bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vasopressin but Not Oxytocin Responds to Birth Stress in Infants
Authors: Fill Malfertheiner Sara , Bataiosu-Zimmer Evelyn , Michel Holger , Fouzas Sotirios , Bernasconi Luca , Bührer Christoph , Wellmann Sven 
Published: September 2021

ContextBirth triggers a large fetal neuroendocrine response, which is more pronounced in infants born vaginally than in those born by elective cesarean section (ECS). The two related peptides arginine vasopressin (AVP) and oxytocin (OT) play an essential role in peripheral and central stress adaptation and have a shared receptor mediating their function. Elevated cord blood levels of AVP and its surrogate marker copeptin, the C-terminal part of AVP prohormone, have been found after vaginal delivery (VD) as compared to ECS, while release of OT in response to birth is controversial. Moreover, AVP, copeptin and OT have not yet been measured simultaneously at birth.ObjectiveTo test the hypothesis that AVP but not OT levels are increased in infants arterial umbilical cord blood in response to birth stress and to characterize AVP secretion in direct comparison with plasma copeptin.MethodsIn a prospective single-center cross-sectional study, we recruited healthy women with a singleton pregnancy and more than 36 completed weeks of gestation delivering via VD or ECS (cesarean without prior uterine contractions or rupture of membranes). Arterial umbilical cord blood samples were collected directly after birth, centrifuged immediately and plasma samples were frozen. Concentrations of AVP and OT were determined by radioimmunoassay and that of copeptin by ultrasensitive immunofluorescence assay.ResultsA total of 53 arterial umbilical cord blood samples were collected, n = 29 from VD and n = 24 from ECS. Ten venous blood samples from pregnant women without stress were collected as controls. AVP and copeptin concentrations were significantly higher in the VD group than in the ECS group (both p &lt; 0.001), median (range) AVP 4.78 (2.38–8.66) vs. 2.38 (1.79–3.88) (pmol/L), copeptin 1692 (72.1–4094) vs. 5.78 (3.14–17.97), respectively, (pmol/L). In contrast, there was no difference in OT concentrations (pmol/L) between VD and ECS, 6.00 (2.71–7.69) vs. 6.14 (4.26–9.93), respectively. AVP and copeptin concentrations were closely related (Rs = 0.700, p &lt; 0.001) while OT did not show any correlation to either AVP or copeptin. In linear regression models, vaginal delivery and biochemical stress indicators, base deficit and pH, were independent predictors for both AVP and copeptin. OT was not linked to base deficit or pH.ConclusionVaginal birth causes a profound secretion of AVP and copeptin in infants. Whereas AVP indicates acute stress events, copeptin provides information on cumulative stress events over a longer period. In contrast, fetal OT is unaffected by birth stress. Thus, AVP signaling but not OT mediates birth stress response in infants. This unique hormonal activation in early life may impact neurobehavioral development in whole life.
The Role of Fortified and Enriched Refined Grains in the US Dietary Pattern: A NHANES 2009–2016 Modeling Analysis to Examine Nutrient Adequacy
Authors: Papanikolaou Yanni , Fulgoni Victor L. III 
Published: September 2021

Background: While dietary recommendations call for greater whole-grain intake and reduced refined grain consumption, there are limited peer-reviewed studies examining the influence of fortified/enriched refined grains on nutrient adequacy.Methods: A modeling analysis using data from National Health and Nutrition Examination Survey (NHANES) 2009–2016 estimated usual daily intake of shortfall nutrients for Dietary Guidelines for Americans (DGA) in the current dietary pattern and when specific percentages of fortified/enriched refined grain foods (bread, ready-to-eat cereals, and all-grained foods) were removed from the diet (19–50-year-old adults, N = 11,169; 51–99-year-old adults, N = 9,641).Results: While American adults are currently falling short of nutrient recommendations, eliminating 25, 50, and 100% of all grains consumed in the US dietary pattern resulted in a greater percentage of adults not meeting recommendations for several shortfall nutrients, including dietary fiber, folate DFE, iron, and magnesium. Removal of all grains led to a reduced energy intake by ~10% in both age groups examined. Currently, ~3.8% of 19–50-year-old adults meet the adequate intake (AI) for dietary fiber. Removal of 25, 50, and 100% of grains from the diet resulted in 2.6 ± 0.3, 1.8 ± 0.2, and 0.7 ± 0.1% of adults exceeded the AI for dietary fiber, respectively. Similarly, 11.0 and 13.8% of younger and older adults, respectively, fall short of folate, DFE recommendations with the current diet. Following the removal of 100% of grains from the diet, 43.4 ± 1.1 and 56.2 ± 1.0%, respectively, were below the estimated average requirement (EAR) for folate DFE. For iron, current dietary pattern consumption shows 8.4% and 0.8% of younger and older adults, respectively, are not meeting iron recommendations, however, removal of 100% of grains from the diet results in nearly 10 and 22% falling short of the EAR. Currently, about 51 and 54% of younger and older adults are below the EAR for magnesium; however, with the removal of 100% of grains, 68 and 73%, respectively, fall below the EAR.Conclusion: Removal of specific refined grains led to an increased percentage of Americans not meeting recommendations for several shortfall nutrients, including dietary fiber, folate, iron, and magnesium.
Twenty-Year Trajectory-Patterns of Percentage Energy From Dietary Fat vs. Carbohydrate Throughout Adult Life and Associations With Cardio-Metabolic Disease and All-Cause Mortality
Authors: Guo Xiaoyu , Xu Xiaoqing , Gao Jian , Wang Weiqi , Hou Wanying , Wu Xiaoyan , Sun Changhao , Li Ying , Han Tianshu 
Published: September 2021

Background: The health impacts of dietary fat-to-energy ratio (FER) compared to carbohydrate-to-energy ratio (CER) are widely discussed topics in public health. This study aimed to assess the health impacts of FER and CER by establishing trajectory-patterns of FER and CER over the course of adult life.Methods: This study used the weighted longitudinal data of the China Health and Nutrition Survey, including eight surveys from 1991 to 2011. The trajectories of FER and CER were determined via latent class trajectory modeling. The trajectories were then cross-grouped into different trajectory-patterns. Multivariate Cox regression models were used to assess the relationship between these trajectory-patterns and cardio-metabolic diseases and all-cause mortality. Ten thousand nine hundred and twenty-six adults with a total of 50,693 observations across eight surveys were included.Results: Compared to the trajectory-pattern of persistently low-FER (increased from 10 to 20%) and moderate-CER (stable and ranging from 55 to 65%) over the adult life-course, the two trajectory-patterns that showed changing to high-FER and low-CER were significantly associated with obesity [HR 1.83 [95% CI, 1.10–3.04]; HR 1.46 [95% CI, 1.02–2.17]], diabetes [HR 1.80 [95% CI, 1.03–3.16]; HR 1.49 [95% CI, 1.01–2.25]], and all-cause mortality [HR 2.29 [95% CI, 1.35–3.87]; HR 1.62 [95% CI, 1.18–2.22]]. In contrast, the trajectory-pattern of a persistently low-FER and high-CER diet was not associated with obesity [HR 1.19 [95% CI, 0.82–1.17]], diabetes [HR 1.41 [95% CI, 0.98–2.02]], cardiovascular-disease [HR 1.48 [95% CI, 0.91–2.39]], and all-cause mortality [HR 1.23 [95% CI, 0.94–1.61]].Conclusions: This study indicates that changing to a high-FER and low-CER diet over the course of adult life was significantly associated with obesity, diabetes, and all-cause mortality in the Chinese adult population. In addition, low-FER and high-CER were not associated with cardio-metabolic disease and all-cause mortality. These observations may provide insights into nutritional policy and dietary guidelines.
Effects of Oats (Avena sativa L.) on Inflammation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Kim Sun Jo , Jung Cheol Woon , Anh Nguyen Hoang , Kim Suk Won , Park Seongoh , Kwon Sung Won , Lee Seul Ji 
Published: September 2021

Background: Oat and its compounds have been found to have anti-inflammatory effects. Through this systematic review and meta-analysis, we aimed to determine an evidence-based link between oat consumption and inflammatory markers.Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. By the end of April 2021, we included randomized controlled trials (RCTs) that investigated the anti-inflammatory effect of oat and oat-related products through screening PubMed, Embase, Web of Science, ClinicalTrial.gov, and CENTRAL. Meta-analysis was conducted with a random-effect model on the standardized mean difference (SMD) of the change scores of inflammatory markers, including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). Subgroup analyses were conducted to stratify confounding variables. The risk of bias was evaluated using the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was applied to report the quality of evidence. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42021245844).Results: Systematic screening of five databases yielded 4,119 studies, of which 23 RCTs were finally selected. For the four systemic inflammatory markers analyzed, no significant alterations were found after oat consumption. However, oat intake was found to significantly decrease CRP levels in subjects with one or more health complications (SMD: −0.18; 95% CI: −0.36, 0.00; P = 0.05; I2 = 10%). Furthermore, IL-6 levels were significantly decreased in subjects with dyslipidemia (SMD = −0.34; 95% CI: −0.59, −0.10; P = 0.006; I2 = 0%). These beneficial effects might be attributed to the effects of avenanthramide and β-glucan.Conclusions: Overall evidence supporting the alleviation of inflammatory response by oat intake was poor, calling for future studies including a larger sample size to confirm the findings.
A Diagnostic Method for Gastric Cancer Using Two-Photon Microscopy With Enzyme-Selective Fluorescent Probes: A Pilot Study
Authors: Noh Choong-Kyun , Lim Chang Su , Lee Gil Ho , Cho Myung Ki , Lee Hyo Won , Roh Jin , Kim Young Bae , Lee Eunyoung , Park Bumhee , Kim Hwan Myung , Shin Sung Jae 
Published: September 2021

BackgroundEndoscopy is the most important tool for gastric cancer diagnosis. However, it relies on naked-eye evaluation by endoscopists, and the histopathologic confirmation is time-consuming. We aimed to visualize and measure the activity of various enzymes through two-photon microscopy (TPM) using fluorescent probes and assess its diagnostic potential in gastric cancer.Methodsβ-Galactosidase (β-gal), carboxylesterase (CES), and human NAD(P)H: quinone oxidoreductase (hNQO1) enzyme activities in the normal mucosa, ulcer, adenoma, and gastric cancer biopsy samples were measured using two-photon enzyme probes. The fluorescence emission ratio at long and short wavelengths (Ch2/Ch1) for each probe was comparatively analyzed. Approximately 8,000 – 9,000 sectional images in each group were obtained by measuring the Ch2/Ch1 ratio according to the tissue depth. Each probe was cross-validated by measuring enzymatic activity from a solution containing lysed tissue.ResultsTotal of 76 subjects were enrolled in this pilot study (normal 21, ulcer 18, adenoma 17, and cancer 20 patients, respectively). There were significant differences in the mean ratio values of β-gal (0.656 ± 0.142 vs. 1.127 ± 0.109, P &lt; 0.001) and CES (0.876 ± 0.049 vs. 0.579 ± 0.089, P &lt; 0.001) between the normal and cancer, respectively. The mean ratio value of cancer tissues was different compared to ulcer and adenoma (P &lt; 0.001). The hNQO1 activity showed no significant difference between cancer and other conditions. Normal mucosa and cancer were visually and quantitatively distinguished through β-gal and CES analyses using TPM images, and enzymatic activity according to depth, was determined using sectional TPM ratiometric images. The results obtained from lysis buffer-treated tissue were consistent with TPM results.ConclusionsTPM imaging using ratiometric fluorescent probes enabled the discrimination of gastric cancer from normal, ulcer, and adenoma. This novel method can help in a visual differentiation and provide quantitative depth profiling in gastric cancer diagnosis.
A Nomogram for the Determination of the Necessity of Concurrent Chemotherapy in Patients With Stage II–IVa Nasopharyngeal Carcinoma
Authors: Yang Kaixuan , Zhang Qian , Zhang Mengxi , Xie Wenji , Li Mei , Zeng Lei , Wang Qiang , Zhao Jianling , Li Yiping , Li Guangjun 
Published: September 2021

BackgroundThe efficiency of concurrent chemotherapy (CC) remains controversial for stage II–IVa nasopharyngeal carcinoma (NPC) patients treated with induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT). Therefore, we aimed to propose a nomogram to identify patients who would benefit from CC.MethodsA total of 434 NPC patients (stage II–IVa) treated with IC followed by IMRT between January 2010 and December 2015 were included. There were 808 dosimetric parameters extracted by the in-house script for each patient. A dosimetric signature was developed with the least absolute shrinkage and selection operator algorithm. A nomogram was built by incorporating clinical factors and dosimetric signature using Cox regression to predict recurrence-free survival (RFS). The C-index was used to evaluate the performance of the nomogram. The patients were stratified into low- and high-risk recurrence according to the optimal cutoff of risk score.ResultsThe nomogram incorporating age, TNM stage, and dosimetric signature yielded a C-index of 0.719 (95% confidence interval, 0.658–0.78). In the low-risk group, CC was associated with a 9.4% increase of 5-year locoregional RFS and an 8.8% increase of 5-year overall survival (OS), whereas it was not significantly associated with an improvement of locoregional RFS (LRFS) and OS in the high-risk group. However, in the high-risk group, patients could benefit from adjuvant chemotherapy (AC) by improving 33.6% of the 5-year LRFS.ConclusionsThe nomogram performed an individualized risk quantification of RFS in patients with stage II–IVa NPC treated with IC followed by IMRT. Patients with low risk could benefit from CC, whereas patients with high risk may require additional AC.
Selective Histone Deacetylase Inhibitor ACY-241 (Citarinostat) Plus Nivolumab in Advanced Non-Small Cell Lung Cancer: Results From a Phase Ib Study
Authors: Awad Mark M. , Le Bruchec Yvan , Lu Brian , Ye Jason , Miller JulieAnn , Lizotte Patrick H. , Cavanaugh Megan E. , Rode Amanda J. , Dumitru Calin Dan , Spira Alexander 
Published: September 2021

BackgroundHistone deacetylase (HDAC) overexpression has been documented in various cancers and may be associated with worse outcomes. Data from early-phase studies of advanced non-small cell lung cancer (NSCLC) suggest encouraging antitumor activity with the combination of an HDAC inhibitor and either platinum-based chemotherapy or an EGFR inhibitor; however, toxicity is a limiting factor in the use of pan-HDAC inhibitors. Selective inhibition of HDAC6 may represent a potential therapeutic target and preclinical studies revealed immunomodulatory effects with HDAC6 inhibition, suggesting the potential for combination with immune checkpoint inhibitors. This phase Ib, multicenter, single-arm, open-label, dose-escalation study investigated the HDAC6 inhibitor ACY-241 (citarinostat) plus nivolumab in patients with previously treated advanced NSCLC who had not received a prior HDAC or immune checkpoint inhibitor.MethodsThe orally administered ACY-241 dose was escalated (180, 360, or 480 mg once daily). Nivolumab was administered at 240 mg (day 15 of cycle 1, then every 2 weeks thereafter). The primary endpoint was to determine the maximum tolerated dose (MTD) of ACY-241 plus nivolumab. Secondary endpoints included safety, tolerability, and preliminary antitumor activity. Pharmacodynamics was an exploratory endpoint.ResultsA total of 18 patients were enrolled, with 17 patients treated. No dose-limiting toxicities (DLTs) occurred with ACY-241 at 180 or 360 mg; 2 DLTs occurred at 480 mg. The MTD of ACY-241 was 360 mg. The most common grade ≥ 3 treatment-emergent adverse events were dyspnea (n = 3; 18%) and pneumonia (n = 3; 18%). At the 180-mg dose, 1 complete response and 2 partial responses (PRs) were observed. At the 360-mg dose, 3 PRs were observed; 1 patient achieved stable disease (SD) and 1 experienced progressive disease (PD). At the 480-mg dose, no responses were observed; 1 patient achieved SD and 3 experienced PD. Acetylation analyses revealed transient increases in histone and tubulin acetylation levels following treatment. An increase in infiltrating total CD3+ T cells was observed following treatment.ConclusionsThe study identified an MTD for ACY-241 plus nivolumab and the data suggest that the combination may be feasible in patients with advanced NSCLC. Responses were observed in patients with advanced NSCLC. Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT02635061 (identifier, NCT02635061).
A Functional Polymorphism in Accessible Chromatin Region Confers Risk of Non-Small Cell Lung Cancer in Chinese Population
Authors: Long Jieyi , Long Tingting , Li Ying , Yuan Peihong , Liu Ke , Li Jiaoyuan , Cheng Liming 
Published: September 2021

BackgroundThe disease-associated non-coding variants identified by genome-wide association studies (GWASs) were enriched in open chromatin regions (OCRs) and implicated in gene regulation. Genetic variants in OCRs thus may exert regulatory functions and contribute to non-small cell lung cancer (NSCLC) susceptibility.ObjectiveTo fine map potential functional variants in GWAS loci that contribute to NSCLC predisposition using chromatin accessibility and histone modification data and explore their functions by population study and biochemical experimental analyses.MethodsWe mapped the chromatin accessible regions of lung tissues using data of assay for transposase-accessible chromatin using sequencing (ATAC-seq) in The Cancer Genome Atlas (TCGA) and prioritized potential regulatory variants within lung cancer GWAS loci by aligning with histone signatures using data of chromatin immunoprecipitation assays followed by sequencing (ChIP-seq) in the Encyclopedia of DNA Elements (ENCODE). A two-stage case–control study with 1,830 cases and 2,001 controls was conducted to explore the associations between candidate variants and NSCLC risk in Chinese population. Bioinformatic annotations and biochemical experiments were performed to further reveal the potential functions of significant variants.ResultsSixteen potential functional single-nucleotide polymorphisms (SNPs) were selected as candidates from bioinformatics analyses. Three variants out of the 16 candidate SNPs survived after genotyping in stage 1 case–control study, and only the results of SNP rs13064999 were successfully validated in the analyses of stage 2 case–control study. In combined analyses, rs13064999 was significantly associated with NSCLC risk [additive model; odds ratio (OR) = 1.17; 95%CI, 1.07–1.29; p = 0.001]. Functional annotations indicated its potential enhancer bioactivity, and dual-luciferase reporter assays revealed a significant increase in luciferase activity for the reconstructed plasmid with rs13064999 A allele, when compared to the one with wild-type G allele (pA549 &lt; 0.001, pSK-MES-1 = 0.004). Further electrophoretic mobility shift assays (EMSA) and super-shift assays confirmed a stronger affinity of HP1γ for the binding motif containing SNP rs13064999 A allele.ConclusionThese findings suggested that the functional variant rs13064999, identified by the integration of ATAC-seq and ChIP-seq data, contributes to the susceptibility of NSCLC by affecting HP1γ binding, while the exact biological mechanism awaits further exploration.
Systematic Lymph Node Dissection May Be Abolished in Patients With Apparent Early-Stage Low-Grade Mucinous and Endometrioid Epithelial Ovarian Cancer
Authors: Chen Jiayu , Yin Jie , Li Yan , Gu Yu , Wang Wei , Shan Ying , Wang Yong-Xue , Qin Meng , Cai Yan , Jin Ying , Pan Lingya 
Published: September 2021

ObjectiveTo investigate whether systematic lymph node dissection can confer clinical benefits in patients with apparent early-stage low-grade epithelial ovarian cancer.MethodsPatients with apparent early-stage low-grade epithelial ovarian cancer seen at Peking Union Medical College Hospital from January 1, 2005, to December 31, 2015, were retrospectively enrolled. Patients with other histological types and those who did not receive necessary adjuvant chemotherapy were excluded. Data collection and long-term follow-up were performed. According to the removed lymph node number, three groups based on surgical methods were used: abnormal lymph node resection, pelvic lymphadenectomy, and systematic lymph node dissection to control surgical quality. Their effects on prognosis were analyzed in pathological subgroups.ResultsA total of 196 patients were enrolled; 30.1% of patients had serous, 42.3% of patients had mucinous, and 27.6% of patients had endometrioid carcinoma, of which 51 (26.0%), 96 (49.0), and 49 (25.0%) patients were treated with the above surgical methods, respectively. The occult lymph node metastasis rate was 14 (7.1%), and only five (2.6%) of apparent early-stage patients were upstaged due to lymph node metastasis alone. Systematic lymph node dissection did not benefit progression-free survival or disease-specific overall survival of apparent early-stage low-grade mucinous and endometrioid epithelial ovarian cancer but prolonged progression-free survival of apparent early-stage low-grade serous patients (OR, 0.231, 95% CI, 0.080, 0.668, p = 0.007).ConclusionsSystematic lymph node dissection may be abolished in patients with apparent early-stage low-grade mucinous and endometrioid epithelial ovarian cancer but may be considered for apparent early-stage low-grade serous patients.