service delivers senior pre‐hospital doctors and advanced critical care practitioners to the scene of time‐critical life‐ and limb‐threatening incidents to provide advanced decision‐making and pre‐hospital clinical care. The impact of the service on 30‐day mortality was evaluated retrospectively using a data linkage system. The study included patients who sustained moderate‐to‐severe blunt traumatic injuries (injury severity score ≥ 9) between 27 April 2015 and 30 November 2018. The association between pre‐hospital management by the Emergency Medical Retrieval and Transfer Service and 30‐day mortality was assessed using multivariable logistic regression. In total, data from 4035 patients were analysed, of which 412 (10%) were treated by the Emergency Medical Retrieval and Transfer Service. A greater proportion of patients treated by the Emergency Medical Retrieval and Transfer Service had an injury severity score ≥ 16 and Glasgow coma scale ≤ 12 (288 (70%) vs. 1435 (40%) and 126 (31%) vs. 325 (9%), respectively). The unadjusted 30‐day mortality rate was 11.7% for patients managed by the Emergency Medical Retrieval and Transfer Service compared with 9.6% for patients managed by standard pre‐hospital care services. However, after adjustment for differences in case‐mix, the 30‐day mortality rate for patients treated by the Emergency Medical Retrieval and Transfer Service was 37% lower (adjusted odds ratio 0.63 (95%CI 0.41–0.97); p = 0.037). The introduction of an emergency medical retrieval service was associated with a reduction in 30‐day mortality for patients with blunt traumatic injury.
Safety of neoadjuvant chemotherapy in patients with muscle‐invasive bladder cancer and malignant ureteric obstruction
Authors: Strother Marshall C. , Kutikov Alexander , Epstein Matthew , Bochner Emily , Deng Mengying , Handorf Elizabeth , Lewis Bianca , Ghatalia Pooja , Greenberg Richard E. , Chen David , Viterbo Rosalia , Anari Fern , Smaldone Marc C. , Zibelman Matthew R. , Uzzo Robert G. , Plimack Elizabeth R. , Geynisman Daniel M.
Published: March 2021

Objectives

To determine whether patients with carcinoma invading bladder muscle (MIBC) and ureteric obstruction can safely receive cisplatin‐based neoadjuvant chemotherapy (C‐NAC), and to determine whether such patients require relief of obstruction with a ureteric stent or percutaneous nephrostomy prior to beginning C‐NAC.

Patients and Methods

We performed a single‐institution retrospective analysis of MIBC patients receiving C‐NAC and falling into three groups: no ureteric obstruction (NO); relieved ureteric obstruction (RO); and unrelieved ureteric obstruction (URO). To address whether patients with obstruction can safely receive C‐NAC, we compared patients with NO to those with RO, with the primary outcome of premature chemotherapy discontinuation. To investigate whether patients with obstruction should have the obstruction relieved prior to NAC, we compared RO to URO patients using a primary composite outcome of grade ≥ 3 adverse events, premature chemotherapy discontinuation, dose reduction, or dose interruption. The primary outcomes were compared using multivariable logistic regression. Sensitivity analyses were performed for the RO vs URO comparison, in which patients with only mild degrees of obstruction were excluded from the URO group.

Results

A total of 193 patients with NO, 49 with RO, and 35 with URO were analysed. There were no statistically significant differences between those with NO and those with RO in chemotherapy discontinuation (15% vs 22%; P = 0.3) or any secondary outcome. There was no statistically significant difference between those with RO and URO in the primary composite outcome (51% vs 53%; P = 1) or any secondary outcome.

Conclusion

Patients with ureteric obstruction can safely receive C‐NAC. Relief of obstruction was not associated with increased safety of C‐NAC delivery.
The Method of Local Restriction: in search of potential great ape culture‐dependent forms
Authors: Motes‐Rodrigo Alba , Tennie Claudio
Published: March 2021

Humans possess a perhaps unique type of culture among primates called cumulative culture. In this type of culture, behavioural forms cumulate changes over time, which increases their complexity and/or efficiency, eventually making these forms culture‐dependent. As changes cumulate, culture‐dependent forms become causally opaque, preventing the overall behavioural form from being acquired by individuals on their own; in other words, culture‐dependent forms must be copied between individuals and across generations. Despite the importance of cumulative culture for understanding the evolutionary history of our species, how and when cumulative culture evolved is still debated. One of the challenges faced when addressing these questions is how to identify culture‐dependent forms that result from cumulative cultural evolution. Here we propose a novel method to identify the most likely cases of culture‐dependent forms. The ‘Method of Local Restriction’ is based on the premise that as culture‐dependent forms are repeatedly transmitted via copying, these forms will unavoidably cumulate population‐specific changes (due to copying error) and therefore must be expected to become locally restricted over time. When we applied this method to our closest living relatives, the great apes, we found that most known ape behavioural forms are not locally restricted (across domains and species) and thus are unlikely to be acquired via copying. Nevertheless, we found 25 locally restricted forms across species and domains, three of which appear to be locally unique (having been observed in a single population of a single species). Locally unique forms represent the best current candidates for culture‐dependent forms in non‐human great apes. Besides these rare exceptions, our results show that overall, ape cultures do not rely heavily on copying, as most ape behaviours appear across sites and/or species, rendering them unlikely to be culture‐dependent forms resulting from cumulative cultural evolution. Yet, the locally restricted forms (and especially the three locally unique forms) identified by our method should be tested further for their potential reliance on copying social learning mechanisms (and in turn, for their potential culture‐dependence). Future studies could use the Method of Local Restriction to investigate the existence of culture‐dependent forms in other animal species and in the hominin archaeological record to estimate how widespread copying is in the animal kingdom and to postulate a timeline for the emergence of copying in our lineage.
Characterizing children hospitalized for suicide‐related thoughts and behaviors
Authors: Marraccini Marisa E. , Drapeau Christopher W. , Stein Rachel , Pittleman Cari , Toole Emily N. , Kolstad Molly , Tow Amanda C. , Suldo Shannon M.
Published: March 2021

Background

Despite alarming increases in suicide deaths among preadolescent children, knowledge of the precipitants of suicide risk and the characteristics of children who seek treatment for suicidality is limited. This study’s purpose is to describe children (ages 6–12) hospitalized for suicide‐related concerns and compare demographic and diagnostic differences between children and adolescent (ages 13–18) patients.

Methods

This retrospective study analyzed medical records of 502 children and adolescents ages 6–18 admitted for suicide‐related risk to one psychiatric inpatient hospital in southeastern United States between 2015 and 2018.

Results

Patients were predominantly White (63.5%), female (64.5%), and non‐Hispanic/Latino (85.1%). We conducted descriptive analyses and a series of logistic regressions comparing children and adolescents with data extracted from discharge summaries, (i.e. primary reasons for admission, environmental stressors, and diagnostic categories). Common environmental stressors included school (63.2%) and family (60.7%), and the most common diagnosis included depressive disorders. Compared to adolescents, children were more likely to be Black (OR = 1.99), male (OR = 1.94), and receive neurodevelopmental disorder (aOR = 3.0) or trauma and stress‐related disorder (aOR = 2.6) diagnoses, but less likely to be diagnosed with a depressive disorder (aOR = 0.4). Across both age‐groups, Black patients were more likely to be diagnosed with neurodevelopmental disorders and less likely to receive internalizing disorder diagnoses.

Conclusions

Characteristics of children hospitalized for suicide‐related risk are relatively similar to characteristics of children dying by suicide. Compared to adolescents, hospitalized children are more likely to be Black, male, and have a neurodevelopmental disorder diagnosis. Proactively identifying and providing strengths‐based supports for Black boys and families appear critical for suicide prevention in children.
Debate: Developmental and integrative approaches in child and adolescent psychiatry inpatient facilities: the case of a tertiary university hospital in Paris
Authors: Cohen David , Hanin Cyril , Benarous Xavier
Published: March 2021

Based on the specific experience of a tertiary university hospital in Paris, France, we propose a theoretical framework encompassing developmental, multidimensional, eco‐systemic, and multifactorial perspectives for child and adolescent psychiatry. Consequently, a modern CAPD should be multidisciplinary and implemented in a large medical setting with close disciplines, should promote tailored and integrative treatment, should include some organizational aspects (e.g., tutoring), and should also be opened to cultural and school interventions. Finally, for complex cases, it should keep ambitious goals in terms of both clinical and functional recovery.
Does affirmative action undermine meritocracy? “Meritocratic inclusion” of the marginalized in Nepal’s bureaucracy
Authors: Sunam Ramesh , Pariyar Bishnu , Shrestha Krishna K
Published: March 2021

Motivation

Affirmative action policies have attracted significant academic and policy interest worldwide. One of the key criticisms of such policies is that they undermine meritocratic principles, but there is little evidence and analysis on how such policies are being implemented and shape meritocracy, particularly in low‐ and middle‐income countries.

Purpose

Drawing on a case study of an affirmative action policy designed for the inclusion of members from marginalized groups in Nepal’s civil service, the article critically examines whether this erodes meritocracy and productivity.

Methods and approach

The article draws on empirical insights and data collected through a critical policy analysis, complemented by surveys and interviews with civil servants benefitted from affirmative action and other civil servants, including policy analysts and public intellectuals.

Findings

Our findings challenge a narrative that affirmative action in the form of reservations or quotas erodes meritocracy and reduces the quality of public services. Rather, we argue that an affirmative action policy can enrich meritocracy by addressing its inherent deficits, including its blindness to horizontal inequalities and forms of social exclusion, which tend to sustain the monopolization of bureaucracy by a dominant group in an already unequal society.

Policy implications

Reconceptualizing an affirmative action policy applied in Nepal’s civil service as a tool of “meritocratic inclusion,” we argue that it rewards competence and promotes workforce diversity and social justice. Our evidence suggests that affirmative action, when it is carefully designed, can be an effective policy tool both to enhance representative bureaucracy and enrich meritocracy.
Photographic assessment of simulated dental luxation injuries
Authors: Joos Marc , Joos Roland , Berli Constantin , Filippi Andreas
Published: March 2021

Background/Aim

Dental photographs are a valid means for documentation of dental luxation injuries. The aim of the study was to evaluate the utility of two photographs from different perspectives in the assessment of dental luxation injuries compared to one perspective only.

Materials and Methods

Photographs of simulated dental luxation injuries were shown to experts in dental traumatology and other dentists who had to estimate the displacement in the vertical and horizontal dimensions. The overall error of estimation as a result of both vertical displacement and horizontal displacement was calculated and statistically analyzed.

Results

The mean overall error of estimation was 0.43 mm and 0.75 mm for experts and dentists, respectively. If two (frontal and occlusal) perspectives were available, the overall error was lower than when only one perspective was available (p < .001). Experts had a lower overall error compared to dentists (p < .015).

Conclusion

Two photographs from two perspectives allowed better interpretation of dental luxation injuries.
The First Episode Rapid Early Intervention for Eating Disorders ‐ Upscaled study: Clinical outcomes
Authors: Austin Amelia , Flynn Michaela , Shearer James , Long Mike , Allen Karina , Mountford Victoria A. , Glennon Danielle , Grant Nina , Brown Amy , Franklin‐Smith Mary , Schelhase Monique , Jones William Rhys , Brady Gabrielle , Nunes Nicole , Connan Frances , Mahony Kate , Serpell Lucy , Schmidt Ulrike
Published: March 2021

Background

First Episode Rapid Early Intervention for Eating Disorders (FREED) is a service model and care pathway for emerging adults aged 16 to 25‐years with a recent onset eating disorder (ED) of <3 years. A previous single‐site study suggests that FREED significantly improves clinical outcomes compared to treatment‐as‐usual (TAU). The present study (FREED‐Up) assessed the scalability of FREED. A multi‐centre quasi‐experimental pre‐post design was used, comparing patient outcomes before and after implementation of FREED in participating services.

Methods

FREED patients (n = 278) were consecutive, prospectively ascertained referrals to four specialist ED services in England, assessed at four time points over 12 months on ED symptoms, mood, service utilization and cost. FREED patients were compared to a TAU cohort (n = 224) of similar patients, identified retrospectively from electronic patient records in participating services. All were emerging adults aged 16–25 experiencing a first episode ED of <3 years duration.

Results

Overall, FREED patients made significant and rapid clinical improvements over time. 53.2% of FREED patients with anorexia nervosa reached a healthy weight at the 12‐month timepoint, compared to only 17.9% of TAU patients (X2 [1, N = 107] = 10.46, p < .001). Significantly fewer FREED patients required intensive (i.e., in‐patient or day‐patient) treatment (6.6%) compared to TAU patients (12.4%) across the follow‐up period (X2 [1, N = 40] = 4.36, p = .037). This contributed to a trend in cost savings in FREED compared to TAU (−£4472, p = .06, CI −£9168, £233).

Discussion

FREED is robust and scalable and is associated with substantial improvements in clinical outcomes, reduction in inpatient or day‐patient admissions, and cost‐savings.
Increased inosine levels in drug‐free individuals with at‐risk mental state: A serum metabolomics study
Authors: Uekusa Shusuke , Onozato Mayu , Umino Maho , Sakamoto Tatsuya , Ichiba Hideaki , Tsujino Naohisa , Funatogawa Tomoyuki , Tagata Hiromi , Nemoto Takahiro , Mizuno Masafumi , Fukushima Takeshi
Published: March 2021

Aim

At‐risk mental state (ARMS) has been recently attracting attention with respect to the improvement of the management and outcome of psychiatric diseases, such as schizophrenia. Since only a few studies have reported on biological alterations in ARMS, serum metabolomics was carried out in ARMS subjects and healthy controls using liquid chromatography with high‐resolution mass spectrometry.

Methods

Serum samples were collected from ARMS subjects (n = 24; male: 12; female 12) and age‐ and sex‐matched healthy controls (n = 23 male: 11, female: 12). After serum pre‐treatment, liquid chromatography with high‐resolution mass spectrometry was performed. Multivariate analyses, such as orthogonal partial least‐squares discriminant and volcano plot analyses, were performed.

Results

Serum inosine, lactate, taurine, 2,3‐dihydroxypropanoate and glutamate levels differed between the two groups. A significant increase in inosine levels was detected in the positive‐ and negative‐ion modes; however, significant differences were not observed in the levels of other purine‐related metabolites (hypoxanthine, xanthine and urate) between the two groups.

Conclusion

Increased inosine levels may serve as biological markers for ARMS, in addition to alterations in the levels of lactate and certain amino acids.
Effects of vitamin K2 combined with methotrexate against mitogen‐activated peripheral blood mononuclear cells of healthy subjects and rheumatoid arthritis patients
Authors: Xu Wencheng , Wu Hongguang , Tahara Koichiro , Chen Shuhe , Wang Xiaoqin , Tanaka Sachiko , Sugiyama Kentaro , Sawada Tetsuji , Hirano Toshihiko
Published: March 2021

Background

Methotrexate (MTX) is used as anchor drug for patients with early and established rheumatoid arthritis (RA). Vitamin K2 administration was also reported to be associated with decreased disease activity in RA.

Objectives

Immunosuppressive pharmacodynamics of vitamin K2 combined with MTX was investigated.

Methods

Mitogen‐activated peripheral blood mononuclear cells (PBMCs) were used to evaluate immunosuppressive pharmacodynamics of drugs in vitro.

Results

Vitamin K2 alone dose‐dependently suppressed T cell mitogen‐activated proliferation of PBMCs of both healthy subjects and RA patients. 446.5 and 2232.5 ng/mL vitamin K2 significantly decreased the IC50 values of MTX on the proliferation of PBMCs of RA patients, with little influences on the pharmacodynamics of MTX in the healthy PBMCs. 4465 ng/mL vitamin K2 potentiated the pharmacodynamics of MTX in both RA patients and healthy PBMCs. The additional effects of vitamin K2 to potentiate the suppressive effects of MTX seemed not to be related to the regulation of CD4+CD25+ T cells or CD4+CD25+Foxp3+ Treg cells. MTX alone at 100 ng/mL significantly decreased the percentage of CD4+ T cells in PBMCs of healthy subjects (p < 0.001) with a slight influence in that of RA patients (not significant) and the combination did not show synergistic inhibitory effect. Vitamin K2 alone tended to suppress the secretion of IL‐17, IFN‐γ, and TNF‐α from the activated PBMCs of RA patients with smaller influences on the cytokine productions from healthy PBMCs. These additional effects of vitamin K2 were also observed in combination with MTX.

Conclusion

The above information may partially elucidate the potentiation effects of vitamin K2 on the immunosuppressive efficacy of MTX.
Designing Solutions for Improved Support within Health, Social Care and Criminal Justice for Adults with Learning Disabilities and/or Autism who Have Offended
Authors: HOLLOMOTZ ANDREA , TALBOT JENNY
Published: March 2021

People with learning disabilities and/or autism encounter considerable challenges on the pathways through the criminal justice and/or forensic health systems. This article presents a thematic analysis of focused discussions between users, professionals and practitioners from health, social care and criminal justice. It is informed by the social model of disability, which dictates its focus on solutions for maximising the full and effective participation of disabled users. Informants raised key challenges, including indirect disability discrimination and risk aversive practice, and evidenced innovative solutions. These include person‐centred, multi‐agency working, screening, information sharing, inclusive service design, nurturing sustainable key relationships and long‐term community support.
Do orthodontic tooth movements induce pulp necrosis? A systematic review
Authors: Weissheimer T. , Silva E. J. N. L. , Pinto K. P. , Só G. B. , Rosa R. A. , Só M. V. R.
Published: March 2021

Background

Orthodontic tooth movements are performed by applying forces on teeth, which may cause alterations within the dental pulp. Previously published systematic reviews on the subject only included a small number of studies that assessed pulp status through reliable diagnostic methods. Since then, new evidence has been published, and a further systematic review on the subject is necessary.

Objectives

To evaluate whether there is scientific evidence to support the possibility that orthodontic tooth movements could induce pulp necrosis.

Methods

A systematic search of articles published until June 2020 was performed using MeSH and free terms in the PubMed, Cochrane Library, LILACS, SciELO, Web of Science, EMBASE, Open Grey and Grey Literature databases. Randomized clinical trials (RCTs), nonrandomized clinical trials (nRCTs) and longitudinal (prospective or retrospective) studies that evaluated the pulp status of teeth subjected to orthodontic movements using laser Doppler flowmetry or pulse oximetry were included. The revised Cochrane risk of bias tools for randomized trials (RoB 2) and nonrandomized interventions (ROBINS‐I) were used to assess the quality of the included studies. Relevant findings were summarized and evaluated. The overall quality of evidence was assessed through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool.

Results

Initial screening of databases resulted in 353 studies. In total, 285 studies were excluded because they were duplicates. Of 68 eligible papers, fourteen met the inclusion criteria and were selected for full‐text reading. Two studies were excluded due to the methods used to evaluate pulp status. Twelve studies (five RCTs, one nRCT and six prospective) were included. Four RCTs were classified as having an unclear risk of bias and one as having a high risk of bias. The nRCT was classified as having a low risk of bias. Two prospective studies were classified as having a moderate risk of bias and four as having a serious risk of bias. The GRADE analysis demonstrated a low to very low quality of evidence.

Discussion

Significant limitations regarding the randomization processes within the included RCTs and a lack of control of confounders on most nonrandomized and longitudinal studies were verified.

Conclusions

This systematic review indicates that orthodontic movements do not induce loss of pulp vitality with low to very low certainty of evidence.