bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined Exposure to 33 Trace Elements and Associations With the Risk of Oral Cancer: A Large-Scale Case-Control Study
Authors: Wang Huiying , Wang Jing , Cao Yujie , Chen Jinfa , Deng Qingrong , Chen Yujia , Qiu Yu , Lin Lisong , Shi Bin , Liu Fengqiong , He Baochang , Chen Fa 
Published: July 2022

BackgroundTrace elements exist widely in the natural environment and mostly enter the human body through drinking water or various types of food, which has raised increasing health concerns. Exposure to a single or a few trace elements has been previously reported to be associated with oral cancer risk, but studies on other elements and combined effects are limited. This study aimed to comprehensively evaluate the independent and joint effects of 33 trace elements on oral cancer risk.MethodsThe concentrations of 33 trace elements from the serum samples of 463 cases and 1,343 controls were measured using inductively coupled plasma mass spectrometry (ICP-MS). Propensity score matching was used to minimize the impact of potential confounders. Conditional logistic regression was utilized to evaluate the association of each element individually with oral cancer risk. Quantile g-computation and Bayesian kernel machine regression (BKMR) models were used to assess the joint effect of the overall element mixture and interactions.ResultsIn single-element models, essential elements (Cu, Se, Zn, Sr, and Cr) and non-essential elements (As, Li, Th, Ce, Ti, and Sc) showed significant association with oral cancer risk. In multiple-element models, a quartile increase in overall non-essential elements was observed for a significant inverse association with oral cancer risk (β = −3.36, 95% CI: −4.22 to −2.51). The BKMR analysis revealed a potential beneficial joint effect of essential metals on the risk of oral cancer. Among these, higher levels of serum Zn and V exhibited an adverse effect, while serum Sr, Se, and Cu displayed favorable effects when all other essential elements were fixed at 25th or 50th percentiles. Of note, Se performed complex interactions among essential metals. As for non-essential elements, there were greater effect estimates for serum Th, Li, and Y when all other elements were held at the 75th percentile.ConclusionThis study provides supportive evidence that the overall mixture effect of essential and non-essential elements might be associated with oral cancer risk, especially for serum Zn, V, Cu, Sr, Se, Th, Li, and Y. Extensive prospective studies and other experiments are warranted to confirm our findings.
Infant Formula With a Specific Blend of Five Human Milk Oligosaccharides Drives the Gut Microbiota Development and Improves Gut Maturation Markers: A Randomized Controlled Trial
Authors: Bosheva Miroslava , Tokodi Istvan , Krasnow Aleksander , Pedersen Helle Krogh , Lukjancenko Oksana , Eklund Aron C. , Grathwohl Dominik , Sprenger Norbert , Berger Bernard , Cercamondi Colin I. ,   5 HMO Study Investigator Consortium
Published: July 2022

BackgroundHuman milk oligosaccharides (HMOs) have important biological functions for a healthy development in early life.ObjectiveThis study aimed to investigate gut maturation effects of an infant formula containing five HMOs (2′-fucosyllactose, 2′,3-di-fucosyllactose, lacto-N-tetraose, 3′-sialyllactose, and 6′-sialyllactose).MethodsIn a multicenter study, healthy infants (7–21 days old) were randomly assigned to a standard cow’s milk-based infant formula (control group, CG); the same formula with 1.5 g/L HMOs (test group 1, TG1); or with 2.5 g/L HMOs (test group 2, TG2). A human milk-fed group (HMG) was enrolled as a reference. Fecal samples collected at baseline (n∼150/formula group; HMG n = 60), age 3 (n∼140/formula group; HMG n = 65) and 6 (n∼115/formula group; HMG n = 60) months were analyzed for microbiome (shotgun metagenomics), metabolism, and biomarkers.ResultsAt both post-baseline visits, weighted UniFrac analysis indicated different microbiota compositions in the two test groups (TGs) compared to CG (P &lt; 0.01) with coordinates closer to that of HMG. The relative abundance of Bifidobacterium longum subsp. infantis (B. infantis) was higher in TGs vs. CG (P &lt; 0.05; except at 6 months: TG2 vs. CG P = 0.083). Bifidobacterium abundance was higher by ∼45% in TGs vs. CG at 6-month approaching HMG. At both post-baseline visits, toxigenic Clostridioides difficile abundance was 75–85% lower in TGs vs. CG (P &lt; 0.05) and comparable with HMG. Fecal pH was significantly lower in TGs vs. CG, and the overall organic acid profile was different in TGs vs. CG, approaching HMG. At 3 months, TGs (vs. CG) had higher secretory immunoglobulin A (sIgA) and lower alpha-1-antitrypsin (P &lt; 0.05). At 6 months, sIgA in TG2 vs. CG remained higher (P &lt; 0.05), and calprotectin was lower in TG1 (P &lt; 0.05) vs. CG.ConclusionInfant formula with a specific blend of five HMOs supports the development of the intestinal immune system and gut barrier function and shifts the gut microbiome closer to that of breastfed infants with higher bifidobacteria, particularly B. infantis, and lower toxigenic Clostridioides difficile.Clinical Trial Registration[https://clinicaltrials.gov/ct2/show/], identifier [NCT03722550].
Stress and Diet Quality Among Ecuadorian Adults During the COVID-19 Pandemic. A Cross-Sectional Study
Authors: Abril-Ulloa Victoria , Santos Sueny Paloma Lima-dos , Morejón-Terán Yadira Alejandra , Carpio-Arias Tannia Valeria , Espinoza-Fajardo Ana Cristina , Vinueza-Veloz María Fernanda 
Published: July 2022

BackgroundStress has been associated with food habits. Stress changes eating patterns and the salience and consumption of hyperpalatable foods. During the lock-down due to the COVID-19 pandemic, stress was very common.ObjectiveWe investigated the association between stress and diet quality in Ecuadorian adults during the COVID-19 pandemic.DesignA cross-sectional study.SettingData was collected using a self-administered online survey. Stress was measured using the Perceived Stress Scale (PSS-14), and diet quality was evaluated using the Global Diet Index (GDI). A linear regression model with restrictive cubic splines was used to investigate the association between stress and diet quality.ParticipantsParticipants were recruited by convenience sampling, including a total of 2602 individuals. Most participants were female (68.57%) and had university education (78.52%), with a median age of 25 (IQR: 25, 37).ResultsStress was reported by 26.06% of participants. The majority of individuals (75.79%) reported having a diet that needed changes or an unhealthy diet. Independently from biological sex, age, level of education, people/room ratio, economic allowance, and expenses for food, stress was statistically significantly associated with diet quality (p = 0.035). The association between stress and diet quality was inverse and non-linear; higher stress levels were associated with poorer diet quality. The consumption of palatable foods was not statistically significant associated with stress.ConclusionsStress is associated with poorer diet quality. Public health measures to improve the mental health and lifestyle of the population are needed during the lock-down of the pandemic.
Deep Learning of Liver Contrast-Enhanced Ultrasound to Predict Microvascular Invasion and Prognosis in Hepatocellular Carcinoma
Authors: Zhang Yafang , Wei Qingyue , Huang Yini , Yao Zhao , Yan Cuiju , Zou Xuebin , Han Jing , Li Qing , Mao Rushuang , Liao Ying , Cao Lan , Lin Min , Zhou Xiaoshuang , Tang Xiaofeng , Hu Yixin , Li Lingling , Wang Yuanyuan , Yu Jinhua , Zhou Jianhua 
Published: July 2022

Background and AimsMicrovascular invasion (MVI) is a well-known risk factor for poor prognosis in hepatocellular carcinoma (HCC). This study aimed to develop a deep convolutional neural network (DCNN) model based on contrast-enhanced ultrasound (CEUS) to predict MVI, and thus to predict prognosis in patients with HCC.MethodsA total of 436 patients with surgically resected HCC who underwent preoperative CEUS were retrospectively enrolled. Patients were divided into training (n = 301), validation (n = 102), and test (n = 33) sets. A clinical model (Clinical model), a CEUS video-based DCNN model (CEUS-DCNN model), and a fusion model based on CEUS video and clinical variables (CECL-DCNN model) were built to predict MVI. Survival analysis was used to evaluate the clinical performance of the predicted MVI.ResultsCompared with the Clinical model, the CEUS-DCNN model exhibited similar sensitivity, but higher specificity (71.4% vs. 38.1%, p = 0.03) in the test group. The CECL-DCNN model showed significantly higher specificity (81.0% vs. 38.1%, p = 0.005) and accuracy (78.8% vs. 51.5%, p = 0.009) than the Clinical model, with an AUC of 0.865. The Clinical predicted MVI could not significantly distinguish OS or RFS (both p &gt; 0.05), while the CEUS-DCNN predicted MVI could only predict the earlier recurrence (hazard ratio [HR] with 95% confidence interval [CI 2.92 [1.1–7.75], p = 0.024). However, the CECL-DCNN predicted MVI was a significant prognostic factor for both OS (HR with 95% CI: 6.03 [1.7–21.39], p = 0.009) and RFS (HR with 95% CI: 3.3 [1.23–8.91], p = 0.011) in the test group.ConclusionsThe proposed CECL-DCNN model based on preoperative CEUS video can serve as a noninvasive tool to predict MVI status in HCC, thereby predicting poor prognosis.
Superficial Temporal Artery and Vein as Alternative Recipient Vessels for Intraoral Reconstruction With Free Flaps to Avoid the Cervical Approach With the Resulting Need for Double Flap Transfer in Previously Treated Necks
Authors: Ritschl Lucas M. , Niu Minli , Pippich Katharina , Schuh Philia , Rommel Niklas , Fichter Andreas M. , Wolff Klaus-Dietrich , Weitz Jochen 
Published: July 2022

BackgroundMicrovascular reconstruction remains challenging in previously operated and irradiated patients, especially when double flaps seem to be the only solution due to osteoradionecrosis. An alternative reconstructive option could be microvascular anastomosis to the temporal vessels to avoid the obligatory cervical incision.Methods and MaterialsAll consecutive cases between January 2013 and 2020 that underwent either mandibular resection and reconstruction with a free fibula flap (FFF) and another soft tissue flap (group I) or pure intraoral resection and reconstruction with an FFF or radial forearm flap (RFF) with temporal microvascular anastomosis (group II) were included. Patients’ general information, indication and extent of surgery, time of ischemia, time of total surgery, and duration of hospital stay as well as incidence of complications were retrospectively recorded and analyzed.ResultsSeventeen (group I) and 11 (group II) cases were included. In group I, FFF was combined with RFF (n = 9), anterolateral thigh flap (ALT, n = 7), or latissimus dorsi flap (n = 1). Group II consisted of six FFFs and five RFFs. Operation time and hospitalization duration were significantly shorter in group II (p &lt; 0.001 and p = 0.025), whereas ischemic time of FFF was significantly shorter in group I (p = 0.002). All patients in group I required a tracheostomy, while only four cases in group II did (p = 0.004). The complication rate regarding hematoma removal, revision of anastomosis, flap loss, delirium, sepsis, pleural effusion, pneumonia, and pulmonary artery embolism showed no significant differences between the two groups.ConclusionsThe superficial temporal vessels served as versatile recipient vessels for intraoral mandibular and soft tissue reconstruction and led to reduced operation time, hospitalization duration, and indication for a primary tracheostomy. Thus, this approach may help to avoid cervical incision for reconstruction in irradiated patients.
A Nomogram Model to Predict Post-Progression Survival in Esophageal Squamous Cell Carcinoma Patients With Recurrence After Radical Resection
Authors: Leng Changsen , Cui Yingying , Chen Junying , Wang Kexi , Yang Hong , Wen Jing , Fu Jianhua , Liu Qianwen 
Published: July 2022

BackgroundEsophageal squamous cell carcinoma (ESCC) is characterized clinically by frequent recurrence, leading to a poor prognosis after radical surgery. The aim of this study was to identify a prognostic nomogram to predict the post-progression survival (PPS) of ESCC patients based on the features of primary tumor and recurrence.MethodsA total of 234 ESCC patients who underwent recurrence after radical surgery were enrolled in this study. The independent prognostic factors screened by the univariate and multivariate Cox regression analysis were subsequently used to construct a nomogram. The predictive performance of the nomogram was evaluated with the concordance index (C-index), decision curve, and the area under the receiver operating characteristic curve (AUC) and validated in two validation cohorts. The Kaplan-Meier curves of different recurrence patterns were analyzed.ResultsThe prognostic nomogram of PPS was established by integrating independent prognostic factors, including age, body mass index, number of lymph node dissection, recurrence pattern, and recurrence treatment. The nomogram demonstrated good performance, with C-index values of 0.756, 0.817, and 0.730 for the training and two validation cohorts. The 1-year AUC values were 0.773, 0.798, and 0.735 and 3-year AUC values were 0.832, 0.871, and 0.791, respectively. Furthermore, we found that patients with bone metastasis displayed the worst PPS compared to other isolated recurrence patterns.ConclusionWe constructed a nomogram to reliably predict PPS, which would be valuable to provide individual managements for ESCC patients after radical surgery.
Effect of Breast Milk Oral Care on Mechanically Ventilated Preterm Infants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Cai Meiling , Lin Lingyu , Peng Yanchun , Chen Liangwan , Lin Yanjuan 
Published: July 2022

BackgroundThe benefits of breast milk oral care in mechanically ventilated preterm infants remain controversial. This study aimed to systematically review the evidence on the benefits of breast milk oral care in mechanically ventilated preterm infants.MethodsThe randomized controlled trials of breast milk oral care for mechanically ventilated preterm infants were searched in EMBASE, PubMed, Cochrane Library, Web of Science, WANFANG Date and China National Knowledge Infrastructure databases. The retrieval language was limited to Chinese and English, and the final search was conducted until March 2022. Outcome measures included ventilator-associated pneumonia (VAP), mechanical ventilation time (MVT), length of stay (LOS), necrotizing enterocolitis (NEC), late-onset sepsis, mortality during hospitalization, time of full intestinal feeding and time of full oral feeding. Two researchers independently screened the literature, extracted the data, and conducted the literature quality assessment. Meta-analysis was mainly performed using RevMan 5.3.ResultsEight articles involving 1,046 preterm infants were included. Our meta-analysis showed that compared with the control group, breast milk oral care could reduce the incidence of VAP [RR = 0.41, 95% CI (0.23, 0.75), P = 0.003] and NEC [RR = 0.54, 95% CI (0.30, 0.95), P = 0.03], and shorten the MVT [MD = −0.45, 95% CI (−0.73, −0.18), P = 0.001] and LOS [MD = −5.74, 95% CI (−10.39, −1.10), P = 0.02]. There were no significant differences in the mortality during hospitalization [RR = 0.94, 95% CI (0.67, 1.33), P = 0.74], the incidence of late-onset sepsis [RR = 0.79, 95% CI (0.40, 1.59), P = 0.51], the time of full intestinal feeding [MD = −2.42, 95% CI (−5.37, 0.52), P = 0.11] and the time of full oral feeding [MD = −3.40, 95% CI (−10.70, 3.91), P = 0.36] between the two groups.ConclusionsOral care of breast milk can reduce the incidence of VAP and NEC, shorten MVT and LOS in mechanically ventilated preterm infants. However, due to the quality and quantity limitations of the included studies, larger sample size and more strictly designed clinical trials are still needed in the future to further confirm the findings of this study.
External Evaluation of Population Pharmacokinetic Models of Busulfan in Chinese Adult Hematopoietic Stem Cell Transplantation Recipients
Authors: Huang Huiping , Liu Qingxia , Zhang Xiaohan , Xie Helin , Liu Maobai , Chaphekar Nupur , Wu Xuemei 
Published: July 2022

Objective: Busulfan (BU) is a bi-functional DNA-alkylating agent used in patients undergoing hematopoietic stem cell transplantation (HSCT). Over the last decades, several population pharmacokinetic (pop PK) models of BU have been established, but external evaluation has not been performed for almost all models. The purpose of the study was to evaluate the predictive performance of published pop PK models of intravenous BU in adults using an independent dataset from Chinese HSCT patients, and to identify the best model to guide personalized dosing.Methods: The external evaluation methods included prediction-based diagnostics, simulation-based diagnostics, and Bayesian forecasting. In prediction-based diagnostics, the relative prediction error (PE%) was calculated by comparing the population predicted concentration (PRED) with the observations. Simulation-based diagnostics included the prediction- and variability-corrected visual predictive check (pvcVPC) and the normalized prediction distribution error (NPDE). Bayesian forecasting was executed by giving prior one to four observations. The factors influencing the model predictability, including the impact of structural models, were assessed.Results: A total of 440 concentrations (110 patients) were obtained for analysis. Based on prediction-based diagnostics and Bayesian forecasting, preferable predictive performance was observed in the model developed by Huang et al. The median PE% was -1.44% which was closest to 0, and the maximum F20 of 57.27% and F30 of 72.73% were achieved. Bayesian forecasting demonstrated that prior concentrations remarkably improved the prediction precision and accuracy of all models, even with only one prior concentration.Conclusion: This is the first study to comprehensively evaluate published pop PK models of BU. The model built by Huang et al. had satisfactory predictive performance, which can be used to guide individualized dosage adjustment of BU in Chinese patients.
Qingluo Tongbi Formula Alleviates Hepatotoxicity Induced by Tripterygium wilfordii Hook. F. by Regulating Excessive Mitophagy Through the PERK-ATF4 Pathway
Authors: Zhang Linluo , Zhou Jie , Feng Zhe , Jiang Baoping , Li Changqing , Zhou Lingling , Zhou Xueping 
Published: July 2022

Qingluo Tongbi Formula (QTF) is an empirical formula of Chinese medicine master Zhongying Zhou for the treatment of rheumatoid arthritis. Although including Tripterygium wilfordii Hook. F. (TW), it has not shown liver toxicity in clinical application for many years. Our previous studies have shown that QTF can significantly reduce TW-caused hepatotoxicity, but the mechanism is still unclear. This study aimed to explore the important roles of mitophagy and endoplasmic reticulum stress (ERS) and the relationship between them in QTF in alleviating TW-induced hepatotoxicity. In vivo, C57BL/6J female mice were used to build a model of TW-induced liver toxicity; Then mice were randomly divided into control, TW, TW + RG, TW + PN, TW + SA, TW + BM, and QTF groups. After intragastric administration for 7 days, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in serum were detected; H and E staining, Oil Red O staining, transmission electron microscopy, Western blotting, and RT-qPCR were used to detect the pathological changes in liver tissue, the levels of ERS and mitophagy related proteins and genes, including GRP78, PERK, DRP1, LC3, etc., In vitro, triptolide (TP), catalpol (CAT), and panax notoginseng saponins (PNS), the main active ingredients of QTF, were selected. The mitophagy inhibitor, ERS inhibitor, and PERK inhibitor were used to further study the relationship between TW-induced ERS and mitophagy in HepaRG cells. The results showed that, QTF reduced excessive mitophagy and ERS in TW-induced hepatotoxicity in C57BL/6J mice, and the attenuating effects of RG and PN in QTF were most obvious, and they also significantly restrained the TW-induced ERS and mitophagy by the PERK-ATF4 pathway. Furthermore, PNS was superior to CAT in inhibiting the expression levels of GRP78, PERK, and ATF4, while CAT was superior to PNS in reversing the expression levels of DRP1, P62, and LC3. The combination of CAT and PNS had the best attenuating effect and the most significant regulation on ERS and mitophagy. In conclusion, QTF can alleviate TW-induced hepatotoxicity by differentially downregulating the PERK-ATF4 pathway and excessive mitophagy by different components.
Current Understanding of Molecular Pathophysiology of Heart Failure With Preserved Ejection Fraction
Authors: Budde Heidi , Hassoun Roua , Mügge Andreas , Kovács Árpád , Hamdani Nazha 
Published: July 2022

Heart Failure (HF) is the most common cause of hospitalization in the Western societies. HF is a heterogeneous and complex syndrome that may result from any dysfunction of systolic or diastolic capacity. Abnormal diastolic left ventricular function with impaired relaxation and increased diastolic stiffness is characteristic of heart failure with preserved ejection fraction (HFpEF). HFpEF accounts for more than 50% of all cases of HF. The prevalence increases with age: from around 1% for those aged &lt;55 years to &gt;10% in those aged 70 years or over. Nearly 50% of HF patients have HFrEF and the other 50% have HFpEF/HFmrEF, mainly based on studies in hospitalized patients. The ESC Long-Term Registry, in the outpatient setting, reports that 60% have HFrEF, 24% have HFmrEF, and 16% have HFpEF. To some extent, more than 50% of HF patients are female. HFpEF is closely associated with co-morbidities, age, and gender. Epidemiological evidence suggests that HFpEF is highly represented in older obese women and proposed as ‘obese female HFpEF phenotype’. While HFrEF phenotype is more a male phenotype. In addition, metabolic abnormalities and hemodynamic perturbations in obese HFpEF patients appear to have a greater impact in women then in men (Sorimachi et al., European J of Heart Fail, 2022, 22). To date, numerous clinical trials of HFpEF treatments have produced disappointing results. This outcome suggests that a “one size fits all” approach to HFpEF may be inappropriate and supports the use of tailored, personalized therapeutic strategies with specific treatments for distinct HFpEF phenotypes. The most important mediators of diastolic stiffness are the cardiomyocytes, endothelial cells, and extracellular matrix (ECM). The complex physiological signal transduction networks that respond to the dual challenges of inflammatory and oxidative stress are major factors that promote the development of HFpEF pathologies. These signalling networks contribute to the development of the diseases. Inhibition and/or attenuation of these signalling networks also delays the onset of disease. In this review, we discuss the molecular mechanisms associated with the physiological responses to inflammation and oxidative stress and emphasize the nature of the contribution of most important cells to the development of HFpEF via increased inflammation and oxidative stress.