bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stalk-derived carbon dots as nanosensors for Fe3+ ions detection and biological cell imaging
Authors: Du Yongchao , Li Yaxi , Liu Yunliang , Liu Naiyun , Cheng Yuanyuan , Shi Qiuzhong , Liu Xiang , Tao Zhimin , Guo Yumeng , Zhang Jianguo , Askaria Najmeh , Li Haitao 
Published: April 2023

Introduction: Iron is one of the most important needed elements for the growth and reproduction of living organisms. The detection of iron levels is important and developing fluorescent probes with excellent sensitivity for Fe3+ ions is of great significance. Carbon dot (CDs) is a new type of fluorescent nanomaterial based on abundant and low-cost carbon elements. The use of widely distributed renewable agricultural waste straw as a carbon precursor to prepare CDs sensor can not only reduce the pollution caused by burning straw to the atmospheric environment, but also achieve the transformation of resources from waste to treasure.Methods: In this study, CDs were obtained from corn stalk powder by pyrolysis and microwave process. The sensitivity and linear response range of CDs sensor was studied through analyzing the effect of different Fe3+ ions concentrations on the fluorescence quenching. The application of CDs in biological cell imaging was investigated using HGC-27 cells.Results: The fluorescence quenching showed a good linear relationship with the Fe3+ concentration in the range from 0 to 128 μM, and a low detection limit of 63 nM. In addition, the CDs have high recognition for Fe3+ ions. Meanwhile, the CDs have a low cytotoxicity and desirable biocompatibility, allowing the multicolor living cell imaging.Conclusion: The prepared CDs can be used as fluorescent sensors for the selective detection of Fe3+ ions and biological cell imaging. Our results supported that the conversion of agricultural waste into carbon nanomaterials has great potential to be developed.
A predictive model for identifying secondary underlying diseases of hemophagocytic lymphohistiocytosis
Authors: Gao Wei-bo , Hu Li-juan , Ma Xiao-lu , Shi Mao-jing , Wang Chun-yu , Ma Yong , Song Xiao-jing , Zhu Ji-hong , Wang Tian-bing 
Published: April 2023

BackgroundSecondary hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disease of immune hyperactivation that arises in the context of infectious, inflammatory, or neoplastic triggers. The aim of this study was to establish a predictive model for the timely differential diagnosis of the original disease resulting in HLH by validating clinical and laboratory findings to further improve the efficacy of therapeutics for HLH.MethodsWe retrospectively enrolled 175 secondary HLH patients in this study, including 92 patients with hematologic disease and 83 patients with rheumatic disease. The medical records of all identified patients were retrospectively reviewed and used to generate the predictive model. We also developed an early risk score using multivariate analysis weighted points proportional to the β regression coefficient values and calculated its sensitivity and specificity for the diagnosis of the original disease resulting in HLH.ResultsThe multivariate logistic analysis revealed that lower levels of hemoglobin and platelets (PLT), lower levels of ferritin, splenomegaly and Epstein−Barr virus (EBV) positivity were associated with hematologic disease, but young age and female sex were associated with rheumatic disease. The risk factors for HLH secondary to rheumatic diseases were female sex [OR 4.434 (95% CI, 1.889-10.407), P =0.001], younger age [OR 6.773 (95% CI, 2.706-16.952), P&lt;0.001], higher PLT level [OR 6.674 (95% CI, 2.838-15.694), P&lt;0.001], higher ferritin level [OR 5.269 (95% CI, 1.995-13.920), P =0.001], and EBV negativity [OR 27.656 (95% CI, 4.499-169.996), P&lt;0.001]. The risk score included assessments of female sex, age, PLT count, ferritin level and EBV negativity, which can be used to predict HLH secondary to rheumatic diseases with an AUC of 0.844 (95% CI, 0.836~0.932).ConclusionThe established predictive model was designed to help clinicians diagnose the original disease resulting in secondary HLH during routine practice, which might be improve prognosis by enabling the timely treatment of the underlying disease.
Changes in HCMV immune cell frequency and phenotype are associated with chronic lung allograft dysfunction
Authors: Rousselière Amélie , Delbos Laurence , Foureau Aurore , Reynaud-Gaubert Martine , Roux Antoine , Demant Xavier , Le Pavec Jérôme , Kessler Romain , Mornex Jean-François , Messika Jonathan , Falque Loïc , Le Borgne Aurélie , Boussaud Véronique , Tissot Adrien , Hombourger Sophie , Bressollette-Bodin Céline , Charreau Béatrice 
Published: April 2023

BackgroundHuman cytomegalovirus (HCMV) infection is common and often severe in lung transplant recipients (LTRs), and it is a risk factor associated with chronic lung allograft dysfunction (CLAD). The complex interplay between HCMV and allograft rejection is still unclear. Currently, no treatment is available to reverse CLAD after diagnosis, and the identification of reliable biomarkers that can predict the early development of CLAD is needed. This study investigated the HCMV immunity in LTRs who will develop CLAD.MethodsThis study quantified and phenotyped conventional (HLA-A2pp65) and HLA-E-restricted (HLA-EUL40) anti-HCMV CD8+ T (CD8 T) cell responses induced by infection in LTRs developing CLAD or maintaining a stable allograft. The homeostasis of immune subsets (B, CD4T, CD8 T, NK, and γδT cells) post-primary infection associated with CLAD was also investigated.ResultsAt M18 post-transplantation, HLA-EUL40 CD8 T responses were less frequently found in HCMV+ LTRs (21.7%) developing CLAD (CLAD) than in LTRs (55%) keeping a functional graft (STABLE). In contrast, HLA-A2pp65 CD8 T was equally detected in 45% of STABLE and 47.8% of CLAD LTRs. The frequency of HLA-EUL40 and HLA-A2pp65 CD8 T among blood CD8 T cells shows lower median values in CLAD LTRs. Immunophenotype reveals an altered expression profile for HLA-EUL40 CD8 T in CLAD patients with a decreased expression for CD56 and the acquisition of PD-1. In STABLE LTRs, HCMV primary infection causes a decrease in B cells and inflation of CD8 T, CD57+/NKG2C+ NK, and δ2−γδT cells. In CLAD LTRs, the regulation of B, total CD8 T, and δ2+γδT cells is maintained, but total NK, CD57+/NKG2C+ NK, and δ2−γδT subsets are markedly reduced, while CD57 is overexpressed across T lymphocytes.ConclusionsCLAD is associated with significant changes in anti-HCMV immune cell responses. Our findings propose that the presence of dysfunctional HCMV-specific HLA-E-restricted CD8 T cells together with post-infection changes in the immune cell distribution affecting NK and γδT cells defines an early immune signature for CLAD in HCMV+ LTRs. Such a signature may be of interest for the monitoring of LTRs and may allow an early stratification of LTRs at risk of CLAD.
Single cell analysis of the localization of the hematopoietic stem cells within the bone marrow architecture identifies niche-specific proliferation dynamics
Authors: Mazzarini Maria , Arciprete Francesca , Picconi Orietta , Valeri Mauro , Verachi Paola , Martelli Fabrizio , Migliaccio Anna Rita , Falchi Mario , Zingariello Maria 
Published: April 2023

IntroductionHematopoietic stem cells (HSC) reside in the bone marrow (BM) in specialized niches which provide support for their self-replication and differentiation into the blood cells. Recently, numerous studies using sophisticated molecular and microscopic technology have provided snap-shots information on the identity of the BM niches in mice. In adults, HSC are localized around arterioles and sinusoids/venules whereas in juvenile mice they are in close to the osteoblasts. However, although it is well recognized that in mice the nature of the hematopoietic niche change with age or after exposure to inflammatory insults, much work remains to be done to identify changes occurring under these conditions. The dynamic changes occurring in niche/HSC interactions as HSC enter into cycle are also poorly defined.MethodsWe exploit mice harboring the hCD34tTA/Tet-O-H2BGFP transgene to establish the feasibility to assess interactions of the HSC with their niche as they cycle. In this model, H2BGFP expression is driven by the TET trans-activator under the control of the human CD34 promoter which in mice is active only in the HSC. Since Doxycycline inhibits TET, HSC exposed to this drug no longer express H2BGFP and loose half of their label every division allowing establishing the dynamics of their first 1-3 divisions. To this aim, we first validated user-friendly confocal microscopy methods to determine HSC divisions by hemi-decrement changes in levels of GFP expression. We then tracked the interaction occurring in old mice between the HSC and their niche during the first HSC divisions.ResultsWe determined that in old mice, most of the HSC are located around vessels, both arterioles which sustain quiescence and self-replication, and venules/sinusoids, which sustain differentiation. After just 1 week of exposure to Doxycycline, great numbers of the HSC around the venules lost most of their GFP label, indicating that they had cycled. By contrast, the few HSC surrounding the arterioles retained maximal levels of GFP expression, indicating that they are either dormant or cycle at very low rates.ConclusionThese results reveal that in old mice, HSC cycle very dynamically and are biased toward interactions with the niche that instructs them to differentiate.
Identification and validation of biomarkers based on cellular senescence in mild cognitive impairment
Authors: Ma Songmei , Xia Tong , Wang Xinyi , Wang Haiyun 
Published: April 2023

BackgroundMild cognitive impairment (MCI), a syndrome defined as decline of cognitive function greater than expected for an individual’s age and education level, occurs in up to 22.7% of elderly patients in United States, causing the heavy psychological and economic burdens to families and society. Cellular senescence (CS) is a stress response that accompanies permanent cell-cycle arrest, which has been reported to be a fundamental pathological mechanism of many age-related diseases. This study aims to explore biomarkers and potential therapeutic targets in MCI based on CS.MethodsThe mRNA expression profiles of peripheral blood samples from patients in MCI and non-MCI group were download from gene expression omnibus (GEO) database (GSE63060 for training and GSE18309 for external validation), CS-related genes were obtained from CellAge database. Weighted gene co-expression network analysis (WGCNA) was conducted to discover the key relationships behind the co-expression modules. The differentially expressed CS-related genes would be obtained through overlapping among the above datasets. Then, pathway and GO enrichment analyses were performed to further elucidate the mechanism of MCI. The protein–protein interaction network was used to extract hub genes and the logistic regression was performed to distinguish the MCI patients from controls. The hub gene-drug network, hub gene-miRNA network as well as transcription factor-gene regulatory network were used to analyze potential therapeutic targets for MCI.ResultsEight CS-related genes were identified as key gene signatures in MCI group, which were mainly enriched in the regulation of response to DNA damage stimulus, Sin3 complex and transcription corepressor activity. The receiver operating characteristic curves of logistic regression diagnostic model were constructed and presented great diagnostic value in both training and validation set.ConclusionEight CS-related hub genes – SMARCA4, GAPDH, SMARCB1, RUNX1, SRC, TRIM28, TXN, and PRPF19 – serve as candidate biomarkers for MCI and display the excellent diagnostic value. Furthermore, we also provide a theoretical basis for targeted therapy against MCI through the above hub genes.
Effects of strength training in fibromyalgia on balance, neuromuscular performance, and symptomatic analysis: a 12-week study protocol
Authors: Albuquerque Maria Luiza L. , Monteiro Diogo , Alvarez Marcos C. , Vilarino Guilherme Torres , Andrade Alexandro , Neiva Henrique P. 
Published: April 2023

Fibromyalgia affects skeletal muscles presenting with muscle stiffness, pain, and fatigue. The exercise practice is wellstabilized and suggested for the reduction of symptoms. However, there are some gaps in the literature related to balance and neuromuscular performance in a strength training protocol. The aim of this study is to structure a protocol to verify the effects of strength training applied over a short period, on balance, neuromuscular performance, and fibromyalgia symptoms. Additionally, we intend to analyze the effects of a short period of cessation of training. Participants will be recruited through flyers, internet advertisements, clinical referrals, health professionals, and email outreach. Volunteers will be randomly assigned to the control group or experimental group. Before the training period, symptoms (Fibromyalgia Impact Questionnaire, Visual Analog Scale), balance (force plate), and neuromuscular performance (medicine ball throw and vertical jump) will be assessed. Participants in the experimental group will perform strength training twice a week (50 min each), on alternate days, for 8 weeks (16 sessions). Then, 4 weeks of detraining will be completed. This training program will be carried out online, using real-time videos, and the participants will be divided into two groups with different schedules. The Borg scale will be used to monitor perceived effort in each session. There is a gap in the literature about exercise prescriptions for fibromyalgia. The supervised online intervention enables a wide range of participation. The strength exercises used (without the use of external materials and/or machines) and load (few repetitions per set) represent a novelty to training programming. Moreover, this training program respects the limitations and individuality of the volunteers, providing exercise adaptations. With positive results, the present protocol could be an easy-to-apply guideline with clear instructions on the details related to exercise prescription. Also, ensure the effectiveness of a low-cost and feasible treatment, especially for fibromyalgia patients.Clinical trial registrationhttps://clinicaltrials.gov/, identifier: NCT05646641.
Low-dose vs. standard-dose intravenous alteplase for acute ischemic stroke with unknown time of onset
Authors: Wang Zekun , Ji Kangxiang , Fang Qi 
Published: April 2023

BackgroundStandard-dose intravenous alteplase for acute ischemic stroke (AIS) in the unknown or extended time window beyond 4.5 h after symptom onset is both effective and safe for certain patients who were selected based on multimodal neuroimaging. However, uncertainty exists regarding the potential benefit of using low-dose alteplase among the Asian population outside the 4.5-h time window.MethodsConsecutive AIS patients who received intravenous alteplase between 4.5 and 9 h after symptom onset or with an unknown time of onset guided by multimodal computed tomography (CT) imaging were identified from our prospectively maintained database. The primary outcome was excellent functional recovery, defined as having a modified Rankin scale (mRS) score of 0–1 at 90 days. Secondary outcomes included functional independence (an mRS score of 0–2 at 90 days), early major neurologic improvement (ENI), early neurologic deterioration (END), any intracranial hemorrhage (ICH), symptomatic ICH (sICH), and 90-day mortality. Propensity score matching (PSM) and multivariable logistic regression models were used to adjust for confounding factors and compare the clinical outcomes between the low- and standard-dose groups.ResultsFrom June 2019 to June 2022, a total of 206 patients were included in the final analysis, of which 143 were treated with low-dose alteplase and 63 were treated with standard-dose alteplase. After accounting for confounding factors, we observed that there were no statistically significant differences between the standard- and low-dose groups with respect to excellent functional recovery [adjusted odds ratio = 1.22 (aOR), 95% confidence interval (CI): 0.62–2.39; adjusted rate difference (aRD) = 4.6%, and 95% CI: −11.2 to 20.3%]. Patients of both groups had similar rates of functional independence, ENI, END, any ICH, sICH, and 90-day mortality. In the subgroup analysis, patients aged ≥70 years were more likely to achieve excellent functional recovery when receiving standard-dose rather than low-dose alteplase.ConclusionThe effectiveness of low-dose alteplase might be comparable to that of standard-dose alteplase in AIS patients aged &lt;70 years with favorable perfusion-imaging profiles in the unknown or extended time window but not in those aged ≥70 years. Furthermore, low-dose alteplase did not significantly reduce the risk of sICH compared to standard-dose alteplase.
Translocator protein PET imaging in temporal lobe epilepsy: A reliable test-retest study using asymmetry index
Authors: Mahmud Mohammad , Wade Charles , Jawad Sarah , Hadi Zaeem , Otoul Christian , Kaminski Rafal M. , Muglia Pierandrea , Kadiu Irena , Rabiner Eugenii , Maguire Paul , Owen David R. , Johnson Michael R. 
Published: April 2023

ObjectiveTranslocator protein (TSPO) targeting positron emission tomography (PET) imaging radioligands have potential utility in epilepsy to assess the efficacy of novel therapeutics for targeting neuroinflammation. However, previous studies in healthy volunteers have indicated limited test-retest reliability of TSPO ligands. Here, we examine test-retest measures using TSPO PET imaging in subjects with epilepsy and healthy controls, to explore whether this biomarker can be used as an endpoint in clinical trials for epilepsy.MethodsFive subjects with epilepsy and confirmed mesial temporal lobe sclerosis (mean age 36 years, 3 men) were scanned twice—on average 8 weeks apart—using a second generation TSPO targeting radioligand, [11C]PBR28. We evaluated the test-retest reliability of the volume of distribution and derived hemispheric asymmetry index of [11C]PBR28 binding in these subjects and compared the results with 8 (mean age 45, 6 men) previously studied healthy volunteers.ResultsThe mean (± SD) of the volume of distribution (VT), of all subjects, in patients living with epilepsy for both test and retest scans on all regions of interest (ROI) is 4.49 ± 1.54 vs. 5.89 ± 1.23 in healthy volunteers. The bias between test and retest in an asymmetry index as a percentage was small (−1.5%), and reliability is demonstrated here with Bland-Altman Plots (test mean 1.062, retest mean 2.56). In subjects with epilepsy, VT of [11C]PBR28 is higher in the (ipsilateral) hippocampal region where sclerosis is present than in the contralateral region.ConclusionWhen using TSPO PET in patients with epilepsy with hippocampal sclerosis (HS), an inter-hemispheric asymmetry index in the hippocampus is a measure with good test-retest reliability. We provide estimates of test-retest variability that may be useful for estimating power where group change in VT represents the clinical outcome.
Expression changes of ER, PR, HER2, and Ki-67 in primary and metastatic breast cancer and its clinical significance
Authors: Hu Xueyang , Chen Wenjun , Li Fanfan , Ren Pengfei , Wu Hongyang , Zhang Congjun , Gu Kangsheng 
Published: April 2023

ObjectiveTo explore the altered expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and cell proliferation index (Ki-67) in primary and metastatic breast cancer lesions and the correlation between the primary tumor size, lymph node metastasis, Tumor Node Metastasis (TNM) stage, molecular typing, and disease-free survival (DFS) and their clinical significance.MethodsA retrospective analysis was conducted on the clinical data of 130 patients with metastatic breast cancer biopsy admitted to the Cancer Center of the Second Affiliated Hospital of Anhui Medical University in Hefei, China, from 2014–2019. The altered expression of ER, PR, HER2, and Ki-67 in primary and metastatic lesions of breast cancer was analyzed with respect to the site of metastasis, size of the primary tumor, lymph node metastasis, disease progression, and prognosis.ResultsThe inconsistent expression rates of ER, PR, HER2, and Ki-67 in primary and metastatic lesions were 47.69%, 51.54%, 28.10%, and 29.23%, respectively. The size of the primary lesion was not, but that accompanied by lymph node metastasis was related to the altered receptor expression. Patients with positive ER and PR expression in both primary and metastatic lesions had the longest DFS, while those with negative expression had the shortest DFS. Also, changes in HER2 expression in primary and metastatic lesions were not associated with DFS. Patients with low expression of Ki-67 in both primary and metastatic lesions had the longest DFS, while patients with high expression had the shortest DFS.ConclusionHeterogeneity was detected in the expression levels of ER, PR, HER2, and Ki-67 in the primary and metastatic breast cancer lesions, which has a guiding significance for the treatment and prognosis of patients.
Comprehensive clinical evaluation of deep learning-based auto-segmentation for radiotherapy in patients with cervical cancer
Authors: Chung Seung Yeun , Chang Jee Suk , Kim Yong Bae 
Published: April 2023

Background and purposeDeep learning-based models have been actively investigated for various aspects of radiotherapy. However, for cervical cancer, only a few studies dealing with the auto-segmentation of organs-at-risk (OARs) and clinical target volumes (CTVs) exist. This study aimed to train a deep learning-based auto-segmentation model for OAR/CTVs for patients with cervical cancer undergoing radiotherapy and to evaluate the model’s feasibility and efficacy with not only geometric indices but also comprehensive clinical evaluation.Materials and methodsA total of 180 abdominopelvic computed tomography images were included (training set, 165; validation set, 15). Geometric indices such as the Dice similarity coefficient (DSC) and the 95% Hausdorff distance (HD) were analyzed. A Turing test was performed and physicians from other institutions were asked to delineate contours with and without using auto-segmented contours to assess inter-physician heterogeneity and contouring time.ResultsThe correlation between the manual and auto-segmented contours was acceptable for the anorectum, bladder, spinal cord, cauda equina, right and left femoral heads, bowel bag, uterocervix, liver, and left and right kidneys (DSC greater than 0.80). The stomach and duodenum showed DSCs of 0.67 and 0.73, respectively. CTVs showed DSCs between 0.75 and 0.80. Turing test results were favorable for most OARs and CTVs. No auto-segmented contours had large, obvious errors. The median overall satisfaction score of the participating physicians was 7 out of 10. Auto-segmentation reduced heterogeneity and shortened contouring time by 30 min among radiation oncologists from different institutions. Most participants favored the auto-contouring system.ConclusionThe proposed deep learning-based auto-segmentation model may be an efficient tool for patients with cervical cancer undergoing radiotherapy. Although the current model may not completely replace humans, it can serve as a useful and efficient tool in real-world clinics.