bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated analysis of genotype and phenotype reveals clonal evolution and cytogenetically driven disruption of myeloid cell maturation in myelodysplastic syndromes
Authors: Cutler Jevon A. , Pugsley Haley R. , Bennington Richard , Fritschle Wayne , Hartmann Luise , Zaidi Nigar , Menssen Andrew J. , Singleton Timothy P. , Xu Dongbin , Loken Michael R. , Wells Denise A. , Brodersen Lisa Eidenschink , Zehentner Barbara K.
Published: November 2021

Background

Myelodysplastic syndromes (MDS) are a heterogenous collection of clonal bone marrow diseases characterized by cytopenias, abnormal karyotypes, molecular abnormalities, and dysplasia by flow cytometry and/or morphology. The progression of MDS to severe cytopenias and/or overt leukemia is associated with the accumulation of additional cytogenetic abnormalities, suggesting clonal evolution. The impact of these accumulated abnormalities on myeloid maturation and the severity of the disease is poorly understood.

Methods

Bone marrow specimens from 16 patients with cytogenetic abnormalities were flow cytometrically sorted into three myeloid populations: progenitors, immature myeloid cells, and mature myeloid cells. Fluorescence in situ hybridization analysis was performed on each to determine the distribution of chromosomal abnormalities during myeloid maturation.

Results

Our findings revealed three distinct distributions of cytogenetic abnormalities across myeloid maturation, each of which corresponded to specific cytogenetic abnormalities. Group 1 had continuous distribution across all maturational stages and contained patients with a single cytogenetic aberration associated with good‐to‐intermediate prognosis; Group 2 had accumulation of abnormalities in immature cells and contained patients with high‐risk monosomy 7; and Group 3 had abnormalities defining the founding clone equally distributed across maturational stages while subclonal abnormalities were enriched in progenitor cells and contained patients with multiple, non‐monosomy 7, abnormalities with evidence of clonal evolution.

Conclusions

Our findings demonstrate that low‐risk abnormalities (e.g., del(20q) and trisomy 8) occurring in the founding clone display a markedly different disease etiology, with respect to myeloid maturation, than monosomy 7 or abnormalities acquired in subclones, which result in a disruption of myeloid cell maturation in MDS.
Fine‐needle aspiration biopsy of growing teratoma syndrome as a diagnostic pitfall of metastatic adenocarcinoma
Authors: Casa Daniel , Sung Simon , Mosquera Juan Miguel , Rao Rema
Published: November 2021

Growing teratoma syndrome (GTS) is a rare clinical entity that can occur in patients with a history of treatment for germ cell tumors (GCTs) and normalized serum tumor markers. Owing to the assortment of tissue types found in teratomas that may exhibit atypical features, distinguishing GTS from metastatic cancer in extragonadal masses can be challenging. Fine‐needle aspiration biopsy (FNAB) can be useful for the rapid diagnosis of metastatic masses and has been effective in distinguishing GCTs from one another. However, discrepancies in cytologic and histologic diagnoses have been reported in the evaluation of GCTs by FNAB. The potential incomplete sampling of metastatic teratomas in GTS by FNAB along with features of cellular atypia commonly found in teratomas can lead to a misdiagnosis of metastatic carcinoma and drastically affect treatment. Correlation of cytologic, histologic, clinical, and radiographic findings are essential in evaluating metastatic masses in patients with a history of GCT. We report a case of a 46‐year‐old man with GTS originally diagnosed on FNAB as metastatic adenocarcinoma compatible with a colorectal primary tumor.
Cross‐talk between EGFR and BMP signals regulates chondrocyte maturation during endochondral ossification
Authors: Lees‐Shepard John B. , Flint Kaitlyn , Fisher Melanie , Omi Minoru , Richard Kelsey , Antony Michelle , Chen Po Jung , Yadav Sumit , Threadgill David , Maihle Nita J. , Dealy Caroline N.
Published: November 2021

Background

Progressive maturation of growth plate chondrocytes drives long bone growth during endochondral ossification. Signals from the epidermal growth factor receptor (EGFR), and from bone morphogenetic protein‐2 (BMP2), are required for normal chondrocyte maturation. Here, we investigated cross‐talk between EGFR and BMP2 signals in developing and adult growth plates.

Results

Using in vivo mouse models of conditional cartilage‐targeted EGFR or BMP2 loss, we show that canonical BMP signal activation is increased in the hypertrophic chondrocytes of EGFR‐deficient growth plates; whereas EGFR signal activation is increased in the reserve, prehypertrophic and hypertrophic chondrocytes of BMP2‐deficient growth plates. EGFR‐deficient chondrocytes displayed increased BMP signal activation in vitro, accompanied by increased expression of IHH, COL10A1, and RUNX2. Hypertrophic differentiation and BMP signal activation were suppressed in normal chondrocyte cultures treated with the EGFR ligand betacellulin, effects that were partially blocked by simultaneous treatment with BMP2 or a chemical EGFR antagonist.

Conclusions

Cross‐talk between EGFR and BMP2 signals occurs during chondrocyte maturation. In the reserve and prehypertrophic zones, BMP2 signals unilaterally suppress EGFR activity; in the hypertrophic zone, EGFR and BMP2 signals repress each other. This cross‐talk may play a role in regulating chondrocyte maturation in developing and adult growth plates.
Implicit approach‐avoidance tendencies toward food and body stimuli absent in individuals with anorexia nervosa, bulimia nervosa, and healthy controls
Authors: Kollei Ines , Leins Judith , Rinck Mike , Waldorf Manual , Kuhn Melanie , Rauh Elisabeth , Steins‐Loeber Sabine
Published: November 2021

Objective

Body and food‐related information are thought to activate cognitive biases and contribute to the maintenance of eating disorders (ED). Approach‐avoidance biases may play an important role in the maintenance of dietary restriction and excessive food intake. Therefore, the present study aimed to examine approach‐avoidance biases toward food and body stimuli in individuals with anorexia nervosa (AN), bulimia nervosa (BN), and healthy controls (HC).

Methods

The study included 42 individuals with AN, 24 individuals with BN, and 38 HCs. We used two implicit Approach‐Avoidance Tasks (AAT) to assess approach‐avoidance biases: participants completed a Food‐AAT (high‐calorie vs. low‐calorie food) and a Body‐AAT (thin vs. normal weight bodies). Additionally, explicit ratings of food and body stimuli were assessed.

Results

There were no significant Group × Stimulus × Direction interactions in the implicit Food‐AAT or implicit Body‐AAT. In explicit ratings, individuals with AN and BN reported less urge to eat and more regret if they ate high‐calorie and low‐calorie food; individuals with AN and BN rated normal weight bodies as less normal weight, less attractive and less desirable than HCs. There were no group differences in explicit ratings of the thin body.

Discussion

We did not find evidence for biased approach‐avoidance tendencies toward food or body stimuli in individuals with AN or BN. Future studies are necessary to understand conflicting findings regarding approach‐avoidance biases toward food and body stimuli in individuals with ED.
A systematic scoping review of research on COVID‐19 impacts on eating disorders: A critical appraisal of the evidence and recommendations for the field
Authors: Linardon Jake , Messer Mariel , Rodgers Rachel F. , Fuller‐Tyszkiewicz Matthew
Published: November 2021

Objective

Research investigating the effects of COVID‐19 on eating disorders is growing rapidly. A comprehensive evaluation of this literature is needed to identify key findings and evidence gaps to better inform policy decisions related to the management of eating disorders during and after this crisis. We conducted a systematic scoping review synthesizing and appraising this literature.

Method

Empirical research on COVID‐19 impacts on eating disorder severity, prevalence, and demand for treatment was searched. No sample restrictions were applied. Findings (n = 70 studies) were synthesized across six themes: (a) suspected eating disorder cases during COVID‐19; (b) perceived pandemic impacts on symptoms; (c) symptom severity pre versus during the pandemic; (d) pandemic‐related correlates of symptom severity; (e) impacts on carers/parents; and (f) treatment experiences during COVID‐19.

Results

Pandemic impacts on rates of probable eating disorders, symptom deterioration, and general mental health varied substantially. Symptom escalation and mental health worsening during―and due to―the pandemic were commonly reported, and those most susceptible included confirmed eating disorder cases, at‐risk populations (young women, athletes, parent/carers), and individuals highly anxious or fearful of COVID‐19. Evidence emerged for increased demand for specialist eating disorder services during the pandemic. The forced transition to online treatment was challenging for many, yet telehealth alternatives seemed feasible and effective.

Discussion

Evidence for COVID‐19 effects is mostly limited to participant self‐report or retrospective recall, cross‐sectional and descriptive studies, and samples of convenience. Several novel pathways for future research that aim to better understand, monitor, and support those negatively affected by the pandemic are formulated.
Spatial patterns of phylogenetic diversity and endemism in the Western Ghats, India: A case study using ancient predatory arthropods
Authors: Bharti D. K. , Edgecombe Gregory D. , Karanth K. Praveen , Joshi Jahnavi
Published: November 2021

The Western Ghats (WG) mountain chain in peninsular India is a global biodiversity hotspot, one in which patterns of phylogenetic diversity and endemism remain to be documented across taxa. We used a well‐characterized community of ancient soil predatory arthropods from the WG to understand diversity gradients, identify hotspots of endemism and conservation importance, and highlight poorly studied areas with unique biodiversity. We compiled an occurrence dataset for 19 species of scolopendrid centipedes, which was used to predict areas of habitat suitability using bioclimatic and geomorphological variables in Maxent. We used predicted distributions and a time‐calibrated species phylogeny to calculate taxonomic and phylogenetic indices of diversity, endemism, and turnover. We observed a decreasing latitudinal gradient in taxonomic and phylogenetic diversity in the WG, which supports expectations from the latitudinal diversity gradient. The southern WG had the highest phylogenetic diversity and endemism, and was represented by lineages with long branch lengths as observed from relative phylogenetic diversity/endemism. These results indicate the persistence of lineages over evolutionary time in the southern WG and are consistent with predictions from the southern WG refuge hypothesis. The northern WG, despite having low phylogenetic diversity, had high values of phylogenetic endemism represented by distinct lineages as inferred from relative phylogenetic endemism. The distinct endemic lineages in this subregion might be adapted to life in lateritic plateaus characterized by poor soil conditions and high seasonality. Sites across an important biogeographic break, the Palghat Gap, broadly grouped separately in comparisons of species turnover along the WG. The southern WG and Nilgiris, adjoining the Palghat Gap, harbor unique centipede communities, where the causal role of climate or dispersal barriers in shaping diversity remains to be investigated. Our results highlight the need to use phylogeny and distribution data while assessing diversity and endemism patterns in the WG.
Great tits do not compensate over time for a radio‐tag‐induced reduction in escape‐flight performance
Authors: Tomotani Barbara M. , Muijres Florian T. , Johnston Bronwyn , van der Jeugd Henk P. , Naguib Marc
Published: November 2021

The use of biologging and tracking devices is widespread in avian behavioral and ecological studies. Carrying these devices rarely has major behavioral or fitness effects in the wild, yet it may still impact animals in more subtle ways, such as during high power demanding escape maneuvers. Here, we tested whether or not great tits (Parus major) carrying a backpack radio‐tag changed their body mass or flight behavior over time to compensate for the detrimental effect of carrying a tag. We tested 18 great tits, randomly assigned to a control (untagged) or one of two different types of a radio‐tag as used in previous studies in the wild (0.9 g or 1.2 g; ~5% or ~6–7% of body mass, respectively), and determined their upward escape‐flight performance 1, 7, 14, and 28 days after tagging. In between experiments, birds were housed in large free‐flight aviaries. For each escape‐flight, we used high‐speed 3D videography to determine flight paths, escape‐flight speed, wingbeat frequency, and actuator disk loading (ratio between the bird weight and aerodynamic thrust production capacity). Tagged birds flew upward with lower escape‐flight speeds, caused by an increased actuator disk loading. During the 28‐day period, all groups slightly increased their body mass and their in‐flight wingbeat frequency. In addition, during this period, all groups of birds increased their escape‐flight speed, but tagged birds did so at a lower rate than untagged birds. This suggests that birds may increase their escape‐flight performance through skill learning; however, tagged birds still remained slower than controls. Our findings suggest that tagging a songbird can have a prolonged effect on the performance of rapid flight maneuvers. Given the absence of tag effects on reproduction and survival in most songbird radio‐tagging studies, tagged birds in the wild might adjust their risk‐taking behavior to avoid performing rapid flight maneuvers.
Mass‐ratio and complementarity effects simultaneously drive aboveground biomass in temperate Quercus forests through stand structure
Authors: Gao Wen‐Qiang , Lei Xiang‐Dong , Gao Dong‐Li , Li Yu‐Tang
Published: November 2021

Forests play a key role in regulating the global carbon cycle, a substantial portion of which is stored in aboveground biomass (AGB). It is well understood that biodiversity can increase the biomass through complementarity and mass‐ratio effects, and the contribution of environmental factors and stand structure attributes to AGB was also observed. However, the relative influence of these factors in determining the AGB of Quercus forests remains poorly understood. Using a large dataset retrieved from 523 permanent forest inventory plots across Northeast China, we examined the effects of integrated multiple tree species diversity components (i.e., species richness, functional, and phylogenetic diversity), functional traits composition, environmental factors (climate and soil), stand age, and structure attributes (stand density, tree size diversity) on AGB based on structural equation models. We found that species richness and phylogenetic diversity both were not correlated with AGB. However, functional diversity positively affected AGB via an indirect effect in line with the complementarity effect. Moreover, the community‐weighted mean of specific leaf area and height increased AGB directly and indirectly, respectively; demonstrating the mass‐ratio effect. Furthermore, stand age, density, and tree size diversity were more important modulators of AGB than biodiversity. Our study highlights that biodiversity–AGB interaction is dependent on the regulation of stand structure that can be even more important for maintaining high biomass than biodiversity in temperate Quercus forests.
Intermediate disturbances are a key driver of long‐term tree demography across old‐growth temperate forests
Authors: Nagel Thomas A. , Firm Dejan , Rozman Andrej
Published: November 2021

Disentangling the relative influence of background versus disturbance related mortality on forest demography is crucial for understanding long‐term dynamics and predicting the influence of global change on forests. Quantifying the rates and drivers of tree demography requires direct observations of tree populations over multiple decades, yet such studies are rare in old‐growth forest, particularly in the temperate zone of Europe. We use multi‐decade (1980–2020) monitoring of permanent plots, including observations of mode of mortality and disturbance events, to quantify rates and drivers of tree demography across a network of old‐growth remnants in temperate mountain forests of Slovenia. Annual rates of mortality and recruitment varied markedly among sites and over time; census intervals that captured intermediate severity canopy disturbances caused subtle peaks in annual mortality (e.g., >2%/year), while rates of background mortality in non‐disturbed intervals averaged about 1%/year. Roughly half of the trees died from modes of mortality associated with disturbance (i.e., uprooting or snapped‐alive). Results of a Bayesian multilevel model indicate that beech (Fagus sylvatica) had a higher likelihood of disturbance related mortality compared to fir (Abies alba), which mainly died standing, and there was a notable increase in the odds of disturbance mortality with increasing diameter for all species. Annual recruitment rates were consistently low at sites (<0.5%) that lacked evidence of disturbance, but often exceeded 3% on sites with higher levels of past canopy mortality. Recruitment was dominated by beech on sites with more diffuse background mortality, while the less shade tolerant maple (Acer pseudoplatanus) recruited following known disturbance events. Our study highlights the important role of stand‐scale, partial canopy disturbance for long‐term forest demography. These results suggest that subtle climate‐driven changes in the regime of intermediate severity disturbances could have an important influence on future forest dynamics and warrant attention.
Transpiration patterns and water use strategies of beech and oak trees along a hillslope
Authors: Fabiani Ginevra , Schoppach Remy , Penna Daniele , Klaus Julian
Published: November 2021

The role of landscape topography in mediating subsurface water availability and ultimately tree transpiration is still poorly understood. To assess how hillslope position affects tree water use, we coupled sap velocity with xylem isotope measurements in a temperate beech‐oak forest along a hillslope transect in Luxembourg. We generally observed greater sap velocities at the upslope locations in trees from average‐sized trees, suggesting the presence of more suited growing conditions. We found a lower difference in sap velocity among hillslope positions for larger trees, likely due to the exploitation of deeper and more persistent water sources and the larger canopy light interception. Beech trees exploited a shallower and seasonally less persistent water source than oak trees, due to the shallower root system than oak trees. The different water exploitation strategy could also explain the stronger stomatal sensitivity of beech to vapour pressure deficit compared to oak trees. Xylem isotopic composition was seasonally variable at all locations, mainly reflecting the contribution of variable soil water sources and suggesting that groundwater did not contribute, or only marginally contributed, to tree transpiration. Overall, our results suggest that trees along the hillslope mainly rely on water stored in the unsaturated zone and that seasonally shallow groundwater table may not necessarily subsidize water uptake for species that do not tolerate anoxic conditions. Contrary to previous studies, at our site, we did not find higher sap velocity downslope as the subsurface hillslope structure promotes vertical water flux over lateral redistribution in the vadose zone.
Nanoporous Polymer Reflectors for Organic Solar Cells
Authors: Yu Shudong , Guo Bing , Johnsen Siegbert , Wiegand Gabriele , Lemmer Uli , Guo Xia , Zhang Maojie , Li Yongfang , Sprau Christian , Hölscher Hendrik , Colsmann Alexander , Gomard Guillaume
Published: November 2021

Due to their high transparency, electrodes fabricated from conductive polymers are often implemented in semitransparent organic solar cells. Opaque solar cells usually employ metal back electrodes with high reflectivity for best photon confinement in the light‐harvesting layer. Herein, a bilayer back electrode comprising conductive polymers and nanofoamed poly(methyl methacrylate) (PMMA) is investigated, the latter of which creates diffuse reflection of the incoming light. By tuning the thickness of the nanofoamed PMMA layer, absorption and transmission of the solar cells can be tailored from opaque to vastly transparent. Due to its diffusive character, this versatile electrode enhances the light absorption in the wavelength regimes with lower absorption coefficient. The solar cells are particularly suited for deployment in frosted window applications.
Research on electric vehicle‐supercapacitor hybrid system participates in the application of tracking PV project output
Authors: Zhao Song , Zhou Lei , Zhang Qian , Dang Shaojia , Yu Haicun , Zhang Guobin , Guo Ruijun , Zhao Wei
Published: November 2021

With the increase in new energy power generation and the continuous augment in the penetration rate of electric vehicles, it is of crucial importance to use electric vehicles as energy storage devices to promote the consumption of new energy. Aiming at the uncertainty of electric vehicles, this paper proposes a method based on multiobjective optimization for electric vehicle‐supercapacitor hybrid energy storage system to track PV project output. The hybrid system consists of electric vehicles and supercapacitor. Electric vehicles and supercapacitors supplement the deviation of PV actual power and predicted power by charging and discharging. The electric vehicle is regarded as a nonspecific way to label a piece of equipment that can store energy. First and foremost, on the basis of traditional method of predicting PV output, a PSO‐BP prediction method based on PCA is proposed to improve the accuracy of PV output prediction. Secondarily, according to the different characteristics of electric vehicles and supercapacitors, the empirical mode decomposition (EMD) method is used to decompose the deviation that the hybrid energy storage system needs to bear with the purpose of initially allocating the energy. Furthermore, a multiobjective optimization model is established for the precise energy distribution of the hybrid energy storage system, and the NSGA‐III algorithm is used to solve it. Ultimately, the data of a domestic PV power station are used for simulation. After optimized control, the result shows that the standard deviation of the system output is reduced from 1967 to 75.77. The research in this article provides a theoretical basis for the application of electric vehicle virtual energy storage technology in the field of auxiliary new energy grid connection.
Provenance of Baker River sediments (Chile, 48°S): Implications for the identification of flood deposits in fjord sediments
Authors: Liu Dawei , Bertrand Sebastien , Vandekerkhove Elke , Renson Virginie
Published: November 2021

Floods are among the most destructive natural hazards on Earth. In paleohydrology, sediments are generally considered as one of the best archives to extend flood records to pre‐historical timescales. Doing so requires being able to identify flood deposits from sediment archives and decipher between flood types. The latter is particularly important in glacierized regions, where meteorological floods frequently co‐occur with glacial lake outburst floods (GLOFs). In Patagonia, results from a recent study suggest that GLOFs are recorded in downstream fjord sediments as fine‐grained and organic‐poor layers, representing the high amount of glacier rock flour transported during lake outbursts, whereas meteorological floods are represented by coarser and more organic deposits. However, not all fine‐grained organic‐poor deposits could be associated with historical GLOFs. Here, we reconstruct the provenance of these Baker River flood deposits using 87Sr/86Sr and εNd, taking advantage of the clear lithological differences that exist between both sides of the watershed. Our results show that both 87Sr/86Sr and εNd are suited to reconstruct sediment provenance in the Baker River watershed but that εNd is the most effective and the least affected by grain‐size variations. Our provenance results confirm that the 21st‐century fine‐grained and organic‐poor deposits represent GLOFs and that the largest winter meteorological flood on record has a distinct coarse and organic‐rich signature. However, our results show that rain‐on‐snow events that occur in summer, and therefore primarily affect the western glacierized part of the watershed, have the same fine‐grained organic‐poor signature as GLOFs. Therefore, this study shows that the sedimentary signature of rain‐on‐snow floods in partially glacierized watersheds depends on the season during which they occur. We anticipate that our findings will contribute to a better interpretation of flood records from partially glacierized watersheds.
From statistical‐ to machine learning‐based network traffic prediction
Authors: Lohrasbinasab Iraj , Shahraki Amin , Taherkordi Amir , Delia Jurcut Anca
Published: November 2021

Nowadays, due to the exponential and continuous expansion of new paradigms such as Internet of Things (IoT), Internet of Vehicles (IoV) and 6G, the world is witnessing a tremendous and sharp increase of network traffic. In such large‐scale, heterogeneous, and complex networks, the volume of transferred data, asbig data, is considered a challenge causing different networking inefficiencies. To overcome these challenges, various techniques are introduced to monitor the performance of networks, called Network Traffic Monitoring and Analysis (NTMA). Network Traffic Prediction (NTP) is a significant subfield of NTMA which is mainly focused on predicting the future of network load and its behavior. NTP techniques can generally be realized in two ways, that is, statistical‐ and Machine Learning (ML)‐based. In this paper, we provide a study on existing NTP techniques through reviewing, investigating, and classifying the recent relevant works conducted in this field. Additionally, we discuss the challenges and future directions of NTP showing that how ML and statistical techniques can be used to solve challenges of NTP.
Upfront progression under pembrolizumab followed by a complete response after encorafenib and cetuximab treatment in BRAF V600E‐mutated and microsatellite unstable metastatic colorectal cancer patient: A case report
Authors: Gallois Claire , Taieb Julien , Sabouret Annabelle , Broudin Chloé , Karoui Mehdi , Garinet Simon , Zaanan Aziz
Published: November 2021

Two new treatments have recently become standard care for patients with metastatic colorectal cancer (mCRC): encorafenib (BRAF inhibitor) associated with cetuximab (anti‐EGFR) in the second or third line of chemotherapy for BRAF V600E tumors, and pembrolizumab (an anti PD‐1 immune checkpoint inhibitor) for tumors harboring microsatellite instability (MSI)‐high and/or deficient mismatch repair (dMMR). Furthermore, 30% of BRAF V600E mutated mCRC are MSI/dMMR through a sporadic hypermethylation of the promoter of hMLH1. We report here, for the first time, the case of a patient with BRAF V600E, PIK3CA, and SMAD4 mutated and dMMR/MSI mCRC, in whom we observed an atypical response pattern under the sequence of pembrolizumab followed by the doublet encorafenib and cetuximab treatment. The patient was progressive after a single cycle of pembrolizumab followed by a rapid complete response after only 2 months of treatment with encorafenib and cetuximab, discovered during R0 cytoreduction surgery for peritoneal carcinomatosis.
Dystrophin deficiency affects human astrocyte properties and response to damage
Authors: Lange Jenny , Gillham Olivia , Alkharji Reem , Eaton Simon , Ferrari Giulia , Madej Monika , Flower Michael , Tedesco Francesco Saverio , Muntoni Francesco , Ferretti Patrizia
Published: November 2021

In addition to progressive muscular degeneration due to dystrophin mutations, 1/3 of Duchenne muscular dystrophy (DMD) patients present cognitive deficits. However, there is currently an incomplete understanding about the function of the multiple dystrophin isoforms in human brains. Here, we tested the hypothesis that dystrophin deficiency affects glial function in DMD and could therefore contribute to neural impairment. We investigated human dystrophin isoform expression with development and differentiation and response to damage in human astrocytes from control and induced pluripotent stem cells from DMD patients. In control cells, short dystrophin isoforms were up‐regulated with development and their expression levels changed differently upon neuronal and astrocytic differentiation, as well as in 2‐dimensional versus 3‐dimensional astrocyte cultures. All DMD‐astrocytes tested displayed altered morphology, proliferative activity and AQP4 expression. Furthermore, they did not show any morphological change in response to inflammatory stimuli and their number was significantly lower as compared to stimulated healthy astrocytes. Finally, DMD‐astrocytes appeared to be more sensitive than controls to oxidative damage as shown by their increased cell death. Behavioral and metabolic defects in DMD‐astrocytes were consistent with gene pathway dysregulation shared by lines with different mutations as demonstrated by bulk RNA‐seq analysis. Together, our DMD model provides evidence for altered astrocyte function in DMD suggesting that defective astrocyte responses may contribute to neural impairment and might provide additional potential therapeutic targets.
Isolating the sources of pipeline‐variability in group‐level task‐fMRI results
Authors: Bowring Alexander , Nichols Thomas E. , Maumet Camille
Published: November 2021

Task‐fMRI researchers have great flexibility as to how they analyze their data, with multiple methodological options to choose from at each stage of the analysis workflow. While the development of tools and techniques has broadened our horizons for comprehending the complexities of the human brain, a growing body of research has highlighted the pitfalls of such methodological plurality. In a recent study, we found that the choice of software package used to run the analysis pipeline can have a considerable impact on the final group‐level results of a task‐fMRI investigation (Bowring et al., 2019, BMN). Here we revisit our work, seeking to identify the stages of the pipeline where the greatest variation between analysis software is induced. We carry out further analyses on the three datasets evaluated in BMN, employing a common processing strategy across parts of the analysis workflow and then utilizing procedures from three software packages (AFNI, FSL, and SPM) across the remaining steps of the pipeline. We use quantitative methods to compare the statistical maps and isolate the main stages of the workflow where the three packages diverge. Across all datasets, we find that variation between the packages' results is largely attributable to a handful of individual analysis stages, and that these sources of variability were heterogeneous across the datasets (e.g., choice of first‐level signal model had the most impact for the balloon analog risk task dataset, while first‐level noise model and group‐level model were more influential for the false belief and antisaccade task datasets, respectively). We also observe areas of the analysis workflow where changing the software package causes minimal differences in the final results, finding that the group‐level results were largely unaffected by which software package was used to model the low‐frequency fMRI drifts.
Flipping the script: The effects of opioid prescription monitoring on specialty‐specific provider behavior
Authors: Ellyson Alice M. , Grooms Jevay , Ortega Alberto
Published: November 2021

Mandatory access Prescription Drug Monitoring Programs (MA‐PDMPs) aim to curb the epidemic at a common point of initiation of use, the prescription. However, there is recent concern about whether opioid policies have been too restrictive and reduced appropriate access to patients with the most need for opioid pharmaceuticals. We assess MA‐PDMP's effect on specialty‐specific opioid prescribing behavior of Medicare providers. Our findings suggest that requiring providers to query a PDMP differentially affects opioid prescribing across provider specialties. We find a three to four percent decrease in prescribing for Primary Care and Internal Medicine providers. This result is driven by healthcare providers at the lower end of the prescribing distribution. There is also suggestive evidence of an increase in opioid use disorder treatment drugs prescribed by these same providers. We also find no evidence for the hypothesis that MA‐PDMPs restrict prescribing by providers who treat patients with potentially high levels of pain, few drug substitutes, or urgency for pain treatment (e.g., Oncology/Palliative care). This result is not dependent on whether a state provides exemptions for these providers. Our results indicate that MA‐PDMPs may help close provider‐patient informational gaps while retaining a provider's ability to supply these drugs to patients with a need for opioids.
The pathophysiology of Wilson’s disease visualized: A human 64Cu PET study
Authors: Sandahl Thomas Damgaard , Gormsen Lars C. , Kjærgaard Kristoffer , Vendelbo Mikkel Holm , Munk Ditte Emilie , Munk Ole Lajord , Bender Dirk , Keiding Susanne , Vase Karina H. , Frisch Kim , Vilstrup Hendrik , Ott Peter
Published: November 2021

Background and Aims

Wilson’s disease (WD) is a genetic disease with systemic accumulation of copper that leads to symptoms from the liver and brain. However, the underlying defects in copper transport kinetics are only partly understood. We sought to quantify hepatic copper turnover in patients with WD compared with heterozygote and control subjects using PET with copper‐64 (64Cu) as a tracer. Furthermore, we assessed the diagnostic potential of the method.

Approach and Results

Nine patients with WD, 5 healthy heterozygote subjects, and 8 healthy controls were injected with an i.v. bolus of 64Cu followed by a 90‐min dynamic PET scan of the liver and static whole‐body PET/CT scans after 1.5, 6, and 20 h. Blood 64Cu concentrations were measured in parallel. Hepatic copper retention and redistribution were evaluated by standardized uptake values (SUVs). At 90 min, hepatic SUVs were similar in the three groups. In contrast, at 20 h postinjection, the SUV in WD patients (mean ± SEM, 31 ± 4) was higher than in heterozygotes (24 ± 3) and controls (21 ± 4; p < 0.001). An SUV‐ratio of hepatic 64Cu concentration at 20 and 1.5 h completely discriminated between WD patients and control groups (p < 0.0001; ANOVA). By Patlak analysis of the initial 90 min of the PET scan, the steady‐state hepatic clearance of 64Cu was estimated to be slightly lower in patients with WD than in controls (p = 0.04).

Conclusions

64Cu PET imaging enables visualization and quantification of the hepatic copper retention characteristic for WD patients. This method represents a valuable tool for future studies of WD pathophysiology, and may assist the development of therapies, and accurate diagnosis.
Factors associated with knowledge and practice of optimal breastfeeding among mothers in Dubai
Authors: Omar Ameesha Aboobaker , Abdul Hakeem Sidrah , Kahloon Huda Bashir , Alhashmi Asma , AlSaadi Reem Abdulla , Carrick Frederick Robert , Abdulrahman Mahera
Published: November 2021

Although breastfeeding has been the primary source of nutrition for infants, many women do not choose to practise breastfeeding due to lack of knowledge, inability to do so or personal choices. This study aimed at determining the breastfeeding practices and examining the sociodemographic factors associated with optimal breastfeeding among mothers attending child welfare clinic at Dubai Health Authority. A structured questionnaire was designed consisting of sociodemographic data, knowledge, attitude and practice towards breastfeeding. The main reasons for not breastfeeding the baby within 30 min after delivery were having had a caesarean section, followed by separation of the baby from the mother. We found better practice among homemakers, non‐United Arab Emirates (UAE) and married women, those with less monthly income, and those with standard delivery. There is a need for better education on optimal breastfeeding, especially in UAE national pregnant women, who have had caesarean sections, or having babies admitted in the intensive care unit.
A systematic review of the health of internal migrants in Bangladesh
Authors: Akhter Sadika , Mahmood Nabila , Rutherford Shannon
Published: November 2021

Internal migrants are more disadvantaged than non‐migrants in terms of their health. However, the extent of this difference is unclear. Following the PRISMA guideline, we conducted a systematic review to explore the existing evidence on the health of internal migrants of Bangladesh. We searched Pubmed, Web of Science and Google Scholar to identify peer‐reviewed literature on health related issues of the internal migrant population and identified 29 papers for inclusion. Included studies reported health issues or risk factors relating to water, sanitisation and hygiene access and practice, risky sexual behaviour and sexually transmitted infection, mental health status, occupational health status, general healthcare availability, healthcare service utilisation and healthcare seeking behaviour. This systematic review reveals that research on health issues of internal migrants of Bangladesh is limited for common communicable and noncommunicable diseases like waterborne and skin disease, tuberculosis, hypertension and diabetes. Further, despite that many of these migrants are labourers, occupational health related issues like work place accidents, musculoskeletal disorders are insufficiently explored. Barriers to healthcare accessibility in this population are poor socioeconomic status, illiteracy and low general health knowledge. For improved development and implementation of health policies targeting this important population, future studies should focus on understudied diseases and disease prevalence and be designed to elicit from the perspectives of internal migrants, their key health needs around risk factors and health services accessibility.
Characterization of O‐mannosylated proteins profiling in bacillus Calmette–Guérin via gel‐based and gel‐free approaches
Authors: Zheng Jianhua , Liu Liguo , Wei Candong , Liu Bo , Jin Qi
Published: November 2021

Posttranslational modifications (PTMs) could influence many aspects of protein behavior and function in organisms. Protein glycosylation is one of the major PTMs observed in bacteria, which is crucial for functional regulations of many prokaryotic and eukaryotic organisms. Mycobacterium bovis bacillus Calmette–Guérin (BCG) vaccine has been recognized as an indispensable tool in the global fight against tuberculosis (TB) worldwide over several decades. Nevertheless, analysis of glycoprotein profiles of BCG has not been clearly investigated. In this study, we performed O‐mannosylated protein analysis in BCG bacteria using gel‐based and gel‐free approaches. In total, 1,670 hexosylated peptides derived from 754 mannosylated proteins were identified. Furthermore, 20 novel protein products supported by 78 unique peptides not annotated in the BCG database were detected. Additionally, the translational start sites of 384 proteins were confirmed, and 78 proteins were validated through the extension of translational start sites based on N‐terminus‐derived peptides. The bioinformatic analysis of the O‐mannosylated proteins was performed and the expression profiles of four randomly selected proteins were validated through Western blotting. A number of proteins involved in metabolic pathways, including the tricarboxylic acid cycle, glycolysis, oxidative phosphorylation, and two‐component system, are discussed. Taken together, these results offer the first O‐mannosylated protein analysis of a member of mycobacteria reported to date by using complementary gel‐based and gel‐free approaches. Some of the proteins identified in this study have important roles involved in metabolic pathways, which could provide insight into the immune molecular mechanisms of this recognized vaccine strain.
Extracellular matrix‐based combination scaffold for guided regeneration of large‐area full‐thickness rabbit burn wounds upon a single application
Authors: Ramakrishnan Rashmi , Harikrishnan Vijayakumar Sreelatha , Anil Arya , Arumugham Sabareeswaran , Krishnan Lissy Kalliyana
Published: November 2021

Regeneration of large acute and chronic wounds is a concern worldwide. The present study evaluates wound healing competence of a completely human‐origin, extracellular matrix (ECM)‐based skin substitute/graft. It comprises cell‐less amniotic membrane (AM), clinical‐grade fibrin (FIB), and hyaluronic acid (HA) termed as AMFIBHA. The use of large‐area third‐degree rabbit burn wounds evaluated the product efficiency. The AMFIBHA induces hemostasis and permits suture‐less positioning on the wound bed. In wet wounds, the AMFIBHA degrades and release biologically active molecules and guide cell migration, proliferation, and regeneration. The study demonstrated the effectiveness of this wound care product in terms of epithelial‐dermal regeneration with angiogenesis. The study assessed injury‐associated inflammation and different wound healing markers after 28 days of experiment and compared with both positive and negative controls‐treated wounds. The regeneration of mature epidermis and dermis with rete pegs and hair follicle‐like structure was evident upon a single application. The active involvement of host cells resulted in supple tissue formation. The ECM organization of AMFIBHA‐treated tissue resulted in re‐gain of mechanical properties comparable to native skin after 56 days. These guided regenerative outcomes reveal a promising translational value of the novel AMFIBHA skin substitute as an off‐the‐shelf product for clinical use.
Establishment of a new protein C detection system based on chromogenic substrate assay and its clinical diagnostic value for deep vein thrombosis
Authors: Lu Wenfei , Ge Anshan , Zhao Jinxia , Rong Hui , Zhu Chao , Lun Limin
Published: November 2021

Background

Deficiency of protein C (PC) affects the balance between blood coagulation and fibrinolysis in the human body. Chromogenic‐based assay is recommended as the preferred screening method for detecting PC deficiency. We established a PC detection system based on the chromogenic substrate assay.

Methods

First, a kit for the determination of PC activity in plasma was elaborately developed and its reaction parameters on XL‐3200c were explored. Then, we evaluated its performance and collected specimens to compare the test results obtained with those of the Siemens detection system. Finally, the clinical diagnostic efficacy of this detection system for deep vein thrombosis (DVT) was assessed.

Results

Optimum conditions for PC detection were 0.25–0.1 U/ml protein C activator Protac® and 2.5–1 mM Pefachrome®PCa5297. The composition and concentration ranges of buffer substances and stabilizers in the kit were also explored. Satisfactory results were observed in performance evaluation. The test results of the newly built detection system were highly correlated with those of the Siemens detection system (R2 = 0.9771 in the control group and R2 = 0.9776 in the DVT group), and Bland‐Altman plots also showed high consistency between the two detection systems. In addition, the area under the curve (AUC) of the newly built PC detection system for DVT was 0.888, indicating this system could effectively improve the diagnostic sensitivity and specificity for DVT.

Conclusion

In this study, a sensitive, wide linear range and reliable PC activity detection system were established.
A longitudinal examination of predictors of nonsuicidal self‐injury disclosures among university students
Authors: Simone Ariana C. , Hamza Chloe A.
Published: November 2021

Objective

There is a paucity of longitudinal research on predictors of disclosures of nonsuicidal self‐injury (NSSI) among emerging adults. However, understanding the factors that facilitate disclosure is critical, as disclosure may serve as a first step in accessing care. To address this gap, the present study examined predictors of prospective NSSI disclosures in a postsecondary student sample.

Methods

A total of 475 university students with a history of NSSI (Mage = 17.96; 74.9% women) reported on several potential predictors of NSSI disclosure, and their disclosure history at baseline and 4‐ and 8‐month follow‐ups.

Results

It was found that 22% of students reported disclosing NSSI during the first year of university; students who had previously disclosed, and who reported greater NSSI severity, were more likely to disclose over time.

Conclusion

Results of the present study suggest that disclosures often occur in the postsecondary context, and students who disclose NSSI may engage in more severe NSSI behaviours.
Development and assessment of an online virtual orthodontic curriculum
Authors: Liu Luwei , Yuan Siyang , Zhang Weibing , Wang Zhendong , Zhao Chunyang , Pan Yongchu , Yan Bin , Wang Lin
Published: November 2021

Introduction

Due to break space and time limits, an entirely new online curriculum of orthodontic education with online evaluation system has been structured and developed in the dental school, based on virtual reality simulation.

Curriculum

At Nanjing Medical University, a new online orthodontic curriculum with programmatic assessment process was constructed and implemented based on competency‐based education (CBE). It was consisted of the online orthodontic theoretical lectures based on the National Open Online Course “Orthodontics,” the online journal club via the online “flipped classroom,” and the online orthodontic pre‐clinical training via the virtual learning network platform. In order to evaluate this curriculum, 94 Year 4 dental students took part to complete the online orthodontic curriculum. The mean total score of all the students was 91.99, and the element scores of the online theoretical lectures, journal club, virtual pre‐clinical training, and online final examination were respectively 96.83, 79.49, 96.00, and 87.02, which showed a good performance. According to the student feedback toward this curriculum via the online questionnaire, nearly 98% of the students showed agreement or strong agreement that the online orthodontic curriculum has enhanced their orthodontic theoretical understanding and orthodontic practical ability.

Conclusion

As a student‐centered CBE, this online orthodontic curriculum with online evaluation system could provide both orthodontic theory and practice teaching for all the dental students at all times and places based on the online virtual mode, which enriched learners’ critical thinking, problem solving, and assessment skills.