bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coexisting Type 1 Diabetes, Persistent Symptoms, and Financial Issues Associate With Poorer Adherence to a Gluten-Free Diet in Celiac Disease After Transition From Pediatrics to Adult Care
Authors: Kivelä Laura , Eurén Anna , Repo Marleena , Huhtala Heini , Kaukinen Katri , Kurppa Kalle 
Published: June 2022

PurposeWe evaluated adherence to a gluten-free diet and associated factors in adult celiac disease patients diagnosed in childhood.MethodsComprehensive medical data on 955 pediatric celiac disease patients was collected and study questionnaires sent to 559 who were now adults. All variables were compared between strictly adherent and non-adherent patients.ResultsAltogether 237 adults (median age 27 years, 69% women) responded to the questionnaires a median of 18 (range 3–51) years after the childhood diagnosis. Altogether 78% were reportedly adherent and 22% non-adherent. The non-adherent patients had more concomitant type 1 diabetes (18% vs. 4%, p = 0.003), whereas the groups did not differ in demographic data or clinical and histological features at diagnosis, or in short-term dietary adherence. In adulthood, non-adherent patients found gluten-free diet more challenging (39% vs. 17%, p &lt; 0.001) and had higher prevalence (39% vs. 19%, p = 0.004) and severity of symptoms. The main motivation factors for dietary adherence were attempts to avoid symptoms and complications, but these were considered less important and price of gluten-free products more important among non-adherent patients. Adherent and non-adherent patients did not differ in socioeconomic or lifestyle factors, comorbidities other than type 1 diabetes, self-reported general health, health concerns, follow-up, or in quality of life.ConclusionMost originally pediatric celiac disease patients reported strict dietary adherence in adulthood. However, particularly those with concomitant type 1 diabetes, persistent symptoms or financial issues may require attention during the transition from pediatric to adult care.
The Gut Microbiome of Preterm Infants Treated With Aminophylline Is Closely Related to the Occurrence of Feeding Intolerance and the Weight Gain
Authors: Shen Wei , Qiu Wen , Lin Qi , Zeng Chao , Liu Yuting , Huang Weimin , Zhou Hongwei 
Published: June 2022

BackgroundAminophylline is widely used in the treatment of preterm infants, but it can cause feeding intolerance events, in which gut microbial dysbiosis may have a role. This study aims to investigate the relationship between the gut microbiome of preterm infants treated with aminophylline and the occurrence of feeding intolerance and weight gain rate.MethodsThis study included a cohort of 118 preterm infants. Survival analysis and multivariate Cox regression were used to evaluate the relationship between aminophylline treatment and the occurrence of feeding intolerance. 16S rRNA V4 region gene sequencing was used to characterize the microbiome of fecal samples from the cohort. Linear discriminant analysis effect size was used to analyze the differential abundance of bacteria related to aminophylline treatment. Wilcoxon test, Kruskal–Wallis test, Spearman correlation coefficients and generalized linear mixed models were used to analyze the correlation between the differential bacteria and feeding intolerance events as well as the weight gain.ResultsThe results showed that the use of aminophylline could significantly increase the occurrence of feeding intolerance. The relative abundances of Streptococcus and Rothia in the gut microbiome of preterm infants were positively correlated with both the occurrence of feeding intolerance and the use of aminophylline, while the relative abundance of Staphylococcus was negatively correlated. In particular, preterm infants with a lower relative abundance of Rothia were more likely to develop feeding intolerance associated with aminophylline, and this difference existed before the onset of feeding intolerance. Moreover, it took longer for individuals with a lower relative abundance of Streptococcus to reach 2 kg weight. The contribution of Streptococcus to weight gain was greater than that of Bifidobacterium or Lactobacillus.ConclusionThe gut microbiome in preterm infants treated with aminophylline was characterized by a decrease in Streptococcus and Rothia and an increase in Staphylococcus. These microbes, especially Rothia, were positively correlated with the occurrence of feeding intolerance. Streptococcus but not Bifidobacter likely participated in the weight gain of preterm infants in early life.
Gene Coexpression Network Characterizing Microenvironmental Heterogeneity and Intercellular Communication in Pancreatic Ductal Adenocarcinoma: Implications of Prognostic Significance and Therapeutic Target
Authors: Wu Chengsi , Liu Yizhen , Wei Dianhui , Tao Li , Yuan Lili , Jing Tiantian , Wang Boshi 
Published: June 2022

BackgroundPancreatic ductal adenocarcinoma (PDAC) is characterized by intensive stromal involvement and heterogeneity. Pancreatic cancer cells interact with the surrounding tumor microenvironment (TME), leading to tumor development, unfavorable prognosis, and therapy resistance. Herein, we aim to clarify a gene network indicative of TME features and find a vulnerability for combating pancreatic cancer.MethodsSingle-cell RNA sequencing data processed by the Seurat package were used to retrieve cell component marker genes (CCMGs). The correlation networks/modules of CCMGs were determined by WGCNA. Neural network and risk score models were constructed for prognosis prediction. Cell–cell communication analysis was achieved by NATMI software. The effect of the ITGA2 inhibitor was evaluated in vivo by using a KrasG12D-driven murine pancreatic cancer model.ResultsWGCNA categorized CCMGs into eight gene coexpression networks. TME genes derived from the significant networks were able to stratify PDAC samples into two main TME subclasses with diverse prognoses. Furthermore, we generated a neural network model and risk score model that robustly predicted the prognosis and therapeutic outcomes. A functional enrichment analysis of hub genes governing gene networks revealed a crucial role of cell junction molecule–mediated intercellular communication in PDAC malignancy. The pharmacological inhibition of ITGA2 counteracts the cancer-promoting microenvironment and ameliorates pancreatic lesions in vivo.ConclusionBy utilizing single-cell data and WGCNA to deconvolute the bulk transcriptome, we exploited novel PDAC prognosis–predicting strategies. Targeting the hub gene ITGA2 attenuated tumor development in a PDAC mouse model. These findings may provide novel insights into PDAC therapy.
A Comprehensive Model for Diagnosis of Primary Breast Lymphoma Differentiated From Breast Cancer and Prognosis Evaluation of Surgical Treatment
Authors: Li Yanan , Zhang Yan , Wang Wei , Wei Chong , Zhao Danqing , Zhang Wei 
Published: June 2022

BackgroundThe objective of this work was to discriminate between primary breast lymphoma (PBL) and breast cancer by systematically analyzing clinical characteristics, laboratory examination results, ultrasound features, and mammography findings to establish a diagnostic model for PBL and to analyze the influence of surgical treatment on the prognosis of PBL patients.MethodWe analyzed 20 PBL and 70 breast cancer patients treated during the same period by comparing several characteristics: clinical features, such as age, tumor position, and breast complaints; laboratory examination findings, such as the lactate dehydrogenase (LDH) level, and imaging features such as the maximum diameter, shape, margins, aspect ratio, and calcification of the mass and axillary lymph node involvement. A diagnostic model was then developed using logistic regression analysis. The impact of surgery on the prognosis of PBL patients was assessed through Kaplan–Meier survival analysis.ResultBreast cancer and PBL could be distinguished based on imaging features, including the maximum diameter, shape, margin, and calcification of the mass, and lymph node involvement (P &lt; 0.05). There were no significant differences between PBL and breast cancer patients in terms of clinical features, or the LDH level. The area under the receiver operating characteristic curve was 0.821. The log-rank test showed that surgery had no significant influence on the prognosis of PBL patients.ConclusionUltrasound and mammography are the most useful methods for detecting malignant breast tumors. Compared with breast cancer tumors, breast lymphoma tumors are larger with a more regular shape and less calcification and are often accompanied by axillary lymph node involvement. Patients with a breast malignancy should not undergo surgical excision without an accurate diagnosis.
A Feasibility Study of Deep Learning-Based Auto-Segmentation Directly Used in VMAT Planning Design and Optimization for Cervical Cancer
Authors: Chen Along , Chen Fei , Li Xiaofang , Zhang Yazhi , Chen Li , Chen Lixin , Zhu Jinhan 
Published: June 2022

PurposeTo investigate the dosimetric impact on target volumes and organs at risk (OARs) when unmodified auto-segmented OAR contours are directly used in the design of treatment plans. Materials and MethodsA total of 127 patients with cervical cancer were collected for retrospective analysis, including 105 patients in the training set and 22 patients in the testing set. The 3D U-net architecture was used for model training and auto-segmentation of nine types of organs at risk. The auto-segmented and manually segmented organ contours were used for treatment plan optimization to obtain the AS-VMAT (automatic segmentations VMAT) plan and the MS-VMAT (manual segmentations VMAT) plan, respectively. Geometric accuracy between the manual and predicted contours were evaluated using the Dice similarity coefficient (DSC), mean distance-to-agreement (MDA), and Hausdorff distance (HD). The dose volume histogram (DVH) and the gamma passing rate were used to identify the dose differences between the AS-VMAT plan and the MS-VMAT plan.Results Average DSC, MDA and HD95 across all OARs were 0.82–0.96, 0.45–3.21 mm, and 2.30–17.31 mm on the testing set, respectively. The D99% in the rectum and the Dmean in the spinal cord were 6.04 Gy (P = 0.037) and 0.54 Gy (P = 0.026) higher, respectively, in the AS-VMAT plans than in the MS-VMAT plans. The V20, V30, and V40 in the rectum increased by 1.35% (P = 0.027), 1.73% (P = 0.021), and 1.96% (P = 0.008), respectively, whereas the V10 in the spinal cord increased by 1.93% (P = 0.011). The differences in other dosimetry parameters were not statistically significant. The gamma passing rates in the clinical target volume (CTV) were 92.72% and 98.77%, respectively, using the 2%/2 mm and 3%/3 mm criteria, which satisfied the clinical requirements.ConclusionsThe dose distributions of target volumes were unaffected when auto-segmented organ contours were used in the design of treatment plans, whereas the impact of automated segmentation on the doses to OARs was complicated. We suggest that the auto-segmented contours of tissues in close proximity to the target volume need to be carefully checked and corrected when necessary.
Free-Breathing Liver Magnetic Resonance Imaging With Respiratory Frequency-Modulated Continuous-Wave Radar-Trigger Technique: A Preliminary Study
Authors: Liang Xinyue , Bi Zhenghong , Yang Chun , Sheng Ruofan , Xia Xinyuan , Zhang Zheng , Dai Yongming , Zeng Mengsu 
Published: June 2022

PurposeThe aim of this study is to evaluate the performance of free-breathing liver MRI with a novel respiratory frequency-modulated continuous-wave radar-trigger (FT) technique on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) for both healthy volunteers and patients in comparison to navigator-trigger (NT) and belt-trigger (BT) techniques.MethodsIn this prospective study, 17 healthy volunteers and 23 patients with known or suspected liver diseases were enrolled. Six sequences (T2WI and DWI with FT, NT, and BT techniques) were performed in each subject. Quantitative evaluation and qualitative assessment were analyzed by two radiologists. Overall image quality, blurring, motion artifacts, and liver edge delineations were rated on a 4-point Likert scale. The liver and lesion signal-to-noise ratio (SNR), the lesion-to-liver contrast-to-noise ratio (CNR), as well as the apparent diffusion coefficient (ADC) value were quantitatively calculated.ResultsFor volunteers, there were no significant differences in the image quality Likert scores and quantitative parameters on T2WI and DWI with three respiratory-trigger techniques. For patients, NT was superior to other techniques for image quality on T2WI; conversely, little difference was found on DWI in qualitative assessment. The mean SNR of the liver on T2WI and DWI with BT, NT, and FT techniques was similar in patients, which is in line with volunteers. FT performed better in terms of higher SNR (705.13 ± 434.80) and higher CNR (504.41 ± 400.69) on DWI at b50 compared with BT (SNR: 651.83 ± 401.16; CNR:429.24 ± 404.11) and NT (SNR: 639.41 ± 407.98; CNR: 420.64 ± 416.61) (p &lt; 0.05). The mean ADC values of the liver and lesion with different techniques in both volunteers and patients showed non-significant difference.ConclusionFor volunteers, the performance of T2WI as well as DWI with three respiratory-trigger techniques was similarly good. As for patients, FT-DWI is superior to BT and NT techniques in terms of higher lesion SNR and CNR at b50.
Tracheobronchial Foreign Bodies in Children: Experience From 1,328 Patients in China
Authors: Ding Ling , Su Shuping , Chen Cheng , Yao Hongbing , Xiao Ling 
Published: June 2022

Objective:To analyze the clinical characteristics of tracheobronchial foreign body (FB) cases in a pediatric Chinese population.MethodsThe clinical data of pediatric patients aged 0–18 years old diagnosed with a tracheobronchial FB in the Children's Hospital of Chongqing Medical University between September 2018 and August 2021 were analyzed retrospectively.ResultsAmong 1,328 included cases, 92.09% of patients were &lt;3 years old, the male to female ratio was 1.86:1. The prevalence of tracheobronchial FB was similar between patients living in rural and urban areas and tracheobronchial FBs were more common in winter. The most common presenting symptoms were cough and wheezing. The most common CT findings was local obstruction or tracheobronchial narrowing, followed by obstructive emphysema of lung and pneumonia. The 11.3% of cases that did not report FB aspiration on admission had a longer time to hospital admission and longer hospitalization time than cases reporting FB aspiration (P &lt; 0.05). The most common FB type was nuts (81.17%). FBs were more frequently located in the right bronchus, and 64 (4.82%) cases involved multiple FBs. FBs were expelled by coughing in only 4.07% of cases. For the other cases, FB removal by first bronchoscopy in our hospital was successful and complete in 96.86% of cases. 1.51% of patients had hypoxic ischemic encephalopathy (HIE) and the location of FBs was a possible risk factor for HIE (P &lt; 0.05).ConclusionsTracheobronchial FBs occurred most commonly in children &lt;3 years old. If asphyxia occurs in children which FBs aspirated, emergency treatment is needed to reduce the occurrence of HIE. Rigid bronchoscopy remains the first-line method for FB removal in children.
Old Drug, New Pain. Roles and Challenges of Methadone Therapy in Pediatric Palliative Care: A Systematic Review
Authors: Benedetti Francesca , Zoletto Silvia , Salerno Annalisa , Avagnina Irene , Benini Franca 
Published: June 2022

BackgroundPediatric palliative care (PPC) is defined as the prevention and relief from suffering of families and children with life-limiting (LLDs) or life-threatening diseases (LTDs). These patients often experience pain, with morphine being the most widely used drug to treat it. Few studies investigated the role of methadone in PPC patients, although it is considered among the most effective and underutilized drugs in PPC.ObjectivesOur aim was to evaluate the efficacy, safety, and dosage of methadone in PPC.MethodsBetween August and October 2021 PubMed, Scopus and the Cochrane Library were searched for studies on the use of methadone in children with LLDs and LTDs. Articles were included if they met the following criteria: published in the last 10 years, English language, patients aged 0–23 years; children enrolled in a PPC center or receiving declared support from a PPC service; reporting of specific data on methadone in interventional trials, observational studies, or case series on &gt;10 patients. The reporting of the article was guided by the PRISMA guidelines, and a critical appraisal of the included studies was performed using the JBI-tool.ResultsAfter duplicates removal and full-text assessment, four studies were included and another one was added after checking the references of the retrieved papers. All were retrospective, and the literature is concordant in documenting the lack of evidence. A total of 116 children received methadone in PPC. From our review emerges the poor quality of data collection: in only one study pain was assessed with standardized scales. All studies documented the effectiveness of methadone in treating complex pain, either nociceptive or neuropathic. No serious adverse events were reported, with no cases of cardiac arrhythmias.ConclusionOur results suggest that methadone could represent a suitable strategy for treating pain in PPC. However, the evidence base is insufficient, and further research is warranted.
A Dual-Labeling Probe for Super-Resolution Imaging to Detect Mitochondrial Reactive Sulfur Species in Live Cells
Authors: Hu Maomao , Wang Boyang , Zhang Hongdan , Wang Han , Li Huixin , Zhang Xinyu , Zhang Jinjin , Lu Qianrun , Fang Guiqian , Wang Juan , Dong Bo 
Published: June 2022

Background: Mitochondria are the main sites of reactive sulfur species (RSS) production in living cells. RSS in mitochondria play an important role in physiological and pathological processes of life. In this study, a dual-labeling probe that could simultaneously label the mitochondrial membrane and matrix was designed to quantitatively detect RSS of mitochondria in living cells using nano-level super-resolution imaging.Methods: A fluorescent probe CPE was designed and synthesized. The cytotoxicity of CPE was determined and co-localization of CPE with a commercial mitochondrial probe was analyzed in HeLa cells. Then, the uptake patterns of CPE in HeLa cells at different temperatures and endocytosis levels were investigated. The staining characteristics of CPE under different conditions were imaged and quantitated under structured illumination microscopy.Results: A fluorescence probe CPE reacting to RSS was developed, which could simultaneously label the mitochondrial membrane with green fluorescence and the mitochondrial matrix with red fluorescence. CPE was able to demonstrate the mitochondrial morphology and detect the changes of RSS in mitochondria. With the increase of mitochondrial RSS concentration, the light of the red matrix will be quenched.Conclusion: CPE provides a strategy for the design of probes and an attractive tool for accurate examination to changes of mitochondrial morphology and RSS in mitochondria in living cells at the nanoscale.
S-Nitroso-L-Cysteine Stereoselectively Blunts the Deleterious Effects of Fentanyl on Breathing While Augmenting Antinociception in Freely-Moving Rats
Authors: Getsy Paulina M. , Baby Santhosh M. , Gruber Ryan B. , Gaston Benjamin , Lewis Tristan H. J. , Grossfield Alan , Seckler James M. , Hsieh Yee-Hsee , Bates James N. , Lewis Stephen J. 
Published: June 2022

Endogenous and exogenously administered S-nitrosothiols modulate the activities of central and peripheral systems that control breathing. We have unpublished data showing that the deleterious effects of morphine on arterial blood-gas chemistry (i.e., pH, pCO2, pO2, and sO2) and Alveolar-arterial gradient (i.e., index of gas exchange) were markedly diminished in anesthetized Sprague Dawley rats that received a continuous intravenous infusion of the endogenous S-nitrosothiol, S-nitroso-L-cysteine. The present study extends these findings by showing that unanesthetized adult male Sprague Dawley rats receiving an intravenous infusion of S-nitroso-L-cysteine (100 or 200 nmol/kg/min) markedly diminished the ability of intravenous injections of the potent synthetic opioid, fentanyl (10, 25, and 50 μg/kg), to depress the frequency of breathing, tidal volume, and minute ventilation. Our study also found that the ability of intravenously injected fentanyl (10, 25, and 50 μg/kg) to disturb eupneic breathing, which was measured as a marked increase of the non-eupneic breathing index, was substantially reduced in unanesthetized rats receiving intravenous infusions of S-nitroso-L-cysteine (100 or 200 nmol/kg/min). In contrast, the deleterious effects of fentanyl (10, 25, and 50 μg/kg) on frequency of breathing, tidal volume, minute ventilation and non-eupneic breathing index were fully expressed in rats receiving continuous infusions (200 nmol/kg/min) of the parent amino acid, L-cysteine, or the D-isomer, namely, S-nitroso-D-cysteine. In addition, the antinociceptive actions of the above doses of fentanyl as monitored by the tail-flick latency assay, were enhanced by S-nitroso-L-cysteine, but not L-cysteine or S-nitroso-D-cysteine. Taken together, these findings add to existing knowledge that S-nitroso-L-cysteine stereoselectively modulates the detrimental effects of opioids on breathing, and opens the door for mechanistic studies designed to establish whether the pharmacological actions of S-nitroso-L-cysteine involve signaling processes that include 1) the activation of plasma membrane ion channels and receptors, 2) selective intracellular entry of S-nitroso-L-cysteine, and/or 3) S-nitrosylation events. Whether alterations in the bioavailability and bioactivity of endogenous S-nitroso-L-cysteine is a key factor in determining the potency/efficacy of fentanyl on breathing is an intriguing question.