bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk–Benefit assessment of foods: Development of a methodological framework for the harmonized selection of nutritional, microbiological, and toxicological components
Authors: Boué Géraldine , Ververis Ermolaos , Niforou Aikaterini , Federighi Michel , Pires Sara M. , Poulsen Morten , Thomsen Sofie T. , Naska Androniki
Published: October 2022

Investigating the impact of diet on public health using risk–benefit assessment (RBA) methods that simultaneously consider both beneficial and adverse health outcomes could be useful for shaping dietary policies and guidelines. In the field of food safety and nutrition, RBA is a relatively new approach facing methodological challenges and being subject to further developments. One of the methodological aspects calling for improvement is the selection of components to be considered in the assessment, currently based mainly on non-harmonized unstandardized experts’ judgment. Our aim was to develop a harmonized, transparent, and documented methodological framework for selecting nutritional, microbiological, and toxicological RBA components. The approach was developed under the Novel foods as red meat replacers—an insight using Risk-Benefit Assessment methods (NovRBA) case study, which attempted to estimate the overall health impact of replacing red meat with an edible insect species, Acheta domesticus. Starting from the compositional profiles of both food items, we created a “long list” of food components. By subsequently applying a series of predefined criteria, we proceeded from the “long” to the “short list.” These criteria were established based on the occurrence and severity of health outcomes related to these components. For nutrition and microbiology, the occurrence of health outcomes was evaluated considering the presence of a component in the raw material, as well as the effect of processing on the respective component. Regarding toxicology, the presence and exposure relative to reference doses and the contribution to total exposure were considered. Severity was graded with the potential contribution to the background diet alongside bioavailability aspects (nutrition), the disability-adjusted life years per case of illness of each hazard (microbiology), and disease incidence in the population, potential fatality, and lifelong disability (toxicology). To develop the “final list” of components, the “short list” was refined by considering the availability and quality of data for a feasible inclusion in the RBA model. The methodology developed can be broadly used in food RBA, to guide and reinforce a harmonized selection of nutritional, microbiological, and toxicological components and will contribute to facilitating RBA implementation, enabling the generation of transparent, robust, and comparable outcomes.
The impact of geriatric nutritional risk index on esophageal squamous cell carcinoma patients with neoadjuvant therapy followed by esophagectomy
Authors: Fang Pinhao , Yang Qian , Zhou Jianfeng , Yang Yushang , Luan Siyuan , Xiao Xin , Li Xiaokun , Gu Yimin , Shang Qixin , Zhang Hanlu , Chen Longqi , Zeng Xiaoxi , Yuan Yong
Published: October 2022

Background

The Geriatric Nutritional Index (GNRI) has been indicated as a nutritional index which is highly associated with complications and mortality in older hospitalized patients. Moreover, early studies had suggested that GNRI is a potential prognostic indicator for some malignances. However, the prognostic value of GNRI in esophageal squamous cell carcinoma (ESCC) patients underwent neoadjuvant therapy followed by esophagectomy remains elusive.

Materials and methods

This retrospective study incorporated 373 patients with ESCC who had underwent neoadjuvant therapy followed by radical esophagectomy at West China Hospital of Sichuan University between April 2011 and September 2021. The GNRI formula was: 1.489 × albumin (g/dl) + 41.7 × current weight/ideal weight. Patients were classified as GNRI-low (GNRI < 98.7) or GNRI high (GNRI ≥ 98.7). The association between GNRI and clinical survival status were assessed utilizing Kaplan-Meier methods and Cox regression analysis.

Results

Three hundred and seventy three patients were retrospectively included in this study. 80 (21.5%) and 293 (78.5%) patients had been divided into the GNRI-low and GNRI-high groups respectively. Pathological T stage and the rate of nodal metastasis were significantly higher in the GNRI low group than in the GNRI high group (P = 0.003 and P = 0.001, respectively) among the examined demographic parameters. Furthermore, GNRI was significantly correlated with postoperative complications, patients with lower GNRI had a higher postoperative complication rate as compared with GNRI high group [Odds ratio: 2.023; 95% confidence interval (CI): 1.208–3.389; P = 0.007]. Univariate analysis of 5-year overall survival (OS) and disease-free survival (DFS) found that the rate of survival was considerably lower in the GNRI-low group than in the GNRI-high group (P < 0.001). However, multivariate analysis demonstrated that GNRI was not an independent risk factor.

Conclusion

In patients with ESCC, low GNRI exhibited a poor nutritional indicator and related to postoperative complications after neoadjuvant therapy. Intensive follow-up after surgery should be performed for ESCC patients with low GNRI.
Folic acid ameliorates alcohol-induced liver injury via gut–liver axis homeostasis
Authors: Zhang Huaqi , Zuo Yuwei , Zhao Huichao , Zhao Hui , Wang Yutong , Zhang Xinyu , Zhang Jiacheng , Wang Peng , Sun Lirui , Zhang Huizhen , Liang Hui
Published: October 2022

The gut–liver axis (GLA) plays an important role in the development of alcohol-induced liver injury. Alcohol consumption is typically associated with folic acid deficiency. However, no clear evidence has confirmed the effect of folic acid supplementation on alcohol-induced liver injury via GLA homeostasis. In this study, male C57BL/6J mice were given 56% (v/v) ethanol and 5.0 mg/kg folic acid daily by gavage for 10 weeks to investigate potential protective mechanisms of folic acid in alcohol-induced liver injury via GLA homeostasis. Histopathological and biochemical analyses showed that folic acid improved lipid deposition and inflammation in the liver caused by alcohol consumption and decreased the level of ALT, AST, TG, and LPS in serum. Folic acid inhibited the expression of the TLR4 signaling pathway and its downstream inflammatory mediators in the liver and upregulated the expression of ZO-1, claudin 1, and occludin in the intestine. But compared with the CON group, folic acid did not completely eliminate alcohol-induced intestine and liver injury. Furthermore, folic acid regulated alcohol-induced alterations in gut microbiota. In alcohol-exposed mice, the relative abundance of Bacteroidota was significantly increased, and the relative abundance of unclassified_Lachnospiraceae was significantly decreased. Folic acid supplementation significantly increased the relative abundance of Verrucomicrobia, Lachnospiraceae_NK4A136_group and Akkermansia, and decreased the relative abundance of Proteobacteria. The results of Spearman’s correlation analysis showed that serum parameters and hepatic inflammatory cytokines were significantly correlated with several bacteria, mainly including Bacteroidota, Firmicutes, and unclassified_Lachnospiraceae. In conclusion, folic acid could ameliorate alcohol-induced liver injury in mice via GLA homeostasis to some extent, providing a new idea and method for prevention of alcohol-induced liver injury.
The comprehensive complication index is more sensitive than the Clavien–Dindo classification for grading complications in elderly patients after radical cystectomy and pelvic lymph node dissection: Implementing the European Association of Urology guideline
Authors: Huang Haiwen , Zhang Zhenan , Hao Han , Wang Haixin , Shang Meixia , Xi Zhijun
Published: October 2022

Objectives

Lack of assessment of 90-d perioperative morbidity in elderly patients after radical cystectomy and pelvic lymph node dissection (PLND) using a standard reporting methodology, and the Clavien–Dindo classification (CDC) does not accurately reflect the burden of complications. We aim to report the 90-d complications of elderly patients after radical cystectomy, and to compare the validity of the Comprehensive Complication Index (CCI) and CDC.

Methods

Retrospective review of 280 patients aged ≥75 years who received radical cystectomy between 2006 and 2021. The 90-d complications of elderly patients after radical cystectomy were reported by implementing the EAU criteria. The CDC and CCI were both used for grading complications. The Spearman rank correlation coefficient was used to estimate the correlation between postoperative stay and CDC/CCI. Logistic regression was used to identify the risk factors for major complications. The sample size for a fictive superiority trial was calculated for different endpoints.

Results

A total of 225 (80.36%) patients suffered from 528 complications. The cumulative CCI had a more accurate prediction of postoperative stay than the CDC (r = 0.378, p < 0.001 vs. r = 0.349, p < 0.001). The need for sample size could decrease when CCI was used for the primary endpoint. More risk factors for major complications were identified when CCI ≥33.7 was defined as the endpoint of major complications.

Conclusion

CCI is better than CDC for grading the severity of complications in elderly patients after radical cystectomy and PLND.
Diagnostic performance of six ultrasound-based risk stratification systems in thyroid follicular neoplasm: A retrospective multi-center study
Authors: Yang Jingjing , Sun Yu , Li Xingjia , Zhao Yueting , Han Xue , Chen Guofang , Ding Wenbo , Li Ruiping , Wang Jianhua , Xiao Fangsen , Liu Chao , Xu Shuhang
Published: October 2022

This study aimed to compare the diagnostic performances of six commonly used ultrasound-based risk stratification systems for distinguishing follicular thyroid adenoma (FTA) from follicular thyroid carcinoma (FTC), including the American Thyroid Association Sonographic Pattern System (ATASPS), ultrasound classification systems proposed by American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinology (AACE/ACE/AME), Korean thyroid imaging reporting and data system (K-TIRADS), European Thyroid Association for the imaging reporting and data system (EU-TIRADS), American College of Radiology for the imaging reporting and data system (ACR-TIRADS), and 2020 Chinese Guidelines for Ultrasound Malignancy Risk Stratification of Thyroid Nodules (C-TIRADS). A total of 225 FTA or FTC patients were retrospectively analyzed, involving 251 thyroid nodules diagnosed by postoperative pathological examinations in three centers from January 2013 to October 2021. The diagnostic performances of six ultrasound-based risk stratification systems for distinguishing FTA from FTC were assessed by plotting the receiver operating characteristic (ROC) curves and compared at different cut-off values. A total of 205 (81.67%) cases of FTA and 46 (18.33%) cases of FTC were involved in the present study. Compared with those of FTA, FTC presented more typical ultrasound features of solid component, hypoechoic, irregular margin and sonographic halo (all P<0.001). There were no significant differences in ultrasound features of calcification, shape and comet-tail artifacts between cases of FTA and FTC. There was a significant difference in the category of thyroid nodules assessed by the six ultrasound-based risk stratification systems (P<0.001). The areas under the curve (AUCs) of ATASPS, AACE/ACE/AME, K-TIRADS, EU-TIRADS, ACR-TIRADS and C-TIRADS in distinguishing FTA from FTC were 0.645, 0.729, 0.766, 0.635, 0.783 and 0.798, respectively. Our study demonstrated that all the six ultrasound-based risk stratification systems present potential in the differential diagnosis of FTA and FTC. Specifically, C-TIRADS exerts the best diagnostic performance among the Chinese patients. ATASPS possesses a high sensitivity, while K-TIRADS possesses a high specificity in distinguishing FTA from FTC.
Case report: Complete resection of invasive thymoma invading the superior vena cava and right atrium under cardiopulmonary bypass support
Authors: Zhang Xiangxin , Chen Liang , Zhou Wenyong , Wang Zhexin , Wang Chong , Shi Jianxin , Yao Feng
Published: October 2022

Here we describe an uncommon case of a 48-year-old male patient with an invasive thymoma invading the superior vena cava, bilateral innominate veins, right internal jugular vein, right subclavian vein, right atrium, azygos vein, and part of the lung tissues. The tumor was resected entirely under cardiopulmonary bypass support, and the venous bypass using a vascular graft was successfully established between the left innominate vein and the right atrium. The postoperative course was uneventful, and the patient was discharged 15 days after surgery without complications.
Knockdown of USP8 inhibits prostate cancer cell growth, proliferation, and metastasis and promotes docetaxel’s activity by suppressing the NF-kB signaling pathway
Authors: Islam Md. Tariqul , Chen Fang-Zhi , Chen Han-Chun , Wahid Abdul
Published: October 2022

Ubiquitin-specific protease 8 (USP8) has been recently reported to be involved in tumorigenesis. Prostate cancer (PCa) is the most diagnosed malignancy among men, but USP8’s role in PCa is not yet investigated comprehensively. Therefore, the PCa cell lines DU145 and PC3 were transfected with USP8 siRNA or overexpressing vector together with or without docetaxel. The silencing USP8 and docetaxel treatment reduced cell viability and migration and promoted apoptosis. In contrast, USP8 knockdown was found to enhance docetaxel antitumor activity. In contrast, increased cell viability and migration were noticed upon USP8 overexpression, thereby decreasing apoptosis and suppressing docetaxel antitumor activity. Notably, although EGFR, PI3K, and NF-kB were found to be increased in both USP8 overexpression and docetaxel treatment, it significantly attenuated the effects in USP8 silencing followed by with or without docetaxel. Although EGFR silencing decreased PI3K and NF-kB activation, overexpression of USP8 was shown to counteract SiEGFR’s effects on NF-kB signaling by increasing PI3K expression. Our findings revealed that USP8 plays an oncogenic role in PCa and can suppress docetaxel activity. Additionally, as EGFR/PI3K/NF-kB was previously reported to develop docetaxel resistance, the combination treatment of USP8 knockdown with docetaxel might be a potential PCa therapeutic.
Recent HPV self-sampling use for cervical cancer screening in Latin America and Caribbean: a systematic review
Authors: Dartibale Camila B. , Prado Gabriela de C. , Carobeli Lucimara R. , Meirelles Lyvia E. de F. , Damke Gabrielle M. Z. F. , Damke Edilson , Morelli Fabrício , Souza Raquel P. ,   Group PREVENT YOURSELF, da Silva Vânia R. S. , Consolaro Marcia E. L.
Published: October 2022

Objective

Cervical cancer is one of the deadliest cancers among women in Latin America and Caribbean (LAC), where most of the countries have not been successful in implementing population-level cytology-based screening programs. An increasing body of evidence supports the validity of self-sampling as an alternative to clinician collection for primary Human papillomavirus (HPV) screening. Therefore, this work aims to summarize recent HPV self-sampling approaches in LAC.

Method

We performed a systematic review to identify studies focused on “Self-sampling”, and “Human Papillomavirus DNA test” and “Latin America” in PubMed, Embase, Web of Science, Cochrane library and SCOPUS databases for publications dating between 01 January 2017 and 15 March 2022 based on the Preferred Reporting Items for systematic reviews and meta-analysis (PRISMA) statement. Additionally, the references of the articles were carefully reviewed.

Results

Of the 97 records selected, 20 studies including 163,787 participants, with sample sizes for individual studies ranging from 24 to 147,590 were included in this review. Studies were conducted in 10 LAC countries (18.5%), most with upper medium-income economies (70%). The range of age was 18 to ≥65 years. The vast majority of the studies (85%) addressed the HPV self-sampling strategy for primary cervical cancer screening with overall success for all women including under/never screened and those from special populations (rural, indigenous and gender minorities). Women generally found HPV self-sampling highly acceptable regardless of age, setting of collection, target population or country of residence.

Conclusions

HPV self-sampling is a promising strategy to overcome the multiple barriers to cervical cancer screening in LAC settings and increasing attendance in underscreened women in countries/territories with well-established screening programs. Furthermore, this strategy is useful even in LAC countries/territories without organized cervical cancer screening and in special populations such as indigenous, rural and transgender women. Therefore, the information generated by the recent initiatives for HPV self-sampling approach in LAC can be beneficial for decision-making in both new and existing programs in the region.
The genetics of myelodysplastic syndromes and the opportunities for tailored treatments
Authors: Kontandreopoulou Christina-Nefeli , Kalopisis Konstantinos , Viniou Nora-Athina , Diamantopoulos Panagiotis
Published: October 2022

Genomic instability, microenvironmental aberrations, and somatic mutations contribute to the phenotype of myelodysplastic syndrome and the risk for transformation to AML. Genes involved in RNA splicing, DNA methylation, histone modification, the cohesin complex, transcription, DNA damage response pathway, signal transduction and other pathways constitute recurrent mutational targets in MDS. RNA-splicing and DNA methylation mutations seem to occur early and are reported as driver mutations in over 50% of MDS patients. The improved understanding of the molecular landscape of MDS has led to better disease and risk classification, leading to novel therapeutic opportunities. Based on these findings, novel agents are currently under preclinical and clinical development and expected to improve the clinical outcome of patients with MDS in the upcoming years. This review provides a comprehensive update of the normal gene function as well as the impact of mutations in the pathogenesis, deregulation, diagnosis, and prognosis of MDS, focuses on the most recent advances of the genetic basis of myelodysplastic syndromes and their clinical relevance, and the latest targeted therapeutic approaches including investigational and approved agents for MDS.
Phosphogluconate dehydrogenase is a predictive biomarker for immunotherapy in hepatocellular carcinoma
Authors: Liu Tiantian , Qi Jianni , Wu Hao , Wang Le , Zhu Lihui , Qin Chengyong , Zhang Jiao , Zhu Qiang
Published: October 2022

Background

Phosphogluconate dehydrogenase (PGD) is involved in the regulation of various tumors. However, its role in hepatocellular carcinoma (HCC) is poorly understood. This study tried to determine the prognostic efficacy of PGD and its value for immunotherapy in HCC.

Methods

The data from the TCGA database was used to explore the predictive power of PGD expression and methylation on the overall survival (OS) of HCC through Cox regression and the Kaplan-Meier analysis. Then, we used the GEO and ICGC database to further verify the predictive power. Finally, the relationship between PGD and immune cells and the relationship between PGD and the efficacy of immunotherapy were explored through bioinformatics analysis in HCC.

Results

PGD is highly expressed in HCC tissues, which is negatively regulated by PGD methylation. Low PGD expression and PGD hypermethylation predict better OS in HCC patients. Besides, a meta-analysis based on the TCGA, GSE14520, and ICGC databases further confirms that low PGD expression is closely related to favorable OS. Then, we find significant differences of immune cell infiltrations between high and low PGD expression groups. Expressions of immune checkpoints, most HLA members and tumor mutation burden (TMB) are higher in the high PGD expression group, which indicates beneficial efficacy of immunotherapy in this group. And the potential mechanisms of PGD are exhibited.

Conclusion

PGD is an independent prognostic factor of HCC patients and plays an important role in immune cell infiltration and immunotherapy, which indicates that PGD can be used as a predictive biomarker for HCC immunotherapy.
Association between glial fibrillary acidic protein, glial-derived neurotrophic factor, and fatty acid-binding protein-2 at birth in the incidence of necrotizing enterocolitis in preterm infants
Authors: Angelika Dina , Etika Risa , Fitriah Munawaroh , Kusumawardani Naomi Nathania , Vita Angelica Diana , Irawan Roedi , Liem Kian Djien , Ugrasena I Dewa Gede
Published: October 2022

Background

This study aimed to analyze the relationship between glial fibrillary acidic protein (GFAP), glial-derived neurotrophic factor (GDNF), and fatty acid-binding protein-2 (FABP-2) in preterm infants on the incidence of NEC.

Methods

Preterm infants with a birth weight <1,500 g and gestational age <34 weeks were included in this study. Biomarker examination was performed using the umbilical vein blood at birth (first sample). Biomarker examination was repeated if the infant developed symptoms of NEC using peripheral vein blood (second sample). Infants were observed for 14 days. If NEC did not exist, a biomarker examination was performed at 14 days.

Results

This study included 30 preterm infants, nine infants experienced NEC. The values of GFAP, GDNF, and FABP-2 (median and range) in the group with NEC were higher than those in the group without NEC in both the first samples {GFAP [1.40 (0.20–6.50) vs. 0.30 (0.10–1.30) P = 0.014], GDNF [2.84 (1.05–14.11) vs. 1.56 (1.07–3.48) P = 0.050], and FABP-2 [621.70 (278.40–2,207.00) vs. 294.20 (211.40–597.50) P = 0.002]} and second samples {GFAP [2.40 (0.30–3.10) vs. 0.30 (0.10–0.60) P = 0.003], GDNF [2.99 (0.56–10.30) vs. 1.46 (0.85–2.24) P = 0.019], and FABP-2 [646.8 (179.20–1,571.00) vs. 314.90 (184.70–521.60) P = 0.040]}. In infants with NEC, the median values of GFAP [2.40 (0.30–3.10) vs. 1.40 (0.20–6.50) P = 0.767], GDNF [2.99 (0.56–10.30) vs. 2.84 (1.05–14.11) P = 0.859], and FABP-2 [646.80 (179.20–1,571.00) vs. 621.70 (278.40–2,207.00) P = 0.953] in the second sample were higher than those in the first sample. Logistic regression demonstrated that GFAP at birth (Odds Ratio [OR] = 15.629, 95% Confidence Interval [CI] = 1.697–143.906, P = 0.015) and FABP-2 levels at birth (OR = 1.008, 95% CI = 1.001–1.015, P = 0.033) were significantly associated with an increased risk of NEC.

Conclusion

Increased GFAP, GDNF, and FABP-2 at birth are associated with NEC occurrence within two weeks of birth. These findings suggest that early-onset NEC is associated with intestinal injury that occurs during the perinatal or even prenatal period.
Total serum IgE levels as predictor of the acquisition of tolerance in children with food allergy: Findings from a pilot study
Authors: Dodi Giulia , Di Filippo Paola , Di Pillo Sabrina , Chiarelli Francesco , Attanasi Marina
Published: October 2022

Background

The gold standard to diagnose food allergy (FA) is a double-blind, placebo-controlled food challenge (OFC), even if it shows potential risk of severe allergic reactions for the patient and is time-consuming. Therefore, easier, and less invasive methods are needed to diagnose FA and predict the tolerance, changing the clinical practice.

Aim

The main aim of this study was to assess whether the total IgE values at the diagnosis of FA were associated with the duration of the tolerance acquisition and thus of the food elimination diet.

Methods

We retrospectively analyzed the medical records of 40 patients allergic to milk or egg who performed an OFC for the reintroduction of the causal food at the Pediatric Allergy and Respiratory Unit of the University of Chieti from January 2018 to December 2020.

Results

We found a positive association of total serum IgE with the elimination diet duration (β = 0.152; CI, 95% 0.04–0.27) after adjusting for age, sex, and type of allergy (milk or egg). We also showed a significant correlation (r = 0.41 and p-value = 0.007) between the total IgE values and the duration of the elimination diet and a significant correlation between the casein specific IgE values at diagnosis of FA and the severity of the clinical presentation (r = 0.66; p-value 0.009).

Conclusion

Total serum IgE at baseline, along with the downward trend of food-specific IgE levels (to milk or egg), may be useful in the prognostication of natural tolerance acquisition.
A novel nomogram for predicting respiratory adverse events during transport after interventional cardiac catheterization in children
Authors: Tong Chaoyang , Liu Peiwen , Zhang Kan , Liu Ting , Zheng Jijian
Published: October 2022

Objective

The rate and predictors of respiratory adverse events (RAEs) during transport discharged from operating room after interventional cardiac catheterization in children remain unclear. This study aimed to investigate the incidence and predictors, and to construct a nomogram for predicting RAEs during transport in this pediatric surgical treatment.

Methods

This prospective cohort study enrolled 290 consecutive pediatric patients who underwent ventricular septal defects (VSD), atrial septal defects (ASD), and patent ductus arteriosus (PDA) between February 2019 and December 2020. Independent predictors were used to develop a nomogram, and a bootstrap resampling approach was used to conduct internal validation. Composite RAEs were defined as the occurrence of at least 1 complication regarding laryngospasm, bronchospasm, apnea, severe cough, airway secretions, airway obstruction, and oxygen desaturation.

Results

The rate of RAEs during transport was 23.1% (67 out of 290). Multivariate analysis identified age (vs. ≤3 years, adjusted odds ratio (aOR) = 0.507, 95% conﬁdence interval (CI), 0.268–0.958, P = 0.036), preoperative upper respiratory tract infections (URI, aOR = 2.335, 95% CI, 1.223–4.460, P = 0.01), type of surgery (vs. VSD, for ASD, aOR =  2.856, 95% CI, 1.272–6.411, P = 0.011; for PDA, aOR = 5.518, 95% CI, 2.425–12.553, P < 0.001), morphine equivalent (vs. ≤0.153 mg/kg, aOR = 2.904, 95% CI, 1.371–6.150, P = 0.005), atropine usage (aOR = 0.463, 95% CI, 0.244–0.879, P = 0.019), and RAEs during extubation to transport (aOR = 5.004, 95% CI, 2.633–9.511, P < 0.001) as independent predictors of RAEs during transport. These six candidate predictors were used to develop a nomogram, which showed a C-statistic value of 0.809 and good calibration (P = 0.844). Internal validation revealed similarly good discrimination (C-statistic, 0.782; 95% CI, 0.726–0.837) and calibration. Decision curve analysis (DCA) also demonstrated the clinical usefulness of the nomogram.

Conclusion

The high rate of RAEs during transport reminds us of the need for more medical care and attention. The proposed nomogram can reliably identify pediatric patients at high risk of RAEs during transport and guide clinicians to make proper transport plans. Our findings have important and meaningful implications for RAEs risk prediction, clinical intervention and healthcare quality control.
Prediction of endotracheal tube size in pediatric patients: Development and validation of machine learning models
Authors: Zhou Miao , Xu Wen.Y. , Xu Sheng , Zang Qing L. , Li Qi , Tan Li , Hu Yong C. , Ma Ning , Xia Jian H. , Liu Kun , Ye Min , Pu Fei Y. , Chen Liang , Song Li J. , Liu Yang , Jiang Lai , Gu Lin , Zou Zui
Published: October 2022

Objective

We aimed to construct and validate machine learning models for endotracheal tube (ETT) size prediction in pediatric patients.

Methods

Data of 990 pediatric patients underwent endotracheal intubation were retrospectively collected between November 2019 and October 2021, and separated into cuffed and uncuffed endotracheal tube subgroups. Six machine learning algorithms, including support vector regression (SVR), logistic regression (LR), random forest (RF), gradient boosting tree (GBR), decision tree (DTR) and extreme gradient boosting tree (XGBR), were selected to construct and validate models using ten-fold cross validation in training set. The optimal models were selected, and the performance were compared with traditional predictive formulas and clinicians. Furthermore, additional data of 71 pediatric patients were collected to perform external validation.

Results

The optimal 7 uncuffed and 5 cuffed variables were screened out by feature selecting. The RF models had the best performance with minimizing prediction error for both uncuffed ETT size (MAE = 0.275 mm and RMSE = 0.349 mm) and cuffed ETT size (MAE = 0.243 mm and RMSE = 0.310 mm). The RF models were also superior in predicting power than formulas in both uncuffed and cuffed ETT size prediction. In addition, the RF models performed slightly better than senior clinicians, while they significantly outperformed junior clinicians. Based on SVR models, we proposed 3 novel linear formulas for uncuffed and cuffed ETT size respectively.

Conclusion

We have developed machine learning models with excellent performance in predicting optimal ETT size in both cuffed and uncuffed endotracheal intubation in pediatric patients, which provides powerful decision support for clinicians to select proper ETT size. Novel formulas proposed based on machine learning models also have relatively better predictive performance. These models and formulas can serve as important clinical references for clinicians, especially for performers with rare experience or in remote areas.
Resveratrol activates CD8+ T cells through IL-18 bystander activation in lung adenocarcinoma
Authors: Zhang Wei , Zhang Ruohao , Chang Zhiguang , Wang Xiaobo
Published: October 2022

Resveratrol, a natural product, has demonstrated anti-tumor effects in various kinds of tumor types, including colon, breast, and pancreatic cancers. Most research has focused on the inhibitory effects of resveratrol on tumor cells themselves rather than resveratrol’s effects on tumor immunology. In this study, we found that resveratrol inhibited the growth of lung adenocarcinoma in a subcutaneous tumor model by using the β-cyclodextrin-resveratrol inclusion complex. After resveratrol treatment, the proportion of M2-like tumor-associated macrophages (TAMs) was reduced and tumor-infiltrating CD8T cells showed significantly increased activation. The results of co-culture and antibody neutralization experiments suggested that macrophage-derived IL-18 may be a key cytokine in the resveratrol anti-tumor effect of CD8T cell activation. The results of this study demonstrate a novel view of the mechanisms of resveratrol tumor suppression. This natural product could reprogram TAMs and CD8T effector cells for tumor treatment.
Efficacy and safety of pharmacological interventions for pruritus in primary biliary cholangitis: A systematic review and meta-analysis
Authors: Xu Chenyi , Yue Rensong , Lv Xuelian , Wang Shengnan , Du Mengmeng
Published: October 2022

Background and objective: Pruritus is a common complication in patients with primary biliary cholangitis (PBC). The pathogenesis is not clear, and also the precise therapeutic measures remain alluring. In order to systematically evaluate the efficacy and safety of drug interventions in the treatment of pruritus associated with PBC, this systemic review and meta-analysis was conducted.

Methods: The randomized controlled trials (RCTs) on drug interventions in the treatment of pruritus associated with primary cholangitis were searched in the electronic databases of PubMed, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov. Two researchers independently screened the literature, extracted and integrated the data, and assessed the bias risk of the selected literature, according to the Cochrane handbook. Finally, the STATA 15.0 software was used for the meta-analysis.

Results: A total of 23 RCTs involving 2,194 patients were studied, that included 12 pharmacological interventions. In terms of itching relief, compared with placebo, UDCA, methotrexate and GSK2330672 had a definite effect in improving pruritus (pruritus remission rate before and after treatment, p < 0.05). In terms of serum indexes, compared with placebo group, UDCA, OCA, rifampicin, cyclosporine, NGM282, seladelpar and colchicine may improve blood alkaline phosphatase (ALP) (p < 0.05), but only rifampicin showed low heterogeneity. UDCA, bezafibrate, OCA, rifampicin, NGM282 and others may improve blood γ-glutamyl transpeptidase (γ-GGT) (p < 0.05), but due to the high heterogeneity and the limitation of research samples, a clear conclusion cannot be drawn. In terms of adverse events, except high (>15 mg/kg/day) and low doses (<13 mg/kg/day) of UDCA increased the incidence of adverse events, there were no risk of increasing the incidence of adverse events compared with placebo (p > 0.05), and a moderate dose of UDCA (13–15 mg/kg/day) and malotilate (1,500 mg/day) may also help in reducing the incidence of adverse events (p < 0.05).

Conclusion: UDCA, methotrexate and GSK2330672 may relieve itching in patients with PBC, but there is a lack of robust evidence to support their effect on ALP or γ-GGT. Due to the heterogeneity in the published studies, based on the present review, we cannot explicitly recommend any specific drug for the treatment of PBC-related pruritus.

Systematic Review Registration:link-https://osf.io/2g8ya, identifier 10.17605/OSF.IO/2G8YA
LTT and HLA testing as diagnostic tools in Spanish vancomycin-induced DRESS cases: A case-control study
Authors: Bellón Teresa , Lerma Victoria , Guijarro Javier , Ramírez Elena , Martínez Celia , Escudero Carmelo , Fiandor Ana M. , Barranco Ruth , de Barrio Manuel , de Abajo Francisco , Cabañas Rosario ,   PIELenRed Study Group
Published: October 2022

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe T-cell-mediated off-target adverse reaction. DRESS cases caused by vancomycin have often been reported. The HLA-A*32:01 allele has been associated with genetic susceptibility to vancomycin-induced DRESS in US citizens of European descent. We have analyzed the association of the HLA-A*32:01 allele in 14 Spanish DRESS cases in which vancomycin was suspected as the culprit drug, and the lymphocyte transformation test (LTT) as an in vitro assay to evaluate vancomycin sensitization. The results were compared to vancomycin-tolerant control donors. LTT was performed in 12 DRESS cases with PBMCs from resolution samples available and in a group of 12 tolerant donors. ROC curves determined that LTT is a suitable tool to identify patients sensitized to vancomycin (AUC = 0.9646; p < 0.0001). When a stimulation index >3 was regarded as a positive result, contingency tables determined 91% sensitivity, 91.67% specificity, 91% positive predictive value, and 91.67% negative predictive value (p = 0.0001, Fisher’s exact test). The HLA A*32:01 allele was determined by an allele-specific PCR assay in 14 cases and 25 tolerant controls. Among the DRESS cases, five carriers were identified (35.7%), while it was detected in only one (4%) of the tolerant donors, [odds ratio (OR) = 13.33; 95% CI: 1.364–130.3; p = 0.016]. The strength of the association increased when only cases with positive LTT to vancomycin were considered (OR = 24.0; 95% CI: 2.28–252.6; p = 4.0 × 10−3). Our results confirm the association of the risk allele HLA-A*32:01 with vancomycin-induced DRESS in Spanish cases, and support LTT as a reliable tool to determine vancomycin sensitization.
Identification and metabolomic characterization of potent anti-MRSA phloroglucinol derivatives from Dryopteris crassirhizoma Nakai (Polypodiaceae)
Authors: Bhowmick Sumana , Beckmann Manfred , Shen Jianying , Mur Luis A. J.
Published: October 2022

Traditional Chinese medicine (TCM) has been used to treat infectious diseases and could offer potential drug leads. This study evaluates the in vitro antimicrobial activities from commercially sourced Dryopteris crassirhizoma Nakai (Polypodiaceae) whose authenticity was confirmed by DNA barcoding based on the ribulose bisphosphate carboxylase (rbcL) gene. Powdered rhizomes were sequentially extracted using n-hexane, dichloromethane, ethyl acetate, and methanol at ambient temperature. The dried extracts at different concentrations were tested for antimicrobial activities against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and Mycobacterium smegmatis. D. crassirhizoma extracts exhibited significant antimicrobial activities only against MRSA (minimum inhibitory concentration: 3.125 μg/ml n-hexane extract). Activity-led fractionations of D. crassirhizoma and characterization by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) targeted a fraction (A3), with two anti-MRSA phloroglucinol derivatives, flavaspidic acid AB and norflavaspidic acid AB—being greatly enriched in the latter. The impact of A3 on MRSA cells was examined using untargeted metabolomic analysis and compared to that of other established antibiotics (all treatments normalized to MIC50 at 6 h). This suggested that norflavaspidic acid AB had distinctive effects, one of which involved targeting bioenergetic transformation, metabolism, and particularly acetyl-CoA, on MRSA cells. No cytotoxicity was observed for the norflavaspidic acid AB-enriched fraction against murine HepG2 cells. This study requires further experimental validation but can have indicated a naturally available compound that could help counter the threat of clinically relevant strains with antibiotic resistance.
Astragalus saponins and its main constituents ameliorate ductular reaction and liver fibrosis in a mouse model of DDC-induced cholestatic liver disease
Authors: Zhang Linzhang , Hu Yonghong , Qi Shenglan , Zhang Congcong , Zhou Qun , Zhang Dingqi , Mu Yongping , Zhang Hua , Chen Gaofeng , Liu Ping , Chen Jiamei , Liu Wei
Published: October 2022

Cholestatic liver disease (CLD) is a chronic liver disease characterized by ductular reaction, inflammation and fibrosis. As there are no effective chemical or biological drugs now, majority of CLD patients eventually require liver transplantation. Astragali radix (AR) is commonly used in the clinical treatment of cholestatic liver disease and its related liver fibrosis in traditional Chinese medicine, however its specific active constituents are not clear. Total astragalus saponins (ASTs) were considered to be the main active components of AR. The aim of this study is to investigate the improvement effects of the total astragalus saponins (ASTs) and its main constituents in cholestatic liver disease. The ASTs from AR was prepared by macroporous resin, the content of saponins was measured at 60.19 ± 1.68%. The ameliorative effects of ASTs (14, 28, 56 mg/kg) were evaluated by 3, 5-Diethoxycarbonyl-1, 4-dihydrocollidine (DDC)-induced CLD mouse model. The contents of hydroxyproline (Hyp), the mRNA and protein expression of cytokeratin 19 (CK19) and α-smooth muscle actin (α-SMA) in liver tissue were dose-dependently improved after treatment for ASTs. 45 astragalus saponins were identified in ASTs by UHPLC-Q-Exactive Orbitrap HRMS, including astragaloside I, astragaloside II, astragaloside III, astragaloside IV, isoastragaloside I, isoastragaloside II, cycloastragenol, etc. And, it was found that ductular reaction in sodium butyrate-induced WB-F344 cell model were obviously inhibited by these main constituents. Finally, the improvement effects of astragaloside I, astragaloside II, astragaloside IV and cycloastragenol (50 mg/kg) were evaluated in DDC-induced CLD mice model. The results showed that astragaloside I and cycloastragenol significantly improved mRNA and protein expression of CK19 and α-SMA in liver tissue. It suggested that astragaloside I and cycloastragenol could alleviate ductular reaction and liver fibrosis. In summary, this study revealed that ASTs could significantly inhibit ductular reaction and liver fibrosis, and astragaloside I and cycloastragenol were the key substances of ASTs for treating cholestatic liver disease.
Research progress on microRNA in gout
Authors: Xie Jing , He Cuixia , Su Yue , Ding Yuzhou , Zhu Xingyu , Xu Yuanyuan , Ding Jiaxiang , Zhou Huan , Wang Hongju
Published: October 2022

Gout is a common form of arthritis caused by the deposition of sodium urate crystals in the joints and tissues around them. MicroRNAs (miRNAs) are noncoding RNAs that have been shown to be involved in regulating the pathogenesis of gout through multiple cellular signaling pathways, which may be potential targets for the treatment of gout. In this review, we systematically discuss the regulatory roles of related miRNAs in gout, which will provide help for the treatment of gout and miRNAs is expected to become a potential biomarker for gout diagnosis.
An Ethnobotanical study of medicinal plants in Taşköprü (Kastamonu–Turkey)
Authors: Senkardes Ismail , Dogan Ahmet , Emre Gizem
Published: October 2022

This pharmaceutical ethnobotanical research was carried out in Taşköprü District in Kastamonu, in northern Anatolia. It assembles the elaborations of plants used as folk medicines, and the ethnopharmacological data collected in the course of in-person semi-structured interviews with an open-ended questionnaire. The study’s aims were two-fold: gathering and identifying plants that the local inhabitants use therapeutically, and recording information related to traditional folk medicine (primarily for humans, and if extant for animals). The plants were gathered during several outings between May 2016 and July 2018. The organization of the data was based on the use-reports (UR) and was done according to the ICPC-2 classification. In addition, cultural importance index (CI) and informant consensus factor (FIC) calculations were made for the data collected. The research identified 101 plant taxa of 31 families used in folk medicine. Of these, 89 were wild and 12 were cultivated taxa. In total, 499 medicinal uses were determined. The CI values indicated that the most significant medicinal plant specimens were Pinus nigra subsp. pallasiana (0.78), P. sylvestris var. hamata (0.75) and Plantago lanceolata, P. major subsp. intermedia and P. major subsp. major (0.58 each). The most prevalent families were Asteraceae (2.14), Rosaceae (1.93), Pinaceae (1.81) and Plantaginaceae (1.74). Respiratory system (0.95), skin and subcutaneous tissue (0.94), nervous system (0.92) and circulatory system disorders (0.88) and ethnoveterinary uses (0.89) had the highest FIC values. The most frequently used preparation process was observed to be decoction (38.4%) and the most commonly utilized plant parts were aerial (21%). Along with recording 20 plant taxa as medicinal plants for the first time, this study documented a total of 303 new therapeutic uses. This study concludes with the finding that traditional knowledge of medicinal plants remains prevalent in Ta rticularly among its rural inhabitants.
Recent developments in nucleic acid-based therapies for Parkinson’s disease: Current status, clinical potential, and future strategies
Authors: Pandey Shivam Kumar , Singh Rakesh Kumar
Published: October 2022

Parkinson’s disease is the second most common progressive neurodegenerative disease diagnosed mainly based on clinical symptoms caused by loss of nigrostriatal dopaminergic neurons. Although currently available pharmacological therapies provide symptomatic relief, however, the disease continues to progress eventually leading to severe motor and cognitive decline and reduced quality of life. The hallmark pathology of Parkinson’s disease includes intraneuronal inclusions known as Lewy bodies and Lewy neurites, including fibrillar α-synuclein aggregates. These aggregates can progressively spread across synaptically connected brain regions leading to emergence of disease symptoms with time. The α-synuclein level is considered important in its fibrillization and aggregation. Nucleic acid therapeutics have recently been shown to be effective in treating various neurological diseases, raising the possibility of developing innovative molecular therapies for Parkinson’s disease. In this review, we have described the advancements in genetic dysregulations in Parkinson’s disease along with the disease-modifying strategies involved in genetic regulation with particular focus on downregulation of α-synuclein gene using various novel technologies, notably antisense oligonucleotides, microRNA, short interfering RNA, short hairpin RNAs, DNA aptamers, and gene therapy of vector-assisted delivery system-based therapeutics. In addition, the current status of preclinical and clinical development for nucleic acid-based therapies for Parkinson’s disease have also been discussed along with their limitations and opportunities.
Precision frequency transfer with fiber frequency combs
Authors: Fermann Martin E. , Lee Kevin F. , Li Peng , Rolland Antoine , Jiang Jie
Published: October 2022

We review methods for precision transfer of frequencies across broad optical wavelength ranges. Single-branch supercontinuum generation allows for a frequency transfer stability of < 1 × 10−17in 1 s across an octave. With supercontinuum stitching, highly coherent supercontinuum spectra spanning across more than two octaves are generated. With noise cancellation techniques a relative frequency transfer stability of ≈ 2 × 10−18in 1 s can be achieved. Highly stable frequency transfer along with a maximization of power per mode at multiple freely selectable frequency bands is further enabledviapulse shaping techniques. We also include a brief review of general fiber combs and research aimed at frequency extension of frequency combs covering the whole spectral range from the XUV to the mid IR, power scaling of frequency combs as well as low noise microwave and mmwave technology enabled with frequency combs.
HUXt—An open source, computationally efficient reduced-physics solar wind model, written in Python
Authors: Barnard Luke , Owens Mathew
Published: October 2022

HUXt is an open source numerical model of the solar wind written in Python. It is based on the solution of the 1D inviscid Burger’s equation. This reduced-physics approach produces solar wind flow simulations that closely emulate the flow produced by 3-D magnetohydrodynamic (MHD) solar wind models at a small fraction of the computational expense. While not intended as a replacement for 3-D MHD, the simplicity and computational efficiency of HUXt offers several key advantages that enable experiments and the use of techniques that would otherwise be cost prohibitive. For example, large ensembles of 102–105 members can easily be run with modest computing resources, which are useful for exploring and quantifying the uncertainty in space weather predictions, as well as for the application of some data assimilation methods. In this article we present the developments in the latest version of HUXt, v4.0, and discuss our plans for future developments and applications of the model. The three key developments in v4.0 are: 1) a restructuring of the models solver to enable fully time-dependent boundary conditions, such that HUXt can in principle be initialised with in-situ observations from any of the fleet of heliospheric monitors; 2) new functionality to trace streaklines through the HUXt flow solutions, which can be used to track features such as the Heliospheric Current Sheet; 3) introduction of a small test-suite so that we can better ensure the reliability and reproducibility of HUXt simulations for all users across future versions. Other more minor developments are discussed in the article. Future applications of HUXt are discussed, including the development of both sequential and variational data assimilation schemes for assimilation of both remote sensing and in-situ plasma measures. Finally, we briefly discuss the progress of transitioning HUXt into an operational model at the UK’s Met Office Space Weather Operations Center as part of the UK governments SWIMMR programme.