bluuebunny/crossref_metadata_2025_split huggingface dataset:
Twenty-year longitudinal evaluation of blood-based DNA methylation biomarkers for early prediction of Alzheimer’s disease
Authors: Hackenhaar Fernanda Schäfer , Josefsson Maria , Adolfsson Annelie Nordin , Landfors Mattias , Kauppi Karolina , Porter Tenielle , Milicic Lidija , Laws Simon M. , Hultdin Magnus , Adolfsson Rolf , Degerman Sofie , Pudas Sara 
Published: November 2022

Abstract
Background: DNA methylation (DNAm) is an epigenetic mechanism reflecting both inherited and environmental influences, and is a promising biomarker of multifactorial aging-related disorders like Alzheimer’s disease (AD). Early prediction of AD is critical, but little is known about the time-course of DNAm biomarkers long before symptom onset.
Methods: The long-term predictive ability of four existing DNAm-based epigenetic age acceleration clocks was tested in a longitudinal case-control sample (50 late-onset AD cases; 51 age- and sex-matched controls) with prospective data up to 16 years prior to clinical onset (mean: 8 years), and a post-onset follow-up. In addition, novel blood-based DNAm biomarkers for AD prediction were generated with epigenome-wide longitudinal linear mixed effects models, as well as sparse partial least squares discriminant analysis applied at time-points 10-16 years pre-onset and 0-7 years post-onset.
Results: Epigenetic age acceleration clocks did not differentiate cases from controls at any point during the 20-year follow up time (ps>0.05). Our new DNA biomarkers, comprising 73, 7, and 27 CpG sites respectively, had excellent in-sample discriminatory and predictive accuracy on average 8 years prior to clinical onset (AUCs=71.1-98.2% including age, sex, and white blood cell proportions). The longitudinal panel of CpGs replicated nominally (p=0.012) in an external cohort (n=146 cases, 324 controls). However, compared with the established genetic marker APOEε4 our panel had a limited effect size (OR=1.38 per 1 SD panel score increase vs. OR=13.58 for ε4-allele carriage) and discriminatory accuracy in the external cohort (AUC=77.2% vs. 87.0% for models with age, sex, and white blood cell proportions). A literature review showed low overlap (n=4) across 3275 CpGs previously reported to be AD-associated in 8 published studies, and no overlap with our currently identified CpGs.
Conclusions: The results extend prior studies showing a limited predictive and prognostic value of epigenetic age acceleration in AD by considering a longer pre-onset follow-up time, and with appropriate control for age, sex, APOE, and white blood cell proportions. The findings further highlight challenges with replicating discriminatory or predictive CpGs across studies.
PARP14 inhibition restores PD-1 immune checkpoint inhibitor response following IFNγ-driven adaptive resistance
Authors: Wong Chun Wai , Evangelou Christos , Sefton Kieran , Leshem Rotem , Sergiou Kleita , Carro Macarena Fernandez , Uzuner Erez , Mole Holly , Telfer Brian , Wilcock Daniel , Smith Michael , Kunii Kaiko , Perl Nicholas , Lorigan Paul , Williams Kaye , Rao Patricia , Nagaraju Raghavendar , Niepel Mario , Hurlstone Adam 
Published: November 2022

Abstract
Adaptive resistance limits immune checkpoint blockade therapy (ICBT) response duration and magnitude. Interferon γ (IFNγ), a critical cytokine that promotes cellular immunity, also induces adaptive resistance to ICBT. Using syngeneic mouse tumour models, we confirmed that chronic IFNγ exposure confers resistance to anti-Programmed cell death protein 1 (α-PD-1) therapy. We identified consistent upregulation of poly-ADP ribosyl polymerase 14 (PARP14) in both chronic IFNγ-treated cancer cells and patient melanoma with elevated IFNG expression. Knockdown or pharmacological inhibition of PARP14 increased effector T cell infiltration into tumours derived from cells pre-treated with IFNγ and decreased the presence of regulatory T cells, leading to restoration of α-PD-1 sensitivity. Finally, we determined that tumours which spontaneously relapsed following α-PD-1 therapy could be re-sensitised upon receiving PARP14 inhibitor treatment, establishing PARP14 as an actionable target to reverse IFNγ-driven ICBT resistance.
AVA-Net: an open-source deep learning network for arterial-venous area segmentation in OCT angiography
Authors: Yao Xincheng , Abtahi Mansour , Le David , Ebrahimi Behrouz , Dadzie Albert , Lim Jennifer 
Published: November 2022

Abstract
Differential artery-vein (AV) analysis in optical coherence tomography angiography (OCTA) holds promise for early detection of eye diseases. However, currently available methods for AV analysis are limited for binary processing of retinal vasculature in OCTA, without quantitative information of vascular perfusion intensity. This study is to develop a deep learning network AVA-Net for automated AV area (AVA) segmentation in OCTA, and thus to enable quantitative AV analysis of vascular perfusion intensity. Seven new OCTA features, including arterial area (AA), venous area (VA), AVA ratio (AVAR), total perfusion intensity density (T-PID), arterial PID (A-PID), venous PID (V-PID), and arterial-venous PID ratio (AV-PIDR), have been developed and validated for early detection of diabetic retinopathy (DR). Each of these seven features was evaluated for quantitative comparison of OCTA images from healthy controls, diabetic patients without DR (NoDR), and mild DR. It was observed that the area features, i.e., AA, VA and AVAR, can reveal significant differences between the control and diabetic eyes (NoDR and mild DR), but cannot separate NoDR and mild DR from each other. Vascular perfusion parameters, including T-PID and V-PID, can differentiate mild DR from control and NoDR groups, but cannot separate control and NoDR from each other. In contrast, the AV-PIDR can disclose significant differences among all three groups, i.e., control, NoDR, and mild DR. The AVA-Net validated in this study is available on GitHub for open access.
Laparoscopic parenchyma-sparing resections for solid pseudopapillary tumors located in the head of pancreas
Authors: Zou Zhengdong , Feng Lu , Peng Bing , Liu Jianhua , Cai Yunqiang 
Published: November 2022

Abstract
Background
Solid pseudopapillary tumor (SPT) of pancreas is a rare low-grade malignant tumor. We aim to identify the safety and feasibility of laparoscopic parenchyma-sparing pancreatectomy for SPT located in the head of pancreas.
Methods
From July 2014 to February 2022, 62 patients with SPT located in the head of pancreas were operated laparoscopically in two institutions. These patients were divided into two groups basing on the operative strategy: laparoscopic parenchyma-sparing pancreatectomy (27 patients, group 1) and laparoscopic pancreaticoduodenectomy (35 patients, group 2). Data were retrospectively collected and analyzed in terms of demographic, peri-operative variables, and long-term follow-up outcomes.
Results
The demographic characteristics of patients in two groups were comparable. Compared with that in group 2, the patients in group 1 required fewer operative time (263.4 ± 37.2 min vs. 332.7 ± 55.6 min, p < 0.001), and suffered from less blood loss (105.1 ± 36. ml vs. 188.3 ± 150.7 ml, p < 0.001). No patients in group 1 suffered from tumor recurrence or metastases. However, 1 (2.5%) patient in group 2 suffered from liver metastases.
Conclusion
Laparoscopic parenchyma-sparing pancreatectomy is safe and feasible for SPT located in the head of pancreas, with favorable long-term functional and oncological results.
Electrocardiographic patterns of ventricular pre-excitation in the dogs with right-sided accessory pathways
Authors: Perego Manuela , Pariaut Romain , Lombardo Sergio Federico , Moise Sidney N , Cavallini Damiano , Santilli Roberto 
Published: November 2022

Abstract
Introduction: The aim of the study was to describe the electrocardiographic features of ventricular pre-excitation (VPE) patterns in dogs with right-sided accessory pathways.
Animals, materials and methods: Twenty-six dogs with confirmed accessory pathway (AP) via electrophysiological mapping were included in the study. The following parameters were determined: P-δQRS interval, δQRS duration, δQRS axis, δQRS morphology, δ-wave polarity, Q-wave, R-wave, R’-wave, S-wave amplitude and R/S ratio.
Results: The median δQRS complex axis in the frontal plane was: + 68° (IQR 52.5) for right anterior APs, - 24 ° (IQR 24) for right postero-septal APs, - 43.5 ° (IQR 27.25) for right posterior APs (P = 0.007). In lead I, R wave was overall taller in right posterior APs (P = 0.04) for differences among medians within groups, and R’ wave in lead II and in lead III was significantly taller in right anterior Aps (respectively P = 0.02 and P = 0.01) for differences among medians within groups. In precordial leads of all dogs, R/S was < 1 in V1 and > 1 in all leads from V2 to V6.
Surface electrocardiogram can be used to distinguish right anterior APs from right posterior and right postero-septal ahead of an invasive electrophysiological study.
Synthesis and characterization of Zn based bi metallic micro porous MOF composites for effective formaldehyde sensing at room temperature
Authors: Reddy A. Jagan Mohan , Nagaraju P. , Namratha E. , Babu M. S. Surendra 
Published: November 2022

Abstract
In the present work, we fabricated 1:1 bimetallic ZnCu(NA); ZnCd(NA); and ZnCo(NA) metal organic frameworks (MOFs) using nicotinic acid (NA) as organic linker by solvothermal method. Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) analysis, X-Ray Photoelectron Spectroscopy (XPS), and scanning electron microscopy (SEM) were used to describe all bimetallic MOF topologies. These compounds were used to develop chemiresistive sensor devices for sensing of formaldehyde vapor at room temperature. Drop-casting method was used to make the sensing device on a glass plate with silver electodes. The resulting bimetallic sensors exhibited excellent sensitivity, good linearity and more stability in the detection of formaldehyde at 1 to 50 ppm concentrations. ZnCo(NA) exhibited more response towards formaldehyde vapor than other bimetallic MOFs. Transient response analysis was used to determine response and recovery times, as well as stability over time. These findings prove the application prospects of bimetallic Zn/Cu, Zn/Cd and Zn/Co MOFs in the selective and sensitive detection of formaldehyde at room temperature.
R-phycocyanin from porphyra haitanensis attenuates apoptosis, ROS accumulation and cell cycle arrest induced by ameliorated cigarette smoke extract through AKT/MAPK/NF-κB signaling in human lung fbroblasts HFL1 cells
Authors: Feng Yanyu , Lu Hanjin , Zheng Baodong , Zhang Yi 
Published: November 2022

Abstract
The risk of human lung diseases and abnormal development under the toxic environmental exposure conditions of passive cigarette smoke is emerging. R-phycocyanin (R-PC) has health benefits for a range of lung diseases including lung injury. The goal of this study was to investigate R-PC improves cigarette smoke-induced cell apoptosis and cycle arrest and its underlying molecular mechanisms in human lung fibroblasts. The effect of R-PC on cytotoxicity, apoptosis, ΔΨm and cell cycle arrest were measured through LDH assay, Hoechst/PI staining, JC-1 assay, flow cytometry, ELISA. The mechanisms of R-PC used DCFH-DA fluorescent probe for reactive oxygen species (ROS) level and western blotting analysis for signaling. Results showed that R-PC have great anti-oxidant activity and can inhibit the generation of radicals, expressed a protective effect against CSE-induced apoptotic HFL1 cells death and cycle phase arrest. Furthermore, CSE added the level of ROS and activated p38 and JNK signaling, inhibited AKT and NF-κB signaling. Pre-treatment with R-PC inhibited CSE-induced p38, JNK phosphorylation and ROS production, activated AKT, ERK, MKK4 and NF-κB signaling pathways. The findings suggested that R-PC treatment ameliorated CSE-induced ROS accumulation, apoptosis and cell cycle arrest by AKT/MAPK/NF-κB signaling pathways in HFL1 cells.
Complete genome sequence of a tentative novel capillovirus isolated from Gerbera jamesonii
Authors: Bak Sangmin , Jeong Wonyoung , Kim Minhui , Lee Su-Heon , Kim Sung Tae , Lee Eunsook , Kim Chang-Kil , Kim San Yeong 
Published: November 2022

Abstract
The currently named gerbera virus A (GeVA) has been identified as a novel capillovirus with a complete genome of 6929 nucleotides (nt) (GenBank accession no. OM525829.1). GeVA was detected in Gerbera jamesonii using high-throughput RNA sequencing analysis. The complete genome represents a single linear RNA with two open reading frames (ORF). The large ORF encodes a polyprotein contains four domains, while the smaller ORF encodes a movement protein. The addition of find two UUAGGU promoters for subgenomic RNA (sgRNA) transcription was also identified in this study. BLAST analysis demonstrated that it shared the highest identity with the rubber tree capillovirus 1 (MN047299.1) (complete nucleotide: 68.54%; polyprotein amino acid: 44.53%). Phylogenetic analysis of complete genome and replication protein sequences place GeVA alongside other genus Capillovirus in the family Betaflexiviridae. These data suggest that GeVA is a new member of the genus Capillovirus.
Conventional versus Video-assisted Laryngoscopy for Perioperative Endotracheal Intubation (COVALENT): A Randomized, Controlled Multicenter Trial
Authors: Schmid Benedikt , Eckert Dominik , Meixner Andreas , Pistner Paul , Malzahn Uwe , Berberich Monika , Happel Oliver , Meybohm Patrick , Kranke Peter 
Published: November 2022

Abstract
Background:Data on the routine use of video-assisted laryngoscopy in peri-operative intubations are rather inconsistent and ambiguous, in part due to small populations and non-uniform outcome measures in past trials. Failed or prolonged intubation procedures are a reason for relevant morbidity and mortality. This study aims to determine whether video-assisted laryngoscopy (with both Macintosh-shaped and hyperangulated blades) is at least equal to the standard method of direct laryngoscopy with respect to the first-pass success rate. Furthermore, validated tools from the field of human factors will be applied to examine within-team communication and task load during this critical medical procedure.
Methods: In this randomized, controlled, three-armed parallel group design, multi-centre trial, a total of more than 2500 adult patients scheduled for perioperative endotracheal intubation will be randomized. In equally large arms, video-assisted laryngoscopy with a Macintosh-shaped or a hyperangulated blade will be compared to the standard of care (direct laryngoscopy with Macintosh blade). In a pre-defined hierarchical analysis, we will test the primary outcome for non-inferiority first. If this goal should be met, the design and projected statistical power also allow for subsequent testing for superiority of one of the interventions.
Various secondary outcomes will account for patient safety considerations as well human factors interactions within the provider team and will allow for further exploratory data analysis and hypothesis generation.
Discussion:This randomized controlled trial will provide a solid base of data in a field where reliable evidence is of major clinical importance. With thousands of endotracheal intubations performed every day in operating rooms around the world, every bit of performance improvement translates into increased patient safety and comfort and may eventually prevent significant burden of disease. Therefore, we feel confident that a large trial has the potential to considerably benefit patients and anaesthetists alike.
Trial registration: ClincalTrials.gov NCT05228288
Protocol version: 1.1, November 15, 2021
Comparing Individual-, Family-, and Community-Level Effects on the Oral Health of Preschool Children: A Multilevel Analysis of National Survey Data
Authors: Lin Ying-Chun , Huang Shun-Te , Yen Cheng-Wei , Huang Yung-Kai , Shieh Tzong-Ming , Hsueh Chi-Wei , Yao Hu-Lin , Ho Pei-Shan 
Published: November 2022

Abstract
Background
Early childhood is a critical stage for the prevention of dental caries. The prevalence of caries in preschool children is still high in Taiwan, where National Health Insurance covers 99% of the population. The effort to improve the oral health of preschool children should be based on conceptual model that encompasses more than individual-level factors. This study input nationwide survey data in a conceptual model to evaluate the effects of comprehensive factors related to the high prevalence of caries in preschool children.
Methods
This observation study examined factors related to the oral health of preschool children by employing a comprehensive multilevel model to analyse nationally representative data from the Taiwan Oral Health Survey of Preschool Children (TOHPC) 2017–2018. Individual-level, family-level and community-level contextual effects were evaluated through multilevel analysis in this study. The proportional change in variance (PCV) was used to compare the multilevel model with the null model and individual-level, family-level, and community-level context effects.
Results
The estimated deft index for preschool children was 1.34 (1.22–1.47) at age 3, 2.20 (2.08–2.32) at age 4, and 3.05 (2.93–3.18) at age 5. The overall prevalence of caries in preschool children in Taiwan was 34.27% (30.76%, 37.78%) at age 3, 51.67% (48.99%, 54.35%) at age 4, and 62.05% (59.66%, 64.44%) at age 5. The model that included the individual-, family-, and community-context levels exhibited the highest reduction of variance (PCV = 53.98%). The PCV was further reduced to 35.61% when only the level of accessibility to dental services for individuals, families, and the community was considered. For the model in which no community-context cofactors were considered and the model considering only the individual level, the PCVs were 20.37% and 5.52%, respectively.
Conclusions
The most notable finding of this study is that to improve the oral health of preschool children, community-level factors should be targeted. Such community-based programs would effectively improve the oral health knowledge and behaviours of the parents and caregivers of preschool children. We suggest training more professional oral health educators to provide more community-based oral health promotion campaigns.
Spatial nonuniformity of landslide dam deposition and its quantitative characterization
Authors: Li Xing , Chen Qun , Liu Zhaozhao , Chen Chen 
Published: November 2022

Abstract
Landslide dams are formed by rapidly depositing landslide bodies with a loose structure and poor stability. The strong spatial nonuniformity of dam soil is a key factor for study on the seepage stability of landslide dams. In this paper, a 500×500×500 mm cubic model box was made and the dam soil was deposited in it by different sliding modes to investigate the nonuniformity of the deposition. Based on the basic principle of grading entropy, the distribution characteristics of the soil in different depositing zones using the entropy parameters A-B coordinates were analyzed. Finally, an index describing the degree of nonuniformity Nd was proposed to assess the deposition quantitatively. It was found that with the increasing sliding angle, the deposition showed prominent sorting characteristics in the sliding direction. The coarser and finer particles were mainly concentrated in the front and back parts of the deposition, respectively. Grading entropy has the advantage of being meticulous compared with traditional characteristic parameters. In the entropy parameters A-B coordinates, the points for the expected uniform deposition are more concentrated. And the points of different zones for the sliding deposition are arch-shaped in this coordinates. The Nd of the expected uniform deposition is only 0.057. And that of the deposition made by the sliding angle of 60° is the largest of 0.173. The research results can provide references for studying the spatial nonuniformity of landslide dam deposition.
COVID-19 in pregnancy influences the progression of labor: A single-institutional and observational study in Japan
Authors: Furuya Kiichiro , Tanaka Yoshitomo , Komatsu Naoto , Hirose Rikuto , Nakamae Akiko , Takemoto Yuki , Kurahashi Hiroki , Hayashida Harue , Fujiwara Sho , Yamashita Saya , Chang Yangsil , Shikado Kayoko , Tsubouchi Hiroaki , Seki Masayuki , Yamato Masaya , Ogita Kazuhide 
Published: November 2022

Abstract
The management of vaginal delivery during the COVID-19 pandemic remains unclear due to lack of information on labor characteristics. We aimed to clarify the effects of COVID-19 on the progression of vaginal labor.
The single-institutional and observational study of COVID-19 women in pregnancy (COVID-19 group, n = 50) delivering from 2020 to 2022, was conducted. Patients’ backgrounds, perinatal outcomes, labor characteristics (labor time and Bishop score), and the details of maternal COVID-19 were analyzed and compared with non-COVID-19 pregnant women (control group, n = 258).
The COVID-19 group showed rapidly progressing labor without adverse effect. The 1st and 2nd stage of labor time, and labor time after rupture of membrane were significantly shorter in the COVID-19 group than in the control group (P < 0.01; P < 0.01; and P < 0.05, respectively). The COVID-19 group had a higher Bishop score on initiation of labor (P < 0.01). Precipitous delivery in the COVID-19 group also significantly increased (P < 0.05). These results indicated that COVID-19 in pregnancy can affect the progression of labor rapidly.
This is the first report focusing on the characteristics of labor progression in COVID-19 women, indicating that COVID-19 can affect the progression of labor without complication.
Use of a real-time PCR method to quantify the primary infection of Plasmopara viticola in commercial vineyards in northwestern China
Authors: Yang Lujia , Chu Bingyao , Yuan Kai , Deng Jie , Jiang Caige , Ma Zhanhong 
Published: November 2022

Abstract
Grapevine downy mildew (GDM), caused by Plasmopara viticola (P. viticola), is a frequent disease of wine grapes in Ningxia Hui Autonomous Region (Ningxia), Northwestern China. At present, however, the primary infection of pathogens in this region has not been deeply investigated. The current study aims to better understand the epidemiological role of overwintering P. viticola and the levels of latent infection before GDM occurrence. We used a previously developed multiplex real-time PCR assay to quantify P. viticola in soil, leaf residue, and asymptomatic leaf samples from ten commercial vineyards in two consecutive years. We found that 60%, 80%, and 100% of the asymptomatic leaves, leaf residues, and soil samples were specific to P. viticola. The molecular disease index (MDI) was used to evaluate the levels of latent infection. Asymptomatic leaves with different levels of P. viticola infection during the latent period and high cumulative MDI correlated with a high area under the disease progress curve in terms of disease index (AUDPC-DI), and the correlation relationship between them was significant at P < 0.01. A well-correlated relationship was found between the AUDPC-DI in the previous year and the MDI data of leaf residues and asymptomatic leaves in the following year, as well as the AUDPC-DI, with corresponding correlation coefficients of 0.504, 0.498, and 0.595, respectively (P < 0.01). The findings indicate that the real-time PCR assay was a useful tool to accurately quantify the primary infection of P. viticola and to efficiently estimate the primary inoculum potentials of GDM epidemics in commercial vineyards.