bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-27 Derived From Macrophages Facilitates IL-15 Production and T Cell Maintenance Following Allergic Hypersensitivity Responses
Authors: Suwanpradid Jutamas , Lee Min Jin , Hoang Peter , Kwock Jeffery , Floyd Lauren P. , Smith Jeffrey S. , Yin Zhinan , Atwater Amber R. , Rajagopal Sudarshan , Kedl Ross M. , Corcoran David L. , Zhang Jennifer Y. , MacLeod Amanda S. 
Published: October 2021

Crosstalk between T cells, dendritic cells, and macrophages in temporal leukocyte clusters within barrier tissues provides a new concept for T cell activation in the skin. Activated T cells from these leukocyte clusters play critical roles in the efferent phase of allergic contact hypersensitivity (CHS). However, the cytokines driving maintenance and survival of pathogenic T cells during and following CHS remain mostly unknown. Upon epicutaneous allergen challenge, we here report that macrophages produce IL-27 which then induces IL-15 production from epidermal keratinocytes and dermal myeloid cells within leukocyte clusters. In agreement with the known role of IL-15 as a T cell survival factor and growth cytokine, this signaling axis enhances BCL2 and survival of skin T cells. Genetic depletion or pharmacological blockade of IL-27 in CHS mice leads to abrogated epidermal IL-15 production resulting in a decrease in BCL2 expression in T cells and a decline in dermal CD8+ T cells and T cell cluster numbers. These findings suggest that the IL-27 pathway is an important cytokine for regulating cutaneous T cell immunity.
Evaluation of Macular and Retinal Ganglion Cell Count Estimates for Detecting and Staging Glaucoma
Authors: Wu Yali , Cun Qing , Tao Yijin , Yang Wenyan , Wei Jia , Fan Daoqing , Zhang Ying , Chen Qin , Zhong Hua 
Published: October 2021

Purpose: To investigate the clinical significance of macular estimated retinal ganglion cell (mRGC) and estimated retinal ganglion cell (eRGC) in the diagnosis and staging of glaucoma.Methods: This is a cross-section study. All enrolled subjects underwent standard automated perimetry (SAP) and optical coherence tomography (OCT) examination. Swedish Interactive Threshold Algorithm (SITA)-FAST detection strategy and 24-2, 10-2 detection programs were employed in SAP assessment. The visual-field parameters and OCT parameters were calculated according to three formulas to obtain the eRGC and mRGC1 or mRGC2. The efficiency of eRGC, mRGC1, and mRGC2 estimates for the staging of glaucoma was compared. The sensitivity and specificity of each parameter for diagnosis of glaucoma were analyzed using the receiver operating characteristic (ROC) curve.Results: A total of 119 eyes were included in the analysis. Compared with the healthy controls, eRGC, mRGC1, and mRGC2 estimates were significantly decreased in patients with glaucoma. As glaucoma progressed, eRGC, mRGC1, and mRGC2 estimates were gradually reduced. In preperimetric glaucoma, mRGC1, mRGC2, and eRGC were reduced by 13.2, 14.5, and 18%, respectively. In the mild stage of glaucoma, mRGC1, mRGC2, and eRGC were reduced by 28, 34, and 38%, respectively. In the advanced stage of glaucoma, mRGC1, mRGC2, and eRGC were reduced by 81, 85, and 92% respectively. The proportion of retinal ganglion cell (RGC) loss in the macula was close to that outside the macula. The specificity at 95% gave a sensitivity of 95.51, 86.52, and 87.64% for eRGC, mRGC1, and mRGC2, respectively. The sensitivity of structural parameters macular ganglion cell complex thickness and retinal nerve fiber layer (RNFL) were 98.88 and 95.51%, respectively. The sensitivity of functional parameters mean deviation (24-2) and visual field index (VFI) were 80.90 and 73.03%, respectively. The area under ROC curve of mRGC1, mRGC2, and eRGC were 0.982, 0.972, and 0.995 (P &lt; 0.0001), respectively.Conclusion: Estimated retinal ganglion cell, mRGC1, and mRGC2 provide value to the staging of glaucoma and better diagnostic performance. Macular RGC estimatesthat integration of both structural and functional damages in macular may serve as a sensitive indicator for assessing macular damage in glaucoma and are of importance for the diagnosis and progression management of glaucoma.
Acetylation Profiles in the Metabolic Process of Glioma-Associated Seizures
Authors: Xu Ya-Wen , Lin Peng , Zheng Shu-Fa , Huang Wen , Lin Zhang-Ya , Shang-Guan Huang-Cheng , Lin Yuan-Xiang , Yao Pei-Sen , Kang De-Zhi 
Published: October 2021

Objective: We test the hypothesis that lysine acetylation is involved in the metabolic process of glioma-associated seizures (GAS).Methods: We used label-free mass spectrometry-based quantitative proteomics to quantify dynamic changes of protein acetylation between gliomas with seizure (CA1 group) and gliomas without seizure (CA2 group). Furthermore, differences of acetyltransferase and deacetylase expression between CA1 and CA2 groups were performed by a quantitative proteomic study. We further classified acetylated proteins into groups according to cell component, molecular function, and biological process. In addition, metabolic pathways and protein interaction networks were analyzed. Regulated acetyltransferases and acetylated profiles were validated by PRM and Western blot.Results: We detected 169 downregulated lysine acetylation sites of 134 proteins and 39 upregulated lysine acetylation sites of 35 proteins in glioma with seizures based on acetylome. We detected 407 regulated proteins by proteomics, from which ACAT2 and ACAA2 were the differentially regulated enzymes in the acetylation of GAS. According to the KEGG analysis, the upregulated acetylated proteins within the PPIs were mapped to pathways involved in the TCA cycle, oxidative phosphorylation, biosynthesis of amino acids, and carbon metabolism. The downregulated acetylated proteins within the PPIs were mapped to pathways involved in fatty acid metabolism, oxidative phosphorylation, TCA cycle, and necroptosis. Regulated ACAT2 expression and acetylated profiles were validated by PRM and Western blot.Conclusions: The data support the hypothesis that regulated protein acetylation is involved in the metabolic process of GAS, which may be induced by acetyl-CoA acetyltransferases.
Case Report: Hypopituitarism Presenting With Nonconvulsive Status Epilepticus
Authors: Li Huimin , Xu Lina , Yang Fengbing , Jia Longbin , Cheng Hongjiang , Liu Wei 
Published: October 2021

Introduction: Hypopituitarism is defined as one or more partial or complete pituitary hormone deficiencies. Nonconvulsive status epilepticus (NCSE) refers to a state of continuous or repetitive seizures without convulsions. In this paper, we review a case of an old female patient with hypopituitarism who presented with NCSE, which is rare in the clinic.Case Report: This paper describes a 67-year-old female patient with hypopituitarism who presented as NCSE. She had surgical resection of pituitary tumor half a year before the seizures and did not get regular hormone replacement therapy. She presented general convulsive status epilepsy as the initial symptom and got sedation and antiepileptic drug in the emergency room. The seizure was terminated but the patient fell in coma in the following days. The patient had magnetic resonance imaging (MRI) and other inspects, and EEG showed epileptic discharges. Combining these clinical symptoms and examinations, we made the diagnosis of NCSE. Finally, she regained consciousness after the treatment with diazepam.Conclusion: This case report and literature review investigated the possible mechanism of hypopituitarism presenting with NCSE.
Hypoalbuminaemia as a Prognostic Biomarker of First-Line Treatment Resistance in Metastatic Non-small Cell Lung Cancer
Authors: Stares Mark , Swan Amanda , Cumming Kirsten , Ding Tze-En , Leach James , Stratton Cory , Thomson Findlay , Barrie Colin , MacLennan Kirsty , Campbell Sorcha , Evans Tamasin , Tufail Aisha , Harrow Stephen , MacKean Melanie , Phillips Iain 
Published: October 2021

Introduction: Despite significant advances in systemic anticancer therapy (SACT) for non-small cell lung cancer (NSCLC), many patients still fail to respond to treatment or develop treatment resistance. Albumin, a biomarker of systemic inflammation and malnutrition, predicts survival in many cancers. We evaluated the prognostic significance of albumin in patients receiving first-line targeted therapy or immunotherapy-based SACT for metastatic NSCLC.Methods: All patients treated with first-line targeted therapy or immunotherapy-based SACT for metastatic NSCLC at a regional Scottish cancer centre were identified. Serum albumin at pre-treatment, after 12-weeks of treatment, and at the time of progressive disease were recorded. The relationship between albumin (≥ 35g/L v &lt;35g/L) and overall survival (OS) was examined.Results: Data were available for 389 patients of both targeted therapy cohort (n = 159) and immunotherapy-based therapy cohort (n = 230). Pre-treatment albumin was predictive of OS in each cohort at HR1.82 (95%CI 1.23–2.7) (p =0.003) and HR2.55 (95%CI 1.78–3.65) (p &lt; 0.001), respectively. Pre-treatment albumin &lt;35 g/L was associated with a significantly higher relative risk of death within 12 weeks in each cohort at RR9.58 (95%CI 2.20–41.72, p = 0.003) and RR3.60 (95%CI 1.74–6.57, p &lt; 0.001), respectively. The 12-week albumin was predictive of OS in each cohort at HR1.88 (95%CI 1.86–4.46) (p &lt; 0.001) and HR2.67 (95%CI 1.74–4.08) (p &lt; 0.001), respectively. 46 out of 133 (35%) evaluable patients treated with targeted therapy and 43 out of 169 (25%) treated with immunotherapy-based therapy crossed over albumin prognostic groups between pre-treatment and 12-week. The prognostic value of 12-week albumin was independent of pre-treatment albumin status. A majority of patients had albumin &lt;35g/L at the time of progressive disease when it was also predictive of survival following progressive disease at HR2.48 (95%CI 1.61–3.82) (p &lt; 0.001) and HR2.87 (95%CI 1.91–4.31) (p &lt; 0.001) respectively).Conclusions: Albumin is a reliable prognostic factor in patients with metastatic NSCLC, predicting survival independent of the class of drug treatment at various time points during the patient journey. Tracking albumin concentrations during systemic therapy may indicate disease activity or treatment response over time.
Predictive Value of Preoperative Positive Urine Cytology for Development of Bladder Cancer After Nephroureterectomy in Patients With Upper Urinary Tract Urothelial Carcinoma: A Prognostic Nomogram Based on a Retrospective Multicenter Cohort Study and Systematic Meta-Analysis
Authors: Fan Bo , Huang Yuanbin , Wen Shuang , Teng Qiliang , Yang Xinrui , Sun Man , Chen Tingyu , Huang Yan , Wang Yumei , Liu Zhiyu 
Published: October 2021

BackgroundUpper urinary tract urothelial carcinoma (UUT-UC) is a rare and severe urinary malignancy. Several studies have explored the relationship between preoperative urine cytology and intravesical recurrence (IVR) in patients with UUT-UC. However, the results of these studies are controversial or even contradictory, and investigations with UUT-UC patients in northeast China are rare.MethodsWe first estimated the prognostic significance of preoperative urine cytology in the outcomes of intravesical recurrence in 231 UUT-UC patients (training cohort = 142, validation cohort = 89) after radical nephroureterectomy (RNU) by the nomogram model. Subsequently, we quantitatively combined our results with the published data after searching several databases to assess whether preoperative positive urine cytology was associated with poor intravesical recurrence-free survival and a high risk of tumor malignant biological behavior.ResultsFirstly, the multicenter retrospective cohort study demonstrated that preoperative positive urine cytology correlated with poor intravesical recurrence-free survival and can serve as significant independent predictors of IVR by Kaplan–Meier curves and Cox regression analysis. The construction of the nomogram demonstrated that predictive efficacy and accuracy were significantly improved when preoperative urine cytology was combined. Meanwhile, meta-analysis showed that preoperative positive urine cytology was associated with a 49% increased risk of IVR. In the subgroup analysis by region, study type, and sample size, the pooled hazard ratios (HRs) were statistically significant for the Japan subgroup (HR 1.32), China subgroup (HR 1.88), cohort study subgroup (HR 1.45), and the single-arm study subgroup (HR 1.63).ConclusionsPreoperative urine cytology was validated as a potential predictor of intravesical recurrence in patients with UUT-UC after RNU, although these results need to be generalized with caution. Large, prospective trials are required to further confirm its significance in prognosis and tumor malignant biological behavior.
Axillary Lymph Node Dissection Rates and Prognosis From Phase III Neoadjuvant Systemic Trial Comparing Neoadjuvant Chemotherapy With Neoadjuvant Endocrine Therapy in Pre-Menopausal Patients With Estrogen Receptor-Positive and HER2-Negative, Lymph Node-Positive Breast Cancer
Authors: Gwark Sungchan , Noh Woo Chul , Ahn Sei Hyun , Lee Eun Sook , Jung Yongsik , Kim Lee Su , Han Wonshik , Nam Seok Jin , Gong Gyungyub , Kim Seon-Ok , Kim Hee Jeong 
Published: October 2021

In this study, we aimed to evaluate axillary lymph node dissection (ALND) rates and prognosis in neoadjuvant chemotherapy (NCT) compare with neoadjuvant endocrine therapy (NET) in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-), lymph node (LN)-positive, premenopausal breast cancer patients (NCT01622361). The multicenter, phase 3, randomized clinical trial enrolled 187 women from July 5, 2012, to May 30, 2017. The patients were randomly assigned (1:1) to either 24 weeks of NCT including adriamycin plus cyclophosphamide followed by intravenous docetaxel, or NET involving goserelin acetate and daily tamoxifen. ALND was performed based on the surgeon’s decision. The primary endpoint was ALND rate and surgical outcome after preoperative treatment. The secondary endpoint was long-term survival. Among the 187 randomized patients, pre- and post- neoadjuvant systemic therapy (NST) assessments were available for 170 patients. After NST, 49.4% of NCT patients and 55.4% of NET patients underwent mastectomy after treatment completion. The rate of ALND was significantly lower in the NCT group than in the NET group (55.2% vs. 69.9%, P=.046). Following surgery, the NET group showed a significantly higher mean number of removed LNs (14.96 vs. 11.74, P=.003) and positive LNs (4.84 vs. 2.92, P=.000) than the NCT group. The axillary pathologic complete response (pCR) rate was significantly higher in the NCT group (13.8% vs. 4.8%, P=.045) than in the NET group. During a median follow-up of 67.3 months, 19 patients in the NCT group and 12 patients in the NET group reported recurrence. The 5-year ARFS (97.5%vs. 100%, P=.077), DFS (77.2% vs. 84.8%, P=.166), and OS (97.5% vs. 94.7%, P=.304) rates did not differ significantly between the groups. In conclusion, although survival did not differ significantly, more NCT patients might able to avoid ALND, with fewer LNs removed with lower LN positivity.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT01622361, identifier NCT01622361.
Comparing Hypofractionated With Conventional Fractionated Radiotherapy After Breast-Conserving Surgery for Early Breast Cancer: A Meta-Analysis of Randomized Controlled Trials
Authors: Gu Lihu , Dai Wei , Fu Rongrong , Lu Hongfeng , Shen Jingyi , Shi Yetan , Zhang Mengting , Jiang Ke , Wu Feng 
Published: October 2021

BackgroundThe purpose of this meta-analysis was to compare the safety and efficacy between hypofractionated and conventional fractionation radiotherapy in patients with early-stage breast cancer after breast-conserving surgery.MethodsWe conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library to identify relevant randomized controlled trials (RCTs) published before February 2021. At the same time, the hazard ratio (HR), risk ratio (RR), and 95% confidence interval (CI) were calculated to evaluate local recurrence (LR), relapse-free survival (RFS), overall survival (OS), adverse events, and cosmetic outcomes.ResultsA total of 14 articles were included in this meta-analysis. Four thousand eight hundred and sixty-nine patients were randomly assigned to the control group to receive conventional radiotherapy (CFRT); 6,072 patients were randomly assigned to the experimental group and treated with hypofractionated radiotherapy (HFRT). The results showed that there was no statistical difference between HFRT and CFRT in LR (HR = 0.99, 95%CI = 0.97–1.02, p = 0.476), RFS (HR = 0.99, 95%CI = 0.97–1.02, p = 0.485), OS (HR = 1.00, 95%CI = 0.97–1.03, p = 0.879), and cosmetic outcomes (RR = 1.03, 95%CI = 0.95–1.12, p = 0.53). In addition, HFRT showed fewer severe adverse reactions such as acute skin toxicity, induration, breast atrophy, and pain.ConclusionOur results suggest that there is no statistical difference between HFRT and CFRT in terms of LR, RFS, OS, and cosmetic outcomes. HFRT reduces the risk of developing toxicity reactions compared to CFRT. HFRT may be a better option for patients with early breast cancer after breast-conserving surgery.
Wheezing Characteristics and Predicting Reactivity to Inhaled β2-Agonist in Children for Home Medical Care
Authors: Habukawa Chizu , Ohgami Naoto , Arai Takahiro , Makata Haruyuki , Nishikido Tomoki , Tomikawa Morimitsu , Murakami Katsumi 
Published: October 2021

Background: Given that wheezing is treated with inhaled β2-agonists, their effect should be reviewed before the condition becomes severe; however, few methods can currently predict reactivity to inhaled β2-agonists. We investigated whether preinhalation wheezing characteristics identified by lung sound analysis can predict reactivity to inhaled β2-agonists.Methods: In 202 children aged 10–153 months, wheezing was identified by auscultation. Lung sounds were recorded for 30 s in the chest region on the chest wall during tidal breathing. We analyzed the wheezing before and after β2-agonist inhalation. Wheezing was displayed as horizontal bars of intensity defined as a wheeze power band, and the wheezing characteristics (number, frequency, and maximum intensity frequency) were evaluated by lung sound analysis. The participants were divided into two groups: non-disappears (wheezing did not disappear after inhalation) and disappears (wheezing disappeared after inhalation). Wheezing characteristics before β2-agonist inhalation were compared between the two groups.The characteristics of wheezing were not affected by body size. The number of wheeze power bands of the non-responder group was significantly higher than those of the responder group (P &lt; 0.001). The number of wheeze power bands was a predictor of reactivity to inhaled β2-agonists, with a cutoff of 11.1. The 95% confidence intervals of sensitivity, specificity, and positive and negative predictive values were 88.8, 42, 44, and 81.1% (P &lt; 0.001), respectively.Conclusions: The number of preinhalation wheeze power bands shown by lung sound analysis was a useful indicator before treatment. This indicator could be a beneficial index for managing wheezing in young children.
Effects of TPMT, NUDT15, and ITPA Genetic Variants on 6-Mercaptopurine Toxicity for Pediatric Patients With Acute Lymphoblastic Leukemia in Yunnan of China
Authors: Mao Xiaoyan , Yin Runxiu , Sun Gaoyuan , Zhou Yan , Yang Chunhui , Fang Chunlian , Wu Yuhong , Cui Tingting , Liu Li , Gan Jiaxin , Tian Xin 
Published: October 2021

Background: 6-Mercaptopurine (6-MP) is the cornerstone of current antileukemia regimen and contributes greatly to improve the survival of pediatric acute lymphoblastic leukemia (ALL) patients. However, 6-MP dose-related toxicities limit its application. TPMT, NUDT15, and ITPA are pharmacogenetic markers predicting 6-MP-related toxicities, but their genetic polymorphisms differ from those of ethnic populations. In Yunnan province, a multiethnic region of China, we had no genetic data to predict 6-MP toxicities. In this study, we evaluated the most common variants involved in 6-MP metabolism—TPMT*3C (rs1142345), NUDT15 c.415C&gt;T (rs116855232), and ITPA c.94C&gt;A (rs1127354) variants—in our cohort of pediatric ALL patients.Methods: A total of 149 pediatric ALL patients in the Affiliated Children's Hospital of Kunming Medical University (Yunnan Children's Medical Center) from 2017 to 2019 were enrolled in this retrospective study. We assessed the TPMT*3C (rs1142345), NUDT15 c.415C&gt;T (rs116855232), and ITPA c.94C&gt;A (rs1127354) frequencies and evaluated association between genotypes and 6-MP toxicities, 6-MP dose, and event-free survival (EFS) in these ALL patients.Results: The allele frequencies of TPMT*3C (rs1142345), NUDT15 c.415C&gt;T (rs116855232), and ITPA c.94C&gt;A (rs1127354) were 1.34%, 14.43%, and 18.79%, respectively. Only NUDT15 c.415C&gt;T (rs116855232) was strongly associated with 6-MP toxicity and 6-MP tolerable dose. NUDT15 c.415C&gt;T was related to leukopenia, p = 0.008, OR = 2.743 (95% CI: 1.305–5.768). The T allele was significantly correlated with 6-MP tolerable dose, dose of NUDT15 c.415C&gt;T wild genotype CC 39.80 ± 1.32 mg/m2, heterozygotes CT 35.20 ± 2.29 mg/m2, and homozygotes TT 18.95 ± 3.95 mg/m2. 6-MP tolerable dose between CC and TT had a significant difference, p = 0.009. Between CC and CT, and CT and TT, they had no significant difference. EFS showed no significant difference among NUDT15 c.415C&gt;T genotypes.Conclusion:NUDT15 c.415C&gt;T (rs116855232) was an optimal predictor for 6-MP toxicity and tolerable dose in pediatric ALL patients from Yunnan province, a multiethnic region in China, and would play an important role in precise therapy for ALL.
Sacral Curvature in Addition to Sacral Ratio to Assess Sacral Development and the Association With the Type of Anorectal Malformations
Authors: Chen Zhen , Zheng Lingling , Zhang Minzhong , Zhang Jie , Kong Ruixue , Chen Yunpei , Liang Zijian , Levitt Marc A. , Wei Chin-Hung , Wang Yong 
Published: October 2021

Introduction: Sacral ratio (SR) is currently the only measurement to quantitatively evaluate sacral development in patients with anorectal malformations (ARM). This study proposes sacral curvature (SC) as a new indicator to qualitatively assess the sacrum and hypothesizes that sacral development, both quantitatively and qualitatively, can be an indicator to predict the type of ARM. The study aims to investigate the difference of SR and SC between ARM types and the association with the type of ARM.Methods and Materials: This study was retrospectively conducted between August 2008 and April 2019. Male patients with ARMs were enrolled and divided into three groups based on the types of ARM: (1) rectoperineal fistulae, (2) rectourethral-bulbar fistulae, and (3) rectourethral-prostatic or rectobladder-neck fistulae. SC was measured in the sagittal views of an MRI or a lateral radiograph of the sacrum.Results: Included in the study were 316 male patients with ARMs. SRs were 0.73 ± 0.12, 0.65 ± 0.12, and 0.57 ± 0.12 in perineal, bulbar, and prostatic/bladderneck fistula, respectively (p &lt; 0.01). The SCs in perineal fistulae and bulbar fistulae were significantly higher than that in prostatic/bladderneck fistulae (0.25 ± 0.04, 0.22 ± 0.14, and 0.14 ± 0.18, p &lt; 0.01). When SR ≥ 0.779, there was an 89.9% of possibility that the child has a perineal fistula. When SR ≤ 0.490 and SC ≤ 0, the possibilities of the child having prostatic/bladderneck fistulae were 91.6 and 89.5%, respectively. SC &lt; 0 was also noted in 27 (27.8%), 19 (10.5%), and no (0%) patients of prostatic/bladderneck, bulbar, and perineal fistulae (p &lt; 0.01), respectively. Sacral defect was noted in 63% of patients with SC ≤ 0, compared to none with SC &gt; 0 (p &lt; 0.01).Conclusions: The higher the rectal level is in an ARM, the lower are the objective measurements of the sacrum. SC ≤ 0 is associated with sacral defects and implies a high likelihood of prostatic/bladderneck fistulae.