bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasonic Characteristics Improve Prediction of Central Lymph Node Metastasis in cN0 Unifocal Papillary Thyroid Cancer
Authors: Liu Yongchen , Huang Jianhao , Zhang Zhiyuan , Huang Yijie , Du Jialin , Wang Sanming , Wu Zeyu 
Published: June 2022

BackgroundPrediction of central lymph node metastasis (CLNM) is vital for clinical decision-making processes in clinically N0 (cN0) unifocal papillary thyroid carcinoma (PTC), but the sensitivity of preoperative detection of CLNM is limited. The aim of the present study was to determine whether there are ultrasonic (US) characteristics associated with CLNM.MethodsIn total, 1657 PTC patients (514 men and 1143 women) were enrolled in the present study between January 2018 and May 2021. The patients met the following inclusion criteria based on preoperative detection: suspected nodule confirmed as PTC by biopsy; the nodule was unifocal and less than 4 cm in diameter; no prior neck radiation exposure; no extrathyroidal extension; and no CLNM or distant metastases on imaging. All the enrolled patients underwent total thyroidectomy with prophylactic central lymph node dissection (CLND). A postoperative pathological diagnosis was made.ResultsCLNM was found in 58.4% of male patients and 36.9% of female patients. In univariate analysis, size, adjacent anterior capsule, distance to the lower pole and color Doppler flow imaging (CDFI) were considered risk factors for the male and female groups (p &lt; 0.05). In multivariate analyses, size, adjacent anterior capsule, distance to the lower pole and CDFI were independent risk factors for male patients. For females, the independent risk factors included size, adjacent anterior capsule, distance to the lower pole and CDFI.ConclusionIn the present cohort, US imaging characteristics, including size, adjacent anterior capsule, distance to the lower pole and CDFI, were identified to be potentially beneficial in preoperative clinical decision-making processes for cN0 unifocal PTC patients.
Genetically Predicted Milk Intake Increased Femoral Neck Bone Mineral Density in Women But Not in Men
Authors: Chen Song , Zheng Changhua , Chen Tianlai , Chen Jinchen , Pan Yuancheng , Chen Shunyou 
Published: June 2022

BackgroundCow milk contains more calcium, magnesium, potassium, zinc, and phosphorus minerals. For a long time, people have believed that increasing milk intake is beneficial to increasing bone density. Many confounding factors can affect milk consumption, and thus the association described to date may not be causal. We explored the causal relationship between genetically predicted milk consumption and Bone Mineral Density (BMD) of the femoral neck and lumbar spine based on 53,236 individuals from 27 studies of European ancestry using the Mendelian randomization (MR) study. 32,961 individuals of European and East Asian ancestry were used for sensitivity analysis.MethodsA genetic instrument used for evaluating milk consumption is rs4988235, a locus located at 13,910 base pairs upstream of the LCT gene. A Mendelian randomization (MR) analysis was conducted to study the effect of selected single nucleotide polymorphisms (SNPs) and BMD. The summary-level data for BMD of the femoral neck and lumbar spine were obtained from two GWAS meta-analyses [‘Data Release 2012’ and ‘Data Release 2015’ in the GEnetic Factors for OSteoporosis Consortium (GEFOS)].Resultswe found that genetically predicted milk consumption was not associated with FN-BMD(OR 1.007; 95% CI 0.991–1.023; P = 0.385), LS-BMD(OR 1.003; 95% CI 0.983–1.024; P = 0.743) by performing a meta-analysis of several different cohort studies. High levels of genetically predicted milk intake were positively associated with increased FN-BMD in Women. The OR for each additional milk intake increasing allele was 1.032 (95%CI 1.005–1.059; P = 0.014). However, no causal relationship was found between milk consumption and FN-BMD in men (OR 0.996; 95% CI 0.964–1.029; P = 0.839). Genetically predicted milk consumption was not significantly associated with LS-BMD in women (OR 1.017; 95% CI 0.991–1.043; P = 0.198) and men (OR 1.011; 95% CI 0.978–1.045; P = 0.523).ConclusionOur study found that women who consume more milk have a higher FN-BMD. When studying the effect of milk consumption on bone density in further studies, we need to pay more attention to women.
Clinical Characteristics of Patients With HNF1-alpha MODY: A Literature Review and Retrospective Chart Review
Authors: Zhao Qinying , Ding Li , Yang Ying , Sun Jinhong , Wang Min , Li Xin , Liu Ming 
Published: June 2022

The clinical manifestation of hepatocyte nuclear factor-1-alpha (HNF1-alpha) maturity-onset diabetes of the young (MODY) is highly variable. This study aims to investigate the clinical characteristics of patients with HNF1-alpha MODY in general, by geographical regions (Asian or non-Asian), HNF1-alpha mutations, and islet autoantibody status. A literature review and a chart review of patients with HNF1-alpha MODY were performed. The means and proportions from studies were pooled using the inverse variance method for pooling, and subgroup analyses were performed. A total of 109 studies involving 1,325 patients [41.5%, 95% confidence interval (CI): 35.2, 48.1; male] were identified. The mean age of diagnosis was 20.3 years (95% CI: 18.3–22.2), and the mean glycated hemoglobin was 7.3% (95% CI: 7.2–7.5). In comparison, Asian patients exhibited significantly higher HbA1c (p = 0.007) and 2-h post-load C-peptide (p = 0.012) levels and lower levels of triglyceride (TG) (p &lt; 0.001), total cholesterol (TC) (p &lt; 0.001), and high-density lipoprotein cholesterol (HDL-c) (p &lt; 0.001) and less often had macrovascular complications (p = 0.014). The age of diagnosis was oldest in patients with mutations in the transactivation domain (p &lt; 0.001). The levels of 2-h post-load C-peptide (p &lt; 0.001), TG (p = 0.007), TC (p = 0.017), and HDL-c (p = 0.001) were highest and the prevalence of diabetic neuropathy was lowest (p = 0.024) in patients with DNA-binding domain mutations. The fasting (p = 0.004) and 2-h post-load glucose (p = 0.003) levels and the prevalence of diabetic neuropathy (p = 0.010) were higher among patients with positive islet autoantibodies. The study demonstrated that the clinical manifestations of HNF1-alpha MODY differed by geographical regions, HNF1-alpha mutations, and islet autoantibody status.
Double Yields and Negative Emissions? Resource, Climate and Cost Efficiencies in Biofuels With Carbon Capture, Storage and Utilization
Authors: Jafri Yawer , Ahlström Johan M. , Furusjö Erik , Harvey Simon , Pettersson Karin , Svensson Elin , Wetterlund Elisabeth 
Published: June 2022

As fossil-reliant industries turn to sustainable biomass for energy and material supply, the competition for biogenic carbon is expected to intensify. Using process level carbon and energy balance models, this paper shows how the capture of residual CO2 in conjunction with either permanent storage (CCS) or biofuel production (CCU) benefits fourteen largely residue-based biofuel production pathways. With a few noteworthy exceptions, most pathways have low carbon utilization efficiencies (30–40%) without CCS/U. CCS can double these numbers and deliver negative emission biofuels with GHG footprints below −50 g CO2 eq./MJ for several pathways. Compared to CCS with no revenue from CO2 sequestration, CCU can offer the same efficiency gains at roughly two-third the biofuel production cost (e.g., 99 EUR/MWh vs. 162 EUR/MWh) but the GHG reduction relative to fossil fuels is significantly smaller (18 g CO2 eq./MJ vs. −99 g CO2 eq./MJ). From a combined carbon, cost and climate perspective, although commercial pathways deliver the cheapest biofuels, it is the emerging pathways that provide large-scale carbon-efficient GHG reductions. There is thus some tension between alternatives that are societally best and those that are economically most interesting for investors. Biofuel pathways vent CO2 in both concentrated and dilute streams Capturing both provides the best environomic outcomes. Existing pathways that can deliver low-cost GHG reductions but generate relatively small quantities of CO2 are unlikely to be able to finance the transport infrastructure required for transformative bio-CCS deployment. CCS and CCU are accordingly important tools for simultaneously reducing biogenic carbon wastage and GHG emissions, but to unlock their full benefits in a cost-effective manner, emerging biofuel technology based on the gasification and hydrotreatment of forest residues need to be commercially deployed imminently.
Statistical Analysis of the Weather Impact on Robusta Coffee Yield in Vietnam
Authors: Dinh Thi Lan Anh , Aires Filipe , Rahn Eric 
Published: June 2022

Weather and climate strongly impact coffee; however, few studies have measured this impact on robusta coffee yield. This is because the yield record is not long enough, and/or the data are only available at a local farm level. A data-driven approach is developed here to 1) identify how sensitive Vietnamese robusta coffee is to weather on district and provincial levels, 2) during which key moments weather is most influential for yield, and 3) how long before harvest, yield could potentially be forecasted. Robusta coffee yield time series were available from 2000 to 2018 for the Central Highlands, where 40% of global robusta coffee is produced. Multiple linear regression has been used to assess the effect of weather on coffee yield, with regularization techniques such as PCA and leave-one-out to avoid over-fitting the regression models. The data suggest that robusta coffee in Vietnam is most sensitive to two key moments: a prolonged rainy season of the previous year favoring vegetative growth, thereby increasing the potential yield (i.e., number of fruiting nodes), while low rainfall during bean formation decreases yield. Depending on location, these moments could be used to forecast the yield anomaly with 3–6 months’ anticipation. The sensitivity of yield anomalies to weather varied substantially between provinces and even districts. In Dak Lak and some Lam Dong districts, weather explained up to 36% of the robusta coffee yield anomalies variation, while low sensitivities were identified in Dak Nong and Gia Lai districts. Our statistical model can be used as a seasonal forecasting tool for the management of coffee production. It can also be applied to climate change studies, i.e., using this statistical model in climate simulations to see the tendency of coffee in the following decades.
Case Report: A Chinese Family of Hypertrophic Cardiomyopathy Caused by a Novel Splicing Mutation in the FLNC Gene
Authors: Huang Chunhui , Zheng Yonghong , Zhang Wei , Chen Zhigang , Huang Zhixin , Fang Yuan 
Published: June 2022

Hypertrophic cardiomyopathy (HCM) is a type of primary cardiomyopathy with genetic etiology, and it carries a high risk of diastolic dysfunction, heart failure, and malignant arrhythmias. We reported the first familial HCM in China, caused by a novel FLNC splicing mutation. We performed duo exome sequencing (ES) to examine the genome of the proband and his mother. For 10 days, a 15-year-old boy was presented to our hospital due to non–exercise-associated chest tightness and asthma. He was diagnosed with HCM [end-diastolic interventricular septal thickness was about 18 mm by transthoracic echocardiography (TTE)]. His mother and sister performed TTE to screen familial cardiomyopathy, which revealed hypertrophic cardiomyopathy only in the proband’s mother. In ES of the mother–son duo, we identified a novel heterozygous mutation of the FLNC gene (chr7:128492808, NM_001127487, c.5905+2T&gt;C, rs1808874360) as the candidate cause of autosomal dominant HCM. Sanger sequencing confirmed this novel mutation in the proband and his mother but absent in the proband’s sister. The potential impact of the novel mutation was predicted by MutationTaster, dbscSNV_ADA_SCORE, dbscSNV_RF_SCORE, CADD_phred, PhyloP20way_mammalian, PhyloP100way_vertebrate, SiPhy_29way_logOdds, and GERP++_RS software. After the administration of furosemide, spironolactone, and metoprolol, the proband’s heart function was improved, and symptoms were alleviated. We presented the first familial HCM caused by a novel FLNC splicing mutation via exome sequencing in China. Therefore, it is necessary that familial screening for patients with HCM should be performed for the early detection of HCM intervention in malignant cardiac events in advance and block genes.
A Novel Ferroptosis-Related LncRNA Pair Prognostic Signature Predicts Immune Landscapes and Treatment Responses for Gastric Cancer Patients
Authors: Li Jiazheng , Xiang Renshen , Song Wei , Wu Jing , Kong Can , Fu Tao 
Published: June 2022

Background: The construction of ferroptosis-related lncRNA prognostic models in malignancies has been an intense area of research recently. However, most of the studies focused on the exact expression of lncRNAs and had limited application values. Herein, we aim to establish a novel prognostic model for gastric cancer (GC) patients and discuss its correlation with immune landscapes and treatment responses.Methods: The present study retrieved transcriptional data of GC patients from the Cancer Genome Atlas (TCGA) database. We identified differentially expressed ferroptosis-related lncRNAs between tumor and normal controls of GC samples. Based on a new method of cyclically single pairing, we constructed a 0 or 1 matrix of ferroptosis-related lncRNA pairs (FRLPs). A risk score signature consisting of 10 FRLPs was established using multi-step Cox regression analysis. Next, we performed a series of systematic analyses to investigate the association of the FRLP model and tumor microenvironment, biological function, and treatment responses. An alternative model to the FRLP risk score signature, the gene set score (GS) model was also constructed, which could represent the former when lncRNA expression was not available.Results: We established a novel prognostic signature of 10 ferroptosis-related lncRNA pairs. High-risk patients in our risk score model were characterized by high infiltration of immune cells, upregulated carcinogenic and stromal activities, and heightened sensitivity to a wide range of anti-tumor drugs, whereas low-risk patients were associated with better responses to methotrexate treatment and elevated immunotherapeutic sensitivity. The practicability of the FRLP risk score model was also validated in two independent microarray datasets downloaded from Gene Expression Omnibus (GEO) using the GS model. Finally, two online dynamic nomograms were built to enhance the clinical utility of the study.Conclusion: In this study, we developed a ferroptosis-related lncRNA pair-based risk score model that did not rely on the exact lncRNA expression level. This novel model might provide insights for the accurate prediction and comprehensive management for GC patients.
Identification of Immune-Related Gene Signature in Stanford Type A Aortic Dissection
Authors: Li Zhaoshui , Wang Jumiao , Yu Qiao , Shen Ruxin , Qin Kun , Zhang Yu , Qiao Youjin , Chi Yifan 
Published: June 2022

Background: Stanford type A aortic dissection (ATAAD) is a common life-threatening event in the aorta. Recently, immune disorder has been linked to the risk factors that cause ATAAD at the molecular level. However, the specific immune-related gene signature during the progression is unclear.Methods: The GSE52093 and GSE98770 datasets related to ATAAD from the Gene Expression Omnibus (GEO) database were acquired. The immune gene expression levels were analyzed by single sample gene set enrichment analysis (ssGSEA). The correlations between gene networks and immune scores were determined by weighted gene correlation network analysis (WGCNA). The different immune subgroups were finally divided by consensus clustering. The differentially expressed genes (DEGs) were identified and subsequent functional enrichment analyses were conducted. The hub genes were identified by protein–protein interaction (PPI) network and functional similarities analyses. The immune cell infiltration proportion was determined by the CIBERSORT algorithm.Results: According to the ssGSEA results, the 13 ATAAD samples from the GEO database were divided into high- and low-immune subgroups according to the ssGSEA, WGCNA, and consensus clustering analysis results. Sixty-eight immune-related DEGs (IRDEGs) between the two subgroups were enriched in inflammatory-immune response biological processes, including leukocyte cell–cell adhesion, mononuclear cell migration, and myeloid leukocyte migration. Among these IRDEGs, 8 genes (CXCR4, LYN, CCL19, CCL3L3, SELL, F11R, DPP4, and VAV3) were identified as hub genes that represented immune-related signatures in ATAAD after the PPI and functional similarities analyses. The proportions of infiltrating CD8 T cells and M1 macrophages were significantly higher in ATAAD patients in the immune-high group than the immune-low group.Conclusion: Eight immune-related genes were identified as hub genes representing potential biomarkers and therapeutic targets linked to the immune response in ATAAD patients.
The Role of Registers in Increasing Knowledge and Improving Management of Children and Adolescents Affected by Familial Hypercholesterolemia: the LIPIGEN Pediatric Group
Authors: Gazzotti Marta , Casula Manuela , Bertolini Stefano , Capra Maria Elena , Olmastroni Elena , Catapano Alberico Luigi , Pederiva Cristina ,   the LIPIGEN Paediatric Group
Published: June 2022

Pathology registers can be a useful tool to overcome obstacles in the identification and management of familial hypercholesterolemia since childhood. In 2018, the LIPIGEN pediatric group was constituted within the Italian LIPIGEN study to focus on FH subjects under 18 years. This work aimed at discussing its recent progress and early outcomes. Demographic, biochemical, and genetic baseline characteristics were collected, with an in-depth analysis of the genetic defects. The analysis was carried out on 1,602 children and adolescents (mean age at baseline 9.9 ± 4.0 years), and almost the whole cohort underwent the genetic test (93.3%). Overall, the untreated mean value of LDL-C was 220.0 ± 97.2 mg/dl, with an increasing gradient from subjects with a negative (N = 317; mean untreated LDL-C = 159.9 ± 47.7 mg/dl), inconclusive (N = 125; mean untreated LDL-C = 166.4 ± 56.5 mg/dl), or positive (N = 1,053; mean untreated LDL-C = 246.5 ± 102.1 mg/dl) genetic diagnosis of FH. In the latter group, the LDL-C values presented a great variability based on the number and the biological impact of involved causative variants. The LIPIGEN pediatric group represents one of the largest cohorts of children with FH, allowing the deepening of the characterization of their baseline and genetic features, providing the basis for further longitudinal investigations for complete details.
Dissolved Organic Carbon Along a Meridional Transect in the Western North Pacific Ocean: Distribution, Variation and Controlling Processes
Authors: Ge Tiantian , Luo Chunle , Ren Peng , Zhang Hongmei , Chen Hongtao , Chen Zhaohui , Zhang Jing , Wang Xuchen 
Published: June 2022

Dissolved organic carbon (DOC) in the ocean is one of the largest reduced and exchangeable organic carbon pools on Earth and plays important roles in carbon cycling and biogeochemical processes in the ocean. Here, we report the concentrations and distributions of DOC in water samples collected along a meridional transect in the western North Pacific (NP) Ocean in November 2019. Concentrations of DOC ranged from 33-102 μM, were higher in surface water, decreased rapidly with depth to 1,000 m, and then remained relatively constant. The labile fraction of DOC accounted for 20-40% of the surface bulk DOC and was respired very rapidly in the upper 200 m depth. The semi-labile fraction of DOC accounted for 15-20% of the surface bulk DOC and was exported downward and turned over at water depths of 200-2,000 m. The formation of NP Intermediate Water (NPIW) in the Kuroshio Extension (KE) region is a major process carrying some surface semi-labile DOC down. The Low concentrations of DOC (33-44 μM) were present in the entire water column below 1,000 m along the transect in the NP. Primary production and microbial consumption played major roles in the concentration and distribution of DOC in the euphotic zone, and hydrodynamic mixing and circulation of different water masses appear to be dominant factors controlling the distribution and dynamics of DOC in the deep water of the western NP.
A Randomized, Controlled Trial of Treat-and-Extend vs. Pro Re Nata Regimen for Neovascular Age-Related Macular Degeneration
Authors: Jia Huixun , Lu Bing , Yuan Yuanzhi , Yuan Fei , Li Lei , Song Yanping , Rong Ao , Zhou Minwen , Wang Fenghua , Sun Xiaodong 
Published: June 2022

PurposeTo compare the efficacy and safety of conbercept using a treat-and-extend (T&amp;E) regimen vs. a pro re nata (PRN) regimen in Chinese patients with neovascular age-related macular degeneration (nAMD).MethodsThis was a randomized, multicenter, non-inferiority study. After an initial loading phase of three consecutive monthly intravitreal injections of 0.5 mg Conbercept, the patients were treated to PRN or T&amp;E regimen. The prespecified retreatment criteria was defined as a more than 5-letter decrease in BCVA from the previous visit or any evidence of new retinal hemorrhages, or the presence of any IRF and any SRF of more than 200 μm in height at the sub-foveal center. The primary outcome was the mean change in best-corrected visual acuity (BCVA) from baseline to 24 months, with a prespecified non-inferiority limit of −5 letters.ResultsFrom July 2016 through August 2018, 141 participants were allocated and treated (T&amp;E, n = 69; PRN, n = 72). About one fifth of the overall participants were dropped out during the 12-month follow-up (28/141, 19.9%), and about one thirds of the overall participants were lost during the 24-month follow-up (51/141, 36%). At 2 years, mean BCVA letter improvement was + 4.0 in the T&amp;E group vs. + 5.1 in the PRN group, and T&amp;E regimen was not non-inferior to PRN regimen [difference, −1.169 letters; 95% confidence interval (CI): −6.864 ∼ 4.526]. Subgroup analyses also demonstrate the similar results in PCV patients, naive patients and no-naive patients. The mean decrease in central subfield thickness were 180 ± 165 μm in the T&amp;E group and 247 ± 230 μm in the PRN group, respectively. The patients in the PRN group had required significantly fewer injections than those in the T&amp;E group (12.4 vs. 14.6 injections, P = 0.041). The types and rates of adverse events were comparable in the two treatment groups.ConclusionThese findings suggest that the T&amp;E regimen was not non-inferior to the PRN regimen in patients with nAMD in terms of BCVA outcomes through 24 months.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT02802657.