bluuebunny/crossref_metadata_2025_split huggingface dataset:
Face Masks, Public Policies and Slowing the Spread of COVID-19: Evidence from Canada
Authors: Karaivanov Alexander , Lu Shih En , Shigeoka Hitoshi , Chen Cong , Pamplona Stephanie 
Published: September 2020

AbstractWe estimate the impact of indoor face mask mandates and other non-pharmaceutical interventions (NPI) on COVID-19 case growth in Canada. Mask mandate introduction was staggered from mid-June to mid-August 2020 in the 34 public health regions in Ontario, Canada’s largest province by population. Using this variation, we find that mask mandates are associated with a 22 percent weekly reduction in new COVID-19 cases, relative to the trend in absence of mandate. Province-level data provide corroborating evidence. We control for mobility behaviour using Google geo-location data and for lagged case totals and case growth as information variables. Our analysis of additional survey data shows that mask mandates led to an increase of about 27 percentage points in self-reported mask wearing in public. Counterfactual policy simulations suggest that adopting a nationwide mask mandate in June could have reduced the total number of diagnosed COVID-19 cases in Canada by over 50,000 over the period July–November 2020. Jointly, our results indicate that mandating mask wearing in indoor public places can be a powerful policy tool to slow the spread of COVID-19.JEL codesI18, I12, C23
Behavioural barriers to COVID-19 testing in Australia
Authors: Bonner Carissa , Batcup Carys , Ayre Julie , Pickles Kristen , Dodd Rachael , Copp Tessa , Cornell Samuel , Cvejic Erin , Dakin Thomas , Isautier Jennifer , Nickel Brooke , McCaffery Kirsten 
Published: September 2020

ABSTRACTBackgroundThe current suppression strategy for COVID-19 in Australia is dependent on people getting tested and self-isolating while they have COVID-19 symptoms. However, there is very little research on the behaviours and behavioural barriers involved in getting tested, both in Australia and worldwide, despite there being some evidence that these barriers do exist.MethodsThe Sydney Health Literacy Lab (SHeLL) has been conducting a national longitudinal survey in Australia since April 2020. A list of testing barriers was included in Wave 3 in June 2020 (n=1369), along with intentions to test and self-isolate if symptomatic. Open responses were also collected. The test barriers identified were categorised using the COM-B framework.ResultsOnly 49% of people strongly agreed they would get tested if they had COVID-19 symptoms, but most people agreed to some extent that they would get tested (96%). The most common barriers selected from the list provided were that testing is painful (11%), not knowing how to get tested (7%), and worry about getting infected at the testing centre (5%). Many participants (10%) indicated other reasons, and open responses included many additional barriers to testing than those provided in the initial list. These covered all components of the COM-B model.ConclusionWe identified a wide range of barriers using both quantitative and qualitative methods, which need to be addressed in order to increase COVID-19 testing behaviour.
Mechanisms and heterogeneity of mineral use by natural colonies of the cyanobacteriumTrichodesmium
Authors: Held Noelle A. , Sutherland Kevin M. , Webb Eric A. , McIlvin Matthew R. , Cohen Natalie R. , Devaux Alexander J. , Hutchins David A. , Waterbury John B. , Hansel Colleen M. , Saito Mak A. 
Published: September 2020

AbstractThe keystone marine nitrogen fixerTrichodesmiumthrives in high dust environments, and while experimental observations suggest thatTrichodesmiumcolonies can access the essential nutrient iron from dust particles, it is not known the extent to which this occurs in the field. Here we demonstrate thatTrichodesmiumcolonies actively process mineral particles in nature with direct molecular impacts. Microscopy and synchrotron-based imaging demonstrated heterogeneous associations with particles consistent with iron oxide and iron silicate minerals. Metaproteomic analysis of individual colonies revealed enrichment of biogeochemically-relevant proteins including photosynthesis proteins and metalloproteins containing iron, nickel, copper and zinc when particles were present. The iron-storage protein ferritin was particularly enriched implying accumulation of particle-derived iron, and multiple iron acquisition pathways including Fe(II), Fe(III), and Fe-siderophore transporters were engaged, including evidence of superoxide-driven particle dissolution. While the particles clearly provided iron, there was also evidence that the concentrated metals had toxic effects. The molecular mechanisms allowingTrichodesmiumto interact with particulate minerals are fundamental to its success and global impact on nitrogen biogeochemistry, and may contribute to the leaching of particulate trace metals with implications for global iron and carbon cycling.
Tissue Dynamics Spectroscopic Imaging: Functional Imaging of Heterogeneous Cancer Tissue
Authors: Li Zhe , Hu Bihe , Li Guang , Fox Sharon E. , Jalal Shadia , Turek John , Brown J. Quincy , Nolte David D. 
Published: September 2020

AbstractSignificanceTumor heterogeneity poses a challenge for the chemotherapeutic treatment of cancer. Tissue dynamics spectroscopy (TDS) captures dynamic contrast and can capture the response of living tissue to applied therapeutics, but the current analysis averages over the complicated spatial response of living biopsy samples.AimTo develop tissue dynamics spectroscopic imaging (TDSI) to map the heterogeneous spatial response of tumor tissue to anticancer drugs.ApproachTDSI is applied to tumor spheroids grown from cell lines and toex vivoliving esophageal biopsy samples. Doppler fluctuation spectroscopy is performed on a voxel basis to extract spatial maps of biodynamic biomarkers. Functional images and bivariate spatial maps are produced using a bivariate color merge to represent the spatial distribution of pairs of signed drug-response biodynamic biomarkers.ResultsWe have mapped the spatial variability of drug responses within biopsies and have tracked sample-to-sample variability. Sample heterogeneity observed in the biodynamic maps is associated with histological heterogeneity observed using inverted Selective-Plane Illumination Microscopy (iSPIM).ConclusionWe have demonstrated the utility of TDSI as a functional imaging method to measure tumor heterogeneity and its potential for use in drug-response profiling.
Functional monovalency amplifies the pathogenicity of anti-MuSK IgG4 in myasthenia gravis
Authors: Vergoossen Dana L.E. , Plomp Jaap J. , Gstöttner Christoph , Fillié-Grijpma Yvonne E. , Augustinus Roy , Verpalen Robyn , Wuhrer Manfred , Parren Paul W.H.I. , Dominguez-Vega Elena , van der Maarel Silvère M. , Verschuuren Jan J. , Huijbers Maartje G. 
Published: September 2020

AbstractHuman IgG4 usually displays anti-inflammatory activity, and observations of IgG4 autoantibodies causing severe autoimmune disorders are therefore poorly understood. In blood, IgG4 antibodies naturally engage in a stochastic process termed Fab-arm exchange in which unrelated IgG4s exchange half-molecules continuously. The resulting IgG4 antibodies are composed of two different binding sites, thereby acquiring monovalent binding and inability to cross-link for each antigen recognized. Here, we demonstrate this process amplifies autoantibody pathogenicity in a classic IgG4-mediated autoimmune disease: muscle-specific kinase (MuSK) myasthenia gravis (MG). In mice, monovalent anti-MuSK IgG4s caused rapid and severe myasthenic muscle weakness, whereas the same antibodies in their parental bivalent form were less potent or did not induce a phenotype. Mechanistically this could be explained by opposing effects on MuSK signaling. Isotype switching to IgG4 in an autoimmune response thereby may be a critical step in the development of disease. Our study establishes functional monovalency as a novel pathogenic mechanism in IgG4-mediated autoimmune disease and potentially other disorders.Graphical abstract
The Phage-shock-protein (PSP) Envelope Stress Response: Discovery of Novel Partners and Evolutionary History
Authors: Ravi Janani , Anantharaman Vivek , Chen Samuel Zorn , Brenner Evan Pierce , Datta Pratik , Aravind L , Gennaro Maria Laura 
Published: September 2020

AbstractBacterial phage shock protein (PSP) systems stabilize the bacterial cell membrane and protect against envelope stress. These systems have been associated with virulence, but despite their critical roles, PSP components are not well-characterized outside proteobacteria. Using comparative genomics and protein sequence-structure-function analyses, we systematically identified and analyzed PSP homologs, phyletic patterns, domain architectures, and gene neighborhoods. This approach underscored the evolutionary significance of the system, revealing that the core PspA gene (Snf7 in ESCRT outside bacteria) was present in the Last Universal Common Ancestor (LUCA), and that this ancestral functionality has since diversified into multiple novel, distinct PSP systems across life. Several novel partners of the PSP system were identified: (i) the Toastrack domain, likely facilitating assembly of sub-membrane stress-sensing and signaling complexes, (ii) the newly-defined HAAS-PadR-like transcriptional regulator pair system, and (iii) multiple independent associations with ATPase, CesT/Tir-like chaperone, and Band-7 domains in proteins thought to mediate sub-membrane dynamics. Our work also uncovered links between the PSP components and other domains, such as novel variants of SHOCT-like domains, suggesting roles in assembling membrane-associated complexes of proteins with disparate biochemical functions. Results are available athttps://jravilab.org/psp.ImportancePhage shock proteins (PSP) are virulence-associated, cell membrane stress-protective systems. They have mostly been characterized in proteobacteria and firmicutes. We now show that PSP systems were present in the Last Universal Common Ancestor, and that homologs have evolved and diversified into newly identified functional contexts. Recognizing the conservation and evolution of PSP systems across bacterial phyla contributes to our understanding of stress response mechanisms in prokaryotes. Moreover, the newly discovered PSP modularity will likely prompt new studies of lineage-specific cell-envelope structures, lifestyles, and adaptation mechanisms. Finally, our results validate use of domain architecture and genetic context for discovery in comparative genomics.
Internal checkpoint regulates T cell neoantigen reactivity and susceptibility to PD1 blockade
Authors: Palmer Douglas C. , Webber Beau R. , Patel Yogin , Johnson Matthew J. , Kariya Christine M. , Lahr Walker S. , Parkhurst Maria R. , Gartner Jared J , Prickett Todd D , Lowery Frank J. , Kishton Rigel J. , Gurusamy Devikala , Franco Zulmarie , Vodnala Suman K. , Diers Miechaleen D. , Wolf Natalie K. , Slipek Nicholas J. , McKenna David H. , Sumstad Darin , Viney Lydia , Henley Tom , Bürckstümmer Tilmann , Baker Oliver , Hu Ying , Yan Chunhua , Meerzaman Daoud , Padhan Kartik , Lo Winnie , Malekzadeh Parisa , Jia Li , Deniger Drew C. , Patel Shashank J. , Robbins Paul F. , McIvor R. Scott , Choudhry Modassir , Rosenberg Steven A. , Moriarity Branden S. , Restifo Nicholas P. 
Published: September 2020

AbstractWhile neoantigen-specific tumor infiltrating lymphocytes (TIL) can be derived from in antigen-expressing tumors, their adoptive transfer fails to consistently elicit durable tumor regression. There has been much focus on the role of activation/exhaustion markers such as PD1, CD39 and TOX in TIL senescence. We found these markers were inversely expressed to Cytokine-Induced SH2 protein (CISH), a negative regulator of TCR signaling and tumor immunity in mice. To evaluate the physiological role of CISH in human TIL we developed a high-efficiency CRIPSR-based method to knock out CISH in fully mature TIL. CISH KO resulted in increased T cell receptor (TCR) avidity, tumor cytolysis and neoantigen recognition. CISH expression in the tumor resections correlated with TIL inactivity against p53 hotspot mutations and CISH KO in TIL unmasked reactivity against these universal neoantigens. While CISH KO resulted in T cell hyperactivation and expansion it did not alter maturation, perhaps by preferential PLCγ-1 and not AKT inhibition. Lastly,CISHKO in T cells increased PD1 expression and the adoptive transfer ofCishKO T cells synergistically combines with PD1 antibody blockade resulting in durable tumor regression and survival in a preclinical animal model. These data offer new insights into the regulation of neoantigen recognition, expression of activation/exhaustion markers, and functional/maturation signals in tumor-specific T cells.
S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates
Authors: Liang Joshua G. , Su Danmei , Song Tian-Zhang , Zeng Yilan , Huang Weijin , Wu Jinhua , Xu Rong , Luo Peiwen , Yang Xiaofang , Zhang Xiaodong , Luo Shuangru , Liang Ying , Li Xinglin , Huang Jiaju , Wang Qiang , Huang Xueqin , Xu Qingsong , Luo Mei , Huang Anliang , Luo Dongxia , Zhao Chenyan , Yang Fan , Han Jian-Bao , Zheng Yong-Tang , Liang Peng 
Published: September 2020

AbstractSARS-CoV-2 is the underlying cause for the COVID-19 pandemic. Like most enveloped RNA viruses, SARS-CoV-2 uses a homotrimeric surface antigen to gain entry into host cells. Here we describe S-Trimer, a native-like trimeric subunit vaccine candidate for COVID-19 based on Trimer-Tag technology. Immunization of S-Trimer with either AS03 (oil-in-water emulsion) or CpG 1018 (TLR9 agonist) plus alum adjuvants induced high-levels of neutralizing antibodies and Th1-biased cellular immune responses in animal models. Moreover, rhesus macaques immunized with adjuvanted S-Trimer were protected from SARS-CoV-2 challenge compared to vehicle controls, based on clinical observations and reduction of viral loads in lungs. Trimer-Tag may be an important new platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.
Vitexin inhibited the invasion, metastasis, and progression of human melanoma cells by targeting STAT3 signaling pathway
Authors: Zhang WenHao , Zhou LiPing , Liu Guo 
Published: September 2020

AbstractIn human melanoma cells, resistance to conventional chemotherapy and radiotherapy and rapid metastasis give melanoma a remarkable feature of the most aggressive and lethal. The low response rate of melanoma to existing treatment modalities is a substantial threat to patients and researchers. It is crucial to identify new therapeutic agents for the fatal malignancy melanoma. Vitexin is a flavonoid compound in many traditional Chinese medicines that exhibits antioxidant, anti-inflammatory and anti-tumour activities in many cancer cells. In our study, we elucidated the inhibitory effects of vitexin on invasion and metastasis in human melanoma A375 and C8161 cellsin vitro. After vitexin treatment for 24 h or 48 h, the invasive ability and migration of melanoma cells were decreased in a dose- and time-dependent manners. In western blot analysis, we verified that vitexin inhibited the expression levels of MMP-2, MMP-9, vimentin, Slug and Twist which are known as the regulators of protein degradation and promote various cell behaviours such as migration and invasion. To further investigate the target signal that may be influenced by vitexin, immunofluorescence assay was performed to observe STAT3 localization and western blot results showed that vitexin decreased the expression of the phosphorylation of kinases that inducing STAT3 activation. Accordingly, we provide inspiring insight into the basic inhibition mechanism of vitexin, which will soon be an issue due to its scientific potential for further development as a novel anti-tumour agent for the clinical therapy of human melanoma.
Adverse drug reactions associated with the use of biological agents
Authors: Machado-Alba Jorge Enrique , Jiménez-Morales Anyi Liliana , Moran-Yela Yulieth Carolina , Parrado-Fajardo Ilsa Yadira , Valladales-Restrepo Luis Fernando 
Published: September 2020

AbstractIntroductionBiotech drugs open new possibilities to treat diseases for which drug therapy is limited, but they may be associated with serious adverse drug reactions (ADRs).ObjectiveTo identify the ADRs associated with the use of biotech drugs in Colombia.MethodsThis was a retrospective study of ADR reports from 2014 to 2019, contained in the database of the pharmacovigilance program of Audifarma SA. The ADRs, groups of associated drugs, and affected organs were classified.ResultsA total of 5,415 reports of ADRs associated with biotech drugs were identified in 78 Colombian cities. A total of 76.1% of the cases corresponded to women. The majority were classified as type A (55.0%) and B (28.9%), and 16.7% were serious cases. The respiratory tract was the most commonly affected organ system (16.8%), followed by the skin and adnexa (15.6%). Antineoplastic and immunomodulatory drugs accounted for 70.6% of the reports, and the drugs related to the greatest number of ADRs were adalimumab (12.2%) and etanercept (11.6%).ConclusionsThere has been an incremental increase in the reporting of ADRs associated with the use of biotech drugs in the pharmacovigilance program, related to the strengthening and appropriation of the patient safety culture and improvement in the quality of the generated information. It is important to empower physicians and entire health teams to ensure the traceability of ADRs and to perform interdisciplinary interventions derived from pharmacovigilance at the individual and population levels.
The School Attachment Monitor - a novel computational tool for assessment of attachment in middle childhood
Authors: Rooksby Maki , Di Folco Simona , Tayarani Mohammad , Vo Dong-Bach , Huan Rui , Vinciarelli Alessandro , Brewster Stephen A. , Minnis Helen 
Published: September 2020

AbstractBackgroundAttachment research has been limited by the lack of quick and easy measures. We report development and validation of the School Attachment Monitor (SAM), a novel measure for largescale assessment of attachment in children aged 5-9, in the general population. SAM offers automatic presentation, on computer, of story-stems based on the Manchester Child Attachment Story Task (MCAST), without the need for trained administrators. SAM is delivered by novel software which interacts with child participants, starting with warm-up activities to familiarise them with the task. Children’s story completion is video recorded and augmented by ‘smart dolls’ that the child can hold and manipulate, with movement sensors for data collection. The design of SAM was informed by children of users’ age range to establish their task understanding and incorporate their innovative ideas for improving SAM software.Methods130 5-9 year old children were recruited from mainstream primary schools. In Phase 1, sixty-one children completed both SAM and MCAST. Inter-rater reliability and rating concordance was compared between SAM and MCAST. In Phase 2, a further 44 children completed SAM complete and, including those children completing SAM in Phase 1 (total n=105), a machine learning algorithm was developed using a “majority vote” procedure where, for each child, 500 non-overlapping video frames contribute to the decision.ResultsUsing manual rating, SAM-MCAST concordance was excellent (89% secure versus insecure; 97% organised versus disorganised; 86% four-way). Comparison of human ratings of SAM versus the machine learning algorithm showed over 80% concordance.ConclusionsWe have developed a new tool for measuring attachment at the population level, which has good reliability compared to a gold-standard attachment measure and has the potential for automatic rating – opening the door to measurement of attachment in large populations.
The Maintenance of Muscle Mass Is Independent of Testosterone in Adult Male Mice
Authors: Davidyan Arik , Baar Keith , Bodine Sue C. 
Published: September 2020

AbstractTestosterone is considered a potent anabolic agent in skeletal muscle with a well-established role in adolescent growth and development in males. However, alterations in the role of testosterone in the regulation of skeletal muscle mass and function throughout the lifespan has yet to be established. While some studies suggest that testosterone is important for the maintenance of skeletal muscle mass, an understanding of the role this hormone plays in young, adult, and old males with normal and low serum testosterone levels is lacking. We investigated the role testosterone plays in the maintenance of muscle mass by examining the effect of orchiectomy-induced testosterone depletion in C57Bl6 male mice at ages ranging from early postnatal through old age; the age groups we used included 1.5-, 5-, 12-, and 24-month old mice. Following 28 days of testosterone depletion, we assessed mass and fiber cross-sectional-area (CSA) of the tibialis anterior, gastrocnemius, and quadriceps muscles. In addition, we measured global rates of protein synthesis and degradation using the SuNSET method, western blots, and enzyme activity assays. 28 days of testosterone depletion resulted in smaller muscle mass in the two youngest cohorts but had no effect in the two older ones. Mean CSA decreased only in the youngest cohort and only in the tibialis anterior muscle. Testosterone depletion resulted in a general increase in proteasome activity at all ages. We did not detect changes in protein synthesis at the terminal time point. This data suggest that within physiological serum concentrations, testosterone is not important for the maintenance of muscle mass in mature male mice; however, in young mice testosterone is crucial for normal growth.
Was facial width-to-height ratio subject to sexual selection pressures? A life course approach
Authors: Hodges-Simeon Carolyn R. , Albert Graham , Richardson George B. , McHale Timothy S. , Weinberg Seth M. , Gurven Michael , Gaulin Steven J.C. 
Published: September 2020

AbstractSexual selection researchers have traditionally focused on adult sex differences; however, the schedule and pattern of sex-specific ontogeny can provide insights unobtainable from an exclusive focus on adults. Recently, it has been debated whether facial width-to-height ratio (fWHR; bi-zygomatic breadth divided by midface height) is a human secondary sexual characteristic (SSC). Here, we review current evidence, then address this debate using ontogenetic evidence, which has been under-explored in fWHR research. Facial measurements collected from males and females aged 3 to 40 (Study 1; US,n=2449), and 7 to 21 (Study 2; Bolivia,n=179) were used to calculate three fWHR variants (which we call fWHRnasion, fWHRstomion, and fWHRbrow) and two other common facial masculinity ratios (facial width-to-lower-face-height ratio, fWHRlower,and cheekbone prominence). We test whether the observed pattern of facial development exhibits patterns indicative of SSCs, i.e. differential adolescent growth in either male or female facial morphology leading to an adult sex difference. Results showed that only fWHRlowerexhibited both adult sex differences as well as the classic pattern of ontogeny for SSCs—greater lower-face growth in male adolescents relative to females. fWHRbrowwas significantly wider among both pre- and post-pubertal males in the 2D sample; post-hoc analyses revealed that the effect was driven by large sex differences in brow height, with females having higher placed brows than males across ages. In both samples, all fWHR measures were inversely associated with age; that is, human facial growth is characterized by greater relative growth in the mid-face and lower face relative to facial width. This trend continues even into middle adulthood. BMI was also a positive predictor of most of the ratios across ages, with greater BMI associated with wider faces. Researchers collecting data on fWHR should target fWHRlowerand fWHRbrowand should control for both age and BMI.