bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional evaluation of constructed pseudo-endogenous microRNA-targeted myocardial ultrasound nanobubble
Authors: Ainiwan Ailifeire , Wei Yuanyuan , Dou Jing , Tang Lingpeng , Mu Yuming , Guan Lina 
Published: September 2023

BackgroundStem cell transplantation is one of the treatment methods for acute myocardial infarction (AMI). MicroRNA-1 contributes to the study of the essential mechanisms of stem cell transplantation for treating AMI by targeted regulating the myocardial microenvironment after stem cell transplantation at the post-transcriptional level. Thus, microRNA-1 participates in regulating the myocardial microenvironment after stem cell transplantation, a promising strategy for the Stem cell transplantation treatment of AMI. However, the naked microRNA-1 synthesized is extremely unstable and non-targeting, which can be rapidly degraded by circulating RNase. Herein, to safely and effectively targeted transport the naked microRNA-1 synthesized into myocardial tissue, we will construct pseudo-endogenous microRNA-targeted myocardial ultrasound nanobubble pAd-AAV-9/miRNA-1 NB and evaluate its characteristics, targeting, and function.MethodsThe pAd-AAV-9/miRNA-1 gene complex was linked to nanobubble NBs by the “avidin-biotin bridging” method to prepare cardiomyocyte-targeted nanobubble pAd-AAV-9/miRNA-1 NB. The shape, particle size, dispersion, and stability of nanobubbles and the connection of pAd-AAV-9/miRNA-1 gene complex to nanobubble NB were observed. The virus loading efficiency was determined, and the myocardium-targeting imaging ability was evaluated using contrast-enhanced ultrasound imaging in vivo. The miRNA-1 expression level in myocardial tissue and other vital organs ex vivo of SD rats was considered by Q-PCR. Also, the cytotoxic effects were assessed.ResultsThe particle size of NBs was 504.02 ± 36.94 nm, and that of pAd-AAV-9/miRNA-1 NB was 568.00 ± 37.39 nm. The particle size and concentration of pAd-AAV-9/miRNA-1 NBs did not change significantly within 1 h at room temperature (p &gt; 0.05). pAd-AAV-9/miRNA-1 NB had the highest viral load rate of 86.3 ± 2.2% (p &lt; 0.05), and the optimum viral load was 5 μL (p &lt; 0.05). pAd-AAV-9/miRNA-1 NB had good contrast-enhanced ultrasound imaging in vivo. Quantitative analysis of miRNA-1 expression levels in vital organs ex vivo of SD rats by Q-PCR showed that pAd-AAV-9/miRNA-1 NB targeted the myocardial tissue. Q-PCR indicated that the expression level of miRNA-1 in the myocardium of the pAd-AAV-9/miRNA-1 NB + UTMD group was significantly higher than that of the pAd-AAV-9/miRNA-1 NB group (p &lt; 0.05). pAd-AAV-9/miRNA-1 NB had no cytotoxic effect on cardiomyocytes (p &gt; 0.05).ConclusionThe pAd-AAV-9/miRNA-1 NB constructed in this study could carry naked miRNA-1 synthesized in vitro for targeted transport into myocardial tissue successfully and had sound contrast-enhanced imaging effects in vivo.
A comparison of clinical outcomes among people living with HIV of different age groups attending queen Elizabeth central hospital outpatient ART Clinic in Malawi
Authors: Chakakala-Chaziya Jessica , Patson Noel , Samuel Vincent , Mbotwa John , Buonsenso Danilo , Chisale Master , Phiri Eddie , O’Hare Bernadette 
Published: September 2023

IntroductionAdherence to Antiretroviral Treatment (ART) in children and adolescents living with HIV in low-resource settings is not extensively studied in large cohort studies including both adults and pediatric patients. We compared rates of virological suppression, adherence and defaulting among children, adolescents and adults attending a family ART clinic at Queen Elizabeth Central Hospital; a tertiary hospital situated in the southern region of Malawi.MethodsThe study was longitudinal and made use of routinely collected data for all 27,229 clinic attendees. Clinical information obtained at routine clinical visits entered electronically since 2008 was extracted in February 2017. This data was used to ascertain differences across the different age groups. Logistic regression and Cox regression models were fitted to compare rates of Virological Suppression (VS), adherence, and defaulting, respectively.ResultsYounger and older adolescents (ages 10–14 years and 15–19 years respectively) were less likely to achieve VS compared to adults in the final model AOR 0.4 (0.2–0.9, 95% CI) and AOR 0.2 (0.1–0.4, 95% CI) respectively. Young children (ages 0–4 years), older children (ages 5–9 years) and younger adolescents were less adherent to ART compared to adults AOR 0.1 (0.1–0.2, 95% CI), AOR 0.2 (0.1–0.3, 95% CI), and AOR 0.4 (0.3–0.5, 95% CI) respectively. Young adults and younger children had an increased likelihood of defaulting compared to adults.ConclusionPoor performance on ART of children and adolescents highlights unaddressed challenges to adherence. Ongoing research to explore these potential barriers and possible interventions needs to be carried out. The adherence assessment methods used and strategies for improving it among children and adolescents need to be revised at the clinic.
Herpetic anterior uveitis following COVID-19 vaccines: a case series
Authors: Ott Muriel , Nagamany Thanoosha , Zandi Souska , Pichi Francesco , Agarwal Aniruddha , Carreño Ester , Gupta Vishali , Grewal Dilraj S. , Cunningham Emmett T. , Munk Marion R. 
Published: September 2023

PurposeTo report a case series of herpetic uveitis following COVID-19 vaccinations.MethodsDemographic, clinical and treatment-related data of herpetic anterior uveitis cases was collected at five tertiary eye hospitals between January 2021 and June 2022. A retrospective database review at one of the centers comparing the number of cases of herpetic eye disease before and after the introduction of COVID-19 vaccination was performed as well.ResultsTwenty-four patients (9 female, 15 male) with a mean age of 54 years (range 28–83 years) were diagnosed with herpetic uveitis, reporting an onset of symptoms 3–42 days after the first, second or third dose of COVID-19 vaccination. Median time between vaccination and onset of herpetic eye disease was 10 days (mean 12.7 ± 10.15 days) days. The administered vaccines were BNT162b2, mRNA-1273, BBIBP-CorV and Ad26.COV2.S. The cases included 11 HSV, 10 VZV and 1 CMV anterior uveitis, 2 were not further specified. There was an equal number of first episodes (n = 12, 50%) and recurrent episodes (n = 12, 50%). Response to established regimens was generally good. The retrospective database review revealed the exact same incidence of herpetic uveitis during the pandemic and ongoing vaccination compared to prior SARS-CoV-2.ConclusionThis report includes 24 cases of herpetic anterior uveitis in a temporal relationship to various COVID-19 vaccines. This study supports the potential risk of herpetic eye disease following COVID-19 vaccines, but proof of a direct, causal relationship is missing.
Auction market placement and a rest stop during transportation affect the respiratory bacterial microbiota of beef cattle
Authors: Uddin Muhammed Salah , Schwartzkopf-Genswein Karen S. , Waldner Matthew , Meléndez Daniela M. , Niu Yan D. , Alexander Trevor W. 
Published: September 2023

BackgroundBovine respiratory disease (BRD) is a significant health problem in beef cattle production, resulting in considerable economic losses due to mortalities, cost of treatment, and reduced feed efficiency. The onset of BRD is multifactorial, with numerous stressors being implicated, including transportation from farms to feedlots. In relation to animal welfare, regulations or practices may require mandatory rest times during transportation. Despite this, there is limited information on how transportation and rest stops affect the respiratory microbiota.ResultsThis study evaluated the effect of cattle source (ranch-direct or auction market-derived) and rest stop duration (0 or 8 h of rest) on the upper respiratory tract microbiota and its relationship to stress response indicators (blood cortisol and haptoglobin) of recently weaned cattle transported for 36 h. The community structure of bacteria was altered by feedlot placement. When cattle were off-loaded for a rest, several key bacterial genera associated with BRD (Mannheimia, Histophilus, Pasteurella) were increased for most sampling times after feedlot placement for the ranch-direct cattle group, compared to animals given no rest stop. Similarly, more sampling time points had elevated levels of BRD-associated genera when auction market cattle were compared to ranch-direct. When evaluated across time and treatments several genera including Mannheimia, Moraxella, Streptococcus and Corynebacterium were positively correlated with blood cortisol concentrations.ConclusionThis is the first study to assess the effect of rest during transportation and cattle source on the respiratory microbiota in weaned beef calves. The results suggest that rest stops and auction market placement may be risk factors for BRD, based solely on increased abundance of BRD-associated genera in the upper respiratory tract. However, it was not possible to link these microbiota to disease outcome, due to low incidence of BRD in the study populations. Larger scale studies are needed to further define how transportation variables impact cattle health.
The retrograde IFT dynein is required for normal function of diverse mechanosensory cilia in Drosophila
Authors: Sharma Yashoda , Jacobs Julie S. , Sivan-Loukianova Elena , Lee Eugene , Kernan Maurice J. , Eberl Daniel F. 
Published: September 2023

IntroductionCilia biogenesis relies on intraflagellar transport (IFT), a conserved transport mechanism which functions bi-directionally to bring protein complexes to the growing ciliary tip and recycle signaling and transport proteins between the cilium and cell body. In Drosophila, anterograde IFT is critical for assembly of sensory cilia in the neurons of both chordotonal (ch) organs, which have relatively long ciliary axonemes, and external sensory (es) organs, which have short axonemal segments with microtubules in distal sensory segments forming non-axonemal bundles. We previously isolated the beethoven (btv) mutant in a mutagenesis screen for auditory mutants. Although many btv mutant flies are deaf, some retain a small residual auditory function as determined both by behavior and by auditory electrophysiology.ResultsHere we molecularly characterize the btv gene and demonstrate that it encodes the IFT-associated dynein-2 heavy chain Dync2h1. We also describe morphological changes in Johnston’s organ as flies age to 30 days, and we find that morphological and electrophysiological phenotypes in this ch organ of btv mutants become more severe with age. We show that NompB protein, encoding the conserved IFT88 protein, an IFT complex B component, fails to be cleared from chordotonal cilia in btv mutants, instead accumulating in the distorted cilia. In macrochaete bristles, a class of es organ, btv mutants show a 50% reduction in mechanoreceptor potentials.DiscussionThus, the btv-encoded Dync2h1 functions as the retrograde IFT motor in the assembly of long ciliary axonemes in ch organs and is also important for normal function of the short ciliary axonemes in es organs.
Effects of anthocyanin supplementation in diet on glycemic and related cardiovascular biomarkers in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials
Authors: Mao Ting , Akshit F. N. U. , Mohan Maneesha S. 
Published: September 2023

PurposeThis study is the first systematic review and meta-analysis based on RCTs on the effects of anthocyanins on patients with type 2 diabetes mellitus (T2DM) and the effect on T2DM-related cardiovascular disease.MethodsRCTs published in English from five electronic databases were evaluated for glycated hemoglobin (HbA1c), fasting blood glucose (FBG), 2-h postprandial blood glucose, fasting insulin, model assessment for insulin resistance, triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, systolic blood pressure, and diastolic blood pressure. The quality of the studies was rated (Cochrane Risk of Bias tool) and weighted mean differences were calculated (DerSimonian-Laird model with random effects). Leave-one-out sensitivity, subgroup, and publication bias analyses were conducted. The strength of the evidence was rated according to the GRADE guidelines.ResultsIn all, 13 RCTs were analyzed out of the 239 identified studies, with a duration longer than 4 weeks (703 participants with T2DM). Our findings indicate that a median dose of 320 mg/day anthocyanins, either from fruit extracts or pure supplements, for a median intervention length of 8 weeks significantly reduced HbA1c [Weighted Mean Difference (WMD) −0.31, p = 0.00], FBG (WMD −0.63, p = 0.00), 2-h postprandial glucose (WMD −1.60, p = 0.00), TG (WMD −0.45, p = 0.01), and LDL (WMD −0.26 p = 0.02). However, the effects of anthocyanins on fasting insulin, HOMA-IR, TC, HDL cholesterol, systolic blood pressure, and diastolic blood pressure in patients with T2DM were not statistically significant. Anthocyanins from fruit extracts or powder exhibited a higher reduction of HbA1c compared to pure anthocyanin supplements.ConclusionThe significant improvements in glycemic parameters and lipid profile, suggest the benefits of anthocyanins, especially from fruit extract or powder, in the management of T2DM, and their ability to delay the onset of lipid disorder-related diseases such as cardiovascular disease associated with T2DM. The mechanism behind this reduction in glycemic markers could be attributed to the antioxidant and anti-inflammatory activity of anthocyanins. Further research with well-designed RCTs is required to determine the optimal dosage of anthocyanins for the treatment of T2DM and to comprehend the consequences.
Serum autoantibody profiling of oral squamous cell carcinoma patients reveals NUBP2 as a potential diagnostic marker
Authors: Abdulla Riaz , Devasia Puthenpurackal Jofy , Pinto Sneha M. , Rekha Punchappady Devasya , Subbannayya Yashwanth 
Published: September 2023

IntroductionOral Squamous Cell Carcinoma (OSCC), a common malignancy of the head and neck region, is frequently diagnosed at advanced stages, necessitating the development of efficient diagnostic methods. Profiling autoantibodies generated against tumor-associated antigens have lately demonstrated a promising role in diagnosis, predicting disease course, and response to therapeutics and relapse.MethodsIn the current study, we, for the first time, aimed to identify and evaluate the diagnostic value of autoantibodies in serum samples of patients with OSCC using autoantibody profiling by an immunome protein array. The utility of anti-NUBP2 antibody and tissue positivity in OSCC was further evaluated.Results and discussionWe identified a total of 53 autoantibodies with significant differential levels between OSCC and control groups, including 25 that were increased in OSCC and 28 that were decreased. These included autoantibodies against Thymidine kinase 1 (TK1), nucleotide-binding protein 2 (NUBP2), and protein pyrroline-5-carboxylate reductase 1 (PYCR1), among others. Immunohistochemical validation indicated positive staining of NUBP2 in a large majority of cases (72%). Further, analysis of OSCC data available in TCGA revealed higher NUBP2 expression correlated with better disease-free patient survival. In conclusion, the differential serum autoantibodies identified in the current study, including those for NUBP2, could be used as potential biomarkers for early diagnosis or as screening biomarkers for OSCC pending investigation in a larger cohort.
Identification of alternative splicing associated with clinical features: from pan-cancers to genitourinary tumors
Authors: Duan Chen , Zhang Yangjun , Li Lu , Liu Kai , Yao Xiangyang , Wu Xiaoliang , Li Bo , Mao Xiongmin , Wu Huahui , Liu Haoran , Zeng Jin , Li Sheng , Gong Yan , Hu Zhiquan , Xu Hua 
Published: September 2023

BackgroundAlternative splicing events (ASEs) are vital causes of tumor heterogeneity in genitourinary tumors and many other cancers. However, the clinicopathological relevance of ASEs in cancers has not yet been comprehensively characterized.MethodsBy analyzing splicing data from the TCGA SpliceSeq database and phenotype data for all TCGA samples from the UCSC Xena database, we identified differential clinical feature-related ASEs in 33 tumors. CIBERSORT immune cell infiltration data from the TIMER2.0 database were used for differential clinical feature-related immune cell infiltration analysis. Gene function enrichment analysis was used to analyze the gene function of ASEs related to different clinical features in tumors. To reveal the regulatory mechanisms of ASEs, we integrated race-related ASEs and splicing quantitative trait loci (sQTLs) data in kidney renal clear cell carcinoma (KIRC) to comprehensively assess the impact of SNPs on ASEs. In addition, we predicted regulatory RNA binding proteins in bladder urothelial carcinoma (BLCA) based on the enrichment of motifs around alternative exons for ASEs.ResultsAlternative splicing differences were systematically analyzed between different groups of 58 clinical features in 33 cancers, and 30 clinical features in 24 cancer types were identified to be associated with more than 50 ASEs individually. The types of immune cell infiltration were found to be significantly different between subgroups of primary diagnosis and disease type. After integrating ASEs with sQTLs data, we found that 63 (58.9%) of the race-related ASEs were significantly SNP-correlated ASEs in KIRC. Gene function enrichment analyses showed that metastasis-related ASEs in KIRC mainly enriched Rho GTPase signaling pathways. Among those ASEs associated with metastasis, alternative splicing of GIT2 and TUBB3 might play key roles in tumor metastasis in KIRC patients. Finally, we identified several RNA binding proteins such as PCBP2, SNRNP70, and HuR, which might contribute to splicing differences between different groups of neoplasm grade in BLCA.ConclusionWe demonstrated the significant clinical relevance of ASEs in multiple cancer types. Furthermore, we identified and validated alternative splicing of TUBB3 and RNA binding proteins such as PCBP2 as critical regulators in the progression of urogenital cancers.
Speculation on optimal numbers of examined lymph node for early-stage epithelial ovarian cancer from the perspective of stage migration
Authors: Li Yuan , Ding Jiashan , Zheng Huimin , Xu Lijiang , Li Weiru , Zhu Minshan , Zhang Xiaolu , Ma Cong , Zhang Fangying , Zhong Peiwen , Liang Dong , Han Yubin , Zhang Siyou , He Linsheng , Li Jiaqi 
Published: September 2023

IntroductionIn early-stage epithelial ovarian cancer (EOC), how to perform lymphadenectomy to avoid stage migration and achieve reliable targeted excision has not been explored in depth. This study comprehensively considered the stage migration and survival to determine appropriate numbers of examined lymph node (ELN) for early-stage EOC and high-grade serous ovarian cancer (HGSOC).MethodsFrom the Surveillance, Epidemiology, and End Results database, we obtained 10372 EOC cases with stage T1M0 and ELN ≥ 2, including 2849 HGSOC cases. Generalized linear models with multivariable adjustment were used to analyze associations between ELN numbers and lymph node stage migration, survival and positive lymph node (PLN). LOESS regression characterized dynamic trends of above associations followed by Chow test to determine structural breakpoints of ELN numbers. Survival curves were plotted using Kaplan-Meier method.ResultsMore ELNs were associated with more node-positive diseases, more PLNs and better prognosis. ELN structural breakpoints were different in subgroups of early-stage EOC, which for node stage migration or PLN were more than those for improving outcomes. The meaning of ELN structural breakpoint varied with its location and the morphology of LOESS curve. To avoid stage migration, the optimal ELN for early-stage EOC was 29 and the minimal ELN for HGSOC was 24. For better survival, appropriate ELN number were 13 and 8 respectively. More ELNs explained better prognosis only at a certain range.DiscussionNeither too many nor too few numbers of ELN were ideal for early-stage EOC and HGSOC. Excision with appropriate numbers of lymph node draining the affected ovary may be more reasonable than traditional sentinel lymph node resection and systematic lymphadenectomy.
Qualitative and quantitative evaluation of computed tomography changes in adults with cystic fibrosis treated with elexacaftor-tezacaftor-ivacaftor: a retrospective observational study
Authors: Dettmer Sabine , Weinheimer Oliver , Sauer-Heilborn Annette , Lammers Oliver , Wielpütz Mark O. , Fuge Jan , Welte Tobias , Wacker Frank , Ringshausen Felix C. 
Published: September 2023

Introduction: The availability of highly effective triple cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination therapy with elexacaftor–tezacaftor–ivacaftor (ETI) has improved pulmonary outcomes and quality of life of people with cystic fibrosis (pwCF). The aim of this study was to assess computed tomography (CT) changes under ETI visually with the Brody score and quantitatively with dedicated software, and to correlate CT measures with parameters of clinical response.Methods: Twenty two adult pwCF with two consecutive CT scans before and after ETI treatment initiation were retrospectively included. CT was assessed visually employing the Brody score and quantitatively by YACTA, a well-evaluated scientific software computing airway dimensions and lung parenchyma with wall percentage (WP), wall thickness (WT), lumen area (LA), bronchiectasis index (BI), lung volume and mean lung density (MLD) as parameters. Changes in CT metrics were evaluated and the visual and quantitative parameters were correlated with each other and with clinical changes in sweat chloride concentration, spirometry [percent predicted of forced expiratory volume in one second (ppFEV1)] and body mass index (BMI).Results: The mean (SD) Brody score improved with ETI [55 (12) vs. 38 (15); p &lt; 0.001], incl. sub-scores for mucus plugging, peribronchial thickening, and parenchymal changes (all p &lt; 0.001), but not for bronchiectasis (p = 0.281). Quantitatve WP (p &lt; 0.001) and WT (p = 0.004) were reduced, conversely LA increased (p = 0.003), and BI improved (p = 0.012). Lung volume increased (p &lt; 0.001), and MLD decreased (p &lt; 0.001) through a reduction of ground glass opacity areas (p &lt; 0.001). Changes of the Brody score correlated with those of quantitative parameters, exemplarily WT with the sub-score for mucus plugging (r = 0.730, p &lt; 0.001) and peribronchial thickening (r = 0.552, p = 0.008). Changes of CT parameters correlated with those of clinical response parameters, in particular ppFEV1 with the Brody score (r = −0.606, p = 0.003) and with WT (r = −0.538, p = 0.010).Discussion: Morphological treatment response to ETI can be assessed using the Brody score as well as quantitative CT parameters. Changes in CT correlated with clinical improvements. The quantitative analysis with YACTA proved to be an objective, reproducible and simple method for monitoring lung disease, particularly with regard to future interventional clinical trials.