bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific shifts in the endocannabinoid system in hibernating brown bears
Authors: Boyer Christian , Cussonneau Laura , Brun Charlotte , Deval Christiane , Pais de Barros Jean-Paul , Chanon Stéphanie , Bernoud-Hubac Nathalie , Daira Patricia , Evans Alina L. , Arnemo Jon M. , Swenson Jon E. , Gauquelin-Koch Guillemette , Simon Chantal , Blanc Stéphane , Combaret Lydie , Bertile Fabrice , Lefai Etienne
Published: November 2020

In small hibernators, global downregulation of the endocannabinoid system (ECS), which is involved in modulating neuronal signaling, feeding behavior, energy metabolism, and circannual rhythms, has been reported to possibly drive physiological adaptation to the hibernating state. In hibernating brown bears (Ursus arctos), we hypothesized that beyond an overall suppression of the ECS, seasonal shift in endocannabinoids compounds could be linked to bear’s peculiar features that include hibernation without arousal episodes and capacity to react to external disturbance. We explored circulating lipids in serum and the ECS in plasma and metabolically active tissues in free-ranging subadult Scandinavian brown bears when both active and hibernating. In winter bear serum, in addition to a 2-fold increase in total fatty acid concentration, we found significant changes in relative proportions of circulating fatty acids, such as a 2-fold increase in docosahexaenoic acid C22:6 n-3 and a decrease in arachidonic acid C20:4 n-6. In adipose and muscle tissues of hibernating bears, we found significant lower concentrations of 2-arachidonoylglycerol (2-AG), a major ligand of cannabinoid receptors 1 (CB1) and 2 (CB2). Lower mRNA level for genes encoding CB1 and CB2 were also found in winter muscle and adipose tissue, respectively. The observed reduction in ECS tone may promote fatty acid mobilization from body fat stores, and favor carbohydrate metabolism in skeletal muscle of hibernating bears. Additionally, high circulating level of the endocannabinoid-like compound N-oleoylethanolamide (OEA) in winter could favor lipolysis and fatty acid oxidation in peripheral tissues. We also speculated on a role of OEA in the conservation of an anorexigenic signal and in the maintenance of torpor during hibernation, while sustaining the capacity of bears to sense stimuli from the environment.
Successfully REBOA performance: does medical specialty matter? International data from the ABOTrauma Registry
Authors:   The ABOTrauma Registry research group, Hilbert-Carius Peter , McGreevy David , Abu-Zidan Fikri M. , Hörer Tal M.
Published: November 2020

Background

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive procedure being increasingly utilized to prevent patients with non-compressible torso hemorrhage from exsanguination. The increased use of REBOA is giving rise to discussion about “Who is and who should be performing it?”

Methods

Data from the international ABO (aortic balloon occlusion) Trauma Registry from between November 2014 and April 2020 were analyzed concerning the question: By who, how, and where is REBOA being performed? The registry collects retrospective and prospective data concerning use of REBOA in trauma patients.

Results

During the study period, 259 patients had been recorded in the registry, 72.5% (n= 188) were males with a median (range) age of 46 (10-96) years. REBOA was performed in the ER in 50.5%, in the OR in 41.5%, and in the angiography suite in 8% of patients. In 54% of the patients REBOA was performed by surgeons (trauma surgeons 28%, vascular surgeons 22%, general surgeons 4%) and in 46% of the patients by non-surgeons (emergency physicians 31%, radiologists 9.5%, anesthetists 5.5%). Common femoral artery (CFA) access was achieved by use of external anatomic landmarks and palpation alone in 119 patients (51%), by cutdown in 57 patients (24%), using ultrasound in 49 patients (21%), and by fluoroscopy in 9 patients (4%). Significant differences between surgeons and non-surgeons were found regarding patient’s age, injury severity, access methods, place where REBOA was performed, location patients were taken to from the emergency room, and mortality.

Conclusion

A substantial number of both surgical and non-surgical medical disciplines are successfully performing REBOA to an almost equal extent. Surgical cutdown is used less frequently as access to the CFA compared with reports in older literature and puncture by use of external anatomic landmarks and palpation alone is used with a high rate of success. Instead of discussing “Who should be performing REBOA?” future research should focus on “Which patient benefits most from REBOA?”
Application of endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis and treatment of mediastinal lymph node tuberculous abscess: a case report and literature review
Authors: Fang Yong , Cheng Liping , Guo Junhong , Wu Chunyan , Gu Ye , You Xiaofang , Sha Wei
Published: November 2020

Background

This study aimed to report the experience of diagnosis and treatment of one rare case of mediastinal lymph node tuberculous abscess (MLNTA) using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA).

Case presentation

An 18-year-old female patient was hospitalized in the Affiliated Hospital of Xuzhou Medical University in November 2017, due to intermittent left chest pain. She was suspected of infecting tuberculosis (TB) and thus received anti-TB treatment. Since April 1, 2018, she began to exhibit symptoms of chest distress. The patient was then admitted to Shanghai Pulmonary Hospital and continued receiving systemic anti-TB treatment during the whole course. On April 11, 2018, she received EBUS-TBNA to puncture pus and inject isoniazid. Simultaneously, the pus was sent for cytopathological and bacteriological examination, both supporting the diagnosis of TB in the patient. On April 24 and May 10, she received two times of EBUS-TBNA treatment. The symptoms of chest distress were relieved, but granulomatous neoplasm occurred at the EBUS-TBNA site on the trachea wall. The patient then received local clamp removal and cryotherapy on May 29 and Jul 19, respectively. Chest computed tomography (CT) reexamination on September 28 revealed that the MLNTA lesion had been completely absorbed, and electronic bronchoscopic reexamination on September 30 demonstrated that the granulomatous neoplasm on the trachea wall was entirely invisible.

Conclusions

Using EBUS-TBNA to puncture and aspirate pus and inject drugs can be effectively used to diagnose and treat MLNTA, which provides a new, less invasive, safe and reliable method for diagnosis and treatment of MLNTA.
CCL2 facilitates spinal synaptic transmission and pain via interaction with presynaptic CCR2 in spinal nociceptor terminals
Authors: Ma Sui-Bin , Xian Hang , Wu Wen-Bin , Ma Shuo-Yao , Liu Yu-Ke , Liang Yu-Tong , Guo Huan , Kang Jun-Jun , Liu Ying-Ying , Zhang Hui , Wu Sheng-Xi , Luo Ceng , Xie Rou-Gang
Published: November 2020

Previous studies have shown that CCL2 may cause chronic pain, but the exact mechanism of central sensitization is unclear. In this article, we further explore the presynaptic role of CCL2. Behavioral experiments show that intervertebral foramen injection CCR2 antagonists into dorsal root ganglion (DRG) can inhibit the inflammatory pain caused by CCL2 in spinal cord. We raised the question of the role of presynaptic CCR2 in the spinal dorsal horn. Subsequent electron microscopy experiments showed that CCR2 was expressed in the presynaptic CGRP terminal in the spinal dorsal horn. CCL2 can enhance presynaptic calcium signal. Whole-cell patch-clamp recordings showed that CCL2 can enhance NMDAR-eEPSCs through presynaptic effects, and further application of glutamate sensor method proved that CCL2 can act on presynaptic CCR2 to increase the release of presynaptic glutamate. In conclusion, we suggest that CCL2 can directly act on the CCR2 on presynaptic terminals of sensory neurons in the spinal dorsal horn, leading to an increase in the release of presynaptic glutamate and participate in the formation of central sensitization.
Molecular and cellular mechanisms of aging in hematopoietic stem cells and their niches
Authors: Zhang Lei , Mack Ryan , Breslin Peter , Zhang Jiwang
Published: November 2020

Aging drives the genetic and epigenetic changes that result in a decline in hematopoietic stem cell (HSC) functioning. Such changes lead to aging-related hematopoietic/immune impairments and hematopoietic disorders. Understanding how such changes are initiated and how they progress will help in the development of medications that could improve the quality life for the elderly and to treat and possibly prevent aging-related hematopoietic diseases. Here, we review the most recent advances in research into HSC aging and discuss the role of HSC-intrinsic events, as well as those that relate to the aging bone marrow niche microenvironment in the overall processes of HSC aging. In addition, we discuss the potential mechanisms by which HSC aging is regulated.
Monocyte Chemoattractant Protein-1 promotes cancer cell migration via c-Raf/MAPK/AP-1 pathway and MMP-9 production in osteosarcoma
Authors: Liu Ju-Fang , Chen Po-Chun , Chang Tsung-Ming , Hou Chun-Han
Published: November 2020

Background

Osteosarcoma is generally reported among younger individuals and has a very poor prognosis, particularly for the development of metastasis. However, more effective metastatic biomarkers and therapeutic methods are absent. Monocyte chemoattractant protein-1 (MCP-1) is involved in cancer progression and inflammatory recruitment. Although previous studies have reported higher serum MCP-1 levels in patients with osteosarcoma, the role of MCP-1 in osteosarcoma progression remains to be addressed.

Methods

The osteosarcoma cell migratory ability was assessed by transwell migration assay. The MCP-1 and MMP-9 expression levels were analyzed by Western blot and qPCR. The signal activation was conducted by Western blot. The in vivo mouse experiment and tumor tissue array were performed to confirm our findings in vitro.

Results

The present study demonstrates that MCP-1 regulates cell mobility through matrix metalloproteinase (MMP)-9 expression in osteosarcoma cells. Moreover, MCP-1 promotes MMP-9 expression, cell migration, and cell invasion by mediating CCR2, c-Raf, MAPK, and AP-1 signal transduction. Using MCP-1 knockdown stable cell lines, we found that MCP-1 knockdown reduces MMP-9 expression and cell mobility. Finally, we found high MCP-1 expression levels in osteosarcoma specimens.

Conclusions

Our results provide prognostic value of MCP-1 in osteosarcoma by promoting MMP-9 expression.
A machine learning framework to determine geolocations from metagenomic profiling
Authors: Huang Lihong , Xu Canqiang , Yang Wenxian , Yu Rongshan
Published: November 2020

Background

Studies on metagenomic data of environmental microbial samples found that microbial communities seem to be geolocation-specific, and the microbiome abundance profile can be a differentiating feature to identify samples’ geolocations. In this paper, we present a machine learning framework to determine the geolocations from metagenomics profiling of microbial samples.

Results

Our method was applied to the multi-source microbiome data from MetaSUB (The Metagenomics and Metadesign of Subways and Urban Biomes) International Consortium for the CAMDA 2019 Metagenomic Forensics Challenge (the Challenge). The goal of the Challenge is to predict the geographical origins of mystery samples by constructing microbiome fingerprints.First, we extracted features from metagenomic abundance profiles. We then randomly split the training data into training and validation sets and trained the prediction models on the training set. Prediction performance was evaluated on the validation set. By using logistic regression with L2 normalization, the prediction accuracy of the model reaches 86%, averaged over 100 random splits of training and validation datasets.The testing data consists of samples from cities that do not occur in the training data. To predict the “mystery” cities that are not sampled before for the testing data, we first defined biological coordinates for sampled cities based on the similarity of microbial samples from them. Then we performed affine transform on the map such that the distance between cities measures their biological difference rather than geographical distance. After that, we derived the probabilities of a given testing sample from unsampled cities based on its predicted probabilities on sampled cities using Kriging interpolation. Results show that this method can successfully assign high probabilities to the true cities-of-origin of testing samples.

Conclusion

Our framework shows good performance in predicting the geographic origin of metagenomic samples for cities where training data are available. Furthermore, we demonstrate the potential of the proposed method to predict metagenomic samples’ geolocations for samples from locations that are not in the training dataset.
The Shamiri group intervention for adolescent anxiety and depression: study protocol for a randomized controlled trial of a lay-provider-delivered, school-based intervention in Kenya
Authors: Osborn Tom L. , Venturo-Conerly Katherine E. , Wasil Akash R. , Rodriguez Micaela , Roe Elizabeth , Alemu Rediet , Arango G. Susana , Gan Jenny , Wasanga Christine , Schleider Jessica L. , Weisz John R.
Published: November 2020

Background

Developing low-cost, socio-culturally appropriate, and scalable interventions for youth depression and anxiety symptoms in low-income regions such as countries in sub-Saharan Africa is a global mental health priority. We developed and intend to evaluate one such intervention for adolescent depression and anxiety in Kenya. The intervention, named Shamiri (a Swahili word for “thrive”), draws upon evidence-based components of brief interventions that involve nonclinical principles rather than treatment of psychopathology (e.g., growth mindset, gratitude, and virtues).

Methods

Four hundred twenty Kenyan adolescents (ages 13–18) with clinically elevated depression and/or anxiety symptoms will be randomized to either the 4-week Shamiri group intervention or a group study-skills control intervention of equal duration and dosage. Participating adolescents will meet in groups of 8–15, led by a high-school graduate trained to deliver Shamiri as a lay-provider. Adolescents will self-report primary outcome measures (depression—measured by the PHQ-8, and anxiety symptoms—measured by the GAD-7) and secondary outcome measures (perceived social support, perceived academic control, self-reported optimism and happiness, loneliness, and academic grades) at the 2-week intervention midpoint, 4-week post-intervention endpoint, and 2-week post-intervention follow-up. We predict that adolescents in the Shamiri group, when compared to the study-skills control group, will show greater improvements in primary outcomes and secondary outcomes.

Discussion

Results may suggest that a brief, lay-provider delivered, school-based intervention may reduce depression and anxiety symptoms, improving academic outcomes and other psychosocial outcomes in adolescents with clinically-elevated symptoms in sub-Saharan Africa.

Trial registration

Pan African Clinical Trials Registry PACTR201906525818462. Registered on 12 June 2019.
An automated structured education intervention based on a smartphone app in Chinese patients with type 1 diabetes: a protocol for a single-blinded randomized controlled trial
Authors: Huang Fansu , Wu Xinyin , Xie Yuting , Liu Fang , Li Juan , Li Xia , Zhou Zhiguang
Published: November 2020

Background

Although evidence had demonstrated the effectiveness of smartphone apps in diabetes care, the majority of apps had been developed for type 2 diabetes mellitus (T2DM) patients and targeted at populations outside of China. The effects of applying a smartphone app with structured education on glycemic control in type 1 diabetes mellitus (T1DM) are unclear. A digital, culturally tailored structured education program was developed in a smartphone app (Yi tang yun qiao) to provide an automated, individualized education program aimed at improving self-management skills in patients with T1DM in China. This trial aims to investigate the effectiveness of this smartphone app among Chinese T1DM patients.

Methods and analysis

This single-blinded, 24-week, parallel-group randomized controlled trial of a smartphone app versus routine care will be conducted in Changsha, China. We plan to recruit 138 patients with T1DM who will be randomly allocated into the intervention group (automated, individualized education through an app) or routine care group. The intervention will last for 24 weeks. The primary outcome will be the change in glycated hemoglobin (HbA1c) from baseline to week 24. The secondary outcomes will include time in range, fasting blood glucose, levels of serum triglycerides and cholesterol, blood pressure, body mass index, quality of life, diabetes self-care activities, diabetes self-efficacy, depression, anxiety, and patient satisfaction. Adverse events will be formally documented. Data analysis will be conducted using the intention-to-treat principle with appropriate univariate and multivariate methods. Missing data will be imputed with a multiple imputation method under the “missing at random” assumption.

Discussion

This trial will investigate the effectiveness of an app-based automated structured education intervention for Chinese patients with T1DM. If the intervention is effective, this study will provide a strategy that satisfies the need for effective lifelong diabetes care to reduce the disease burden and related complications resulting from T1DM.

Trial registration

ClinicalTrials.govNCT04016987. Registered on 29 October 2019.
Effect of targeted vs standard fortification of breast milk on growth and development of preterm infants (≤ 32 weeks): study protocol for a randomized controlled trial
Authors: Seliga-Siwecka Joanna , Chmielewska Anna , Jasińska Katarzyna
Published: November 2020

Background

Human milk is recommended for all very low birth weight infants. Breastmilk is highly variable in nutrient content, failing to meet the nutritional demands of this group. Fortification of human milk is recommended to prevent extrauterine growth retardation and associated poor neurodevelopmental outcome. However, standard fortification with fixed dose multicomponent fortifier does not account for the variability in milk composition. Targeted fortification is a promising alternative and needs further investigation.

Methods

This randomized controlled trial will recruit preterm infants (≤ 32 weeks of gestation) within the first 7 days of life. After reaching 80 ml/kg/day of enteral feeding, patients will be randomized to receive standard fortification (HMF, Nutricia) or targeted fortification (modular components: Bebilon Bialka, Nutricia—protein; Polycal, Nutricia—carbohydrates; Calogen, Nutricia—lipids). The intervention will continue until 37 weeks of post-conception age or hospital discharge. Parents and outcome assessors will be blinded to the intervention. The primary outcome measure is velocity of weight, length, and head growth until 36 weeks post-conceptional age or discharge. Secondary outcomes include neurodevelopment at 12 months assessed with Bayley Scale of Development III, repeated at 36 months; body composition at discharge and at 4 months; and incidence of necrotizing enterocolitis, sepsis, retinopathy of prematurity, and bronchopulmonary dysplasia.

Discussion

Targeted fortification has previously been shown as doable in the neonatal intensive care unit context. If it shows to improve growth and neonatal outcome, choosing the targeted fortification as a first line nutritional approach in very low birth weight infants may become a recommendation.

Trial registration

ClinicalTrials.govNCT03775785, Registered on July 2019.
UVR-sensor wearable device intervention to improve sun behaviors and reduce sunburns in melanoma survivors: study protocol of a parallel-group randomized controlled trial
Authors: Vogel Rachel I. , Nagler Rebekah H. , Ahmed Rehana L. , Brown Katherine , Luo Xianghua , Martinson Brian C. , Lazovich DeAnn
Published: November 2020

Background

Individuals who have been diagnosed with melanoma have more than a 9-fold increased risk of developing another melanoma. Ultraviolet radiation (UVR) exposure following a melanoma diagnosis can be modified to reduce risk of a new melanoma diagnosis. Yet research shows that many melanoma survivors do not report optimal sun protection practices. The objective of this study is to evaluate the effectiveness of a UVR-sensor wearable device to improve sun protection behaviors and reduce sunburns in a randomized controlled trial (RCT) in melanoma survivors.

Methods

We will conduct an RCT among 368 melanoma survivors in two waves (Summer 2020, Summer 2021). This approach allows for adequate recruitment of the required sample and potential improvements to recruitment, compliance, and retention strategies between waves. The intervention includes an informational brochure about sun protection behaviors and a commercially available UVR-sensor wearable device (Shade), which accurately measures UVR. The device, along with its associated mobile application, measures and stores UVR exposure. As UVR exposure accumulates, the device provides notifications to increase sun protection action. Survivors in the control group receive the device and a separate mobile application that does not provide notifications or summary UVR exposure data. Participants will be asked to wear the device for 12 weeks. They will complete surveys about their sun behaviors at study entry, every 4 weeks during the intervention, and 1 year later. At the end of the intervention period, intervention and control groups will be compared for differences in a summary measure of sun protection habits and experience of a sunburn. We will also measure self-reported physical activity, depression, and anxiety to examine potential unintended negative consequences of the intervention.

Discussion

The study intervention will be completed Fall 2021, with anticipated results available in 2022. If this intervention improves sun protection behaviors in melanoma survivors, these findings would support expanding the use of this technology with other populations at high risk for melanoma.

Trial registration

ClinicalTrials.gov NCT03927742. Registered on April 15, 2019.
Planned early delivery versus expectant management to reduce adverse pregnancy outcomes in pre-eclampsia in a low- and middle-income setting: study protocol for a randomised controlled trial (CRADLE-4 Trial)
Authors: Beardmore-Gray Alice , Vousden Nicola , Charantimath Umesh , Katageri Geetanjali , Bellad Mrutyunjaya , Kapembwa Kunda , Chinkoyo Sebastian , Vwalika Bellington , Clark Matthew , Hunter Rachael , Seed Paul , Goudar Shivaprasad , Chappell Lucy C. , Shennan Andrew
Published: November 2020

Background

Pre-eclampsia is a pregnancy complication characterised by high blood pressure and multi-organ dysfunction in the mother. It is a leading contributor to maternal and perinatal mortality, with 99% of these deaths occurring in low- and middle-income countries (LMIC). Whilst clear guidelines exist for management of early-onset (< 34 weeks) and term (≥ 37 weeks) disease, the optimal timing of delivery in pre-eclampsia between 34+ 0 and 36+ 6 weeks is less clear. In a high-income setting, delivery may improve maternal outcomes without detriment to the baby, but this intervention is yet to be evaluated in LMIC.

Methods

The CRADLE-4 Trial is a non-masked, randomised controlled trial comparing planned early delivery (initiation of delivery within 48 h of randomisation) with routine care (expectant management) in women with pre-eclampsia between 34+ 0 and 36+ 6 weeks’ gestation in India and Zambia. The primary objective is to establish whether a policy of planned early delivery can reduce adverse maternal outcomes, without increasing severe neonatal morbidity.

Discussion

The World Health Organization recommends delivery for all women with pre-eclampsia from 37 weeks onwards, based on evidence showing clear maternal benefit without increased neonatal risk. Before 34 weeks, watchful waiting is preferred, with delivery recommended only when there is severe maternal or fetal compromise, due to the neonatal risks associated with early preterm delivery. Currently, there is a lack of guidance for clinicians managing women with pre-eclampsia between 34+ 0 and 36+ 6 weeks. Early delivery benefits the mother but may increase the need for neonatal unit admission in the infant (albeit without serious morbidity at this gestation). On the other hand, waiting to deliver may increase the risk of stillbirth, fetal growth restriction and hypoxic brain injury in the neonate as a result of severe maternal complications. This is especially true for LMIC where there is a higher prevalence of adverse events. The balance of risks and benefits therefore needs to be carefully assessed before making firm recommendations. This is the first trial evaluating the optimal timing of delivery in pre-eclampsia in LMIC, where resources and disease burden are considerably different.

Trial registration

ISRCTN 10672137. Registered on 28 November 2019.
An investigation into the factors affecting investigator-initiated trial start-up in Ireland
Authors: Leddy Lauren , Sukumar Prasanth , O’Sullivan Lydia , Keane Fionnuala , Devane Declan , Doran Peter
Published: November 2020

Background

In common with many countries, Ireland has seen an increasing trend in the number of clinical trials conducted over the past few years. Yet, as elsewhere, trialists in Ireland face several problems and barriers in the starting-up of clinical trials. These barriers impede trial activity significantly, with consequent impacts on patient care. It is critical to understand these issues, to develop approaches to facilitate trial start up. This study identifies the challenges in conducting clinical trials in Ireland and specifically the contractual, ethical, logistical, and regulatory barriers that hinder the start-up of investigator-led trials in Ireland.

Methods

Data for this study were collected in two stages. In the first stage, a survey was conducted among trialists in Ireland. A total of 44 trialists responded to the survey, and information was collected about their experience in conducting clinical trials, the scale and nature of their most recently completed trial, and the details of specific barriers they encountered during the starting-up of the trial. In the second stage, nine semi-structured interviews were conducted with the awardees of 2018 Irish Health Research Board’s Definitive Intervention Feasibility Award. These interviews facilitated a deeper exploration of issues and problems in conducting clinical trials in Ireland.

Results

This study identified several issues and bottlenecks in starting-up clinical trials in Ireland with contracts and ethical approval cited as the major issues. The data shows that site identification and activation was also problematic in some cases. Several respondents reported difficulties in accessing dedicated time for protocol development and believe that support in this area can be greatly beneficial. It was reported that availability of skilled staff members like statisticians and data managers was as an issue, especially for small trials.

Conclusion

This study found that several factors impact trial initiation and progression in Ireland. Delays associated with obtaining contract and ethics approval are perceived as major barriers. Specialist supports in areas such as ethics and regulatory affairs and availability of specialised staff members in areas such as statistics and data management are key actions to enable enhanced clinical trial activity in Ireland.
Integrated analysis of microbiome and host transcriptome reveals correlations between gut microbiota and clinical outcomes in HBV-related hepatocellular carcinoma
Authors: Huang Hechen , Ren Zhigang , Gao Xingxing , Hu Xiaoyi , Zhou Yuan , Jiang Jianwen , Lu Haifeng , Yin Shengyong , Ji Junfang , Zhou Lin , Zheng Shusen
Published: November 2020

Background

The gut-liver axis plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC). However, the correlations between the gut microbiome and the liver tumor transcriptome in patients with HCC and the impact of the gut microbiota on clinical outcome are less well-understood.

Methods

Fecal samples collected from HBV-related HCC patients (n = 113) and healthy volunteers (n = 100) were subjected to 16S rRNA sequencing of the microbiome. After a rigorous selection process, 32 paired tumor and adjacent non-tumor liver tissues from the HCC group were subjected to next-generation sequencing (NGS) RNA-seq. The datasets were analyzed individually and integrated with clinical characteristics for combined analysis using bioinformatics approaches. We further verified the potential of the gut microbiota to predict clinical outcome by a random forest model and a support vector machine model.

Results

We found that Bacteroides, Lachnospiracea incertae sedis, and Clostridium XIVa were enriched in HCC patients with a high tumor burden. By integrating the microbiome and transcriptome, we identified 31 robust associations between the above three genera and well-characterized genes, indicating possible mechanistic relationships in tumor immune microenvironment. Clinical characteristics and database analysis suggested that serum bile acids may be important communication mediators between these three genera and the host transcriptome. Finally, among these three genera, six important microbial markers associated with tumor immune microenvironment or bile acid metabolism showed the potential to predict clinical outcome (AUC = 81%).

Conclusions

This study revealed that changes in tumor immune microenvironment caused by the gut microbiota via serum bile acids may be important factors associated with tumor burden and adverse clinical outcome. Gut microbes can be used as biomarkers of clinical features and outcomes, and the microbe-associated transcripts of host tumors can partly explain how gut microbiota promotes HCC pathogenesis.
Associations of dietary inflammatory index, serum levels of MCP-1 and body composition in Iranian overweight and obese women: a cross-sectional study
Authors: Ghodoosi Nasim , Mirzababaei Atieh , Rashidbeygi Elahe , Badrooj Negin , Sajjadi Seyedeh Forough , Setayesh Leila , Yekaninejad Mir Saeed , Keshavarz Seyed Ali , Shiraseb Farideh , Mirzaei Khadijeh
Published: November 2020

Objective

Although, several studies have illustrated that there is a relation between dietary inflammatory index (DII) with obesity-related parameters, and inflammation, their results were controversial. This study aimed to investigate this relationship among Iranian women.

Results

Multivariable linear regression showed that fat mass was 0.14 kg lower in the anti-inflammatory diet group, with respect to the pro-inflammatory group, after adjusting covariates such as age, physical activity, economic and job status (β = − 0.142, 95% CI − 4.44, − 1.71,P = 0.03). Fat-free mass (FFM) was 1.5 kg more in the anti-inflammatory diet group, compared to the pro-inflammatory diet group, after adjusting for potentials cofounders (β = 1.50, 95% CI 0, 3.01, p = 0.05). Furthermore, after adjusting for potentials cofounders, it was revealed that the subjects with lower DII had lower monocyte chemoattractant protein-1 (MCP-1) levels in serum (β = − 18.81, 95% CI − 35.84, − 1.79,p = 0.03). These findings suggest an inverse and significant relationship between DII and FFM and also DII is directly related to Fat mass and the level of MCP-1. This finding can be used for developing interventions that aim to promote healthy eating to prevent inflammation and non-communicable disease development among obese females.
Combined frequency-tagging EEG and eye-tracking measures provide no support for the “excess mouth/diminished eye attention” hypothesis in autism
Authors: Vettori Sofie , Van der Donck Stephanie , Nys Jannes , Moors Pieter , Van Wesemael Tim , Steyaert Jean , Rossion Bruno , Dzhelyova Milena , Boets Bart
Published: November 2020

Background

Scanning faces is important for social interactions. Difficulty with the social use of eye contact constitutes one of the clinical symptoms of autism spectrum disorder (ASD). It has been suggested that individuals with ASD look less at the eyes and more at the mouth than typically developing (TD) individuals, possibly due to gaze aversion or gaze indifference. However, eye-tracking evidence for this hypothesis is mixed. While gaze patterns convey information about overt orienting processes, it is unclear how this is manifested at the neural level and how relative covert attention to the eyes and mouth of faces might be affected in ASD.

Methods

We used frequency-tagging EEG in combination with eye tracking, while participants watched fast flickering faces for 1-min stimulation sequences. The upper and lower halves of the faces were presented at 6 Hz and 7.5 Hz or vice versa in different stimulation sequences, allowing to objectively disentangle the neural saliency of the eyes versus mouth region of a perceived face. We tested 21 boys with ASD (8–12 years old) and 21 TD control boys, matched for age and IQ.

Results

Both groups looked longer at the eyes than the mouth, without any group difference in relative fixation duration to these features. TD boys looked significantly more to the nose, while the ASD boys looked more outside the face. EEG neural saliency data partly followed this pattern: neural responses to the upper or lower face half were not different between groups, but in the TD group, neural responses to the lower face halves were larger than responses to the upper part. Face exploration dynamics showed that TD individuals mostly maintained fixations within the same facial region, whereas individuals with ASD switched more often between the face parts.

Limitations

Replication in large and independent samples may be needed to validate exploratory results.

Conclusions

Combined eye-tracking and frequency-tagged neural responses show no support for the excess mouth/diminished eye gaze hypothesis in ASD. The more exploratory face scanning style observed in ASD might be related to their increased feature-based face processing style.
Artificial intelligence-based education assists medical students’ interpretation of hip fracture
Authors: Cheng Chi-Tung , Chen Chih-Chi , Fu Chih-Yuan , Chaou Chung-Hsien , Wu Yu-Tung , Hsu Chih-Po , Chang Chih-Chen , Chung I-Fang , Hsieh Chi-Hsun , Hsieh Ming-Ju , Liao Chien-Hung
Published: November 2020

Background

With recent transformations in medical education, the integration of technology to improve medical students’ abilities has become feasible. Artificial intelligence (AI) has impacted several aspects of healthcare. However, few studies have focused on medical education. We performed an AI-assisted education study and confirmed that AI can accelerate trainees’ medical image learning.

Materials

We developed an AI-based medical image learning system to highlight hip fracture on a plain pelvic film. Thirty medical students were divided into a conventional (CL) group and an AI-assisted learning (AIL) group. In the CL group, the participants received a prelearning test and a postlearning test. In the AIL group, the participants received another test with AI-assisted education before the postlearning test. Then, we analyzed changes in diagnostic accuracy.

Results

The prelearning performance was comparable in both groups. In the CL group, postlearning accuracy (78.66 ± 14.53) was higher than prelearning accuracy (75.86 ± 11.36) with no significant difference (p = .264). The AIL group showed remarkable improvement. The WithAI score (88.87 ± 5.51) was significantly higher than the prelearning score (75.73 ± 10.58, p < 0.01). Moreover, the postlearning score (84.93 ± 14.53) was better than the prelearning score (p < 0.01). The increase in accuracy was significantly higher in the AIL group than in the CL group.

Conclusion

The study demonstrated the viability of AI for augmenting medical education. Integrating AI into medical education requires dynamic collaboration from research, clinical, and educational perspectives.
Spinal osteoblastoma: a retrospective study of 35 patients’ imaging findings with an emphasis on MRI
Authors: Liu Jianfang , Han Songbo , Li Jie , Yuan Yuan , Guo Wei , Yuan Huishu
Published: November 2020

Objective

To investigate the values of multimodal imaging approaches in the diagnosis of spinal osteoblastomas with an emphasis on MRI findings.

Materials and methods

We retrospectively evaluated the imaging findings of 35 patients with spinal osteoblastomas. The imaging methods included radiography, whole-body bone scintigraphy (WBBS), CT and MRI.

Results

Radiography detected 87.1% (27/31) of the lesions; WBBS demonstrated increased radionuclide activity in all the lesions. CT could precisely show and localize all niduses, and calcification was always detected. MRI usually could adequately delineate the niduses of osteoblastomas, especially on T2WI (88.2%; 30/34). 71.9% (23/32) of osteoblastomas were surrounded with moderate or extensive bone marrow edema (BME) with soft tissue edema (STE). STE always extended along the muscle bundle adjacent to the lesion; there was no subcutaneous fat involvement. BME was eccentrically distributed in the vertebral body and spread inward from the sides of the nidus. The extent of BME in the vertebral body tended to be inversely proportional to the distance from the nidus. In addition, rare magnifications of osteoblastoma including multifocal diseases (n = 2), vertebra plana (n = 1) or with aneurysmal bone cysts (n = 6) were also observed in our study.

Conclusions

In patients showing moderate or extensive BME together with STE on MRI, both CT and MRI should be used to confirm nidus presence. The above-mentioned characteristics of edema on MRI of patients with spinal osteoblastoma are helpful in not only localizing the nidus, but also enhancing the diagnostic confidence.
Plasma radio-metabolite analysis of PET tracers for dynamic PET imaging: TLC and autoradiography
Authors: Li Fiona , Hicks Justin W. , Yu Lihai , Desjardin Lise , Morrison Laura , Hadway Jennifer , Lee Ting-Yim
Published: November 2020

Background

In molecular imaging with dynamic PET, the binding and dissociation of a targeted tracer is characterized by kinetics modeling which requires the arterial concentration of the tracer to be measured accurately. Once in the body the radiolabeled parent tracer may be subjected to hydrolysis, demethylation/dealkylation and other biochemical processes, resulting in the production and accumulation of different metabolites in blood which can be labeled with the same PET radionuclide as the parent. Since these radio-metabolites cannot be distinguished by PET scanning from the parent tracer, their contribution to the arterial concentration curve has to be removed for the accurate estimation of kinetic parameters from kinetic analysis of dynamic PET. High-performance liquid chromatography has been used to separate and measure radio-metabolites in blood plasma; however, the method is labor intensive and remains a challenge to implement for each individual patient. The purpose of this study is to develop an alternate technique based on thin layer chromatography (TLC) and a sensitive commercial autoradiography system (Beaver, Ai4R, Nantes, France) to measure radio-metabolites in blood plasma of two targeted tracers—[18F]FAZA and [18F]FEPPA, for imaging hypoxia and inflammation, respectively.

Results

Radioactivity as low as 17 Bq in 2 µL of pig’s plasma can be detected on the TLC plate using autoradiography. Peaks corresponding to the parent tracer and radio-metabolites could be distinguished in the line profile through each sample (n = 8) in the autoradiographic image. Significant intersubject and intra-subject variability in radio-metabolites production could be observed with both tracers. For [18F]FEPPA, 50% of plasma activity was from radio-metabolites as early as 5-min post injection, while for [18F]FAZA, significant metabolites did not appear until 50-min post. Simulation study investigating the effect of radio-metabolite in the estimation of kinetic parameters indicated that 32–400% parameter error can result without radio-metabolites correction.

Conclusion

TLC coupled with autoradiography is a good alternative to high-performance liquid chromatography for radio-metabolite correction. The advantages of requiring only small blood samples (~ 100 μL) and of analyzing multiple samples simultaneously, make the method suitable for individual dynamic PET studies.
CXCR7: a β-arrestin-biased receptor that potentiates cell migration and recruits β-arrestin2 exclusively through Gβγ subunits and GRK2
Authors: Nguyen Huong Thi , Reyes-Alcaraz Arfaxad , Yong Hyo Jeong , Nguyen Lan Phuong , Park Hee-Kyung , Inoue Asuka , Lee Cheol Soon , Seong Jae Young , Hwang Jong-Ik
Published: November 2020

Background

Some chemokine receptors referred to as atypical chemokine receptors (ACKRs) are thought to non-signaling decoys because of their inability to activate typical G-protein signaling pathways. CXCR7, also known as ACKR3, binds to only two chemokines, SDF-1α and I-TAC, and recruits β-arrestins. SDF-1α also binds to its own conventional receptor, CXCR4, involving in homeostatic modulation such as development and immune surveillance as well as pathological conditions such as inflammation, ischemia, and cancers. Recently, CXCR7 is suggested as a key therapeutic target together with CXCR4 in such conditions. However, the molecular mechanisms underlying cellular responses and functional relation with CXCR7 and CXCR4 have not been elucidated, despite massive studies. Therefore, we aimed to reveal the molecular networks of CXCR7 and CXCR4 and compare their effects on cell migration.

Methods

Base on structural complementation assay using NanoBiT technology, we characterized the distinct mechanisms underlying β-arrestin2 recruitment by both CXCR4 and CXCR7. Crosslinking and immunoprecipitation were conducted to analyze complex formation of the receptors. Gene deletion using CRISPR and reconstitution of the receptors were applied to analysis of ligand-dependent ERK phosphorylation and cell migration. All experiments were performed in triplicate and repeated more than three times. Unpaired Student’s t-tests or ANOVA using PRISM5 software were employed for statistical analyses.

Results

Ligand binding to CXCR7 does not result in activation of typical signaling pathways via Gα subunits but activation of GRK2 via βγ subunits and receptor phosphorylation with subsequent β-arrestin2 recruitment. In contrast, CXCR4 induced Gαi activation and recruited β-arrestin2 through C-terminal phosphorylation by both GRK2 and GRK5. SDF-1α-stimulated ERK phosphorylation was facilitated by CXCR4, but not CXCR7. Heterodimerization of CXCR4 and CXCR7 was not confirmed in this study, while homodimerization of them was verified by crosslinking experiment and NanoBiT assay. Regarding chemotaxis, SDF-1α-stimulated cell migration was mediated by both CXCR4 and CXCR7.

Conclusion

This study demonstrates that SDF-1α-stimulated CXCR7 mediates β-arrestin2 recruitment via different molecular networking from that of CXCR4. CXCR7 may be neither a simple scavenger nor auxiliary receptor but plays an essential role in cell migration through cooperation with CXCR4.
Meal replacement in dietary management of type-2 diabetes mellitus: a scoping review protocol
Authors: Chen Lew Leong , Mat Ludin Arimi Fitri , Shahar Suzana , Manaf Zahara Abdul , Tohit Noorlaili Mohd
Published: November 2020

Background

The prevalence of type-2 diabetes mellitus (T2DM) has been increasing globally. Without proper management, T2DM can develop into serious complications and even death. Diet modification is one of the most effective tools in managing T2DM at the early stage, but it requires knowledge and compliance from the patients. Thus, meal replacement (MR) has gained its popularity as a tool for diet modification to improve glycemic control and also reducing weight in T2DM patients. There are several existing meal replacement studies but not much is known on the general scope and effect of these existing MRs. Hence, this review is aimed to provide an overview of the existing evidences regarding the application of meal replacement on T2DM patients and identify the gaps or limitations in the studies.

Methodology

The scoping review will be carried out in six stages: (1) identifying the research question, (2) identifying relevant studies through electronic databases (i.e., PubMed, Scopus, Cochrane Reviews, Google Scholar, EBSCOHOST, Science Direct) and also gray literature, and (3) selection of studies to be included based on inclusion criteria. Search and initial screening of studies to be included will be conducted by two independent reviewers. Discrepancies will then be solved through discussion with other reviewers; (4) charting and categorizing extracted data in a pretested data extraction form; (5) collating, summarizing, and reporting the results; and lastly, (6) conducting consultation with stakeholders and experts in diabetes.

Discussion

This scoping review protocol is aimed to provide a framework enabling us to map and summarize the findings from existing studies involving meal replacement. It will help researchers to identify the research gap and provide recommendations for future meal replacement studies. The results from this scoping review will be useful to various stakeholders in healthcare. It is also part of a research project in which the information obtained will be utilized in a clinical trial of a developed meal replacement plan. Dissemination of knowledge will also be done through presentations at related scientific conferences.
Poly-Dedekind sums associated with poly-Bernoulli functions
Authors: Ma Yuankui , Kim Dae San , Lee Hyunseok , Kim Taekyun
Published: November 2020

Apostol considered generalized Dedekind sums by replacing the first Bernoulli function appearing in Dedekind sums by any Bernoulli functions and derived a reciprocity relation for them. Recently, poly-Dedekind sums were introduced by replacing the first Bernoulli function appearing in Dedekind sums by any type 2 poly-Bernoulli functions of arbitrary indices and were shown to satisfy a reciprocity relation. In this paper, we consider other poly-Dedekind sums that are obtained by replacing the first Bernoulli function appearing in Dedekind sums by any poly-Bernoulli functions of arbitrary indices. We derive a reciprocity relation for these poly-Dedekind sums.
Multivalued weak cyclic δ-contraction mappings
Authors: Konar Pulak , Bhandari Samir Kumar , Chandok Sumit , Mukheimer Aiman
Published: November 2020

In this paper, we propose some new type of weak cyclic multivalued contraction mappings by generalizing the cyclic contraction using theδ-distance function. Several novel fixed point results are deduced for such class of weak cyclic multivalued mappings in the framework of metric spaces. Also, we construct some examples to validate the usability of the results. Various existing results of the literature are generalized.