bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insecticidal activity of Simparica and Simparica Trio against Aedes aegypti in dogs
Authors: Geurden Thomas , Chapin Sara , McCall John W. , Mansour Abdelmoneim , Mahabir Sean P. , Kryda Kristina , McTier Tom 
Published: March 2023

Abstract
Background
Aedes aegypti is one of the main species responsible for the transmission of mosquito-borne pathogens worldwide. The isoxazoline Sarolaner has excellent efficacy as an acaricide against ticks and mites and as an insecticide against fleas, and potential efficacy against other insects.

Methods
In each of two laboratory studies, 24 dogs were randomly allocated (n = 8/group) to an untreated control group, a Simparica-treated group (at the minimum dose of 2.0 mg/kg sarolaner), or a Simparica Trio-treated group (at the minimum dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel), based on pre-treatment mosquito counts. Treatments were administered orally once on day 0. Each dog was exposed to 50 unfed female adult A. aegypti mosquitoes for 1 h on days 1, 7, 14, 21, 28 and 35. After each exposure, mosquitoes were counted for each dog and characterized as live, moribund or dead, and as fed or unfed. Dead mosquitoes were counted and removed at 12, 24 and 48 h post-exposure in study 1 and at 24, 48, 72, 96 and 120 h post-exposure in study 2. In study 2, mosquito eggs were collected from 72 h post-exposure until 120 h post-exposure. Insecticidal efficacy was calculated based on the reduction of the arithmetic mean live fed-mosquito counts in each of the treated groups versus the untreated control group for every timepoint post-exposure.

Results
Adequate challenge was demonstrated in both studies, with arithmetic mean live fed-mosquito counts ranging from 35.5 to 45.0 for the untreated group. Mean mosquito counts for dogs treated with Simparica and Simparica Trio were significantly (P < 0.0001) reduced within 48 h after exposure on all study days. In study 1, Simparica treatment provided ≥ 96.8% reduction in the arithmetic mean live fed-mosquito counts for 28 days, and Simparica Trio treatment provided ≥ 90.3% reduction for 21 days. In study 2, Simparica treatment provided ≥ 99.4% reduction for 35 days (from 48 h onwards), and Simparica Trio treatment provided ≥ 97.8% reduction for 28 days (from 72 h onwards).

Conclusions
Both studies demonstrated that a single oral dose of Simparica or Simparica Trio provides high efficacy against mosquitoes in dogs within 24–72 h after exposure for an entire month.

Graphical Abstract
Pharmacogenomic profiling reveals molecular features of chemotherapy resistance in IDH wild-type primary glioblastoma
Authors: Nam Yoonhee , Koo Harim , Yang Yingxi , Shin Sang , Zhu Zhihan , Kim Donggeon , Cho Hee Jin , Mu Quanhua , Choi Seung Won , Sa Jason K. , Seo Yun Jee , Kim Yejin , Lee Kyoungmin , Oh Jeong-Woo , Kwon Yong-Jun , Park Woong-Yang , Kong Doo-Sik , Seol Ho Jun , Lee Jung-Il , Park Chul-Kee , Lee Hye Won , Yoon Yeup , Wang Jiguang 
Published: March 2023

AbstractBackgroundAlthough temozolomide (TMZ) has been used as a standard adjuvant chemotherapeutic agent for primary glioblastoma (GBM), treating isocitrate dehydrogenase wild-type (IDH-wt) cases remains challenging due to intrinsic and acquired drug resistance. Therefore, elucidation of the molecular mechanisms of TMZ resistance is critical for its precision application.MethodsWe stratified 69 primary IDH-wt GBM patients into TMZ-resistant (n= 29) and sensitive (n= 40) groups, using TMZ screening of the corresponding patient-derived glioma stem-like cells (GSCs). Genomic and transcriptomic features were then examined to identify TMZ-associated molecular alterations. Subsequently, we developed a machine learning (ML) model to predict TMZ response from combined signatures. Moreover, TMZ response in multisector samples (52 tumor sectors from 18 cases) was evaluated to validate findings and investigate the impact of intra-tumoral heterogeneity on TMZ efficacy.ResultsIn vitro TMZ sensitivity of patient-derived GSCs classified patients into groups with different survival outcomes (P= 1.12e−4 for progression-free survival (PFS) and 3.63e−4 for overall survival (OS)). Moreover, we found that elevated gene expression ofEGR4,PAPPA,LRRC3, andANXA3was associated to intrinsic TMZ resistance. In addition, other features such as 5-aminolevulinic acid negative, mesenchymal/proneural expression subtypes, and hypermutation phenomena were prone to promote TMZ resistance. In contrast, concurrent copy-number-alteration inPTEN,EGFR, andCDKN2A/Bwas more frequent in TMZ-sensitive samples (Fisher’s exactP= 0.0102), subsequently consolidated by multi-sector sequencing analyses. Integrating all features, we trained a ML tool to segregate TMZ-resistant and sensitive groups. Notably, our method segregated IDH-wt GBM patients from The Cancer Genome Atlas (TCGA) into two groups with divergent survival outcomes (P= 4.58e−4 for PFS and 3.66e−4 for OS). Furthermore, we showed a highly heterogeneous TMZ-response pattern within each GBM patient using in vitro TMZ screening and genomic characterization of multisector GSCs. Lastly, the prediction model that evaluates the TMZ efficacy for primary IDH-wt GBMs was developed into a webserver for public usage (http://www.wang-lab-hkust.com:3838/TMZEP).ConclusionsWe identified molecular characteristics associated to TMZ sensitivity, and illustrate the potential clinical value of a ML model trained from pharmacogenomic profiling of patient-derived GSC against IDH-wt GBMs.
Automated prioritization of sick newborns for whole genome sequencing using clinical natural language processing and machine learning
Authors: Peterson Bennet , Hernandez Edgar Javier , Hobbs Charlotte , Malone Jenkins Sabrina , Moore Barry , Rosales Edwin , Zoucha Samuel , Sanford Erica , Bainbridge Matthew N. , Frise Erwin , Oriol Albert , Brunelli Luca , Kingsmore Stephen F. , Yandell Mark 
Published: March 2023

Abstract
Background
Rapidly and efficiently identifying critically ill infants for whole genome sequencing (WGS) is a costly and challenging task currently performed by scarce, highly trained experts and is a major bottleneck for application of WGS in the NICU. There is a dire need for automated means to prioritize patients for WGS.

Methods
Institutional databases of electronic health records (EHRs) are logical starting points for identifying patients with undiagnosed Mendelian diseases. We have developed automated means to prioritize patients for rapid and whole genome sequencing (rWGS and WGS) directly from clinical notes. Our approach combines a clinical natural language processing (CNLP) workflow with a machine learning-based prioritization tool named Mendelian Phenotype Search Engine (MPSE).

Results
MPSE accurately and robustly identified NICU patients selected for WGS by clinical experts from Rady Children’s Hospital in San Diego (AUC 0.86) and the University of Utah (AUC 0.85). In addition to effectively identifying patients for WGS, MPSE scores also strongly prioritize diagnostic cases over non-diagnostic cases, with projected diagnostic yields exceeding 50% throughout the first and second quartiles of score-ranked patients.

Conclusions
Our results indicate that an automated pipeline for selecting acutely ill infants in neonatal intensive care units (NICU) for WGS can meet or exceed diagnostic yields obtained through current selection procedures, which require time-consuming manual review of clinical notes and histories by specialized personnel.
Response to “Similarities in clinical course and outcome between juvenile idiopathic arthritis (JIA)-associated and ANA-positive idiopathic anterior uveitis: data from a population-based nationwide study in Germany”
Authors: Zhou Avery , Babiker Fatima , Philip Andrew M. , Anesi Stephen D. , Foster C. Stephen 
Published: March 2023

Abstract
We have read the article entitled “Similarities in clinical course and outcome between juvenile idiopathic arthritis (JIA)-associated and ANA-positive idiopathic anterior uveitis: data from a population-based nationwide study in Germany” by Heiligenhaus et al. While we appreciate the work conducted by the authors, we have several comments we would like to address. First, the follow-up interval of 2 years is too short to conclude that the clinical course between two chronic pathologies is not significantly different. Second, remission status was determined by uveitis inactivity during the 2-year follow-up visit without any mention of flare frequency or length of remission, which is not a reliable measure of uveitis control. Third, ANA-positive idiopathic anterior uveitis is not a classification with a distinct clinical phenotype, and additional reports of serologic investigations would have been helpful.
Fecal microbiota from MRL/lpr mice exacerbates pristane-induced lupus
Authors: Yi Xiaoqing , Huang Cancan , Huang Chuyi , Zhao Ming , Lu Qianjin 
Published: March 2023

Abstract
Background
The roles of gut microbiota in the pathogenesis of SLE have been receiving much attention during recent years. However, it remains unknown how fecal microbiota transplantation (FMT) and microbial metabolites affect immune responses and lupus progression.

Methods
We transferred fecal microbiota from MRL/lpr (Lpr) mice and MRL/Mpj (Mpj) mice or PBS to pristane-induced lupus mice and observed disease development. We also screened gut microbiota and metabolite spectrums of pristane-induced lupus mice with FMT via 16S rRNA sequencing, metagenomic sequencing, and metabolomics, followed by correlation analysis.

Results
FMT from MRL/lpr mice promoted the pathogenesis of pristane-induced lupus and affected immune cell profiles in the intestine, particularly the plasma cells. The structure and composition of microbial communities in the gut of the FMT-Lpr mice were different from those of the FMT-Mpj mice and FMT-PBS mice. The abundances of specific microbes such as prevotella taxa were predominantly elevated in the gut microbiome of the FMT-Lpr mice, which were positively associated with functional pathways such as cyanoamino acid metabolism. Differential metabolites such as valine and L-isoleucine were identified with varied abundances among the three groups. The abundance alterations of the prevotella taxa may affect the phenotypic changes such as proteinuria levels in the pristane-induced lupus mice.

Conclusion
These findings further confirm that gut microbiota play an important role in the pathogenesis of lupus. Thus, altering the gut microbiome may provide a novel way to treat lupus.
Clinical characteristics of rheumatoid arthritis patients with interstitial lung disease: baseline data of a single-center prospective cohort
Authors: Kim Hyoungyoung , Cho Soo-Kyung , Song Yeo-Jin , Kang Juyeon , Jeong Seung-A , Kim Hye Won , Choi Chan-Bum , Kim Tae-Hwan , Jun Jae-Bum , Bae Sang-Cheol , Yoo Dae-Hyun , Lee Hyun , Park Dong Won , Sohn Jang Won , Yoon Ho Joo , Hong Su Jin , Yoo Seung-Jin , Choi Yo Won , Lee Youkyung , Kim Sang Heon , Sung Yoon-Kyoung 
Published: March 2023

Abstract
Background
To introduce a prospective cohort for rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) and to identify their clinical features in comparison with RA patients without ILD.

Methods
Using a multidisciplinary collaborative approach, a single-center cohort for RA patients with ILD (RA-ILD) was established in May 2017, and enrolment data from May 2017 to March 2021 were used to compare the clinical features of RA patients without ILD (RA-non ILD). Multivariable logistic regression analysis was used to identify factors associated with ILD in RA patients.

Results
Among 148 RA-ILD and 410 RA-non ILD patients, participants in the RA-ILD group were older (65.8 ± 9.9 vs. 58.0 ± 10.4 years, P < 0.001) and included more males (35.8% vs. 14.6%, P < 0.001) than in the RA-non ILD group. The RA-ILD group had a higher proportion of late-onset RA patients (age ≥ 60 years) than in the comparator group (43.9% vs. 14.2%, P < 0.001). Multivariable logistic regression analysis showed that higher age at RA onset (OR 1.056, 95% CI 1.021–1.091), higher body mass index (BMI; OR 1.65, 95% CI 1.036–2.629), smoking history (OR 2.484, 95% CI 1.071–5.764), and oral glucocorticoid use (OR 3.562, 95% CI 2.160–5.874) were associated with ILD in RA patients, whereas methotrexate use was less likely to be associated with ILD (OR 0.253, 95% CI 0.155–0.412).

Conclusions
Higher age at RA onset, smoking history, and higher BMI were associated with the presence of ILD among RA patients. Oral glucocorticoids were more frequently used whereas methotrexate was less likely to be used in RA-ILD patients.
Utility of hand-held ultrasound for image acquisition and interpretation by trained Kenyan providers
Authors: Wanjiku Grace , Dreizler Lindsay , Wu Shirley , Baird Janette , Wachira Benjamin 
Published: March 2023

Abstract
Background
Point-of-care ultrasound (POCUS) plays a prominent role in the timely recognition and management of multiple medical, surgical, and obstetric conditions. A POCUS training program for primary healthcare providers in rural Kenya was developed in 2013. A significant challenge to this program is the acquisition of reasonably priced ultrasound machines with adequate image quality and the ability to transmit images for remote review. The goal of this study is to compare the utility of a smartphone-connected, hand-held ultrasound with a traditional ultrasound device for image acquisition and interpretation by trained healthcare providers in Kenya.

Methods
This study took place during a routine re-training and testing session for healthcare providers who had already received POCUS training. The testing session involved a locally validated Observed Structured Clinical Exam (OSCE) that assessed trainees’ skills in performing the Extended Focused Assessment with Sonography for Trauma (E-FAST) and focused obstetric exams. Each trainee performed the OSCE twice, once using a smartphone-connected hand-held ultrasound and once using their notebook ultrasound model.

Results
Five trainees obtained a total of 120 images and were scored on image quality and interpretation. Overall E-FAST imaging quality scores were significantly higher for the notebook ultrasound compared to the hand-held ultrasound but there was no significant difference in image interpretation. Overall focused obstetric image quality and image interpretation scores were the same for both ultrasound systems. When separated into individual E-FAST and focused obstetric views, there were no statistically significant differences in the image quality or image interpretation scores between the two ultrasound systems. Images obtained using the hand-held ultrasound were uploaded to the associated cloud storage using a local 3G-cell phone network. Upload times were 2–3 min.

Conclusion
Among POCUS trainees in rural Kenya, the hand-held ultrasound was found to be non-inferior to the traditional notebook ultrasound for focused obstetric image quality, focused obstetric image interpretation, and E-FAST image interpretation. However, hand-held ultrasound use was found to be inferior for E-FAST image quality. These differences were not observed when evaluating each E-FAST and focused obstetric views separately. The hand-held ultrasound allowed for rapid image transmission for remote review.
Start spreading the news: a deliberate approach to POCUS program development and implementation
Authors: Gaudreau-Simard Mathilde , Kilabuk Elaine , Halman Samantha , Wooller Krista , Woo Michael Y. , Arntfield Robert , Ma Irene , Forster Alan J. 
Published: March 2023

AbstractWhile there is an expanding body of literature on Point-of-Care Ultrasound (POCUS) pedagogy, administrative elements that are necessary for the widespread adoption of POCUS in the clinical environment have received little attention. In this short communication, we seek to address this gap by sharing our institutional experience with POCUS program development and implementation. The five pillars of our program, selected to tackle local barriers to POCUS uptake, are education, workflow, patient safety, research, and sustainability. Our program logic model outlines the inputs, activities, and outputs of our program. Finally, key indicators for the monitoring of program implementation efforts are presented. Though designed for our local context, this approach may readily be adapted toward other clinical environments. We encourage others leading the integration of POCUS at their centers to adopt this approach not only to achieve sustainable change but also to ensure that quality safeguards are in place.
Inter-observer and intra-observer variability in ultrasound assessment of gastric content and volume in critically ill patients receiving enteral nutrition
Authors: Ruiz Ávila Héctor Andrés , Espinosa Almanza Carmelo José , Fuentes Barreiro Cindy Yohana 
Published: March 2023

Abstract
Background
The assessment of gastric content and volume using bedside ultrasound (US) has become a useful tool in emergency departments, anesthesiology departments and inpatient wards, as it provides a rapid and dynamic assessment of the gastric content of patients, which, allows making decisions regarding the risk of regurgitation or the need to adjust the strategy used to induce general anesthesia in patients with a full stomach. This assessment consists of two evaluations: a qualitative one, in which the status of the antrum, in terms of gastric content, is classified into three categories (empty, liquid content and full), and a quantitative one, where gastric volume is estimated. The objective of this study was to estimate the intra-observer and inter-observer agreement in ultrasound assessment of gastric content and volume in critically ill patients receiving enteral nutrition.

Results
A total of 41 patients were included and each examiner performed 64 gastric US (n = 128). Participants’ average age was 56.5 years (SD ± 12.6) and 63.4% were men. Regarding the qualitative evaluation of the antrum, in supine position both examiners classified the gastric content as grade 0 in 1 gastric US (1.5%), grade 1 in 4 gastric US (6.2%) and grade 2 in 59 (92.1%). Regarding intra-observer variability in the measurement of the area of the antrum, Lin's concordance correlation coefficient (CCC), the difference of means between measurements and the 95% limits of agreement of Bland and Altman values were 0.95 (95% CI 0.940–0.977), − 0.47 cm2 (SD ± 1.64) and − 3.70 cm2 to 2.75 cm2, respectively, in EC1, and 0.94 (95% CI 0.922–0.973), − 0.18 cm2 (SD ± 2.18) and − 4.47 cm2 to 4.09 cm2 in EC2. Concerning to inter-observer variability (EC1 vs EC2) in the measurement of the area of the antrum and of gastric volume, the following CCC, mean difference between measurements and 95% limits of agreement of Bland and Altman values were obtained: measurement of the area of the antrum: 0.84 (95% CI 0.778–0.911), − 0.86 cm2 (SD ± 3.38) and − 7.50 cm2 to 5.78 cm2; gastric volume measurement: 0.84 (95% CI 0.782–0.913), − 12.3 mL (SD ± 49.2) and − 108.8 mL to 84.0 mL.

Conclusions
The assessment of gastric content and volume using bedside US in critically ill patients on mechanical ventilation and receiving enteral nutrition showed a good intra and inter-rater reliability. Most of the patients included in the study had a high risk of pulmonary aspiration, since, according to the results of the gastric US evaluation, they had gastric volumes > 1.5 mL/kg.
Association of triglyceride-glucose index with atherosclerotic cardiovascular disease and mortality among familial hypercholesterolemia patients
Authors: Wen Jun , Pan Qi , Du Lei-Lei , Song Jing-Jing , Liu Yu-Peng , Meng Xiang-Bin , Zhang Kuo , Gao Jun , Shao Chun-Li , Wang Wen-Yao , Zhou Hao , Tang Yi-Da 
Published: March 2023

Abstract
Background
Familial hypercholesterolemia (FH) is an inherited metabolic disorder with a high level of low-density lipoprotein cholesterol and the worse prognosis. The triglyceride-glucose (TyG) index, an emerging tool to reflect insulin resistance (IR), is positively associated with a higher risk of atherosclerotic cardiovascular disease (ASCVD) in healthy individuals, but the value of TyG index has never been evaluated in FH patients. This study aimed to determine the association between the TyG index and glucose metabolic indicators, insulin resistance (IR) status, the risk of ASCVD and mortality among FH patients.

Methods
Data from National Health and Nutrition Examination Survey (NHANES) 1999–2018 were utilized. 941 FH individuals with TyG index information were included and categorized into three groups: < 8.5, 8.5–9.0, and > 9.0. Spearman correlation analysis was used to test the association of TyG index and various established glucose metabolism-related indicators. Logistic and Cox regression analysis were used to assess the association of TyG index with ASCVD and mortality. The possible nonlinear relationships between TyG index and the all-cause or cardiovascular death were further evaluated on a continuous scale with restricted cubic spline (RCS) curves.

Results
TyG index was positively associated with fasting glucose, HbA1c, fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR) index (all p < 0.001). The risk of ASCVD increased by 74% with every 1 unit increase of TyG index (95%CI: 1.15–2.63, p = 0.01). During the median 114-month follow-up, 151 all-cause death and 57 cardiovascular death were recorded. Strong U/J-shaped relations were observed according to the RCS results (p = 0.0083 and 0.0046 for all-cause and cardiovascular death). A higher TyG index was independently associated with both all-cause death and cardiovascular death. Results remained similar among FH patients with IR (HOMA-IR ≥ 2.69). Moreover, addition of TyG index showed helpful discrimination of both survival from all-cause death and cardiovascular death (p < 0.05).

Conclusion
TyG index was applicable to reflect glucose metabolism status in FH adults, and a high TyG index was an independent risk factor of both ASCVD and mortality.
Association between antidepressant use and liver fibrosis in patients with type 2 diabetes: a population based study
Authors: Shi Lin , Jia Fangyuan 
Published: March 2023

Abstract
Background
The prevalence of liver fibrosis among diabetic patients is increasing rapidly. Our study aims at exploring the relationship between antidepressant use and liver fibrosis in diabetic patients.

Methods
We conducted this cross-sectional study through the cycle of National Health and Nutrition Examination Survey (NHANES) 2017–2018. The study population were consisted of patients with type 2 diabetes and reliable vibration-controlled transient elastography (VCTE) results. The presence of liver fibrosis and steatosis were assessed by the median values of liver stiffness measurement (LSM) and controlled attenuation parameter (CAP), respectively. Antidepressants included selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), serotonin and norepinephrine reuptake inhibitors (SNRIs) and serotonin antagonists and reuptake inhibitors (SARIs). Patients with evidence of viral hepatitis and significant alcohol consumption were excluded. Logistic regression analysis was performed to evaluate the association between antidepressant use and both steatosis and significant (≥ F3) liver fibrosis after adjustment for potential confounders.

Results
Our study population consisted of 340 women and 414 men, of whom 87 women(61.3%) and 55(38.7%) men received antidepressants. The most commonly used antidepressants were SSNIs(48.6%), SNRIs(22.5%) and TCAs(12.7%), followed by SARIs(10.6%) and other antidepressants(5.6%). 165 participants had significant liver fibrosis by VCTE, with a weighted overall prevalence of 24%(95% CI 19.2–29.5). In addition, 510 patients had evidence of hepatic steatosis by VCTE with a weighted overall prevalence of 75.4%(95% CI 69.2–80.7). After adjusting confounders, no significant association was observed between antidepressant use and significant liver fibrosis or cirrhosis.

Conclusions
In conclusion, in this cross-sectional study, we found that antidepressant drugs was not associated with liver fibrosis and cirrhosis in patients with type 2 diabetes in a nationwide population.