bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunotherapy with engineered bacteria by targeting the STING pathway for anti-tumor immunity
Authors: Leventhal Daniel S. , Sokolovska Anna , Li Ning , Plescia Christopher , Kolodziej Starsha A. , Gallant Carey W. , Christmas Rudy , Gao Jian-Rong , James Michael J. , Abin-Fuentes Andres , Momin Munira , Bergeron Christopher , Fisher Adam , Miller Paul F. , West Kip A. , Lora Jose M. 
Published: June 2020

AbstractSynthetic biology is a powerful tool to create therapeutics which can be rationally designed to enable unique and combinatorial functionalities. Here we utilize non-pathogenic E coli Nissle as a versatile platform for the development of a living biotherapeutic for the treatment of cancer. The engineered bacterial strain, referred to as SYNB1891, targets STING-activation to phagocytic antigen-presenting cells (APCs) in the tumor and activates complementary innate immune pathways. SYNB1891 treatment results in efficacious antitumor immunity with the formation of immunological memory in murine tumor models and robust activation of human APCs. SYNB1891 is designed to meet manufacturability and regulatory requirements with built in biocontainment features which do not compromise its efficacy. This work provides a roadmap for the development of future therapeutics and demonstrates the transformative potential of synthetic biology for the treatment of human disease when drug development criteria are incorporated into the design process for a living medicine.
Two linear epitopes on the SARS-CoV-2 spike protein that elicit neutralising antibodies in COVID-19 patients
Authors: Poh Chek Meng , Carissimo Guillaume , Wang Bei , Amrun Siti Naqiah , Lee Cheryl Yi-Pin , Chee Rhonda Sin-Ling , Fong Siew-Wai , Yeo Nicholas Kim-Wah , Lee Wen-Hsin , Torres-Ruesta Anthony , Leo Yee-Sin , Chen Mark I-Cheng , Tan Seow-Yen , Chai Louis Yi Ann , Kalimuddin Shirin , Kheng Shirley Seah Gek , Thien Siew-Yee , Young Barnaby Edward , Lye David C. , Hanson Brendon John , Wang Cheng-I , Renia Laurent , Ng Lisa F. P. 
Published: June 2020

AbstractGiven the ongoing SARS-CoV-2 pandemic, identification of immunogenic targets against the coronavirus spike glycoprotein will provide crucial advances towards the development of sensitive diagnostic tools and potential vaccine candidate targets. In this study, using pools of overlapping linear B-cell peptides, we report two IgG immunodominant regions on SARS-CoV-2 spike glycoprotein that are recognised by sera from COVID-19 convalescent patients. Notably, one is specific to SARS-CoV-2, which is located in close proximity to the receptor binding domain. The other region, which is localised at the fusion peptide, could potentially function as a pan-SARS target. Functionally, antibody depletion assays demonstrate that antibodies targeting these immunodominant regions significantly alter virus neutralisation capacities. Taken together, identification and validation of these neutralising B-cell epitopes will provide insights towards the design of diagnostics and vaccine candidates against this high priority coronavirus.
A large-area AgNW-modified textile with high-performance electromagnetic interference shielding
Authors: Liu Junchen , Lin Sen , Huang Kai , Jia Chao , Wang Qingmin , Li Ziwei , Song Jianan , Liu Zhenglian , Wang Haiyang , Lei Ming , Wu Hui 
Published: June 2020

AbstractManufacturing a flexible, light, large-area, and high-efficiency electromagnetic shielding materials in a straightforward and cost-effective manner presently remains a significant challenge. In this work, we propose a conductive network design and verify its electromagnetic interference (EMI) shielding effectiveness (SE) by simulation. Using the structure and parameters obtained by simulation, we prepare a flexible EMI shielding material using silver nanowires (AgNWs)/polyvinyl butyral (PVB) ethanol solution and textile substructure via a facile immersing method. In the frequency range of 5–18 GHz, the AgNWs/PVB textile with 1.4 mm thickness achieves an EMI SE of 59 dB, which exceeds the requirements for commercial applications. Due to the low density of 56 mg/cm3, specific shielding effectiveness (SSE) of this material reaches 1053 dB m3/g. It is found that the AgNWs/PVB textile is more resistant to washing with water and oxidation than AgNWs textile without a PVB protector. As a result, the conductivity of AgNWs/PVB textile exhibits no change after washing with water and varies slightly after being kept in hot air. We find that a signal monitor is unable to detect a signal emitted by a mobile phone from a jacket lined with AgNWs/PVB textile. AgNWs/PVB textile with these properties can be mass-produced as high-efficiency EMI shielding material for commercial applications.
The Help for Hay Fever community pharmacy-based pilot randomised controlled trial for intermittent allergic rhinitis
Authors: Smith Sarah , Porteous Terry , Bond Christine , Francis Jill , Lee Amanda J. , Lowrie Richard , Scotland Graham , Sheikh Aziz , Thomas Mike , Wyke Sally , Smith Lorraine 
Published: June 2020

AbstractManagement of intermittent allergic rhinitis (IAR) is suboptimal in the UK. An Australian community pharmacy-based intervention has been shown to help patients better self-manage their IAR. We conducted a pilot cluster RCT in 12 Scottish community pharmacies to assess transferability of the Australian intervention. Trained staff in intervention pharmacies delivered the intervention to eligible customers (n = 60). Non-intervention pharmacy participants (n = 65) received usual care. Outcome measures included effect size of change in the mini-Rhinoconjunctivitis Quality of Life Questionnaire (miniRQLQ) between baseline, 1-week and 6-week follow-up. Trial procedures were well received by pharmacy staff, and customer satisfaction with the intervention was high. The standardised effect size for miniRQLQ total score was −0.46 (95% CI, −1.05, 0.13) for all participants and −0.14 (95% CI,−0.86, 0.57) in the complete case analysis, suggesting a small overall treatment effect in the intervention group. A full-scale RCT is warranted to fully evaluate the effectiveness of this service.
The sub-band structure of atomically sharp dopant profiles in silicon
Authors: Mazzola Federico , Chen Chin-Yi , Rahman Rajib , Zhu Xie-Gang , Polley Craig M. , Balasubramanian Thiagarajan , King Phil D. C. , Hofmann Philip , Miwa Jill A. , Wells Justin W. 
Published: June 2020

AbstractThe downscaling of silicon-based structures and proto-devices has now reached the single-atom scale, representing an important milestone for the development of a silicon-based quantum computer. One especially notable platform for atomic-scale device fabrication is the so-called Si:P δ-layer, consisting of an ultra-dense and sharp layer of dopants within a semiconductor host. Whilst several alternatives exist, it is on the Si:P platform that many quantum proto-devices have been successfully demonstrated. Motivated by this, both calculations and experiments have been dedicated to understanding the electronic structure of the Si:P δ-layer platform. In this work, we use high-resolution angle-resolved photoemission spectroscopy to reveal the structure of the electronic states which exist because of the high dopant density of the Si:P δ-layer. In contrast to published theoretical work, we resolve three distinct bands, the most occupied of which shows a large anisotropy and significant deviation from simple parabolic behaviour. We investigate the possible origins of this fine structure, and conclude that it is primarily a consequence of the dielectric constant being large (ca. double that of bulk Si). Incorporating this factor into tight-binding calculations leads to a major revision of band structure; specifically, the existence of a third band, the separation of the bands, and the departure from purely parabolic behaviour. This new understanding of the band structure has important implications for quantum proto-devices which are built on the Si:P δ-layer platform.
Emotion dysregulation mediates the relationship between nightmares and psychotic experiences: results from a student population
Authors: Akram Umair , Gardani Maria , Irvine Kamila , Allen Sarah , Ypsilanti Antonia , Lazuras Lambros , Drabble Jennifer , Stevenson Jodie C. , Akram Asha 
Published: June 2020

AbstractSleep disruption is commonly associated with psychotic experiences. While sparse, the literature to date highlights nightmares and related distress as prominent risk factors for psychosis in students. We aimed to further explore the relationship between specific nightmare symptoms and psychotic experiences in university students while examining the mediating role of emotion dysregulation. A sample (N = 1273) of student respondents from UK universities completed measures of psychotic experiences, nightmare disorder symptomology and emotion dysregulation. Psychotic experiences were significantly more prevalent in students reporting nightmares (n = 757) relative to those who did not (n = 516). Hierarchical linear regression analysis showed that psychotic experiences were significantly associated (Adjusted R2 = 32.4%) with perceived nightmare intensity, consequences and resulting awakenings, and with emotion regulation difficulties. Furthermore, multiple mediation analysis showed that the association between psychotic experiences and nightmare factors was mediated by emotion regulation difficulties. Adaptive regulation of dream content during rapid eye-movement sleep has previously been demonstrated to attenuate surges in affective arousal by controlling the intensity and variability of emotional content. Difficulties in emotion regulation may partially explain the experience of more intense and disruptive nightmares among individuals with psychotic experiences. Emotion regulation may represent an important control mechanism that safeguards dream content and sleep quality.
Novel biomarkers of a peripheral blood interferon signature associated with drug-naïve early arthritis patients distinguish persistent from self-limiting disease course
Authors: Seyhan Attila A. , Gregory Bernard , Cribbs Adam P. , Bhalara Sundeept , Li Yizheng , Loreth Christine , Zhang Ying , Guo Yongjing , Lin Lih-Ling , Feldmann Marc , Williams Lynn M. , Brennan Fionula M. , Taylor Peter C. 
Published: June 2020

AbstractWe profiled gene expression signatures to distinguish rheumatoid arthritis (RA) from non-inflammatory arthralgia (NIA), self-limiting arthritis (SLA), and undifferentiated arthritis (UA) as compared to healthy controls as novel potential biomarkers for therapeutic responsiveness. Global gene expression profiles of PBMCs from 43 drug-naïve patients presenting with joint symptoms were evaluated and differentially expressed genes identified by comparative analysis with 24 healthy volunteers. Patients were assessed at presentation with follow up at 6 and 12 months. Gene ontology and network pathway analysis were performed using DAVID Bioinformatics Resources v6.7. Gene expression profiles were also determined after disease-modifying anti-rheumatic drug (DMARD) treatment in the inflammatory arthritis groups (i.e. RA and UA) and confirmed by qRT-PCR. Receiver operating characteristic (ROC) curves analysis and Area Under the Curve (AUC) estimation were performed to assess the diagnostic value of candidate gene expression signatures. A type I interferon (IFN) gene signature distinguished DMARD-naïve patients who will subsequently develop persistent inflammatory arthritis (i.e. RA and UA) from those with NIA. In patients with RA, the IFN signature is characterised by up-regulation of SIGLEC1 (p = 0.00597) and MS4A4A (p = 0.00000904). We also identified, EPHB2 (p = 0.000542) and PDZK1IP1 (p = 0.0206) with RA-specific gene expression profiles and elevated expression of the ST6GALNAC1 (p = 0.0023) gene in UA. ROC and AUC risk score analysis suggested that MSA4A (AUC: 0.894, 0.644, 0.720), PDZK1IP1 (AUC: 0.785, 0.806, 0.977), and EPHB2 (AUC: 0.794, 0.723, 0.620) at 0, 6, and 12 months follow-up can accurately discriminate patients with RA from healthy controls and may have practical value for RA diagnosis. In patients with early inflammatory arthritis, ST6GALNAC1 is a potential biomarker for UA as compared with healthy controls whereas EPHB2, MS4A4A, and particularly PDZK1IP1 may discriminate RA patients. SIGLEC1 may also be a useful marker of disease activity in UA.
Detecting cardiac pathologies via machine learning on heart-rate variability time series and related markers
Authors: Agliari Elena , Barra Adriano , Barra Orazio Antonio , Fachechi Alberto , Franceschi Vento Lorenzo , Moretti Luciano 
Published: June 2020

AbstractIn this paper we develop statistical algorithms to infer possible cardiac pathologies, based on data collected from 24 h Holter recording over a sample of 2829 labelled patients; labels highlight whether a patient is suffering from cardiac pathologies. In the first part of the work we analyze statistically the heart-beat series associated to each patient and we work them out to get a coarse-grained description of heart variability in terms of 49 markers well established in the reference community. These markers are then used as inputs for a multi-layer feed-forward neural network that we train in order to make it able to classify patients. However, before training the network, preliminary operations are in order to check the effective number of markers (via principal component analysis) and to achieve data augmentation (because of the broadness of the input data). With such groundwork, we finally train the network and show that it can classify with high accuracy (at most ~85% successful identifications) patients that are healthy from those displaying atrial fibrillation or congestive heart failure. In the second part of the work, we still start from raw data and we get a classification of pathologies in terms of their related networks: patients are associated to nodes and links are drawn according to a similarity measure between the related heart-beat series. We study the emergent properties of these networks looking for features (e.g., degree, clustering, clique proliferation) able to robustly discriminate between networks built over healthy patients or over patients suffering from cardiac pathologies. We find overall very good agreement among the two paved routes.
Destabilization of light NREM sleep by thalamic PLCβ4 deletion impairs sleep-dependent memory consolidation
Authors: Hong Joohyeon , Ha Go Eun , Kwak Hankyul , Lee Yelin , Jeong Hyeonyeong , Suh Pann-Ghill , Cheong Eunji 
Published: June 2020

AbstractSleep abnormality often accompanies the impairment of cognitive function. Both rapid eye movement (REM) and non-REM (NREM) sleep have associated with improved memory performance. However, the role of composition in NREM sleep, consisting of light and deep NREM, for memory formation is not fully understood. We investigated how the dynamics of NREM sleep states influence memory consolidation. Thalamocortical (TC) neuron-specific phospholipase C β4 (PLCβ4) knockout (KO) increased the total duration of NREM sleep, consisting of destabilized light NREM and stabilized deep NREM. Surprisingly, the longer NREM sleep did not improve memory consolidation but rather impaired it in TC-specific PLCβ4 KO mice. Memory function was positively correlated with the stability of light NREM and spindle activity occurring in maintained light NREM period. Our study suggests that a single molecule, PLCβ4, in TC neurons is critical for tuning the NREM sleep states and thus affects sleep-dependent memory formation.
Characterisation of a subpopulation of CD133+ cancer stem cells from Chinese patients with oral squamous cell carcinoma
Authors: Ma Zhen , Zhang Chong , Liu Xiaotong , Fang Fang , Liu Shiqi , Liao Xianxiang , Tao Shicheng , Mai Huaming 
Published: June 2020

AbstractCancer stem cells (CSCs) play a critical role in cancer development and growth. The aim of this study was to identify and isolate CSCs from populations of primary oral squamous cell carcinoma (OSCC) cells, which were obtained from OSCC specimens and identified by cell morphology and immunohistochemical staining for keratin. CD133+ cells detected by flow cytometry comprised 0.41 ± 0.06% of primary OSCC cells and were isolated from primary OSCC cell populations using magnetic-activated cell sorting, revealing that 93.39% of high-purity CD133+ cells were in the G0/G1 phase of the cell cycle. Additionally, the growth rate of CD133+ cells was higher than that of CD133− cells, and in vivo tumourigenesis experiments showed that the tumourigenic ability of CD133+ cells was markedly stronger than that of CD133− cells. Moreover, CD133+ cells showed increased chemotherapeutic resistance to cisplatin and higher self-renewal ability according to sphere-formation assay, as well as higher mRNA levels of stemness-associated genes, including NANOG, SOX2, ALDH1A1, and OCT4. These results indicated that OSCC cells, which share certain characteristics of CSCs, harbour CD133+ cells potentially responsible for OSCC aggressiveness, suggesting CD133 as a potential prognostic marker and therapeutic target.
Proanthocyanidin-rich grape seed extract improves bone loss, bone healing, and implant osseointegration in ovariectomized animals
Authors: Tenkumo Taichi , Aobulikasimu Alkebaier , Asou Yoshinori , Shirato Midori , Shishido Shunichi , Kanno Taro , Niwano Yoshimi , Sasaki Keiichi , Nakamura Keisuke 
Published: June 2020

AbstractThe purpose of the present study was to confirm if proanthocyanidin-rich grape seed extract (GSE) had the ability to improve bone health such as bone loss, bone healing, and implant osseointegration (defined as the direct connection between bone tissue and an implant) in ovariectomized (OVX) animals. We demonstrated that daily oral administration of GSE prevented bone loss in the lumbar vertebrae and femur in OVX mice. In addition, osteoclastogenesis in the lumbar spine bone of OVX mice, as assessed by histological and histomorphometric analyses, was accelerated but GSE prevented this dynamization, suggesting that GSE could counteract OVX-induced accelerated osteoclastogenic activity. In rats, OVX clearly impaired the healing of defects created on the calvaria, and GSE overcame this OVX-impaired healing. In the same way, osseointegration of a tibial implant in rats was retarded by OVX, and GSE counteracted the OVX-induced poor osseointegration, likely promoting bone healing by preventing imbalanced bone turnover. These results suggest that orally administered GSE improved implant osseointegration by mitigating the impaired bone health induced by OVX as a model of estrogen deficiency.
Mouse intestinal tuft cells express advillin but not villin
Authors: Esmaeilniakooshkghazi Amin , George Sudeep P. , Biswas Ritwika , Khurana Seema 
Published: June 2020

AbstractTuft (or brush) cells are solitary chemosensory cells scattered throughout the epithelia of the respiratory and alimentary tract. The actin-binding protein villin (Vil1) is used as a marker of tuft cells and the villin promoter is frequently used to drive expression of the Cre recombinase in tuft cells. While there is widespread agreement about the expression of villin in tuft cells there are several disagreements related to tuft cell lineage commitment and function. We now show that many of these inconsistencies could be resolved by our surprising finding that intestinal tuft cells, in fact, do not express villin protein. Furthermore, we show that a related actin-binding protein, advillin which shares 75% homology with villin, has a tuft cell restricted expression in the gastrointestinal epithelium. Our study identifies advillin as a marker of tuft cells and provides a mechanism for driving gene expression in tuft cells but not in other epithelial cells of the gastrointestinal tract. Our findings fundamentally change the way we identify and study intestinal tuft cells.
Clarifying relationships between cranial form and function in tapirs, with implications for the dietary ecology of early hominins
Authors: DeSantis Larisa R. G. , Sharp Alana C. , Schubert Blaine W. , Colbert Matthew W. , Wallace Steven C. , Grine Frederick E. 
Published: June 2020

AbstractPaleontologists and paleoanthropologists have long debated relationships between cranial morphology and diet in a broad diversity of organisms. While the presence of larger temporalis muscle attachment area (via the presence of sagittal crests) in carnivorans is correlated with durophagy (i.e. hard-object feeding), many primates with similar morphologies consume an array of tough and hard foods—complicating dietary inferences of early hominins. We posit that tapirs, large herbivorous mammals showing variable sagittal crest development across species, are ideal models for examining correlations between textural properties of food and sagittal crest morphology. Here, we integrate dietary data, dental microwear texture analysis, and finite element analysis to clarify the functional significance of the sagittal crest in tapirs. Most notably, pronounced sagittal crests are negatively correlated with hard-object feeding in extant, and several extinct, tapirs and can actually increase stress and strain energy. Collectively, these data suggest that musculature associated with pronounced sagittal crests—and accompanied increases in muscle volume—assists with the processing of tough food items in tapirs and may yield similar benefits in other mammals including early hominins.
Temperate insects with narrow seasonal activity periods can be as vulnerable to climate change as tropical insect species
Authors: Johansson Frank , Orizaola Germán , Nilsson-Örtman Viktor 
Published: June 2020

AbstractThe magnitude and ecological impact of climate change varies with latitude. Several recent models have shown that tropical ectotherms face the greatest risk from warming because they currently experience temperatures much closer to their physiological optimum than temperate taxa. Even a small increase in temperature may thus result in steep fitness declines in tropical species but increased fitness in temperate species. This prediction, however, is based on a model that does not account for latitudinal differences in activity periods. Temperate species in particular may often experience considerably higher temperatures than expected during the active season. Here, we integrate data on insect warming tolerance and temperature-dependent development to re-evaluate latitudinal trends in thermal safety margins after accounting for latitudinal trends in insect seasonal activity. Our analyses suggest that temperate and tropical species differ far less in thermal safety margins than commonly assumed, and add to the recent number of studies suggesting that tropical and temperate species might face similar levels of threat from climate change.