bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multilevel cervical disc arthroplasty: a review of optimal surgical management and future directions
Authors: Tu Tsung-Hsi , Wang Ching-Ying , Chen Yu-Chun , Wu Jau-Ching 
Published: December 2022

OBJECTIVE
Cervical disc arthroplasty (CDA) has been recognized as a popular option for cervical radiculopathy or myelopathy caused by disc problems that require surgery. There have been prospective randomized controlled trials comparing CDA to anterior cervical discectomy and fusion (ACDF) for 1- and 2-level disc herniations. However, the indications for CDA have been extended beyond the strict criteria of these clinical trials after widespread real-world experiences in the past decade. This article provides a bibliometric analysis with a review of the literature to understand the current trends of clinical practice and research on CDA.

METHODS
The PubMed database was searched using the keywords pertaining to CDA in human studies that were published before August 2022. Analyses of the bibliometrics, including the types of papers, levels of evidence, countries, and the number of disc levels involved were conducted. Moreover, a systematic review of the contents with the emphasis on the current practice of multilevel CDA and complex cervical disc problems was performed.

RESULTS
A total of 957 articles published during the span of 22 years were analyzed. Nearly one-quarter of the articles (232, 24.2%) were categorized as level I evidence, and 33.0% were categorized as levels I or II. These studies clearly demonstrated the viability and effectiveness of CDA regarding clinical and radiological outcomes, including neurological improvement, maintenance, and preservation of segmental mobility with relatively low risks for several years postoperation. Also, there have been more papers published during the last decade focusing on multilevel CDA and fewer involving the comparison of ACDF. Overall, there was a clustering of CDA papers published from the US and East Asian countries. Based on substantial clinical data of CDA for 1- and 2-level disc diseases, the practice and research of CDA show a trend toward multilevel and complex disease conditions.

CONCLUSIONS
CDA is an established surgical management procedure for 1- and 2-level cervical disc herniation and spondylosis. The success of motion preservation by CDA—with low rates of complications—has outscored ACDF in patients without deformity. For more than 2-level disc diseases, the surgery shows a trend toward multiple CDA or hybrid ACDF–CDA according to individual evaluation for each level of degeneration.
Perbandingan Kadar Flavonoid Total Berdasarkan Perbedaan Konsentrasi Pelarut Etanol Dari Ekstrak Daun Pegagan (Centella asiatica [L] Urban)
Authors: Khairunnisa Syifa , Hakim Ali Rakhman , Audina Mia 
Published: December 2022

Latar belakang: Daun pegagan (Centella asiatica [L] Urban) secara empiris digunakan untuk pengobatan jerawat. Kandungan senyawa kimia yang memiliki efek farmakologis tersebut salah satunya flavonoid. Senyawa flavonoid yang bersifat polar dapat ditarik menggunakan pelarut polar berdasarkan tingkat kepolaran yang berbeda, dimana dapat mempengaruhi hasil kadar flavonoid total yang didapatkan.
Tujuan: Mengetahui konsentrasi pelarut etanol yang efektif dan optimal untuk mendapatkan kadar flavonoid total dari ekstrak daun pegagan (Centella asiatica [L.] Urban).
Metode: Penelitian ini menggunakan metode pre eksperimental dengan desain rancangan acak kelompok dan metode penelitian dengan melakukan ekstraksi maserasi, uji kualitatif pereaksi warna dan kromatografi lapis tipis serta penentuan kadar flavonoid total menggunakan Spektrofotometri UV-Vis. Analisis data untuk mengetahui pengaruh perbedaan konsentrasi pelarut etanol menggunakan uji non parametik Mann-Whitney.
Hasil: Hasil uji kualitatif pereaksi warna dan kromatografi lapis tipis positif mengandung flavonoid. Penentuan kadar flavonoid total ekstrak etanol 70% sebesar 4,339 mg QE /g dan ekstrak etanol 96% sebesar 1,895 mg QE /g. Hasil analisis data konsentrasi pelarut etanol berpengaruh signifikan terhadap kadar flavonoid total.
Kesimpulan: Berdasarkan hasil penelitian ekstrak etanol 70% dan 96% positif mengandung senyawa metabolit sekunder flavonoid dari hasil pengukuran kadar flavonoid total ekstrak etanol 70% lebih efektif dalam menyari flavonoid dan konsentrasi pelarut etanol berpengaruh terhadap kadar flavonoid total
Efficient depolymerization of lignin through microwave-assisted Ru/C catalyst cooperated with metal chloride in methanol/formic acid media
Authors: Shao Lupeng , Wang Chao , Liu Yu , Wang Meng , Wang Luyan , Xu Feng 
Published: December 2022

Lignin, an abundant aromatic biopolymer, has the potential to produce various biofuels and chemicals through biorefinery activities and is expected to benefit the future circular economy. Microwave-assisted efficient degradation of lignin in methanol/formic acid over Ru/C catalyst cooperated with metal chloride was investigated, concerning the effect of type and dosage of metal chloride, dosage of Ru/C, reaction temperature, and reaction time on depolymerized product yield and distribution. Results showed that 91.1 wt% yield of bio-oil including 13.4 wt% monomers was obtained under the optimum condition. Yields of guaiacol-type compounds and 2,3-dihydrobenzofuran were promoted in the presence of ZnCl2. Formic acid played two roles: (1) acid-catalyzed cleavage of linkages; (2) acted as an in situ hydrogen donor for hydrodeoxygenation in the presence of Ru/C. A possible mechanism for lignin degradation was proposed. This work will provide a beneficial approach for efficient depolymerization of lignin and controllable product distribution.
Empagliflozin inhibits coronary microvascular dysfunction and reduces cardiac pericyte loss in db/db mice
Authors: Tu Yimin , Li Qing , Zhou Yuanchen , Ye Zixiang , Wu Chao , Xie Enmin , Li Yike , Li Peizhao , Wu Yaxin , Guo Ziyu , Yu Changan , Zheng Jingang , Gao Yanxiang 
Published: December 2022

BackgroundCoronary microvascular dysfunction (CMD) is a pathophysiological feature of diabetic heart disease. However, whether sodium-glucose cotransporter 2 (SGLT2) inhibitors protect the cardiovascular system by alleviating CMD is not known.ObjectiveWe observed the protective effects of empagliflozin (EMPA) on diabetic CMD.Materials and methodsThe mice were randomly divided into a db/db group and a db/db + EMPA group, and db/m mice served as controls. At 8 weeks of age, the db/db + EMPA group was given empagliflozin 10 mg/(kg⋅d) by gavage for 8 weeks. Body weight, fasting blood glucose and blood pressure were dynamically observed. Cardiac systolic and diastolic function and coronary flow reserve (CFR) were detected using echocardiography. The coronary microvascular structure and distribution of cardiac pericytes were observed using immunofluorescence staining. Picrosirius red staining was performed to evaluate cardiac fibrosis.ResultsEmpagliflozin lowered the increased fasting blood glucose levels of the db/db group. The left ventricular ejection fraction, left ventricular fractional shortening, E/A ratio and E/e′ ratio were not significantly different between the three groups. CFR was decreased in the db/db group, but EMPA significantly improved CFR. In contrast to the sparse and abnormal expansion of coronary microvessels observed in the db/db group, the number of coronary microvessels was increased, and the capillary diameter was decreased in the db/db + EMPA group. The number and microvascular coverage of cardiac pericytes were reduced in the db/db mice but were improved by EMPA. The cardiac fibrosis was increased in db/db group and may alleviate by EMPA.ConclusionEmpagliflozin inhibited CMD and reduced cardiac pericyte loss in diabetic mice.
Dissecting CD8+ T cell pathology of severe SARS-CoV-2 infection by single-cell immunoprofiling
Authors: Schreibing Felix , Hannani Monica T. , Kim Hyojin , Nagai James S. , Ticconi Fabio , Fewings Eleanor , Bleckwehl Tore , Begemann Matthias , Torow Natalia , Kuppe Christoph , Kurth Ingo , Kranz Jennifer , Frank Dario , Anslinger Teresa M. , Ziegler Patrick , Kraus Thomas , Enczmann Jürgen , Balz Vera , Windhofer Frank , Balfanz Paul , Kurts Christian , Marx Gernot , Marx Nikolaus , Dreher Michael , Schneider Rebekka K. , Saez-Rodriguez Julio , Costa Ivan , Hayat Sikander , Kramann Rafael 
Published: December 2022

IntroductionSARS-CoV-2 infection results in varying disease severity, ranging from asymptomatic infection to severe illness. A detailed understanding of the immune response to SARS-CoV-2 is critical to unravel the causative factors underlying differences in disease severity and to develop optimal vaccines against new SARS-CoV-2 variants.MethodsWe combined single-cell RNA and T cell receptor sequencing with CITE-seq antibodies to characterize the CD8+ T cell response to SARS-CoV-2 infection at high resolution and compared responses between mild and severe COVID-19.ResultsWe observed increased CD8+ T cell exhaustion in severe SARS-CoV-2 infection and identified a population of NK-like, terminally differentiated CD8+ effector T cells characterized by expression of FCGR3A (encoding CD16). Further characterization of NK-like CD8+ T cells revealed heterogeneity among CD16+ NK-like CD8+ T cells and profound differences in cytotoxicity, exhaustion, and NK-like differentiation between mild and severe disease conditions.DiscussionWe propose a model in which differences in the surrounding inflammatory milieu lead to crucial differences in NK-like differentiation of CD8+ effector T cells, ultimately resulting in the appearance of NK-like CD8+ T cell populations of different functionality and pathogenicity. Our in-depth characterization of the CD8+ T cell-mediated response to SARS-CoV-2 infection provides a basis for further investigation of the importance of NK-like CD8+ T cells in COVID-19 severity.
Impact of neutrophil extracellular traps on fluid properties, blood flow and complement activation
Authors: Burmeister Antonia , Vidal-y-Sy Sabine , Liu Xiaobo , Mess Christian , Wang Yuanyuan , Konwar Swagata , Tschongov Todor , Häffner Karsten , Huck Volker , Schneider Stefan W. , Gorzelanny Christian 
Published: December 2022

IntroductionThe intravascular formation of neutrophil extracellular traps (NETs) is a trigger for coagulation and blood vessel occlusion. NETs are released from neutrophils as a response to strong inflammatory signals in the course of different diseases such as COVID-19, cancer or antiphospholipid syndrome. NETs are composed of large, chromosomal DNA fibers decorated with a variety of proteins such as histones. Previous research suggested a close mechanistic crosstalk between NETs and the coagulation system involving the coagulation factor XII (FXII), von Willebrand factor (VWF) and tissue factor. However, the direct impact of NET-related DNA fibers on blood flow and blood aggregation independent of the coagulation cascade has remained elusive.MethodsIn the present study, we used different microfluidic setups in combination with fluorescence microscopy to investigate the influence of neutrophil-derived extracellular DNA fibers on blood rheology, intravascular occlusion and activation of the complement system.ResultsWe found that extended DNA fiber networks decelerate blood flow and promote intravascular occlusion of blood vessels independent of the plasmatic coagulation. Associated with the DNA dependent occlusion of the flow channel was the strong activation of the complement system characterized by the production of complement component 5a (C5a). Vice versa, we detected that the local activation of the complement system at the vascular wall was a trigger for NET release.DiscussionIn conclusion, we found that DNA fibers as the principal component of NETs are sufficient to induce blood aggregation even in the absence of the coagulation system. Moreover, we discovered that complement activation at the endothelial surface promoted NET formation. Our data envisions DNA degradation and complement inhibition as potential therapeutic strategies in NET-induced coagulopathies.
EGFR-targeted bacteriophage lambda penetrates model stromal and colorectal carcinoma tissues, is taken up into carcinoma cells, and interferes with 3-dimensional tumor formation
Authors: Huh Haein , Chen Ding-Wen , Foldvari Marianna , Slavcev Roderick , Blay Jonathan 
Published: December 2022

IntroductionColorectal cancer and other adult solid cancers pose a significant challenge for successful treatment because the tumor microenvironment both hinders the action of conventional therapeutics and suppresses the immune activities of infiltrating leukocytes. The immune suppression is largely the effect of enhanced local mediators such as purine nucleosides and eicosanoids. Genetic approaches have the promise of interfering with these mechanisms of local immunosuppression to allow both intrinsic and therapeutic immunological anticancer processes. Bacterial phages offer a novel means of enabling access into tissues for therapeutic genetic manipulations.MethodsWe generated spheroids of fibroblastic and CRC cancer cells to model the 3-dimensional stromal and parenchymal components of colorectal tumours. We used these to examine the access and effects of both wildtype (WT) and epidermal growth factor (EGF)-presenting bacteriophage λ (WT- λ and EGF-λ) as a means of delivery of targeted genetic interventions in solid cancers. We used both confocal microscopy of spheroids exposed to AF488-tagged phages, and the recovery of viable phages as measured by plaque-forming assays to evaluate access; and measures of mitochondrial enzyme activity and cellular ATP to evaluate the outcome on the constituent cells.ResultsUsing flourescence-tagged derivatives of these bacteriophages (AF488-WT-λ and AF488-EGF-λ) we showed that phage entry into these tumour microenvironments was possible and that the EGF ligand enabled efficient and persistent uptake into the cancer cell mass. EGF-λ became localized in the intracellular portion of cancer cells and was subjected to subsequent cellular processing. The targeted λ phage had no independent effect upon mature tumour spheroids, but interfered with the early formation and growth of cancer tissues without the need for addition of a toxic payload, suggesting that it might have beneficial effects by itself in addition to any genetic intervention delivered to the tumour. Interference with spheroid formation persisted over the duration of culture.DiscussionWe conclude that targeted phage technology is a feasible strategy to facilitate delivery into colorectal cancer tumour tissue (and by extension other solid carcinomas) and provides an appropriate delivery vehicle for a gene therapeutic that can reduce local immunosuppression and/or deliver an additional direct anticancer activity.
Isotope constraints on nitrogen dynamics in the upper water column of the South China Sea
Authors: Yan Xiuli , Yang Jin-Yu Terence , Xu Min Nina , Tan Ehui , Zheng Zhenzhen , Zou Wenbin , Dai Minhan , Kao Shuh-Ji 
Published: December 2022

The supply of nitrogen (N) from various external and internal sources into the euphotic zone, e.g., atmospheric N deposition (AND), upwelling, lateral intrusion, and remineralization, modulates the biogeochemical and climatic roles of oligotrophic oceans and complicates N dynamics in the upper water column (≤200 m). However, our ability to resolve the mechanisms controlling upper-ocean N cycling is limited by the lack of high-resolution vertical observations. Here, we analyzed concentrations and dual isotopes of nitrate (NO3–) in the upper 200 m of the oligotrophic South China Sea. By examining dual isotopic signatures of NO3– (δ15NNO3 and δ18ONO3) and multiple associated parameters vertically throughout the upper water column, we resolved the dominant N sources and processes, including AND/N2-fixation, assimilative fractionation, and nitrification, and quantitatively evaluated their contributions in the vertical distribution of NO3–, which can be separated into the Δδ18ONO3-positive (δ18ONO3−obs−δ18ONO3−200m&gt;0) and Δδ18ONO3-negative layers (δ18ONO3−obs−δ18ONO3−200m&lt;0) according to the deviation in δ18ONO3 at a given depth (δ18ONO3-obs) from that at 200 m (δ18ONO3-200m). In the Δδ18ONO3-positive layer, the NO3– assimilated by phytoplankton was largely sourced from nitrification (39 ± 11%) and AND/N2 fixation (17-28%), whereas these two processes accounted for 17 ± 10% and 7 ± 6% of the total NO3– pool in the Δδ18ONO3-negative layer. Considering a substantial contribution of the regenerated (nitrification-sourced) NO3– to the total NO3– pool especially in the Δδ18ONO3-positive layer, caution should be taken that the new production assessed by the rates of NO3– uptake may be significantly overestimated in the SCS. These findings not only highlight the importance of these biogeochemical processes to NO3– dynamics in the upper water column of marginal seas, but also with important implications for the estimation of biological carbon pump and/or the f-ratio.
Effects of straw returning combined with earthworm addition on nitrification and ammonia oxidizers in paddy soil
Authors: Chu Xiangqian , Bai Naling , Zheng Xianqing , Wang Quanhua , Pan Xi , Li Shuangxi , Zhang Juanqin , Zhang Haiyun , He Wenjie , Zhong Feng , Lv Weiguang , Zhang Hanlin 
Published: December 2022

HighlightsStraw returning combined with earthworm increased the richness of ammonia oxidizers.NH4+-N was a critical driver for altering the ammonia oxidizer community structure.Earthworm addition significantly increased soil PNR.Under the alkaline paddy soil, AOB dominated in soil nitrification.
Regional activity alterations in Parkinson’s disease patients with anxiety disorders: A resting-state functional magnetic resonance imaging study
Authors: Zhang Peiyao , Zhang Yanling , Luo Yuan , Wang Lu , Wang Kang 
Published: December 2022

BackgroundPrevious studies have revealed alteration of functional connectivity (FC) in Parkinson’s disease patients with anxiety (PD-A), but local brain activities associated with anxiety in Parkinson’s disease (PD) patients remain to be elucidated. Regional homogeneity (ReHo) analysis was employed to investigate alterations of regional brain activities in PD-A patients.MethodsResting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 42 PD-A patients, 41 PD patients without anxiety (PD-NA), and 40 age-and gender-matched healthy control (HC) subjects. ReHo analysis was used to investigate the synchronization of neuronal activities in brain regions in the three groups. The relationship between ReHo value and anxiety score in the PD-A group was also investigated.ResultsParkinson’s disease patients with anxiety showed increased ReHo values in the bilateral frontal lobes, caudate nucleus, and anterior cingulate gyrus [Gaussian random field (GRF) correction, voxel size p &lt; 0.01, cluster size p &lt; 0.05], compared with PD-NA patients and HC subjects, but the ReHo values of the right cerebellar hemisphere and posterior cerebellar lobe decreased (GRF correction, voxel size p &lt; 0.01, cluster size p &lt; 0.05). The increased ReHo values of the right superior frontal gyrus (r = 0.633, p = 0.001) and anterior cingulate gyrus (r = 0.45, p = 0.01) were positively correlated with anxiety scores in PD-A patients.ConclusionThe development of PD-A may be associated with dysfunctional local activities in multiple brain regions, including the frontal cortex, cerebella, basal ganglia, and limbic system. Abnormal ReHo values in these brain regions may serve as neuroimaging markers for the early diagnosis of PD-A. The results suggest that using ReHo analysis to identify functional changes in core regions may advance our understanding of the pathophysiological mechanisms underlying PD-A.
What does a “good life” mean for people living with dementia? A protocol for a think-aloud study informing the value of care
Authors: Kinchin Irina , Leroi Iracema , Kennelly Sean P. , Kochovska Slavica , Brady Conor , Fitzhenry Deborah , McHale Cathy , Kinghorn Philip , Coast Joanna 
Published: December 2022

IntroductionEconomic evaluation currently focuses almost exclusively on the maximization of health, using the Quality-Adjusted Life-Year (QALY) framework with instruments such as the EQ-5D, with a limited number of health-focused dimensions providing the assessment of health benefit. This evaluative framework is likely to be insufficient for setting priorities in dementia care because of its exclusive concern with health. Data are also often collected from the perspective of a proxy, limiting the voice of those living with dementia in decision-making. This protocol describes a research project that aims to gather the perspectives of people living with dementia, their insights, and preferences for assessing their quality of life to inform economic evaluation outcome measurement and design with a goal of creating a more robust evidence base for the value of healthcare services. Specifically, this study will elucidate what a “good life” means to people living with dementia and how well instruments currently used in economic evaluation meet this description. This project will further test the acceptability of capability wellbeing instruments as self-report instruments and compare them to generic and dementia-specific preference-based instruments.Methods and analysisPeople living with dementia, diagnosed, or waiting to receive a formal diagnosis and with the capacity to participate in research, will be invited to participate in an hour “think aloud” interview. Participants will be purposefully selected to cover a range of dementia diagnoses, age, and sex, recruited through the integrated care, geriatric, and post-diagnostic clinics at St James’ and Tallaght University Hospitals and dementia support groups in the Ireland. During the interview, participants will be invited to reflect on a “good life” and “think aloud” while completing four economic quality of life instruments with a perspective that goes beyond health (AD-5D/QOL-AD, AQOL-4D, ICECAP-O, ICECAP-SCM). An interviewer will then probe areas of difficulty when completing the instruments in a semi-structured way. The analysis will identify the frequency of errors in comprehension, retrieval, judgment, and response from verbatim transcripts. Qualitative data will be analyzed using constant comparison.EthicsThe St James’s Hospital and Tallaght University Hospital Joint Research Ethics Committee approved the study (Approval Date: 11 April 2022).