bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating tumor cell characterization of lung cancer brain metastasis in the cerebrospinal fluid through single-cell transcriptome analysis
Authors: Ruan Haoyu , Zhou Yihang , Shen Jie , Zhai Yue , Xu Ying , Pi Linyu , Huang RuoFan , Chen Kun , Li Xiangyu , Ma Weizhe , Wu Zhiyuan , Deng Xuan , Wang Xu , Zhang Chao , Guan Ming 
Published: January 2020

AbstractMetastatic lung cancer accounts for about half of the brain metastases (BM). Development of leptomeningeal metastases (LM) are becoming increasingly common, and its prognosis is still poor despite the advances in systemic and local approaches. Cytology analysis in the cerebrospinal fluid (CSF) remains the diagnostic gold standard. Although several previous studies performed in CSF have offered great promise for the diagnostics and therapeutics of LM, a comprehensive characterization of circulating tumor cells (CTCs) in CSF is still lacking. To fill this critical gap of lung adenocarcinoma LM (LUAD-LM), we analyzed the transcriptomes of 1,375 cells from 5 LUAD-LM patient and 3 control samples using single-cell RNA sequencing technology. We defined CSF-CTCs based on abundant expression of epithelial markers and genes with lung origin, as well as the enrichment of metabolic pathway and cell adhesion molecules, which are crucial for the survival and metastases of tumor cells. Elevated expression ofCEACAM6andSCGB3A2was discovered in CSF-CTCs, which could serve as candidate biomarkers of LUAD-LM. We identified substantial heterogeneity in CSF-CTCs among LUAD-LM patients and within patient among individual cells. Cell-cycle gene expression profiles and the proportion of CTCs displaying mesenchymal and cancer stem cell properties also vary among patients. In addition, CSF-CTC transcriptome profiling identified one LM case as cancer of unknown primary site (CUP). Our results will shed light on the mechanism of LUAD-LM and provide a new direction of diagnostic test of LUAD-LM and CUP cases from CSF samples.
Exploring perspectives from stroke survivors, carers and clinicians on virtual reality as a precursor to using telerehabilitation for spatial neglect post-stroke
Authors: Morse Helen , Biggart Laura , Pomeroy Valerie , Rossit Stéphanie 
Published: January 2020

AbstractSpatial neglect is a common and severe cognitive consequence of stroke, yet there is currently no effective rehabilitation tool. Virtual Reality (VR) telerehabilitation tools have the potential to provide multisensory and enjoyable neuropsychological therapies and remotely monitor adherence without the presence of a therapist at all times. Researchers and industry need to better understand end-user perspectives about these technologies to ensure these are acceptable and user-friendly and, ultimately, optimize adherence and efficacy. Therefore, this study aims to explore end-user perspectives on the use of self-administered VR for spatial neglect in a university environment to identify barriers and facilitators prior to extending its use remotely or within the home as a VR telerehabilitation tool. We used a mixed-method design including focus groups, self-administered questionnaires and individual interviews with stroke survivors (N = 7), their carers (N = 3) and stroke clinicians (N = 6). End-user perspectives identified clarity of instructions, equipment (cost, available resources) and for some, level of experience with technology as barriers of use. Perceived facilitators of use were performance feedback, engagement and enjoyment, and psychological benefits associated by self-administered VR telerehabilitation. Overall, end-users were positive and interested in using VR telerehabilitation for spatial neglect. These perspectives enabled us to produce practical recommendations to inform development, enhance engagement and uptake of self-administered VR telerehabilitation and inform feasibility and usability studies.
Neutrophil-lymphocyte ratio across psychiatric diagnoses: An electronic health record investigation
Authors: Brinn Aimee , Stone James M 
Published: January 2020

AbstractObjectivesThe main objective of this study was to compare neutrophil-lymphocyte ratio, a marker of systemic inflammation, between patients diagnosed with ICD-10 psychiatric disorders and control participants.DesignA cross-sectional methodology was employed to retrospectively analyse electronic health records and records derived from a national health survey.SettingA secondary mental health care service consisting of four boroughs in South London.ParticipantsA diverse sample of 13,888 psychiatric patients extracted from South London and Maudsley electronic health records database and 3,920 control participants extracted from National Health and Nutrition Survey (2015-2016) were included in the study.Primary and secondary outcome measuresPrimary: NLR levels in patients with mental health diagnoses, NLR between patients with different mental health diagnoses. Secondary: Relationship of NLR to length of hospitalisation and to mortality.ResultsNLR was elevated compared to controls in patients with diagnoses including dementia, alcohol dependence, schizophrenia, bipolar affective disorder, depression, non-phobic anxiety disorders, and mild mental retardation (p < 0.05). NLR also correlated with age, antipsychotic use and hypnotic use. NLR was found to be higher in individuals of “White” ethnicity and lower in individuals of “Black” ethnicity. Elevated NLR was associated with increased mortality (β = 0.103, p = 2.9e-08) but not with hospital admissions or face-to-face contacts.ConclusionsElevated NLR may reflect a transdiagnostic pathological process occurring in a subpopulation of psychiatric patients. NLR may be useful to identify and stratify patients who could benefit from adjunctive anti-inflammatory treatment.Article SummaryStrengths and limitations of this studyLargest study to date of cross-diagnostic neutrophil-lymphocyte measurements in a psychiatric population.Sample is representative of diverse adult psychiatric patients in South London.Systematic differences between patients and controls reduce the validity of these comparisons.This study was retrospective and thus, confounding measures such as body mass index, smoking status and diet were unavailable.
A blood miRNA signature associates with sporadic Creutzfeldt-Jakob disease diagnosis
Authors: Norsworthy Penny J. , Thompson Andrew G.B. , Mok Tze H. , Guntoro Fernando , Dabin Luke C. , Nihat Akin , Paterson Ross W. , Schott Jonathan M. , Collinge John , Mead Simon , Viré Emmanuelle A. 
Published: January 2020

AbstractSporadic Creutzfeldt-Jakob disease (sCJD) presents as a rapidly progressive dementia which is usually fatal within six months. No clinical blood tests are currently available for diagnosis or disease monitoring. Here, we profiled blood microRNA (miRNA) expression in sCJD. Small RNA-sequencing of 57 sCJD patients and 48 healthy controls revealed differential expression of hsa-let-7i-5p, hsa-miR-16-5p, hsa-miR-93-5p and hsa-miR-106b-3p. Downregulation of hsa-let-7i-5p, hsa-miR-16-5p and hsa-miR-93-5p replicated in an independent cohort using quantitative PCR, with concomitant upregulation of four of their mRNA targets. Absence of correlation in cross-sectional analysis with clinical phenotypes paralleled the lack of association between rate of decline in miRNA expression and rate of disease progression in a longitudinal cohort of 50 samples from 21 sCJD patients. Finally, the miRNA signature showed a high level of accuracy in discriminating sCJD from Alzheimer’s disease (AD). These findings highlight novel molecular alterations in the periphery in sCJD which can provide information about differential diagnosis and improve mechanistic understanding of human prion diseases.
Propranolol promotes bone formation and limits resorption through novel mechanisms during anabolic parathyroid hormone treatment in female C57BL/6J mice
Authors: Treyball Annika , Bergeron Audrey C. , Brooks Daniel J. , Langlais Audrie L. , Hashmi Hina , Nagano Kenichi , Barlow Deborah , Nevola Kathleen T. , Houseknecht Karen L. , Baron Roland , Bouxsein Mary L. , Guntur Anyonya R. , Motyl Katherine J. 
Published: January 2020

AbstractAlthough the non-selective β-blocker, propranolol, improves bone density with PTH treatment in mice, the mechanism of this effect is unclear. To address this, we used a combination ofin vitroandin vivoapproaches to address how propranolol influences bone remodeling in the context of PTH treatment. In female C57BL/6J mice, intermittent PTH and propranolol had complementary effects in the trabecular bone of the distal femur and L5 vertebra, with combination treatment achieving micro-architectural parameters beyond that of PTH alone. Combined treatment improved the serum bone formation marker, P1NP, but did not impact other histomorphometric parameters relating to osteoblast function at the L5.In vitro, propranolol amplified the acute, PTH-induced, intracellular calcium signal in osteoblast-like cells. The most striking finding, however, was suppression of PTH-induced bone resorption. Despite this, PTH-induced receptor activator of nuclear factor kappa-B ligand (RANKL) mRNA and protein levels were unaltered by propranolol, which led us to hypothesize that propranolol could act directly on osteoclasts. Usingin situmethods, we foundAdrb2expression in osteoclastsin vivo, suggesting β-blockers may directly impact osteoclasts. Taken together, this work suggests a strong anti-osteoclastic effect of non-selective β-blockersin vivo, indicating that combining propranolol with PTH could be beneficial to patients with extremely low bone density.
Investigating the impact of combination phage and antibiotic therapy: a modeling study
Authors: Banuelos Selenne , Gulbudak Hayriye , Horn Mary Ann , Huang Qimin , Nandi Aadrita , Ryu Hwayeon , Segal Rebecca 
Published: January 2020

AbstractAntimicrobial resistance (AMR) is a serious threat to global health today. The spread of AMR, along with the lack of new drug classes in the antibiotic pipeline, has resulted in a renewed interest in phage therapy, which is the use of bacteriophages to treat pathogenic bacterial infections. This therapy, which was successfully used to treat a variety of infections in the early twentieth century, had been largely dismissed due to the discovery of easy to use antibiotics. However, the continuing emergence of antibiotic resistance has motivated new interest in the use of phage therapy to treat bacterial infections. Though various models have been developed to address the AMR-related issues, there are very few studies that consider the effect of phage-antibiotic combination therapy. Moreover, some of biological details such as the effect of the immune system on phage have been neglected. To address these limitations, we utilized a mathematical model to examine the role of the immune response in concert with phage-antibiotic combination therapy compounded with the effects of the immune system on the phages being used for treatment. We explore the effect of phage-antibiotic combination therapy by adjusting the phage and antibiotics dose or altering the timing. The model results show that it is important to consider the host immune system in the model and that frequency and dose of treatment are important considerations for the effectiveness of treatment. Our study can lead to development of optimal antibiotic use and further reduce the health risks of the human-animal-plant-ecosystem interface caused by AMR.
Auto-regulatory J-domain interactions control Hsp70 recruitment to the DnaJB8 chaperone
Authors: Ryder Bryan D. , Matlahov Irina , Bali Sofia , Vaquer-Alicea Jaime , van der Wel Patrick C.A. , Joachimiak Lukasz A. 
Published: January 2020

AbstractThe Hsp40/Hsp70 chaperone families combine versatile folding capacity with high substrate specificity, which is mainly facilitated by Hsp40s. The structure and function of many Hsp40s remain poorly understood, particularly oligomeric Hsp40s that suppress protein aggregation. Here, we used a combination of biochemical and structural approaches to shed new light on the domain interactions of the Hsp40 DnaJB8, and how they regulate recruitment of partner Hsp70s. We identify an interaction between the J-Domain (JD) and C-terminal domain (CTD) of DnaJB8 that sequesters the JD surface, preventing Hsp70 interaction. We propose a new model for DnaJB8-Hsp70 regulation, whereby the JD-CTD interaction of DnaJB8 acts as a reversible autoinhibitory switch that can control the binding of Hsp70. These findings suggest that the evolutionarily conserved CTD of DnaJB8 is a regulatory element of chaperone activity in the proteostasis network.
Fundamental resource specialization of herbivorous butterflies decreases toward lower latitudes
Authors: Nakadai Ryosuke , Nyman Tommi , Hashimoto Koya , Iwasaki Takaya , Valtonen Anu 
Published: January 2020

AbstractAimIt is generally assumed that the degree of resource specialization in herbivorous insects increases towards lower latitudes. However, latitudinal patterns in herbivore diet breadth at large spatial scales remain poorly understood. In this work, we investigated drivers of latitudinal variation in lepidopteran “fundamental” resource specialization, which we defined as the host breadth when not limited by interspecific interactions at the same trophic level.LocationThe Japanese archipelago (22°N–45°N), including hemiboreal, temperate, and subtropical zones.TaxonHerbivorous butterflies.MethodsSpecies-specific fundamental host breadth was calculated based on pooled geographical occurrence and host-use records. We investigated the latitudinal pattern and significant drivers of the degree of specialization in regional species pools at a 10-km grid level. As potential drivers, we focused on geography, current climate, and diversity and body size of butterflies. Through Bayesian structural equation modeling, we investigated the complicated relationships between these variables and community-level resource specialization represented by three different indices of host breadth.ResultsWe found that fundamental resource specialization of butterfly communities increases toward higher latitudes. This pattern is contrary to the presumed general trend found in studies based on realized resource specialization within local communities. We found that the observed pattern is driven mainly by factors related to climate, butterfly diversity, and body size in each community. Above all, annual mean temperature most strongly drove community-level fundamental host breadth of butterflies.Main conclusionsOur findings suggest that fundamental resource specialization may show different latitudinal patterns from the conventional prediction based on knowledge of realized resource specialization. Our results emphasize the importance of the current climate as a major factor regulating butterfly morphology and fundamental host breadth, regardless of whether the impact is direct or indirect.
Millipede genomes reveal unique adaptation of genes and microRNAs during myriapod evolution
Authors: Qu Zhe , Nong Wenyan , So Wai Lok , Barton-Owen Tom , Li Yiqian , Li Chade , Leung Thomas C.N. , Baril Tobias , Wong Annette Y.P. , Swale Thomas , Chan Ting-Fung , Hayward Alexander , Ngai Sai-Ming , Hui Jerome H.L. 
Published: January 2020

AbstractThe Myriapoda including millipedes and centipedes is of major importance in terrestrial ecology and nutrient recycling. Here, we sequenced and assembled two chromosomal-scale genomes of millipedesHelicorthomorpha holstii(182 Mb, N50 18.11 Mb mainly on 8 pseudomolecules) andTrigoniulus corallinus(449 Mb, N50 26.78 Mb mainly on 15 pseudomolecules). Unique defense systems, genomic features, and patterns of gene regulation in millipedes, not observed in other arthropods, are revealed. Millipedes possesses a unique ozadene defensive gland unlike the venomous forcipules in centipedes. Sets of genes associated with anti-microbial activity are identified with proteomics, suggesting that the ozadene gland is not primarily an antipredator adaptation (at least inT. corallinus). Macro-synteny analyses revealed highly conserved genomic blocks between centipede and the two millipedes. Tight Hox and the first loose ecdysozoan ParaHox homeobox clusters are identified, and a myriapod-specific genomic rearrangement including Hox3 is also observed. The Argonaute proteins for loading small RNAs are duplicated in both millipedes, but unlike insects, an argonaute duplicate has become a pseudogene. Evidence of post-transcriptional modification in small RNAs, including species-specific microRNA arm switching that provide differential gene regulation is also obtained. Millipede genomes reveal a series of unique genomic adaptations and microRNA regulation mechanisms have occurred in this major lineage of arthropod diversity. Collectively, the two millipede genomes shed new light on this fascinating but poorly understood branch of life, with a highly unusual body plan and novel adaptations to their environment.
Mathematical investigation of microbial quorum sensing under various flow conditions
Authors: Jung Heewon , Meile Christof 
Published: January 2020

AbstractMicroorganisms efficiently coordinate phenotype expressions through a decision-making process known as quorum sensing (QS). We investigated QS amongst heterogeneously distributed microbial aggregates under various flow conditions using a process-driven numerical model. Model simulations assess the conditions suitable for QS induction and quantify the importance of advective transport of signaling molecules. In addition, advection dilutes signaling molecules so that faster flow conditions require higher microbial densities, faster signal production rates, or higher sensitivities to signaling molecules to induce QS. However, autoinduction of signal production can substantially increase the transport distance of signaling molecules in both upstream and downstream directions. We present approximate analytical solutions of the advection-diffusion-reaction equation that describe the concentration profiles of signaling molecules for a wide range of flow and reaction rates. These empirical relationships, which predict the distribution of dissolved solutes following zero-order production kinetics along pore channels, allow to quantitatively estimate the effective communication distances amongst multiple microbial aggregates without further numerical simulations.Author SummaryMicrobes can interact with their surrounding environments by producing and sensing small signaling molecules. When the microbes experience a high enough concentration of the signaling molecules, they express certain phenotypes which is often energetically expensive. This microbial decision-making process known as quorum sensing (QS) has been understood to confer evolutionary benefits. However, it is still not completely understood how transport of the produced signaling molecules affects QS. Using a mathematical approach investigating QS across a range of environmentally relevant flow conditions, we find that advective transport promotes QS downstream yet also dilutes the concentration of signaling molecules. We quantify the importance of microbial cell location with respect to both other microbes and flow direction. By analyzing complex numerical simulation results, we provide analytical approximations to assess the distribution of signaling molecules in pore channels across a range of flow and reaction conditions.
Phylogenetic diversity and activity screening of cultivable actinobacteria isolated from marine sponges and associated environments from the western coast of India
Authors: Baig Ulfat , Dahanukar Neelesh , Shintre Neha , Holkar Ketki , Pund Anagha , Lele Uttara , Gujarathi Tejal , Patel Kajal , Jakati Avantika , Singh Ruby , Vidwans Harshada , Tamhane Vaijayanti , Deshpande Neelima , Watve Milind 
Published: January 2020

AbstractPhylogenetic diversity of cultivable actinobacteria isolated from sponges (Haliclonaspp.) and associated environments of intertidal zones, along the northern parts of west coast of India, were studied using 16S rRNA gene sequences. A subset of actinobacteria were screened for three activities, namely predatory behavior, antibacterial activity and enzyme inhibition. We recovered 237 isolates of actinobacteria belonging to 19 families and 28 genera, which could be attributed to 95 putative species using maximum likelihood partition and 100 putative species using Bayesian partition in Poisson Tree Processes. Although the trends in the discovery of actinobacterial genera isolated from sponges was consistent with previous studies from different study areas, we provide first report of nine actinobacterial species from sponges. We observed widespread non-obligate epibiotic predatory behavior in eight actinobacterial genera and we provide first report of predatory activity inBrevibacterium,Glutamicibacter,Micromonospora,Nocardiopsis,RhodococcusandRothia. Sponge associated actinobacteria showed significantly more predatory behavior than environmental isolates. While antibacterial activity by actinobacterial isolates mainly affected Gram-positive target bacteria with little to no effect on Gram-negative bacteria, predation targeted both Gram-positive and Gram-negative prey with equal propensity. Actinobacterial isolates from both sponge and associated environment produced inhibitors of serine proteases and angiotensin converting enzyme. Predatory behavior was strongly associated with inhibition of trypsin and chymotrypsin. Our study suggests that sponge and associated environment of western coast of India are rich in actinobacterial diversity with widespread predatory activity, antibacterial activity and production of enzyme inhibitors. Understanding diversity and associations among various actinobacterial activities, with each other and the source of isolation, can provide new insights in marine microbial ecology and provide opportunities to isolate novel therapeutic agents.
DLG2 knockout reveals neurogenic transcriptional programs underlying neuropsychiatric disorders and cognition
Authors: Sanders Bret , D’Andrea Daniel , Collins Mark O. , Rees Elliott , Steward Tom G. J. , Zhu Ying , Chapman Gareth , Legge Sophie E. , Pardiñas Antonio F. , Harwood Adrian J. , Gray William P. , O’Donovan Michael C. , Owen Michael J. , Errington Adam C. , Blake Derek J. , Whitcomb Daniel J. , Pocklington Andrew J. , Shin Eunju 
Published: January 2020

AbstractBrain development requires a complex choreography of cell proliferation, specialisation, migration and network formation, guided by the activation and repression of gene expression programs. It remains unclear how this process is disrupted in neuropsychiatric disorders. Here we integrate human genetics with transcriptomic data from the differentiation of human embryonic stem cells into cortical excitatory neurons. This reveals a cascade of transcriptional programs, activated during early corticoneurogenesis in vitro and in vivo, in which genetic variation is robustly associated with neuropsychiatric disorders and cognitive function. Within these early neurogenic programs, genetic risk is concentrated in loss-of-function intolerant (LoFi) genes, capturing virtually all LoFi disease association. Down-regulation of these programs in DLG2 knockout lines delays expression of cell-type identity alongside marked deficits in neuronal migration, morphology and action potential generation, validating computational predictions. These data implicate specific cellular pathways and neurodevelopmental processes in the aetiology of multiple neuropsychiatric disorders and cognition.