bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thirteen-fold variation between states in clozapine prescriptions to United States Medicaid patients
Authors: Benito Rizelyn A. , Gatusky Michael H. , Panoussi Mariah W. , McCall Kenneth L. , Suparmanian Anisa S. , Piper Brian J. 
Published: April 2022

AbstractBackgroundClozapine was the first atypical antipsychotic for treating schizophrenia, with a long history of controversy over its usage. Guidelines currently recommend clozapine for patients diagnosed with refractory schizophrenia. However, this agent may be underutilized because of the costs associated with close monitoring of its adverse effects, particularly agranulocytosis. This is unfortunate because clozapine has demonstrated greater effectiveness compared with other antipsychotics. It is essential to examine clozapine usage to determine if it is being adequately utilized among United States (US) Medicaid patients.MethodsMedicaid data, including the number of quarterly clozapine prescriptions and the number of Medicaid enrollees in each state from 2015-2019, was collected and used to evaluate clozapine use over time. Data-analysis and figures were prepared with Excel and GraphPad Prism. Exploratory correlations were completed between prescriptions per enrollee and other factors.ResultsThe number of prescriptions, corrected for the number of enrollees in Medicaid, was generally consistent over time. However, average prescriptions per quarter were markedly lower in 2017 compared with other years, decreasing by 44.4% from 2016 average prescriptions per quarter. From 2015 to 2019, states from the upper Midwest and Northeast regions of the country had the highest average clozapine prescriptions per 10,000 Medicaid enrollees (ND: 190.0, SD: 176.6, CT: 166.2). States from the Southeast and Southwest had much lower average rates (NV: 17.9, KY: 19.3, MS: 19.7). There was an over ten-fold difference in clozapine prescriptions between states from 2015-2019 (2015 = 19.9-fold, 2016=11.4 fold, 2017=11.6 fold, 2018=13.3 fold, and 2019=13.0 fold). There was a moderate correlation of (r(48) = 0.49,p< .05) between prescriptions per 10,000 enrollees and the Medicaid spending per enrollee in each state in 2019. There was a small, but significant, correlation between prescriptions per enrollee and percent white (r(48) = 0.30,p< .05).ConclusionClozapine is an important pharmacotherapy for refractory schizophrenia. Overall, clozapine use tends to be highest among the upper Midwest and Northeast states. Further research is ongoing to better understand the origins of the thirteen-fold regional disparities in clozapine use in 2019 and the state level variation in Medicaid spending.
SARS-CoV-2 hyperimmune globulin for severely immunocompromised patients with COVID-19: a randomised, controlled, double-blind, phase 3 trial
Authors: Huygens Sammy , Hofsink Quincy , Nijhof Inger S , Goorhuis Abraham , Kater Arnon P , te Boekhorst Peter AW , Swaneveld Francis , Novotný Věra MJ , Bogers Susanne , Welkers Matthijs RA , Papageorgiou Grigorios , Rijnders Bart J , Heijmans Jarom 
Published: April 2022

SummaryBackgroundSeverely immunocompromised patients are at risk for severe COVID-19. Benefit from convalescent plasma in these patients is suggested but data from randomised trials are lacking. The aim of this study is to determine efficacy of SARS-CoV-2 hyperimmune globulin (“COVIG”) in treatment of severely immunocompromised, hospitalised COVID-19 patients.MethodsIn this randomised, controlled, double-blind, multicentre, phase 3 trial, severely immunocompromised patients who were hospitalised with symptomatic COVID-19 were randomly assigned (1:1) to receive 15 grams of COVIG or 15 grams of intravenous immunoglobulin without SARS-CoV-2 antibodies (IVIG, control). Patients included were solid organ transplant patients with three drugs from different immunosuppressive classes or patient with disease or treatment severely affecting B-cell function. Patients that required mechanical ventilation or high flow nasal oxygen were excluded. All investigators, research staff, and participants were masked to group allocation. The primary endpoint was occurrence of severe COVID-19 evaluated up until day 28 after treatment, defined as the need for mechanical ventilation, high-flow nasal oxygen, readmission for COVID-19 after hospital discharge or lack of clinical improvement on day seven or later. This trial is registered with Netherlands Trial Register (NL9436).FindingsFrom April, 2021, to July, 2021, 18 participants were enrolled at three sites in the Netherlands; 18 patients were analysed. Recruitment was halted prematurely when casirivimab/imdevimab became the recommended therapy in the Dutch COVID-19 treatment guideline for seronegative, hospitalised COVID-19 patients. Median age was 58 years and all but two were negative for SARS-CoV-2 spike IgG at baseline. Severe COVID-19 was observed in two out of ten (20%) patients treated with COVIG compared to seven of eight (88%) in the IVIG control group (p= 0·015, Fisher’s exact test).InterpretationCOVIG reduced the incidence of severe COVID-19 in severely immunocompromised patients, hospitalised with COVID-19. COVIG may be a valuable treatment in this patient group and can be used when no monoclonal antibody therapies are available.FundingThe Netherlands Organisation for Health Research and Development, Sanquin Blood Supply Foundation.
Priorities setting in mental health research: a scoping review
Authors: Benito-Amat C. , Güell E. , Molas-Gallart J. 
Published: April 2022

AbstractObjectiveResearch processes are opening to stakeholders beyond the scientific community. We analyse the user involvement in the definition of research priorities in the field of mental health. Mental disorders represent a significant disease burden at a global scale and their identification and treatment involves caregivers, patients and related social groups such as family and friends. Therefore it is an area conducive to the application of participatory methods in priority setting. We present a scoping review of participatory methods in mental health priority setting for the period 2010-2020 to shed light on their spread and characteristics, the types of groups involved and the link with the priorities identified.MethodsFirst we describe the eligibility criteria for the scoping review. We selected peer-reviewed documents published between 2010 and 2020 using MEDLINE/PubMed, PsycINFO, the Core Collection of the Web of Science and Scopus, applying controlled terms of search. We initially identified 330 documents from which we selected seventy-four after further discarding studies that were not specifically addressing priority setting in mental disorders research. We noted and classified the interest groups participating in every study.ResultsPriority setting partnerships are becoming the most frequent participatory instruments for priority setting in mental health. We identify regional differences in the extent to which such methods are being applied. When research beneficiaries participate in priority setting, prioritised research focuses on therapy, standards, education and psychology of mental disorders. When participation is limited to scientists, therapy, diagnosis, methods and standards, receive more attention.
DeepToA: An Ensemble Deep-Learning Approach to Predicting the Theater of Activity of a Microbiome
Authors: Zeng Wenhuan , Gautam Anupam , Huson Daniel H. 
Published: April 2022

AbstractMotivationMetagenomics is the study of microbiomes using DNA sequencing. A microbiome consists of an assemblage of microbes that is associated with a “theater of activity” (ToA). To what degree does the taxonomic and functional content of the former depend on the (details of the) latter? More technically, given a taxonomic and/or functional profile estimated from metagenomic sequencing data, how to predict the associated ToA? Here we present a deep learning approach to this question. We use both taxonomic and functional profiles as input. We apply node2vec to embed hierarchical taxonomic profiles into numerical vectors. We then perform dimension reduction using clustering, to address the sparseness of the taxonomic data and thus make it more amenable to deep learning algorithms. Functional features are combined with textual descriptions of protein families or domains. We present an ensemble deep-learning framework DeepToA for predicting the ‘theater of activity” of microbial community, based on taxonomic and functional profiles. We use SHAP (SHapley Additive exPlanations) values to determine which taxonomic and functional features are important for the prediction.ResultsBased on 7,560 metagenomic profiles downloaded from MGnify, classified into ten different theaters of activity, we demonstrate that DeepToA has an accuracy of 98.61%. We show that adding textual information to functional features increases the accuracy.AvailabilityOur approach is available at http://ab.inf.uni-tuebingen.de/software/deeptoa.Contactdaniel.huson@uni-tuebingen.deSupplementary informationSupplementary data are available at Bioinformatics online.
Small silencing RNAs expressed from W-linked retrocopies of Masculinizer target the male-determining gene PxyMasc during female sex determination in the Diamondback moth Plutella xylostella
Authors: Harvey-Samuel T. , Xu X. , Anderson M. A. E. , Carabajal Paladino L. , Kumar Purusothaman D. , Norman V.C. , Reitmayer C.M. , You M. , Alphey L. 
Published: April 2022

AbstractThe Lepidoptera are an insect order of cultural, economic and environmental importance, representing c. 10% of all described living species. Yet, for all but one of these species (silkmoth, Bombyx mori) the molecular genetics of how sexual fate is determined remains unknown. We investigated this in the diamondback moth (DBM - Plutella xylostella), a globally important, highly invasive and economically damaging pest of cruciferous crops. Our previous work uncovered a regulator of male sex determination in DBM – PxyMasc, a homologue of B. mori Masculinizer - which although initially expressed in embryos of both sexes, is then reduced in female embryos, leading to female-specific splicing of doublesex. Here, through sequencing small RNA libraries generated from early embryos and sexed larval pools, we identified a variety of small silencing RNAs (predominantly piRNAs) complementary to PxyMasc, whose temporal expression correlated with the reduction in PxyMasc transcript observed previously in females. Analysis of these small RNAs showed that they are expressed from tandemly-arranged, multi-copy arrays found exclusively on the W (female-specific) chromosome, which we term ‘Pxyfem’. Analysis of the Pxyfem sequences showed that they are partial cDNAs of PxyMasc mRNA transcripts, likely integrated into transposable element graveyards by the non-canonical action of retrotransposons (retrocopies), and that their apparent similarity to B. mori feminizer more probably represents convergent evolution. Our study helps elucidate the sex determination cascade in this globally important pest and highlights the ‘shortcuts’ which retrotransposition events can facilitate in the evolution of complex molecular cascades, including sex determination.Significance statementUncovering the mechanisms which species have evolved to determine sex is of fundamental interest and provides avenues for pest management through genetic manipulation of these pathways. In insects, much of what is known regarding sex determination is concentrated within the Diptera and Hymenoptera, despite other orders (e.g. Lepidoptera) being of great ecological and economic importance. Here, using small RNA sequencing of embryonic and early larval samples, we uncover an RNAi-based sex determination system which silences the male determining gene PxyMasc in the Diamondback moth (Plutella xylostella) – a global pest of cruciferous crops. We track production of these silencing RNAs back to the W-chromosome where they are expressed from partial cDNA copies of PxyMasc. Our analysis suggests these are PxyMasc ‘retrocopies’, integrated via the non-canonical action of LTR retrotransposons and that similarities between this system and the feminizer system in Bombyx mori likely represent convergent evolution.
Increased adipose tissue indices of androgen catabolism and aromatization in women with metabolic dysfunction
Authors: Ostinelli Giada , Laforest Sofia , Scott.G Denham , Gauthier Marie-Frederique , Drolet-Labelle Virginie , Scott Emma , Hould Frédéric-Simon , Marceau Simon , Homer Natalie.Z.M. , Bégin Catherine , Andrew Ruth , Tchernof André 
Published: April 2022

ABSTRACTBackgroundBody fat distribution is a risk factor for obesity-associated comorbidities, and adipose tissue dysfunction plays a role in this association. In humans, there is a sex difference in body fat distribution, and steroid hormones are known to regulate several cellular processes within adipose tissue. Our aim was to investigate if intra-adipose steroid concentration and expression or activity of steroidogenic enzymes were associated with features of adipose tissue dysfunction in individuals with severe obesity.MethodsSamples from 40 bariatric candidates (31 women, 9 men) were included in the study. Visceral (VAT) and subcutaneous adipose tissue (SAT) were collected during surgery. Adipose tissue morphology was measured by a combination of histological staining and semi-automated quantification. Following extraction, intra-adipose and plasma steroid concentrations were determined by liquid chromatography, electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Aromatase activity was estimated using product-over-substrate ratio, while AKR1C2 activity was measured directly by fluorogenic probe. Gene expression was measured by quantitative PCR.ResultsVAT aromatase activity was positively associated with VAT adipocyte hypertrophy (p-valueadj < 0.01) and negatively with plasma HDL-cholesterol (p-valueadj < 0.01), while SAT aromatase activity predicted dyslipidemia in women even after adjustment for waist circumference, age and hormonal contraceptive use. We additionally compared women with high and low visceral adiposity index (VAI) and found that VAT excess is characterized by adipose tissue dysfunction, increased androgen catabolism mirrored by increased AKR1C2 activity and higher aromatase expression and activity indices.ConclusionIn women, increased androgen catabolism or aromatization is associated with visceral adiposity and adipose tissue dysfunction.DISCLOSURE SUMMARYAT obtained consulting fees form Bausch Health, Novo Nordisk and research funding from Johnson & Johnson Medical Companies as well as Medtronic and GI Windows for studies unrelated to this manuscript. The other authors have nothing to disclose.
A one-step CRISPR-based strategy for endogenous gene tagging in Drosophila melanogaster
Authors: Xiao Yangbo , Yuan Ye , Yadlapalli Swathi 
Published: April 2022

ABSTRACTThe ability to tag endogenous genes to create fluorescent fusion proteins has revolutionized the studies of protein subcellular localization and dynamics and regulation in live cells. Here, we report a precise, rapid, and one-step endogenous gene tagging system in Drosophila melanogaster, which allows us to screen for engineered lines without the visible eye marker. Specifically, we developed an efficient screening strategy for the identification of the homologous integration events by employing a PCR-based method to characterize individual flies using only a small segment of their middle leg. Here, we detail design and construction of gRNA plasmids and donor plasmid, and methods for screening, and confirmation of engineered lines. Together, these protocols make tagging any endogenous protein in Drosophila more efficient and faster, enabling studies of a wide range of cellular processes in live cells within intact organisms.
Estimation of lift characteristics of a subscale fighter using low-cost experimental methods
Authors: Nepomuceno Leonardo Murilo , Silva Roberto Gil Annes da , Sobron Alejandro , Krus Petter , Lundström David 
Published: April 2022

Purpose
While computational methods are prevalent in aircraft conceptual design, recent advances in mechatronics and manufacturing are lowering the cost of practical experiments. Focussing on a relatively simple property, the lift curve, this study aims to increase understanding of how basic aerodynamic characteristics of a complex stealth configuration can be estimated experimentally using low-cost equipment, rapid prototyping methods and remotely piloted aircraft.

Design/methodology/approach
Lift curve estimates are obtained from a wind tunnel test of a three-dimensional-printed, 3.8%-scale model of a generic fighter and from flight testing a 14%-scale demonstrator using both a simple and a more advanced identification technique based on neural networks. These results are compared to a computational fluid dynamics study, a panel method and a straightforward, theoretical approach based on radical geometry simplifications.

Findings
Besides a good agreement in the linear region, discrepancies at high angles of attack reveal the shortcomings of each method. The remotely piloted model manages to provide consistent results beyond the physical limitations of the wind tunnel although it seems limited by instrumentation capabilities and unmodelled thrust effects.

Practical implications
Physical models can, even though low-cost experiments, expand the capabilities of other aerodynamic tools and contribute to reducing uncertainty when other estimations diverge.

Originality/value
This study highlights the limitations of commonly used aerodynamic methods and shows how low-cost prototyping and testing can complement or validate other estimations in the early study of a complex configuration.
The invisible crisis: the determinants of local food insecurity in Gauteng municipalities, South Africa
Authors: Mazenda Adrino , Molepo Nonkosazana , Mushayanyama Tinashe , Ngarava Saul 
Published: April 2022

PurposeThe purpose of this study is to estimate the determinants of household food insecurity in the Gauteng City-Region, South Africa. This is motivated by the fact that food insecurity remains a key challenge at the household level in South Africa. Furthermore, the Gauteng Province has been rapidly urbanising due to a migrant influx, both locally and internationally. The findings will assist the country in achieving its mandate on the local economic development policy, Agenda 2063 and the Sustainable Development Goals 1 and 2.Design/methodology/approachThe study adopted a quantitative cross-section design, utilising the binary logistic regression technique, drawing on the Gauteng City-Region Observatory Quality of Life 2020/2021 data, consisting of 13,616 observations, randomly drawn from nine municipalities in Gauteng City-Region.FindingsThe main findings of the study highlight unemployment, health status, education, household size, indigency and income as the main determinants of food insecurity in Gauteng City-Region. Policies towards sustainable urban agriculture, improving access to education, increasing employment and income, and health for all can help improve the food insecurity status of households in the Gauteng City-Region.Research limitations/implicationsFurther studies would require an in-depth assessment of household coping mechanisms, as well as the influence of household income (notably government social grants) and access to credit on household food security status, to better understand the dynamics of food security in the Gauteng City-Region.Practical implicationsDeterminants of food insecurity should be considered when developing and implementing policies to reduce food insecurity in urban municipalities.Social implicationsThe study is of interest as it interdicts food insecurity issues, which have an effect on socio-economic well-being.Originality/valueThe study adds value by providing evidence on the determinants of food insecurity in an urban setting in a developing country. Gauteng is the richest of all provinces in South Africa and is also at the receiving end of internal and international migration. Factors affecting food insecurity have changed in the nine cities. This compromises nutrition safety and calls for targeted policy interventions.
Invoking blockchain technology in e-government services: a cybernetic perspective
Authors: Saxena Stuti , Shao Deo , Nikiforova Anastasija , Thapliyal Richa 
Published: April 2022

Purpose
This paper aims to provide insights into the integration of blockchain technology in e-government services.

Design/methodology/approach
The article invokes an exploratory approach to emphasize the possibilities of integrating blockchain technology in e-government services. A cybernetic model is detailed in the paper for bridging the gulf between blockchain and e-government.

Findings
The integration of blockchain technology in e-government services is capable of enhancing the efficiency and effectiveness of service delivery. Furthermore, this integration would facilitate in maintaining the privacy of the online transactions.

Originality/value
Hitherto, studies have focused on the blockchain technology in many sectors; however, the integration and utility of blockchain technology for the government sector have remained unexplored. The current study seeks to fill this gap.
Akshayakalpa farms – a case of rural innovation
Authors: Guruprasad Leena S. , T.K. Ashwini , Bhat Prathima K. 
Published: April 2022

Learning outcomes
1. Analyze the factors influencing the creation of a social enterprise, while appreciating the theoretical perspectives on social entrepreneurship and social innovations. 2. Analyze the impact of social enterprises on sustainable development. 3. Recognize the need for different types of strategies in the varied situation. 4. Analyze the business model.

Case overview/synopsis
Shashi Kumar, the CEO of Akshayakalpa Farms & Foods Pvt Ltd (Akshayakalpa), is determined to take the business to the next growth level. He has integrated technology to measure and monitor the quality of milk and to reach out to tech-savvy customers. Owing to the preservative-free and short life of milk, he believes that redesigning the marketing and distribution strategies is the only way to ensure the massive expansion and growth that will enable Akshayakalpa to reach out to customers directly and quickly. Another issue he was facing was a lag in receivables. Their receivables from vendors were delayed and held up because of issues related to product spoilage and returns. This has posed a liquidity challenge to Akshayakalpa. Amidst all these challenges, he wants to develop the best strategy to take the business forward to the next level.

Complexity academic level
This case can be used in undergraduate or postgraduate courses in Management, Social Entrepreneurship and Business Sustainability with special relevance to social enterprise creation, enterprise growth strategies, sustainable development, sustainable business models, etc.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 3: Entrepreneurship.