bluuebunny/crossref_metadata_2025_split huggingface dataset:
PTPRO-related CD8+ T-cell signatures predict prognosis and immunotherapy response in patients with breast cancer
Authors: Dong Hongmei , Xie Chaoyu , Yao Zhimeng , Zhao Ruijun , Lin Yusheng , Luo Yichen , Chen Shuanglong , Qin Yanfang , Chen Yexi , Zhang Hao 
Published: August 2022

BackgroundPoor immunogenicity and extensive immunosuppressive T-cell infiltration in the tumor immune microenvironment (TIME) have been identified as potential barriers to immunotherapy success in “immune-cold” breast cancers. Thus, it is crucial to identify biomarkers that can predict immunotherapy efficacy. Protein tyrosine phosphatase receptor type O (PTPRO) regulates multiple kinases and pathways and has been implied to play a regulatory role in immune cell infiltration in various cancers.MethodsESTIMATE and single-sample gene set enrichment analysis (ssGSEA) were performed to uncover the TIME landscape. The correlation analysis of PTPRO and immune infiltration was performed to characterize the immune features of PTPRO. Univariate and multivariate Cox analyses were applied to determine the prognostic value of various variables and construct the PTPRO-related CD8+ T-cell signatures (PTSs). The Kaplan–Meier curve and the receiver operating characteristic (ROC) curve were used to estimate the performance of PTS in assessing prognosis and immunotherapy response in multiple validation datasets.ResultsHigh PTPRO expression was related to high infiltration levels of CD8+ T cells, as well as macrophages, activated dendritic cells (aDCs), tumor-infiltrating lymphocytes (TILs), and Th1 cells. Given the critical role of CD8+ T cells in the TIME, we focused on the impact of PTPRO expression on CD8+ T-cell infiltration. The prognostic PTS was then constructed using the TCGA training dataset. Further analysis showed that the PTS exhibited favorable prognostic performance in multiple validation datasets. Of note, the PTS could accurately predict the response to immune checkpoint inhibitors (ICIs).ConclusionPTPRO significantly impacts CD8+ T-cell infiltration in breast cancer, suggesting a potential role of immunomodulation. PTPRO-based PTS provides a new immune cell paradigm for prognosis, which is valuable for immunotherapy decisions in cancer patients.
The hemodynamic stability of remimazolam compared with propofol in patients undergoing endoscopic submucosal dissection: A randomized trial
Authors: Qiu Yuwei , Gu Wei , Zhao Mingye , Zhang Yunyun , Wu Jingxiang 
Published: August 2022

ObjectiveHypotension is common in propofol anesthesia. Whether remimazolam could reduce intraoperative hypotension remains unknown. We therefore tested the primary hypothesis that remimazolam reduces the incidence of intraoperative hypotension compared with propofol in adult patients undergoing endoscopic submucosal dissection (ESD) surgery.Materials and methodsWe conducted a prospective trial to compare patients who received either remimazolam or propofol bolus induction and thereafter intravenous infusion. The hemodynamic parameters were measured using CNAP® Monitor 500 system. Our primary analysis was to compare the incidence of hypotension defined as systolic blood pressure below 90 mmHg between remimazolam and propofol during the whole anesthesia period.ResultsThe incidence of hypotension decreased by 50%, from 67.9% in propofol group to 32.1% in remimazolam group (p &lt; 0.01). Patients received less amount of intraoperative phenylephrine in the remimazolam group than the propofol group (0 [0–40] μg vs. 80 [0–200] μg, p &lt; 0.01). Time-weighted average and cumulative time of hypotension was lower in remimazolam group compared with propofol group (p &lt; 0.05). Cardiac output continuously measured by CNAP was preserved much better in remimazolam group compared with propofol group (p = 0.01), while systemic vascular resistance did not differ between the groups. The median time from discontinuation until full alertness was 4 [3–11.8] min in the remimazolam group compared with 15 [12.0–19.8] min in the propofol group (p &lt; 0.01).ConclusionRemimazolam has better hemodynamic stability than propofol in adult patients undergoing ESD surgery. The benefits of remimazolam on hemodynamic stability and hypotension prevention may be partly contributed to its better preservation of cardiac output.Clinical Trial Registration[http://www.chictr.org.cn/com/25/showproj.aspx?proj=61104], identifier [ChiCTR2000037975].
Comparison of the Performance of 24 Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Assays in the Diagnosis of Coronavirus Disease 2019 Patients
Authors: Wu Shiji , Hou Hongyan , Li Huijun , Wang Ting , Wei Wei , Zhang Minxia , Yin Botao , Huang Min , Sun Ziyong , Wang Feng 
Published: August 2022

BackgroundThe accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the key to control Coronavirus Disease-2019 (COVID-19). The performance of different antibody detection methods for diagnosis of COVID-19 is inconclusive.MethodsBetween 16 February and 28 February 2020, 384 confirmed COVID-19 patients and 142 healthy controls were recruited. 24 different serological tests, including 4 enzyme-linked immunosorbent assays (EIAs), 10 chemiluminescent immunoassays (CLIAs), and 10 lateral flow immunoassays (LFIAs), were simultaneously performed.ResultsThe sensitivities of anti-SARS-CoV-2 IgG and IgM antibodies with different reagents ranged from 75 to 95.83% and 46.09 to 92.45%, respectively. The specificities of both anti-SARS-CoV-2 IgG and IgM were relatively high and comparable among different reagents, ranged from 88.03 to 100%. The area under the curves (AUCs) of different tests ranged from 0.733 to 0.984, and the AUCs of EIAs or CLIAs were significantly higher than those of LFIAs. The sensitivities of both IgG and IgM gradually increased with increase of onset time. After 3–4 weeks, the sensitivities of anti-SARS-CoV-2 IgG were maintained at a certain level but the sensitivities of IgM were gradually decreased. Six COVID-19 patients who displayed negative anti-SARS-CoV-2 results were associated with the factors such as older age, having underlying diseases, and using immunosuppressant.ConclusionBesides the purpose of assessing the impact of the SARS-CoV-2 pandemic in the population, SARS-CoV-2 antibody assays may have an adjunct role in the diagnosis and exclusion of COVID-19, especially by using high-throughput technologies (EIAs or CLIAs).
Analysis of Brain Lipids in the Early-Onset Tay–Sachs Disease Mouse Model With the Combined Deficiency of β-Hexosaminidase A and Neuraminidase 3
Authors: Can Melike , Sengül Tugce , Demir Secil Akyildiz , İnci Orhan K. , Basırlı Hande , Seyrantepe Volkan 
Published: August 2022

Introduction: Tay–Sachs disease is an autosomal recessively inherited lysosomal storage disease that results from loss-of-function mutations in the HEXA gene coding β-hexosaminidase A. HEXA gene deficiency affects the central nervous system owing to GM2 ganglioside accumulation in lysosomes resulting in progressive neurodegeneration in patients. We recently generated a novel mice model with a combined deficiency of β-hexosaminidase A and neuraminidase 3 (Hexa−/−Neu3−/−) that mimics both the neuropathological and clinical abnormalities of early-onset Tay–Sachs disease. Here, we aimed to explore the secondary accumulation of lipids in the brain of Hexa−/−Neu3−/− mice.Materials and Methods: In the cortex and hippocampus of five-month-old WT, Hexa−/−, Neu3−/−, and Hexa−/−Neu3−/− mice, lipid levels belonging to glycerolipids, glycerophospholipids, and sterol lipids were evaluated using a shotgun lipidomics approach. The levels of myelin were also assessed by luxol fast blue staining and immunohistochemistry using antibodies against myelin basic protein. We further examined glycoconjugate and cholesterol levels by periodic acid–Schiff and filipin staining, respectively. Toluidine blue staining was also performed to display axonal degeneration.Results: Among glycerophospholipids, we demonstrated elevated levels of phosphatidylcholine-ether and lysophosphatidylcholine while decreased levels of phosphatidylcholine and phosphatidylserine in both cortex and hippocampus of Hexa−/−Neu3−/− mice. In the glycerolipid class, we showed an alleviated level of sphingomyelin in both cortex and hippocampus, but the higher levels of diacylglycerol and triacylglycerol were detected in only the hippocampus of Hexa−/−Neu3−/− mice. The lower level of sterol was also detected in the cortex of Hexa−/−Neu3−/− mice but not in the hippocampus.Histochemical studies showed a decrease in the myelin level and axonal degeneration indicating neuronal pathology in the brain of Hexa−/−Neu3−/− mice. Although glycoconjugate accumulation was evident both in the cortex and hippocampus, we did not detect any changes in the level of cholesterol.Conclusion: Our results indicate that alterations in lipid metabolism and neuropathology, such as demyelination and axonal degeneration, might be related to the dysfunctionality of lipid-related cellular pathways like autophagy. Understanding of brain-specific lipid alterations contributes to evaluating the effectiveness of treatments in Hexa−/−Neu3−/− mice in future studies.
The discriminant validity of single-question assessments of subjective cognitive complaints in an Asian older adult population
Authors: Pang Ting , Zhao Xuhao , He Xindi , Kan Cheuk Ni , Venketasubramanian Narayanaswamy , Cheng Ching-Yu , Yuan Changzheng , Chen Christopher , Xu Xin 
Published: August 2022

ObjectiveTo compare the discriminant validity of three different single-question assessments of subjective cognitive complaints (SCC) for dementia in a community-based older adult population in Singapore.MethodsEligible older adults aged ≥60 were recruited into phase I for identifying those who require further assessment using the Abbreviated Mental Test (AMT) and progressive forgetfulness question (PFQ). Participants who failed either tests entered phase II and were administered various single-question assessments of SCC, such as the 8th question on the patient Ascertain Dementia 8 (AD8-8pt), informant AD8 (AD8-8info), and the 10th item on the Geriatric Depression Scale (GDS-10), followed by the Montreal Cognitive Assessment (MoCA) and a formal neuropsychological battery to identify the participant’s cognitive status by a research diagnosis and DSM-IV criteria. Differences in characteristics among diagnostic groups were compared. All discriminatory indices (sensitivity, specificity, positive, and negative predictive values, overall accuracy) for these single-question assessments and their combinations with the MoCA were calculated and reported to confirm their discriminant validity in identifying the existence of subjective complaints and objective impairment.ResultsA total of 3,780 participants were assessed at phase I, of which 957 entered and completed phase II. Of whom, 911 were dementia-free and 46 had dementia. The MoCA (13/14) displayed good sensitivity (95.6%), specificity (81.5%), and overall accuracy (82.1%) for dementia detection. The GDS-10 and AD8-8pt showed poor discriminant validity, while the AD8-8info had the highest specificity (83.2%) and the greatest overall accuracy (82.5%) for dementia. Compensatory combination of the AD8-8info with MoCA, the sensitivity and positive predictive values were optimized (100%), while the conjunctive combination of two tools achieved excellent specificity (96.3%) and overall accuracy (94.8%) in discriminating dementia patients.Conclusion and implicationsCombining a reliable single-question SCC assessment with an objective tool can efficiently discriminate dementia patients from healthy older adults in the community.
Glymphatic system dysfunction in patients with early chronic kidney disease
Authors: Heo Chang Min , Lee Dong Ah , Park Kang Min , Lee Yoo Jin , Park Sihyung , Kim Yang Wook , Ko Junghae , Yoo Byeong Cheol , Park Bong Soo 
Published: August 2022

IntroductionIt is a recent finding that glymphatic system dysfunction contributes to various neurological problems. The purpose of this research was to assess the function of the glymphatic system in neurologically asymptomatic early chronic kidney disease (CKD) patients and healthy controls, using diffusion tensor image analysis along perivascular space (DTI-ALPS) index.MethodsIn a prospective study, we included patients with early CKD who were asymptomatic for neurological issues and obtained clinical and laboratory data. In all participants, brain magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) was conducted. We used DSI program for DTI preprocessing and DTI-ALPS index estimation. The DTI-ALPS index was compared between patients with early CKD and healthy controls, and the association between clinical characteristics and the DTI-ALPS index was investigated.ResultsEighteen patients with early CKD and 18 healthy controls were included in this study. Patients with early CKD had lower DTI-ALPS index than healthy controls (1.259 ± 0.199 vs. 1.477 ± 0.232, p = 0.004). In the correlation analysis, the DTI-ALPS index had no significant relationship with other clinical factors.ConclusionWe suggest dysfunction of glymphatic system in patients with early chronic kidney disease using the DTI-ALPS index. This may be related to the pathophysiology of neurological problems including impairment of cognition in patients with early CKD.
Iron deposition in the precuneus is correlated with mild cognitive impairment in patients with cerebral microbleeds: A quantitative susceptibility mapping study
Authors: Tu Jing , Yan Jin , Liu Juan , Liu Dandan , Wang Xiaomeng , Gao Fei 
Published: August 2022

PurposeThe purpose of this study was to define whether mild cognitive impairment (MCI) is associated with iron deposition in rich-club nodes distant from cerebral microbleeds (CMBs) in patients with cerebral small vessel disease (CSVD).MethodsA total of 64 participants underwent magnetic resonance imaging (MRI) scanning and were separated into three groups, namely, CMB(+), CMB(–), and healthy controls (HCs). We compared their characteristics and susceptibility values of rich-club nodes [e.g., superior frontal gyrus (SFG), precuneus, superior occipital gyrus (SOG), thalamus, and putamen]. We then divided the CMB(+) and CMB(–) groups into subgroups of patients with or without MCI. Then, we analyzed the relationship between iron deposition and MCI by comparing the susceptibility values of rich-club nodes. We assessed cognitive functions using the Montreal Cognitive Assessment (MoCA) and quantified iron content using quantitative susceptibility mapping (QSM).ResultsIn the putamen, the CMB(+) and CMB(–) groups had significantly different susceptibility values. Compared with the HCs, the CMB(+) and CMB(–) groups had significantly different susceptibility values for the SFG and SOG. In addition, we found significant differences in the putamen susceptibility values of the CMB(+)MCI(+) group and the two CMB(–) groups. The CMB(+)MCI(+) and CMB(+)MCI(–) groups had significantly different precuneus susceptibility values. The binary logistic regression analysis revealed that only higher susceptibility values of precuneus were associated with a cognitive decline in patients with CMBs, and it indicated statistical significance.ConclusionIron deposition in the precuneus is an independent risk factor for MCI in patients with CMBs. CMBs might influence iron content in remote rich-club nodes and be relevant to MCI.
Lower Energy-Adjusted Nutrient Intakes Occur Among Food Energy Under-Reporters With Poor Mental Health
Authors: Davison Karen M. , Araujo Almeida Vanessa , Gondara Lovedeep 
Published: August 2022

BackgroundFood energy under-reporting is differentially distributed among populations. Currently, little is known about how mental health state may affect energy-adjusted nutrient intakes among food energy under-reporters.MethodsStratified analysis of energy-adjusted nutrient intake by mental health (poor vs. good) and age/sex was conducted using data from Canadian Community Health Survey (CCHS) respondents (14–70 years; n = 8,233) who were deemed as under-reporters based on Goldberg's cutoffs.ResultsMost were experiencing good mental health (95.2%). Among those reporting poor mental health, significantly lower energy-adjusted nutrient intakes tended to be found for fiber, protein, vitamins A, B2, B3, B6, B9, B12, C, and D, and calcium, potassium, and zinc (probability measures (p) &lt; 0.05). For women (51–70 years), all micronutrient intakes, except iron, were significantly lower among those reporting poor mental health (p &lt; 0.05). For men (31–50 years), B vitamin and most mineral intakes, except sodium, were significantly lower among those reporting poor mental health (p &lt; 0.05). Among women (31–50 years) who reported poor mental health, higher energy-adjusted intakes were reported for vitamin B9 and phosphorus (p &lt; 0.05).ConclusionsAmong food energy under-reporters, poor mental health tends to lower the report of specific energy-adjusted nutrient intakes that include ones critical for mental health. Future research is needed to discern if these differences may be attributed to deviations in the accurate reports of food intakes, measurement errors, or mental health states.
Comparison of hook-wire and medical glue for CT-guided preoperative localization of pulmonary nodules
Authors: Zhang Huijun , Li Ying , Chen Xiaofeng , He Zelai 
Published: August 2022

BackgroundPreoperative localization is challenging due to the small diameter of pulmonary nodules or their deep location in the lung parenchyma during VATS surgery. The purpose of this study was to compare the efficacy and safety of both hook-wire and medical glue for pre-operative localization of pulmonary nodules.MethodsIn the current study, 158 patients were retrospectively analyzed (January 2019 and January 2020). The patients underwent hook-wire or medical glue for pre-operative localization of pulmonary nodules. Among them, 74 patients in the hook-wire group and 84 patients in the medical glue group underwent VATS anatomic segmentectomy or wedge resection after localization of pulmonary nodules. Pre-operative localization data from all patients were compiled. Moreover, the efficacy and safety of the two methods were evaluated according to localization success rates and localization-related complications.ResultsThe success rate of localization in the medical glue group was 100% while 97.3% in the hook-wire group. After localization of the pulmonary nodules, the incidence of minor pneumothorax in the medical glue group (11.9%) was lower than that in the hook-wire group (37.8%) (p=0.01). The incidence of mild pulmonary parenchymal hemorrhage in the medical glue group (13.1%) was also lower than that in the hook-wire group (24.3%) (p=0.000). The mean time from the completion of localization to the start of surgery was also longer in the medical glue group than in the hook-wire group (p=0.000). The mean visual analog scale (VAS) scores after localization were higher in the hook-wire group than in the medical glue group (p=0.02). In both groups, parenchymal hemorrhage was significantly associated with the needle length in hook-wire localization and the depth of the medical glue in the lung parenchyma (p = 0.009 and 0.001, respectively).ConclusionThese two localization methods are safe and effective in pre-operative pulmonary nodule localization. The medical glue localization method had a lower risk of complications, a higher localization success rate, less pain after localization and more flexibility in the arrangement of operation time.
Review: Precise sarcoma patient-derived orthotopic xenograft (PDOX) mouse models enable identification of novel effective combination therapies with the cyclin-dependent kinase inhibitor palbociclib: A strategy for clinical application
Authors: Higuchi Takashi , Igarashi Kentaro , Yamamoto Norio , Hayashi Katsuhiro , Kimura Hiroaki , Miwa Shinji , Bouvet Michael , Tsuchiya Hiroyuki , Hoffman Robert M. 
Published: August 2022

IntroductionSarcomas are rare heterogeneous malignant tumors that originate and develop in soft tissue or bone. Effective treatment for sarcomas is still limited to traditional chemotherapy and surgery that are often ineffective for recurrent disease. Cyclin-dependent kinases (CDKs) promote abnormal cell cycling and cell division in many cancers including sarcomas. Therefore, our hypothesis was that CDK inhibitors may be useful candidates for sarcoma treatment. Patient-derived orthotopic xenograft (PDOX) mouse models mimic the clinical disease for all major cancer types and have identified effective treatments that hold much clinical promise. The present report reviews sarcoma PDOX models that we have established for their potential to discover effective combination treatments based on CDK inhibitors for recalcitrant sarcoma.MethodsWe have previously reported six sarcoma PDOX studies evaluating the CDK inhibitor palbociclib on sarcoma, including osteosarcoma, Ewing sarcoma, de-differentiated liposarcoma, and peritoneal metastatic leiomyosarcoma.ResultsPalbociclib monotherapy significantly inhibited, but not regressed, the PDOX growth of osteosarcoma, Ewing sarcoma, de-differentiated liposarcoma, and peritoneal metastatic leiomyosarcoma. A combination of palbociclib and a mammalian target of rapamycin (mTOR) inhibitor, everolimus, significantly inhibited, but did not regress, the PDOX growth of osteosarcoma. Combinations of palbociclib with a multikinase inhibitor, sorafenib, and palbociclib combined with recombinant methioninase were effective and regressed the osteosarcoma and de-differentiated liposarcoma PDOX models, respectively.ConclusionsNovel effective drug combinations using the CDK inhibitor palbociclib were identified in PDOX models of the major types of sarcomas. Methionine restriction effected by methioninase increased the efficacy of palbociclib. Combination therapy with palbociclib is a promising future strategy for improved sarcoma therapy in the clinic.