bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Evaluated Glomerular Filtration Rate and Incident Diabetes Mellitus: A Secondary Retrospective Analysis Based on a Chinese Cohort Study
Authors: Mo Zihe , Hu Haofei , Du Xiaoqing , Huang Qingli , Chen Ping , Lai Linjing , Yu Zhiqun 
Published: January 2022

BackgroundPrevious studies have revealed that chronic kidney disease (CKD) is a significant risk factor for insulin resistance and diabetes. However, few studies are on the association between estimated glomerular filtration rate (eGFR) and incident diabetes, especially in the Chinese population with eGFR&gt;60 mL/min·1.73 m2. This study explored the relationship between eGFR and incident diabetes in a large cohort in the Chinese community.MethodsThis study was a retrospective cohort study. A total of 1,99,435 adults from Rich Healthcare Group in China were studied, including all medical records for participants who received a health check from 2010 to 2016. The target-independent and target-dependent variables were eGFR measured at baseline, and incident diabetes mellitus appeared during the follow-up. After testing the proportion hypothesis, Cox proportional hazards regression was used to investigate the association between eGFR and incident diabetes. A Cox proportional hazards regression with cubic spline functions and smooth curve fitting (the cubic spline smoothing) was used to identify non-linear relationships between eGFR and the risk of diabetes. Additionally, we also performed subgroup analysis and a series sensitivity analysis. It was stated that the data had been uploaded to the DATADRYAD website.ResultAfter adjusting gender, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), smoking and drinking status, and family history of diabetes, the result showed that eGFR was negatively associated with incident diabetes [HR = 0.986, 95% CI (0.984, 0.988)]. A non-linear relationship was detected between eGFR and incident diabetes, with an inflection point of eGFR of 98.034 mL/min·1.73 m2. The effect sizes and the confidence intervals (Cis) on the left and right sides of the inflection point were 0.998 (0.993, 1.003) and 0.976 (0.972, 0.980), respectively. Subgroup analysis showed a stronger association in the population with FPG &lt;6.1 mmol/L, BMI &lt;24 kg/m2, SBP &lt;140 mmHg, DBP &lt;90 mmHg and family history without diabetes. The same trend was also seen in women and the population who never smoke.ConclusionEstimated glomerular filtration rate is independently associated with incident diabetes. The relationship between eGFR and incident diabetes is also non-linear. eGFR is strongly related to incident diabetes when eGFR was above 98.034 mL/min·1.73 m2.
Differential Treatment Effects for Renal Transplant Recipients With DSA-Positive or DSA-Negative Antibody-Mediated Rejection
Authors: Koslik Marius Andreas , Friebus-Kardash Justa , Heinemann Falko Markus , Kribben Andreas , Bräsen Jan Hinrich , Eisenberger Ute 
Published: January 2022

BackgroundAntibody-mediated rejection (ABMR) is the main cause of renal allograft loss. The most common treatment strategy is based on plasmapheresis plus the subsequent administration of intravenous immunoglobulin (IVIG). Unfortunately, no approved long-term therapy is available for ABMR. The current study was designed to analyze the effect of various ABMR treatment approaches on allograft survival and to compare treatment effects in the presence or absence of donor-specific antibodies (DSAs).MethodsThis single-center study retrospectively analyzed 102 renal allograft recipients who had biopsy-proven ABMR after transplant. DSA was detectable in 61 of the 102 patients. Initial standard treatment of ABMR consisted of plasmapheresis (PS) or immunoadsorption (IA), followed by a single course of IVIG. In case of nonresponse or recurrence, additional immunosuppressive medications, such as rituximab, bortezomib, thymoglobulin, or eculizumab, were administered. In a second step, persistent ABMR was treated with increased maintenance immunosuppression, long-term therapy with IVIG (more than 1 year), or both.ResultsOverall graft survival among transplant patients with ABMR was &lt;50% after 3 years of follow-up. Compared to the use of PS/IA and IVIG alone, the use of additional immunosuppressive medications had no beneficial effect on allograft survival (p = 0.83). Remarkably, allografts survival rates were comparable between patients treated with the combination of PS/IA and IVIG and those treated with a single administration of IVIG (p = 0.18). Renal transplant patients with ABMR but without DSAs benefited more from increased maintenance immunosuppression than did DSA-positive patients with ABMR (p = 0.01). Recipients with DSA-positive ABMR exhibited significantly better allograft survival after long-term application of IVIG for more than 1 year than did recipients with DSA-negative ABMR (p = 0.02).ConclusionsThe results of our single-center cohort study involving kidney transplant recipients with ABMR suggest that long-term application of IVIG is more favorable for DSA-positive recipients, whereas intensification of maintenance immunosuppression is more effective for recipients with DSA-negative ABMR.
C4d as a Screening Tool and an Independent Predictor of Clinical Outcomes in Lupus Nephritis and IgA Nephropathy
Authors: Yang Xiaoqian , Yuan Yanhong , Shao Xinghua , Pang Huihua , Che Xiajing , Cao Liou , Zhang Minfang , Xu Yao , Ni Zhaohui , Qi Chaojun , Wang Qin , Mou Shan 
Published: January 2022

BackgroundAs an indispensable marker of complement cascades activation, C4d was confirmed of its crucial role in the pathogenesis of both lupus nephritis (LN) and IgA nephropathy (IgAN). While the studies directly comparing the diagnostic value, and outcomes predicting function of C4d between LN and IgAN are still absent.MethodsA cohort of 120 LN patients, 120 IgAN patients who were diagnosed by renal biopsy between January 2015 and December 2017 and 24 healthy age matched controls were prospectively analyzed. The patients were followed till December 2020. The outcomes were adverse disease treatment response (disease relapse) and kidney disease progression event (decline of estimated glomerular filtration rate by more than 20% or end-stage kidney disease). The renal C4d deposition proportion and pattern were compared between IgAN and LN patients. In addition, the relationship between renal C4d deposition and disease subtypes, disease relapse as well as disease progression for LN and IgAN patients were also analyzed.ResultsThe LN, IgAN patients and healthy controls were well matched in ages. The follow-up period was 38.5 (30.3–60.8) months for LN patients and 45.0 (30.5–57.0) months for IgAN patients. 78 patients (65.0%) with LN had renal C4d deposition, compared with only 39 IgAN patients (32.5%) with C4d deposition in renal tissues (P &lt; 0.001). The LN patients shared different renal C4d distribution patterns with IgAN patients. Compared with IgAN patients, the C4d deposition in LN patients was significantly more in renal glomerulus (P &lt; 0.001) and less in renal tubules (P = 0.003). For disease subtypes, renal C4d deposition was especially strong in class V membranous LN and IgAN with tubulointerstitial fibrosis (T1/T2) lesions. Renal C4d deposition was independently correlated with the disease relapse of LN patients (HR = 1.007, P = 0.040), and acted as an independent predictor of disease progression during the follow-up period for IgAN patients (HR = 1.821, P = 0.040).ConclusionsRenal C4d distribution proportion and pattern differed between LN and IgAN patients. The presence of C4d in renal tissue acted as an independent predictor of relapse for LN patients and disease progression for IgAN patients.
Schwann Cell-Derived Exosomes Induce the Differentiation of Human Adipose-Derived Stem Cells Into Schwann Cells
Authors: Zhou Nan , Xu Zhao , Li Xiang , Ren Sen , Chen Jing , Xiong Hewei , Wang Cheng , Guo Jiahe , Kang Yu , Chen Zhenbing , Li Wenqing , Yang Xiaofan , Zhang Xing , Xu Xiang 
Published: January 2022

Adipose-derived stem cells (ADSCs) can differentiate into Schwann cells (SCs) at the site of nerve injury, where Schwann cell-derived exosomes (SC-Exos) are suspected to exert an induction effect. Our study aimed to induce the differentiation of ADSCs in vitro using SC-Exos and to investigate the mechanisms involved through miRNA sequencing. Subcutaneous fat was used to extract ADSCs. Exosomes were extracted from Schwann cell lines (RSC96) using ultracentrifugation and were able to be taken up by human ADSCs. After 8 days of induction of ADSCs by SC-Exos, phenotypic characteristics were observed by examining the expression of SC markers (S100ß, NGFR, MPZ, GFAP) through RT-qPCR, Western blot and immunofluorescence. The RNA and protein expression levels of S100ß, NGFR, MPZ, and GFAP were found to be significantly higher in the SC-Exo induction group than in the uninduced group, which was also consistent with the immunofluorescence results. Additionally, miRNA sequencing was performed on exosome-induced ADSCs, followed by bioinformatic analysis and validation of the results. According to the sequencing results, there were a total of 94 differentially expressed miRNAs. Bioinformatics analysis indicated that 3506 Gene Ontology terms and 98 Kyoto Encyclopedia of Genes and Genomes pathways were significantly enriched. Ten miRNAs, 5 target mRNAs and elevated expression of the PIK3CD/Akt pathway were validated by RT-qPCR or Western blot, which is consistent with the sequencing results. Our study demonstrates that the utility of SC-Exos is effective in inducing the differentiation of ADSCs into SCs, in which these validated differentially expressed miRNAs exert a vital effect. This work provides a new paradigm via rationally applying Schwann cell-derived exosomes as a promising therapeutic option for repairing peripheral nerve injury.
Prediction of Communication Impairment in Children With Bilateral Cerebral Palsy Using Multivariate Lesion- and Connectome-Based Approaches: Protocol for a Multicenter Prospective Cohort Study
Authors: Hu Jie , Zhang Jingjing , Yang Yanli , Liang Ting , Huang Tingting , He Cheng , Wang Fuqin , Liu Heng , Zhang Tijiang 
Published: January 2022

BackgroundBilateral cerebral palsy (BCP) is the most common type of CP in children and is often accompanied by different degrees of communication impairment. Several studies have attempted to identify children at high risk for communication impairment. However, most prediction factors are qualitative and subjective and may be influenced by rater bias. Individualized objective diagnostic and/or prediction methods are still lacking, and an effective method is urgently needed to guide clinical diagnosis and treatment. The aim of this study is to develop and validate an objective, individual-based model for the prediction of communication impairment in children with BCP by the time they enter school.MethodsA multicenter prospective cohort study will be conducted in four Chinese hospitals. A total of 178 children with BCP will undergo advanced brain magnetic resonance imaging (MRI) at baseline (corrected age, before the age of 2 years). At school entry, communication performance will be assessed by a communication function classification system (CFCS). Three-quarters of children with BCP will be allocated as a training cohort, whereas the remaining children will be allocated as a test cohort. Multivariate lesion- and connectome-based approaches, which have shown good predictive ability of language performance in stroke patients, will be applied to extract features from MR images for each child with BCP. Multiple machine learning models using extracted features to predict communication impairment for each child with BCP will be constructed using data from the training cohort and externally validated using data from the test cohort. Prediction accuracy across models in the test cohort will be statistically compared.DiscussionThe findings of the study may lead to the development of several translational tools that can individually predict communication impairment in children newly diagnosed with BCP to ensure that these children receive early, targeted therapeutic intervention before they begin school.Trial registrationThe study has been registered with the Chinese Clinical Trial Registry (ChiCTR2100049497).
Transarterial Chemoembolization for Hepatocellular Carcinoma in Clinical Practice: Temporal Trends and Survival Outcomes of an Iterative Treatment
Authors: Pelizzaro Filippo , Haxhi Selion , Penzo Barbara , Vitale Alessandro , Giannini Edoardo G. , Sansone Vito , Rapaccini Gian Ludovico , Di Marco Maria , Caturelli Eugenio , Magalotti Donatella , Sacco Rodolfo , Celsa Ciro , Campani Claudia , Mega Andrea , Guarino Maria , Gasbarrini Antonio , Svegliati-Baroni Gianluca , Foschi Francesco Giuseppe , Olivani Andrea , Masotto Alberto , Nardone Gerardo , Raimondo Giovanni , Azzaroli Francesco , Vidili Gianpaolo , Brunetto Maurizia Rossana , Trevisani Franco , Farinati Fabio 
Published: January 2022

BackgroundTransarterial chemoembolization (TACE) is one of the most frequently applied treatments for hepatocellular carcinoma (HCC) worldwide. In this study, we aimed at evaluating whether and how TACE application and repetition, as well as the related outcome, have changed over the last three decades in Italy.MethodsData of 7,184 patients with HCC were retrieved from the Italian Liver Cancer (ITA.LI.CA) database. Patients were divided according to the period of diagnosis in six cohorts: P1 (1988–1993), P2 (1994–1998), P3 (1999–2004), P4 (2005–2009), P5 (2010–2014), and P6 (2015–2019). All the analyses were repeated in the overall patient population and in Barcelona Clinic Liver Cancer (BCLC) B patients, who are the subgroup of HCC patients originally supposed to receive TACE according to guidelines. TACE was defined as either the first or the main (more effective) treatment.ResultsThe proportion of patients receiving TACE as first or main therapy declined over time, and less than 50% of BCLC B patients were treated with chemoembolization from P3 onward. Conversely, TACE was widely used even outside the intermediate stage. Survival of TACE-treated patients progressively increased from P1 to P6. Although TACE was performed only once in the majority of patients, there was an increasing proportion of those receiving 2 or ≥3 treatments sessions over time. The overall survival (OS) of patients undergoing repeated treatments was significantly higher compared to those managed with a single TACE (median OS 40.0 vs. 65.0 vs. 71.8 months in 1, 2, and ≥3 TACE groups, respectively; p &lt; 0.0001). However, after a first-line TACE, the adoption of curative therapies provided longer survival than repeating TACE (83.0 vs. 42.0 months; p &lt; 0.0001), which in turn was associated with better outcomes compared to systemic therapies or best supportive care (BSC).ConclusionsDespite a decline in the percentage of treated patients over time, TACE has still an important role in the management of HCC patients. The survival of TACE-treated patients gradually improved over time, probably due to a better patient selection. Iterative TACE is effective, but an upward shift to curative therapies provides better outcomes while transition to systemic therapies and BSC leads to a worse prognosis.
Imaging Glioblastoma With 18F-Fluciclovine Amino Acid Positron Emission Tomography
Authors: Scarpelli Matthew L. , Healey Debbie R. , Mehta Shwetal , Quarles C. Chad 
Published: January 2022

IntroductionConventional methods of imaging brain tumors fail to assess metabolically active tumor regions, which limits their capabilities for tumor detection, localization, and response assessment. Positron emission tomography (PET) with 18F-fluciclovine (fluciclovine) provides regional assessment of amino acid uptake in tumors that could overcome some of the limitations of conventional imaging. However, the biological basis of enhanced fluciclovine uptake is insufficiently characterized in brain tumors, which confounds clinical interpretation and application. This study sought to address this gap by correlating multiple biologic quantities with fluciclovine PET uptake across a range of human glioblastoma xenograft models.MethodsThirty-one rats underwent orthotopic implantations with one of five different human glioblastoma cell lines. After tumors were established, fluciclovine PET and magnetic resonance imaging (MRI) scans were performed. The fluciclovine tumor-to-normal-brain (TN) uptake ratio was used to quantify fluciclovine uptake. MRI scans were used to assess tumor volume and gadolinium enhancement status. Histologic assessments quantified tumor cell proliferation, tumor cell density, and tumor cell amino acid transporters (LAT1 and ASCT2). Multivariate linear regression models related fluciclovine uptake with the other measured quantities.ResultsWithin the multivariate regression, the fluciclovine TN uptake ratio (measured 15 to 35 minutes after fluciclovine injection) was most strongly associated with tumor ASCT2 levels (β=0.64; P=0.001). The fluciclovine TN uptake ratio was also significantly associated with tumor volume (β=0.45; P=0.001) and tumor enhancement status (β=0.40; P=0.01). Tumor cell proliferation, tumor cell density, and LAT1 levels were not significantly associated with fluciclovine uptake in any of the multivariate models. In general, both enhancing and non-enhancing tumors could be visualized on fluciclovine PET images, with the median TN uptake ratio across the five tumor lines being 2.4 (range 1.1 to 8.9).ConclusionsIncreased fluciclovine PET uptake was associated with increased levels of the amino acid transporter ASCT2, suggesting fluciclovine PET may be useful for assessing brain tumor amino acid metabolism. Fluciclovine PET uptake was elevated in both enhancing and non-enhancing tumors but the degree of uptake was greater in larger tumors and tumors with enhancement, indicating these variables could confound fluciclovine metabolic measurements if not accounted for.
The Effects of Acute and Chronic Selective Phosphodiesterase 1 Inhibition on Smooth Muscle Cell-Associated Aging Features
Authors: Golshiri Keivan , Ataabadi Ehsan Ataei , Jüttner Annika A. , Snyder Gretchen L. , Davis Robert E , Lin Amy , Zhang Lei , de Vries René , Garrelds Ingrid M , Leijten Frank P. J. , Danser A. H. Jan , Roks Anton J. M. 
Published: January 2022

Age-related cardiovascular diseases (CVDs) remain among the leading global causes of death, and vascular smooth muscle cell (VSMC) remodeling plays an essential role in its pathology. Reduced NO-cGMP pathway signaling is a major feature and pathogenic mechanism underlying vasodilator dysfunction. Recently, we identified phosphodiesterase (PDE) 1, an enzyme that hydrolyzes and inactivates the cyclic nucleotides cAMP and cGMP, and thereby provides a potential treatment target for restoring age-related vascular dysfunction due to aging of VSMC. Based on this hypothesis, we here tested the effects of PDE1 inhibition in a model of SMC-specific accelerated aging mice. SMC-KO and their WT littermates received either vehicle or the PDE1 inhibitor lenrispodun for 8 weeks. Vascular function was measured both in vivo (Laser Doppler technique) and ex vivo (organ bath). Moreover, we deployed UV irradiation in cell culture experiments to model accelerated aging in an in vitro situation. SMC-KO mice display a pronounced loss of vasodilator function in the isolated aorta, the cutaneous microvasculature, and mesenteric arteries. Ex vivo, in isolated vascular tissue, we found that PDE1 inhibition with lenrispodun improves vasodilation, while no improvement was observed in isolated aorta taken from mice after chronic treatment in vivo. However, during lenrispodun treatment in vivo, an enhanced microvascular response in association with upregulated cGMP levels was seen. Further, chronic lenrispodun treatment decreased TNF-α and IL-10 plasma levels while the elevated level of IL-6 in SMC-KO mice remained unchanged after treatment. PDE1 and senescence markers, p16 and p21, were increased in both SMC-KO aorta and cultured human VSMC in which DNA was damaged by ultraviolet irradiation. This increase was lowered by chronic lenrispodun. In contrast, lenrispodun increased the level of PDE1A in both situations. In conclusion, we demonstrated that PDE1 inhibition may be therapeutically useful in reversing aspects of age-related VSMC dysfunction by potentiating NO-cGMP signaling, preserving microvascular function, and decreasing senescence. Yet, after chronic treatment, the effects of PDE1 inhibition might be counteracted by the interplay between differential PDE1A and C expression. These results warrant further pharmacodynamic profiling of PDE enzyme regulation during chronic PDE1 inhibitor treatment.
A Cryogenic Hydrogen Ribbon for Laser Driven Proton Acceleration at Hz-Level Repetition Rate
Authors: Chagovets T. , Viswanathan J. , Tryus M. , Grepl F. , Velyhan A. , Stancek S. , Giuffrida L. , Schillaci F. , Cupal J. , Koubikova L. , Garcia D. , Manzagol J. , Bonnay P. , Souris F. , Chatain D. , Girard A. , Margarone D. 
Published: January 2022

We report on recent progress in deploying a continuous solid hydrogen ribbon as a debris-free and renewable laser-driven source of pure proton beams generated by a 30-fs laser with ∼1-J laser energy focused on target at relativistic intensities of ∼1019 W/cm2 and repetition rate of 0.1 Hz. The stability of the ribbon position versus the laser interaction point and maximum repetition rate was tested up to 3.3 Hz. The acceleration of protons with cut-off energies up to 1.5 MeV is demonstrated using a 100-μm thick hydrogen ribbon as proof-of-principle capability of the relatively thick target delivery system. The laser-target geometry presented demonstrates an experimental technique that can potentially enables the operation of a laser–plasma source at Hz-level repetition rate.