bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical experience of noninvasive prenatal testing for rare chromosome abnormalities in singleton pregnancies
Authors: Hu Ting , Wang Jiamin , Zhu Qian , Zhang Zhu , Hu Rui , Xiao Like , Yang Yunyuan , Liao Na , Liu Sha , Wang He , Niu Xiaoyu , Liu Shanling 
Published: September 2022

Objectives: The study aimed to investigate the clinical use of noninvasive prenatal testing (NIPT) for common fetal aneuploidies as a prenatal screening tool for the detection of rare chromosomal abnormalities (RCAs).Methods: Gravidas with positive NIPT results for RCAs who subsequently underwent amniocentesis for a single nucleotide polymorphism array (SNP array) were recruited. The degrees of concordance between the NIPT and SNP array were classified into full concordance, partial concordance, and discordance. The positive predictive value (PPV) was used to evaluate the performance of NIPT.Results: The screen-positivity rate of NIPT for RCAs was 0.5% (842/158,824). Of the 528 gravidas who underwent amniocentesis, 29.2% (154/528) were confirmed to have positive prenatal SNP array results. PPVs for rare autosomal trisomies (RATs) and segmental imbalances were 6.1% (7/115) and 21.1% (87/413), respectively. Regions of homozygosity/uniparental disomy (ROH/UPD) were identified in 9.5% (50/528) of gravidas. The PPV for clinically significant findings was 8.0% (42/528), including 7 cases with mosaic RATs, 30 with pathogenic/likely pathogenic copy number variants, and 5 with imprinting disorders.Conclusion: NIPT for common fetal aneuploidies yielded low PPVs for RATs, moderate PPVs for segmental imbalances, and incidental findings for ROH/UPD. Due to the low PPV for clinically significant findings, NIPT for common fetal aneuploidies need to be noticed for RCAs.
Effect of metformin on the epigenetic age of peripheral blood in patients with diabetes mellitus
Authors: Li Man , Bao Litao , Zhu Ping , Wang Shuxia 
Published: September 2022

Background: Metformin has been proven to have an antiaging effect. However, studies on how metformin affects global epigenetic regulation and its effect on the epigenetic clock in diabetes mellitus (DM) patients are limited. This study aims to investigate the impact of metformin on the epigenetic age in subjects with type 2 DM.Results: We collected the peripheral blood of the metformin group and the no-metformin group of the 32 DM patients. Three previously established epigenetic clocks (Hannum, Horvath, and DNAmPhenoAge) were used to estimate the epigenetic age acceleration of the two groups. We defined biological age acceleration for each group by comparing the estimated biological age with the chronological age. Results were presented as follows: 1) all three epigenetic clocks were strongly correlated with chronological age. 2) We found a strong association between metformin intake and slower epigenetic aging by Horvath’s clock and Hannum’s clock.Conclusions: Here, we found an association between metformin intake and slower epigenetic aging.
Comprehensive analysis of PTPN gene family revealing PTPN7 as a novel biomarker for immuno-hot tumors in breast cancer
Authors: Wang Fengxu , Wang Xuehai , Liu Lei , Deng Siyuan , Ji Wenqian , Liu Yang , Wang Xiangdong , Wang Rui , Zhao Xinyuan , Gao Erli 
Published: September 2022

Background: The non-receptor protein tyrosine phosphatase (PTPN) gene family has been considered to be involved in the oncogenesis and development of multiple cancers. However, its prognostic utility and immunological relevance in breast cancer (BrCa) have not been clarified.Methods: A transcriptional level interpretation of the expressions and prognostic values was analyzed using the data from The Cancer Genome Atlas (TCGA) cohort. In addition, GO and DAVID pinpoint the functional enrichment of PTPNs. Moreover, the immune correlations of PTPN7 in BrCa and pan-cancer were further investigated based on the TCGA cohort and were testified using the in-house and the Gene Expression Omnibus (GEO) cohorts.Results: For systematic analysis of the PTPN family, we found that the expression levels of PTPN1, PTPN6, PTPN7, PTPN18, PTPN20, and PTPN22 was promoted in tumor tissues while comparing with paraneoplastic tissues during our study. We further investigated their functions and protein-protein interactions (PPI), and these results strongly suggested that PTPN family was associated with protein dephosphorylation. Next, we performed an immunological relevance analysis and found that PTPN7 was correlated with immune infiltration, suggesting a stronger association of PTPN7 with immuno-hot tumors in BrCa. In addition, results from the in-house cohort confirmed the positive correlation between PTPN7 and PD-L1. The pan-cancer analysis revealed that PTPN7 was related to PD-L1 and CTLA-4 expression in almost all cancer types. Finally, the predictive value of PTPN7 for immunotherapy was significant in two independent GEO cohorts.Conclusion: In conclusion, this is the first extensive research on the correlation between PTPN family expression and immune characterization in BrCa. As results, PTPN7 expression is associated with immuno-hot tumors and could be a promising predictive biomarker for immunotherapy in not only BrCa but multiple cancers.
Synthetic MRI in the detection and quantitative evaluation of sacroiliac joint lesions in axial spondyloarthritis
Authors: Zhang Ke , Liu Chaoran , Zhu Yunfei , Li Wenjuan , Li Ximeng , Zheng Jing , Hong Guobin 
Published: September 2022

ObjectiveOur primary objective was to verify the hypothesis that synthetic magnetic resonance imaging (MRI) is similar to conventional MRI in detecting sacroiliac joint lesions in patients with axial spondyloarthritis (axSpA). A secondary objective was to assess the quantitative value of synthetic mapping in bone marrow edema (BME) and fat metaplasia.MethodsA total of 132 axSpA patients who underwent synthetic and conventional MRI from October 2019 to March 2021 were included in this prospective study. Two independent readers visually evaluated active inflammatory (BME, capsulitis, enthesitis, and inflammation at site of erosion) and structural lesions (erosion, sclerosis, ankylosis, and fat metaplasia) of the sacroiliac joints on conventional and synthetic magnetic resonance (MR) images. In addition, T1, T2, and proton density (PD) values, which were generated by synthetic mapping, were used to further quantitatively evaluate BME and fat metaplasia. A McNemar test was used to compare the differences between the two methods in the detection of sacroiliac joint lesions. Intraclass correlation coefficients (ICCs) were used to assess the inter-reader consistency of quantitative values. Mann–Whitney tests were performed, and receiver operating characteristic (ROC) curves were created for all quantitative analyses.ResultsThere were no statistical difference between synthetic and conventional MRI in the detection of sacroiliac joint lesions (all p-values &gt; 0.05). A total of 103 images of BME and 111 images of fat metaplasia were quantitatively evaluated using T1, T2, and PD values. The consistency of quantitative values among readers was good (ICC 0.903–0.970). T1 and T2 values were consistently higher in BME than in normal marrow (p &lt; 0.001), but PD values were not significantly different (p = 0.830). T2 and PD values were higher in fat metaplasia than in normal marrow, but T1 values were lower (p &lt; 0.001). In the case of BME, T1 values had greater diagnostic efficiency [area under the curve (AUC) 0.99] than T2 values (AUC 0.78). There were no significant differences in the diagnostic efficiency of T1 (AUC 0.88), T2 (AUC 0.88), and PD (AUC 0.88) values in the case of fat metaplasia.ConclusionSynthetic MRI is as effective as conventional MRI in detecting sacroiliac joint lesions in patients with axSpA. Furthermore, synthetic mapping can accurately quantify BME and fat metaplasia.
Case Report: Successful engraftment of allogeneic hematopoietic stem cells using CAR-T cell therapy as the conditioning regimen in R/R Ph+ B cell acute lymphoblastic leukemia
Authors: Han Lu , Zhao Ran , Yang Jingyi , Zu Yingling , Liu Yanyan , Zhou Jian , Li Linlin , Huang Zhenghua , Zhang Jishuai , Gao Quanli , Song Yongping , Zhou Keshu 
Published: September 2022

BackgroundConsolidative allogeneic hematopoietic stem cells (allo-HSCs) after chimeric antigen receptor T cells (CAR-T) therapy is an emerging modality in hematologic malignancies. Knowledge about the success of allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CAR-T therapy without a conditioning regimen is limited.Case presentationWe report a patient with relapsed/refractory (R/R) Ph+ B-cell acute lymphoblastic leukemia (ALL) who underwent anti-CD19 CAR-T immunotherapy. After 1 month of treatment, bone marrow hyperplasia remained reduced with no hematopoietic improvements. In line with this, allogeneic hematopoietic stem cells (HSCs) were extracted from an HLA-matched sibling donor and administered to the patient on day 33 after CAR-T cell therapy to support hematopoiesis. On day 40, the level of immature bone marrow lymphocytes was at 0% and minimal residual disease-negative, and the fusion gene BCR/ABL 190 was negative. Chimerism analysis showed full donor chimerism. Three months after CAR-T cells infusion, the patient was still in complete remission with full donor chimerism. However, decreased liver function with skin pigmentation and festering, indicative of acute graft versus host disease, was noted. The treatment was halted owing to financial reasons.ConclusionWe report the successful engraftment of allogeneic HSCs using CAR-T cell therapy as a conditioning regimen for R/R B-ALL patients.
SARS-CoV-2 IgG spike protein antibody response in mRNA-1273 Moderna® vaccinated patients on maintenance immunoapheresis – a cohort study
Authors: Gaggl Martina , Aschauer Constantin , Aigner Christof , Bond Gregor , Vychytil Andreas , Strassl Robert , Wagner Ludwig , Sunder-Plassmann Gere , Schmidt Alice 
Published: September 2022

BackgroundThe SARS-CoV-2 pandemic increased mortality and morbidity among immunocompromised populations. Vaccination is the most important preventive measure, however, its effectiveness among patients depending on maintenance immunoglobulin G (IgG) apheresis to control autoimmune disease activity is unknown. We aimed to examine the humoral immune response after mRNA-1273 Moderna® vaccination in immunoapheresis patients.MethodsWe prospectively monitored SARS-CoV-2 IgG spike (S) protein antibody levels before and after each IgG (exposure) or lipid (LDL) apheresis (controls) over 12 weeks and once after 24 weeks. Primary outcome was the difference of change of SARS-CoV-2 IgG S antibody levels from vaccination until week 12, secondary outcome was the difference of change of SARS-CoV-2 IgG S antibody levels by apheresis treatments across groups.ResultsWe included 6 IgG and 18 LDL apheresis patients. After 12 weeks the median SARS-CoV-2 IgG S antibody level was 115 (IQR: 0.74, 258) in the IgG and 1216 (IQR: 788, 2178) in the LDL group (p=0.03). Median SARS-CoV-2 IgG S antibody reduction by apheresis was 76.4 vs. 23.7% in the IgG and LDL group (p=0.04). The average post- vs. pre-treatment SARS-CoV-2 IgG S antibody rebound in the IgG group vs. the LDL group was 46.1 and 6.44%/week from prior until week 12 visit.ConclusionsIgG apheresis patients had lower SARS-CoV-2 IgG S antibody levels compared to LDL apheresis patients, but recovered appropriately between treatment sessions. We believe that IgG apheresis itself probably has less effect on maintaining the immune response compared to concomitant immunosuppressive drugs. Immunization is recommended independent of apheresis treatment.
An overlook on the current registries for rare and complex connective tissue diseases and the future scenario of TogethERN ReCONNET
Authors: Bandeira Matilde , Di Cianni Federica , Marinello Diana , Arnaud Laurent , Cannizzo Sara , Carta Claudio , Cornet Alain , Barril Sara M. , Bulina Inita , Ferraris Alessandro , Fonseca João , Gaglioti Andrea , Limper Marteen , Lorenzoni Valentina , Majnik Judith , Matucci-Cerinic Marco , Palla Ilaria , Rednic Simona , Schneider Matthias , Smith Vanessa , Sulli Alberto , Søndergaard Klaus , Ticciati Simone , Tincani Angela , Turchetti Giuseppe , Talarico Rosaria , Cutolo Maurizio , Mosca Marta , Taruscio Domenica 
Published: September 2022

BackgroundPatient registries play a crucial role in supporting clinical practice, healthcare planning and medical research, offering a real-world picture on rare and complex connective tissue diseases (rCTDs). ERN ReCONNET launched the first European Registry Infrastructure with the aim to plan, upgrade and link registries for rCTDs, with the final goal to promote a harmonized data collection approach all over Europe for rCTDs.MethodsAn online survey addressed to healthcare professionals and patients' representatives active in the field of rCTDs was integrated by an extensive database search in order to build a mapping of existing registries for rCTDs.FindingsA total of 140 registries were found, 38 of which include multiple diseases. No disease-specific registry was identified for relapsing polychondritis, mixed connective tissue disease and undifferentiated connective tissue disease.DiscussionThis overview on the existing registries for rCTDs provides a useful starting point to identify the gaps and the strengths of registries on the coverage of rCTDs, and to develop a common data set and data collection approach for the establishment of the TogethERN ReCONNET Infrastructure.
Metabolic parameters on baseline 18F-FDG PET/CT are potential predictive biomarkers for immunotherapy in patients with head and neck squamous cell carcinoma
Authors: Kwon Hye Ryeong , Cho Junhun , Park Sehhoon , Lee Se-Hoon , Ahn Myung-Ju , Choi Joon Young , Lee Kyung-Han , Jung Hyun Ae , Moon Seung Hwan 
Published: September 2022

PurposeWe evaluated baseline 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters for predicting prognosis in patients with head and neck squamous cell carcinoma (HNSCC) who were receiving immune checkpoint inhibitors (ICIs). In addition, we also investigated the relationships between immunohistochemical (IHC) biomarkers and metabolic parameters.Materials and methodsA total of 39 patients with HNSCC who underwent 18F-FDG PET/CT prior to ICI therapy between November 2015 and December 2020 were enrolled. PET parameters of tumor lesions included standardized uptake values, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and spleen-to-liver ratio (SLR). Clinical variables, IHC markers, and derived neutrophil-to-lymphocyte ratio (dNLR) were also obtained. Analysis was performed using Cox proportional hazard model, Kaplan-Meier method with log-rank test, and Spearman's correlation.ResultsTotal MTV (TMTV), total TLG (TTLG), and a combined parameter consisting of TMTV and dNLR were significant predictors for progression-free survival (PFS) in univariable analysis (TMTV, p = 0.018; TTLG, p = 0.027; combined parameter, p = 0.021). Above all, the combined parameter was an independent prognostic factor for PFS in multivariable analysis. The group with low TMTV and low dNLR had longer PFS than the group with high TMTV and high dNLR (p = 0.036). SLR was the only significant predictor for overall survival (p = 0.019). Additionally, there was a negative correlation between programmed cell death-ligand 1 expression (one of the IHC markers) and MTV in subgroup analysis.ConclusionPET parameters on baseline 18F-FDG PET/CT were predictive biomarkers for prognosis in patients with HNSCC undergoing ICI therapy. With dNLR, more accurate prognostic prediction could be possible.
Caloric and video head impulse test dissociated results in dizzy patients
Authors: Waissbluth Sofia , Sepúlveda Valeria , Leung Jai-Sen , Oyarzún Javier 
Published: September 2022

IntroductionWe are now able to detect abnormalities for any semicircular canal with the use of the video head impulse test (vHIT). Prior to the vHIT, the gold standard for unilateral canal paresis of the lateral canal was considered the caloric test. Clinical cases where the caloric test and vHIT are discordant are not uncommon.MethodsRetrospective study. All consecutive cases of dizziness seen from 11/2020 to 12/2021 for which the patient underwent both caloric and vHIT tests performed within 10 days, were reviewed. Patients with discordant results were included. We evaluated the caloric response, vHIT gains for all canals and saccades, with and without gain abnormalities.ResultsWe included 74 cases of dizziness with dissociated results. The most common finding was a normal caloric response with abnormal vHIT results (60.8%); the main abnormal finding on vHIT was the presence of saccades. In this group, 37.7% of patients had normal gains and refixation saccades. In addition, the most found low gain was for the posterior canal. The main diagnosis in this group was vestibular migraine. For the group with unilateral caloric paresis and normal vHIT gain in the lateral canal, the main diagnosis was Ménière's disease.DiscussionThe most common disorders with discordant results were Ménière's disease and vestibular migraine. The caloric test and vHIT are complementary and combining both tests provide greater clinical information. Further research is needed to understand refixation saccades with normal gains.
Microstructural changes of the vestibulocochlear nerve in patients with Ménière's disease using diffusion tensor imaging
Authors: Yuan Xiaojia , Li Xiaozhen , Xu Yu , Zhong Liqun , Yan Zhanfeng , Chen Zhengguang 
Published: September 2022

ObjectiveTo evaluate the microstructural changes of the vestibulocochlear nerve in patients with Ménière's disease.MethodsA total of 26 subjects, 13 patients with MD and 13 healthy controls, underwent diffusion tensor imaging (DTI) on a 3T scanner. The independent sample t-test was used to compare the differences in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) between the two groups. A Pearson correlation was used between DTI and the dizziness handicap inventory (DHI) scores.ResultsThere was a significant decrease in FA and an increase in ADC of the vestibulocochlear nerve in MD patients compared with healthy controls (P = 0.04, P = 0.001). FA had negative correlations with the DHI score (r = −0.62, P = 0.02) and DHI-functional score (r = −0.64, P = 0.02).ConclusionThese results are the first evidence of possible changes in the microstructure of the vestibulocochlear nerves in patients with MD. DTI is a potential technique for evaluating the vestibulocochlear nerve in patients with MD.
Carotenoids in orange carrots mitigate non-alcoholic fatty liver disease progression
Authors: Balbuena Emilio , Cheng Junrui , Eroglu Abdulkerim 
Published: September 2022

BackgroundCarotenoids are abundant in colored fruits and vegetables. Non-alcoholic fatty liver disease (NAFLD) is a global burden and risk factor for end-stage hepatic diseases. This study aims to compare the anti-NAFLD efficacy between carotenoid-rich and carotenoid-deficient vegetables.Materials and methodsMale C57BL/6J mice were randomized to one of four experimental diets for 15 weeks (n = 12 animals/group): Low-fat diet (LFD, 10% calories from fat), high-fat diet (HFD, 60% calories from fat), HFD with 20% white carrot powders (HFD + WC), or with 20% orange carrot powders (HFD + OC).ResultsWe observed that carotenoids in the orange carrots reduced HFD-induced weight gain, better than white carrots. Histological and triglyceride (TG) analyses revealed significantly decreased HFD-induced hepatic lipid deposition and TG content in the HFD + WC group, which was further reduced in the HFD + OC group. Western blot analysis demonstrated inconsistent changes of fatty acid synthesis-related proteins but significantly improved ACOX-1 and CPT-II, indicating that orange carrot carotenoids had the potential to inhibit NAFLD by improving β-oxidation. Further investigation showed significantly higher mRNA and protein levels of PPARα and its transcription factor activity.ConclusionCarotenoid-rich foods may display more potent efficacy in mitigating NAFLD than those with low carotenoid levels.
A risk-based approach to measuring population micronutrient status from blood biomarker concentrations
Authors: Ghosh Santu , Kurpad Anura V. , Sachdev Harshpal S. , Thomas Tinku 
Published: September 2022

BackgroundNutrient biomarkers and their definitive cut-offs are used to classify individuals as nutrient-deficient or sufficient. This determinism does not consider any uncertainty, and a probability approach, using biomarker distributions, is then preferable to define the risk of nutrition deficiency when in populations.MethodHealthy 1–19-year-old children and adolescents were selected from the Comprehensive National Nutrition Survey (CNNS), to obtain probability distributions of their retinol, zinc and vitamin B12, along with erythrocyte folate. Model-based estimates of location, scale and shape parameters of these distributions were obtained across ages. Subsequently, in the entire sample of 1–19 year old children of CNNS, the population risk of deficiency (PRD) which is average risk of deficiency in individuals in the population was computed, which is “of concern” when &gt;50%. When individual risk of deficiency is &gt;97.5% it is called “severe risk of deficiency” (SRD).ResultsIn the entire CNNS sample, the PRD of concern was low for serum retinol (3.6–8.2%), zinc (0–5.5%), and SRD of vitamin B12 and erythrocyte folate were 2.3–7.2% and 4.2–9.7%, respectively, across age and sex groups.ConclusionThis proposed method assesses the adequacy of nutrient exposures without relying on pre-defined deterministic biomarker cut-offs to define micronutrient deficiency and avoids errors in exposure assessment.
Serum creatinine to cystatin C ratio and clinical outcomes in adults with non-dialysis chronic kidney disease
Authors: Hyun Young Youl , Lee Kyu-Beck , Kim Hyoungnae , Kim Yaeni , Chung Wookyung , Park Hayne Cho , Han Seung Hyeok , Oh Yun Kyu , Park Sue Kyung , Oh Kook-Hwan 
Published: September 2022

BackgroundStudies have suggested that the serum creatinine/cystatin C (Cr/CysC) ratio is a surrogate marker for muscle wasting is associated with adverse outcomes in several disease conditions. To clarify the utility of the Cr/CysC ratio as a prognostic marker in chronic kidney disease (CKD) we evaluated the association between the Cr/CysC ratio clinical outcomes in patients with non-dialysis CKD.MethodsThis prospective observational cohort study included 1,966 participants of the KoreaN cohort study Outcomes in patients With CKD (KNOW-CKD). We evaluated associated factors with the serum Cr/CysC ratio and association between the serum Cr/CysC ratio and composite outcomes of all-cause death and cardiovascular events (CVEs).ResultsThe mean age was 54 ± 12 (SD) years and 61% were men. The mean serum Cr/CysC ratio was 10.97 ± 1.94 in men and 9.10 ± 1.77 in women. The Cr/CysC ratio correlated positively with urinary creatinine excretion, a marker of muscle mass. In the fully adjusted Cox proportional hazard model, the Cr/CysC ratio was associated with the occurrence of adverse outcomes through a median follow-up of 5.9 years [hazard ratio (HR) = 0.92, 95% confidence interval (CI) = 0.85–0.99 for the composite outcomes, HR = 0.87, 95% CI, 0.78 − 0.97 for all-cause death, and HR = 0.93; 95% CI, 0.84–1.04 for CVEs]. In subgroup analyses, there were interactions of the Cr/CysC ratio with age and sex for risk of the clinical outcomes, but not eGFR group.ConclusionA higher Cr/CysC ratio is associated with a lower risk of the composite outcomes, especially all-cause mortality, even after adjusting for eGFR. These suggest that the Cr/CysC ratio is a useful prognostic marker in CKD.