bluuebunny/crossref_metadata_2025_split huggingface dataset:
Better CRT Response in Patients Who Underwent Atrioventricular Node Ablation or Upgrade From Pacemaker: A Nomogram to Predict CRT Response
Authors: Xiao Pei-Lin , Cai Cheng , Zhang Pei , Han Jie , Mulpuru Siva K. , Deshmukh Abhishek J. , Yin Yue-Hui , Cha Yong-Mei 
Published: November 2021

Background: Response rates for cardiac resynchronization therapy (CRT) in patients without intrinsic left bundle-branch block (LBBB) morphology are poor.Objective: We sought to develop a nomogram model to predict response to CRT in patients without intrinsic LBBB.Methods: We searched electronic health records for patients without intrinsic LBBB who underwent CRT at Mayo Clinic. Logistic regression and Cox proportional hazards regression analysis were performed for the odds of response to CRT and risk of death, respectively. Results were used to develop the nomogram model.Results: 761 patients without intrinsic LBBB were identified. Six months after CRT, 47.8% of patients demonstrated improvement of left ventricular ejection fraction by more than 5%. The 1-, 3-, and 5-year survival rates were 95.9, 82.4, and 66.70%, respectively. Patients with CRT upgrade from pacemaker [odds ratio (OR), 1.67 (95% CI, 1.05–2.66)] or atrioventricular node (AVN) ablation [OR, 1.69 (95% CI, 1.09–2.64)] had a greater odds of CRT response than those patients who had new implant, or who did not undergo AVN ablation. Patients with right bundle-branch block had a low response rate (39.2%). Patients undergoing AVN ablation had a lower mortality rate than those without ablation [hazard ratio, 0.65 (95% CI, 0.46–0.91)]. Eight clinical variables were automatically selected to build a nomogram model and predict CRT response. The model had an area under the receiver operating characteristic curve of 0.71 (95% CI, 0.63–0.78).Conclusions: Among patients without intrinsic LBBB undergoing CRT, upgrade from pacemaker and AVN ablation were favorable factors in achieving CRT response and better long-term outcomes.
Preoperative Liver Function Test Abnormalities Were Associated With Short-Term and Long-Term Prognosis in Cardiac Surgery Patients Without Liver Disease
Authors: Shang Liqun , Ao Yuanhan , Lv Linhua , Lv Lihua , Zhang Yubi , Hou Jian , Yao Jianping , Wu Zhongkai 
Published: November 2021

Aims: To explore the value of preoperative liver function tests (LFTs) for the prognosis of cardiac surgery patients without liver disease.Methods: The Medical Information Mart for Intensive Care III (MIMIC-III) database was used to extract the clinical data. Adult cardiac patients (≥18 years) without liver disease in the database were enrolled. The association of LFTs with the time of hospital stay and ICU stay was analyzed with the Spearman correlation. Survival curves were estimated using the Kaplan-Meier method and compared by the log-rank test. Multivariable logistic regression was used to identify LFTs that were independent prognostic factors of mortality.Results: A total of 2,565 patients were enrolled in this study. Albumin (ALB) was negatively associated with the time of hospital stay and ICU stay, while alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin were positively associated with the time of hospital stay and ICU stay (all p &lt; 0.001). Abnormal ALB, ALT, AST, and total bilirubin were associated with lower 90-day and 4-year survival (all p &lt; 0.001) and could be used as independent risk factors for hospital mortality and 90-day mortality. However, only ALB and total bilirubin were independent risk factors for 4-year mortality.Conclusion: Preoperative LFT abnormalities were associated with short-term and long-term prognosis of cardiac surgery patients without liver disease.
Systematical Evaluation of Three Gridded Daily Precipitation Products Against Rain Gauge Observations Over Central Asia
Authors: Dilinuer Tuoliewubieke , Yao Junqiang , Chen Jing , Zhao Yong , Mao Weiyi , Li Jiangang , Yang Lianmei 
Published: November 2021

Understanding the precipitation variability and extreme precipitation over arid Central Asia (CA) has largely been hampered by the lack of daily precipitation observations. The gridded precipitation datasets over CA are large discrepancies. Here, three gauge-based gridded daily precipitation products from Asian Precipitation Highly-Resolved Observational Data Integration Towards Evaluation (APHRODITE), Global Precipitation Climatology Center (GPCC), and Climate Prediction Center Based Analysis of Global Daily Precipitation (CPC_global) were assessed and compared with 49 rain gauge daily observations precipitation (OBS) from January 1985 to December 2015 using different time-scales over CA and different climate regimes, specifically Northern CA with temperate continental climate (NCA), Southwestern CA with dry arid desert climate (SWCA), and Southeastern CA with Mediterranean continental climate (SECA). Four accuracy indices [correlation coefficient (R), Bias, root mean square error (RMSE), and relative bias (RBias)] were employed to evaluate the performance of the three products in depicting the spatiotemporal features of precipitation variation over CA at multiple time scales (including daily, monthly, seasonal, and yearly). The mean annual and daily precipitation of OBS and three gridded products exhibit the trend of a gradual precipitation decreased from SECA to NCA and SWCA. The best overall performance was obtained for APHRODITE and GPCC for daily and annual time-scale, whereas CPC shows noticeable underestimation precipitation in SECA. The monthly precipitation depicted distinct features with a bimodal pattern with a peak in March and another in December, include the SECA and SWCA regions. In contrast, precipitation was concentrated in summer with the peak in July over the NCA region. At monthly scale terms, APHRODITE was more accurate in the wet seasons (winter and spring months) in SWCA and SECA. Additionally, GPCC has fairly better capability in summer months in NCA. Considering the spatial distribution, the bias variability was largerly in mountainous areas than in the plains. Temporally, the bias largerly in the dry seasons than in the wet seasons. At the interannual variability scale, GPCC was capable of qualitatively increasing the CA (NCA and SECA) precipitation during the last 21 years, while APHRODITE underestimated the trends. The CPC overestimated the precipitation trends over all regions. This study can serve as a reference for selecting daily precipitation products with low densities of stations, complex topographies, and similar climatic regions.
Single-Cell Transcriptomic Analysis of Ecosystems in Papillary Thyroid Carcinoma Progression
Authors: Yan Ting , Qiu Wangwang , Weng Huaiyu , Fan Youben , Zhou Guangwen , Yang Zhili 
Published: November 2021

BackgroundDespite extensive research, the papillary thyroid carcinoma (PTC) ecosystem is poorly characterized and, in particular, locoregional progression. Available evidence supports that single-cell transcriptome sequencing (Sc-RNA seq) can dissect tumor ecosystems.MethodsTissue samples from one PTC patient, including matched primary tumor (Ca), lymph node (LN) metastasis, and paracancerous tissue (PCa), were subjected to Sc-RNA seq with 10×Genomics. Dual-label immunofluorescence and immunohistochemistry were used to confirm the existence of cell subtypes in a separate cohort.Results11,805 cell transcriptomes were profiled, cell landscapes of PTC were composed of malignant follicular epithelial cells (MFECs), CD8+ and CD4+ T cells, B cells, vascular endothelial cells, fibroblasts and cancer-associated fibroblasts (CAFs). Between Ca and LN ecosystems, the proportions of MFEC and interstitial cells were similar, less than 1/25(229/6,694, 361/3,895), while the proportion of normal follicular epithelial cells (NFECs) and interstitial cells was &gt; 2 in PCa (455/171). NFECs in PCa formed a separate cluster, while MFECs in Ca and LN exhibited a profound transcriptional overlap, and the interstitial cells among these samples had an overall concordance in their identity and representation, albeit with some distinctions in terms of the cell percentage per subset. A fraction of the B cell subpopulation in Ca expressed inhibitory receptors, while their respective ligand genes were clearly transcribed in T cell and malignant epithelial cell clusters, while some CD8+ T cells in both Ca and LN produced high levels of inhibitory receptors whose respective ligands were overexpressed in some CD4+ T cells. Three CAF subtypes in Ca and LN were identified, which may be due to mutual transitions.ConclusionsOur data provide new insights into the PTC ecosystem and highlight the differences in ecosystems in PTC progression, which updates our understanding of PTC biology and will improve individualized patient treatment.
Dietary Modification for Reproductive Health in Women With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis
Authors: Shang Yujie , Zhou Huifang , He Ruohan , Lu Wentian 
Published: November 2021

ObjectiveDiet has been reported as the first-line management of polycystic ovary syndrome (PCOS). However, the relationship between diet and fertility in PCOS is still controversial. This meta-analysis aimed to evaluate whether diet could promote reproductive health in women with PCOS while providing evidence-based nutrition advice for clinical practice.MethodsSeven databases, including Cochrane Central Register of Controlled Trials, PubMed, Embase, Web of Science, and some Chinese database, were searched up to January 31, 2021. Randomized controlled trials evaluating the effects of diet in women with PCOS were included. Based on a preregistered protocol (PROSPERO CRD42019140454), the systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Two reviewers made study selection, data extraction and bias assessment independently. Risk ratios and mean difference with 95% confidence intervals were assessed by a random-effects model. Statistical heterogeneity within comparisons was evaluated by Cochran’s Q test and quantified by the I-squared (I2) statistic.ResultsTwenty RCTs with 1113 participants were included. Results showed diet significantly related to improved fertility outcomes (increasing clinical pregnancy, ovulation and menstrual regularity rate; reducing miscarriage rate), reproductive endocrine [increasing sex hormone-binding globulin (SHBG); decreasing Anti-Müllerian Hormone (AMH), free androgen index (FAI), total testosterone (T)] and clinical hyperandrogenism (hirsutism assessed by Ferriman-Gallwey score) in PCOS. Specifically, subgroup analyses indicated low-carbohydrate diets were superior in optimizing reproductive outcomes and calorie restriction was critical in ameliorating hyperandrogenism. Additionally, the positive effects were associated with the treatment duration. The longer the duration, the greater the improvement was.ConclusionOverall, diet is an effective intervention for improving fertility health, thus professional and dynamic dietary advice should be offered to all PCOS patients, based on the changeable circumstances, personal needs and expectations of the individuals.
Distinct Genetic Structure Reflects Ploidy Level Differentiation in Newly Discovered, Extremely Small Populations of Xanthocyparis vietnamensis from Southwestern China
Authors: Jiang Yuliang , Ju Tsam , Neaves Linda E. , Li Jialiang , Tan Weining , Huang Yusong , Liu Yan , Mao Kangshan 
Published: November 2021

Population genetic assessment is crucial for the conservation and management of threatened species.Xanthocyparis vietnamensisis an endangered species that is currently restricted to karst mountains in southwestern China and Vietnam. This rare conifer was first recorded in 2002 from northern Vietnam and then in 2013 from Guangxi, China, yet nothing is known about its genetic diversity nor ploidy level variation, although previous cytological study suggest that Vietnamese populations are tetraploids. There have been about 45 individuals found to date in Guangxi, China. Here, we genotyped 33X. vietnamensisindividuals using 20 newly developed, polymorphic microsatellite loci, to assess the genetic variability of its extremely small populations. The genetic diversity ofX. vietnamensis(HE= 0.511) was lower than that of two other heliophile species,Calocedrus macrolepisandFokienia hodginsii, which have similar distribution ranges. This is consistent with the signature of a genetic bottleneck detected inX. vietnamensis. Although the population genetic differentiation coefficient across loci is moderate (FST= 0.125), STRUCTURE analysis revealed two distinct genetic clusters, namely the northern and southern population groups; DAPC analysis grouped the southern populations together in one cluster separate from the northern populations; AMOVA analysis detected a significant genetic differentiation between the two population groups (FRT= 0.089,p&lt; 0.05), and BARRIER analysis detected a genetic barrier between them. Moreover, we detected differentiation in ploidy level between northern and southern populations, sampled individuals from the former and the later are all diploid and tetraploid cytotypes with mean genome sizes of 26.08 and 48.02 pg/2C, respectively. We deduced that heterogeneous geomorphology and historical events (e.g., human deforestation, Quaternary climate oscillations) may have contributed to population fragmentation and small population size inX. vietnamensis. Considering both genetic and ploidy level differentiation, we propose that two different management units (northern and southern) should be considered and a combination ofin situandex situconservation measures should be employed to preserve populations of this endangered species in southwestern China in the light of our findings.
Low APOA-1 Expression in Hepatocellular Carcinoma Patients Is Associated With DNA Methylation and Poor Overall Survival
Authors: Guo Yingyun , Huang Binglu , Li Ruixue , Li Jiao , Tian Shan , Peng Cheng , Dong Weiguo 
Published: November 2021

Background: Hepatocellular carcinoma (HCC) is the most frequent fatal malignancy, and it has a poor prognosis. Apolipoprotein 1 (APOA-1), the main protein component of high-density lipoproteins, is involved in numerous biological processes. Thus, this study was performed to detect the clinical significance of APOA-1 mRNA, APOA-1 expression, and APOA-1DNA methylation in patients with HCC.Methods: Data mining was performed using clinical and survival data from the Cancer Genome Atlas (TCGA) and Oncomine databases. The serum concentration of APOA-1 was measured in 316 patients with HCC and 100 healthy individuals at Renmin Hospital of Wuhan University, and the intact clinical information was reviewed and determined using univariate and multivariate Cox hazard models.Results: Bioinformatic analysis revealed that APOA-1 mRNA was present at lower levels in the serum of patients with HCC than in that of healthy individuals, and there was a strong negative correlation between levels of APOA-1 mRNA and APOA-1 DNA methylation. High expression of APOA-1 transcription correlated with better overall survival (p = 0.003), and APOA-1 hypermethylation correlated with progress-free survival (p = 0.045) in HCC sufferers. Next, the clinical data analysis demonstrated that APOA-1 protein levels in the serum were significantly lower in patients with HCC than in healthy controls. Furthermore, the expression of APOA-1 was significantly associated with some significant clinical indexes, and elevated APOA-1 expression was significantly associated with favorable (OS; HR:1.693, 95% CI: 1.194–2.401, p = 0.003) and better progression-free survival (PFS; HR = 1.33, 95% CI = 1.194–2.401, p = 0.045). Finally, enrichment analysis suggested that co-expressed genes of APOA-1 were involved in lipoprotein metabolism and FOXA2/3 transcription factor networks.Conclusion: APOA-1 mRNA expression is negatively regulated by DNA methylation in HCC. Low expression of APOA-1 might be a potential risk biomarker to predict survival in patients with HCC.
DC-SIGN Mediates the Interaction Between Neutrophils and Leishmania amazonensis-Infected Dendritic Cells to Promote DC Maturation and Parasite Elimination
Authors: Tiburcio Rafael , Melo Léon Dimitri , Nunes Sara , Barbosa Ana Luísa Augusto , de Oliveira Elaine Carvalho , Suarez Martha , Borges Valéria M. , Tavares Natalia , Brodskyn Claudia Ida 
Published: November 2021

BackgroundLeishmaniasis is a neglected arthropod-borne disease that affects millions of people worldwide. Successful Leishmania infections require the mitigation of immune cell functions leading to parasite survival and proliferation. A large body of evidence highlights the involvement of neutrophils (PMNs) and dendritic cells (DCs) in the establishment of immunological responses against these parasites. However, few studies, contemplate to what extent these cells interact synergistically to constrain Leishmania infection.ObjectiveWe sought to investigate how PMNs and infected DCs interact in an in vitro model of Leishmania amazonensis infection.Material and MethodsBriefly, human PMNs and DCs were purified from the peripheral blood of healthy donors. Next, PMNs were activated with fibronectin and subsequently co-cultured with L. amazonensis-infected DCs.ResultsWe observed that L. amazonensis-infected DC exhibited lower rates of infection when co-cultivated with either resting or activated PMNs. Surprisingly, we found that the release of neutrophil enzymes was not involved in Leishmania killing. Next, we showed that the interaction between PMNs and infected-DCs was intermediated by DC-SIGN, further suggesting that parasite elimination occurs in a contact-dependent manner. Furthermore, we also observed that TNFα and ROS production was dependent on DC-SIGN-mediated contact, as well as parasite elimination is dependent on TNFα production in the co-culture. Finally, we observed that direct contact between PMNs and DCs are required to restore the expression of DC maturation molecules during L. amazonensis infection.ConclusionOur findings suggest that the engagement of direct contact between PMNs and L. amazonensis-infected DC via DC-SIGN is required for the production of inflammatory mediators with subsequent parasite elimination and DC maturation.
Immune Profiling of Cord Blood From Preterm and Term Infants Reveals Distinct Differences in Pro-Inflammatory Responses
Authors: Anderson Jeremy , Thang Cao Minh , Thanh Le Quang , Dai Vo Thi Trang , Phan Van Thanh , Nhu Bui Thi Hong , Trang Do Ngoc Xuan , Trinh Phan Thi Phuong , Nguyen Thuong Vu , Toan Nguyen Trong , Harpur Christopher M. , Mulholland Kim , Pellicci Daniel G. , Do Lien Anh Ha , Licciardi Paul V. 
Published: November 2021

BackgroundPreterm infants are highly vulnerable to infectious disease. While many factors are likely to contribute to this enhanced susceptibility, the immature nature of the preterm immune system is postulated as one key factor.MethodsIn our study, we used high-dimensional flow cytometry and cytokine assays to characterise the immune profiles in 25 preterm (range: 30.4-34.1 weeks gestational age) and 25 term infant (range: 37-40 weeks gestational age) cord blood samples.ResultsWe found that preterm infants exhibit reduced frequencies of monocytes, CD56bright NK cells, CD8+ T-cells, γδ T-cells and an increased frequency of intermediate monocytes, CD4+ T-cells, central memory CD4+ and CD8+ T-cells, Tregs and transitional B-cells compared to term infants. Pro-inflammatory cytokines IL-1β, IL-6 and IL-17A were lower in preterm infants in addition to chemokines IL-8, eotaxin, MIP-1α and MIP-1β. However, IL-15 and MCP-1 were higher in preterm infants.ConclusionOverall, we identify key differences in pro-inflammatory immune profiles between preterm and term infants. These findings may help to explain why preterm infants are more susceptible to infectious disease during early life and facilitate the development of targeted interventions to protect this highly vulnerable group.
Effects of SGLT2 Inhibitors on Renal Outcomes in Patients With Chronic Kidney Disease: A Meta-Analysis
Authors: Li Ning , Lv Dan , Zhu Xiangjun , Wei Ping , Gui Yuan , Liu Shijia , Zhou Enchao , Zheng Min , Zhou Dong , Zhang Lu 
Published: November 2021

Introduction: The effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on renal outcomes in patients with chronic kidney disease (CKD) were initially demonstrated in recent trials. However, the magnitude of renal benefits for CKD patients with different baseline features and underlying diseases remains unclear.Method: We systematically searched the Embase, PubMed, Web of Science, and Cochrane library databases from inception to April 15, 2021 to identify eligible trials. The primary outcome was a composite of worsening kidney function, end-stage kidney disease (ESKD), or renal death. Efficacy and safety outcomes were stratified by baseline features, such as type 2 diabetes, heart failure, atherosclerotic cardiovascular disease, proteinuria, and renal function.Results: A total of nine studies were included. These studies included 25,749 patients with estimated glomerular filtration rate (eGFR)&lt;60 mL/min/1.73 m2 and 12,863 patients with urine albumin-to-creatinine ratio (UACR) &gt;300 mg/g. SGLT2 inhibitors reduced the risk of the primary renal outcome by 30% in patients with eGFR&lt;60 mL/min/1.73 m2 (HR 0.70, [95% CI 0.58–0.83], I2 = 0.00%) and by 43% in patients with UACR &gt; 300 mg/g (HR 0.57, [95% CI 0.48–0.67], I2 = 16.59%). A similar benefit was observed in CKD patients with type 2 diabetes. SGLT2 inhibitors had no clear effects on renal outcomes in patients with eGFR&lt;60 mL/min/1.73 m2 combined with atherosclerotic cardiovascular disease (HR 0.74, [95% CI 0.51–1.06], I2 = 0.00%). However, they reduced the risk of major renal outcomes by 46% (HR 0.54, [95% CI 0.38–0.76], I2 = 0.00%) in patients with atherosclerotic cardiovascular disease and macroalbuminuria (defined as UACR &gt; 300 mg/g). SGLT2 inhibitors did not significantly reduce the risk of major renal outcomes in CKD patients with heart failure (eGFR&lt;60 mL/min/1.73 m2: HR 0.81, [95% CI 0.47–1.38], I2 = 0.00%; UACR &gt; 300 mg/g: HR 0.66, [95% CI 0.41–1.07], I2 = 0.00%). SGLT2 inhibitors showed consistent renal benefits across different levels of eGFR (P interaction = 0.48).Conclusion: SGLT2 inhibitors significantly reduced the risk of the primary outcome in CKD patients. However, for patients with different features and underlying diseases, there exists differences in the renal protective effect.
Biomarker and Companion Diagnostics—A Review of Medicinal Products Approved by the European Medicines Agency
Authors: Orellana García Laura Patricia , Ehmann Falk , Hines Philip A. , Ritzhaupt Armin , Brand Angela 
Published: November 2021

Background: An increasing number of medicines authorised in Europe recommend or require biomarker-based patient selection. For some of these the use of a companion diagnostic (CDx), a subset of in vitro diagnostics (IVDs), to identify patient populations eligible for a specific medicinal product may be required. The information and recommendations of use of a medicinal product for which a CDx is required is particularly important to healthcare professionals for correct patient identification.Methods: We reviewed the existing information in SmPCs and European Public Assessment Reports (EPARs) of EU medicinal products approved via the centralised procedure at EMA where reference was made to biomarker testing, including by CDx, for patient selection.Results: The results show that varying levels of detail are provided for the biomarker and the diagnostic test, including variability in where the information was presented. The overall results demonstrate transparent but sometimes heterogeneous reporting of CDx in the SmPC and EPAR.Conclusions: With the introduction of the new Regulation (EU) 2017/746 on in vitro diagnostic medical devices, medicines regulatory authorities' will be required to be consulted during the review of CDx conformity assessment and so, there is opportunity for more consistent and transparent information on CDx to be provided in the SmPC and EPAR.