bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunotherapy and cardiovascular diseases: novel avenues for immunotherapeutic approaches
Authors: Bonfiglio C A , Weber C , Atzler D , Lutgens E 
Published: July 2021

Abstract
As current therapies for cardiovascular disease (CVD), predominantly based on lipid lowering, still face an unacceptable residual risk, novel treatment strategies are being explored. Besides lipids, inflammatory processes play a major role in the pathogenesis of atherosclerosis, the underlying cause of the majority of CVD. The first clinical trials targeting the interleukin-1β-inflammasome axis have shown that targeting this pathway is successful in reducing cardiovascular events but did not decrease overall CVD mortality. Hence, novel and improved immunotherapeutics to treat CVD are being awaited.
ROS-responsive biomimetic nanoparticles for potential application in targeted anti-atherosclerosis
Authors: Tang Dan , Wang Yi , Wijaya Andy , Liu Boyan , Maruf Ali , Wang Jinxuan , Xu Jianxiong , Liao Xiaoling , Wu Wei , Wang Guixue 
Published: July 2021

Abstract
The development of nanomedicines provides new opportunities for the treatment of atherosclerosis (AS) due to their great advantages such as the improved drug solubility, enhanced bioavailability and reduced side effects. Despite these advantages, nanomedicines are still facing some challenges. The problems remain in the short circulation life, lack of specific targeting and poor drug release controllability. In order to overcome the shortages of conventional nanomedicines, the combination of biomimetic strategy with smart nanoagents has been proposed. In light with the high reactive oxygen species (ROS) level in AS microenvironment and the fact that macrophages play a critical role in the pathogenesis of AS, we fabricated ROS-responsive biomimetic nanoparticles (NPs), which camouflaged macrophage membrane (MM) on ROS-responsive NPs loaded with rapamycin (RNPs) for potential application in AS therapy. The resulting ROS-responsive biomimetic NPs (MM/RNPs) exhibited favorable hydrodynamic size with negative surface charge, retained the functional proteins from MM, and showed ROS-responsive drug release. Because of the biomimetic camouflaging on surface, MM/RNPs could effectively escape from macrophages uptake and target to inflammatory endothelial cells. Meanwhile, MM/RNPs could inhibit the proliferation of macrophages and smooth muscle cells in vitro. Furthermore, the MM-coated NPs were found to be nontoxic in both cytotoxicity assay and in vivo toxicity evaluation. Consequently, these results demonstrated that MM/RNPs could be a potential candidate of drug delivery system for safe and effective anti-AS applications.
Bbc3 Loss Enhances Survival and Protein Clearance in Neurons Exposed to the Organophosphate Pesticide Chlorpyrifos
Authors: Anderson Faith L , von Herrmann Katharine M , Young Alison L , Havrda Matthew C 
Published: July 2021

Abstract
Exposure to environmental toxicants can increase the risk of developing age-related neurodegenerative disorders. Exposure to the widely used organophosphate pesticide chlorpyrifos (CPF) is associated with increased risk of developing Alzheimer’s disease and Parkinson’s disease, but the cellular mechanisms underlying CPF toxicity in neurons are not completely understood. We evaluated CPF toxicity in mouse primary cortical neuronal cultures, using RNA-sequencing to identify cellular pathways modulated by CPF. CPF exposure altered the expression of genes associated with intrinsic apoptosis, significantly elevating expression of the pro-apoptotic mediator Bbc3/Puma. Bbc3 loss attenuated CPF driven neurotoxicity, induction of other intrinsic apoptosis regulatory genes including Trp53 and Pmaip1 (encoding the NOXA protein), and cleavage of apoptosis executors caspase 3 and poly (ADP-ribose) polymerase (PARP). CPF exposure was associated with enhanced expression of endoplasmic reticulum stress-related genes and proteins and the accumulation of high molecular weight protein species in primary neuronal cultures. No evidence of alterations in the ubiquitin-proteosome system were observed, however, autophagy-related proteins were upregulated in CPF-treated Bbc3−/− neuronal cultures compared with identically exposed WT cultures. Elevated autophagy-related protein expression in Bbc3−/− neuronal cultures was associated with a reduction in CPF-induced high molecular weight alpha-synuclein and tau immunoreactive protein aggregates. Studies indicate that Bbc3−/− neuronal cultures enhance the endoplasmic reticulum stress response and upregulate protein clearance mechanisms as a component of resistance to CPF-mediated toxicity.
A qualitative study of patient, caregiver, doctor and nurse views of factors influencing lumbar puncture uptake in Zambia
Authors: Elafros Melissa A , Belessiotis-Richards Clara , Birbeck Gretchen L , Bond Virginia , Sikazwe Izukanji , Kvalsund Michelle P 
Published: July 2021

AbstractBackgroundUptake of lumbar puncture (LP) remains low in regions with a high prevalence of central nervous system (CNS) infections like Zambia. Efforts to improve uptake are hindered by limited understanding of factors influencing LP uptake.MethodsSemistructured qualitative interviews were conducted with patients with suspected CNS infection, caregivers, doctors and nurses at the University Teaching Hospitals in 2016. Questions focused on LP experiences, knowledge, the consent process and health system barriers to LP among patients with an LP indication. Interviews were transcribed, translated to English and analysed using a thematic approach.ResultsWe recruited 24 adult patients, 36 caregivers of adult patients, 63 caregivers of paediatric patients, 20 doctors and 30 nurses (173 in total). LP barriers arose from both patients/caregivers and health providers and included community apprehension about LP, proxy (family) consensus consent practices, competing clinical demands, wariness of patient/caregiver responses, limitations in consumables and time to complete the LP. This could result in consent not being obtained correctly. LP enablers included patient/caregiver perceived LP utility, provider comfort with LP and in-person counselling.ConclusionsLP uptake is a complex sociocultural process influenced by patient, healthcare and community-level factors. Interventions to improve uptake must address multiple barriers to be successful.
Paraphyly and low levels of genetic divergence in morphologically distinct taxa: revision of the Pseudoanthidium scapulare complex of carder bees (Apoidea: Megachilidae: Anthidiini)
Authors: Litman Jessica R , Fateryga Alexander V , Griswold Terry L , Aubert Matthieu , Proshchalykin Maxim Yu , Le Divelec Romain , Burrows Skyler , Praz Christophe J 
Published: July 2021

Abstract
The Palaearctic complex of anthidiine bees closely related to Pseudoanthidium scapulare has long been a source of unresolved taxonomic and systematic issues. Until now, the number of species in the complex and their geographical distributions were largely unclear, thus complicating the compilation of accurate species checklists and hindering conservation efforts. In order to address these issues, we use morphology and mitochondrial cytochrome c oxidase subunit I (COI) sequences, combined with a thorough examination of the relevant literature and type material, to delimit species within this complex, assign names to species and clarify geographical ranges. An unexpected result was that a certain number of morphologically distinct taxa exhibited low levels of genetic divergence at the COI locus, resulting in species paraphyly. A set of ultra-conserved elements (UCEs) was also sequenced in order to further investigate relationships among these taxa. One morphologically distinct species was also paraphyletic using UCE data, hinting at recent species divergences and genetic exchange at zones of contact between morphologically well-differentiated taxa. The results of our study reveal the presence of ten species in this complex, including a previously overlooked species for western continental Europe. A complete diagnosis of the males and females of these species is provided, as are maps detailing the geographic distributions of each. An illustrated identification key to the males and females of each species is presented. Two new species are described, Pseudoanthidium kaspareki sp. nov. and P. rozeni sp. nov. New synonymy is established for several species and Pseudoanthidium palestinicum and P. tropicum are raised to species level. The new combination, Icteranthidium floripetum comb. nov. is also established. Lectotypes are designated for the following species: Anthidium eversmanni, A. floripetum, A. frontale, A. karakalense, A. nanum and A. reptans. Previously unpublished lectotype designations are published here for A. sinuatum and A. tenellum.
Staged Treatment of Asymmetrical Age-related Changes in the Eyelid and Thyroid Eye Disease
Authors: Takahira Tokuei , Akita Shinsuke , Maei Haruka , Kubota Yoshitaka , Mitsukawa Nobuyuki 
Published: July 2021

Summary:
Blepharoplasty for thyroid eye disease (TED) has been indicated for the purpose of improving upper and lower eyelid retraction caused by exophthalmos. Both aponeurotic blepharoptosis and aging lower eyelid are common conditions that require plastic surgeries and could be complicated with other disease conditions, such as TED. This is the first report of planned and staged treatment of the contradictory pathophysiologies of aging changes of upper and lower eyelids associated with TED. A 59-year-old woman suffered complicated bilateral asymmetric aponeurosis blepharoptosis of the lower and upper eyelids, caused by both advanced aging and TED. To achieve aesthetic improvement, three-stage surgical treatments were planned, as follows: (1) Orbital decompression for exophthalmos; (2) Extraocular muscle surgery, if necessary; (3) Blepharoplasty for functional and aesthetic abnormalities due to loosening of the upper and lower eyelids. After medial and lateral orbital floors were opened bilaterally, the patient did not need extraocular surgery. As the final step, levator aponeurosis advancement procedure was performed in the upper eyelids for bilateral asymmetrical aponeurotic blepharoptosis, and transitional lower blepharoplasty using a skin-muscle flap technique via a sub-ciliary incision was performed in the lower eyelids for age-related loosening. The typical face displayed by Graves’ disease disappeared, and the symptoms associated with loosening of the upper and lower eyelids improved substantially. Improvement of exophthalmos by orbital decompression revealed the severity of the blepharoptosis and the aging change of lower eyelid. Step-by-step planning from decompression surgery to upper and lower blepharoplasty could lead to sufficient improvement in the facial appearance in TED.
Alpha Before Beta
Authors: Satapathy Swayamjeet , Sood Ashwani , Das Chandan Krushna , Kavanal Anwin Joseph , Mittal Bhagwant Rai 
Published: July 2021

Abstract
The utility of β-emitter 177Lu-DOTATATE in patients of neuroendocrine tumors (NETs) with widespread skeletal metastases is limited by its relatively modest response rates and a significant concern for hematotoxicity. In such situations, targeted α therapy with 225Ac-DOTATATE can be potentially beneficial. In this report, a 46-year-old man with rectal NET and extensive skeletal metastases was treated upfront with 6 cycles of 225Ac-DOTATATE at 8 weeks’ intervals. The patient showed excellent symptomatic, biochemical, and radiological response with no grade 3/4 adverse events. The first-line use of 225Ac-DOTATATE, therefore, presents a novel strategy for metastatic NETs with high skeletal disease burden.
A brief review of vertebrate sex evolution with a pledge for integrative research: towards ‘sexomics’
Authors: Stöck Matthias , Kratochvíl Lukáš , Kuhl Heiner , Rovatsos Michail , Evans Ben J. , Suh Alexander , Valenzuela Nicole , Veyrunes Frédéric , Zhou Qi , Gamble Tony , Capel Blanche , Schartl Manfred , Guiguen Yann 
Published: July 2021

Triggers and biological processes controlling male or female gonadal differentiation vary in vertebrates, with sex determination (SD) governed by environmental factors or simple to complex genetic mechanisms that evolved repeatedly and independently in various groups. Here, we review sex evolution across major clades of vertebrates with information on SD, sexual development and reproductive modes. We offer an up-to-date review of divergence times, species diversity, genomic resources, genome size, occurrence and nature of polyploids, SD systems, sex chromosomes, SD genes, dosage compensation and sex-biased gene expression. Advances in sequencing technologies now enable us to study the evolution of SD at broader evolutionary scales, and we now hope to pursue asexomicsintegrative research initiative across vertebrates. The vertebratesexomecomprises interdisciplinary and integrated information on sexual differentiation, development and reproduction at all biological levels, from genomes, transcriptomes and proteomes, to the organs involved in sexual and sex-specific processes, including gonads, secondary sex organs and those with transcriptional sex-bias. Thesexomealso includes ontogenetic and behavioural aspects of sexual differentiation, including malfunction and impairment of SD, sexual differentiation and fertility. Starting from data generated by high-throughput approaches, we encourage others to contribute expertise to building understanding of thesexomesof many key vertebrate species.This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part I)’.
Vaccine Confidence and Hesitancy at the start of COVID-19 vaccine deployment in the UK: An embedded mixed-methods study
Authors: Roberts Chrissy h , Brindle Hannah , Rogers Nina T , Eggo Rosalind M , Enria Luisa , Lees Shelley 
Published: July 2021

ABSTRACTIntroductionApproval for the use of COVID-19 vaccines has been granted in a number of countries but there are concerns that vaccine uptake may be low amongst certain groups.MethodsThis study used a mixed methods approach based on online survey and an embedded quantitative/qualitative design to explore perceptions and attitudes that were associated with intention to either accept or refuse offers of vaccination in different demographic groups during the early stages of the UK’s mass COVID-19 vaccination programme (December 2020). Analysis used multivariate logistic regression, structural text modelling and anthropological assessments.ResultsOf 4,535 respondents, 85% (n=3,859) were willing to have a COVID-19 vaccine. The rapidity of vaccine development and uncertainties about safety were common reasons for COVID-19 vaccine hesitancy. There was no evidence for the widespread influence of mis-information, although broader vaccine hesitancy was associated with intentions to refuse COVID-19 vaccines (OR 20.60, 95% CI 14.20-30.30, p<0.001). Low levels of trust in the decision-making (OR 1.63, 95% CI 1.08, 2.48, p=0.021) and truthfulness (OR 8.76, 95% CI 4.15-19.90, p<0.001) of the UK government were independently associated with higher odds of refusing COVID-19 vaccines. Compared to political centrists, conservatives and liberals were respectively more (OR 2.05, 95%CI 1.51-2.80, p<0.001) and less (OR 0.30, 95% CI 0.22-0.41, p<0.001) likely to refuse offered vaccines. Those who were willing to be vaccinated cited both personal and public protection as reasons, with some alluding to having a sense of collective responsibility.ConclusionDominant narratives of COVID-19 vaccine hesitancy are misconceived as primarily being driven by misinformation. Key indicators of UK vaccine acceptance include prior behaviours, transparency of the scientific process of vaccine development, mistrust in science and leadership and individual political views. Vaccine programmes should leverage the sense of altruism, citizenship and collective responsibility that motivated many participants to get vaccinated.
Sequencing SARS-CoV-2 in Slovakia: An Unofficial Genomic Surveillance Report
Authors: Brejová Broňa , Hodorová Viktória , Boršová Kristína , Čabanová Viktória , Szemes Tomáš , Mišík Matej , Klempa Boris , Nosek Jozef , Vinař Tomáš 
Published: July 2021

AbstractWe present an unofficial SARS-CoV-2 genomic surveillance report from Slovakia based on approximately 3500 samples sequenced between March 2020 and May 2021. Early samples show multiple independent imports of SARS-CoV-2 from other countries. In Fall 2020, three virus variants (B.1.160, B.1.1.170, B.1.258) dominated as the number of cases increased. In November 2020, B.1.1.7 (alpha) variant was introduced in Slovakia and quickly became the most prevalent variant in the country (> 75% of new cases by early February 2021 and > 95% in mid-March).
Racial Inequalities in Alcohol Use Disorder Diagnosis in a Sample of 700,000 Veterans
Authors: Vickers-Smith Rachel , Justice Amy C. , Becker William C. , Rentsch Christopher T. , Curtis Brenda , Fernander Anita , Hartwell Emily E. , Ighodaro Eseosa T. , Kember Rachel L. , Tate Janet , Kranzler Henry R. 
Published: July 2021

AbstractBackgroundStudies show that Black and Hispanic Veterans have a higher prevalence of alcohol use disorder (AUD) than White Veterans. We examined whether the relationship between self-reported race/ethnicity and AUD diagnosis varies by self-reported alcohol consumption.MethodsThe sample included 700,013 Black, Hispanic, and White Veterans enrolled in the Million Veteran Program cohort. Alcohol consumption was defined as an individual’s maximum score on the Alcohol Use Disorders Identification Test–Consumption (AUDIT-C) questionnaire, a screen for hazardous or harmful drinking. The primary outcome, AUD, was defined by the presence of ICD-9/10 codes in the electronic health record. We used logistic regression with interactions to assess the association between race/ethnicity and AUD by maximum AUDIT-C score.ResultsBlack and Hispanic Veterans were more likely to have an AUD diagnosis than White Veterans despite similar levels of alcohol consumption. The difference was greatest between Black and White men. At all but the lowest and highest levels of alcohol consumption, Black men had 24%-111% greater odds of an AUD diagnosis. The association between race/ethnicity and AUD diagnosis remained after adjustment for alcohol consumption, alcohol-related disorders, and other potential confounders.ConclusionsThe large discrepancy in AUD diagnosis across groups despite a similar distribution of alcohol consumption measures suggests that Veterans are differentially assigned an AUD diagnosis by race/ethnicity. Efforts are needed to examine the causes of the observed differences and to implement changes, such as structured diagnostic methods, to address a likely contributor to racial differences (i.e., bias) in AUD diagnosis.
Gender Based Differences in Risks and Comorbidities in Patients Hospitalized with Acute Exacerbation of COPD: A Retrospective Observational study in Eastern-Nepal
Authors: Baral Nischit , Karki Nabin R. , Parajuli Prem Raj , Bell Laura , Paudel Bidhan Raj , Paudel Anish C. , Adhikari Nirajan , Luitel Pankaj , Bhatta Narendra 
Published: July 2021

AbstractBackgroundAcute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) share a complex relationship with gender, risk, and co-morbidities. There is paucity of data on the gender-based differences in the prevalence of risks and co-morbidities in AECOPD in Nepal.MethodsWe performed a retrospective cross-sectional study where data were collected from medical records of adult patients (age >40 years), hospitalized with clinical diagnosis of AECOPD in a tertiary level University hospital in eastern Nepal from April 15, 2014 to October 15, 2014 were included. Data analysis was performed by using SPSS software (Version 26.0, 2020; SPSS Inc., Chicago, IL).ResultsOf the 256 patients with the primary diagnosis of AECOPD, mean age was 69 years and 65.63% (n=168) of hospitalizations were female population. Compared to males, 64.32 % (n=137) of active smokers were females p= 0.299, 76.19% (n=32) of diabetics were females p= 0.155, 72.86% (n=51) of hypertensive were females, p= 0.143, 50% (n= 6) of underlying Atrial fibrillation were in females p= 0.350, 57.50% (n= 23) of anemics were females p= 0.278, 100% (n= 3) of asthmatics were females p= 0.553, 44.44% (n= 8) of Pulmonary tuberculosis were in females p= 0.070, and 78.76% (n= 89) of indoor air pollution exposure was in females p <0.001.ConclusionFemales have higher association to indoor air pollution exposure compared to male and this association was found to be statistically significant. The higher incidence of AECOPD hospitalization in females can be explained by these findings. We need larger studies to validate these findings.
Sequencing SARS-CoV-2 from Antigen Tests
Authors: Nazario-Toole Ashley , Nguyen Holly M. , Xia Hui , Frankel Dianne N. , Kieffer John W. , Gibbons Thomas F. 
Published: July 2021

AbstractGenomic surveillance empowers agile responses to SARS-CoV-2 by enabling scientists and public health analysts to issue recommendations aimed at slowing transmission, prioritizing contact tracing, and building a robust genomic sequencing surveillance strategy. Since the start of the pandemic, real time RT-PCR diagnostic testing from upper respiratory specimens, such as nasopharyngeal (NP) swabs, has been the standard. Moreover, respiratory samples in viral transport media are the ideal specimen for SARS-CoV-2 whole-genome sequencing (WGS). In early 2021, many clinicians transitioned to antigen-based SARS-CoV-2 detection tests, which use anterior nasal swabs for SARS-CoV-2 antigen detection. Despite this shift in testing methods, the need for whole-genome sequence surveillance remains. Thus, we developed a workflow for whole-genome sequencing with antigen test-derived swabs as an input rather than nasopharyngeal swabs. In this study, we use excess clinical specimens processed using the BinaxNOW™ COVID-19 Ag Card. We demonstrate that whole-genome sequencing from antigen tests is feasible and yields similar results from RT-PCR-based assays utilizing a swab in viral transport media.