bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and functional basis for pan-CoV fusion inhibitors against SARS-CoV-2 and its variants with preclinical evaluation
Authors: Xia Shuai , Lan Qiaoshuai , Zhu Yun , Wang Chao , Xu Wei , Li Yutang , Wang Lijue , Jiao Fanke , Zhou Jie , Hua Chen , Wang Qian , Cai Xia , Wu Yang , Gao Jie , Liu Huan , Sun Ge , Münch Jan , Kirchhoff Frank , Yuan Zhenghong , Xie Youhua , Sun Fei , Jiang Shibo , Lu Lu 
Published: July 2021

AbstractThe COVID-19 pandemic poses a global threat to public health and economy. The continuously emerging SARS-CoV-2 variants present a major challenge to the development of antiviral agents and vaccines. In this study, we identified that EK1 and cholesterol-coupled derivative of EK1, EK1C4, as pan-CoV fusion inhibitors, exhibit potent antiviral activity against SARS-CoV-2 infection in both lung- and intestine-derived cell lines (Calu-3 and Caco2, respectively). They are also effective against infection of pseudotyped SARS-CoV-2 variants B.1.1.7 (Alpha) and B.1.1.248 (Gamma) as well as those with mutations in S protein, including N417T, E484K, N501Y, and D614G, which are common in South African and Brazilian variants. Crystal structure revealed that EK1 targets the HR1 domain in the SARS-CoV-2 S protein to block virus-cell fusion and provide mechanistic insights into its broad and effective antiviral activity. Nasal administration of EK1 peptides to hACE2 transgenic mice significantly reduced viral titers in lung and intestinal tissues. EK1 showed good safety profiles in various animal models, supporting further clinical development of EK1-based pan-CoV fusion inhibitors against SARS-CoV-2 and its variants.
Sociodemographic characteristics of missing data in digital phenotyping
Authors: Kiang Mathew V. , Chen Jarvis T. , Krieger Nancy , Buckee Caroline O. , Alexander Monica J. , Baker Justin T. , Buckner Randy L. , Coombs Garth , Rich-Edwards Janet W. , Carlson Kenzie W. , Onnela Jukka-Pekka 
Published: July 2021

AbstractThe ubiquity of smartphones, with their increasingly sophisticated array of sensors, presents an unprecedented opportunity for researchers to collect longitudinal, diverse, temporally-dense data about human behavior while minimizing participant burden. Researchers increasingly make use of smartphones for “digital phenotyping,” the collection and analysis of raw phone sensor and log data to study the lived experiences of subjects in their natural environments using their own devices. While digital phenotyping has shown promise in fields such as psychiatry and neuroscience, there are fundamental gaps in our knowledge about data collection and non-collection (i.e., missing data) in smartphone-based digital phenotyping. In this meta-study using individual-level data from six different studies, we examined accelerometer and GPS sensor data of 211 participants, amounting to 29,500 person-days of observation, using Bayesian hierarchical negative binomial regression with study- and user-level random intercepts. Sensitivity analyses including alternative model specification and stratified models were conducted. We found that iOS users had lower GPS non-collection than Android users. For GPS data, rates of non-collection did not differ by race/ethnicity, education, age, or gender. For accelerometer data, Black participants had higher rates of non-collection, but rates did not differ by sex, education, or age. For both sensors, non-collection increased by 0.5% to 0.9% per week. These results demonstrate the feasibility of using smartphone-based digital phenotyping across diverse populations, for extended periods of time, and within diverse cohorts. As smartphones become increasingly embedded in everyday life, the insights of this study will help guide the design, planning, and analysis of digital phenotyping studies.
Kras-driven intratumoral heterogeneity triggers infiltration of M2 polarized macrophages via the circHIPK3/PTK2 immunosuppressive circuit
Authors: Katopodi Theodora , Petanidis Savvas , Domvri Kalliopi , Zarogoulidis Paul , Anestakis Doxakis , Charalampidis Charalampos , Tsavlis Drosos , Bai Chong , Huang Haidong , Freitag Lutz , Hohenforst-Schmidt Wolfgang , Matthaios Dimitris , Porpodis Konstantinos 
Published: July 2021

AbstractIntratumoral heterogeneity in lung cancer is essential for evasion of immune surveillance by tumor cells and establishment of immunosuppression. Gathering data reveal that circular RNAs (circRNAs), play a role in the pathogenesis and progression of lung cancer. Particularly Kras-driven circRNA signaling triggers infiltration of myeloid-associated tumor macrophages in lung tumor microenvironment thus establishing immune deregulation, and immunosuppression but the exact pathogenic mechanism is still unknown. In this study, we investigate the role of oncogenic Kras signaling in circRNA-related immunosuppression and its involvement in tumoral chemoresistance. The expression pattern of circRNAs HIPK3 and PTK2 was determined using quantitative polymerase chain reaction (qPCR) in lung cancer patient samples and cell lines. Apoptosis was analyzed by Annexin V/PI staining and FACS detection. M2 macrophage polarization and MDSC subset analysis (Gr1−/CD11b−, Gr1−/CD11b+) were determined by flow cytometry. Tumor growth and metastatic potential were determined in vivo in C57BL/6 mice. Findings reveal intra-epithelial CD163+/CD206+ M2 macrophages to drive Kras immunosuppressive chemoresistance through myeloid differentiation. In particular, monocytic MDSC subsets Gr1−/CD11b−, Gr1−/CD11b+ triggered an M2-dependent immune response, creating an immunosuppressive tumor-promoting network via circHIPK3/PTK2 enrichment. Specifically, upregulation of exosomal cicHIPK3/PTK2 expression prompted Kras-driven intratumoral heterogeneity and guided lymph node metastasis in C57BL/6 mice. Consequent co-inhibition of circPTK2/M2 macrophage signaling suppressed lung tumor growth along with metastatic potential and prolonged survival in vivo. Taken together, these results demonstrate the key role of myeloid-associated macrophages in sustaining lung immunosuppressive neoplasia through circRNA regulation and represent a potential therapeutic target for clinical intervention in metastatic lung cancer.
Asymmetrical plasmonic absorber and reflector based on tilted Weyl semimetals
Authors: Abdol Somayeh Oskoui , Abdollahipour Babak 
Published: July 2021

AbstractWe investigate the surface plasmon polariton dispersion and optical spectra of a thin film of tilted Weyl semimetal. Tilted Weyl semimetals possess tilted Weyl cones at the Weyl nodes and are categorized to type-I with closed Fermi surfaces and type-II with overtilted Weyl cones and open Fermi surfaces. We find that the surface plasmon polariton dispersion of this system is nonreciprocal even in the absence of the external magnetic field. Moreover, we demonstrate that the tilt parameter has a profound effect in controlling this nonreciprocity. We reveal that the thin film of type-II Weyl semimetal hosts the surface plasmon polariton modes with the negative group velocity. Furthermore, we show that the angular optical spectra of this structure are highly asymmetric and this angular asymmetry in the absorptivity and reflectivity depends profoundly on the tilt parameter of the tilted Weyl semimetal. These exciting features propose employing the tilted Weyl semimetals in optical sensing devices, optical data storage, and devices for quantum information processing.
Glutamic acid promotes hair growth in mice
Authors: Jara Carlos Poblete , de Andrade Berti Beatriz , Mendes Natália Ferreira , Engel Daiane Fátima , Zanesco Ariane Maria , Pereira de Souza Gabriela Freitas , de Medeiros Bezerra Renan , de Toledo Bagatin Julia , Maria-Engler Silvya Stuchi , Morari Joseane , Velander William H. , Velloso Lício A. , Araújo Eliana Pereira 
Published: July 2021

AbstractGlutamic acid is the main excitatory neurotransmitter acting both in the brain and in peripheral tissues. Abnormal distribution of glutamic acid receptors occurs in skin hyperproliferative conditions such as psoriasis and skin regeneration; however, the biological function of glutamic acid in the skin remains unclear. Using ex vivo, in vivo and in silico approaches, we showed that exogenous glutamic acid promotes hair growth and keratinocyte proliferation. Topical application of glutamic acid decreased the expression of genes related to apoptosis in the skin, whereas glutamic acid increased cell viability and proliferation in human keratinocyte cultures. In addition, we identified the keratinocyte glutamic acid excitotoxic concentration, providing evidence for the existence of a novel skin signalling pathway mediated by a neurotransmitter that controls keratinocyte and hair follicle proliferation. Thus, glutamic acid emerges as a component of the peripheral nervous system that acts to control cell growth in the skin. These results raise the perspective of the pharmacological and nutritional use of glutamic acid to treat skin diseases.
Kea (Nestor notabilis) fail a loose-string connectivity task
Authors: Bastos Amalia P. M. , Wood Patrick M. , Taylor Alex H. 
Published: July 2021

AbstractNaïve individuals of some bird species can rapidly solve vertical string-pulling tasks with virtually no errors. This has led to various hypotheses being proposed which suggest that birds mentally simulate the effects of their actions on strings. A competing embodied cognition hypothesis proposes that this behaviour is instead modulated by perceptual-motor feedback loops, where feedback of the reward moving closer acts as an internal motivator for functional behaviours, such as pull-stepping. To date, the kea parrot has produced some of the best performances of any bird species at string-pulling tasks. Here, we tested the predictions of the four leading hypotheses for the cognition underpinning bird string-pulling by presenting kea with a horizontal connectivity task where only one of two loose strings was connected to the reward, both before and after receiving perceptual-motor feedback experience. We find that kea fail the connectivity task both before and after perceptual-motor feedback experience, suggesting not only that kea do not mentally simulate their string-pulling actions, but also that perceptual-motor feedback alone is insufficient in eliciting successful performance in the horizontal connectivity task. This suggests a more complex interplay of cognitive factors underlies this iconic example of animal problem-solving.
The role of sheep ked (Melophagus ovinus) as potential vector of protozoa and bacterial pathogens
Authors: Werszko Joanna , Asman Marek , Witecka Joanna , Steiner-Bogdaszewska Żaneta , Szewczyk Tomasz , Kuryło Grzegorz , Wilamowski Konrad , Karbowiak Grzegorz 
Published: July 2021

AbstractThe sheep ked (Melophagus ovinus) hematophagous insect may act as a potential vector of vector-borne pathogens. The aim of this study was to detect the presence of Trypanosoma spp., Bartonella spp., Anaplasma phagocytophilum and Borrelia burgdorferi sensu lato in sheep ked collected from sheep in Poland. In total, Trypanosoma spp. was detected in 58.91% of M. ovinus, whereas Bartonella spp. and B. burgdorferi s.l. were found in 86.82% and 1.55% of the studied insects, respectively. A. phagocytophilum was not detected in the studied material. In turn, co-infection by Trypanosoma spp. and Bartonella spp. was detected in 50.39%, while co-infection with Trypanosoma spp. and Bartonella spp. and B. burgdorferi s.l. was found in 1.55% of the studied insects. The conducted study showed for the first time the presence of B. burgdorferi s. l. in M. ovinus, as well as for the first time in Poland the presence of Trypanosoma spp. and Bartonella spp. The obtained results suggest that these insects may be a potential vector for these pathogens, but further-more detailed studies are required.
A novel orally active HDAC6 inhibitor T-518 shows a therapeutic potential for Alzheimer’s disease and tauopathy in mice
Authors: Onishi Tomohiro , Maeda Ryouta , Terada Michiko , Sato Sho , Fujii Takahiro , Ito Masahiro , Hashikami Kentaro , Kawamoto Tomohiro , Tanaka Maiko 
Published: July 2021

AbstractAccumulation of tau protein is a key pathology of age-related neurodegenerative diseases such as Alzheimer's disease and progressive supranuclear palsy. Those diseases are collectively termed tauopathies. Tau pathology is associated with axonal degeneration because tau binds to microtubules (MTs), a component of axon and regulates their stability. The acetylation state of MTs contributes to stability and histone deacetylase 6 (HDAC6) is a major regulator of MT acetylation status, suggesting that pharmacological HDAC6 inhibition could improve axonal function and may slow the progression of tauopathy. Here we characterize N-[(1R,2R)-2-{3-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-5-oxo-5H,6H,7H-pyrrolo[3,4-b]pyridin-6-yl}cyclohexyl]-2,2,3,3,3-pentafluoropropanamide (T-518), a novel, potent, highly selective HDAC6 inhibitor with clinically favorable pharmacodynamics. T-518 shows potent inhibitory activity against HDAC6 and superior selectivity over other HDACs compared with the known HDAC6 inhibitors in the enzyme and cellular assays. T-518 showed brain penetration in an oral dose and blocked HDAC6-dependent tubulin deacetylation at Lys40 in mouse hippocampus. A 2-week treatment restored impaired axonal transport and novel object recognition in the P301S tau Tg mouse, tauopathy model, while a 3-month treatment also decreased RIPA-insoluble tau accumulation. Pharmaceutical inhibition of HDAC6 is a potential therapeutic strategy for tauopathy, and T-518 is a particularly promising drug candidate.
Colour and motion affect a dune wasp’s ability to detect its cryptic spider predators
Authors: Rodríguez-Morales Dulce , Tapia-McClung Horacio , Robledo-Ospina Luis E. , Rao Dinesh 
Published: July 2021

AbstractAmbush predators depend on cryptic body colouration, stillness and a suitable hunting location to optimise the probability of prey capture. Detection of cryptic predators, such as crab spiders, by flower seeking wasps may also be hindered by wind induced movement of the flowers themselves. In a beach dune habitat, Microbembex nigrifrons wasps approaching flowerheads of the Palafoxia lindenii plant need to evaluate the flowers to avoid spider attack. Wasps may detect spiders through colour and movement cues. We tracked the flight trajectories of dune wasps as they approached occupied and unoccupied flowers under two movement conditions; when the flowers were still or moving. We simulated the appearance of the spider and the flower using psychophysical visual modelling techniques and related it to the decisions made by the wasp to land or avoid the flower. Wasps could discriminate spiders only at a very close range, and this was reflected in the shape of their trajectories. Wasps were more prone to making errors in threat assessment when the flowers are moving. Our results suggest that dune wasp predation risk is augmented by abiotic conditions such as wind and compromises their early detection capabilities.
Rapid signaling reactivation after targeted BRAF inhibition predicts the proliferation of individual melanoma cells from an isogenic population
Authors: Khoshkenar Payam , Lowry Emily , Mitchell Amir 
Published: July 2021

AbstractCancer cells within tumors display a high degree of phenotypic variability. This variability is thought to allow some of the cells to survive and persist after seemingly effective drug treatments. Studies on vemurafenib, a signaling inhibitor that targets an oncogenic BRAF mutation common in melanoma, suggested that cell-to-cell variation in drug resistance, measured by long-term proliferation, originates from epigenetic differences in gene expression that pre-exist treatment. However, it is still unknown whether reactivation of signaling downstream to the inhibited BRAF, thought to be a key step for resistance, is heterogeneous across cells. While previous studies established that signaling reactivation takes place many hours to days after treatment, they monitored reactivation with bulk-population assays unsuitable for detecting cell-to-cell heterogeneity. We hypothesized that signaling reactivation is heterogeneous and is almost instantaneous for a small subpopulation of resistant cells. We tested this hypothesis by monitoring signaling dynamics at a single-cell resolution and observed that despite highly uniform initial inhibition, roughly 15% of cells reactivated signaling within an hour of treatment. Moreover, by tracking cell lineages over multiple days, we established that these cells indeed proliferated more than neighboring cells, thus establishing that rapid signaling reactivation predicts long-term vemurafenib resistance.
Prevalence of and factors associated with hypertension according to JNC 7 and ACC/AHA 2017 guidelines in Bangladesh
Authors: Rahman Md. Ashfikur , Halder Henry Ratul , Yadav Uday Narayan , Mistry Sabuj Kanti 
Published: July 2021

AbstractMost studies either followed Joint National Committee 7 (JNC 7) or World Health Organization-International Society of Hypertension (WHO-ISH) guidelines to ascertain the prevalence of hypertension among Bangladeshi adults. The American College of Cardiology/American Heart Association (ACC/AHA) revised the definition of hypertension in 2017, which has significant public health importance. In Bangladesh, the new guideline has resulted changes in prevalence and risk factors for hypertension compared to the JNC7 guideline. This study used data from the most recent round (2017–2018) of the Bangladesh Demographic and Health Survey (BDHS). According to the 2017 ACC/AHA guideline, the participants were categorized as hypertensive if they had blood pressure (BP) ≥ 130/80 mmHg, but it was ≥ 140/90 mmHg in JNC 7 guideline. A total of 11,959 participants were involved in the analysis. The median (IQR) age of the respondents was 34.0 (18.0–95.0) years. The prevalence of hypertension was 24.0% according to the JNC 7 guideline, which was 50.5% according to the 2017 ACC/AHA guideline. Participants who were overweight and obese, aged, member of affluent households, Rangpur and Rajshahi division inhabitants had significantly higher odds of being hypertensive according to both guidelines. The new guideline suggests that half of the adult population in Bangladesh is hypertensive when measured according to the new guideline, urging the policymakers and public health practitioners to take immediate action to address the already established modifiable risk factors.
Recent trends in revision knee arthroplasty in Germany
Authors: Rupp Markus , Walter Nike , Lau Edmund , Worlicek Michael , Kurtz Steven M. , Alt Volker 
Published: July 2021

AbstractWe aimed to answer the following questions: (1) How did numbers of revision knee arthroplasty procedures develop in Germany over the last decade compared to primary TKA? (2) How high was the percentage of septic interventions in knee prosthesis revisions? (3) Which treatment strategy was chosen for surgical treatment of knee PJI? Revision arthroplasty rates as a function of age, gender, infection and type of prosthesis were quantified based on Operation and Procedure Classification System codes using revision knee arthroplasty data from 2008 to 2018, provided by the Federal Statistical Office of Germany (Destatis). In 2018, a total number 23,812 revision knee arthroplasties were performed in Germany, yielding an overall increase of 20.76% between 2008 and 2018. In comparison, primary TKA procedures increased by 23.8% from 152,551 performed procedures in 2008 to 188,866 procedures in 2018. Hence, 12.6% of knee arthroplasties required a revision in 2018. Septic interventions increased by 51.7% for all revisions. A trend towards higher numbers in younger patients was observed. Compared to 2008, 17.41% less DAIR procedures were performed, whereby single-stage and two- or multi-stage change increased by 38.76% and 42.76% in 2018, respectively. The increasing number of revision knee arthroplasty in Germany, especially in younger patients and due to infection, underlines the need for future efforts to improve treatment strategies to delay primary arthroplasty and avoid periprosthetic joint infection.
In search of blue-light effects on cognitive control
Authors: Lee Hsing-Hao , Tu Yun-Chen , Yeh Su-Ling 
Published: July 2021

AbstractPeople are constantly exposed to blue light while engaging in work. It is thus crucial to understand if vast exposure to blue light influences cognitive control, which is essential for working efficiently. Previous studies proposed that the stimulation of intrinsically photosensitive retinal ganglion cells (ipRGCs), a newly discovered photoreceptor that is highly sensitive to blue light, could modulate non-image forming functions. Despite studies that showed blue light (or ipRGCs) enhances brain activations in regions related to cognitive control, how exposure to blue light changes our cognitive control behaviorally remains elusive. We examined whether blue light influences cognitive control through three behavioral tasks in three studies: the sustained attention to response task (SART), the task-switching paradigm, and the Stroop task. Classic effects of the SART, switch cost, and the Stroop effect were found, but no differences were observed in results of different background lights across the six experiments. Together, we conclude that these domains of cognitive control are not influenced by blue light and ipRGCs, and whether the enhancement of blue light on brain activities extends to the behavioral level should be carefully re-examined.
Torpor enhances synaptic strength and restores memory performance in a mouse model of Alzheimer’s disease
Authors: de Veij Mestdagh Christina F. , Timmerman Jaap A. , Koopmans Frank , Paliukhovich Iryna , Miedema Suzanne S. M. , Goris Maaike , van der Loo Rolinka J. , Krenning Guido , Li Ka Wan , Mansvelder Huibert D. , Smit August B. , Henning Robert H. , van Kesteren Ronald E. 
Published: July 2021

AbstractHibernation induces neurodegeneration-like changes in the brain, which are completely reversed upon arousal. Hibernation-induced plasticity may therefore be of great relevance for the treatment of neurodegenerative diseases, but remains largely unexplored. Here we show that a single torpor and arousal sequence in mice does not induce dendrite retraction and synapse loss as observed in seasonal hibernators. Instead, it increases hippocampal long-term potentiation and contextual fear memory. This is accompanied by increased levels of key postsynaptic proteins and mitochondrial complex I and IV proteins, indicating mitochondrial reactivation and enhanced synaptic plasticity upon arousal. Interestingly, a single torpor and arousal sequence was also sufficient to restore contextual fear memory in an APP/PS1 mouse model of Alzheimer’s disease. Our study demonstrates that torpor in mice evokes an exceptional state of hippocampal plasticity and that naturally occurring plasticity mechanisms during torpor provide an opportunity to identify unique druggable targets for the treatment of cognitive impairment.