bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical and Biological Factors Underlying Long-Term Decline of Dissolved Oxygen Concentrationin the East/Japan Sea
Authors: Kim Haejin , Hirose Naoki , Takayama Katsumi 
Published: May 2022

A substantial decrease in the dissolved oxygen (DO) concentration over the lower layers of the East/Japan Sea (EJS), including the deep and bottom waters (1500 to 2500 m and 2500 to 3500 m, respectively), has been reported during the last few decades. This study quantitatively explain the mechanisms underlying the long-term decline in the DO concentration of the EJS for the first time using a coupled physical-biogeochemical model. We demonstrated that the cessation of new water formation was a major factor underlying the long-term decline in the DO concentration over the lower layers, and its contribution exceeded the net decrease. In addition, our simulations confirmed that the enhanced primary production in the euphotic zone accompanying increases in organic matter exported to the lower layers accelerates the DO decline in a quantitative respect. It was accounted for 12% of the net DO change at the lower layers from 1980 to 2015. The enhanced primary production resulted from increases in available nutrients due to the intensified vertical mixing caused by the strengthened inflow transport through the Korea/Tsushima Strait. Physical activities such as vertical transport of oxygen from the central water increased the DO concentration of the lower layers, and offset 42% of the net decrease in DO concentration due to organic matter decomposition.
Diel Vertical Distribution of Mesozooplankton Functional Groups in the North Pacific Subtropical Gyre: A Case Study
Authors: Ge Ruping , Li Yixuan , Chen Hongju , Lei Facan , Zhuang Yunyun , Liu Guangxing 
Published: May 2022

Understanding the diel vertical migration (DVM) patterns of zooplankton has important implications for biological pumping and pelagic food webs. The functional traits of zooplankton generally determine their distribution in the environment. However, knowledge about the DVM patterns of zooplankton with different functional traits is limited. Here, we used a trait-based approach to study the vertical distributions of zooplankton in the North Pacific Subtropical Gyre (NPSG). Four functional traits, namely, body length, feeding type, trophic group, and reproductive mode, were selected in this study. A high biodiversity of zooplankton (165 taxa) was recorded in the NPSG. Zooplankton was mainly concentrated above 100 m and exhibited normal DVM. Zooplankton with small and medium body sizes (&lt;2 mm, 69% ± 16%), current feeding (43% ± 14%), and omnivore–herbivores (54% ± 14%) were dominant in the NPSG. The proportion of sac spawners in total abundance (52% ± 14%) was higher than that of broadcast spawners (48% ± 14%), which differed from that in the coastal regions. Sixteen functional groups of zooplankton were identified. Different functional groups exhibited distinct DVM patterns due to the influence of different factors. The DVM patterns of current-feeding omnivore–herbivores were significantly correlated with chlorophylla, whereas giant ambush-feeding carnivores exhibited normal DVM patterns and were substantially correlated with the vertical distribution of their food organisms. However, the small omnivore–carnivores showed reverse DVM patterns. Overall, this study provided a new perspective for studies on zooplankton DVM from the aspect of functional traits.
Platelet Parameters and Their Relationships With the Thickness of the Retinal Nerve Fiber Layer and Ganglion Cell Complex in Primary Open-Angle Glaucoma
Authors: Ma Yi , Li Shengjie , Shao Mingxi , Cao Wenjun , Sun Xinghuai 
Published: May 2022

ObjectiveGlaucoma is a neurodegenerative disease of the visual system. Platelet parameters are correlated with visual field mean deviation (MD) in glaucoma, but there is a lack of relative data on their relationship with structural changes in the retina. This study aimed to explore the relationship between platelet parameters and retinal nerve fiber layer (RNEL), ganglion cell complex (GCC) thickness, and cup/disk area ratio, evaluated by optical coherence tomography (OCT) in primary open-angle glaucoma (POAG).MethodsA total of 118 consecutive patients with POAG and 120 age- and sex-matched control subjects were included in this retrospective study. Demographic data, platelet parameters in blood tests, visual field, and OCT results were evaluated. The RNFL was divided into the temporal, superior, nasal, and inferior quadrants. Based on the visual field MD, the patients were stratified into mild (MD ≤ 6.0 dB), moderate (6 dB &lt; MD ≤ 12 dB), and severe (MD &gt; 12.0 dB) subgroups.ResultsPatients with POAG had significantly lower platelet (PLT) levels and significantly higher platelet distribution width (PDW) and mean platelet volume (MPV) levels than controls. As the visual field MD increased, structural evaluation by OCT identified loss of disk rim area, average GCC thickness, and average RNFL thickness (all P &lt; 0.001), as well as increased PDW (P &lt; 0.001) and MPV (P = 0.004) levels in patients with POAG. The Spearman's rank correlation analysis showed that PDW levels were significantly correlated with OCT parameters such as RNFL thickness (r = −0.370, P &lt; 0.001), GCC thickness (r = −0.294, P = 0.001), and cup/disk area ratio (r = 0.322, P &lt; 0.001), as well as visual field MD (r = 0.607, P &lt; 0.001) and mean sensitivity (MS) (r = −0.570, P &lt; 0.001). Significantly correlations were also found between MPV and RNFL thickness (r = −0.321, P &lt; 0.001), GCC thickness (r = −0.194, P = 0.041), and cup/disk area ratio (r = 0.237, P = 0.010). All the quadrants showed similar negative correlations between PDW, MPV, and RNFL thickness. The multiple linear regression analyses showed significant association between PDW and RNFL thickness (β = −0.331, P &lt; 0.001), PDW and GCC thickness (β = −0.288, P = 0.002), MPV and RNFL thickness (β = −0.313, P = 0.001), and MPV and GCC thickness (β = −0.188, P = 0.048).ConclusionThis study found significantly negative association between PDW, MPV levels and RNFL, GCC thickness, as well as positive association between PDW, MPV levels, and cup/disk area ratio in patients with POAG, suggesting that platelet activation may contribute to glaucomatous optic neuropathy.
Estimation of Human Cerebral Atrophy Based on Systemic Metabolic Status Using Machine Learning
Authors: Sakatani Kaoru , Oyama Katsunori , Hu Lizhen , Warisawa Shin'ichi 
Published: May 2022

BackgroundBased on the assumption that systemic metabolic disorders affect cognitive function, we have developed a deep neural network (DNN) model that can estimate cognitive function based on basic blood test data that do not contain dementia-specific biomarkers. In this study, we used the same DNN model to assess whether basic blood data can be used to estimate cerebral atrophy.MethodsWe used data from 1,310 subjects (58.32 ± 12.91years old) enrolled in the Brain Doc Bank. The average Mini Mental State Examination score was 28.6 ± 1.9. The degree of cerebral atrophy was determined using the MRI-based index (GM-BHQ). First, we evaluated the correlations between the subjects' age, blood data, and GM-BHQ. Next, we developed DNN models to assess the GM-BHQ: one used subjects' age and blood data, while the other used only blood data for input items.ResultsThere was a negative correlation between age and GM-BHQ scores (r = -0.71). The subjects' age was positively correlated with blood urea nitrogen (BUN) (r = 0.40), alkaline phosphatase (ALP) (r = 0.22), glucose (GLU) (r = 0.22), and negative correlations with red blood cell counts (RBC) (r = −0.29) and platelet counts (PLT) (r = −0.26). GM-BHQ correlated with BUN (r = −0.30), GLU (r = −0.26), PLT (r = 0.26), and ALP (r = 0.22). The GM-BHQ estimated by the DNN model with subject age exhibited a positive correlation with the ground truth GM-BHQ (r = 0.70). Furthermore, even if the DNN model without subject age was used, the estimated GM-BHQ showed a significant positive correlation with ground truth GM-BHQ (r = 0.58). Age was the most important variable for estimating GM-BHQ.DiscussionAging had the greatest effect on cerebral atrophy. Aging also affects various organs, such as the kidney, and causes changes in systemic metabolic status, which may contribute to cerebral atrophy and cognitive impairment. The DNN model may serve as a new screening test for dementia using basic blood tests for health examinations. Finally, the blood data reflect systemic metabolic disorders in each subject—this method may thus contribute to personalized care.
Brain Mechanism of Acupuncture Treatment of Chronic Pain: An Individual-Level Positron Emission Tomography Study
Authors: Xu Jin , Xie Hongjun , Liu Liying , Shen Zhifu , Yang Lu , Wei Wei , Guo Xiaoli , Liang Fanrong , Yu Siyi , Yang Jie 
Published: May 2022

ObjectiveAcupuncture has been shown to be effective in the treatment of chronic pain. However, their neural mechanism underlying the effective acupuncture response to chronic pain is still unclear. We investigated whether metabolic patterns in the pain matrix network might predict acupuncture therapy responses in patients with primary dysmenorrhea (PDM) using a machine-learning-based multivariate pattern analysis (MVPA) on positron emission tomography data (PET).MethodsForty-two patients with PDM were selected and randomized into two groups: real acupuncture and sham acupuncture (three menstrual cycles). Brain metabolic data from the three special brain networks (the sensorimotor network (SMN), default mode network (DMN), and salience network (SN)) were extracted at the individual level by using PETSurfer in fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) data. MVPA analysis based on metabolic network features was employed to predict the pain relief after treatment in the pooled group and real acupuncture treatment, separately.ResultsPaired t-tests revealed significant alterations in pain intensity after real but not sham acupuncture treatment. Traditional mass-univariate correlations between brain metabolic and alterations in pain intensity were not significant. The MVPA results showed that the brain metabolic pattern in the DMN and SMN did predict the pain relief in the pooled group of patients with PDM (R2 = 0.25, p = 0.005). In addition, the metabolic pattern in the DMN could predict the pain relief after treatment in the real acupuncture treatment group (R2 = 0.40, p = 0.01).ConclusionThis study indicates that the individual-level metabolic patterns in DMN is associated with real acupuncture treatment response in chronic pain. The present findings advanced the knowledge of the brain mechanism of the acupuncture treatment in chronic pain.
A Survey of Resources and Nursing Workforce for Clinical Research Delivery in Paediatric Intensive Care Within the UK / Ireland
Authors: Menzies Julie C. , Jennings Claire , Marshall Rebecca 
Published: May 2022

IntroductionClinical research within Paediatric Intensive Care (PICU) is necessary to reduce morbidity and mortality associated within this resource-intensive environment. With UK PICUs encouraged to be research-active there was a drive to understand how centres support research delivery.AimTo identify the research workforce available within UK/Ireland PICUs to support clinical research delivery.MethodAn electronic survey, endorsed by the Paediatric Critical Care Society (PCCS), was designed and reported in accordance with CHERRIES guidelines. The survey was distributed by email to all UK/Ireland Nurse Managers and Medical/ Nursing Research leads, aiming for one response per site during the period of April-June 2021. Only one response per site was included in analysis.Results44 responses were received, representing 24/30 UK/Ireland sites (80% response rate). Responses from n = 21/30 units are included (three excluded for insufficient data). 90% (n = 19/21) units were research active, although only 52% (n = 11) had permanent research roles funded within their staffing establishment. The majority of units (n = 18, 86%) had less than two WTE research nurses. Resources were felt to be sufficient for current research delivery by 43% of units (n = 9), but this confidence diminished to 19% (n = 4) when considering their ability to support future research. The top barriers to research conduct were insufficiently funded/unfunded studies (52%; n = 11), clinical staff too busy to support research activity (52%; n = 11) and short-term/fixed-term contracts for research staff (38%; n = 8).ConclusionDespite the perceived importance of research and 90% of responding UK/Ireland PICUs being research active, the majority have limited resources to support research delivery. This has implications for their ability to participate in future multi-centre trials and opportunities to support the development of future medical/nursing clinical academics. Further work is required to identify optimum models of clinical research delivery.
Analysis of Clinical and Genetic Characterization of Three Ataxia–Telangiectasia Pedigrees With Novel ATM Gene Mutations
Authors: Huang Peng , Zhang Lu , Tang Li , Ren Yi , Peng Hong , Xiong Jie , Liu Lingjuan , Xu Jie , Xiao Yangyang , Li Jian , Mao Dingan , Liu Liqun 
Published: May 2022

ObjectiveThe clinical manifestations of ataxia–telangiectasia (AT) are very complex and are easily misdiagnosed and missed. The purpose of this study was to explore the clinical characteristics and genetic features of five pediatric patients with AT from three pedigrees in china.MethodsRetrospectively collected and analyzed the clinical data and genetic testing results of five AT patients diagnosed by the Whole-exome sequencing followed by Sanger sequencing. The five patients with AT were from three pedigrees, including two female patients (case 1 and case 2) in pedigree I, one male patient (case 3) in pedigree II, and two male patients (case 4 and case 5) in pedigree III. According to the United Kingdom Association for Clinical Genomic Science Best Practice Guidelines for Variants Classification in Rare Disease 2020 to grade the genetic variants.ResultsFive patients had mainly clinical presentations including unsteady gait, dysarthria, bulbar conjunctive telangiectasia, cerebellar atrophy, intellectual disability, stunted growth, increase of alpha-fetoprotein in serum, lymphopenia. Notably, one patient with classical AT presented dystonia as the first symptom. One patient had recurrent infections, five patients had serum Immunoglobulin (Ig) A deficiency, and two patients had IgG deficiency. In three pedigrees, we observed five pathogenic variants of the ATM gene, which were c.1339C&gt;T (p.Arg447Ter), c.7141_7151delAATGGAAAAAT (p.Asn2381GlufsTer18), c.437_440delTCAA (p.Leu146GlnfsTer6), c.2482A&gt;T (p.Lys828Ter), and c.5495_5496+2delAAGT (p.Glu1832GlyfsTer4). Moreover, the c.437_440delTCAA, c.2482A&gt;T, and c.5495_5496+2delAAGT were previously unreported variants.ConclusionsPediatric patients with classical AT may present dystonia as the main manifestation, or even a first symptom, besides typical cerebellar ataxia, bulbar conjunctive telangiectasia, etc. Crucially, we also found three novel pathogenic ATM gene variants (c.437_440delTCAA, c.2482A&gt;T, and c.5495_5496+2delAAGT), expanding the ATM pathogenic gene mutation spectrum.
Hepatoprotective Effect of Oplopanax elatus Nakai Adventitious Roots Extract by Regulating CYP450 and PPAR Signaling Pathway
Authors: Jiang Xiao-Long , Luo Pan-Yue , Zhou Yan-Ying , Luo Zhi-Hui , Hao Yue-Jun , Fan Ming-Zhi , Wu Xiao-Han , Gao Hao , Bi Hui-Chang , Zhao Zhi-Bin , Lian Mei-Lan , Lian Zhe-Xiong 
Published: May 2022

O. elatus Nakai is a traditional medicine that has been confirmed to exert effective antioxidant and anti-inflammatory functions, and is used for the treatment of different disorders. However, its potential beneficial effects on drug induced hepatotoxicity and relevant molecular mechanisms remain unclear. This study investigated the protective effect and further elucidated the mechanisms of action of O. elatus on liver protection. O. elatus chlorogenic acids-enriched fraction (OEB), which included chlorogenic acid and isochlorogenic acid A, were identified by HPLC-MS/MS. OEB was administrated orally daily for seven consecutive days, followed by a single intraperitoneal injection of an overdose of APAP after the final OEB administration. The effects of OEB on immune cells in mice liver were analyzed using flow cytometry. APAP metabolite content in serum was detected using HPLC-MS/MS in order to investigate whether OEB affects CYP450 activities. The intestinal content samples were processed for 16 s microbiota sequencing. Results demonstrated that OEB decreased alanine aminotransferase, aspartate aminotransferase contents, affected the metabolism of APAP, and decreased the concentrates of APAP, APAP-CYS and APAP-NAC by inhibiting CYP2E1 and CYP3A11 activity. Furthermore, OEB pretreatment regulated lipid metabolism by affecting the peroxisome proliferator-activated receptors (PPAR) signaling pathway in mice and also increased the abundance of Akkermansia and Parabacteroides. This study indicated that OEB is a potential drug candidate for treating hepatotoxicity because of its ability to affect drug metabolism and regulate lipid metabolism.
Characteristics of Early Phase Clinical Trials for Rare Cancers: Insights From Interviews With Stakeholders
Authors: Dooms M , Saesen R , Steemans I , Lansens J , Huys I 
Published: May 2022

Background: Rare cancers occur with an incidence of no more than six cases per 100,000 people according to the definition used by the Surveillance of Rare Cancers in Europe project. For a variety of reasons (low prevalence, cytotoxicity), it is challenging to perform the necessary clinical studies to investigate the safety and efficacy of investigational medicines against such rare malignancies, reformulating even at the earliest stages of the drug development process. This article investigates the differences between phase I rare cancer trials performed in commercial (companies) and non-commercial settings (academic hospitals).Materials and Methods: The differences were explored through the conduct of semi-structured interviews with three different stakeholder groups: representatives from academia (n = 7), representatives from companies (n = 4) and representatives from patient organizations (n = 4). All the interviews were transcribed verbatim and analyzed in NVivo using the framework method.Results: According to the interviewees, the academic and commercial stakeholders collaborate in the majority of phase I rare cancer trials. In general, the commercial partner finances the trial, whereas academia is responsible for the execution of the study procedures. The average cost of undertaking these trials is difficult to estimate because it depends on what is specifically requested during the trial. The 3 + 3 study design remains the most widely used design and the use of expansion cohorts is controversial. With regard to the regulatory aspects of phase I rare cancer trials, it was expressed that a good regulatory framework facilitates the conduct of these studies, but that increased regulation and oversight also has drawbacks, e.g., differences in standards between different ethics committees, over interpretation of the rules, insufficient availability of qualified personnel and higher workloads. The patient organization representatives claimed that patients experience no differences in terms of accommodation, compensation and paperwork between the academic and commercial settings or the degree of follow-up. They also believed that the direct input of patients can bring added value to such studies not only with regard to the recruitment process and the feasibility of the study but also the legibility of the informed consent forms.Conclusion: The growing need for first-in-man trials in rare malignancies needs to be highlighted, as difficult as they are to undertake and to co-develop, not only because rare cancer patients deserve an appropriate treatment, but also because these medicines represent the future of cancer therapy in the precision medicine era. Cooperation of commercial and academic sites are needed. Patient organizations need to be educated to take part in this process.
Developing a Core Outcome Set for Clinical Trials of Chinese Medicine for Hyperlipidemia
Authors: Li Geng , Han Ruxue , Lin Mingjun , Wen Zehuai , Chen Xiankun 
Published: May 2022

Background: Chinese medicine (CM) is widely used for treating hyperlipidemias, especially in China. However, the heterogeneity of outcomes measured and reported across trials exacerbates the obstacles of evidence synthesis and effectiveness comparison. In this study, we develop a core outcome set (COS) for CM clinical trials for hyperlipidemia (COS-CM-Hyperlipidemia) to tackle the outcome issues.Methods: We generated candidate outcomes through a systematic review of interventional and observational studies of Chinese medicine for hyperlipidemias. The comprehensive search strategy was employed. Study selection and data collection were independently done by two researchers. We searched clinical trial registry platform to supplement the outcomes list extracted by systematic review. Then, we conducted a three-round Delphi survey. The stakeholders were hyperlipidemia patients, clinicians or researchers, in either CM/integrated Chinese or Western medicine, clinical pharmacy, clinical epidemiology or statisticians, or editors of important relevant journals and an ethicist. They used a 9-point Likert scale to determine how important they felt each outcome was in determining treatment success. A consensus meeting was held to confirm the final COS, based on the Delphi survey results.Results: We identified a total of 433 outcomes from 3,547 articles, and 28 outcomes from 367 registered trials. After standardization, we selected 71 outcomes to develop a preliminary outcome list for further consensus. After three Delphi survey rounds and one consensus meeting, the most important outcomes were determined for COS-CM-Hyperlipidemia. It included cardiovascular events, low-density lipoprotein cholesterol, risk of cardiovascular disease, total cholesterol, carotid intima-media thickness, high-density lipoprotein cholesterol, triglycerides, cerebrovascular events, adverse drug reactions and patient-reported symptoms.Conclusion: COS-CM-Hyperlipidemia may improve outcome reporting consistency in clinical trials. Further work is needed to explore the optimal methods for measuring these outcomes.Registration: The Core Outcome Measures in Effectiveness Trials Initiative (COMET): http://www.cometinitiative.org/studies/details/983. Registered on 25 April 2017.