bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enteroviral infections are not associated with type 2 diabetes
Authors: Liu Huan , Geravandi Shirin , Grasso Ausilia Maria , Sikdar Saheri , Pugliese Alberto , Maedler Kathrin 
Published: October 2023

IntroductionFor more than a century, enteroviral infections have been associated with autoimmunity and type 1 diabetes (T1D). Uncontrolled viral response pathways repeatedly presented during childhood highly correlate with autoimmunity and T1D. Virus responses evoke chemokines and cytokines, the “cytokine storm” circulating through the body and attack cells especially vulnerable to inflammatory destruction. Intra-islet inflammation is a major trigger of β-cell failure in both T1D and T2D. The genetic contribution of islet inflammation pathways is apparent in T1D, with several mutations in the interferon system. In contrast, in T2D, gene mutations are related to glucose homeostasis in β cells and insulin-target tissue and rarely within viral response pathways. Therefore, the current study evaluated whether enteroviral RNA can be found in the pancreas from organ donors with T2D and its association with disease progression.MethodsPancreases from well-characterized 29 organ donors with T2D and 15 age- and BMI-matched controls were obtained from the network for pancreatic organ donors with diabetes and were analyzed in duplicates. Single-molecule fluorescence in-situ hybridization analyses were performed using three probe sets to detect positive-strand enteroviral RNA; pancreas sections were co-stained by classical immunostaining for insulin and CD45.ResultsThere was no difference in the presence or localization of enteroviral RNA in control nondiabetic and T2D pancreases; viral infiltration showed large heterogeneity in both groups ranging from 0 to 94 virus+ cells scattered throughout the pancreas, most of them in the exocrine pancreas. Very rarely, a single virus+ cell was found within islets or co-stained with CD45+ immune cells. Only one single T2D donor presented an exceptionally high number of viruses, similarly as seen previously in T1D, which correlated with a highly reduced number of β cells.DiscussionNo association of enteroviral infection in the pancreas and T2D diabetes could be found. Despite great similarities in inflammatory markers in islets in T1D and T2D, long-term enteroviral infiltration is a distinct pathological feature of T1D-associated autoimmunity and in T1D pancreases.
Long-term changes in coarse woody debris abundance in three Appalachian headwater streams with differing best management practices
Authors: Sena Kenton L. , Flynn Jerrica K. , Leuenberger Wendy , Kolka Randall , Barton Christopher D. 
Published: October 2023

IntroductionTimber harvests influence coarse woody debris (CWD) dynamics both initially and long-term—contributing a significant amount of CWD as slash immediately after harvest, but also removing some or all of the mature trees necessary to produce CWD over time. Whereas shelterwood and other similar timber harvest systems retain varying amounts of the overstory, preserving CWD production after harvest, commercial clearcutting essentially eliminates sources of fresh CWD until regenerating trees are large enough to contribute CWD through fallen limbs or trunks, often decades after harvest. Forestry best management practices (BMPs) are critical for reducing the water quality impacts of timber harvest, but their effects on riparian and stream CWD are not well understood.MethodsThe current project explores CWD dynamics (surveyed in 2001, 2004, 2009, and 2020) in three eastern Kentucky watersheds receiving differing timber harvest treatments in 1983: unharvested control, BMPs (clearcut with a protected streamside management zone), and no BMPs (clearcut).ResultsAnalysis of hydrology data over the period of record demonstrated significant flooding in 2004 that likely “reset” CWD in the study watersheds. Coarse woody debris volume was higher in control (3.33 m3/ha) than no BMP (1.03 m3/ha) in 2020, with CWD accumulation rates ranging from 0.039 m3/ha in the no BMP watershed to 0.19 m3/ha in the control.DiscussionWhile not significantly different, CWD volume was nominally higher in the BMP watershed than the No BMP watershed, suggesting that, in addition to their many other benefits, streamside management zones help facilitate CWD provisioning during stand initiation after a commercial clearcut harvest. Furthermore, this study suggests that provisioning of CWD may not recover after clearcut harvesting for 100 years or more.
Novel mediator in anaphylaxis: decreased levels of miR-375-3p in serum and within extracellular vesicles of patients
Authors: Nuñez-Borque Emilio , Fernandez-Bravo Sergio , Rodríguez Del Rio Pablo , Palacio-García Lucia , Di Giannatale Angela , Di Paolo Virginia , Galardi Angela , Colletti Marta , Pascucci Luisa , Tome-Amat Jaime , Cuesta-Herranz Javier , Ibañez-Sandin María Dolores , Laguna José Julio , Benito-Martin Alberto , Esteban Vanesa 
Published: October 2023

IntroductionAnaphylaxis is among the most severe manifestations of allergic disorders, but its molecular basis remains largely unknown and reliable diagnostic markers are not currently available. MicroRNAs (miRNAs) regulate several pathophysiological processes and have been proposed as non-invasive biomarkers. Therefore, this study aims to evaluate their involvement in anaphylactic reaction and their value as biomarkers.MethodsAcute (anaphylaxis) and baseline (control) serum samples from 67 patients with anaphylaxis were studied. Among them, 35 were adults with drug-induced anaphylaxis, 13 adults with food-induced anaphylaxis and 19 children with food-induced anaphylaxis. The circulating serum miRNAs profile was characterized by next-generation sequencing (NGS). For this purpose, acute and baseline samples from 5 adults with drug-induced anaphylaxis were used. RNA was extracted, retrotranscribed, sequenced and the readings obtained were mapped to the human database miRBase_20. In addition, a system biology analysis (SBA) was performed with its target genes and revealed pathways related to anaphylactic mediators signaling. Moreover, functional and molecular endothelial permeability assays were conducted with miR-375-3p-transfected cells in response to cAMP.ResultsA total of 334 miRNAs were identified, of which 21 were significant differentially expressed between both phases. Extracellular vesicles (EVs) were characterized by Western blot, electron microscopy and NanoSight. A decrease of miR-375-3p levels was determined by qPCR in both serum and EVs of patients with anaphylaxis (****p&lt;.0001). Precisely, the decrease of miR-375-3p correlated with the increase of two inflammatory cytokines: monocyte chemoattractant protein-1 (MCP-1) and granulocyte macrophage colony-stimulating factor (GM-CSF). On the other hand, functional and molecular data obtained showed that miR-375-3p partially blocked the endothelial barrier maintenance and stabilization by disassembly of cell-cell junctions exhibiting low Rac1-Cdc42 levels.DiscussionThese findings demonstrate a differential serum profile of circulating miRNAs in patients with anaphylaxis and exhibit the miR-375-3p modulation in serum and EVs during drug- and food-mediated anaphylactic reactions. Furthermore, the in silico and in vitro studies show a negative role for miR-375-3p/Rac1-Cdc42 in the endothelial barrier stability.
Real world experience on the effectiveness and safety of pirfenidone in patients with idiopathic pulmonary fibrosis in Taiwan
Authors: Chang Cheng-Yu , Wei Yu-Feng , Chen Chung-Yu , Lai Yi-Chun , Hu Po-Wei , Hung Jui-Chi , Chu Chi-Hsiang , Chuang Hsin-Tzu , Chang Shih-Chieh 
Published: October 2023

IntroductionRandomized controlled trials have demonstrated a reduction in the decline of lung function and a reduced risk of acute exacerbation in patients with idiopathic pulmonary fibrosis treated with the antifibrotic prifenidone. The present study aimed to investigate the real-world effectiveness and safety profile of pirfenidone treatment for patients with IPF in Taiwan.MethodsBetween January 1, 2019 and December 31, 2020, we enrolled 50 patients who were newly diagnosed with IPF and had at least 12 months follow-up period after pirfenidone administration.ResultThe primary outcome of pharmacologic effect showed that the mean differences in the absolute values of forced vital capacity from baseline were 0.2 liter (n = 36), 0.13 liter (n = 32), 0.04 liter (n = 26), and − 0.004 liter (n = 26) after 3, 6, 9, and 12 months of administration, respectively. A slight improvement in quality of life, including scores of chronic obstructive pulmonary disease assessment test and St. George’s respiratory questionnaire scores. The most common adverse effects were gastrointestinal upset and dermatological problems. No new safety concerns were observed in the present study.ConclusionOur real-world study describe for the first time in Taiwan, the use of pirfenidone over a 12 months period. This drug preserves the lung function and improves quality of life with tolerable side effects.
Antibacterial and antibiofilm activity of Abroma augusta stabilized silver (Ag) nanoparticles against drug-resistant clinical pathogens
Authors: Kumar Sachin , Khan Haris M. , Husain Fohad Mabood , Ahmad Rafiq , Qais Faizan Abul , Khan Mo Ahamad , Jalal Mohammad , Tayyaba Uzma , Ali Syed Ghazanfar , Singh Amardeep , Shahid Mohammad , Lee Byeong-Il 
Published: October 2023

Infectious diseases remain among the most pressing concerns for human health. This issue has grown even more complex with the emergence of multidrug-resistant (MDR) bacteria. To address bacterial infections, nanoparticles have emerged as a promising avenue, offering the potential to target bacteria at multiple levels and effectively eliminate them. In this study, silver nanoparticles (AA-AgNPs) were synthesized using the leaf extract of a medicinal plant, Abroma augusta. The synthesis method is straightforward, safe, cost-effective, and environment friendly, utilizing the leaf extract of this Ayurvedic herb. The UV-vis absorbance peak at 424 nm indicated the formation of AA-AgNPs, with the involvement of numerous functional groups in the synthesis and stabilization of the particles. AA-AgNPs exhibited robust antibacterial and antibiofilm activities against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). The MIC values of AA-AgNPs ranged from 8 to 32 μg/mL. Electron microscopic examination of the interaction of AA-AgNPs with the test bacterial pathogens showed a deleterious impact on bacterial morphology, resulting from membrane rupture and leakage of intracellular components. AA-AgNPs also demonstrated a dose-dependent effect in curtailing biofilm formation below inhibitory doses. Overall, this study highlights the potential of AA-AgNPs in the successful inhibition of both the growth and biofilms of MRSA and VRE bacteria. Following studies on toxicity and dose optimization, such AgNPs could be developed into effective medical remedies against infections.
Effect of recombinant human nerve growth factor treatment on corneal nerve regeneration in patients with neurotrophic keratopathy
Authors: Balbuena-Pareja Ana , Bogen Chloe S. , Cox Stephanie M. , Hamrah Pedram 
Published: October 2023

IntroductionNeurotrophic Keratopathy (NK) is a neurodegenerative corneal disease that results in diminished corneal sensation. Previous studies have found that Cenegermin 0.002%, a recombinant human nerve growth factor (rhNGF), improves corneal epithelial healing in stage 2 and 3 NK patients. However, rhNGF effect on corneal sensation and nerve regeneration has not been well established. Thus, this study aims to analyze the effect of rhNGF on corneal nerve regeneration using in vivo confocal microscopy (IVCM) and on corneal sensitivity in NK patients.MethodsThis is a retrospective, longitudinal, case–control study that included patients with NK, treated with rhNGF for at least 4 weeks, with pre- and post-treatment IVCM images available for analysis. Chart reviews were conducted documenting prior medical and surgical history, clinical signs and symptoms, and corneal sensation using Cochet-Bonnet esthesiometry. Corneal nerve parameters were assessed by IVCM. Sex- and age-matched reference controls were selected from a database of healthy subjects for comparison.ResultsThe study included 25 patients, with 22 (88%) stage 1, two (8%) stage 2, and 1 (4%) stage 3 NK patients, with a median age of 64 years (range: 30–93 years). Total, main, and branch nerve densities [median (range) in mm/mm2] were lower in the NK group pre-treatment [2.3 (0.0–21.1); 1.7 (0.0–13.0); 0.5 (0.0–10.2); respectively] vs. controls [22.3 (14.9–29.0); 10.1 (3.2–15.4); and 12.1 (6.2–18.4), (p &lt; 0.0001 for all), respectively]. Post-treatment nerve densities increased compared to pre-treatment to 5.3 (0.0–19.4, p = 0.0083) for total, 3.5 (0.0–13.2, p = 0.0059) for main, and 2.0 (0.0–10.4, p = 0.0251) for branch nerves, but remained lower than controls (p &lt; 0.0001 for all). Corneal sensation increased from 2.3 ± 1.1 cm pre-treatment to 4.1 ± 1.4 cm post-treatment (p = 0.001). Median best corrected visual acuity significantly increased following rhNGF treatment from 0.4 (0.0–1.6) to 0.12 (−0.1 to 1.6) (p = 0.007).ConclusionPatients with NK treated with at least 4 weeks of rhNGF, showed a significant increase in corneal nerve densities after treatment. A significant increase in corneal sensation, as well as best corrected visual acuity, was observed following treatment.
Maximum intensity projection based on high frame rate contrast-enhanced ultrasound for the differentiation of breast tumors
Authors: Li Jia , Wei Cong , Ma Xinxin , Ying Tao , Sun Di , Zheng Yuanyi 
Published: October 2023

ObjectiveWe explored the role of maximum intensity projection (MIP) based on high frame rate contrast-enhanced ultrasound (H-CEUS) for the differentiation of breast tumors.MethodsMIP imaging was performed in patients with breast tumors who underwent H-CEUS examinations. The microvasculature morphology of breast tumors was assessed. The receiver operating characteristic curve was plotted to evaluate the diagnostic performance of MIP.ResultsForty-three breast tumors were finally analyzed, consisting of 19 benign and 24 malignant tumors. For the ≤30-s and &gt;30-s phases, dot-, line-, or branch-like patterns were significantly more common in benign tumors. A tree-like pattern was only present in the benign tumors. A crab claw-like pattern was significantly more common in the malignant tumors. Among the tumors with crab claw-like patterns, three cases of malignant tumors had multiple parallel small spiculated vessels. There were significant differences in the microvasculature morphology for the ≤30-s and &gt;30-s phases between the benign and malignant tumors (all p &lt; 0.001). The area under the curve, sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the ≤30-s phase were all higher than those of the &gt;30-s phase for the classification of breast tumors.ConclusionMIP based on H-CEUS can be used for the differentiation of breast tumors, and the ≤30-s phase had a better diagnostic value. Multiple parallel small spiculated vessels were a new finding, which could provide new insight for the subsequent study of breast tumors.
Do disease-modifying antirheumatic drugs and non-steroidal anti-inflammatory drugs increase the burden on ankylosing spondylitis patients with mild-moderate COVID-19? evidence from a retrospective cohort study
Authors: Li Yan , Hu Zhengyuan , Guo Yufei , Zhao Zheng , Li Kunpeng , Wang Xiuru , Zhang Jie , Liang Dongfeng , Zhang Jianglin , Hu Xiaoyue , Zhu Jian , Huang Feng 
Published: October 2023

Objectives: The impact of non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and tumor necrosis factor inhibitors (TNFi) on the outcomes of mild-moderate COVID-19 in patients with ankylosing spondylitis (AS) remains unclear. This study aimed to evaluate the effects of NSAIDs, csDMARDs, and TNFi on AS patients with mild-moderate COVID-19.Methods: This cohort study utilized patient-reported PCR/antigen tests to determine the occurrence of COVID-19 and assessed clinical manifestations to determine its severity. The study focused on two primary outcomes: an increased number of COVID-19 symptoms and a prolonged disease course (longer than 10 or 28 days). Modified Poisson regression was performed to analyze the association between exposures and outcomes.Results: A total of 521 patients were included in the analysis. The median age was 34.8 (inter-quartile range: 27.2–46.7), with 420 (80.6%) being men. Among the patients, 52 (10.0%) had comorbidities and 443 (85%) had been vaccinated. After adjusting for confounding factors, there was no significant association between csDMARDs or TNFi and the presence of more than 5 symptoms in mild-moderate COVID-19 (adjusted relative risk (RRa) 1.08, 95% CI: 0.84–1.40 or 1.09, 0.92–1.29 for csDMARDs or TNFi, respectively), whereas the prevalence of experiencing more than 5 symptoms increased in patients with NSAID monotherapy (RRa 1.22, 95% CI: 1.01–1.46). Similarly, there was no significant association with having more than 10 symptoms (RRa 0.65, 95% CI: 0.26–1.64; 0.95, 0.36–2.54; and 1.01, 0.53–1.91 for NSAIDs, csDMARDs, and TNFi, respectively). Patients who had pre-existing use of NSAIDs, csDMARDs and TNFi had similar odds of experiencing a disease course longer than 10 days (RRa 1.17, 95% CI: 0.82–1.66; 1.18, 0.78–1.77; and 1.22, 0.92–1.63 for NSAIDs, csDMARDs, and TNFi, respectively) and longer than 28 days (RRa 0.94, 95% CI: 0.31–2.81; 0.97, 0.25–3.74 and 1.05, 0.44–2.49, respectively) compared to those not using medication.Conclusion: AS patients treated with csDMARDs or TNFi did not show inferior outcomes in terms of symptom burden or recovery compared to those not using medication in mild-moderate COVID-19. The observed inverse association between pre-existing NSAIDs use and COVID-19 symptom burden in AS deserves further investigation.
Exodus of Lebanese doctors in times of crisis: a qualitative study
Authors: Nemr Elie , Moussallem Marianne , Nemr Rita , Kosremelli Asmar Michèle 
Published: October 2023

IntroductionSince 2019, Lebanon is experiencing an unprecedented exodus of doctors, seriously threatening the national health system, which is expected to continue without quick and effective solutions. Therefore, this study aimed to understand the factors that push Lebanese doctors to migrate and the factors that retain others in the country. Additionally, this study aims to propose solutions to preserve an adequate supply of medical care amidst the crisis.MethodsQualitative semi-structured interviews and focus group discussions were conducted using pre-developed guides. Purposive and snowball sampling was adopted to recruit physicians who emigrated and physicians staying in Lebanon. Transcripts of interviews and focus groups were coded using Dedoose software and analyzed through a combination of inductive and deductive approaches.ResultsEmigration was found to be the result of numerous interconnected factors. The main drivers for emigration were declining income, career problems, reduced quality of care, unhealthy work environment, and the deteriorated political and socio-economic contexts leading to instability and insecurity. As for the retention factors, they included affective attachment and sense of belonging to the professional environment and the country, followed by recognition and valorization at work. Several recommendations were developed to maintain quality of care delivery, including reforms of the health system, development of focused human resource retention strategies based on resource mapping evidence, negotiations with recruiting institutions to endorse the code ethics ending unethical practices draining countries' human resources, provision of financial incentives to doctors, and the recognition and valorization of physicians. Other rapid interventions were suggested, such as short-term medical missions to mitigate shortages in certain specialties, telemedicine, adaptation of recruitment processes to compensate for resources shortages in certain specialties, and adoption of task-shifting approaches to alleviate the workload on overburdened specialists.DiscussionThe findings of this study shed the light on the different factors influencing migration while framing them in the Lebanese context. These findings and recommendations should inform stakeholders and policy makers about the interventions needed to restore the quality of care. The feasibility and sustainability of most formulated recommendations depend on several factors, with political and socio-economic security and stability being the most crucial ones.
Compact Physics Hot-Carrier Degradation Model Valid over a Wide Bias Range
Authors: Tyaginov Stanislav , Bury Erik , Grill Alexander , Yu Zhuoqing , Makarov Alexander , De Keersgieter An , Vexler Mikhail , Vandemaele Michiel , Wang Runsheng , Spessot Alessio , Chasin Adrian , Kaczer Ben 
Published: October 2023

We develop a compact physics model for hot-carrier degradation (HCD) that is valid over a wide range of gate and drain voltages (Vgs and Vds, respectively). Special attention is paid to the contribution of secondary carriers (generated by impact ionization) to HCD, which was shown to be significant under stress conditions with low Vgs and relatively high Vds. Implementation of this contribution is based on refined modeling of carrier transport for both primary and secondary carriers. To validate the model, we employ foundry-quality n-channel transistors and a broad range of stress voltages {Vgs,Vds}.
Volatile Composition, Antimicrobial Activity, and In Vitro Innate Immunomodulatory Activity of Echinacea purpurea (L.) Moench Essential Oils
Authors: Dosoky Noura S. , Kirpotina Liliya N. , Schepetkin Igor A. , Khlebnikov Andrei I. , Lisonbee Brent L. , Black Jeffrey L. , Woolf Hillary , Thurgood Trever L. , Graf Brittany L. , Satyal Prabodh , Quinn Mark T. 
Published: October 2023

Echinacea purpurea (L.) Moench is a medicinal plant commonly used for the treatment of upper respiratory tract infections, the common cold, sore throat, migraine, colic, stomach cramps, and toothaches and the promotion of wound healing. Based on the known pharmacological properties of essential oils (EOs), we hypothesized that E. purpurea EOs may contribute to these medicinal properties. In this work, EOs from the flowers of E. purpurea were steam-distilled and analyzed by gas chromatography–mass spectrometry (GC–MS), GC with flame-ionization detection (GC–FID), and chiral GC–MS. The EOs were also evaluated for in vitro antimicrobial and innate immunomodulatory activity. About 87 compounds were identified in five samples of the steam-distilled E. purpurea EO. The major components of the E. purpurea EO were germacrene D (42.0 ± 4.61%), α-phellandrene (10.09 ± 1.59%), β-caryophyllene (5.75 ± 1.72%), γ-curcumene (5.03 ± 1.96%), α-pinene (4.44 ± 1.78%), δ-cadinene (3.31 ± 0.61%), and β-pinene (2.43 ± 0.98%). Eleven chiral compounds were identified in the E. purpurea EO, including α-pinene, sabinene, β-pinene, α-phellandrene, limonene, β-phellandrene, α-copaene, β-elemene, β-caryophyllene, germacrene D, and δ-cadinene. Analysis of E. purpurea EO antimicrobial activity showed that they inhibited the growth of several bacterial species, although the EO did not seem to be effective for Staphylococcus aureus. The E. purpurea EO and its major components induced intracellular calcium mobilization in human neutrophils. Additionally, pretreatment of human neutrophils with the E. purpurea EO or (+)-δ-cadinene suppressed agonist-induced neutrophil calcium mobilization and chemotaxis. Moreover, pharmacophore mapping studies predicted two potential MAPK targets for (+)-δ-cadinene. Our results are consistent with previous reports on the innate immunomodulatory activities of β-caryophyllene, α-phellandrene, and germacrene D. Thus, this study identified δ-cadinene as a novel neutrophil agonist and suggests that δ-cadinene may contribute to the reported immunomodulatory activity of E. purpurea.