bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primaquine-loaded transdermal patch for treating malaria: design, development, and characterization
Authors: Sharma Pankaj , Tailang Mukul 
Published: October 2022

Abstract
Background
The goal of the current study was to create, improve, and test a transdermal patch loaded with primaquine for the treatment of malaria. Several ingredients were used to create the transdermal patch. For the choosing of polymers, placebo patches were created. The optimization of polymer ratios for patch development and testing their impact on tensile strength, in vitro drug release, in vitro drug permeation, and ex vivo drug permeation employed response surface methods. The F5 formulation was chosen as the optimal formulation based on these answers to the data. The stability of the F5 formulation was examined. According to the findings of trials on acute skin irritation, no place where transdermal patches were given showed any signs of clinical abnormalities or a change in body weight. No erythema or edema of the skin was seen in the rabbit’s skin.

Results
It was observed that tensile strength of the transdermal films formulated with Eudragit RL100 and hydroxypropyl methylcellulose (Pmix) was found between 0.32 ± 0.017 and 0.59 ± 0.013 kg/cm2, which were 0.32 ± 0.017 (F1), 0.36 ± 0.012 (F2), 0.35 ± 0.015 (F3) for Pmix ratio 1:1, 0.42 ± 0.011 (F4), 0.49 ± 0.010 (F5), 0.55 ± 0.016 (F6) for Pmix ratio 1:2 and 0.56 ± 0.014 (F7), 0.57 ± 0.010 (F8), 0.59 ± 0.013 (F9) for Pmix ratio 1:3. Data fitting to the Peppas, Hixon–Crowell, Higuchi, and Zero-order models was used to examine the optimized transdermal patch (F5) release kinetic mechanism. Data comparison was done using the correlation coefficient (R2). Zero-order had an observed correlation coefficient (R2) of 0.9988, which was greater than that for other models. Therefore, it was clear that the medication was released from the formulation after the Zero-order release.

Conclusion
The ideal thickness, percent elongation, and tensile strength of the primaquine therapeutic transdermal patches were prepared for transdermal delivery. The therapeutic transdermal patch was prepared by using Eudragit RL100: HPMC K15M (1:2) into the patch because this combination was responsible for the significant delivery of the drug into the bloodstream. The therapeutic transdermal patch has a notable penetration rate. Dimethyl sulfoxide was used as a permeation enhancer, which helped to obtain a high penetration rate. The statistical analysis was used to support the improved formulation. The therapeutic transdermal patch is a potential vehicle for the administration of primaquine, according to stability studies.
Two-way language immersion in Estonia: parents’ expectations, experiences, and assessment of programme performance
Authors: Gusjuk Natalja , Tuul Maire , Õun Tiia 
Published: October 2022

Globaliseeruvas ühiskonnas muutub järjest olulisemaks mitme keele õppimine juba koolieelses eas. Pakkumaks eesti ja vene emakeelega lastele võrdseid võimalusi teise keele omandamiseks, avati 2015. aasta sügisel Eestis esimesed kahesuunalise keelekümbluse rühmad. Artikli eesmärk on anda nelja esimese kahesuunalise keelekümbluse rühma laste vanemate kirjalikule küsitlusele tuginedes ülevaade lastevanemate ootustest, kogemustest ja hinnangutest programmi tulemuslikkusele lapsega kodus räägitavast keelest lähtuvalt. Kirjalikus küsitluses osales 54 lapsevanemat, kellest 31-l oli kodune keel eesti keel ning 23-l vene keel. Selgus, et kuigi erineva kodukeelega laste vanemate põhjendused, miks kahesuunalise keelekümbluse kasuks otsustati, olid erinevad, ollakse kodukeelest sõltumata enamasti väga rahul nii lapse arengu kui ka programmiga tervikuna. Samas toodi välja arenguvõimalusi mudeli rakendamisel, näiteks leiti, et rühmas võiks käia ühevanuselised lapsed.
Summary
Online Learning via Offline Greedy Algorithms: Applications in Market Design and Optimization
Authors: Niazadeh Rad , Golrezaei Negin , Wang Joshua , Susan Fransisca , Badanidiyuru Ashwinkumar 
Published: October 2022

Motivated by online decision making in time-varying combinatorial environments, we study the problem of transforming offline algorithms to their online counterparts. We focus on offline combinatorial problems that are amenable to a constant factor approximation using a greedy algorithm that is robust to local errors. For such problems, we provide a general framework that efficiently transforms offline robust greedy algorithms to online ones using Blackwell approachability. We show that the resulting online algorithms have [Formula: see text] (approximate) regret under the full information setting. We further introduce a bandit extension of Blackwell approachability that we call Bandit Blackwell approachability. We leverage this notion to transform greedy robust offline algorithms into a [Formula: see text] (approximate) regret in the bandit setting. Demonstrating the flexibility of our framework, we apply our offline-to-online transformation to several problems at the intersection of revenue management, market design, and online optimization, including product ranking optimization in online platforms, reserve price optimization in auctions, and submodular maximization. We also extend our reduction to greedy-like first-order methods used in continuous optimization, such as those used for maximizing continuous strong DR monotone submodular functions subject to convex constraints. We show that our transformation, when applied to these applications, leads to new regret bounds or improves the current known bounds. We complement our theoretical studies by conducting numerical simulations for two of our applications, in both of which we observe that the numerical performance of our transformations outperforms the theoretical guarantees in practical instances. This paper was accepted by George Shanthikumar, data science. Funding: R. Niazadeh was supported by research funding from University of Chicago Booth School of Business. N. Golrezaei was supported in part by the Young Investigator Program Award from the Office of Naval Research [N00014-21-1-2776] and the MIT Research Support Award. Supplemental Material: The Online Appendix is available at https://doi.org/10.1287/mnsc.2022.4558
iPiDA-GCN: Identification of piRNA-disease associations based on Graph Convolutional Network
Authors: Hou Jialu , Wei Hang , Liu Bin 
Published: October 2022

Motivation
Piwi-interacting RNAs (piRNAs) play a critical role in the progression of various diseases. Accurately identifying the associations between piRNAs and diseases is important for diagnosing and prognosticating diseases. Although some computational methods have been proposed to detect piRNA-disease associations, it is challenging for these methods to effectively capture nonlinear and complex relationships between piRNAs and diseases because of the limited training data and insufficient association representation.

Results
With the growth of piRNA-disease association data, it is possible to design a more complex machine learning method to solve this problem. In this study, we propose a computational method called iPiDA-GCN for piRNA-disease association identification based on graph convolutional networks (GCNs). The iPiDA-GCN predictor constructs the graphs based on piRNA sequence information, disease semantic information and known piRNA-disease associations. Two GCNs (Asso-GCN and Sim-GCN) are used to extract the features of both piRNAs and diseases by capturing the association patterns from piRNA-disease interaction network and two similarity networks. GCNs can capture complex network structure information from these networks, and learn discriminative features. Finally, the full connection networks and inner production are utilized as the output module to predict piRNA-disease association scores. Experimental results demonstrate that iPiDA-GCN achieves better performance than the other state-of-the-art methods, benefitted from the discriminative features extracted by Asso-GCN and Sim-GCN. The iPiDA-GCN predictor is able to detect new piRNA-disease associations to reveal the potential pathogenesis at the RNA level. The data and source code are available at http://bliulab.net/iPiDA-GCN/.
Homocysteine thiolactone contributes to the prognostic value of fibrin clot structure/function in coronary artery disease
Authors: Sikora Marta , Skrzydlewski Paweł , Perła-Kaján Joanna , Jakubowski Hieronim 
Published: October 2022

Fibrin clot structure/function contributes to cardiovascular disease. We examined sulfur-containing metabolites as determinants of fibrin clot lysis time (CLT) and maximum absorbance (Absmax) in relation to outcomes in coronary artery disease (CAD) patients. Effects of B-vitamin/folate therapy on CLT and Absmax were studied. Plasma samples were collected from 1,952 CAD patients randomized in a 2 x 2 factorial design to (i) folic acid, vitamins B12, B6; (ii) folic acid, vitamin B12; (iii) vitamin B6; (iv) placebo for 3.8 years in the Western Norway B-Vitamin Intervention Trial. Clot lysis time (CLT) and maximum absorbance (Absmax) were determined using a validated turbidimetric assay. Acute myocardial infarction (AMI) and mortality were assessed during a 7-year follow-up. Data were analyzed using bivariate and multiple regression. Survival free of events was studied using Kaplan Mayer plots. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. Baseline urinary homocysteine (uHcy)-thiolactone and plasma cysteine (Cys) were significantly associated with CLT while plasma total Hcy was significantly associated with Absmax, independently of fibrinogen, triglycerides, vitamin E, glomerular filtration rate, body mass index, age, sex plasma creatinine, CRP, HDL-C, ApoA1, and previous diseases. B-vitamins/folate did not affect CLT and Absmax. Kaplan-Meier analysis showed associations of increased baseline CLT and Absmax with worse outcomes. In Cox regression analysis, baseline CLT and Absmax (>cutoff) predicted AMI (CLT: HR 1.58, 95% CI 1.10–2.28; P = 0.013. Absmax: HR 3.22, CI 1.19–8.69; P = 0.021) and mortality (CLT: HR 2.54, 95% CI 1.40–4.63; P = 0.002. Absmax: 2.39, 95% CI 1.17–4.92; P = 0.017). After adjustments for other prognostic biomarkers these associations remained significant. Cys and uHcy-thiolactone, but not tHcy, were significant predictors of AMI in Cox regression models that included CLT. Conclusions uHcy-thiolactone and plasma Cys are novel determinants of CLT, an important predictor of adverse CAD outcomes. CLT and Absmax were not affected by B-vitamin/folate therapy, which could account for the lack of efficacy of such therapy in CAD.
Trial registration: URL: http://clinicaltrials.gov. Identifier: NCT00354081.
Healthcare claims-based Lyme disease case-finding algorithms in the United States: A systematic literature review
Authors: Nam Young Hee , Willis Sarah J. , Mendelsohn Aaron B. , Forrow Susan , Gessner Bradford D. , Stark James H. , Brown Jeffrey S. , Pugh Sarah 
Published: October 2022

Background and objective
Lyme disease (LD) is the fifth most commonly reported notifiable infectious disease in the United States (US) with approximately 35,000 cases reported in 2019 via public health surveillance. However, healthcare claims-based studies estimate that the number of LD cases is >10 times larger than reported through surveillance. To assess the burden of LD using healthcare claims data and the effectiveness of interventions for LD prevention and treatment, it is important to use validated well-performing LD case-finding algorithms (“LD algorithms”). We conducted a systematic literature review to identify LD algorithms used with US healthcare claims data and their validation status.

Methods
We searched PubMed and Embase for articles published in English since January 1, 2000 (search date: February 20, 2021), using the following search terms: (1) “Lyme disease”; and (2) “claim*” or “administrative* data”; and (3) “United States” or “the US*”. We then reviewed the titles, abstracts, full texts, and bibliographies of the articles to select eligible articles, i.e., those describing LD algorithms used with US healthcare claims data.

Results
We identified 15 eligible articles. Of these, seven studies used LD algorithms with LD diagnosis codes only, four studies used LD diagnosis codes and antibiotic dispensing records, and the remaining four studies used serologic test order codes in combination with LD diagnosis codes and antibiotics records. Only one of the studies that provided data on algorithm performance: sensitivity 50% and positive predictive value 5%, and this was based on Lyme disease diagnosis code only.

Conclusions
US claims-based LD case-finding algorithms have used diverse strategies. Only one algorithm was validated, and its performance was poor. Further studies are warranted to assess performance for different algorithm designs and inform efforts to better assess the true burden of LD.
Is there an association between left atrial outpouching structures and recurrence of atrial fibrillation after catheter ablation?
Authors: Celik Erkan , Hokamp Nils Große , Goertz Lukas , Fehske Wolfgang , Nguyen Dinh Quang , Lichtenberg Lutz , Reimer Robert Peter , Maintz David , Düber Christoph , Achenbach Tobias 
Published: October 2022

ObjectiveThe aim of this study was to investigate the impact of left atrial diverticula (LADs), left sided septal pouches (LSSPs) and middle right pulmonary veins (MRPVs) on recurrent atrial fibrillation (rAF) in patients undergoing laser pulmonary vein isolation procedure (PVI).Material and methodsThis retrospective study enrolled 139 patients with pre-procedural multiple detector computed tomography (MDCT) imaging and 12 months follow-up examination. LADs, LSSPs and MRPV were identified by two radiologists on a dedicated workstation using multiplanar reconstructions and volume rendering technique. Univariate and bivariate regression analyses with patient demographics and cardiovascular risk factors as covariates were performed to reveal independent factors associated with rAF.ResultsLADs were recorded in 41 patients (29%), LSSPs in 20 (14%) and MRPVs in 15 (11%). The right anterosuperior wall of the left atrium was the most prevalent location of LADs (68%). rAF occured in 20 patients, thereof, 15 exhibited an outpouching structure of the left atrium (LAD: 9, LSSP: 2 and MRPV: 3). Presence of an LAD (HR: 2.7, 95%CI: 1.0–8.4, p = 0.04) and permanent AF (HR: 4.8, 95%CI: 1.5–16.3, p = 0.01) were independently associated with rAF.ConclusionsLAD, LSSP and MRPV were common findings on pre-procedural cardiac computed tomography. LADs were revealed as potential independent risk factor of rAF, which might be considered for treatment planning and post-treatment observation.
Human IgG responses to Aedes mosquito salivary peptide Nterm-34kDa and its comparison to Anopheles salivary antigen (gSG6-P1) IgG responses measured among individuals living in Lower Moshi, Tanzania
Authors: Kassam Nancy A. , Laswai Daniel , Kulaya Neema , Kaaya Robert D. , Kajeguka Debora C. , Schmiegelow Christentze , Wang Christian W. , Alifrangis Michael , Kavishe Reginald A. 
Published: October 2022

Background
The level of human exposure to arbovirus vectors, the Aedes mosquitoes, is mainly assessed by entomological methods which are labour intensive, difficult to sustain at a large scale and are affected if transmission and exposure levels are low. Alternatively, serological biomarkers which detect levels of human exposure to mosquito bites may complement the existing epidemiologic tools as they seem cost-effective, simple, rapid, and sensitive. This study explored human IgG responses to an Aedes mosquito salivary gland peptide Nterm-34kDa in Lower Moshi, a highland area with evidence of circulating arboviruses and compared the Aedes IgG responses to Anopheles mosquitoes’ salivary antigen (GSG6-P1) IgG responses.

Methods
Three cross-sectional surveys were conducted in 2019: during the first dry season in March, at the end of the rainy season in June and during the second dry season in September in five villages located in Lower Moshi. Blood samples were collected from enrolled participants above six months of age (age span: 7 months to 94 years) and analysed for the presence of anti-Nterm-34kDa IgG antibodies. Possible associations between Nterm-34kDa seroprevalence and participants’ characteristics were determined. Levels of IgG responses and seroprevalence were correlated and compared to the already measured IgG responses and seroprevalence of Anopheles mosquitoes’ salivary antigen, GSG6-P1.

Results
During the first dry season, Nterm-34kDa seroprevalence was 34.1% and significantly increased at the end of the rainy season to 45.3% (Chi square (χ2) = 6.42 p = 0.011). During the second dry season, the seroprevalence significantly declined to 26.5% (χ2 = 15.12 p<0.001). During the rainy season, seroprevalence was significantly higher among residents of Oria village (adjusted odds ratio (AOR) = 2.86; 95% CI = 1.0–7.8; p = 0.041) compared to Newland. Moreover, during the rainy season, the risk of exposure was significantly lower among individuals aged between 16 and 30 years (AOR = 0.25; 95% CI = 0.1 = 0.9; p = 0.036) compared to individuals aged between 0 and 5 years. There was weak to moderate negative correlation between N-term 34kDa IgG and gSG6-P1 antigens. N-term 34kDa seroprevalence were higher compared to gSG6-P1 seroprevalence.

Conclusion
The findings of this study support that IgG antibody responses towards the Aedes mosquito salivary peptide Nterm-34kDa are detectable among individuals living in lower Moshi and vary with season and geographical area. More individuals are exposed to Aedes mosquito bites than Anopheles mosquito and those exposed to Aedes bites are not necessarily exposed to Anopheles mosquitoes.
Low serum uromodulin levels and their association with lupus flares
Authors: David Bonilla-Lara , Ivan Gamez-Nava Jorge , Emilio Perez-Guerrero Edsaul , Daniela Murillo-Saich Jessica , Betsabe Contreras-Haro , Luisa Vazquez-Villegas Maria , Selene Fajardo-Robledo Nicte , Guadalupe Aguilar-Chavez Erika Anita , Miriam Saldaña-Cruz Ana , Alfredo Celis , Arturo Nava-Valdivia Cesar , Mercedes Hernandez-Corona Diana , German Cardona-Muñoz Ernesto , Gonzalez-Lopez Laura 
Published: October 2022

Background
Only two previous studies in systemic lupus erythematosus (SLE) patients have identified that the blood concentrations of uromodulin are lower in nephritis. However, none of them had evaluated whether a low serum uromodulin adjusted by the glomerular filtration rate (sUromod/eGFR index) contributed to identify patients in risk of lupus nephritis (LN) using multivariable models.

Aim
Therefore, this study aimed two objectives to evaluate the association between low serum uromodulin levels and low sUromod adjusted by eGFR with renal flares in SLE excluding effects of potential confounders in multivariable analyses; and to identify the value of low sUmod and low sUmod/eGFR index as a potential diagnostic marker of LN.

Patients and methods
Design: Cross-sectional study. SLE patients (n = 114) were investigated for lupus flare with renal SLEDAI. Two groups: a) SLE with renal flare (renal-SLEDAI≥4, n = 41) and b) SLE non-renal flare (renal SLEDAI<4, n = 73). SLE patients were evaluated by other indices including a global disease activity index (SLEDAI) and SLICC renal disease activity score. Serum uromodulin levels (ng/mL) were quantified by ELISA. Serum uromodulin was adjusted by eGFR (sUromod/eGFR index). Cutt-offs of low sUromodulin and low sUromod/eGFR index were computed, ROC curves were performed and values of diagnostic tests were obtained. Multivariable logistic regression models were performed to identify if low sUromod/eGFR index is associated to renal flares.

Results
Low serum uromodulin and low sUromod/eGFR index correlated to high scores of renal-SLEDAI, SLICC-renal and proteinuria. SLE patients with a renal flare had lower uromodulin levels compared to SLE patients without renal flare (p = 0.004). After adjusting by potential confounders, the low sUromod/eGFR index (<0.80 ng/mL) increased the risk of a renal flare (OR, 2.91; 95%CI, 1.21 to 6.98; p = 0.02).

Conclusions
We propose the low sUromod/eGFR index as a potential new marker of renal disease activity in SLE.
Birth preparedness and complication readiness practice and associated factors among pregnant women in Central Ethiopia, 2021: A cross-sectional study
Authors: Girma Derara , Waleligne Addisu , Dejene Hiwot 
Published: October 2022

Background
Birth preparedness and complication readiness (BP/CR) is an intervention designated by the World Health Organization (WHO) as an essential element of the antenatal (ANC) package with a concept of a global strategy to reduce maternal mortality. In Ethiopia, the proportion of pregnant women preparing for birth and related complications has remained low. Whereas, the need for additional study is indicated to add more evidence to the country’s efforts to end preventable maternal death.

Methods
A facility-based cross-sectional study was conducted from March 01 to May 01, 2021. A systematic random sampling technique was applied to recruit 422 pregnant women. Bivariable and multivariable binary logistic regression was fitted to identify factors associated with BP/CR practice. Variables with a p-value ≤ 0.25 on the bivariable analysis were included in multivariable analysis. Adjusted odds ratios (AOR) with the respective 95% confidence interval (CI) and a p-value <0.05 was used to set statistically significant variables in the multivariable analysis.

Results
A total of 414 pregnant women have participated in the study. The overall BP/CR practice level was 44.9% (95% CI: 40.1, 49.7). Preconception care utilization (PCC) (AOR = 2.31; 95% CI:1.38–3.86), urban residents (AOR = 2.00; 95% CI:1.21–3.31), knowledge of BP/CR (AOR = 2.29; 95% CI:1.27–3.47), knowledge of danger signs during pregnancy (AOR = 2.05; 95% CI:1.21–3.47), knowledge of danger signs in newborns (AOR = 2.06; 95% CI:1.21–3.47), starting ANC visits in the 1st and 2nd trimester (AOR = 2.52; 95% CI:1.40–4.52), number of ANC visit ≥ three (AOR = 1.66; 95% CI;1.01–2.74), knowing Expected Date of Delivery (EDD) (AOR = 3.71; 95% CI:2.01–6.82), and joint decision-making on obstetric services (AOR = 3.51; 95% CI;1.99–6.20) were factors significantly associated with BP/CR practice.

Conclusion
Based on the WHO standard, this study revealed a low level of BP/CR practice among pregnant women, with only less than half of women adequately prepared for childbirth and its complications. Moreover, it has been shown that BP/CR practice is influenced by socio-economic, maternal knowledge, and health service-related factors. Therefore, improving the status of BP/CR practice by expanding awareness creation opportunities, strengthening PCC and early ANC initiation by improving pregnant women’s understanding, and promoting joint decision-making on obstetric services are recommended.