bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacterial community structures and dynamics associated with rotated positioning syndrome in gilthead sea bream (Sparus aurata) larviculture
Authors: Bel Mokhtar Naima , Apostolopoulou Georgia , Koumoundouros George , Tzokas Kostas , Toskas Kosmas , Gourzioti Evgenia , Stathopoulou Panagiota , Tsiamis George 
Published: January 2024

IntroductionThe availability of high-quality gilthead seabream (Sparus aurata) larvae in larviculture represents a major bottleneck to the aquaculture. This challenge can be compounded by losses resulting from the emergence of a clinical disorder’s symptomatology. In this study, the observed syndrome included a rotated positioning of the larval sagittal plane and in most cases leading eventually to death. MethodsHerein, we examined using amplicon sequencing of the 16S rDNA the bacterial communities associated with S. aurata larvae at different conditions (including both fish with no evidence of the syndrome and fish with syndrome) during the early developmental stages along with the contribution of rearing water, organic matter and provided feed in the microbiota during an experiment of 18 days. ResultsOver the development of larvae, differences were observed in the bacterial composition between healthy and symptomatic larvae as well as between components of the system. A remarkable presence of members of the Psychrobacter genus was observed in symptomatic larvae with a significant increase at 18dph. The healthy larvae harbor different bacterial profile with a dominance of Vibrio and Bacillus genera during 3-8dph, various members of Alphaproteobacteria during 11-14dph and Marinifilum at 18dph. The rearing water showed a different bacterial profile compared to the other components, with a slight effect of healthy larvae at 3-8dph. The bacteriome of feeds provided during the rearing of larvae was found to be diverse. Chlorella was mainly dominated by members of Firmicutes, while Rotifer and Artemia were mainly dominated by members of Proteobacteria including different species of Psychrobacter. At 18dph, Artemia feed seems to affect the symptomatic larvae bacteriome, where it enhanced the presence of Psychrobacter spp.DiscussionInterestingly, the comparative network analysis at 18dph indicated that the bacterial associations in symptomatic larvae were primarily driven by members of the Psychrobacter genus. While various phyla contributed to bacterial associations in healthy larvae with different frequencies including mainly members of Proteobacteria, Bacteroidota and Firmicutes phyla. Finally, the Gammaproteobacteria/Alphaproteobacteria ratio was found to be related to the health condition of larvae. This study provides valuable information which can be used as indicators for monitoring the health status of S. aurata larvae.
Genomic risk prediction of cardiovascular diseases among type 2 diabetes patients in the UK Biobank
Authors: Ye Yixuan , Hu Jiaqi , Pang Fuyuan , Cui Can , Zhao Hongyu 
Published: January 2024

Background: Polygenic risk score (PRS) has proved useful in predicting the risk of cardiovascular diseases (CVD) based on the genotypes of an individual, but most analyses have focused on disease onset in the general population. The usefulness of PRS to predict CVD risk among type 2 diabetes (T2D) patients remains unclear.Methods: We built a meta-PRSCVD upon the candidate PRSs developed from state-of-the-art PRS methods for three CVD subtypes of significant importance: coronary artery disease (CAD), ischemic stroke (IS), and heart failure (HF). To evaluate the prediction performance of the meta-PRSCVD, we restricted our analysis to 21,092 white British T2D patients in the UK Biobank, among which 4,015 had CVD events.Results: Results showed that the meta-PRSCVD was significantly associated with CVD risk with a hazard ratio per standard deviation increase of 1.28 (95% CI: 1.23–1.33). The meta-PRSCVD alone predicted the CVD incidence with an area under the receiver operating characteristic curve (AUC) of 0.57 (95% CI: 0.54–0.59). When restricted to the early-onset patients (onset age ≤ 55), the AUC was further increased to 0.61 (95% CI 0.56–0.67).Conclusion: Our results highlight the potential role of genomic screening for secondary preventions of CVD among T2D patients, especially among early-onset patients.
Lithium and cobalt co-doped mesoporous bioactive glass nanoparticles promote osteogenesis and angiogenesis in bone regeneration
Authors: Zhang Xin , Nan Kai , Zhang Yuankai , Song Keke , Geng Zilong , Shang Donglong , Fan Lihong 
Published: January 2024

Healing of severe fractures and bone defects involves many complex biological processes, including angiogenesis and osteogenesis, presenting significant clinical challenges. Biomaterials used for bone tissue engineering often possess multiple functions to meet these challenges, including proangiogenic, proosteogenic, and antibacterial properties. We fabricated lithium and cobalt co-doped mesoporous bioactive glass nanoparticles (Li-Co-MBGNs) using a modified sol-gel method. Physicochemical analysis revealed that the nanoparticles had high specific surface areas (&gt;600 m2/g) and a mesoporous structure suitable for hydroxyapatite (HA) formation and sustained release of therapeutic ions. In vitro experiments with Li-Co-MBGNs showed that these promoted angiogenic properties in HUVECs and pro-osteogenesis abilities in BMSCs by releasing Co2+ and Li+ ions. We observed their antibacterial activity against Staphylococcus aureus and Escherichia coli, indicating their potential applications in bone tissue engineering. Overall, our findings indicate the feasibility of its application in bone tissue engineering.
Galectin-3 and peripheral artery disease: a Mendelian randomization study
Authors: Gou Yang , Chen Miao , Zhu Zhi , Cui Chi 
Published: January 2024

BackgroundMultiple clinical studies have found a significant correlation between elevated galectin-3 (Gal-3) in circulation and the diagnosis and severity of peripheral arterial disease (PAD). The current study used the Mendelian randomization (MR) technique to evaluate the possible causal relationship between Gal-3 and PAD.MethodsGenome-wide association study (GWAS) data of Gal-3 and PAD were obtained through the MR-Base platform. Then, using Gal-3 as the exposure and PAD as the outcome, a two-sample MR analysis was performed utilizing several regression techniques, including MR-Egger regression, inverse variance weighted (IVW), weighted median, and weighted mode.ResultsSix single-nucleotide polymorphisms (SNPs) were identified and designated as instrumental variables (IVs) that exhibited significant correlations with Gal-3 (linkage disequilibrium r2 &lt; 0.001; P &lt; 5 × 10−8). Various statistical methods showed that there was an absence of a significant link between Gal-3 and PAD (IVW: odds ratio (OR) = 0.9869, 95% confidence interval (CI) = 0.8792–1.1078, P = 0.8232). In addition, the presence of genetic pleiotropy did impact the putative causal relationship between PAD and Gal-3 (MR-Egger intercept = 0.0099, P = 0.659).ConclusionsThere is no current evidence to establish a causal relationship between the level of Gal-3 in circulation and PAD.
Zinc-aspirin preconditioning reduces endothelial damage of arterial grafts in a rodent model of revascularization
Authors: Benke Kálmán , Stengl Roland , Stark Klára Aliz , Bai Yang , Radovits Tamás , Loganathan Sivakkanan , Korkmaz-Icöz Sevil , Csonka Máté , Karck Matthias , Szabó Gábor , Veres Gábor 
Published: January 2024

IntroductionCoronary artery bypass grafting (CABG) is the most common cardiac surgical procedure. The prognosis of revascularization via CABG is determined by the patency of the used grafts, for which an intact endothelium is essential. The degree of ischemia-reperfusion injury (IRI), which occurs during the harvest and implantation of the grafts, is an important determinant of graft patency. Preconditioning with aspirin, a nonsteroidal anti-inflammatory drug has been shown to reduce the functional and molecular damage of arterial grafts in a rodent model. Studies have found that the zinc-aspirin complex may be able to exert an even better protective effect in pathological cardiovascular conditions. Thus, our aim was to characterize the protective effect of zinc-aspirin complex on free arterial grafts in a rodent model of revascularization.MethodsDonor Lewis rats were treated with either zinc-aspirin, aspirin, or placebo (n = 8) for 5 days, then the aortic arches were harvested and stored in cold preservation solution and implanted heterotopically in the abdominal cavity of the recipient rats, followed by 2 h of reperfusion. There was also a non-ischemia-reperfusion control group (n = 8). Functional measurements using organ bath and histomorphological changes using immunohistochemistry were analyzed.ResultsThe endothelium dependent maximal vasorelaxation was improved (non-transplanted control group: 82% ± 3%, transplanted control group: 14% ± 2%, aspirin group: 31% ± 4%, zinc-aspirin group: 52% ± 4%), the nitro-oxidative stress and cell apoptosis decreased, and significant endothelial protection was shown in the groups preconditioned with aspirin or zinc-aspirin. However, zinc-aspirin proved to be more effective in the reduction of IRI, than aspirin alone.DiscussionPreconditioning with zinc-aspirin could be a promising way to protect the function and structural integrity of free arterial grafts, thus improving the outcomes of CABG.
Diagnostic value of qualitative and quantitative parameters of contrast-enhanced ultrasound for differentiating differentiated thyroid carcinomas from benign nodules
Authors: Fan Jinfang , Tao Lingling , Zhan Weiwei , Li Weiwei , Kuang Lijun , Zhao Yingyan , Zhou Wei 
Published: January 2024

ObjectiveTo explore the diagnostic value of contrast-enhanced ultrasound (CEUS) of qualitative and quantitative parameters for differentiating differentiated thyroid cancers from benign nodules.MethodA total of 290 thyroid nodules that were pathologically confirmed were enrolled in this study. The univariate analysis was performed for the clinical characteristics and CEUS qualitative and quantitative parameters of the inside and peripheral zone of nodules, including age, gender, nodule size, intensity of enhancement, homogeneity, wash-in and wash-out patterns, margin after CEUS, ring enhancement, peak intensity, sharpness, time to peak(TP), and area under the curve(AUC), and the meaningful indicators in the single-factor analysis were further included in multivariate logistic regression analysis.ResultsMultivariate analysis showed that there were significant differences in age (p=0.031), nodule size (p&lt;0.001), heterogeneous enhancement (p&lt;0.001), hypo-enhancement (p=0.001), unclear margin after CEUS(p=0.007), inside peak (p&lt;0.001), and outside sharpness(p&lt;0.001) between benign and malignant nodules. However, there were no significant differences in gender, ring enhancement, wash-in, wash-out, outside TP, outside AUC between benign and malignant thyroid nodules (P&gt;0.05, for all).ConclusionCEUS might be useful in the differential diagnosis of differentiated thyroid cancers and benign nodules, which could provide a certain basis for clinical treatment.
Computational analysis of cas proteins unlocks new potential in HIV-1 targeted gene therapy
Authors: Dampier Will , Berman Rachel , Nonnemacher Michael R. , Wigdahl Brian 
Published: January 2024

Introduction: The human immunodeficiency virus type 1 (HIV-1) pandemic has been slowed with the advent of anti-retroviral therapy (ART). However, ART is not a cure and as such has pushed the disease into a chronic infection. One potential cure strategy that has shown promise is the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas gene editing system. It has recently been shown to successfully edit and/or excise the integrated provirus from infected cells and inhibit HIV-1 in vitro, ex vivo, and in vivo. These studies have primarily been conducted with SpCas9 or SaCas9. However, additional Cas proteins are discovered regularly and modifications to these known proteins are being engineered. The alternative Cas molecules have different requirements for protospacer adjacent motifs (PAMs) which impact the possible targetable regions of HIV-1. Other modifications to the Cas protein or gRNA handle impact the tolerance for mismatches between gRNA and the target. While reducing off-target risk, this impacts the ability to fully account for HIV-1 genetic variability.Methods: This manuscript strives to examine these parameter choices using a computational approach for surveying the suitability of a Cas editor for HIV-1 gene editing. The Nominate, Diversify, Narrow, Filter (NDNF) pipeline measures the safety, broadness, and effectiveness of a pool of potential gRNAs for any PAM. This technique was used to evaluate 46 different potential Cas editors for their HIV therapeutic potential.Results: Our examination revealed that broader PAMs that improve the targeting potential of editors like SaCas9 and LbCas12a have larger pools of useful gRNAs, while broader PAMs reduced the pool of useful SpCas9 gRNAs yet increased the breadth of targetable locations. Investigation of the mismatch tolerance of Cas editors indicates a 2-missmatch tolerance is an ideal balance between on-target sensitivity and off-target specificity. Of all of the Cas editors examined, SpCas-NG and SPRY-Cas9 had the highest number of overall safe, broad, and effective gRNAs against HIV.Discussion: Currently, larger proteins and wider PAMs lead to better targeting capacity. This implies that research should either be targeted towards delivering longer payloads or towards increasing the breadth of currently available small Cas editors. With the discovery and adoption of additional Cas editors, it is important for researchers in the HIV-1 gene editing field to explore the wider world of Cas editors.
Systematic comparison of variant calling pipelines of target genome sequencing cross multiple next-generation sequencers
Authors: Feng Baosheng , Lai Juan , Fan Xue , Liu Yongfeng , Wang Miao , Wu Ping , Zhou Zhiliang , Yan Qin , Sun Lei 
Published: January 2024

Targeted genomic sequencing (TS) greatly benefits precision oncology by rapidly detecting genetic variations with better accuracy and sensitivity owing to its high sequencing depth. Multiple sequencing platforms and variant calling tools are available for TS, making it excruciating for researchers to choose. Therefore, benchmarking study across different platforms and pipelines available for TS is imperative. In this study, we performed a TS of Reference OncoSpan FFPE (HD832) sample enriched by TSO500 panel using four commercially available sequencers, and analyzed the output 50 datasets using five commonly-used bioinformatics pipelines. We systematically investigated the sequencing quality and variant detection sensitivity, expecting to provide optimal recommendations for future research. Four sequencing platforms returned highly concordant results in terms of base quality (Q20 &gt; 94%), sequencing coverage (&gt;97%) and depth (&gt;2000×). Benchmarking revealed good concordance of variant calling across different platforms and pipelines, among which, FASTASeq 300 platform showed the highest sensitivity (100%) and precision (100%) in high-confidence variants calling when analyzed by SNVer and VarScan 2 algorithms. Furthermore, this sequencer demonstrated the shortest sequencing time (∼21 h) at the sequencing mode PE150. Through the intersection of 50 datasets generated in this study, we recommended a novel set of variant genes outside the truth set published by HD832, expecting to replenish HD832 for future research on tumor variant diagnosis. Besides, we applied these five tools to another panel (TargetSeq One) for Twist cfDNA Pan-cancer Reference Standard, comprehensive consideration of SNP and InDel sensitivity, SNVer and VarScan 2 performed best among them. Furthermore, SNVer and VarScan 2 also performed best for six cancer cell lines samples regarding SNP and InDel sensitivity. Considering the dissimilarity of variant calls across different pipelines for datasets from the same platform, we recommended an integration of multiple tools to improve variant calling sensitivity and accuracy for the cancer genome. Illumina and GeneMind technologies can be used independently or together by public health laboratories performing tumor TS. SNVer and VarScan 2 perform better regarding variant detection sensitivity for three typical tumor samples. Our study provides a standardized target sequencing resource to benchmark new bioinformatics protocols and sequencing platforms.
Clinical signs and symptoms of Wilson disease in a real-world cohort of patients in the United States: a medical chart review study
Authors: Medici Valentina , Kebede Nehemiah , Stephens Jennifer , Kunjappu Mary , Vierling John M. 
Published: January 2024

IntroductionThere are limited data from the United States regarding the real-world signs and symptoms of Wilson disease (WD). This retrospective, observational medical chart review was conducted to identify real-world characteristics of patients with WD in the United States, as well as WD signs and symptoms at diagnosis and over time.MethodsDe-identified clinical data were abstracted from medical charts of US patients diagnosed with WD between January 1, 2012, and June 30, 2017. Hepatic, neurologic, and psychiatric biochemical findings, signs, and symptoms were characterized at diagnosis and follow-up/during treatment.ResultsIn total, 225 WD patients were included in the study. The mean (SD) age at diagnosis was 24.7 (9.8) years, and 65.3% were male. Median (Q1–Q3) follow-up after diagnosis was 39.5 (33.8–60.4) months. The most common disease presentation at WD diagnosis was combined neurologic/psychiatric and hepatic (52.9%), followed by neurologic/psychiatric (20.0%), hepatic (16.9%), and asymptomatic (10.2%). Common clinical characteristics at diagnosis were Kayser-Fleischer rings (77.2%), low ceruloplasmin levels (95.2%), high hepatic copper (97.8%), elevated 24-hour urinary copper excretion (90.2%), and abnormal liver function tests (38.7%–85.1%). At diagnosis, the most common biochemical findings or hepatic sign/symptoms were abnormal liver enzymes (50.7%), abdominal pain (16.6%), and fatigue (15.7%). The most common neurologic signs/symptoms were headache (18.3%), dysarthria (17.4%), and ataxia (17.0%). Common psychiatric signs/symptoms included anxiety/depression/other mood changes (36.2%), emotional lability (12.8%), and increased irritability/anger outbursts (9.2%). Prevalence of biochemical abnormalities or signs/symptoms among patients at diagnosis and after ~1-year follow-up were neurologic (60.1% and 44.0%), hepatic (69.6% and 37.8%), and psychiatric (53.7% and 37.6%), respectively. Common new onset symptoms at ~1-year post-WD diagnosis were abnormal liver enzymes (5.6%), headache (6.2%), and anxiety/depression/other mood changes (7.2%).ConclusionsThese real-world, descriptive data highlight the clinical complexity and heterogeneity of WD and the need for better education about diagnostic testing and multidisciplinary support. Although rare, the neurologic, psychiatric, and hepatic signs/symptoms of WD have a substantial clinical impact.
Humoral and cell-mediated immune responses in HIV-vertically infected young patients after three doses of the BNT162b2 mRNA SARS-CoV-2 vaccine
Authors: Vanetti Claudia , Stracuzzi Marta , Crivellaro Elisa , Ciciliano Federica , Garziano Micaela , Fenizia Claudio , Biasin Mara , Rubinacci Valeria , Amendola Antonella , Tanzi Elisabetta , Zuccotti Gian Vincenzo , Clerici Mario , Giacomet Vania , Trabattoni Daria 
Published: January 2024

BackgroundData on the efficacy of three SARS-CoV-2 mRNA BNT162b2 vaccine doses and the role of previous SARS-CoV-2-infection in enhancing vaccine immunogenicity in HIV-vertically-infected people living with HIV (PLWH) are limited, as is the duration of vaccine-induced responses.MethodsSARS-CoV-2 plasma neutralizing activity (NA) against the European (B.1), Delta (B.1.617.2) and Omicron (B.1.1.529) variants and cell-mediated immunity (CMI) were analyzed in 29 ART-treated young PLWH (mean age 27.9 years) and 30 healthy controls (HC) who received three BNT162b2 vaccine doses. Individuals were stratified based on the presence/absence of previous SARS-CoV-2 infection (infected and vaccinated -SIV-; uninfected and vaccinated -SV-). Analyses were performed before vaccination (T0), 25 days from the second dose (T1), the day the third dose was administered (T2), and 3 months after the third dose (T3).ResultsIn PLWH: i) NA against all variants was higher in SIV compared to SV at T2 and was increased at T3; ii) switched-memory plasmablasts were augmented in SIV alone at T2 and T3; iii) a SARS-CoV-2 specific T cell memory was generated; iv) IFN-γ-secreting CD4+ and CD8+ T lymphocytes were boosted at T3 mainly in SV. CMI magnitude was reduced in PLWH compared to HC. Notably, after the third dose of vaccine viremia was unmodified, but CD4 T cell counts were reduced&gt;20% in 3/29 PHLW.ConclusionA third dose of BNT162b2 vaccine induces strong humoral and CMI responses in young ART-treated PLWH independently from a previous SARS-CoV-2 natural infection. The lower magnitude of CMI responses should be considered when planning mRNA vaccine booster doses in PLWH.
Prediction of six macrophage phenotypes and their IL-10 content based on single-cell morphology using artificial intelligence
Authors: Selig Mischa , Poehlman Logan , Lang Nils C. , Völker Marita , Rolauffs Bernd , Hart Melanie L. 
Published: January 2024

IntroductionThe last decade has led to rapid developments and increased usage of computational tools at the single-cell level. However, our knowledge remains limited in how extracellular cues alter quantitative macrophage morphology and how such morphological changes can be used to predict macrophage phenotype as well as cytokine content at the single-cell level.MethodsUsing an artificial intelligence (AI) based approach, this study determined whether (i) accurate macrophage classification and (ii) prediction of intracellular IL-10 at the single-cell level was possible, using only morphological features as predictors for AI. Using a quantitative panel of shape descriptors, our study assessed image-based original and synthetic single-cell data in two different datasets in which CD14+ monocyte-derived macrophages generated from human peripheral blood monocytes were initially primed with GM-CSF or M-CSF followed by polarization with specific stimuli in the presence/absence of continuous GM-CSF or M-CSF. Specifically, M0, M1 (GM-CSF-M1, TNFα/IFNγ-M1, GM-CSF/TNFα/IFNγ-M1) and M2 (M-CSF-M2, IL-4-M2a, M-CSF/IL-4-M2a, IL-10-M2c, M-CSF/IL-10-M2c) macrophages were examined.ResultsPhenotypes were confirmed by ELISA and immunostaining of CD markers. Variations of polarization techniques significantly changed multiple macrophage morphological features, demonstrating that macrophage morphology is a highly sensitive, dynamic marker of phenotype. Using original and synthetic single-cell data, cell morphology alone yielded an accuracy of 93% for the classification of 6 different human macrophage phenotypes (with continuous GM-CSF or M-CSF). A similarly high phenotype classification accuracy of 95% was reached with data generated with different stimuli (discontinuous GM-CSF or M-CSF) and measured at a different time point. These comparably high accuracies clearly validated the here chosen AI-based approach. Quantitative morphology also allowed prediction of intracellular IL-10 with 95% accuracy using only original data.DiscussionThus, image-based machine learning using morphology-based features not only (i) classified M0, M1 and M2 macrophages but also (ii) classified M2a and M2c subtypes and (iii) predicted intracellular IL-10 at the single-cell level among six phenotypes. This simple approach can be used as a general strategy not only for macrophage phenotyping but also for prediction of IL-10 content of any IL-10 producing cell, which can help improve our understanding of cytokine biology at the single-cell level.