bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upper Oligocene–Lower Miocene Gangdese Conglomerate Along the Yarlung-Zangbo Suture Zone and its Implications for Palaeo-Yarlung-Zangbo Initiation
Authors: Ai Keke , Zhang Kexin , Song Bowen , Shen Tianyi , Ji Junliang 
Published: February 2022

The upper Oligocene–lower Miocene Gangdese conglomerate is deposited along the Yarlung-Zangbo suture zone, which extends 1,500 km from west to east and is located in the core area of the India–Eurasia plate collision zone. The Gangdese conglomerate records richly uplift and denudation histories of the Lhasa terrane and Tethyan Himalaya on both sides of the suture zone, thus revealing the growth process of the southern Tibetan Plateau during the Late Oligocene–Early Miocene. In this study, we documented the detailed sedimentology and chronology of the Gangdese conglomerate. The Gangdese conglomerate is dominated by conglomerate and sandstone, with minor volumes of siltstone and tuff deposited in an alluvial fan and fluvial system. Based on sedimentology and structural relationships, we suggest that the Gangdese conglomerate was deposited in an extensional tectonic environment in the early period and an extrusion tectonic environment in the late period, which was controlled by Indian slab shearing and breakoff during the Late Oligocene–Miocene. According to the new magnetostratigraphy and detrital zircon U-Pb dating, the main depositional age of the Gangdese conglomerate was likely the Late Oligocene–Early Miocene (26–18 Ma), and it trended younger from west to east. Moreover, paleocurrent data from the Gangdese conglomerate showed westward axial sediment transport; thus, we inferred that a westward axial palaeo-Yarlung-Zangbo River occurred along the whole Yarlung-Zangbo suture zone during the Late Oligocene–Early Miocene, and its flow was opposite to that of the current Yarlung-Zangbo River.
Chemokines in Gestational Diabetes Mellitus
Authors: Liu Hongying , Liu Aizhong , Kaminga Atipatsa C. , McDonald Judy , Wen Shi Wu , Pan Xiongfeng 
Published: February 2022

BackgroundStudies investigating chemokines in gestational diabetes mellitus (GDM) have yielded mixed results. The purpose of this meta-analysis was to explore whether concentrations of chemokines in patients with GDM differed from that of the controls.MethodsFollowing Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched Web of Science, Embase, Cochrane Library, and PubMed databases for articles, published in any language, on chemokines and GDM through August 1st, 2021. The difference in concentrations of chemokines between patients with GDM and controls was determined by a standardized mean difference (SMD) with a 95% confidence interval (CI), calculated in the meta-analysis of the eligible studies using a random-effects model with restricted maximum-likelihood estimator.ResultsSeventeen studies met the inclusion criteria for the meta-analysis. Altogether, they included nine different chemokines comparisons involving 5,158 participants (1,934 GDM patients and 3,224 controls). Results showed a significant increase of these chemokines (CCL2, CXCL1, CXCL8, CXCL9, and CXCL12) in the GDM patients compared with the controls. However, there was a significant decrease of the chemokines, CCL4, CCL11 and CXCL10, in the GDM patients compared with the controls. Moreover, subgroup analysis revealed a potential role of chemokines as biomarkers in relation to laboratory detection (different sample type and assay methods) and clinical characteristics of GDM patients (ethnicity and body mass index).ConclusionGDM is associated with several chemokines (CCL2, CCL4, CCL11, CXCL1, CXCL8, CXCL9, CXCL10 and CXCL12). Therefore, consideration of these chemokines as potential targets or biomarkers in the pathophysiology of GDM development is necessary. Notably, the information of subgroup analysis underscores the importance of exploring putative mechanisms underlying this association, in order to develop new individualized clinical and therapeutic strategies.
Characteristics and Prognostic Value of Tertiary Lymphoid Organs in Membranous Nephropathy: A Retrospective Study
Authors: Wang Zu-feng , Cheng Yi-chun , Li Yue-Qiang , Liu Liu , Ge Shu-Wang , Xu Gang 
Published: February 2022

BackgroundTertiary lymphoid organs play an essential role in the inflammation of the kidney. The clinical association between TLOs and membranous nephropathy (MN) is not clear yet.MethodsConsecutive patients with the histologically confirmed membranous nephropathy in Tongji Hospital from July 19, 2012, to September 26, 2019, were included in this study. TLOs in renal biopsy tissues were detected by periodic acid–Schiff-stained and immunohistochemistry. Logistic regression was performed to evaluate the correlations of TLOs and clinical features of patients with MN. Kaplan–Meier analysis was utilized to examine the relationship between TLOs and remission of proteinuria.ResultsA total of 442 patients with MN were included in this study, of which the average age was 46.4 years old, and 58.8% were male. Moreover, 33% of patients with MN had TLOs in this study. The median value of proteinuria among patients with MN with TLOs was 4.9 g/24 h, which was much greater than no-TLOs ones (3.2 g/24 h, p &lt; 0.001). Moreover, the patients with TLOs had higher serum creatinine and lower serum albumin. The severity of clinical features among the patients with MN aggravated with the increase in the grade of TLOs. In addition, the patients who had TLOs were more likely to be positive of anti-phospholipase A2 receptor autoantibodies. Meanwhile, the patients without TLOs showed significantly higher complete remission and total remission of proteinuria.ConclusionIn this study, we demonstrated that TLOs were common among patients with MN. Moreover, the patients with MN with TLOs showed a worse clinical manifestation and an outcome compared with the patients without TLOs.
The Aftermath of Tapering Tocilizumab After Achieving Treatment Target in Patients With Rheumatoid Arthritis: A Nationwide Cohort Study
Authors: Park Jun Won , Kim Min Jung , Kim Hyoun-Ah , Kim Jin Hyun , Lee Eun Bong , Shin Kichul 
Published: February 2022

BackgroundAlthough recent guidelines recommend that tapering of biologic disease-modifying anti-rheumatic drugs (bDMARDs) can be considered in patients with rheumatoid arthritis (RA), there has been little evidence supporting the strategy during the non-tumor necrosis factor inhibitor treatment. This study aims to investigate the effectiveness and safety of tapering tocilizumab (TCZ) dose in patients with RA who attain low disease activity (LDA) after TCZ therapy in a nationwide cohort.MethodsData were collected from a nationwide cohort of patients with RA receiving biologic disease-modifying anti-rheumatic drugs in South Korea (KOBIO-RA). This study included 350 patients who were treated with TCZ and achieved Clinical Disease Activity Index-low disease activity (CDAI)-LDA (CDAI ≤ 10) after 1 year of treatment. We performed longitudinal analysis considering clinical data measured at all 1-year intervals for the included patients using the generalized estimating equation. A total of 575 intervals were classified into two groups according to their dose quotient (DQ) of TCZ (tapering group vs. standard-dose group). The main outcome was maintaining CDAI-LDA in the following 1-year interval.ResultsTapering TCZ dose strategy was used in 282 (49.0%) intervals with a mean (SD) DQ of 66.0 (15.5) %. Loss of CDAI-LDA occurred in 91 (15.1%) intervals. Multivariable GEE showed that the tapering group was associated with more frequent failure to sustain CDAI-LDA (adjusted OR [95% CI]: 0.57 [0.33–0.99]), which subsequently led to impaired functional status. The likelihood of achieving DAS28-deep remission (DAS28-ESR &lt;1.98) was also significantly lower in the tapering group (adjusted OR 0.68 [0.46–0.99]). CDAI remission was achieved in only 69 (12.0%) of the total intervals, with no significant difference in the proportion of intervals achieving the target between the two groups. Incidence of adverse events was comparable in both groups except for hypercholesterolemia, which was lower in the tapering group.ConclusionsTapering TCZ dose after achieving LDA increases the risk of losing LDA without a significant merit in safety.
Stereopsis and Eye Movement Abnormalities in Parkinson’s Disease and Their Clinical Implications
Authors: Ba Fang , Sang Tina T. , He Wenjing , Fatehi Jaleh , Mostofi Emanuel , Zheng Bin 
Published: February 2022

BackgroundParkinson’s disease (PD) is not exclusively a motor disorder. Among non-motor features, patients with PD possess sensory visual dysfunctions. Depth perception and oculomotor deficits can significantly impact patients’ motor performance. Stereopsis and eye behavioral study using 3D stimuli may help determine their implications in disease status.ObjectiveThe objective of this study is to investigate stereopsis and eye movement abnormalities in PD with reliable tools and their correlation with indicators of PD severity. We hypothesize that patients with PD exhibit different eye behaviors and that these differences may correlate to the severity of motor symptoms and cognitive status.MethodsControl and PD participants were first evaluated for visual acuity, visual field, contrast acuity, and stereo perception with 2D and Titmus stereotests, followed by the assessment with a 3D active shutter system. Eye movement behaviors were assessed by a Tobii X2-60 eye tracker.ResultsScreening visual tests did not reveal any differences between the PD and control groups. With the 3D active shutter system, the PD group demonstrated significantly worse stereopsis. The preserved cognitive function was correlated to a more intact stereo function. Patients with PD had longer visual response times, with a higher number of fixations and bigger saccade amplitude, suggesting fixation stabilization difficulties. Such changes showed a positive correlation with the severity of motor symptoms and a negative correlation with normal cognitive status.ConclusionWe assessed stereopsis with a 3D active shutter system and oculomotor behaviors with the Tobii eye tracker. Patients with PD exhibit poorer stereopsis and impaired oculomotor behaviors during response time. These deficits were correlated with PD motor and cognitive status. The visual parameters may potentially serve as the clinical biomarkers for PD.
Topological Abnormalities of Pallido-Thalamo-Cortical Circuit in Functional Brain Network of Patients With Nonchemotherapy With Non-small Cell Lung Cancer
Authors: Liu Siwen , Yin Na , Li Chenchen , Li Xiaoyou , Ni Jie , Pan Xuan , Ma Rong , Wu Jianzhong , Feng Jifeng , Shen Bo 
Published: February 2022

IntroductionSome previous studies in patients with lung cancer have mainly focused on exploring the cognitive dysfunction and deficits of brain function associated with chemotherapy. However, little is known about functional brain alterations that might occur prior to chemotherapy. Therefore, this study aimed to evaluate brain functional changes in patients with nonchemotherapy before chemotherapy with non-small cell lung cancer (NSCLC).MethodsResting-state functional MRI data of 35 patients with NSCLC and 46 matched healthy controls (HCs) were acquired to construct functional brain networks. Graph theoretical analysis was then applied to investigate the differences of the network and nodal measures between groups. Finally, the receiver operating characteristic (ROC) curve analysis was performed to distinguish between NSCLC and HC.ResultsDecreased nodal strength was found in the left inferior frontal gyrus (opercular part), inferior frontal gyrus (triangular part), inferior occipital gyrus, and right inferior frontal gyrus (triangular part) of patients with NSCLC while increased nodal strength was found in the right pallidum and thalamus. NSCLC also showed decreased nodal betweenness in the right superior occipital gyrus. Different hub regions distribution was found between groups, however, no hub regions showed group differences in the nodal measures. Furthermore, the ROC curve analysis showed good performance in distinguishing NSCLC from HC.ConclusionThese results suggested that topological abnormalities of pallido-thalamo-cortical circuit in functional brain network might be related to NSCLC prior to chemotherapy, which provided new insights concerning the pathophysiological mechanisms of NSCLC and could serve as promising biological markers for the identification of patients with NSCLC.
ANXA2P2: A Potential Immunological and Prognostic Signature in Ovarian Serous Cystadenocarcinoma via Pan-Carcinoma Synthesis
Authors: Zhang Yanna , Du Ting , Chen Xiancheng 
Published: February 2022

BackgroundAlthough the effect of pseudogene ANXA2P2 on some tumors has been reported in a few literatures, the therapeutic potential and prognostic value of ANXA2P2 in ovarian serous cystadenocarcinoma (OV) have not been elucidated.MethodsThe correlation for ANXA2P2 expression patterns to prognostic characteristics, tumor immune microenvironment, immune cell infiltration level, tumor mutation burden (TMB), tumor microsatellite instability (MSI), drug sensitivity, and pathway function enrichment were investigated in pan-carcinoma via TCGA and GTEx databases. Subsequently, the role of ANXA2P2 expression levels in the pathway enrichments and prognosis prediction in OV were further explored using weighted correlation network analysis (WGCNA) analysis, gene mutation analysis, and risk-independent prognostic analysis.ResultsANXA2P2 was frequently overexpressed in a variety of tumors compared with normal tissues. The correlation analysis for prognostic characteristics, tumor immune microenvironment, immune cell infiltration level, TMB, MSI, drug sensitivity, and pathway function enrichment revealed that ANXA2P2 expression patterns might deal a significant impact on the pathogenesis, development, and prognosis of various tumors. Then, GSVA, GSEA, WGCNA, gene mutation, and independent prognostic analysis for OV have indicated that high expression in ANXA2P2 could be mostly enriched in TNF-α signaling-via-NF-κB, epithelial-mesenchymal transition, apical junction, IL-6-JAK STAT3 signaling, etc., which were also proved to act as crucial factors on tumorigenesis, development, invasion, and metastasis. The mutation of TP53 (94%), TTN (24%), and CSMD3 (9%) in the biological process of tumor had been confirmed by relevant studies. Finally, the independent prognostic analysis demonstrated that ANXA2P2 expression in OV contributes greatly to the dependability of 3- and 5-year survival prediction.ConclusionIn summary, our findings might provide a helpful foundation for prospective explorative researches, afford new strategies for the clinical treatment, deal prognosis prediction, and give new hope for OV patients.
Perioperative Low Dose Dexmedetomidine and Its Effect on the Visibility of the Surgical Field for Middle Ear Microsurgery: A Randomised Controlled Trial
Authors: Wu Jinhong , Han Yuan , Lu Yu , Zhuang Yan , Li Wenxian , Jia Ji’e 
Published: February 2022

Background and Purpose: There are many benefits of administering dexmedetomidine perioperatively. The pharmacokinetics (PK) and pharmacodynamics (PD) of intravenous, intranasal and oral dexmedetomidine that was administered before anesthesia were compared in this study, and the effects of dexmedetomidine on the surgical field visibility in tympanoplasty was evaluated.Methods: A single-blind, randomized controlled trial was conducted in a university-affiliated hospital where 45 patients who underwent tympanoplasty under general anesthesia were randomly allocated into three groups. Dexmedetomidine was administered by intravenous infusion at 0.8 μg.kg−1 for 10 min, intranasal instillation at a drop rate of 1 μg.kg−1 and oral intake at 4 μg.kg−1 ten minutes before the induction of anesthesia. The PK and PD of dexmedetomidine after a single low dose administration and its effect on the surgical field in tympanoplasty were analysed.Results: A plasma concentration of dexmedetomidine of 220 pg/ml was achieved immediately after intravenous infusion and at 13.2 and 70.3 min for intranasal and oral administration, respectively. Dexmedetomidine decreased the heart rate (HR) and mean arterial pressure (MAP) in all three groups, although these values remained higher in the oral dexmedetomidine group at all eight time points. Intravenous dexmedetomidine provided the best visualization of the surgical field for opening of the tympanic sinus, 30 min after the start of the infusion (p &lt; 0.05). Intranasal dexmedetomidine provided a significantly better visual field than oral dexmedetomidine for the repair of a tympanic membrane perforation using the fascia temporal muscle (p &lt; 0.05).Conclusion: A single low dose of dexmedetomidine administered intravenously or intranasally could decrease HR and MAP, improve surgical field visibility and be appropriate for deliberate hypotension for surgical procedures of 1–2 h in length.Trial registration: Clinicaltrials.gov identifier: NCT03800641.
Tissue Pharmacokinetic Properties and Bystander Potential of Hypoxia-Activated Prodrug CP-506 by Agent-Based Modelling
Authors: Jackson-Patel Victoria , Liu Emily , Bull Matthew R. , Ashoorzadeh Amir , Bogle Gib , Wolfram Anna , Hicks Kevin O. , Smaill Jeff B. , Patterson Adam V. 
Published: February 2022

Hypoxia-activated prodrugs are bioactivated in oxygen-deficient tumour regions and represent a novel strategy to exploit this pharmacological sanctuary for therapeutic gain. The approach relies on the selective metabolism of the prodrug under pathological hypoxia to generate active metabolites with the potential to diffuse throughout the tumour microenvironment and potentiate cell killing by means of a “bystander effect”. In the present study, we investigate the pharmacological properties of the nitrogen mustard prodrug CP-506 in tumour tissues using in silico spatially-resolved pharmacokinetic/pharmacodynamic (SR-PK/PD) modelling. The approach employs a number of experimental model systems to define parameters for the cellular uptake, metabolism and diffusion of both the prodrug and its metabolites. The model predicts rapid uptake of CP-506 to high intracellular concentrations with its long plasma half-life driving tissue diffusion to a penetration depth of 190 µm, deep within hypoxic activating regions. While bioreductive metabolism is restricted to regions of severe pathological hypoxia (&lt;1 µM O2), its active metabolites show substantial bystander potential with release from the cell of origin into the extracellular space. Model predictions of bystander efficiency were validated using spheroid co-cultures, where the clonogenic killing of metabolically defective “target” cells increased with the proportion of metabolically competent “activator” cells. Our simulations predict a striking bystander efficiency at tissue-like densities with the bis-chloro-mustard amine metabolite (CP-506M-Cl2) identified as a major diffusible metabolite. Overall, this study shows that CP-506 has favourable pharmacological properties in tumour tissue and supports its ongoing development for use in the treatment of patients with advanced solid malignancies.
A Global Survey of COVID-19 Vaccine Acceptance Among Healthcare Workers
Authors: Noushad Mohammed , Rastam Samer , Nassani Mohammad Zakaria , Al-Saqqaf Inas Shakeeb , Hussain Mudassir , Yaroko Ali Ango , Arshad Mohammed , Kirfi Abdullahi Musa , Koppolu Pradeep , Niazi Fayez Hussain , Elkandow Ali , Darwish Mahmoud , Abdalla Nassar Ahmad Salim , Abuzied Mohammed Sami Osman , Abdalrady Hassan Nasser Hassan , Abusalim Ghadah Salim , Samran Abdulaziz , Alsalhani Anas B , Demachkia Amir Mohiddin , de Melo Renata Marques , Luddin Norhayati , Husein Adam , Habib Adnan , Suleyman Firas , Osman Hussein Ali , Al-Awar Mohammed Sadeg , Dimashkieh Mohiddin R. , Swapna Lingam Amara , Barakat Ali , Alqerban Ali 
Published: February 2022

ObjectivesEven though several effective vaccines are available to combat the COVID-19 pandemic, wide disparities in vaccine distribution, and vaccine acceptance rates between high- and low-income countries appear to be major threats toward achieving population immunity. Our global descriptive study aims to inform policymakers on factors affecting COVID-19 vaccine acceptance among healthcare workers (HCWs) in 12 countries, based on income index. We also looked for possible predictors of vaccine acceptance among the study sample.MethodsA structured questionnaire prepared after consultation with experts in the field and guided by the “Report of the SAGE working group on vaccine hesitancy” was administered among 2,953 HCWs. Upon obtaining informed consent, apart from demographic information, we collected information on trust in vaccines and health authorities, and agreement to accept a COVID-19 vaccine.ResultsAlthough 69% of the participants agreed to accept a vaccine, there was high heterogeneity in agreement between HCWs in low and lower-middle income countries (L-LMICs) and upper-middle- and high-income countries (UM-HICs), with acceptance rates of 62 and 75%, respectively. Potential predictors of vaccine acceptance included being male, 50 years of age or older, resident of an UM-HIC, updating self about COVID-19 vaccines, greater disease severity perception, greater anxiety of contracting COVID-19 and concern about side effects of vaccines.ConclusionsCOVID-19 vaccine acceptance among HCWs in L-LMICs was considerably low as compared to those from UM-HICs. The lowest vaccine acceptance rates were among HCWs from the African continent. This underlines the need for the implementation of country-specific vaccine promotion strategies, with special focus on increasing vaccine supply in L-LMICs.
Development of an American Indian Diabetes Education Cultural Supplement: A Qualitative Approach
Authors: Wilson Jamie , Thomson Cynthia , Sabo Samantha , Edleman Anathea , Kahn-John Michelle 
Published: February 2022

ObjectiveThe purpose of this study was to culturally enhance a diabetes education program for Diné (Navajo) community members with Type 2 diabetes. Though the recommendation to culturally adapt health education curricula was meant to improve health education for American Indians and Alaskan Natives (AIANs), it has inadvertently created a “one size fits all” approach. This approach does not properly address the need for tribe-specific cultural health messaging, defined as incorporating cultural elements deemed relevant to the population. Tribe-specific health information and programming, such as integrating Diné worldviews and Indigenous knowledge among Diné people as described here, are essential to creating a culturally relevant and effective and meaningful approach to disease self-management.MethodsA conversation guide, based on the Hózhó Resilience Model—a Diné framework on healthy living, was used to engage key cultural experts in interviews about traditional stories and teachings regarding health and wellness. Three specific self-care behaviors relevant to Type 2 diabetes self-management were discussed: (1) healthy eating, (2) physical activity, and (3) healthy coping. Interviews were audio-recorded, transcribed and analyzed using a qualitative thematic analysis method.ResultsDiné healers and cultural experts informed the development of an educational tool called Diné Health. Key themes that emerged from the data included the importance of discipline, positivity and mindfulness in the context of Hózhó.ConclusionCulturally safe and meaningful engagement with cultural leaders and the use of qualitative research methods can inform deep-level cultural adaptations essential to developing tribe-specific diabetes education programs. The approaches used here can guide the development, implementation, and testing of culturally-informed health education for AIAN populations.