bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma exosomal IRAK1 can be a potential biomarker for predicting the treatment response to renin-angiotensin system inhibitors in patients with IgA nephropathy
Authors: Wu Jianping , Wei Xiaona , Li Jiajia , Gan Yangang , Zhang Rui , Han Qianqian , Liang Peifen , Zeng Yuchun , Yang Qiongqiong 
Published: August 2022

BackgroundRenin-angiotensin system inhibitors (RASi) are the first choice and basic therapy for the treatment of IgA nephropathy (IgAN) with proteinuria. However, approximately 40% of patients have no response to RASi treatment. The aim of this study was to screen potential biomarkers for predicting the treatment response of RASi in patients with IgAN.MethodsWe included IgAN patients who were treatment-naive. They received supportive treatment, including a maximum tolerant dose of RASi for 3 months. According to the degree of decrease in proteinuria after 3 months of follow-up, these patients were divided into a sensitive group and a resistant group. The plasma of the two groups of patients was collected, and the exosomes were extracted for high-throughput sequencing. The screening of hub genes was performed using a weighted gene co-expression network (WGCNA) and filtering differentially expressed genes (DEGs). We randomly selected 20 patients in the sensitive group and 20 patients in the resistant group for hub gene validation by real-time quantitative polymerase chain reaction (qRT−PCR). A receiver operating characteristic (ROC) curve was used to evaluate hub genes that predicted the efficacy of the RASi response among the 40 validation patients.ResultsAfter screening 370 IgAN patients according to the inclusion and exclusion criteria and the RASi treatment response evaluation, there were 38 patients in the sensitive group and 32 patients in the resistant group. IRAK1, ABCD1 and PLXNB3 were identified as hub genes by analyzing the high-throughput sequencing of the plasma exosomes of the two groups through WGCNA and DEGs screening. The sequencing data were consistent with the validation data showing that these three hub genes were upregulated in the resistant group compared with the sensitive group. The ROC curve indicated that IRAK1 was a good biomarker to predict the therapeutic response of RASi in patients with IgAN.ConclusionsPlasma exosomal IRAK1 can be a potential biomarker for predicting the treatment response of RASi in patients with IgAN.
Cascading effects of calanoid copepod functional groups on the biological carbon pump in the subtropical South Atlantic
Authors: Oliveira Lívia Dias Fernandes de , Bode-Dalby Maya , Schukat Anna , Auel Holger , Hagen Wilhelm 
Published: August 2022

Life strategies, ecophysiological performances and diel vertical migration (DVM) of zooplankton key species affect the efficiency and strength of the biological carbon pump (BCP). However, it is unclear to what extent different functional groups affect the BCP. Depth-stratified day and night samples (0-800 m) from the subtropical South Atlantic were analyzed focusing on the calanoid copepod community. Calanoid abundance, biomass distribution and species-specific impact on the passive (fecal pellets) and active (via DVM) vertical flux of carbon were determined. Species were assigned to different migrant groups where, their contributions were estimated by using the proportion of the migratory community instead of simple day-night differences in biomass. This novel approach leads to more robust flux estimates, particularly for small sample sizes. According to migration ranges and day/night residence depth, functional groups were characterized, i.e. small- and large-scale epipelagic and mesopelagic migrants. Epipelagic small-scale migrants transported respiratory (1.5 mg C m-2 d-1) and fecal pellet (1.1 mg C m-2 d-1) carbon from the upper to the lower epipelagic zone, where the latter can fuel the microbial loop, and thus deep chlorophyll maxima, or be ingested by other zooplankton. Large-scale migrants actively transported up to 10.5 mg C m-2 d-1 of respiratory carbon from the epipelagic layer into the twilight zone. The majority was transported by Pleuromamma borealis (5.7 mg C m-2 d-1) into the upper mesopelagic. In addition, up to 8.0 mg C m-2 d-1 was potentially egested as fecal material by large-scale zone shifters. Mesopelagic migrants transported respiratory (0.2 mg C m-2 d-1) and fecal pellet carbon (0.1 mg C m-2 d-1) even deeper into the ocean. Community consumption of migrants in the epipelagic layer during the night was 98 mg C m-2 d-1, while non-migrants consumed 98-208 mg C m-2 d-1 in the epipelagic zone, with a potential subsequent egestion of 29-62 mg C m-2 d-1. This carbon may fuel omnivorous-detritivorous feeding, the microbial loop and/or may sink as fecal pellets. This case study shows how calanoid functional groups mediate carbon fluxes in the subtropical South Atlantic Ocean and demonstrates how detailed community analyses can elucidate the complexity of pelagic carbon budgets.
In vivo imaging of tau deposition in Alzheimer’s disease using both [18F]-THK5317 and [18F]-S16: A pilot human study
Authors: Fu Liping , Zhang Jinming , Zhou Kaixiang , Zhang Xiaojun , Xie Hengge , Zhu Mingwei , Cui Mengchao , Wang Ruimin 
Published: August 2022

ObjectiveTo evaluate the effectiveness of a new tracer (S)-1-(4-(6-(dimethylamino)quinoxalin-2-yl)phenoxy)-3-fluoropropan-2-ol ([18F]-S16), in distinguishing patients with AD from HCs.MethodsPaired [18F]-S16 and [18F]-THK5317 scans were acquired in five patients with AD, six HCs, one subject with a semantic variant of primary progressive aphasia (sv-PPA) and one subject with probable progressive supranuclear palsy (PSP). Dynamic PET scanning was performed over 90 min after injection of the tracers. Standardized uptake values (SUV) and cortical-to-cerebellum standardized uptake value ratios (SUVRs) were used for tau deposition semi-quantization. A voxel-based analysis was employed to assess the uptake difference between populations.Results[18F]-S16 exhibited excellent blood-brain-barrier penetration. AD patients showed increased cortical [18F]-THK5317 and [18F]-S16 binding. Compared to HCs, AD patients showed significantly increased cortical [18F]-S16 uptake in the bilateral occipital cortex, posterior cingulated cortex/precuneus, and lateral frontal cortex. Notable [18F]-S16 uptake was observed in the basal ganglia and brainstem compared to the neocortex. A substantial [18F]-S16 signal was detected in the basal ganglia and midbrain in a patient with probable PSP and in the bilateral anterior temporal cortex in a sv-PPA patient.Conclusion[18F]-S16 might be of help to detect tau protein in vivo.
Theory of Mind in migraine and medication-overuse headache: A cross-sectional study
Authors: Romozzi Marina , Di Tella Sonia , Rollo Eleonora , Quintieri Paolo , Silveri Maria Caterina , Vollono Catello , Calabresi Paolo 
Published: August 2022

BackgroundTheory of Mind (ToM) is the ability to predict and anticipate others' behaviors through the mental state attribution process. This study aims to investigate the ToM in patients with medication-overuse headache (MOH) and episodic migraine (EM) and to compare it with healthy controls (HC).MethodsThis study enrolled patients with MOH, patients with EM, and HC. ToM was assessed through the Theory of Mind Assessment Scale (ThOMAS), which includes four subscales: Scale A, I-Me, Scale B, Other-Self, Scale C, I-Other, and Scale D, Other-Me, through the Reading the Mind in the Eyes test (RMET), which measures complex emotion recognition, and through the Toronto Alexithymia Scale (TAS-20), which measures alexithymia. Concomitant psychiatric disturbances were evaluated through the Hamilton Anxiety Rating Scale, the Hamilton Depression Rating Scale, and the Dissociative Experiences Scale-II.ResultsThe study involved 21 patients with EM, 22 patients with MOH, and 18 HC. In all the four subscales of the ThOMAS, there was a significant difference between HC, EM, and MOH patients: Scale A (p = 0.009), Scale B (p = 0.004), Scale C (p = 0.039), and Scale D (p = 0.008). In the RMET, MOH patients had worse performances than EM patients and HC (p = 0.039). MOH group exhibited higher levels of alexithymia when compared to the HC (p = 0.033) and higher levels of anxiety than HC (p = 0.001).ConclusionMOH patients showed a subtle psychopathological pattern characterized by impaired social adaptation.
Socioeconomic deprivation and survival outcomes in primary central nervous system lymphomas
Authors: Deng Xiangyang , Yang Xionggang , Yang Chunlei , Chen Kezhu , Ren Junwei , Zeng Jun , Zhang Quan , Li Tianwen , Tang Qisheng , Zhu Jianhong 
Published: August 2022

ObjectiveTo our knowledge, the impact of area-level socioeconomic status (SES) has not yet been described in primary central nervous system lymphomas (PCNSLs). Current study sought to explore the association of socioeconomic deprivation, measured using the Area Deprivation Index (ADI), with PCNSL outcomes.MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was used to identify PCNSL patients diagnosed between 2006 and 2015 for our analyses. The impact of ADI on overall survival (OS) and cancer-specific survival (CSS) were investigated. Survival analyses were conducted using Kaplan-Meier method with log-rank tests. The Inverse Probability Weighting (IPW) analysis and multivariate cox proportional hazards regression analysis were employed to make covariate adjustments. Multiple mediation analysis (MMA) was performed to estimate the mediating effects.ResultsA total of 3159 PCNSL patients classified into low and high ADI subgroups according to the median ADI score were studied. The Kaplan-Meier analyses showed that low ADI was significantly associated with higher OS rates (HR 1.15, 95%CI 1.06-1.26, P&lt;0.01) and CSS rates (HR 1.15, 95%CI 1.05-1.27, P&lt;0.01). Similar results were observed in analyses adjusted via IPW and multivariate cox methods. Subgroup analyses revealed that ADI could remain a prognostic indictor among different subsets. MMA revealed that several factors including chemotherapy and HIV status making up about 40% of the overall effect, mediated PCNSL survival disparities related to the ADI. Finally, multivariable logistic regression analysis showed that ADI as well as several other factors were independently related to receipt of chemotherapy.ConclusionsOur study highlights the role of area-level SES in prognosis of PCNSLs. And several factors including chemotherapy and HIV status of PCNSL patents contributed to the CSS disparities between ADI subgroups were uncovered by MMA. Such relationships would highlight the importance of policies development to enhance healthcare delivery and promote awareness of HIV prevention and treatment in low-resource neighborhoods.
Machine learning prediction of prostate cancer from transrectal ultrasound video clips
Authors: Wang Kai , Chen Peizhe , Feng Bojian , Tu Jing , Hu Zhengbiao , Zhang Maoliang , Yang Jie , Zhan Ying , Yao Jincao , Xu Dong 
Published: August 2022

ObjectiveTo build a machine learning (ML) prediction model for prostate cancer (PCa) from transrectal ultrasound video clips of the whole prostate gland, diagnostic performance was compared with magnetic resonance imaging (MRI).MethodsWe systematically collated data from 501 patients—276 with prostate cancer and 225 with benign lesions. From a final selection of 231 patients (118 with prostate cancer and 113 with benign lesions), we randomly chose 170 for the purpose of training and validating a machine learning model, while using the remaining 61 to test a derived model. We extracted 851 features from ultrasound video clips. After dimensionality reduction with the least absolute shrinkage and selection operator (LASSO) regression, 14 features were finally selected and the support vector machine (SVM) and random forest (RF) algorithms were used to establish radiomics models based on those features. In addition, we creatively proposed a machine learning models aided diagnosis algorithm (MLAD) composed of SVM, RF, and radiologists’ diagnosis based on MRI to evaluate the performance of ML models in computer-aided diagnosis (CAD). We evaluated the area under the curve (AUC) as well as the sensitivity, specificity, and precision of the ML models and radiologists’ diagnosis based on MRI by employing receiver operator characteristic curve (ROC) analysis.ResultsThe AUC, sensitivity, specificity, and precision of the SVM in the diagnosis of PCa in the validation set and the test set were 0.78, 63%, 80%; 0.75, 65%, and 67%, respectively. Additionally, the SVM model was found to be superior to senior radiologists’ (SR, more than 10 years of experience) diagnosis based on MRI (AUC, 0.78 vs. 0.75 in the validation set and 0.75 vs. 0.72 in the test set), and the difference was statistically significant (p&lt; 0.05).ConclusionThe prediction model constructed by the ML algorithm has good diagnostic efficiency for prostate cancer. The SVM model’s diagnostic efficiency is superior to that of MRI, as it has a more focused application value. Overall, these prediction models can aid radiologists in making better diagnoses.
GREM1 is a novel serum diagnostic marker and potential therapeutic target for pancreatic ductal adenocarcinoma
Authors: Yang Sen , Zhang Yalu , Hua Yuze , Cui Ming , Wang Mengyi , Gao Junyi , Liu Qiaofei , Liao Quan 
Published: August 2022

ObjectivePancreatic ductal adenocarcinoma (PDAC) is a highly malignant neoplasm with rising incidence worldwide. Gremlin 1 (GREM1), a regulator of bone morphogenetic protein (BMP) signaling, fine-tunes extensive biological processes, including organ morphology, cellular metabolism, and multiple pathological developments. The roles of GREM1 in PDAC remain unknown.MethodsVarieties of public databases and online software were employed to analyze the expressions at transcription and protein levels of GREM1 in multiple malignant neoplasms including PDAC, and in addition, its potential pro-tumoral functions in PDAC were further evaluated. A total of 340 serum samples of pancreatic disease, including PDAC, low-grade malignant pancreatic neoplasm, benign pancreatic neoplasm, pancreatitis, and 132 healthy controls, were collected to detect GREM1. The roles of serum GREM1 in the diagnosis and prediction of survival of PDAC after radical resection were also analyzed.ResultsBioinformatics analyses revealed that GREM1 was overexpressed in PDAC and predicted a poorer survival in PDAC. A higher protein level of GREM1 in PDAC correlated with stroma formation and immunosuppression by recruiting varieties of immunosuppressive cells, including T regulatory cells (Tregs), M2 macrophages, myeloid-derived suppressor cells (MDSCs), and exhaustion T cells into the tumor microenvironment. A higher level of serum GREM1 was observed in PDAC patients, compared to healthy control (p &lt; 0.001). Serum GREM1 had a good diagnostic value (area under the curve (AUC) = 0.718, p &lt; 0.001), and its combination with carbohydrate antigen 199 (CA199) achieved a better diagnostic efficacy (AUC = 0.914, p &lt; 0.001), compared to CA199 alone. The cutoff value was calculated by receiver operating characteristic (ROC) analysis, and PDAC patients were divided into two groups of low and high GREM1. Logistic analyses showed serum GREM1 positively correlated with tumor size (hazard ratio (HR) = 7.097, p = 0.032) and histopathological grades (HR = 2.898, p = 0.014). High-level serum GREM1 (1,117.8 pg/ml) showed a shorter postoperative survival (p = 0.0394).ConclusionHigher intra-tumoral expression of GREM1 in PDAC contributes to tumor stroma and immunosuppressive tumor microenvironment, presenting its therapeutic potential. High-level serum GREM1 predicts poorer survival after resection. A combination of serum CA199 and GREM1 shows a stronger diagnostic efficacy in PDAC.
Prevalence and associated factors of psychosocial and behavioral problems in Indonesian adolescent students during the COVID-19 pandemic
Authors: Sutomo Retno , Ramadhani Fadhila Pratama Rizqi , Hanifa Intan Noor 
Published: August 2022

BackgroundThe COVID-19 pandemic and the subsequent measures to control it, such as social distancing, school closure, and online learning, put adolescent students at higher risk of psychosocial and behavioral problems (PSBP). The adverse potential is more concerning as the outbreak continues, especially in limited-resource countries, and requires further mitigation.ObjectiveTo assess the prevalence and factors associated with PSBP in Indonesian adolescent students in the COVID-19 pandemicSubject/methodsWe conducted a cross-sectional study in Yogyakarta Province, Indonesia, involving junior high school students. An anonymous online questionnaire in google form format was used to collect demographic data and the potential variables and screen the PSBP with the Strengths and Difficulties Questionnaire (SDQ). Logistic regression was applied to determine the independent variables.ResultsSix hundred seventy-six subjects participated, including 237 males (35.1%) and 439 females (64.9%). There were 34.6% subjects with PSBP, with a peer-relation problem as the most common one. The multivariable logistic regression showed that subjects with longer screen time duration and more family conflicts were more likely to have PSBP, with an adjusted odds ratio (OR) of 1.5 (95% CI: 1.1–2.1, p = 0.025) and 2.4 (95% CI: 1.5–3.8, p &lt; 0.001), respectively, whereas whom with better family cohesion are less likely to have the problem with an adjusted OR of 0.4 (95% CI: 0.3–0.6, p &lt; 0.001).ConclusionsThere is a high prevalence of PSBP among Indonesian adolescent students during the COVID-19 pandemic. Longer screen time duration and more family conflict are associated with higher prevalence, whereas better family cohesion with lower prevalence of PSBP.
Barriers and enablers to kangaroo mother care prior to stability from perspectives of Gambian health workers: A qualitative study
Authors: Cho Ying Chun , Gai Abdou , Diallo Brahima A. , Samateh Ahmadou Lamin , Lawn Joy E. , Martinez-Alvarez Melisa , Brotherton Helen 
Published: August 2022

AimsKangaroo mother care (KMC) is an evidence-based intervention recommended for stable newborns &lt;2,000 g. Recent trials have investigated survival benefits of earlier initiation of KMC, including prior to stability, with WHO's iKMC trial showing 25% relative risk reduction for mortality of neonates 1–1.8 kg at tertiary Indian and African neonatal units (NNU). However, evidence is lacking about how to safely deliver this intervention to the most vulnerable neonates in resource limited settings (RLS). Our study aimed to understand barriers and enablers for early KMC prior to stability from perspectives of neonatal health care workers (HCW) in a high neonatal mortality RLS.MethodsThis qualitative study was conducted at Edward Francis Small Teaching Hospital (EFSTH), the main neonatal referral unit in The Gambia. It was ancillary study to the eKMC clinical trial. Ten semi-structured interviews were conducted with all neonatal HCW cadres (4 nurses; 1 nurse attendant; 5 doctors; all Gambian). Study participants were purposively selected, and saturation was reached. Thematic analysis was conducted using Atun's conceptual framework for evaluation of new health interventions with methods to ensure data reliability and trustworthiness.ResultsHCW's perceptions of early KMC prior to stability included recognition of potential benefits as well as uncertainty about effectiveness and safety. Barriers included: Unavailability of mothers during early neonatal unit admission; safety concerns with concomitant intravenous fluids and impact on infection prevention control; insufficient beds, space, WASH facilities and staffing; and lack of privacy and respectful care. Enablers included: Education of HCW with knowledge transfer to KMC providers; paternal and community sensitization and peer-to-peer support.ConclusionsAddressing health systems limitations for delivery of KMC prior to stability is foundational with linkage to comprehensive HCW and KMC provider education about effectiveness, safe delivery and monitoring. Further context specific research into safe and respectful implementation is required from varied settings and should include perceptions of all stakeholders, especially if there is a shift in global policy toward KMC for all small vulnerable newborns.
Therapeutic effect of modified zengye decoction on primary Sjogren’s syndrome and its effect on plasma exosomal proteins
Authors: Zeng Yimin , Peng Xin , Wang Yun , Hou Lei , Ma Wukai , Yang Peng 
Published: August 2022

Background: Modified Zengye Decoction (MZD), a traditional Chinese medicine, is an effective treatment for patients with primary Sjögren’s syndrome (pSS).Purpose: To evaluate the efficacy of MZD and investigate its effect on plasma exosomal proteins.Methods: Eighteen pSS patients were treated with MZD for 2 weeks. The therapeutic effect was evaluated by observing the changes in clinical symptoms, laboratory parameters, and plasma cytokines before and after treatment. Then, the differentially expressed proteins (DEPs) in the plasma exosomes before and after treatment were identified via label-free proteomics, while Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the possible biological functions and signaling pathways involved in the exosomal DEPs.Results: MZD can effectively relieve the clinical symptoms of pSS patients, downregulate the plasma IgG and IgM levels, and inhibit plasma cytokine production. Thirteen DEPs were identified via label-free proteomics in the plasma exosomes before and after MZD treatment, of which 12 were downregulated proteins. GO analysis showed that these downregulated proteins were mainly related to the insulin response involved in dryness symptoms and the Gram-negative bacterial defense response and proteoglycan binding involved in infection. KEGG enrichment analysis showed that these downregulated proteins were primarily associated with the porphyrin metabolism involved in oteoarthrosis and the NF-κB and TLR4 pathways involved in infection.Conclusion: MZD can effectively alleviate SS symptoms, while its mechanism may be associated with the reduced protein expression in insulin response, porphyrin metabolism, and the TLR4/NF-κB pathway.