bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased absolute number of peripheral regulatory T cells in patients with idiopathic retroperitoneal fibrosis
Authors: Liu Lu , Yan Huanhuan , Wang Yanyan , Xie Yuhuan , Jiang Lei , Zhao Jinfang , Gao Chong , Li Xiaofeng , Wang Caihong 
Published: November 2022

ObjectiveIn order to determine whether the immune balance of T helper 17(Th17)/regulatory T(Treg) is related to the pathogenesis of idiopathic retroperitoneal fibrosis (IRPF), we analyzed the differences in peripheral blood lymphocytes, CD4+T cell subsets and cytokines between patients with IRPF and healthy people to clarify the CD4+T cell subsets, especially Treg cell subsets, and the role of cytokines in the pathogenesis of IRPF.MethodsThis study included 22 patients with IRPF, 36 patients with IgG4-related diseases (IgG4-RD) without retroperitoneal fibrosis (RPF), and 28 healthy controls. The absolute numbers and percentage of peripheral blood lymphocyte subsets and CD4+T cell subsets in each group were detected by flow cytometry, and the serum cytokine level was detected by flow cytometric bead array (CBA).ResultsCompared with the healthy group, the absolute value of B cells in peripheral blood of IRPF patients was significantly decreased, and T, natural killer (NK), CD4+ and CD8+ were not significantly abnormal. The absolute numbers of Th2 cells were lower than healthy group(p=0.043). In particular, the absolute numbers of Treg cells were significantly lower than healthy group(p&lt;0.001), while the absolute numbers of Th17 cells increased(p=0.682). Th17/Treg was significantly higher than healthy group (p&lt; 0.001). Cytokine analysis showed that the level of interleukin (IL)-4 in IRPF patients was higher than healthy group(p=0.011), IL-6, IL-10, IL-17, TNF-α and IFN-γ were significantly higher than healthy group (all p&lt;0.001). Receiver operating characteristic (ROC) curves showed that IL-10 and TNF-α could distinguish bilateral ureteral dilatation in IRPF patients, with areas under the ROC curve (AUCs) of 0.813 (95% CI:0.607-1.000, p=0.026) and 0.950 (95% CI:0.856-1.000, p=0.001), respectively. IL-6 could distinguish bilateral ureteral obstruction, with an AUC of 0.861 (95% CI: 0.682-1.000, p=0.015).ConclusionsOur study showed that IRPF patients had reduced Treg cells and indeed had Th17/Treg imbalance, which may be related to the pathogenesis of the disease. The levels of IL-6, IL-10 and TNF-α appear to be associated with the progression of IRPF.
Case report: CD38-directed CAR-T cell therapy: A novel immunotherapy targeting CD38- positive blasts overcomes TKI and chemotherapy resistance of myeloid chronic myeloid leukemia in blastic phase
Authors: Cui Qingya , Liang Peiqi , Dai Haiping , Cui Wei , Cai Mengjie , Ding Zixuan , Ma Qinfen , Yin Jia , Li Zheng , Liu Sining , Kang Liqing , Yao Li , Cen Jiannong , Shen Hongjie , Zhu Mingqing , Yu Lei , Wu Depei , Tang Xiaowen 
Published: November 2022

Resistance to tyrosine kinase inhibitor (TKI) is a tough problem in the treatment of chronic myeloid leukemia in blastic phase (CML-BP), which was often associated with acquired mutations in the kinase domain and not eliminating the leukemic stem cells. The efficacy of TKI or combination with chemotherapy in CML-BP remains unsatisfactory. Chimeric antigen receptor T (CAR-T) cell immunotherapy may overcome TKI and chemotherapy resistance. However, lack of ideal targetable antigens is a major obstacle for treating patients with myeloid malignancies. CD38 is known to be expressed on most (acute myeloid leukemia) AML cells, and its lack of expression on hematopoietic stem cells renders it as a potential therapeutic target for myeloid CML-BP. We develop a CD38-directed CAR-T cell therapy for AML, and two patients with myeloid CML-BP were enrolled (NCT04351022). Two patients, harboring E255K and T315I mutation in the ABL kinase domain, respectively, were resistant to multiple TKIs (imatinib, dasatinib, nilotinib, and ponatinib) and intensive chemotherapy. The blasts in the bone marrow of two patients exhibited high expression of CD38. After tumor reduction chemotherapy and lymphodepletion chemotherapy, 1 × 107 CAR-T-38 cells per kilogram of body weight were administered. They achieved minimal residual disease–negative and BCR::ABL1-negative complete remission and experienced grade II cytokine release syndrome manifesting as fever. Our data highlighted that CAR-T-38 cell therapy may overcome TKI and chemotherapy resistance in patients with myeloid CML-BP.
Combined proteomics and single cell RNA-sequencing analysis to identify biomarkers of disease diagnosis and disease exacerbation for systemic lupus erythematosus
Authors: Li Yixi , Ma Chiyu , Liao Shengyou , Qi Suwen , Meng Shuhui , Cai Wanxia , Dai Weier , Cao Rui , Dong Xiangnan , Krämer Bernhard K. , Yun Chen , Hocher Berthold , Hong Xiaoping , Liu Dongzhou , Tang Donge , He Jingquan , Yin Lianghong , Dai Yong 
Published: November 2022

IntroductionSystemic lupus erythematosus (SLE) is a chronic autoimmune disease for which there is no cure. Effective diagnosis and precise assessment of disease exacerbation remains a major challenge.MethodsWe performed peripheral blood mononuclear cell (PBMC) proteomics of a discovery cohort, including patients with active SLE and inactive SLE, patients with rheumatoid arthritis (RA), and healthy controls (HC). Then, we performed a machine learning pipeline to identify biomarker combinations. The biomarker combinations were further validated using enzyme-linked immunosorbent assays (ELISAs) in another cohort. Single-cell RNA sequencing (scRNA-seq) data from active SLE, inactive SLE, and HC PBMC samples further elucidated the potential immune cellular sources of each of these PBMC biomarkers.ResultsScreening of the PBMC proteome identified 1023, 168, and 124 proteins that were significantly different between SLE vs. HC, SLE vs. RA, and active SLE vs. inactive SLE, respectively. The machine learning pipeline identified two biomarker combinations that accurately distinguished patients with SLE from controls and discriminated between active and inactive SLE. The validated results of ELISAs for two biomarker combinations were in line with the discovery cohort results. Among them, the six-protein combination (IFIT3, MX1, TOMM40, STAT1, STAT2, and OAS3) exhibited good performance for SLE disease diagnosis, with AUC of 0.723 and 0.815 for distinguishing SLE from HC and RA, respectively. Nine-protein combination (PHACTR2, GOT2, L-selectin, CMC4, MAP2K1, CMPK2, ECPAS, SRA1, and STAT2) showed a robust performance in assessing disease exacerbation (AUC=0.990). Further, the potential immune cellular sources of nine PBMC biomarkers, which had the consistent changes with the proteomics data, were elucidated by PBMC scRNAseq.DiscussionUnbiased proteomic quantification and experimental validation of PBMC samples from two cohorts of patients with SLE were identified as biomarker combinations for diagnosis and activity monitoring. Furthermore, the immune cell subtype origin of the biomarkers in the transcript expression level was determined using PBMC scRNAseq. These findings present valuable PBMC biomarkers associated with SLE and may reveal potential therapeutic targets.
Circulating tissue inhibitor of metalloproteinases 1 (TIMP-1) at COVID-19 onset predicts severity status
Authors: Brusa Stefano , Terracciano Daniela , Bruzzese Dario , Fiorenza Mariano , Stanziola Lucia , Pinchera Biagio , Valente Valeria , Gentile Ivan , Cittadini Antonio , Mormile Ilaria , Mormile Mauro , Portella Giuseppe 
Published: November 2022

BackgroundSystemic biomarkers for severity of SARS-CoV-2 infection are of great interest. In this study, we evaluated a set of collagen metabolites and extracellular matrix remodeling biomarkers including procollagen type III amino terminal propeptide (PIIINP), tissue inhibitor of metalloproteinases 1 (TIMP-1) and hyaluronic acid (HA) as prognostic indicators in COVID-19 patients.MethodsNinety COVID-19 patients with the absence of chronic liver diseases were enrolled. Serum PIIINP, TIMP-1, and HA were measured and correlated with inflammatory indices and clinical variables. Patients were stratified for disease severity according to WHO criteria in two groups, based on the requirement of oxygen support.ResultsSerum TIMP-1, but not PIIINP and HA was significantly higher in patients with WHO score ≥5 compared to patients with WHO score &lt;5 [PIIINP: 7.2 (5.4–9.5) vs. 7.1 (4.5–9.9), p = 0.782; TIMP-1: 298.1 (20.5–460) vs. 222.2 (28.5–452.8), p = 0.01; HA: 117.1 (55.4–193.7) vs. 75.1 (36.9–141.8), p = 0.258]. TIMP-1 showed moderate correlation with CRP (r = 0.312, p = 0.003) and with LDH (r = 0.263, p = 0.009). CRP and serum LDH levels were significantly higher in COVID-19 patients with WHO score ≥5 compared to the group of patients with WHO score &lt; 5 [15.8 (9–44.5) vs. 9.3 (3.4–33.8), p = 0.039 and 373 (282–465) vs. 289 (218–383), p = 0.013, respectively].ConclusionIn patients with COVID-19, circulating TIMP-1 was associated with disease severity and with systemic inflammatory index, suggesting that TIMP-1 could represent a promising non-invasive prognostic biomarker in COVID-19 patients. Interestingly, our results prompted that serum TIMP-1 level may potentially be used to select the patients for therapeutic approaches targeting matrix metalloproteases pathway.
Comprehensive assessment of age-specific mortality rate and its incremental changes using a composite measure: A sub-national analysis of rural Indian women
Authors: Sharma Divya , Kiran Tanvi , Goel Kapil , Junaid K. P. , Rajagopal Vineeth , Gupta Madhu , Kaundal Himika , Sharma Saraswati , Bahl Ankit 
Published: November 2022

BackgroundDiverse socio-economic and cultural issues contribute to adverse health outcomes and increased mortality rates among rural Indian women across different age categories. The present study aims to comprehensively assess age-specific mortality rates (ASMR) and their temporal trends using a composite measure at the sub-national level for rural Indian females to capture cross-state differences.Materials and methodsA total of 19 states were included in the study to construct a composite age-specific mortality index for 2011 (base year) and 2018 (reference year) and examine the incremental changes in the index values across these years at the sub-national level in India. Sub-index values were calculated for each component age group and were subsequently used to compute the composite ASMR index using the geometric mean method. Based on the incremental changes, the performance of states was categorized into four different typologies.ResultsImprovement in mortality index scores in the 0–4 years age group was documented for all states. The mortality rates for the 60+ age group were recorded to be high for all states. Kerala emerged as the overall top performer in terms of mortality index scores, while Bihar and Jharkhand were at the bottom of the mortality index table. The overall mortality composite score has shown minor improvement from base year to reference year at all India level.ConclusionAn overall reduction in the mortality rates of rural Indian women has been observed over the years in India. However, in states like Bihar and Jharkhand, mortality is high and has considerable scope for improvement. The success of public health interventions to reduce the under-five mortality rate is evident as the female rural mortality rates have reduced sizably for all states. Nevertheless, there is still sizable scope for reducing mortality rates for other component age groups. Additionally, there is a need to divert attention toward the female geriatric (60+ years) population as the mortality rates are still high.
Changes in soil properties and the phoD-harboring bacteria of the alfalfa field in response to phosphite treatment
Authors: Li Zhenyi , Wang Jixiang , Wu Yao , Hu Jingyun , Cong Lili , Yang Chao , Fu Jinmin , Sun Juan 
Published: November 2022

Phosphite, a reduced form of orthophosphate, is characterized by high solubility, and transportation efficiency and can be used as potential phosphorus fertilizer, plant biostimulant and supplemental fertilizer in agriculture. However, the effects of phosphite fertilizer on soil properties and microorganisms are poorly understood. This study evaluated the effects of phosphate and phosphite fertilizers on the different forms of phosphorus, alkaline phosphatase (ALP) activity, and phoD-harboring bacterial community in the alfalfa (Medicago sativa) field. The study used four concentrations (30, 60, 90, and 120 mg P2O5 kg−1 soil) of phosphate (KH2PO4) and phosphite (KH2PO3) fertilizers for the alfalfa field treatment. The results showed that both phosphite and phosphate fertilizers increased the total phosphorus (TP) and available phosphorus (AP) contents in the soil. The phosphorus content of the phosphite-treated soil was lower than that of the phosphate-treated one. TP, inorganic phosphate (Pi), and AP negatively regulated ALP activity, which decreased with increasing phosphate and phosphite fertilizers concentrations. Furthermore, high-throughput sequencing analysis identified 6 phyla and 29 families, which were classified from the altered operational taxonomic units (OTUs) of the soil samples. The redundancy analysis (RDA) revealed that pH, TP, AP and Pi were significantly related to the phoD-harboring bacterial community constructure. The different fertilizer treatments altered the key families, contributing to soil ALP activities. Frankiaceae, Sphingomonadaceae, and Rhizobiaceae positively correlated with ALP activity in phosphite-treated soil. Moreover, the structural equation model (SEM) revealed that ALP activity was affected by the phoD-harboring bacterial community through altered organic phosphorus (Po), AP, total nitrogen (TN), soil organic carbon (SOC), and pH levels under phosphate fertilizer treatment. However, the effect was achieved through positive regulation of pH and AP under phosphite fertilizer. Thus, the changes in soil properties and phoD-harboring bacteria in response to phosphate and phosphite treatments differed in the alfalfa field. This study is the first to report the effects of phosphite on the soil properties of an alfalfa field and provides a strong basis for phosphite utilization in the future.Highlights– Phosphite and phosphate increase the total phosphorus and available phosphorus.– The pH was the dominant factor influencing the phoD-harboring bacterial community under phosphite fertilizer.– The response of soil properties and phoD-harboring bacterial community to phosphate and phosphite fertilizers differed in the alfalfa field.
Oxidative stress strongly restricts the effect of codon choice on the efficiency of protein synthesis in Escherichia coli
Authors: Leiva Lorenzo Eugenio , Elgamal Sara , Leidel Sebastian A. , Orellana Omar , Ibba Michael , Katz Assaf 
Published: November 2022

IntroductionThe response of enterobacteria to oxidative stress is usually considered to be regulated by transcription factors such as OxyR and SoxR. Nevertheless, several reports have shown that under oxidative stress the levels, modification and aminoacylation of tRNAs may be altered suggesting a role of codon bias in regulation of gene expression under this condition.MethodsIn order to characterize the effects of oxidative stress on translation elongation we constructed a library of 61 plasmids, each coding for the green fluorescent protein (GFP) translationally fused to a different set of four identical codons.ResultsUsing these reporters, we observed that GFP production levels vary widely (~15 fold) when Escherichia coli K-12 is cultured in minimal media as a consequence of codon choice variations. When bacteria are cultured under oxidative stress caused by paraquat the levels of GFP produced by most clones is reduced and, in contrast to control conditions, the range of GFP levels is restricted to a ~2 fold range. Restricting elongation of particular sequences does not increase the range of GFP production under oxidative stress, but altering translation initiation rates leads to an increase in this range.DiscussionAltogether, our results suggest that under normal conditions the speed of translation elongation is in the range of the speed of initiation and, consequently, codon choice impacts the speed of protein synthesis. In contrast, under oxidative stress translation initiation becomes much slower than elongation, limiting the speed of translation such that codon choice has at most only subtle effects on the overall output of translation.
Machine learning in renal pathology
Authors: Basso Matthew Nicholas , Barua Moumita , Meyer Julien , John Rohan , Khademi April 
Published: November 2022

IntroductionWhen assessing kidney biopsies, pathologists use light microscopy, immunofluorescence, and electron microscopy to describe and diagnose glomerular lesions and diseases. These methods can be laborious, costly, fraught with inter-observer variability, and can have delays in turn-around time. Thus, computational approaches can be designed as screening and/or diagnostic tools, potentially relieving pathologist time, healthcare resources, while also having the ability to identify novel biomarkers, including subvisual features.MethodsHere, we implement our recently published biomarker feature extraction (BFE) model along with 3 pre-trained deep learning models (VGG16, VGG19, and InceptionV3) to diagnose 3 glomerular diseases using PAS-stained digital pathology images alone. The BFE model extracts a panel of 233 explainable features related to underlying pathology, which are subsequently narrowed down to 10 morphological and microstructural texture features for classification with a linear discriminant analysis machine learning classifier. 45 patient renal biopsies (371 glomeruli) from minimal change disease (MCD), membranous nephropathy (MN), and thin-basement membrane nephropathy (TBMN) were split into training/validation and held out sets. For the 3 deep learningmodels, data augmentation and Grad-CAM were used for better performance and interpretability.ResultsThe BFE model showed glomerular validation accuracy of 67.6% and testing accuracy of 76.8%. All deep learning approaches had higher validation accuracies (most for VGG16 at 78.5%) but lower testing accuracies. The highest testing accuracy at the glomerular level was VGG16 at 71.9%, while at the patient-level was InceptionV3 at 73.3%.DiscussionThe results highlight the potential of both traditional machine learning and deep learning-based approaches for kidney biopsy evaluation.
The diagnostic value of the ocular tilt reaction plus head tilt subjective visual vertical (±45°) in patients with acute central vascular vertigo
Authors: Feng Yufei , Zhao Tongtong , Wu Yuexia , Ling Xia , Zhang Menglu , Song Ning , Kim Ji-Soo , Yang Xu 
Published: November 2022

ObjectivesTo investigate the localization diagnostic value of the ocular tilt reaction (OTR) plus head tilt subjective visual vertical (SVV) in patients with acute central vascular vertigo (ACVV).MethodsWe enrolled 40 patients with acute infarction, 20 with unilateral brainstem infarction (BI) and 20 with unilateral cerebellar infarction (CI). We also included 20 patients with unilateral peripheral vestibular disorders (UPVD) as the control group. The participants completed the OTR and SVV during head tilt (±45°) within 1 week of symptom onset.ResultsIn patients with ACVV, including that caused by lateral medullary infarction (100%, 2/2), partial pontine infarction (21%, 3/14), and cerebellum infarction (35%, 7/20), we observed ipsiversive OTR, similar to that seen in UPVD patients (80.0%, 16/20). Some of the patients with medial medullary infarction (50%, 1/2), partial pons infarction (42%, 6/14), midbrain infarction (100%, 2/2), and partial cerebellum infarction (30.0%, 6/20) showed contraversive OTR. The skew deviation (SD) of the BI group with ACVV was significantly greater than that of the UPVD group (6.60 ± 2.70° vs. 1.80 ± 1.30°, Z = −2.50, P = 0.012), such that the mean SD of the patients with a pons infarction was 9.50° and that of patients with medulla infarction was 5.00°. In ACVV patients with no cerebellar damage, the area under the curve of the receiver operating characteristic curve corresponding to the use of SD to predict brainstem damage was 0.92 (95%CI: 0.73–1.00), with a sensitivity of 100% and a specificity of 80% when SD ≥ 3°. We found no statistical difference in SD between the UPVD and CI groups (1.33 ± 0.58° vs. 1.80 ± 1.30°, Z = −0.344, P = 0.73). Compared with the UPVD patients, the ACVV patients with a partial pons infarction (43%, 6/14, χ2 = 13.68, P = 0.002) or medulla infarction (25%, 1/4, χ2 = 4.94, P = 0.103) exhibited signs of the ipsiversive E-effect with the contraversive A-effect, while those with a partial medulla infarction (50%, 2/4), pons infarction (43%, 6/14), or cerebellar infarction (60%, 12/20) exhibited a pathological symmetrical increase in the E-effect.ConclusionsThe evaluation of OTR plus head tilt SVV (±45°) in vertigo patients is helpful for identifying and diagnosing ACVV, especially when SD is ≥ 3° or the E-effect is symmetrically increased.
Visual disorders and driving ability in persons with dementia: A mini review
Authors: Papageorgiou Eleni , Tsirelis Daniil , Lazari Katerina , Siokas Vasileios , Dardiotis Efthimios , Tsironi Evangelia E. 
Published: November 2022

BackgroundImpaired driving ability in patients with Alzheimer’s disease (AD) is associated with a decline in cognitive processes and a deterioration of their basic sensory visual functions. Although a variety of ocular abnormalities have been described in patients with AD, little is known about the impact of those visual disorders on their driving performance.AimAim of this mini-review is to provide an update on the driving ability of patients with dementia and summarize the primary visual disorders affecting their driving behavior.MethodsDatabases were screened for studies investigating dementia, associated visual abnormalities and driving ability.ResultsThere is consistent evidence that dementia affects driving ability. Patients with dementia present with a variety of visual disorders, such as visual acuity reduction, visual field defects, impaired contrast sensitivity, decline in color vision and age-related pathological changes, that may have a negative impact on their driving ability. However, there is a paucity in studies describing the impact of oculovisual decline on the driving ability of AD subjects. A bidirectional association between cognitive and visual impairment (VI) has been described.ConclusionGiven the bidirectional association between VI and dementia, vision screening and cognitive assessment of the older driver should aim to identify at-risk individuals and employ timely strategies for treatment of both cognitive and ocular problems. Future studies should characterize the basic visual sensory status of AD patients participating in driving studies, and investigate the impact of vision abnormalities on their driving performance.