bluuebunny/crossref_metadata_2025_split huggingface dataset:
Respondent Burden and Readability of Patient-Reported Outcome Measures for People With Aphasia
Authors: Engelhoven Amy E. R. , Bislick Lauren , Gray Sara , Pompon Rebecca Hunting 
Published: August 2022

Purpose:
Patient-reported outcome measures (PROMs) for persons with aphasia (PWA) are commonly used to measure various outcomes. Persons with aphasia commonly present with language deficits that can likely increase respondent burden. Elements that contribute to respondent burden include readability, design, and formatting methods. The aims of this study were to determine how PROMs for PWA rate in level of respondent burden and on readability levels.

Method:
Irwin's 2012 review of PROMs for PWA was used for inclusion criteria and additional PROMs developed after 2012 were identified. This method resulted in 14 PROMs, which were rated on proposed respondent burden criteria and also underwent a readability analysis.

Results:
Six PROMs achieved a 7 or higher with the proposed 10-point respondent burden measure, indicating lower respondent burden. Eight PROMs met the nationally recommended reading level of sixth grade.

Conclusions:
Results indicated that the several PROMs available for PWA fail to minimize respondent burden.
A Scoping Review of the Relationship Between Nonlinguistic Cognitive Factors and Aphasia Treatment Response
Authors: Diedrichs Victoria A. , Jewell Courtney C. , Harnish Stacy M. 
Published: August 2022

Purpose:
The purpose of this article was to explore the extent to which nonlinguistic cognitive factors demonstrate a relationship with aphasia treatment outcomes. To that end, we conducted a scoping review to broadly characterize the state of the literature related to this topic.

Methods:
Reporting guidelines from the PRISMA extension for scoping reviews were used to conduct our study, which queried two common databases used in the health science literature, PubMed and Web of Science. Search terms and eligibility criteria are provided. Results are organized by the four nonlinguistic domains of cognition explored across the included studies (i.e., attention, memory, executive functioning, and visuospatial skills).

Results:
Of 949 unique articles identified from our database searches, 17 articles with 18 distinct studies were included in the final scoping review. Notably, most studies included in the scoping review targeted impairment-based aphasia treatments. Most studies also examined multiple domains of nonlinguistic cognition. A relationship between cognition and poststroke aphasia therapy outcomes was identified in nine of 15 studies addressing executive functioning, four of nine studies examining memory, four of eight studies examining visuospatial skills, and two of five studies exploring attention.

Discussion:
The results among included studies were mixed, with few discernible patterns within each of the four cognitive domains, though it appears that the influence of nonlinguistic cognition may depend on the timing (i.e., immediate vs. delayed post-treatment) and type (i.e., trained vs. untrained, generalized) of aphasia therapy outcomes. Future study designs should address maintenance, by including outcome measures at follow-up, and generalization, by including measures of performance on either untrained stimuli or trained stimuli in untrained contexts. Future work should also strive for larger sample sizes, perhaps through collaborations, or prioritize replicability to produce more reliable conclusions.
Nanoscale engagement and clusterization of Programmed death ligand 1 (PD-L1) in the membrane lipid rafts of Non-Small Cell Lung Cancer cells
Authors: Ruglioni Martina , Civita Simone , Salvadori Tiziano , Cristiani Sofia , Carnicelli Vittoria , Barachini Serena , Petrini Iacopo , Nepita Irene , Castello Marco , Diaspro Alberto , Bianchini Paolo , Storti Barbara , Bizzarri Ranieri , Fogli Stefano , Danesi Romano 
Published: August 2022

ABSTRACTProgrammed death ligand 1 (PD-L1) plays a key role in several human tumors, and it has recently become a crucial target for cancer therapy. Yet, its subtle regulatory roles beside the well characterized immunosuppression in PD-1/PD-L1 immune checkpoint are still obscure and should be strictly related to its molecular properties in different cell settings. In this study we targeted the plasma membrane organization of PD-L1 in a Non-Small Cell Lung Cancer (NSCLC) cell line by a multiscale fluorescence imaging toolbox that included super-resolution microscopy approaches to reach the nanoscale. Our findings revealed for the first time that PD-L1 is prevalently engaged in the cholesterol-enriched “raft” regions of the cell membrane. Clusterization and engagement in membrane rafts may afford novel targets for the immuno-oncology strategies in the framework of NSCLC and, possibly, other tumor types.
Cost-Utility and Cost-Effectiveness Analysis of disease-modifying drugs of Relapsing-Remitting Multiple Sclerosis: A Systematic Review
Authors: gallehzan Nasrin Abulhasanbeigi , Khosravi Majid , Soleimanpour Samira , Hoseini Saeed , Mir Habibeh , Alipour Vahid , Rezapour Aziz 
Published: August 2022

AbstractBackgroundMultiple sclerosis is a chronic demyelinating disorder of the central nervous system that is categorized as an immune-mediated inflammatory disease. This study aimed to systematically review the cost-benefit and cost-effectiveness of relapsing-remitting drugs for multiple sclerosis.MethodsTo find related research and articles, articles published in Iranian and international databases by using a combination of MeSH (Medical Subject Headings) terms and based on inclusion and exclusion criteria were searched and reviewed. We included studies that addressed interventions, ICER, per QALY, and those which were published in a journal for different methods of infertility treatment, or a major general journal till 2019.ResultsOut of 1,360 records found, finally, 21 records were included in the research. Ten articles were published in the European continent, six articles in the Americ continent, and finally, five articles in the Asia continent. The most common limitations of published economic evaluation studies were in methodology or presentation of incremental analyses, sensitivity analyses, and discounts. The lowest and highest numerical value of outcome measures were -1,623,918 and 2,297,141.53, resprectively. Furthermore, the lowest and highest numerical value of the cost of disease-modifying drugs of RRMS were $180.67, and $1474840.19, resprectively.ConclusionsBased on the results of all studies, it can be concluded that for the treatment of patients with AF, care-oriented strategies should be preferred to drug strategies. Also, among the drug strategies with different prescribing methods, oral disease-modifying drugs of RRMS should be preferred to injectable drugs and intravenous infusions.
Temporal evolution of multiday, epileptic functional networks prior to seizure occurrence
Authors: Laiou Petroula , Biondi Andrea , Bruno Elisa , Viana Pedro , Winston Joel S , Rashid Zulqarnain , Ranjan Yatharth , Conde Pauline , Stewart Callum , Sun Shaoxiong , Zhang Yuezhou , Folarin Amos , Dobson Richard JB , Schulze-Bonhage Andreas , Duempelmann Matthias , Richardson Mark P ,   RADAR-Consortium
Published: August 2022

AbstractEpilepsy is one of the most common neurological disorders, characterized by the occurrence of repeated seizures. Given that epilepsy is considered a network disorder, tools derived from network neuroscience may confer the valuable ability to quantify properties of epileptic brain networks. In this study we use well-established brain network metrics (i.e., mean strength, variance of strength, eigenvector centrality, betweenness centrality) to characterize the temporal evolution of epileptic functional networks over several days prior to seizure occurrence. We infer the networks using long-term electroencephalographic recordings from 12 people with epilepsy. We found that brain network metrics are variable across days and show a circadian periodicity. In addition, we found that in 9 out of 12 patients the distribution of variance of strength in the day (or even two last days) prior to seizure occurrence is significantly different compared to the corresponding distributions on all previous days. Our results suggest that brain network metrics computed from EEG recordings could potentially be used to characterize brain network changes that occur prior to seizures, and ultimately contribute to seizure warning systems.
Genomic deletion of Bcl6 differentially affects conventional dendritic cell subsets and compromises Tfh/Tfr/Th17 cell responses
Authors: Xiao Hongkui , Ulmert Isabel , Bach Luisa , Huber Johanna , Narasimhan Hamsa , Kurochkin Ilia , Chang Yinshui , Holst Signe , Mörbe Urs , Zhang Lili , Schlitzer Andreas , Pereira Filipe , Schraml Barbara U. , Baumjohann Dirk , Lahl Katharina 
Published: August 2022

ABSTRACTConventional dendritic cells (cDC) play key roles in immune induction, but what drives their heterogeneity and functional specialization is still ill-defined. Here we show that cDC-specific deletion of the transcriptional repressor Bcl6 in mice alters the phenotype and transcriptome of cDC1s and cDC2s, while their lineage identity is preserved. Bcl6-deficient cDC1s are diminished in the periphery but maintain their ability to cross-present antigen to CD8+T cells, confirming general maintenance of this subset. Surprisingly, the absence of Bcl6 in cDCs causes a complete loss of Notch2-dependent cDC2s in the spleen and intestinal lamina propria. DC-targeted Bcl6-deficient mice induced fewer T follicular helper cells despite a profound impact on T follicular regulatory cells in response to immunization and mounted diminished Th17 immunity toCitrobacter rodentiumin the colon. Our findings establish Bcl6 as an essential transcription factor for subsets of cDC and add to our understanding of the transcriptional landscape underlying cDC heterogeneity.
Systematic characterization of chromodomain proteins reveals an H3K9me1/2 reader regulating aging inC. elegans
Authors: Hou Xinhao , Xu Mingjing , Zhu Chengming , Gao Jianing , Li Meili , Chen Xiangyang , Sun Cheng , Nashan Björn , Zang Jianye , Guang Shouhong , Feng Xuezhu 
Published: August 2022

ABSTRACTThe chromatin organization modifier domain (chromodomain) is an evolutionally conserved motif across eukaryotic species. The chromodomain mainly functions as a histone methyl-lysine reader to modulate gene expression, chromatin spatial conformation and genome stability. Mutations or aberrant expression of chromodomain proteins can result in cancer and other human diseases. Here, we systematically tagged chromodomain proteins with green fluorescent protein (GFP) using CRISPR/Cas9 technology inC. elegans. By combining ChIP-seq analysis and imaging, we delineated a comprehensive expression and functional map of chromodomain proteins. We then conducted a candidate-based RNAi screening and identified factors that regulate the expression and subcellular localization of the chromodomain proteins. Specifically, we revealed a new H3K9me1/2 reader, CEC-5, both by in vitro biochemistry and in vivo ChIP assays. MET-2, an H3K9me1/2 writer, is required for CEC-5 association with heterochromatin. Both MET-2 and CEC-5 are required for the normal lifespan ofC. elegans. Furthermore, a forward genetic screening identified a conserved Arginine124 of CEC-5’s chromodomain, which was essential for CEC-5’s association with chromatin and life span regulation. Thus, our work will serve as a reference to explore chromodomain functions and regulation inC. elegansand allow potential applications in aging-related human diseases.
LRTK: A platform agnostic toolkit for linked-read analysis of both human genomes and metagenomes
Authors: Yang Chao , Zhang Zhenmiao , Huang Yufen , Xie Xuefeng , Liao Herui , Xiao Jin , Veldsman Werner Pieter , Yin Kejing , Fang Xiaodong , Zhang Lu 
Published: August 2022

AbstractLinked-read sequencing technologies generate high base quality reads that contain extrapolative information on long-range DNA connectedness. These advantages of linked-read technologies are well known and has been demonstrated in many human genomic and metagenomic studies. However, existing linked-read analysis pipelines (e.g., Long Ranger) were primarily developed to process sequencing data from the human genome and are not suited for analyzing metagenomic sequencing data. Moreover, linked-read analysis pipelines are typically limited to one specific sequencing platform. To address these limitations, we present the Linked-Read ToolKit (LRTK), a unified and versatile toolkit for platform agnostic processing of linked-read sequencing data from both human genomes and metagenomes. LRTK provides functions to perform linked-read simulation, barcode error correction, read cloud assembly, barcode-aware read alignment, reconstruction of long DNA fragments, taxonomic classification and quantification, as well as barcode-assisted genomic variant calling and phasing. LRTK has the ability to process multiple samples automatically, and provides the user with the option to generate reproducible reports during processing of raw sequencing data and at multiple checkpoints throughout downstream analysis. We applied LRTK on two benchmarking and three real linked-read data sets from both the human genome and metagenome. We showcase LRTK’s ability to generate comparative performance results from the preceding benchmark study and to report these results in publication-ready HTML document plots. LRTK provides comprehensive and flexible modules along with an easy-to-use Python-based workflow for processing linked-read sequencing datasets, thereby filling the current gap in the field caused by platform-centric genome-specific linked-read data analysis tools.
Growth arrest ofStaphylococcus aureusinduces daptomycin tolerance via cell wall remodelling
Authors: Ledger Elizabeth V. K. , Edwards Andrew M. 
Published: August 2022

AbstractAlmost all bactericidal drugs require bacterial replication and/or metabolic activity for their killing activity. When these processes are inhibited by bacteriostatic antibiotics, bacterial killing is significantly reduced. One notable exception is the lipopeptide antibiotic daptomycin, which has been reported to efficiently kill non-dividing bacteria. However, these studies employed only brief periods of growth arrest. We found that a bacteriostatic concentration of the protein synthesis inhibitor tetracycline led to a time-dependent induction of daptomycin tolerance inS. aureus, with~100,000-fold increase in survival after 16 h growth arrest relative to exponential phase bacteria. Daptomycin tolerance required glucose and was associated with increased production of the cell wall polymers peptidoglycan and wall-teichoic acids. However, whilst accumulation of peptidoglycan was required for daptomycin tolerance, only a low abundance of wall teichoic acid was necessary. Therefore, whilst tolerance to most antibiotics occurs passively due to a lack of metabolic activity and/or replication, daptomycin tolerance arises via active cell wall remodelling.
TRAIL-induces Src mediated MEK/ERK, SMAD3 and β-catenin signalling in apoptosis resistant NSCLC cells
Authors: de Looff Margot , Heng Win Sen , de Jong Steven , Kruyt Frank A.E. 
Published: August 2022

AbstractTumour-necrosis factor related apoptosis-inducing ligand (TRAIL) receptors (TRAIL-R1 and -R2) are appealing therapeutic targets to eradicate tumours specifically via caspase-dependent apoptosis. However, resistance is often observed and TRAIL-R activation can even activate pro-tumorigenic non-canonical signalling pathways. Previously, we found that TRAIL-induced RIPK1-Src-STAT3 signalling was mediating cell migration and invasion in resistant non-small cell lung cancer (NSCLC). Here, the contribution of Src in TRAIL signalling in NSCLC cell lines was further examined. TRAIL sensitive H460 and resistant A549 NSCLC cells showed distinct time-dependent rhTRAIL-induced Src phosphorylation patterns with early activation in A549 cells. Pharmacological Src inhibition as well as shRNA knockdown or CRISPR/CAS9-dependent knockout of Src expression did not alter sensitivity to rhTRAIL-induced apoptosis in both cell lines. Silencing of secondary complex proteins showed that TRADD, but not TRAF2, FADD nor caspase-8, was required for Src activation in A549 cells. Possible mediators of Src-dependent rhTRAIL signalling were identified by Src co-IP-LC-mass spectrometric analyses. In A549 cells the number of Src-interacting proteins increased after rhTRAIL treatment, whereas protein numbers decreased in H460 cells. In rhTRAIL treated A549 cells, Src biding proteins included components of the RAF-MEK1/2-ERK, Wnt and SMAD3 signalling pathways. Functional analyses showed that Src mediated phosphorylation of MEK1/2 and ERK, prevented phosphorylation of SMAD3 and was required for nuclear translocation of ERK and β-catenin in A549 cells. Clonogenic growth of both Src proficient and deficient A549 cells was not affected by rhTRAIL exposure, although Src depletion and MEK1/2 inhibition reduced colony size and numbers significantly. In conclusion, rhTRAIL-induced and Src dependent MEK/ERK, SMAD3 and β-catenin signalling may contribute to the known pro-tumorigenic effects of rhTRAIL in resistant NSCLC cells. However, this needs to be further examined, as well as the potential therapeutic implications of targeting these pathways when combined with TRAIL receptor agonists.
Negative interactions and virulence differences drive the dynamics in multispecies bacterial infections
Authors: Schmitz Désirée A. , Allen Richard C. , Kümmerli Rolf 
Published: August 2022

Bacterial infections are often polymicrobial, leading to intricate pathogen-pathogen and pathogen-host interactions. There is increasing interest in studying the molecular basis of pathogen interactions and how such mechanisms impact host morbidity. However, much less is known about the ecological dynamics between pathogens and how they affect virulence and host survival. Here we address these open issues by co-infecting larvae of the insect model hostGalleria mellonellawith one, two, three or four bacterial species, all of which are opportunistic human pathogens. We found that host mortality was always determined by the most virulent species regardless of the number of species and pathogen combinations injected. In certain combinations, the more virulent pathogen simply outgrew the less virulent pathogen. In other combinations, we found evidence for negative interactions between pathogens inside the host, whereby the more virulent pathogen typically won a competition. Taken together, our findings reveal positive associations between a pathogen’s growth inside the host, its competitiveness towards other pathogens, and its virulence. Beyond being generalizable across species combinations, our findings predict that treatments against polymicrobial infections should target the most virulent species to reduce host morbidity, a prediction we validated experimentally.ImportanceThere is increasing evidence that polymicrobial infections are common and that host morbidity is impacted by interactions between the co-infecting pathogens. In this study, we infected the larvae of the insect hostGalleria mellonellawith four opportunistic human pathogens as mono or multispecies bacterial infections in all possible combinations and followed host survival and pathogen interactions over time. We discovered that species followed the exact same rank order in terms of their virulence, their growth inside the host, and their competitive ability against co-infecting pathogens. As consequence of this consistent rank order, we found that the most virulent species determines host survival dynamics in mixed infections. Beyond revealing a generalizable predictive pattern for virulence outcomes, our findings also predict that treatments should target the most virulent species in polymicrobial infections, a prediction we validated experimentally.
Phylogenomics revealed migration routes and adaptive radiation timing of Holarctic malaria vectors of the Maculipennis group
Authors: Yurchenko Andrey A. , Naumenko Anastasia N. , Artemov Gleb N. , Karagodin Dmitry A. , Hodge James M. , Velichevskaya Alena I. , Kokhanenko Alina A. , Bondarenko Semen M. , Abai Mohammad R. , Kamali Maryam , Gordeev Mikhail I. , Moskaev Anton V. , Caputo Beniamino , Aghayan Sargis A. , Baricheva Elina M. , Stegniy Vladimir N. , Sharakhova Maria V. , Sharakhov Igor V. 
Published: August 2022

AbstractBackgroundUnderstanding the evolutionary relationships between closely related taxa is important for mosquitoes that transmit human diseases. Six out of 41 dominant malaria vectors in the world belong to the Maculipennis group, which is subdivided into two North American subgroups (Freeborni and Quadrimaculatus), and one Eurasian (Maculipennis) subgroup. Although previous studies considered the Nearctic subgroups as ancestral, details about their relationship with the Palearctic subgroup, and their migration times and routes from North America to Eurasia remain controversial. The Eurasian speciesAn. beklemisheviis currently included in the North American Quadrimaculatus subgroup adding to the uncertainties in mosquito systematics.ResultsTo reconstruct historic relationships between the North American and Eurasian mosquitoes, we conducted a phylogenomic analysis of 11 Palearctic and 2 Nearctic species based on 1271 orthologous genes using their transcriptomic or genomic sequences. The analysis indicated that the Palearctic speciesAn. beklemisheviclusters together with other Eurasian species and represents a basal lineage among them. Also,An. beklemisheviis related more closely toAn. freeborni,which inhabits the Western United States, rather than toAn. quadrimaculatus,a species from the Eastern United States. The time-calibrated tree suggests a migration of mosquitoes in the Maculipennis group from North America to Eurasia about 20-25 million years ago through the Bering Land Bridge. A Hybridcheck analysis demonstrated highly significant signatures of introgression events between allopatric speciesAn. labranchiaeandAn. beklemishevi. The analysis also identified ancestral introgression events betweenAn. sacharoviand its Nearctic relativeAn. freebornidespite their current geographic isolation.ConclusionsOur phylogenomic analyses reveal migration routes and adaptive radiation timing of Holarctic malaria vectors and strongly support inclusion ofAn. beklemisheviinto the Maculipennis subgroup. The vectorial capacity and the ability to diapause during winter evolved multiple times in Maculipennis evolution. Detailed knowledge of the evolutionary history in the Maculipennis subgroup will help us better understand the current and future patterns of malaria transmission in Eurasia.