bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of two-sample methods for Mendelian randomization analyses on single large datasets
Authors: Minelli Cosetta , Del Greco M. Fabiola , van der Plaat Diana A , Bowden Jack , Sheehan Nuala A , Thompson John 
Published: April 2021

Abstract

Background
With genome-wide association data for many exposures and outcomes now available from large biobanks, one-sample Mendelian randomization (MR) is increasingly used to investigate causal relationships. Many robust MR methods are available to address pleiotropy, but these assume independence between the gene-exposure and gene-outcome association estimates. Unlike in two-sample MR, in one-sample MR the two estimates are obtained from the same individuals, and the assumption of independence does not hold in the presence of confounding.

Methods
With simulations mimicking a typical study in UK Biobank, we assessed the performance, in terms of bias and precision of the MR estimate, of the fixed-effect and (multiplicative) random-effects meta-analysis method, weighted median estimator, weighted mode estimator and MR-Egger regression, used in both one-sample and two-sample data. We considered scenarios differing by the: presence/absence of a true causal effect; amount of confounding; and presence and type of pleiotropy (none, balanced or directional).

Results
Even in the presence of substantial correlation due to confounding, all two-sample methods used in one-sample MR performed similarly to when used in two-sample MR, except for MR-Egger which resulted in bias reflecting direction and magnitude of the confounding. Such bias was much reduced in the presence of very high variability in instrument strength across variants (IGX2 of 97%).

Conclusions
Two-sample MR methods can be safely used for one-sample MR performed within large biobanks, expect for MR-Egger. MR-Egger is not recommended for one-sample MR unless the correlation between the gene-exposure and gene-outcome estimates due to confounding can be kept low, or the variability in instrument strength is very high.
Animal Models of COVID-19 II. Comparative Immunology
Authors: Veenhuis Rebecca T , Zeiss Caroline J 
Published: April 2021

Abstract
Developing strong animal models is essential for furthering our understanding of how the immune system functions in response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. The alarming speed at which SARS-CoV-2 has spread, and the high mortality rate of severe Coronavirus Disease 2019 (COVID-19), has required both basic science and clinical research to move at an unprecedented pace. Models previously developed to study the immune response against SARS-CoV have been rapidly deployed to now study SARS-CoV-2. To date, both small and large animal models are remarkably consistent when infected with SARS-CoV-2; however, certain models have proven more useful when answering specific immunological questions than others. Small animal models, such as Syrian hamsters, ferrets, and mice carrying the hACE2 transgene, appear to reliably recapitulate the initial cytokine surge seen in COVID-19 as well as show significant innate and adaptive cell infiltration in to the lung early in infection. Additionally, these models develop strong antibody responses to the virus, are protected from reinfection, and genetically modified versions exist that can be used to ask specific immunological questions. Large animal models such as rhesus and cynomologus macaques and African green monkeys are critical to understanding how the immune system responds to SARS-CoV-2 infection because they are considered to be the most similar to humans. These models are considered the gold standard for assessing vaccine efficacy and protection, and recapitulate the initial cytokine surge, immune cell infiltration into the lung, certain aspects of thrombosis, and the antibody and T-cell response to the virus. In this review, we discuss both small and large animal model studies previously used in SARS-CoV-2 research that may be useful in elucidating the immunological contributions to hallmark syndromes observed with COVID-19.
Resistance to Fipronil in the Common Bed Bug (Hemiptera: Cimicidae)
Authors: González-Morales María A , DeVries Zachary , Sierras Angela , Santangelo Richard G , Kakumanu Madhavi L , Schal Coby 
Published: April 2021

AbstractCimex lectularius L. populations have been documented worldwide to be resistant to pyrethroids and neonicotinoids, insecticides that have been widely used to control bed bugs. There is an urgent need to discover new active ingredients with different modes of action to control bed bug populations. Fipronil, a phenylpyrazole that targets the GABA receptor, has been shown to be highly effective on bed bugs. However, because fipronil shares the same target site with dieldrin, we investigated the potential of fipronil resistance in bed bugs. Resistance ratios in eight North American populations and one European population ranged from 1.4- to &gt;985-fold, with highly resistant populations on both continents. We evaluated metabolic resistance mechanisms mediated by cytochrome P450s, esterases, carboxylesterases, and glutathione S-transferases using synergists and a combination of synergists. All four detoxification enzyme classes play significant but variable roles in bed bug resistance to fipronil. Suppression of P450s and esterases with synergists eliminated resistance to fipronil in highly resistant bed bugs. Target-site insensitivity was evaluated by sequencing a fragment of the Rdl gene to detect the A302S mutation, known to confer resistance to dieldrin and fipronil in other species. All nine populations were homozygous for the wild-type genotype (susceptible phenotype). Highly resistant populations were also highly resistant to deltamethrin, suggesting that metabolic enzymes that are responsible for pyrethroid detoxification might also metabolize fipronil. It is imperative to understand the origins of fipronil resistance in the development or adoption of new active ingredients and implementation of integrated pest management programs.
The nature of the Eastern Extent in the outer halo of M31
Authors: Preston Janet , Collins Michelle , Rich R Michael , Ibata Rodrigo , Martin Nicolas F , Fardal Mark 
Published: April 2021

ABSTRACT
We present the first comprehensive spectroscopic study of the Andromeda galaxy’s Eastern Extent. This ∼4° long filamentary structure, located 70–90 kpc from the centre of M31, lies perpendicular to Andromeda’s minor axis and the Giant Stellar Stream and overlaps Stream C. In this work, we explore the properties of the Eastern Extent to look for possible connections between it, the Giant Stellar Stream and Stream C. We present the kinematics and photometry for ∼50 red giant branch stars in seven fields along the Eastern Extent. We measure the systemic velocities for these fields and find them to be −368  km s−1 ≲ $\textit {v}$ ≲ −331  km s−1, with a slight velocity gradient of −0.51 ± 0.21  km s−1 kpc−1 towards the Giant Stellar Stream. We derive the photometric metallicities for stars in the Eastern Extent, finding them to be metal-poor with values of −1.0 ≲ [Fe/H]phot ≲ −0.7 with an 〈[Fe/H]phot〉 ∼ −0.9. We find consistent properties for the Eastern Extent, Stream B and one of the substructures in Stream C, Stream Cr, plausibly linking these features. Stream Cp and its associated globular cluster, EC4, have distinctly different properties indicative of a separate structure. When we compare the properties of the Eastern Extent to those of the Giant Stellar Stream, we find them to be consistent, albeit slightly more metal-poor, such that the Eastern Extent could plausibly comprise stars stripped from the progenitor of the Giant Stellar Stream.
Chemogenetics: Beyond Lesions and Electrodes
Authors: Poth Kelly M , Texakalidis Pavlos , Boulis Nicholas M 
Published: April 2021

Abstract
The field of chemogenetics has rapidly expanded over the last decade, and engineered receptors are currently utilized in the lab to better understand molecular interactions in the nervous system. We propose that chemogenetic receptors can be used for far more than investigational purposes. The potential benefit of adding chemogenetic neuromodulation to the current neurosurgical toolkit is substantial. There are several conditions currently treated surgically, electrically, and pharmacologically in clinic, and this review highlights how chemogenetic neuromodulation could improve patient outcomes over current neurosurgical techniques. We aim to emphasize the need to take these techniques from bench to bedside.
Strategies for Disseminating and Implementing COVID-19 Vaccines in Rural Areas
Authors: Prusaczyk Beth 
Published: April 2021

Abstract
The United States has well-documented rural–urban health disparities, and it is imperative that these are not exacerbated by an inefficient rollout of coronavirus disease 2019 (COVID-19) vaccines to rural areas. In addition to the preexisting barriers to delivering and receiving health care in rural areas, such as high patient:provider ratios and long geographic distances between patients and providers, rural residents are significantly more likely to say they have no intention of receiving a COVID-19 vaccine, compared with urban residents. To overcome these barriers and ensure that rural residents receive the vaccine, officials and communities should look to previous research on how to communicate vaccine information and implement successful vaccination programs in rural areas for guidance and concrete strategies to use in their local efforts.
Graphical Abstract
Lymphopenia Is Associated With Poor Outcomes of Patients With Community-Acquired Pneumonia and Sepsis
Authors: Cilloniz Catia , Peroni Héctor José , Gabarrús Albert , García-Vidal Carolina , Pericàs Juan M , Bermejo-Martin Jesús , Torres Antoni 
Published: April 2021

Abstract

Background
Lymphopenia is a marker of poor prognosis in patients with community-acquired pneumonia (CAP), yet its impact on outcomes in patients with CAP and sepsis remains unknown. We aim to investigate the impact of lymphopenia on outcomes, risk of intensive care unit (ICU) admission, and mortality in CAP patients with sepsis.

Methods
This was a retrospective, observational study of prospectively collected data from an 800-bed tertiary teaching hospital (2005–2019).

Results
Of the 2203 patients with CAP and sepsis, 1347 (61%) did not have lymphopenia, while 856 (39%) did. When compared with the nonlymphopenic group, patients with sepsis and lymphopenia more frequently required ICU admission (P = .001), had a longer hospital length of stay (P ˂ .001), and presented with a higher rate of in-hospital (P ˂ .001) and 30-day mortality (P = .001). Multivariable analysis showed that C-reactive protein ≥15 mg/dL, lymphopenia, pleural effusion, and acute respiratory distress syndrome within 24 hours of admission were risk factors for ICU admission; age ≥80 years was independently associated with decreased ICU admission. In addition, age ≥80 years, chronic renal disease, chronic neurologic disease, being a nursing home resident, lymphopenia, and pleural effusion were independently associated with increased 30-day mortality, whereas pneumococcal vaccination, diabetes mellitus, and fever were independently associated with reduced 30-day mortality.

Conclusions
Lymphopenia was independently associated with risk of ICU admission and higher in-hospital and 30-day mortality in patients with CAP and sepsis. Early identification of lymphopenia could help identify septic patients with CAP who require or will shortly require critical care.
What Factors Shape the Substantive Representation of Lesbians, Gays and Bisexuals in Parliament? Testing the Impact of Minority Membership, Political Values and Awareness
Authors: Bönisch Lea Ewe 
Published: April 2021

AbstractThe importance of minority parliamentarians for substantive representation is widely acknowledged, but little research exists on further explanations. By studying the substantive representation of the interests of lesbians, gays, and bisexuals (LGBs), this study analyses why parliamentarians stand in for interests of minorities with an invisible characteristic. A quantitative content analysis of more than 950,000 British and Irish parliamentary questions provides the basis for the analysis (2002–2017). The study considers parliamentarians’ characteristics as explanatory factors. The results indicate that parliamentary presence is vital for LGBs. However, the most active parliamentarians are non-minority members: political values and awareness are also at play. Moreover, there are differences between the two parliaments.
Perspectives on Police Specialization in Art Theft Investigations
Authors: Runhovde Siv Rebekka 
Published: April 2021

AbstractThe concept of specialization is accepted in many fields of policing, yet most national law enforcement authorities do not regard art and cultural heritage crime as one deserving of specialist attention. Drawing on interviews with Norwegian and international stakeholders, the analysis identifies what separates art theft investigations from other investigations and when specialist knowledge becomes necessary. Findings reveal compelling arguments for specialization and establishing dedicated art crime units. Respondents voiced clear concerns regarding the level of prioritization and knowledge of art theft in the police; yet, the analysis cannot conclude that art theft investigations in Norway have necessarily suffered from an absence of specialization. To justify the establishment of a dedicated unit, first there is a need to develop consistent crime recording practices, create a national database for stolen or missing art and conduct comprehensive and systematic research to determine what characterizes the crimes and the current criminal justice response.
Translating evidence-based behavioral weight loss into a multi-level, community intervention within a community-based participatory research framework: the Wellness Engagement (WE) Project
Authors: LaRose Jessica Gokee , Lanoye Autumn , Ferrell Dwala , Lu Juan , Mosavel Maghboeba 
Published: April 2021

AbstractBlack Americans and individuals from economically disadvantaged backgrounds are at disproportionate risk for obesity, yet are underrepresented in behavioral weight loss (BWL) trials and experience less benefit from traditional programs. The Wellness Engagement (WE) Project sought to translate evidence-based BWL within a CBPR framework to promote change across multiple domains of influence in an under-resourced, predominantly Black community. The purpose of this paper is to describe the efforts we undertook to translate data from our extensive formative phase into programming well suited to meet the needs of the Petersburg community. In addition, we present data from our pilot work on feasibility and acceptability. Formative data were collected using a variety of methods including a community-wide survey, asset mapping, house chats, focus groups, and key informant interviews. In collaboration with key stakeholders and community members, evidence-based approaches to weight loss were adapted to meet the needs of the community with respect to both content and delivery modality. Materials were adapted to focus on small, realistic changes appropriate for the specific context. Behavioral groups, experiential nutrition and exercise sessions, and walking groups leveraged existing assets and were open to all community members. Feasibility and acceptability ratings were promising. Furthermore, the WE Project appeared to contribute to a culture of wellness. CBPR might be a viable approach for engaging under-resourced Black communities in behavioral weight management; larger scale implementation and evaluation efforts are needed.
Naturalistic assessment of patterns and predictors of acute headache medication use among women with comorbid migraine and overweight or obesity
Authors: Smith Kathryn E , Thomas J Graham , Steffen Kristine J , Lipton Richard B , Farris Samantha G , Pavlovic Jelena M , Bond Dale S 
Published: April 2021

Lay SummaryObesity may contribute to more severe migraine symptoms and negatively impact migraine treatment outcomes. The present study aimed to understand patterns of acute medication use among 170 women with migraine and obesity who were seeking behavioral migraine treatment. Data were collected in participants’ natural environment using experience sampling methodology, during which participants reported daily migraine symptoms for 4 weeks. Approximately, 30% of attacks were not treated with any medications, and one in five attacks (i.e., 20%) was treated with migraine-specific medication. Participants were more likely to use medication during longer and more severe attacks that started earlier in the day. Participants were also more likely to use migraine-specific medication when attacks were precipitated by an aura and associated with work-related pain interference. Questionnaire-assessed factors were not related to medication use, although older age and higher educational attainment related to more frequent use. In general, these results also suggest that naturalistically assessed factors are more salient correlates of medication use compared to questionnaires. Additional investigation of barriers to medication use is needed among younger individuals and those of lower socioeconomic status.
Investigating the mechanisms of indocyanine green (ICG) cellular uptake in sarcoma
Authors: Chan Corey D , Brookes Marcus J , Tanwani Riya , Hope Chloe , Pringle Toni A , Knight James C , Rankin Kenneth S 
Published: April 2021

AbstractIntroductionIndocyanine green (ICG) is a near infrared (NIR) dye which has been used clinically for over 50 years and has recently been utilised for fluorescence guided surgery in a number of cancer types, including sarcoma. ICG is taken up and retained by sarcoma tumours to a greater extent than normal tissue, demonstrating its potential to aid in visualisation of tumour margins. However, the mechanisms surrounding preferential ICG uptake in tumours are poorly understood.MethodsIn vitroICG cellular uptake studies were performed across a panel of four sarcoma cell lines and one breast cancer cell line, exhibiting varying proliferation rates and phenotypes. The effects of ICG concentration, incubation time, inhibition of clathrin mediated endocytosis and cell line proliferation rate on the cellular uptake of ICG were investigated using fluorescence microscopy and flow cytometry. The spatial orientation of ICG was also assessed in a patient specimen.ResultsThe level of ICG cellular uptake was dependent on ICG concentration and incubation time. Cell line proliferation rate correlated significantly to ICG uptake within 30 minutes (Rs= 1, p<0.001), whilst retention of ICG after 24hrs did not (Rs= 0.3, p=0.624). From our data, the primary mechanism of ICG uptake in sarcoma cells is via clathrin mediated endocytosis. Following the resection of a grade 3 leiomyosarcoma, ICG signal was detectable macroscopically and on 3μm sections, whilst being negative on the muscle control.ConclusionsThe use of ICG for tumour detection in sarcoma surgery may demonstrate higher utility in high grade tumours compared to low grade tumours, due to the observation of higher ICG uptake in more proliferative cell lines. It is likely that the enhanced permeability and retention (EPR) effect plays a significant role in the retention of ICG within tumours. Future work on the detection of ICG at the cellular level within human tissue sections is required, with the aid of purpose built NIR microscopes.
An intein-split transactivator for intersectional neural imaging and optogenetic manipulation
Authors: Chen Hao-Shan , Zhang Xiao-Long , Yang Rong-Rong , Wang Guang-Ling , Zhu Xin-Yue , Xu Yuan-Fang , Wang Dan-Yang , Zhang Na , Qiu Shou , Zhan Li-Jie , Shen Zhi-Ming , Xu Xiao-Hong , Long Gang , Xu Chun 
Published: April 2021

AbstractThe complexity of brain circuitry is manifested by numerous cell types based on genetic marker, location and neural connectivity. Cell-type specific recording and manipulation is essential to disentangle causal neural mechanisms in physiology and behavior; however, many current approaches are largely limited by number of intersectional features, incompatibility of common effectors and insufficient gene expression. To tackle these limitations, we devise an intein-based intersectional synthesis of transactivator (IBIST) to selectively control gene expression of common effectors in specific cell types defined by a combination of multiple features. We validate the specificity and sufficiency of IBIST to control common effectors including fluorophores, optogenetic opsins and Ca2+indicators in various intersectional conditionsin vivo. Using IBIST-based Ca2+imaging, we show that the IBIST can intersect up to five features, and that hippocampal cells tune differently to distinct emotional valences depending on the pattern of projection targets. Collectively, the IBIST multiplexes the capability to intersect cell-type features and is compatible with common effectors to effectively control gene expression, monitor and manipulate neural activities.
Identification of biomarkers and pathways of mouse embryonic fibroblasts with the dysfunction of mitochondrial DNA
Authors: Gu Hanming 
Published: April 2021

AbstractMitochondrial diseases are clinically heterogeneous which involve multiple systems such as organs that are highly dependent on metabolism. Dysfunction of mtDNA is the main cause of mitochondrial diseases that trigger inflammation and immune responses. Here, we aim to identify the biological function and pathways of MEFs with the dysfunction of mtDNA through deletion of YME1L. The gene expression profiles of GSE161735 dataset were originally created by the Illumina NovaSeq 6000 (Mus musculus) for gene biogenesis and function panel. The biological and functional pathways were analyzed by the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG), Gene Ontology (GO), and Reactom visual map. KEGG and GO results showed the metabolism and immune responses were mostly affected by the loss of mtDNA. Moreover, we discovered several interacting genes including POLR2F, HIST1H2BJ, PPP1CC, HOXB4, ARG1, APITD1, BUB1B, POLR2K, HOXC4, and HOXB3 were involved in the regulation of metabolic or cancer diseases. Further, we predicted several regulators that had the ability to affect mitochondria during the dysfunction of mtDNA by L1000fwd analysis. Thus, this study provides further insights into the mechanism of mtDNA in metabolic diseases.