bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor Necrosis Factor Inhibitor Use Increases Birthweight in Pregnant Women With Rheumatoid Arthritis Independently of the Soluble Fms‐Like Tyrosine Kinase‐1/Placental Growth Factor Ratio
Authors: Quaak Cornelia H. , Kluivers Anna C. M. , Baart Sara J. , Smeele Hieronymus T. W. , Neuman Rugina I. , Saleh Langeza , Visser Willy , Danser A. H. Jan , Dolhain Radboud J. E. M. 
Published: March 2024

Background
To study whether the use of TNF (tumor necrosis factor) inhibitors (TNFi) by pregnant women with rheumatoid arthritis affects sFlt‐1 (soluble Fms‐like tyrosine kinase‐1), PlGF (placental growth factor), or their impact on birthweight.

Methods and Results

sFlt‐1 and PlGF were measured in all trimesters of pregnancy in the Preconception Counseling in Active Rheumatoid Arthritis study and were compared according to the use of TNFi. The association of sFlt‐1 and PlGF with birthweight in relation to TNFi was determined. The study included 158 women, of whom 52.5% used TNFi during pregnancy. Both sFlt‐1 and PlGF increased during pregnancy, whereas their ratio declined. Taking into consideration the trimester‐related variation in levels of sFlt‐1 and PlGF, after correction for relevant confounders, the sFlt‐1/PlGF ratio was not significantly different between patients who did or did not use TNFi (sFlt‐1/PlGF ratio in the second trimester compared with the first trimester: estimated change 8.17 [95% CI, 2.54–26.29],
P
=0.79; sFlt‐1/PlGF ratio in the third trimester compared with the first trimester: estimated change 6.25 [95% CI, 1.73–22.50],
P
=0.25). In women who did not use TNFi, birthweight was significantly lower (3180 versus 3302 g;
P
=0.03), and sFlt‐1 displayed a negative correlation with birthweight (
r
=−0.462,
P
<0.001) and birthweight percentile (
r
=−0.332,
P
=0.008). In TNFi users, these correlations were absent.

Conclusions
TNF inhibitor use increases birthweight in pregnant women with rheumatoid arthritis independently of the sFlt‐1/PlGF ratio.

Registration

http://clinicaltrials.gov
. Unique identifier: NCT01345071.
Conservative Versus Surgical Therapy in Patients With Infective Endocarditis and Surgical Indication—Meta‐Analysis of Reconstructed Time‐to‐Event Data
Authors: Caldonazo Tulio , Hagel Stefan , Doenst Torsten , Kirov Hristo , Sá Michel Pompeu , Jacquemyn Xander , Tasoudis Panagiotis , Franz Marcus , Diab Mahmoud 
Published: March 2024

Background
Infective endocarditis represents a life‐threatening disease with high mortality rates. A fraction of patients receives exclusively conservative antibiotic treatment due to their comorbidities and high operative risk, despite fulfilling criteria for surgical therapy. The aim of the present study is to compare outcomes in patients with infective endocarditis and indication for surgical therapy in those who underwent or did not undergo valve surgery.

Methods and Results

Three databases were systematically assessed. A pooled analysis of Kaplan–Meier–derived reconstructed time‐to‐event data from studies with longer follow‐up comparing conservative and surgical treatment was performed. A landmark analysis to further elucidate the effect of surgical intervention on mortality was carried out. Four studies with 3003 patients and median follow‐up time of 7.6 months were included. Overall, patients with an indication for surgery who were surgically treated had a significantly lower risk of mortality compared with patients who received conservative treatment (hazard ratio [HR], 0.27 [95% CI, 0.24–0.31],
P
<0.001). The survival analysis in the first year showed superior survival for patients who underwent surgery when compared with those who did not at 1 month (87.6% versus 57.6%; HR, 0.31 [95% CI, 0.26–0.37],
P
<0.01), at 6 months (74.7% versus 34.6%) and at 12 months (73.3% versus 32.7%).

Conclusions
Based on the findings of this study‐level meta‐analysis, patients with infective endocarditis and formal indication for surgical intervention who underwent surgery are associated with a lower risk of short‐ and long‐term mortality when compared with conservative treatment.
Magnetic Resonance Imaging Assists With Determining Etiology After Transient Ischemic Attack or Minor Stroke
Authors: Moores Margaret , Joundi Raed A. , Singh Nishita , Penn Andrew M. , Votova Kristine , Smith Eric E. , Coutts Shelagh B. 
Published: March 2024

Background
Magnetic resonance imaging infarct topography may assist with determining stroke etiology. The influence of diffusion‐weighted imaging (DWI)‐positive lesions on etiology determination in patients with transient ischemic attack or minor stroke is not well studied.

Methods and Results

We prospectively enrolled patients between 2010 and 2017 in 2 studies; participants with a final diagnosis of probable or definite transient ischemic attack or stroke were pooled for analysis. The primary outcome was the adjudicated ischemic etiology. We compared proportion of each etiology (cardioembolic, large‐vessel, small‐vessel disease, other) in patients who had DWI positivity compared with DWI negativity. We used logistic regression to determine the adjusted odds ratio (OR) for each etiology compared with undetermined by DWI positivity. The final analysis included 1498 patients: 832 (55.5%) were DWI‐positive. DWI‐positive patients were more likely to be diagnosed with small‐vessel disease (19.1% versus 5.3%) and less likely with undetermined etiology (36.9% versus 53.0%;
P
<0.001). After adjustment, the presence of any DWI lesion was associated with increased odds of assigning any etiology (OR, 1.8 [95% CI, 1.3–2.5]). A single DWI lesion was associated with increased odds of small‐vessel disease diagnosis (OR, 9.5 [95% CI, 6.4–14.0]), and multiple DWI lesions with reduced odds of small‐vessel disease (OR, 0.2 [95% CI, 0.1–0.4]) but increased odds of all other etiologies compared with undetermined etiology.

Conclusions
Any DWI‐positive lesion after suspected transient ischemic attack or minor stroke was associated with increased odds of assigning a etiology. Presence and topography of DWI lesions on magnetic resonance imaging may assist with etiology determination and may impact stroke prevention therapies.
Efficacy of diadynamic currents as an adjunct to exercise to manage symptoms of knee osteoarthritis in adults: A randomized controlled clinical trial
Authors: Alfredo Patrícia Pereira , Johnson Mark I , Bjordal Jan Magnus , Santos Adriana Teresa Silva , Peres Giovani Bravin , Junior Washington Steagall , Casarotto Raquel Aparecida 
Published: March 2024

Objective To investigate the effect of diadynamic currents administered prior to exercises on pain and disability in patients with osteoarthritis of the knee. Design A randomized-controlled trial. Setting Special Rehabilitation Services in Taboão da Serra. Participants Patients with bilateral knee osteoarthritis. Intervention Participants were randomly allocated to Group I (diadynamic currents and exercises; n = 30, 60 knees) or Group II (exercises alone; n = 30, 60 knees) and were treated three times a week for 8 weeks. Main outcome measures The primary outcome measures were change in knee pain evaluated by visual analog scale and disability Index Score (Lequesne). Secondary outcomes included change in mobility (Timed Up and Go test), range of motion (goniometer), muscle strength (dynamometer), a composite score for pain and disability (Western Ontario and McMaster Universities Osteoarthritis questionnaire), and a drug diary to measure consumption of rescue pain medication (paracetamol). All measurements were collected at baseline, 8 weeks, and 6 months from baseline (follow-up). Results There were 60 participants with a mean (SD) age of 63.40 (8.20) years. Between-group differences in the follow-up (8 weeks and 6 months) were observed for pain at rest, pain during activities of daily living and disability. There was improvement in Group I that was maintained for the three variables 6 months after treatment. Mean difference for pain at rest was −3.08 points (95% confidence interval −4.13; −2.02), p < 0.01 with an effect size of 1.4; mean difference for pain during activities of daily living was −2.40 points (95% confidence interval −3.34; −1.45), p < 0.01 with an effect size of 1.24; and mean difference for disability was −4.08 points (95% confidence interval −5.89; −2.26), p < 0.01 with an effect size of 1.04. Conclusion Patients with symptomatic knee osteoarthritis receiving 8 weeks of treatment with diadynamic currents as an adjunct to a program of exercises had significantly greater improvements in pain and disability than those receiving exercises alone. Beneficial effects were sustained for 6 months.
Enhancing quality control in emulsion-type sausage production: Predicting chemical composition of intact samples with near infrared spectroscopy
Authors: Ritthiruangdej Pitiporn , Vangnai Kanithaporn , Kasemsumran Sumaporn , Somboonying Supapich , Charoensin Pimwaree , Hiriotappa Arisara , Lowleraha Papawarin 
Published: March 2024

This research actively explores the potential of near infrared spectroscopy (NIR) for analyzing the chemical composition of emulsion-type sausages, focusing on critical factors like residual nitrite, moisture, protein, and fat content. To establish robust and generalizable models, we utilized a dataset of 100 experimentally prepared sausages encompassing a wide range of pork back fat replacement levels (5%, 15%, 30%, 45%, and 60%) and added sodium nitrite amounts (0, 80, 125, 250, and 375 ppm). An external validation set of 20 commercially sourced sausages further assessed the model’s real-world applicability. Partial least squares (PLS) regression calibration models with multiplicative scatter correction (MSC) pre-treatment demonstrated impressive accuracy for moisture (RMSECV = 0.57%, RPD = 9.8), fat (RMSECV = 1.17%, RPD = 9.5), and protein (RMSECV = 0.30%, RPD = 7.6). While residual nitrite prediction presented challenges due to its inherent complexity, the external validation yielded a competitive root mean square error of prediction (RMSEP) of 12.02 ppm, surpassing the average performance reported in similar studies (RMSEP ∼15 ppm) by 3 ppm. Importantly, sample homogenization did not significantly affect parameter prediction, highlighting the robustness of the NIR-based approach. These findings suggest that NIR spectroscopy, with its non-destructive, rapid, and cost-effective nature, could provide valuable tools for quality control and monitoring in the emulsion-type sausage industry. More importantly, improved nitrite prediction could pave the way for enhanced precision and control in sausage production, ultimately contributing to improved food safety and sustainability.
Iguratimod, an allosteric inhibitor of macrophage migration inhibitory factor (MIF), prevents mortality and oxidative stress in a murine model of acetaminophen overdose
Authors: Bloom Joshua , Pantouris Georgios , He Mingzhu , Aljabari Bayan , Mishra Lopa , Manjula Ramu , Parkins Andrew , Lolis Elias J. , Al-Abed Yousef 
Published: March 2024

Abstract
Background
Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that has been implicated in multiple inflammatory and non-inflammatory diseases, including liver injury induced by acetaminophen (APAP) overdose. Multiple small molecule inhibitors of MIF have been described, including the clinically available anti-rheumatic drug T-614 (iguratimod); however, this drug’s mode of inhibition has not been fully investigated.

Methods
We conducted in vitro testing including kinetic analysis and protein crystallography to elucidate the interactions between MIF and T-614. We also performed in vivo experiments testing the efficacy of T-614 in a murine model of acetaminophen toxicity. We analyzed survival in lethal APAP overdose with and without T-614 and using two different dosing schedules of T-614. We also examined MIF and MIF inhibition effects on hepatic hydrogen peroxide (H2O2) as a surrogate of oxidative stress in non-lethal APAP overdose.

Results
Kinetic analysis was consistent with a non-competitive type of inhibition and an inhibition constant (Ki) value of 16 µM. Crystallographic analysis revealed that T-614 binds outside of the tautomerase active site of the MIF trimer, with only the mesyl group of the molecule entering the active site pocket. T-614 improved survival in lethal APAP overdose when given prophylactically, but this protection was not observed when the drug was administered late (6 h after APAP). T-614 also decreased hepatic hydrogen peroxide concentrations during non-lethal APAP overdose in a MIF-dependent fashion.

Conclusions
T-614 is an allosteric inhibitor of MIF that prevented death and decreased hepatic hydrogen peroxide concentrations when given prophylactically in a murine model of acetaminophen overdose. Further studies are needed to elucidate the mechanistic role of MIF in APAP toxicity.
A transcriptome-wide identification of ATP-binding cassette (ABC) transporters revealed participation of ABCB subfamily in abiotic stress management of Glycyrrhiza glabra L
Authors: Devi Ritu , Goyal Pooja , Verma Bhawna , Hussain Shahnawaz , Chowdhary Fariha , Arora Palak , Gupta Suphla 
Published: March 2024

AbstractTranscriptome-wide survey divulged a total of 181 ABC transporters in G. glabra which were phylogenetically classified into six subfamilies. Protein–Protein interactions revealed nine putative GgABCBs (-B6, -B14, -B15, -B25, -B26, -B31, -B40, -B42 &-B44) corresponding to five AtABCs orthologs (-B1, -B4, -B11, -B19, &-B21). Significant transcript accumulation of ABCB6 (31.8 folds), -B14 (147.5 folds), -B15 (17 folds), -B25 (19.7 folds), -B26 (18.31 folds), -B31 (61.89 folds), -B40 (1273 folds) and -B42 (51 folds) was observed under the influence of auxin. Auxin transport-specific inhibitor, N-1-naphthylphthalamic acid, showed its effectiveness only at higher (10 µM) concentration where it down regulated the expression of ABCBs, PINs (PIN FORMED) and TWD1 (TWISTED DWARF 1) genes in shoot tissues, while their expression was seen to enhance in the root tissues. Further, qRT-PCR analysis under various growth conditions (in-vitro, field and growth chamber), and subjected to abiotic stresses revealed differential expression implicating role of ABCBs in stress management. Seven of the nine genes were shown to be involved in the stress physiology of the plant. GgABCB6, 15, 25 and ABCB31 were induced in multiple stresses, while GgABCB26, 40 & 42 were exclusively triggered under drought stress. No study pertaining to the ABC transporters from G. glabra is available till date. The present investigation will give an insight to auxin transportation which has been found to be associated with plant growth architecture; the knowledge will help to understand the association between auxin transportation and plant responses under the influence of various conditions.
Bioinformatics integration reveals key genes associated with mitophagy in myocardial ischemia-reperfusion injury
Authors: Chen Zhian , Liu Tianying , Yuan Hao , Sun Han , Liu Sitong , Zhang Shuai , Liu Li , Jiang Shuang , Tang Yong , Liu Zhi 
Published: March 2024

Background
Myocardial ischemia is a prevalent cardiovascular disorder associated with significant morbidity and mortality. While prompt restoration of blood flow is essential for improving patient outcomes, the subsequent reperfusion process can result in myocardial ischemia–reperfusion injury (MIRI). Mitophagy, a specialized autophagic mechanism, has consistently been implicated in various cardiovascular disorders. However, the specific connection between ischemia–reperfusion and mitophagy remains elusive. This study aims to elucidate and validate central mitophagy-related genes associated with MIRI through comprehensive bioinformatics analysis.

Methods
We acquired the microarray expression profile dataset (GSE108940) from the Gene Expression Omnibus (GEO) and identified differentially expressed genes (DEGs) using GEO2R. Subsequently, these DEGs were cross-referenced with the mitophagy database, and differential nucleotide sequence analysis was performed through enrichment analysis. Protein–protein interaction (PPI) network analysis was employed to identify hub genes, followed by clustering of these hub genes using cytoHubba and MCODE within Cytoscape software. Gene set enrichment analysis (GSEA) was conducted on central genes. Additionally, Western blotting, immunofluorescence, and quantitative polymerase chain reaction (qPCR) analyses were conducted to validate the expression patterns of pivotal genes in MIRI rat model and H9C2 cardiomyocytes.

Results
A total of 2719 DEGs and 61 mitophagy-DEGs were identified, followed by enrichment analyses and the construction of a PPI network. HSP90AA1, RPS27A, EEF2, EIF4A1, EIF2S1, HIF-1α, and BNIP3 emerged as the seven hub genes identified by cytoHubba and MCODE of Cytoscape software. Functional clustering analysis of HIF-1α and BNIP3 yielded a score of 9.647, as determined by Cytoscape (MCODE). In our MIRI rat model, Western blot and immunofluorescence analyses confirmed a significant elevation in the expression of HIF-1α and BNIP3, accompanied by a notable increase in the ratio of LC3II to LC3I. Subsequently, qPCR confirmed a significant upregulation of HIF-1α, BNIP3, and LC3 mRNA in the MIRI group. Activation of the HIF-1α/BNIP3 pathway mediates the regulation of the degree of Mitophagy, thereby effectively reducing apoptosis in rat H9C2 cardiomyocytes.

Conclusions
This study has identified seven central genes among mitophagy-related DEGs that may play a pivotal role in MIRI, suggesting a correlation between the HIF-1α/BNIP3 pathway of mitophagy and the pathogenesis of MIRI. The findings highlight the potential importance of mitophagy in MIRI and provide valuable insights into underlying mechanisms and potential therapeutic targets for further exploration in future studies.
Upregulation of CIRP by its agonist prevents the development of heart failure in myocardial infarction rats
Authors: Zhang Jingjing , Liu Tao , Wei Yanzhao , Peng Jianye , Zeng Gaofeng , Zhong Peng 
Published: March 2024

Abstract
Background
Downregulated expression of cold-inducible RNA binding protein (CIRP), a stress-response protein, has been demonstrated in the hearts of patients with heart failure (HF). However, whether CIRP plays a critical role in the pathogenesis of HF remains unknown. Zr17-2 is a recently identified CIRP agonist, which can enhance the expression of CIRP in hearts. Herein, we evaluated the effects of zr17-2 on the development of HF in a rat model of myocardial infarction (MI).

Methods
Male SD rats were pretreated with CIRP agonist zr17-2 or vehicle saline for 6 consecutive days, followed by MI induction. 1-week post-MI, cardiac function, and structural and molecular changes were determined by echocardiography and molecular biology methods.

Results
Excitingly, we found that pretreatment with zr17-2 significantly attenuated MI-induced cardiac dysfunction and dilation, coupled with reduced infarction size and cardiac remodeling. In addition, increased inflammatory response in the peri-infarcted heart including macrophage infiltration and the expression of inflammatory genes were all significantly decreased by zr17-2 pretreatment, suggesting an anti-inflammatory effect of zr17-2. Moreover, zr17-2 pretreatment also upregulated the antioxidant genes (e.g. NQO-1, Nrf2, and HO-1) level in the hearts. In isolated cultured cardiomyocytes, pretreatment with zr17-2 markedly attenuated cell injury and apoptosis induced by oxidative injury, along with elevation of Nrf2-related antioxidant genes and CIRP. However, silencing CIRP abolished zr17-2’s antioxidant effects against oxidative injury, confirming that zr17-2’s role is dependent on CIRP.

Conclusion
Collectively, our study suggests CIRP plays a crucial role in the development of HF and a beneficial effect of CIRP agonist in preventing MI-induced HF, possibly via anti-inflammatory and anti-oxidant pathways.
Food insecurity in urban American Indian and Alaska Native populations during the COVID-19 pandemic
Authors: Nelson Katie , Jackson Alexandra M. , Nguyen Cassandra J. , Noonan Carolyn , Muller Clemma , MacLehose Richard F. , Manson Spero M. , Dillard Denise A. , Buchwald Dedra ,   CONCERTS Collaborative, Madesclaire Odile , Henderson Austin , Quandelacey Talia 
Published: March 2024

Abstract
Background
Food insecurity is an important social determinant of health that was exacerbated by the COVID-19 pandemic. Both food insecurity and COVID-19 infection disproportionately affect racial and ethnic minority groups, particularly American Indian and Alaska Native communities; however, there is little evidence as to whether food insecurity is associated with COVID-19 infection or COVID-19 preventive behaviors such as vaccination uptake. The purpose of this study was to evaluate associations between food insecurity, COVID-19 infection, and vaccination status among urban American Indian and Alaska Native adults seen at 5 clinics serving urban Native people.

Methods
In partnership with health organizations in Alaska, Colorado, Kansas, Minnesota, and New Mexico, the study team conducted a cross-sectional survey in 2021 to assess food security status and attitudes, barriers, and facilitators for COVID-19 testing and vaccination. Logistic regression was used to examine the association of food security status with sociodemographic factors and COVID-19 infection and vaccination status. Marginal standardization was applied to present results as prevalence differences.

Results
Among 730 American Indian and Alaska Native adults, the prevalence of food insecurity measured during the pandemic was 38%. For participants who reported persistent food security status before and during the pandemic (n = 588), the prevalence of food insecurity was 25%. Prevalence of COVID-19 infection and vaccination did not vary by food security status after adjustment for confounders.

Conclusions
High rates of food insecurity among American Indian and Alaska Native communities likely increased during the COVID-19 pandemic. However, despite the high prevalence of food insecurity, community-led efforts to reduce COVID-19 infection and increase vaccination uptake across Indian Health Service and Tribal healthcare facilities may have mitigated the negative impacts of the pandemic for families experiencing food insecurity. These successful approaches serve as an important reference for future public health efforts that require innovative strategies to improve overall health in American Indian and Alaska Native communities.