bluuebunny/crossref_metadata_2025 huggingface dataset:
Eltrombopag in paediatric immune thrombocytopenia: Iron metabolism modulation in mesenchymal stromal cells
Authors: Di Paola Alessandra , Palumbo Giuseppe , Tortora Chiara , Argenziano Maura , Catanoso Marialuigia , Di Leva Caterina , Ceglie Giulia , Perrotta Silverio , Locatelli Franco , Rossi Francesca
Published: December 2021

Immune thrombocytopenia (ITP) is an autoimmune disease caused by platelet destruction mediated by auto‐antibody production. It is characterized by a compromised immune system and alteration of the inflammatory response. Mesenchymal stromal cells (MSCs) play an important role in modulating immune and inflammatory processes, exerting immune‐suppressing and anti‐inflammatory properties. In ITP‐MSCs the activity and survival are strongly impaired. Eltrombopag (ELT) is a thrombopoietin receptor agonist approved in chronic ITP for stimulating platelet production. It has immunomodulating properties by stimulating T and B regulatory cell activity and by promoting a macrophage switch from the pro‐inflammatory to the anti‐inflammatory phenotype. ELT also exhibits iron‐chelating properties. Iron is a crucial element involved in several physiologic processes, but its intracellular accumulation determines cell damages. Therefore, for the first time we analysed the effect of ELT on ITP‐MSCs demonstrating its ability to restore survival and activity of MSCs directly and to promote their survival and proliferation indirectly, by iron metabolism modulation.
The interactional production and breach of new norms in the time of COVID‐19: Achieving physical distancing in public spaces
Authors: Drury John , Stokoe Elizabeth
Published: December 2021

A key requirement of COVID‐19 pandemic behavioural regulations in many countries was for people to ‘physically distance’ from one another, which meant departing radically from established norms of everyday human sociality. Previous research on new norms has been retrospective or prospective, focusing on reported levels of adherence to regulations or the intention to do so. In this paper, we take an observational approach to study the embodied and spoken interactional practices through which people produce or breach the new norm. The dataset comprises 20 ‘self‐ethnographic’ fieldnotes collected immediately following walks and runs in public spaces between March and September 2020, and these were analysed in the ethnomethodological tradition. We show that and how the new norm emerged through the mutual embodied and spoken conduct of strangers in public spaces. Orientations to the new norm were observed as people torqued their bodies away from each other in situations where there was insufficient space to create physical distance. We also describe how physical distance was produced unilaterally or was aggressively resisted by some people. Finally, we discuss the practical and policy implications of our observations both for deciding what counts as physical distancing and how to support the public to achieve it.
Identification of an IDO1‐based immune classifier for survival prediction of upper tract urothelial carcinoma
Authors: Zhong Wenlong , Yang Meng , Cheng Sida , Hou Weibin , Wang Bo , Chen Junyu , Yu Hao , Ouyang Yi , Wang Xiaofei , Ou Ziwei , Xu Peiqi , Li Xuesong , Zhou Liqun , Huang Jian , Wang Chunhui , Lin Tianxin
Published: December 2021

The limited response rate of immunotherapy in upper tract urothelial carcinoma (UTUC) might be attributed to additional immunosuppressive mechanisms in vivo. As a promising immune checkpoint target, the expression and prognostic role of indoleamine 2,3‐dioxygenase 1 (IDO1) in UTUC remains unknown. In this study, the expression and prognostic value of IDO1 was analyzed in 251 patients from 3 independent cohorts. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to construct an IDO1‐based immune classifier and external validation was performed to further validate the classifier. RNA sequencing and immunofluorescence were used to explore the immune contexture of different risk groups stratified by classifier. We found that high IDO1 expression on tumor cells (TC) indicated a poorer overall survival and disease‐free survival in all cohorts. Patients with high expression of IDO1 TC possessed increased infiltration of CD4+, CD8+ and Foxp3+ T cells. An immune classifier based on intratumoral CD8+ lymphocytes, IDO1 TC, and stromal PD‐L1 expression status was developed, with its area under the curves (AUCs) values for overall survival at 5 y being 0.79 (95% confidence interval [CI] 0.65‐0.93) in the discovery cohort, 0.75 (95% CI 0.58‐0.92) and 0.78 (95% CI 0.65‐0.92) in the internal and external validation cohorts, respectively. The high‐risk group stratified by the immune classifier was associated with immunosuppressive contexture, accompanied by enhanced CD8+ T cells exhaustion patterns. Our IDO1‐based immune classifier can provide a superior accuracy for survival prediction and lead to individual stratification of UTUC immune subtypes.
Cat allergen exposure in a naturalistic exposure chamber: A prospective observational study in cat‐allergic subjects
Authors: Yang William H. , Kelly Suzanne , Haya Laura , Mehri Rym , Ramesh Divya , DeVeaux Michelle , Wang Claire Q. , Meier Pretty , Narula Sumit , Shawki Furat , Pennington Ryan , Perlee Lorah , O’Brien Meagan P.
Published: December 2021

Background

To determine the proportion and reproducibility of cat‐allergic mild asthmatics with early asthmatic response (EAR) during cat allergen exposure in a naturalistic exposure chamber (NEC).

Methods

This was a prospective, observational study in 30 cat‐allergic mild asthmatics who received two 180‐min cat‐allergen (Felis domesticus allergen 1 [Fel d 1]) challenges 27 days apart in an NEC.

Results

An EAR (≥20% reduction from baseline in forced expiratory volume in 1 s [FEV1]) was observed in 67% and 52% of subjects at first and second NEC exposure, respectively, with similar median time to EAR; 44% of subjects had an EAR on days 1 and 28. Late asthmatic response (≥15% reduction in FEV1 within 24 h of NEC exit) was observed in 33% of subjects following either exposure. Average FEV1 and total nasal symptom score during NEC exposure were highly correlated within subjects between NEC exposures (r = 0.91, p < 0.0001; r = 0.73, p < 0.001), but total ocular symptom score was not. Time to EAR, but not average FEV1, was significantly associated with NEC Fel d 1 concentration, which was variable. There were no serious adverse events; 12/30 subjects experienced 20 adverse events (including asthma, 10%; headache, 10%).

Conclusions

The NEC model demonstrates that average FEV1 change is highly reproducible and has a low correlation with cat allergen levels. However, time to EAR and incidence of EAR are less reproducible and are highly correlated with NEC allergen levels. Average FEV1, rather than incidence of EAR or time to EAR, could be considered as an endpoint for interventional trials testing cat‐specific anti‐allergy therapies using an NEC.
Heart valve surgery and the obesity paradox: A systematic review
Authors: EL‐Andari Ryaan , Bozso Sabin J. , Kang Jimmy J. H. , Bedard Alexandre M. A. , Adams Corey , Wang Wei , Nagendran Jeevan
Published: December 2021

Obesity has been associated with increased incidence of comorbidities and shorter life expectancy, and it has generally been assumed that patients with obesity should have inferior outcomes after surgery. Previous literature has often demonstrated equivalent or even improved rates of mortality after cardiac surgery when compared to their lower‐weight counterparts, coined the obesity paradox. Herein, we aim to review the literature investigating the impact of obesity on surgical valve interventions. PubMed and Embase were systematically searched for articles published from 1 January 2000 to 15 October 2021. A total of 1315 articles comparing differences in outcomes between patients of varying body mass index (BMI) undergoing valve interventions were reviewed and 25 were included in this study. Patients with higher BMI demonstrated equivalent or reduced rates of postoperative myocardial infarction, stroke, reoperation rates, acute kidney injury, dialysis and bleeding. Two studies identified increased rates of deep sternal wound infection in patients with higher BMI, although the majority of studies found no significant difference in deep sternal wound infection rates. The obesity paradox has described counterintuitive outcomes predominantly in coronary artery bypass grafting and transcatheter aortic valve replacement. Recent literature has identified similar trends in other heart valve interventions. While the obesity paradox has been well characterized, its causes are yet to be identified. Further study is essential in order to identify the causes of the obesity paradox so patients of all body sizes can receive optimal care.
Wilderness forms and their implications for global environmental policy and conservation
Authors: Pérez‐Hämmerle Katharina‐Victoria , Moon Katie , Venegas‐Li Rubén , Maxwell Sean , Simmonds Jeremy S. , Venter Oscar , Garnett Stephen T. , Possingham Hugh P. , Watson James E. M.
Published: December 2021

With the intention of securing industry‐free land and seascapes, protecting wilderness entered international policy as a formal target for the first time in the zero draft of the Post‐2020 Global Biodiversity Framework under the Convention on Biological Diversity. Given this increased prominence in international policy, it is timely to consider the extent to which the construct of wilderness supports global conservation objectives. We evaluated the construct by overlaying recently updated cumulative human pressure maps that offer a global‐scale delineation of industry‐free land as wilderness with maps of carbon stock, species richness, and ground travel time from urban centers. Wilderness areas took variable forms in relation to carbon stock, species richness, and proximity to urban centers, where 10% of wilderness areas represented high carbon and species richness, 20% low carbon and species richness, and 3% high levels of remoteness (>48 h), carbon, and species richness. Approximately 35% of all remaining wilderness in 2013 was accessible in <24 h of travel time from urban centers. Although the construct of wilderness can be used to secure benefits in specific contexts, its application in conservation must account for contextual and social implications. The diverse characterization of wilderness under a global environmental conservation lens shows that a nuanced framing and application of the construct is needed to improve understanding, communication, and retention of its variable forms as industry‐free places.
3D face expression recognition with ensemble deep learning exploring congruent features among expressions
Authors: Rajagopal Suganya Devi , Ramachandran Baskaran
Published: December 2021

Automatic and accurate 3D face expression categorization has been a challenging task in many computer vision applications. This article presents a novel approach named 3D face expression recognition with ensemble deep learning (3D‐FER‐EDL). The framework comprises three levels. Each of the first two levels gives preference to a subset of labels, considering the congruent features among expressions. Each 3D expressive face is represented as a CDS features vector, which combines corner, distance, and slope features. CDS feature vector is given as input to the first level learners. Expression probability vectors from the first level learners are jointly given as the input to the second level learners. The probability vectors from level one and two are given as the input to the third level, which is the meta classifier. The experiments are conducted on the Bosphorus database and the CASIA 3D face database to evaluate the effectiveness of the proposed approach.
A global map of human pressures on tropical coral reefs
Authors: Andrello Marco , Darling Emily S. , Wenger Amelia , Suárez‐Castro Andrés F. , Gelfand Sharla , Ahmadia Gabby N.
Published: December 2021

As human activities on the world's oceans intensify, mapping human pressure is essential to develop appropriate conservation strategies and prioritize investments with limited resources. Here, we map six human (nonclimatic) pressures on coral reefs using the latest quantitative data on fishing, water pollution (nitrogen and sediments), coastal population, industrial development, and tourism. Using a percentile approach to rank different stressors, we identify the top‐ranked local pressure and estimate a cumulative pressure index for 54,596 global coral reef pixels at 0.05° (∼5 km) resolution. We find that coral reefs are exposed to multiple intense local pressures: fishing and water pollution (nutrients and sediments) are the most common top‐ranked pressures worldwide (in 30.8% and 32.3% of reef cells, respectively), although each pressure was ranked as a top pressure in some locations. We also find that local pressures are similar inside and outside a proposed global portfolio of coral reef climate refugia, suggesting that even potential climate refugia have high levels of local human pressure that require effective management. Our findings and datasets provide the best available information that can ensure local pressures are effectively managed across the world's coral reefs.
Cutaneous collagenous vasculopathy: A report of three cases
Authors: Grossman Marc E. , Cohen Marc , Ravits Margaret , Blume Ralph , Magro Cynthia M.
Published: December 2021

Cutaneous collagenous vasculopathy is a rare pauci‐inflammatory, superficial, cutaneous vasculopathy characterized by progressive fine‐branching telangiectasias clinically, while light microscopically one observes dilated venules and capillaries within the superficial dermis exhibiting excessive Type IV collagen within the vessel wall. We present three cases of collagenous vasculopathy. Two cases were associated with certain autoimmune stigmata, including a positive serologic anti‐endothelial cell antibody assay and positive lupus anticoagulant in one, while the third case had positive anti‐ribonucleoprotein (RNP) antibodies. The latter case was associated with chronic hydroxyurea therapy for an underlying myeloproliferative disorder. We explore the role of immune‐ and non‐immune‐based endothelial cell injury in the pathogenesis of collagenous vasculopathy.
Technical efficiency of financial inclusion and human development: Insights from the Indian states
Authors: Singh Bhanu Pratap , Yadava Anup Kumar
Published: December 2021

Financial inclusion programs are used as a major economic development tool in emerging economies. Human development is the major determinant of financial inclusion, creating opportunities for people to better access financial services. The study's major aim is to examine the technical efficiency of financial inclusion of Indian states by Data Envelopment Analysis using human development as input. To achieve this objective, a 3‐dimensional Financial Inclusion Index (FII) is constructed for 28 major Indian states from 2010 to 2017. Empirical findings suggest most Indian states are under low and medium financial inclusion, and states with better human development have better FII status. Crucially, technical efficiency results reveal states with better human development perform better in terms of FII. The inconsistency in FII and human development ranks is majorly found in North‐eastern and high‐income Indian states. Therefore, policymakers in India should focus on promoting human development in low Human Development Index states.
Relics of beavers past: time and population density drive scale‐dependent patterns of ecosystem engineering
Authors: Johnson‐Bice Sean M. , Gable Thomas D. , Windels Steve K. , Host George E.
Published: December 2021

Like many ecological processes, natural disturbances exhibit scale‐dependent dynamics that are largely a function of the magnitude, frequency and scale at which they are assessed. Ecosystem engineers create patch‐scale disturbances that affect ecological processes, yet we know little about how these effects scale across space or vary through time. Here, we investigate how patch disturbances by beavers Castor canadensis, ecosystem engineers renowned for their pond‐creation behavior, affect ecological processes across space and time. We evaluated how beaver population recovery influenced surface water dynamics in relation to population density over 70 years across multiple spatial scales (pond, watershed and regional) in northern Minnesota. Surface water area was positively related to population density at the watershed scale; however, despite variation in beaver densities (and therefore surface water area) at the watershed scale, regional‐scale surface water area was stable through time. This stability appears to have been driven by asynchronous beaver density fluctuations among watersheds, combined with the increasing importance of abandoned ponds. Beavers initially created and occupied larger ponds with greater surface water area, but through time shifted towards occupying smaller ponds. As ponds accumulated on the landscape proportionally more surface water was stored within abandoned ponds, which offset the smaller size of occupied ponds. Beaver engineering – driven by density‐dependent mechanisms and the legacy effects from abandoned ponds – not only follows general patterns of patch disturbance dynamics by creating a spatial mosaic of patches, but the organism‐created mosaic also appears to generate ecological stability at greater spatial scales. We suggest restoring beavers to landscapes is a viable method for increasing surface water storage and will ultimately help advance numerous conservation and rewilding objectives. Our study demonstrates that ecosystem engineering effects can be scale‐dependent, indicating researchers should evaluate the ecological impact of engineers across diverse spatiotemporal scales to fully understand their functional roles in ecosystems.
First report of anthracnose caused by Colletotrichum siamense on Hibiscus tiliaceus in Brazil
Authors: Rocha Virgínia A. L. , Barguil Beatriz Meireles , Rego Tamiris Joana Santos , Beserra José Evando Aguiar
Published: December 2021

Plants of the genus Hibiscus are commonly cultivated in Brazil as ornamentals. Symptoms of leaf spot in Hibiscus tiliaceus trees are frequently observed. The objective of this study was to identify and characterize the etiological agent of the H. tiliaceus leaf spot. Leaves with symptoms were collected in Teresina, state of Piauí, Brazil and a Colletotrichum species was consistently isolated from them. Morphological identification, phylogeny of ITS region, GAPDH and ACT genes, a pathogenicity test and re‐isolation of the fungus from symptomatic artificially inoculated plants confirmed Colletotrichum siamense as the causative agent of the disease. This is the first record of C. siamense causing anthracnose in H. tiliaceus in Brazil.
Attitudes and knowledge of dental radiography amongst students of dentistry and related fields
Authors: Mahasneh Arwa M. , Al‐Mousa Dana S. , Khabour Omar F. , Al‐Sa’di Amani G. , Alakhras Maram
Published: December 2021

Objectives

This study aimed to evaluate the level of knowledge and attitude towards quality control in dental radiography amongst students of dentistry, allied dental sciences and radiologic technology programmes.

Methods

A cross‐sectional survey was conducted using self‐administered questionnaire on a convenience sample of 580 students from three universities in Jordan. The questionnaire was divided into sections that include personal sociodemographic variables, knowledge about quality assurance in dental radiography and attitude towards quality assurance in dental radiography.

Results

A total of 286 students completed the questionnaire (response rate = 49.3%), of whom 70% were women. The respondents’ knowledge scores ranged from 12.2% (n = 35) to 35.2% (n = 100). The mean of the quality assurance knowledge scores for the whole study sample was 20.3% ± 14.5%, with no significant difference between men and women (p = .643). Allied dental sciences students showed significantly higher knowledge scores (25.0 ± 13.0) than dentistry (17.8 ± 14.40) or radiologic technology students (20.9 ± 14.8). The average attitude scores towards quality assurance in dental radiography were fairly good (69.5 ± 26.4) with no statistically significant differences by study programme.

Conclusion

Knowledge of students about quality assurance in the three programmes is inadequate. The participants' attitude towards quality assurance was fairly good. The study provides feedback to dental schools to improve their curriculum by including quality assurance into student clinical practices. Further studies are requested to investigate the reasons behind this low level of knowledge.
Optimal design of experiments to improve the characterisation of atrazine degradation pathways in soil
Authors: Chavez Rodriguez Luciana , González‐Nicolás Ana , Ingalls Brian , Streck Thilo , Nowak Wolfgang , Xiao Sinan , Pagel Holger
Published: December 2021

Contamination of soils with pesticides and their metabolites is a global environmental threat. Deciphering the complex process chains involved in pesticide degradation is a prerequisite for finding effective solution strategies. This study applies prospective optimal design (OD) of experiments to identify laboratory sampling strategies that allow model‐based discrimination of atrazine (AT) degradation pathways. We simulated virtual AT degradation experiments with a first‐order model that reflects a simple reaction chain of complete AT degradation. We added a set of Monod‐based model variants that consider more complex AT degradation pathways. Then, we applied an extended constraint‐based parameter search algorithm that produces Monte‐Carlo ensembles of realistic model outputs, in line with published experimental data. Differences between‐model ensembles were quantified with Bayesian model analysis using an energy distance metric. AT degradation pathways following first‐order reaction chains could be clearly distinguished from those predicted with Monod‐based models. As expected, including measurements of specific bacterial guilds improved model discrimination further. However, experimental designs considering measurements of AT metabolites were most informative, highlighting that environmental fate studies should prioritise measuring metabolites for elucidating active AT degradation pathways in soils. Our results suggest that applying model‐based prospective OD will maximise knowledge gains on soil systems from laboratory and field experiments.

Highlights

Bayesian model analysis can help to distinguish the active degradation pathway of pesticides.

Information on degradation metabolites is crucial to understand pesticide fate.

Measurements of specific guilds improve the distinction of active pesticide pathways.

Prospective optimal design maximizes information gain in soil sciences.
Abnormal dynamic brain activity and functional connectivity of primary motor cortex in blepharospasm
Authors: Luo Yuhan , Guo Yaomin , Zhong Linchang , Liu Ying , Dang Chao , Wang Ying , Zeng Jinsheng , Zhang Weixi , Peng Kangqiang , Liu Gang
Published: December 2021

Background and purpose

Accumulating evidence indicates that dynamic amplitude of low‐frequency fluctuations (dALFF) or dynamic functional connectivity (dFC) can provide complementary information, distinct from static amplitude of low‐frequency fluctuations (sALFF) or static functional connectivity (sFC), in detecting brain functional abnormalities in brain diseases. We aimed to examine whether dALFF and dFC can offer valuable information for the detection of functional brain abnormalities in patients with blepharospasm.

Methods

We collected resting‐state functional magnetic resonance imaging data from 46 patients each of blepharospasm, hemifacial spasm (HFS), and healthy controls (HCs). We examined intergroup differences in sALFF and dALFF to investigate abnormal regional brain activity in patients with blepharospasm. Based on the dALFF results, we conducted seed‐based sFC and dFC analyses to identify static and dynamic connectivity changes in brain networks centered on areas showing abnormal temporal variability of local brain activity in patients with blepharospasm.

Results

Compared with HCs, patients with blepharospasm displayed different brain functional change patterns characterized by increased sALFF in the left primary motor cortex (PMC) but increased dALFF variance in the right PMC. However, differences were not found between patients with HFS and HCs. Additionally, patients with blepharospasm exhibited decreased dFC strength, but no change in sFC, between right PMC and ipsilateral cerebellum compared with HCs; these findings were replicated when patients with blepharospasm were compared to those with HFS.

Conclusions

Our findings highlight that dALFF and dFC are complementary to sALFF and sFC and can provide valuable information for detecting brain functional abnormalities in blepharospasm. Blepharospasm may be a network disorder involving the cortico‐ponto‐cerebello‐thalamo‐cortical circuit.
Crayfish connections: Linking ecology and hydrogeology in Alabama’s Black Prairie using crayfish distribution patterns
Authors: Bearden Rebecca A. , Tompkins Emily M. , Weaver Christopher R. , Huryn Alexander D.
Published: December 2021

Floodplain ecosystems host diverse surface‐water habitats (e.g., lotic, lentic, ephemeral) and groundwater features that support high levels of species diversity. Our understanding of species–habitat relationships within these complex ecosystems, however, remains incomplete, potentially hindering conservation efforts. Understanding associations between burrowing crayfish and habitat features of floodplains is particularly valuable because crayfish, through burrowing, play an important role in establishing aquatic‐terrestrial connections which enhance local biodiversity. Species of crayfish that persist in floodplains must burrow deep enough to access shallow groundwater. Consequently, burrow presence may indicate a preference for specific surface and subsurface habitat characteristics. The primary goal of our study was to evaluate specific habitat attributes as predictors of burrowing crayfish presence/absence, and our secondary goal was to evaluate species‐specific habitat associations with respect to the same environmental variables.

We evaluated burrowing crayfish presence/absence and crayfish species composition with respect to groundwater depth, flood frequency (standing surface water), soil characteristics, and tree size in the Bogue Chitto Creek catchment, Dallas County, Alabama, U.S.A. Active burrows were expected at sites with access to water (a shallow water table) and at sites with environmental variables more conducive to burrow stability (fine‐grained soils and mature trees). Species composition was predicted to vary with groundwater depth and flood frequency.

Groundwater depth was the primary driver of burrowing crayfish presence/absence in our system; active burrows were more likely to be present in areas with relatively shallow groundwater depths. Within occupied sites, differences in crayfish species composition were significantly associated with the degree of flooding during the 1‐year study period.

Species associated with a high dependence on surface waters were collected alongside species dependent on burrowing to access groundwater, suggesting that the environmental features of floodplains satisfy a diverse set of requirements. In particular, sites offering a mosaic of accessible groundwater depths and floodplain pools may provide critical habitat for diverse assemblages of burrowing crayfish species.

Our study revealed a strong association between the presence/absence of active crayfish burrows and the depth to groundwater, a result that supports using burrowing crayfish as indicators of accessible groundwater. This will be increasingly important in the context of how climate change might influence water availability and local species diversity.
Remote sensing of cytotype and its consequences for canopy damage in quaking aspen
Authors: Blonder Benjamin , Brodrick Philip G. , Walton James A. , Chadwick Katherine Dana , Breckheimer Ian K. , Marchetti Suzanne , Ray Courtenay A. , Mock Karen E.
Published: December 2021

Mapping geographic mosaics of genetic variation and their consequences via genotype x environment interactions at large extents and high resolution has been limited by the scalability of DNA sequencing. Here, we address this challenge for cytotype (chromosome copy number) variation in quaking aspen, a drought‐impacted foundation tree species. We integrate airborne imaging spectroscopy data with ground‐based DNA sequencing data and canopy damage data in 391 km2 of southwestern Colorado. We show that (1) aspen cover and cytotype can be remotely sensed at 1 m spatial resolution, (2) the geographic mosaic of cytotypes is heterogeneous and interdigitated, (3) triploids have higher leaf nitrogen, canopy water content, and carbon isotope shifts (δ13C) than diploids, and (4) canopy damage varies among cytotypes and depends on interactions with topography, canopy height, and trait variables. Triploids are at higher risk in hotter and drier conditions.
The importance of establishing genetic phase in clinical medicine
Authors: Tait Brian D.
Published: December 2021

Haplotyping or determination of genetic phase has always played a pivotal role in MHC (HLA studies) both in helping to understand inheritance patterns in diseases such as type 1 diabetes (T1D) and in ensuring better matching in transplantation scenarios such as haematopoietic stem cell transplantation (HSCT), using donors genetically related to the patient. In recent years the need to establish genetic phase in a number of clinical scenarios has become apparent. These include:

Genetic phasing for hematopoietic stem cell transplants using unrelated donors, where the HLA haplotypes are not known but where haplotype‐matched recipients fare better clinically than allele matched, but haplotype mismatched patients.

The use of checkpoint inhibitors is one of the most innovative and exciting developments in cancer treatment in years. An example is the use of the monoclonal ipilimumab to block the CTLA‐4 receptor which is known to contain polymorphic sites. Until the phase of these polymorphisms is known it will not be possible to determine how effectively this monoclonal will perform in individual patients.

The role of miRNA single strand molecules and their effect on gene expression. Thousands of non‐coding genes have been identified and have been shown to be polymorphic, as have their target genes. Genetic phasing of polymorphism both in the miRNA source genes and their targets is clearly a fertile area of research

In areas such a drug metabolism where the polymorphic family of CYP genes is responsible for the metabolism of the majority of prescription drugs, determining phase of SNPs is critical to understanding drug metabolism and efficacy.

In multigenic disease studies combinations of single nucleotide polymorphisms (SNPs) in participating genes require accurate phasing in order to fully appreciate their role in the disease process. In addition, the level of expression of genes (point 3) is also important in understanding disease processes at the functional level.

This review outlines the techniques that are currently available for approximating phase and discusses the clinical relevance of establishing genetic phase in areas of clinical medicine outlined in points 1–3.
Metabolic manipulation of the tumour immune microenvironment
Authors: Wan Mengtian , Ding Yuzhu , Li Zheng , Wang Xu , Xu Min
Published: December 2021

In the past few years, the evolution of immunotherapy has resulted in a shift in cancer treatment models. However, with immunosuppressive effects of the tumour microenvironment continues to limit advances in tumour immunotherapy. The tumour microenvironment induces metabolic reprogramming in cancer cells, which results in competition for nutrients between tumour cells and host immunocytes. Metabolic and waste products originating in tumour cells can influence the activation and effector properties of immunocytes in numerous ways and ultimately promote the survival and propagation of tumour cells. In this paper, we discuss metabolic reprogramming in tumour cells and the influence of metabolite by‐products on the immune microenvironment, providing novel insights into tumour immunotherapy.
Amelanotic nodular appearance within superficial spreading melanoma
Authors: Tas Betul , Ozen Aynur , Caglar Aysel
Published: December 2021

Usual clinical types of malignant melanoma (MM) are lentigo maligna, superficial spreading, nodular, and acral lentiginous MMs. Rarer variants of MM are amelanotic, neurotropic, desmoplastic, metastatic, invisible, pedunculatedmelanoma (PM), or nodal melanoma (NM), which constitute less than 5% of cases. Recognition and discrimination of these variants are important to avoid misdiagnosis of MM. We report a 42‐year‐old Caucasian woman presented with a superficial spreading malignant melanoma (SSM) with an amelanotic nodular center. The lesion simulated a NM or PM clinically, but its histopathology showed an SSM. This misleading appearance of SSM has not been reported previously.
Continuous positive airway pressure adherence in people with obstructive sleep apnoea
Authors: Borriboon Chestharid , Chaiard Jindarat , Tachaudomdach Chiraporn , Turale Sue
Published: December 2021

Objectives

This cross‐sectional study aimed to identify whether five factors of the health belief model were related to continuous positive airway pressure adherence in Thai people with obstructive sleep apnoea.

Background

Obstructive sleep apnoea is a disorder impacting health, social wellbeing and the economy. Continuous positive airway pressure is a gold standard of treatment; however, poor adherence to treatment is an important issue that is related to a multiplicity of psychological and behavioural factors.

Methods

The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cross‐sectional studies was used to report the study. Purposive sampling was used to recruit 94 patients newly diagnosed with sleep apnoea and using CPAP devices from a sleep clinic. Participants completed a demographic record, the Thai versions of the Functional Outcomes of Sleep Questionnaire, the Perceived Barriers Questionnaire and the Self‐Efficacy Measure for Sleep Apnea. CPAP adherence was measured by using information downloaded from the smart card of the devices. Data were analysed using descriptive statistics and logistic regression.

Results

Only 54.3% of participants adhered to CPAP treatment using standard protocols. Perceived seriousness of their condition was significantly associated with CPAP adherence, whereas perceived susceptibility, benefits, barriers and self‐efficacy were not.

Conclusions

We found a low rate of CPAP adherence among participants. The only factor related to CPAP adherence was perceived seriousness.

Relevance for the clinical practice

With a low rate of CPAP adherence, healthcare professionals, especially nurses, should encourage patients to use CPAP regularly by providing them with support and education regarding the severity of the disease if untreated and the benefits of CPAP treatment on the disease. Healthcare professionals should be aware of psychological factors impacting patients’ perception of sleep apnoea and CPAP treatment. Interventions dealing with these factors should be developed and implemented in practice.
U.S. Mexican‐Origin Adolescents’ Well‐Being in the Context of Neighborhood White Concentration
Authors: White Rebecca M. B. , Kho Carmen , Nair Rajni L.
Published: December 2021

To address injustices that privilege whiter neighborhoods, many advocate for residential integration. The developmental consequences of greater exposure to whiteness associated with integration, however, are unclear. Research examining BIPOC adolescent development within the context of intraindividual changes in neighborhood white concentration—the changes that take place if an adolescent moves to a whiter neighborhood or if their neighborhood becomes whiter—is needed. We examined trajectories of internalizing and externalizing symptoms in a longitudinal sample of U.S. Mexican adolescents (N = 749; 48.9% girls; 70.2% born in the United States). When adolescents experienced an uptick in neighborhood white concentration, they experienced a corresponding uptick in externalizing symptoms. We discuss the impacts of navigating whiter neighborhoods for U.S. Mexican adolescent well‐being.
Practitioner perspectives on best practice in non‐treatment factors that support the delivery of repetitive transcranial magnetic stimulation (rTMS) for depression
Authors: Mallon Sharon , Walker Kate , Bayley Zana , Griffiths Chris
Published: December 2021

Accessible Summary

What is known about the subject?

The practices of mental health nurses in the administration of repetitive transcranial magnetic stimulation (rTMS) treatments for depression in outpatient clinic are crucial for patient outcomes

To date, most research has focused directly on procedural aspects of treatment delivery with limited focus on the delivery of holistic care and treatment.

There is a lack of best practice guidance based on the experiences of those involved in clinical delivery to inform and improve rTMS practices

What this paper adds to existing knowledge?

This study provides unique insights into service and personalized non‐treatment factors associated with rTMS delivery that may reduce stress and improve the experiences of rTMS patients

It reviews and updates understanding of the factors that contribute to the delivery of effective rTMS.

What are the implications for practice?

The need to apply findings for the development of best practice guidance

Factors to improve practice include (a) rTMS machine demonstrations; (b) constructive, individualized, friendly, and therapeutic conversations; (c) a relaxing, comfortable, 'homely' physical environment; (d) long term supportive management; and (e) careful engagement of nursing and support staff.
Effects of dietary xylooligosaccharide prebiotic supplementation on growth, antioxidant and intestinal immune‐related genes expression in common carp Cyprinus carpio fed a high‐fat diet
Authors: Abasubong Kenneth Prudence , Li Xiang‐Fei , Adjoumani Jean‐Jacques Y. , Jiang Guang‐Zhen , Desouky Hesham E. , Liu Wen‐bin
Published: December 2021

This study investigated the effects of xylooligosaccharide (XOS) supplementation on growth, intestinal enzyme, antioxidant and immune‐related genes in common carp Cyprinus carpio fed a high‐fat diet (HFD). One hundred and ninety two fish with an initial weight of 19.61 ± 0.96 g were allocated into 24 tanks (eight fish per tank in four replicate) and were fed the control diet, HFD, HFD with 0.5%, 1%, 2% and 3% XOS supplementation. From the result, fish offered HFD with 1% XOS supplementation significantly obtained a higher body mass index and feed efficiency ratio, whereas condition factor was higher in fish fed HFD supplemented with 2% XOS but no difference was attributed to other supplemented group compared to control group. Also, fish fed HFD supplemented with 1%–2% XOS significantly improved protease, lipase, creatine kinase and sodium/potassium ATPase activities compared to other groups. Fish offered HFD were significantly lower in superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX), myeloperoxidase, acid phosphatase, lysozyme activities and immunoglobulin content, but the opposite result was found for aspartate transaminase, alanine transaminase activities, malondialdehyde, protein carbonyl and cortisol content as compared with the control. However, this effect was reversed with HFD supplemented with XOS. Also, interleukin 1β, interleukin 8, tumour necrosis factors, interferons, caspase‐3 and caspase‐9 in the intestine were all up‐regulated in the HFD group, while the reverse pattern was found in SOD, GPX, lysozyme‐C, complement 3 and mucin 5b (muc5b), than the control group. These effects were all enhanced by feeding the XOS diet, especially those fed 1%–3% supplementation. In conclusion, XOS inclusion can improve the growth, digestive enzymes, antioxidants and immune response of common carp fed HFD.
Spirited away: Race, slavery and childhood in early modern England
Authors: Chakravarty Urvashi
Published: December 2021

This essay explores the insidious but persistent desire to affix whiteness to modes of bondage and to argue for an original ‘white slavery’ located in early modern forms of traffic, indenture and forced transport. This essay aims to recover the genealogy of this belief, beginning with one of its conceptual origins: the practice of ‘spiriting’ in the seventeenth century. Reading accounts of ‘spiriting’, I firstly trace the narrative genealogies of English bondage to argue that consent emerges as a racialised rubric. Secondly, I think in particular about the representation of (very different kinds of) spirits in contemporary literary and cultural texts, includingThe Tempest, to suggest that even as they engage and anticipate the practice of ‘spiriting’, they also strategically elide their own histories of the traffic and transport of non‐white bodies. As one early modern understanding of ‘spiriting’ specifically comes to associate the practice with the capture and bondage of children, the nexus of slavery, race and children emerges as particularly fraught. If ‘white slavery’ denotes the limit case for the legibility of slavery, the photographs of ‘white’ enslaved children later circulated by white abolitionists in the nineteenth century to invoke sympathy for their cause played on the fundamental irreconcilability of ‘whiteness’ and bondage even as they re‐asserted the imbrication of slavery and sanguinity. This study attends to the trajectory of discourses of slavery written on and in the body to explore the histories of both a contemporary and an insistently current investment in frameworks of ‘white slavery’, as it attempts to discover the early modern frameworks for the legibility of race and slavery as they were co‐articulated ‘before’ the supposed ‘emergence’ of either.
A distributed deep reinforcement learning–based integrated dynamic bus control system in a connected environment
Authors: Shi Haotian , Nie Qinghui , Fu Sicheng , Wang Xin , Zhou Yang , Ran Bin
Published: December 2021

The bus bunching problem caused by the uncertain interstation travel time and passenger demand rate is a critical issue that impairs transit efficiency. Most current bus control studies focus on single or combined strategies while ignoring the bus system's real‐time environmental information. This paper proposed a distributed deep reinforcement learning (DRL)‐based generic bus dynamic control method to solve the bus bunching problem by maintaining the schedule adherence, headway regularity, and achieving the consensus in the multiagent system. This study built a bus system that utilizes the bus historical and traffic information by incorporating these characteristics into the environment. After that, a distributed DRL‐based bus dynamic control strategy is developed based on the bus system, enabling each bus to adjust its motion by any generic method utilizing the weighted downstream buses' information. Regarding the training process, a distributed proximal policy optimization algorithm is adopted for improving the converging performance. Simulated experiments are conducted to verify the control performance, robustness, feasibility, resilience, and generalization capability, which shows that our strategy can significantly reduce the schedule and headway deviations, prevent the accumulation of deviation downstream, and avoid bus bunching.
A case of a heterozygous ABCC6 mutation showing recurrent ischemic strokes and intracranial hemorrhages
Authors: Nomura Emi , Kawahara Yuko , Omote Yoshio , Takahashi Yoshiaki , Matsumoto Namiko , Ikegami Ken , Takemoto Mami , Hishikawa Nozomi , Nakano Yumiko , Yunoki Taijun , Morihara Ryuta , Uemura Masahiro , Abe Koji , Yamashita Toru
Published: December 2021

Mutations in the ATP‐binding cassette subfamily C member 6 (ABCC6) gene are responsible for pseudoxanthoma elasticum (PXE). PXE is a rare genetic metabolic disease with autosomal recessive inheritance that shows ectopic mineralization in skin, eyes, and blood vessels and causes cerebrovascular disease. There are few reports of intracranial hemorrhages in patients with the ABCC6 mutation. We report the first Japanese case with a heterozygous ABCC6 mutation displaying recurrent ischemic strokes and intracranial hemorrhages. We propose that the ABCC6 mutation may be one cause of neurovascular diseases with a family history.
Obstructive sleep apnoea in pycnodysostosis: A three‐dimensional upper airway analysis
Authors: Ferlias Nikolaos , Gjørup Hans , Doherty Mia Aagaard , Haagerup Annette , Pedersen Thomas Klit
Published: December 2021

Aim

To assess the upper airway (UA) morphology in patients with pycnodysostosis with a 3D analysis, compare results with normative data and investigate the correlation of the total volume (TV) with other UA morphology variables.

Materials and methods

Cone beam computed tomography (CBCT) images of eight Danish patients with pycnodysostosis (4 males and 4 females with a mean age of 31.8 years, SD: 16.3 years) were analyzed using Mimics® (Materialise®) and compared with a sex‐ and age‐matched control group (6 males and 8 females with a mean age of 33.6 years, SD: 18.6 years).

Results

The distance from the tip of the epiglottis (E) to the Frankfurt horizontal plane (Fp) was significantly shorter in the pycnodysostosis group (P < .042). Regarding the cross‐sectional measurements, at the ‘maximum constriction’ (P < .005), the ‘upper airway limit’ (P < .001) and the ‘lower airway limit’ (P < .035) cross‐sections were significantly smaller in the pycnodysostosis group. The volumes ‘nasopharynx’ (P < .002) and ‘total airway’ (TV) (P < .01) were also significantly smaller.

Conclusion

Patients with pycnodysostosis have a reduced total airway as well as nasopharyngeal volume compared with matched controls. Additionally, they have a reduced cross‐sectional area in the upper and lower borders of the UA, and the area of maximum constriction is also reduced. These factors might explain the high prevalence of obstructive sleep apnoea in pycnodysostosis.

Total airway is positively correlated with total length and cross‐sections at all levels including the maximum constriction area as well as the anteroposterior dimension at the upper and lower airway borders.