bluuebunny/crossref_metadata_2025 huggingface dataset:
Perspectives of deprived patients on diabetes self-management programmes delivered by the local primary care team: a qualitative study on facilitators and barriers for participation, in France
Authors: Allory Emmanuel , Lucas Hélène , Maury Arnaud , Garlantezec Ronan , Kendir Candan , Chapron Anthony , Fiquet Laure
Published: September 2020

Background

Diabetes self-management education (DSME) is an effective intervention for patients with type 2 diabetes mellitus (T2DM); nevertheless, patient participation in this type of programme is low. Implementation of DSME programmes in primary care practices by the local multi-professional team is a potential strategy to improve access to DSME for T2DM patients. The aim of this study was to identify perceived facilitators and barriers by patients to participation in local DSME delivered by primary care professionals in France.

Method

T2DM patients, informed and recruited during consulting with their usual care provider, who had attended a structured and validated DSME programme delivered by 13 primary care providers within a multi-professional primary care practice in a deprived area of 20,000 inhabitants, were invited to participate in this study. A qualitative study with semi-structured, in-depth interviews was conducted with study participants, between July 2017 and February 2018. A reflexive thematic analysis of the interviews was carried out. Coding schemes were developed to generate thematic trends in patient descriptions of facilitators and barriers to DSME participation.

Results

Nineteen interviews (mean length 31 min; [20–44 min]) were completed with T2DM patients. Four themes on facilitators for programme participation emerged from the data: geographical proximity of a DSME programme held in the local multi-professional primary care practice; effective promotion of the DSME programme by the local multi-professional team; pre-existing relationship between patients and their healthcare providers; and potential to establish new social interactions within the neighbourhood by participating in the programme. Three themes on barriers to attendance emerged: integrating the DSME programme into their own schedules; difficulties in expressing themselves in front of a group; and keeping the motivation for self-managing their T2DM.

Conclusions

From the patient perspective, the programme geographical proximity and the pre-existing patient-healthcare provider relationship were important factors that contributed to participation. Healthcare providers should consider these factors to improve access to DSME programmes and diabetes self-management in deprived populations. Longitudinal studies should be performed to measure the impact of these programmes.
Epigenetic loci for blood pressure are associated with hypertensive target organ damage in older African Americans from the genetic epidemiology network of Arteriopathy (GENOA) study
Authors: Kho Minjung , Zhao Wei , Ratliff Scott M. , Ammous Farah , Mosley Thomas H. , Shang Lulu , Kardia Sharon L. R. , Zhou Xiang , Smith Jennifer A.
Published: September 2020

Background

Hypertension is a major modifiable risk factor for arteriosclerosis that can lead to target organ damage (TOD) of heart, kidneys, and peripheral arteries. A recent epigenome-wide association study for blood pressure (BP) identified 13 CpG sites, but it is not known whether DNA methylation at these sites is also associated with TOD.

Methods

In 1218 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study, a cohort of hypertensive sibships, we evaluated the associations between methylation at these 13 CpG sites measured in peripheral blood leukocytes and five TOD traits assessed approximately 5 years later.

Results

Ten significant associations were found after adjustment for age, sex, blood cell counts, time difference between CpG and TOD measurement, and 10 genetic principal components (FDR q < 0.1): two with estimated glomerular filtration rate (eGFR, cg06690548, cg10601624), six with urinary albumin-to-creatinine ratio (UACR, cg16246545, cg14476101, cg19693031, cg06690548, cg00574958, cg22304262), and two with left ventricular mass indexed to height (LVMI, cg19693031, cg00574958). All associations with eGFR and four associations with UACR remained significant after further adjustment for body mass index (BMI), smoking status, and diabetes. We also found significant interactions between cg06690548 and BMI on UACR, and between 3 CpG sites (cg19693031, cg14476101, and cg06690548) and diabetes on UACR (FDR q < 0.1). Mediation analysis showed that 4.7% to 38.1% of the relationship between two CpG sites (cg19693031 and cg00574958) and two TOD measures (UACR and LVMI) was mediated by blood pressure (Bonferroni-corrected P < 0.05). Mendelian randomization analysis suggests that methylation at two sites (cg16246545 and cg14476101) in PHGDH may causally influence UACR.

Conclusions

In conclusion, we found compelling evidence for associations between arteriosclerotic traits of kidney and heart and previously identified blood pressure-associated DNA methylation sites. This study may lend insight into the role of DNA methylation in pathological mechanisms underlying target organ damage from hypertension.
The role of surgery type in postoperative atrial fibrillation and in-hospital mortality in esophageal cancer patients with preserved left ventricular ejection fraction
Authors: Chen Laite , Zhang Lu , Shi Lu , Fu Guosheng , Jiang Chenyang
Published: September 2020

Background

Postoperative atrial fibrillation (POAF) is one of the most common complications of esophagectomy, which may extend the inpatient hospital stay. Minimally invasive esophagectomy (MIE) has been increasingly used in clinical practice; however, its POAF risk and short-term mortality remain unclear. This study aimed to examine the POAF risk and in-hospital mortality rate between patients receiving MIE and open esophagectomy (OE).

Methods

Esophageal cancer patients who underwent MIE or OE from a retrospective cohort study were evaluated. A multivariate logistic regression model was built to assess the associations between esophagectomy (MIE vs. OE) and various outcomes (POAF, in-hospital mortality). Covariates included age, sex, body mass index, neoadjuvant therapy, tumor stage, surgery incision type, comorbidities, cardia conditions, peri-operative medication, and complications.

Results

Of the 484 patients with esophageal cancer, 63 received MIE. A total of 53 patients developed POAF. Compared to patients receiving OE, MIE patients had 81% reduced odds of POAF (adjusted odds ratio [aOR] 0.185, 95% CI 0.039–0.887, P = 0.035). No statistically significant association was found for in-hospital mortality (aOR 0.709, 95% CI 0.114–4.409, P = 0.712).

Conclusions

MIE is associated with a lower risk of POAF, compared to traditional surgery. No significant short-term survival benefit was found for MIE.
Development of competency model for family physicians against the background of ‘internet plus healthcare’ in China: a mixed methods study
Authors: Ni Ziling , Wang Xiaohe , Zhou Siyu , Zhang Tao
Published: September 2020

Background

Identification of the service competences of family physicians is central to ensuring high-quality primary care and improving patient outcomes. However, little is known about how to assess the family physicians’ service competences in primary care settings. It is necessary to develop and validate a general model of core competences of the family physician under the stage of construction of family doctor system and implementation of ‘Internet Plus Healthcare’ service model in China.

Methods

The literature review, behavioural event interviews, expert consultation and questionnaire survey were performed. The scale’s 35 questions were measured by response rate, highest score, lowest score, and average score for each. Delphi method was used to assess content validity, Cronbach’s α to estimate reliability, and factor analysis to test structural validity. Respondents were randomly divided into two groups; data for one group were used for exploratory factor analysis (EFA) to explore possible model structure. Confirmatory factor analysis (CFA) was then performed.

Results

Effective response rate was 93.56%. Cronbach’s α coefficient of the scale was 0.977. Factor analysis showed KMO of 0.988. Bartlett’s test showed χ2 of 22 917.515 (df = 630), p < .001. Overall authority grade of expert consultation was 0.80, and Kendall’s coefficient of concordance W was 0.194. By EFA, the five-factor model was retained after thorough consideration, and four items with factor loading less than 0.4 were proposed to obtain a five-dimension, 32-item scale. CFA was performed on the new structure, showing high goodness-of-fit test (NFI = 0.98, TLI = 0.91, SRMSR = 0.05, RMSEA = 0.04). Overall Cronbach’s α coefficients of the scale and each sub-item were greater than 0.9.

Conclusions

The scale has good reliability, validity, and credibility and can therefore serve as an effective tool for assessment of Chinese family physicians’ service competences.
Bullying victimization, physical inactivity and sedentary behavior among children and adolescents: a meta-analysis
Authors: García-Hermoso Antonio , Hormazabal-Aguayo Ignacio , Oriol-Granado Xavier , Fernández-Vergara Omar , del Pozo Cruz Borja
Published: September 2020

Background

Physical activity and sedentary behavior are related with psycho-social variables among youth, however its relationship with bullying victimization is unclear. The aim of the study was to clarify the associations between physical activity and sedentary behaviors with bullying victimization among children and adolescents.

Methods

Two independent authors searched in four databases. The studies were selected/included only if participants were children and/or adolescents and the relationship between physical activity and/or sedentary behavior with bullying victimization was reported. Random-effects meta-analyses were used.

Results

A total of 18 cross-sectional studies (including 386,740 children and adolescents, 51.8% females) were reviewed. Our study found that not meeting the physical activity guidelines (Odds Ratio [OR] = 1.14, 95% confidence interval [CI], 1.04 to 1.23) and excessive sedentary behavior (i.e., 2 h per day or more of screen time) (OR = 1.21, 95% CI, 1.14 to 1.28) were associated with 14 and 21% higher bullying victimization, respectively. Consistent associations were also found when we analyzed specific forms of bullying for sedentary behavior, including traditional and cyberbullying.

Conclusions

The present study establishes the first quantitative framework for understanding the influence of physical activity and sedentary behavior on bullying victimization, and lays the groundwork for future studies and interventions aimed to its promotion.

Trial registration

CRD42018099388.
Classification of Parkinson’s disease and essential tremor based on balance and gait characteristics from wearable motion sensors via machine learning techniques: a data-driven approach
Authors: Moon Sanghee , Song Hyun-Je , Sharma Vibhash D. , Lyons Kelly E. , Pahwa Rajesh , Akinwuntan Abiodun E. , Devos Hannes
Published: September 2020

Background

Parkinson’s disease (PD) and essential tremor (ET) are movement disorders that can have similar clinical characteristics including tremor and gait difficulty. These disorders can be misdiagnosed leading to delay in appropriate treatment. The aim of the study was to determine whether balance and gait variables obtained with wearable inertial motion sensors can be utilized to differentiate between PD and ET using machine learning. Additionally, we compared classification performances of several machine learning models.

Methods

This retrospective study included balance and gait variables collected during the instrumented stand and walk test from people with PD (n = 524) and with ET (n = 43). Performance of several machine learning techniques including neural networks, support vector machine, k-nearest neighbor, decision tree, random forest, and gradient boosting, were compared with a dummy model or logistic regression using F1-scores.

Results

Machine learning models classified PD and ET based on balance and gait characteristics better than the dummy model (F1-score = 0.48) or logistic regression (F1-score = 0.53). The highest F1-score was 0.61 of neural network, followed by 0.59 of gradient boosting, 0.56 of random forest, 0.55 of support vector machine, 0.53 of decision tree, and 0.49 of k-nearest neighbor.

Conclusions

This study demonstrated the utility of machine learning models to classify different movement disorders based on balance and gait characteristics collected from wearable sensors. Future studies using a well-balanced data set are needed to confirm the potential clinical utility of machine learning models to discern between PD and ET.
Quantitative description of upper extremity function and activity of people with spinal muscular atrophy
Authors: Janssen Mariska M. H. P. , Peeters Laura H. C. , de Groot Imelda J. M.
Published: September 2020

Background

Therapeutic management of the upper extremity (UE) function of people with spinal muscular atrophy (SMA) requires sensitive and objective assessment. Therefore, we aimed to measure physiologic UE function of SMA patients with different functional abilities and evaluate the relation between these physiologic measures and functional UE scales.

Methods

12 male and 5 female SMA patients (mean age 42 years; range 6–62 years) participated in this explorative study. Concerning the physiologic level, the maximal muscle torque, the maximal and normalized surface electromyography (sEMG) amplitudes, and the maximal passive and active joint angles were measured. Concerning the activity level, the Performance of the Upper Limb (PUL) scale was used, and hand function was examined using the Nine-Hole Peg Test and the Timed Test of In-Hand Manipulation (TIHM).

Results

Outcome measures that significantly related to the functional ability were: the PUL score (all dimensions); the finger to palm task of the Timed TIHM; biceps, triceps, and forearm extensor strength; and the active range of motion of shoulder abduction, shoulder flexion, and wrist extension. In addition, the following physiologic variables were related to the activity level (PUL score): hand function (the Nine-Hole Peg Test; Rs = − 0.61), the Timed TIHM (Rs = − 0.53), the maximal muscle torque (Rs = 0.74), the maximal sEMG amplitude (Rs = 0.79), and the maximal active joint angle (Rs = 0.88).

Conclusions

Muscle functions in SMA patients are already affected before activity limitations are noticeable. Consequently, monitoring the maximal muscle strength and the normalized muscle activity during task performance could play a role in the early detection of UE limitations. The mechanism behind the loss of arm activities due to SMA is primarily caused by decreasing muscle capacity, which influences the ability to move an arm actively. In clinical practices, these dimensions should be considered separately when monitoring disease progression in order to better evaluate the need for interventions.
Spotlight on Ki67 as a prognostic marker in early breast cancer: all that glitters may not be gold
Authors: Maltoni Roberta , Palleschi Michela , Ravaioli Sara , Tumedei Maria Maddalena , Altini Mattia , Bravaccini Sara
Published: September 2020

Kang and colleagues evaluated on a case series of 1848 breast cancer (BC) patients operated for a first primary ER positive HER2 negative BC if Ki67 expression is a significant prognostic factor only when PgR expression is low. The authors concluded that Ki67 with 10% cut off value is a prognostic factor only under low PgR expression level in early BC. We would like to underline, that as already stated in our previous papers, we believe that proliferation is important to define the decision-making of adjuvant therapies in early BC. The issue on Ki67 detection is the poor reproducibility due to different antibody clones, platforms and scoring methods. Not less important is that different Ki67 cut off values have been used by San Gallen guidelines and changed overtime. Then, despite the interesting results, we believe it would be better to use Ki67 biomarker in according to the standard Ki67 cut off according to San Gallen guidelines. Nowadays, standardization and optimization of Ki67 is still an urgent need.
Clinicopathological heterogeneity between primary and metastatic sites of gastroenteropancreatic neuroendocrine neoplasm
Authors: Shi Huiying , Jiang Chen , Zhang Qin , Qi Cuihua , Yao Hailing , Lin Rong
Published: September 2020

Background

Chromogranin A (CgA), synaptophysin (Syn) and the Ki-67 index play significant roles in diagnosis or the evaluation of the proliferative activity of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). However, little is known about whether these biological markers change during tumor metastasis and whether such changes have effect on prognosis.

Methods

We analyzed 35 specimens of both primary and metastatic tumor from 779 patients who had been diagnosed as GEP-NENs at Wuhan Union Hospital from August 2011 to October 2019. The heterogeneity of CgA, Syn and Ki-67 index was evaluated by immunohistochemical analysis.

Results

Among these 779 patients, the three most common sites of NENs in the digestive tract were the pancreas, rectum and stomach. Metastases were found in 311 (39.9%) patients. Among the 35 patients with both primary and metastatic pathological specimens, differences in the Ki-67 level were detected in 54.3% of the patients, while 37.1% showed a difference in CgA and only 11.4% showed a difference in Syn. Importantly, due to the difference in the Ki-67 index between primary and metastatic lesions, the WHO grade was changed in 8.6% of the patients. In addition, a Kaplan–Meier survival analysis showed that patients with Ki-67 index variation had a shorter overall survival (p = 0.0346), while neither Syn variation nor CgA variation was related to patient survival (p = 0.7194, p = 0.4829).

Conclusions

Our data indicate that primary and metastatic sites of GEP-NENs may exhibit pathological heterogeneity. Ki-67 index variation is closely related to the poor prognosis of patients with tumor metastasis, but neither Syn variation nor CgA variation is related to patient prognosis. Therefore, clinicopathologic evaluation of the primary tumor and metastatic sites could be helpful for predicting the prognosis.
Arthroscopic treatment of synovial chondromatosis of hip joint
Authors: Liu Yufeng , Li Ji , Ma Ning , An Mingyang , Gao Feng , Hu Bo , Zhang Boqing , Wang Zhigang , Liu Yujie , Li Chunbao
Published: September 2020

Purpose

This retrospective study summarized the clinical, radiographic, and arthroscopic manifestation of synovial chondromatosis (SC) of the hip, along with the post-operative effect to discuss the curative effect of arthroscopic management of hip SC.

Methods

Twenty-one patients who underwent arthroscopic surgery from the same surgeon for hip SC were followed up for an average of 45 months. T-shaped capsulotomy was routinely performed in each case. Visual analog scale, range of motion, modified Harris Hip Score, and International Hip Outcome Tool score were collected preoperatively and at the time of the latest follow-up. All patients’ demographics, radiographs, and arthroscopic images were collected to summarize and conclude the similarities and differences of their manifestation.

Results

Large wedged clumps of loose bodies demonstrated distinguishable radiographic, arthroscopic appearance and demanded a different surgical strategy. Postoperative scores were all significantly improved. One case of residual pain and two cases of residual loose bodies with no symptom related were reported at the final follow-up. All but one patient were satisfied with the outcome.

Conclusion

Arthroscopy treatment of hip SC with T-shaped capsulotomy has demonstrated a good result in terms of clinical outcome score, recurrence rate, and complication rate. On the basis of this study, we concluded the clinical performance of large wedged clumps of loose bodies of hip SC.
Selective antagonism of cJun for cancer therapy
Authors: Brennan Andrew , Leech James T. , Kad Neil M. , Mason Jody M.
Published: September 2020

The activator protein-1 (AP-1) family of transcription factors modulate a diverse range of cellular signalling pathways into outputs which can be oncogenic or anti-oncogenic. The transcription of relevant genes is controlled by the cellular context, and in particular by the dimeric composition of AP-1. Here, we describe the evidence linking cJun in particular to a range of cancers. This includes correlative studies of protein levels in patient tumour samples and mechanistic understanding of the role of cJun in cancer cell models. This develops an understanding of cJun as a focal point of cancer-altered signalling which has the potential for therapeutic antagonism. Significant work has produced a range of small molecules and peptides which have been summarised here and categorised according to the binding surface they target within the cJun-DNA complex. We highlight the importance of selectively targeting a single AP-1 family member to antagonise known oncogenic function and avoid antagonism of anti-oncogenic function.
Identification of circular RNAs in the ovarian follicles of Meishan and Duroc sows during the follicular phase
Authors: Xie Su , Li Mengxun , Chen Yansen , Liu Yi , Ma Lipeng , Sun Xiaomei , Sun Yishan , Gao Ruonan , Huang Tao
Published: September 2020

Circular RNAs (circRNAs) are a newly discovered class of endogenous non-coding RNAs that play an important role in growth and development by regulating gene expression and participating in a variety of biological processes. However, the role of circRNAs in porcine follicles remains unclear. Therefore, this study examined middle-sized ovarian follicles obtained from Meishan and Duroc sows at day 4 of the follicular phase. High-throughput RNA sequencing (RNA-seq) was utilized to construct circRNAs, and differential expression was identified. The findings were validated using reverse transcription PCR (RT-PCR) and DNA sequencing, GO and KEGG analyses were performed, and potential miRNA targets were identified. The RNA-seq identified a total of 15,866 circRNAs, with 244 differentially expressed in the Meishan relative to the Duroc (111 up-regulated and 133 down-regulated). The RT-PCR finding confirmed the RNA-seq results, and quantitative real-time PCR (qPCR) analysis examining a subset of the circRNAs showed that they are resistant to RNase R digestion. Bioinformatics analysis (GO and KEGG) showed that the host genes associated with the differentially expressed circRNAs are involved in reproduction and follicular development signaling pathways. Furthermore, many of the circRNAs were found to interact with miRNAs that are associated with follicular development. This study presents a new perspective for studying circRNAs and provides a valuable resource for further examination into the potential roles of circRNAs in porcine follicular development.
Massive hemothorax due to bleeding from thoracic spinal fractures: a case series and systematic review
Authors: Ninomiya Kohei , Kuriyama Akira , Uchino Hayaki
Published: September 2020

Background

Massive hemothorax secondary to thoracic spinal fractures is rare, and its clinical characteristics, treatment, and prognosis are unknown. We present two cases of thoracic spinal fracture-induced massive hemothorax and a systematic review of previously reported cases.

Methods

This study included patients with traumatic hemothorax from thoracic spinal fractures at a Japanese tertiary care hospital. A systematic review of published cases was undertaken through searches in PubMed, EMBASE, and ICHUSHI from inception to October 13, 2019.

Results

Case 1: An 81-year-old man developed hemodynamic instability from a right hemothorax with multiple rib fractures following a pedestrian–vehicle accident; > 1500 mL blood was evacuated through the intercostal drain. Thoracotomy showed hemorrhage from a T8-burst fracture, and gauze packing was used for hemostasis. Case 2: A 64-year-old man with right hemothorax and hypotension after a fall from height had hemorrhage from a T7-burst fracture, detected on thoracotomy, which was sealed with bone wax. Hypotension recurred during transfer; re-thoracotomy showed bleeding from a T7 fracture, which was packed with bone wax and gauze for hemostasis. The systematic review identified 10 similar cases and analyzed 12 cases, including the abovementioned cases. Inferior part of thoracic spines was prone to injury and induced right-sided hemothorax. Most patients developed hemodynamic instability, and some sustained intra-transfer hemorrhage; direct compression (gauze packing, bone wax, and hemostatic agents) was the commonest hemostatic procedure. The mortality rate was 33.3%.

Conclusions

Hemothorax due to thoracic spinal fracture can be fatal. Thoracotomy with direct compression is necessary in hemodynamically unstable patients.
Real-time AI prediction for major adverse cardiac events in emergency department patients with chest pain
Authors: Zhang Pei-I , Hsu Chien-Chin , Kao Yuan , Chen Chia-Jung , Kuo Ya-Wei , Hsu Shu-Lien , Liu Tzu-Lan , Lin Hung-Jung , Wang Jhi-Joung , Liu Chung-Feng , Huang Chien-Cheng
Published: September 2020

Background

A big-data-driven and artificial intelligence (AI) with machine learning (ML) approach has never been integrated with the hospital information system (HIS) for predicting major adverse cardiac events (MACE) in patients with chest pain in the emergency department (ED). Therefore, we conducted the present study to clarify it.

Methods

In total, 85,254 ED patients with chest pain in three hospitals between 2009 and 2018 were identified. We randomized the patients into a 70%/30% split for ML model training and testing. We used 14 clinical variables from their electronic health records to construct a random forest model with the synthetic minority oversampling technique preprocessing algorithm to predict acute myocardial infarction (AMI) < 1 month and all-cause mortality < 1 month. Comparisons of the predictive accuracies among random forest, logistic regression, support-vector clustering (SVC), and K-nearest neighbor (KNN) models were also performed.

Results

Predicting MACE using the random forest model produced areas under the curves (AUC) of 0.915 for AMI < 1 month and 0.999 for all-cause mortality < 1 month. The random forest model had better predictive accuracy than logistic regression, SVC, and KNN. We further integrated the AI prediction model with the HIS to assist physicians with decision-making in real time. Validation of the AI prediction model by new patients showed AUCs of 0.907 for AMI < 1 month and 0.888 for all-cause mortality < 1 month.

Conclusions

An AI real-time prediction model is a promising method for assisting physicians in predicting MACE in ED patients with chest pain. Further studies to evaluate the impact on clinical practice are warranted.
It is unprecedented: trial management during the COVID-19 pandemic and beyond
Authors: Mitchell Eleanor J. , Ahmed Khaled , Breeman Suzanne , Cotton Seonaidh , Constable Lynda , Ferry Gillian , Goodman Kirsteen , Hickey Helen , Meakin Garry , Mironov Katy , Quann Niamh , Wakefield Natalie , McDonald Alison
Published: September 2020

The COVID-19 pandemic has presented unique challenges for the clinical trial community, both in the rapid establishment of COVID-19 clinical trials and many existing non-COVID-19 studies either being temporarily paused (whether that is a complete pause or pause in some activities) and/or adapting their processes. Trial managers have played a key role in decision-making, undertaking risk assessments and adapting trial processes, working closely with other members of the research team. This article presents some of the ways in which trial management processes have been altered and the key role that trial managers have played. It has been born out of discussions between trial managers in the UK who are members of the UK Trial Managers’ Network (UKTMN), a national network of trial management professionals managing non-commercial trials.

In these unprecedented times, clinical trials have faced many uncertainties and broad-ranging challenges encompassing a range of activities including prioritising patient safety amidst the pandemic, consenting and recruiting new participants into trials, data collection and management and intervention delivery. In many cases, recruitment has been paused whilst mitigations have been put in place to continue data collection. Innovative solutions have been implemented to ensure we continue, where possible, to deliver high-quality clinical trials. Technology has provided many solutions to these challenges, and trial managers have adapted to new ways of working whilst continuing to deliver their clinical trials. Trial management groups are now faced with new uncertainties around re-starting clinical trials, and it is unclear currently how this will go, though working together with sponsors, funders and site teams is clearly a priority.

Clinical trial teams have worked together to ensure their trials have adapted quickly whilst ensuring participant safety is given utmost importance. There are clear examples where the trial community have come together to share experiences and expertise, and this should continue in the future to ensure the innovative practices developed become embedded in the design and conduct of clinical trials in the future.
Epigenetic stratification of head and neck cancer survivors reveals differences in lycopene levels, alcohol consumption, and methylation of immune regulatory genes
Authors: Moody Laura , Crowder Sylvia L. , Fruge Andrew D. , Locher Julie L. , Demark-Wahnefried Wendy , Rogers Laura Q. , Delk-Licata Ashley , Carroll William R. , Spencer Sharon A. , Black Molly , Erdman John W. , Chen Hong , Pan Yuan-Xiang , Arthur Anna E.
Published: September 2020

Background

Inflammation has been associated with higher rates of recurrence and mortality in head and neck cancer (HNC). While the biological mechanisms predisposing patients to heightened inflammatory states remain largely unknown, DNA methylation has been proposed to reflect systemic inflammation. In this analysis, we attempt to identify meaningful epigenetic patterns in HNC survivors by stratifying individuals based on DNA methylation profiles in leukocytes.

Results

We used hierarchical clustering to uncover three distinct methylation patterns among HNC survivors. Each group displayed a unique methylation signature in inflammatory pathways including cytokine and B-cell receptor signaling. Additionally, we examined physiological, clinical, and lifestyle parameters related to inflammation, such as circulating carotenoid and cytokine levels, cancer treatment type, and alcohol consumption. Specifically, we identified one group of survivors who had significant differential methylation of transcriptional and translational regulators as well as genes in the T-cell receptor signaling pathway, including hypermethylation of CD40 ligand (CD40LG) and Tec protein tyrosine kinase (TEC) and hypomethylation ofCD8A. This group also displayed high circulating lycopene levels. We identified another group that had distinctive methylation in the toll-like receptor (TLR) signaling pathway, including hypomethylation ofTLR5, a component of the inhibitor of nuclear factor-kappa B kinase complex (CHUK), and two mitogen-activated protein kinases (MAP3K8andMAP2K3). This group also had hypermethylation of mitochondrial ribosomal genes along with higher rates of alcohol consumption.

Conclusion

The correlation between lycopene, alcohol consumption, DNA methylation, and inflammation warrants further investigation and may have implications in future recommendations and interventions to impact health outcomes in HNC survivors.
Surgical management of subhepatic perforated appendicitis: a case report
Authors: Hakim Mumin , Mostafa Rania , Al Shehri Mohammed , Sharawy Sherif
Published: September 2020

Background

Subhepatic appendicitis is an exceedingly rare presentation, accounting for 0.01% of acute appendicitis cases. It is of prime importance to be aware of variants and manage such challenging cases accordingly.

Case presentation

We present a case of a middle-aged Saudi woman with subhepatic perforated appendicitis and peritonitis who underwent an exploratory laparotomy and appendectomy.

Conclusions

The initial diagnosis and surgical management of such patients is challenging due to an atypical presentation. The surgical management of such patients is discussed with a brief review of the literature.
Tabersonine ameliorates osteoblast apoptosis in rats with dexamethasone-induced osteoporosis by regulating the Nrf2/ROS/Bax signalling pathway
Authors: Sun Xi , Gan Lijun , Li Nan , Sun Shuyi , Li Na
Published: September 2020

We explored how tabersonine (Tab) protected against dexamethasone (Dex)-induced osteoporosis. Osteoblasts were treated with Dex (100 µM) with or without Table (5 or 10 µM). We measured cell viability, alkaline phosphatase (ALP) activity, and mitochondrial
superoxide and reactive oxygen species levels. We used flow cytometry to explore the effects of Tab on mitochondrial membrane potential and osteoblast apoptosis. We used RT-PCR and western blotting to examine the effect of Tab on protein expression. We evaluated the effects of Tab on bone histopathology and bone mineral density in rats with Dex-induced osteoporosis. Tab increased cell viability and ALP activity, and reduced the mitochondrial superoxide, reactive oxygen species and matrix metalloproteinase levels and osteoblast apoptosis. Tab significantly reduced the levels of nuclear factor erythroid 2-related factor 2 (Nrf2), haem oxygenase-1 and NAD(P)H quinone dehydrogenase 1. Moreover, it increased the levels of mRNAs encoding runt-related transcription factor 2, bone morphogenetic protein-2 and osterix. These data suggest that Tab ameliorates Dex-induced osteoporosis by regulating the Nrf2 signalling pathway.
Rap1b but not Rap1a in the forebrain is required for learned fear
Authors: Chen Wen-Bing , Pan Han-Qing , He Ye , Wang Xue-Hui , Zhang Wen-Hua , Pan Bing-Xing
Published: September 2020

Background

Fear is an adaptive response across species in the face of threatening cues. It can be either innate or learned through postnatal experience. We have previously shown that genetic deletion of both Rap1a and Rap1b, two isoforms of small GTPase Rap1 in forebrain, causes impairment in auditory fear conditioning. However, the specific roles of these two isoforms are not yet known.

Results

In the present study, employing mice with forebrain-restricted deletion of Rap1a or Rap1b, we found that they are both dispensable for normal acquisition of fear learning. However, Rap1b but not Rap1a knockout (KO) mice displayed impairment in the retrieval of learned fear. Subsequently, we found that the expression of c-Fos, a marker of neuronal activity, is specifically decreased in prelimbic cortex (PL) of Rap1b KO mice after auditory fear conditioning, while remained unaltered in the amygdala and infralimbic cortex (IL). On the other hand, neither Rap1a nor Rap1b knockout altered the innate fear of mice in response to their predator odor, 2,5-Dihydro-2,4,5-Trimethylthiazoline (TMT).

Conclusion

Thus, our results indicate that it is Rap1b but not Rap1a involved in the retrieval process of fear learning, and the learned but not innate fear requires Rap1 signaling in forebrain.
A collaborative healthcare framework for shared healthcare plan with ambient intelligence
Authors: Javed Abdul Rehman , Sarwar Muhammad Usman , Beg Mirza Omer , Asim Muhammad , Baker Thar , Tawfik Hissam
Published: September 2020

The fast propagation of the Internet of Things (IoT) devices has driven to the development of collaborative healthcare frameworks to support the next generation healthcare industry for quality medical healthcare. This paper presents a generalized collaborative framework namedcollaborative shared healthcare plan (CSHCP)for cognitive health and fitness assessment of people using ambient intelligent application and machine learning techniques.CSHCPprovides support for daily physical activity recognition, monitoring, assessment and generate a shared healthcare plan based on collaboration among different stakeholders: doctors, patient guardians, as well as close community circles. The proposed framework shows promising outcomes compared to the existing studies. Furthermore, the proposed framework enhances team communication, coordination, long-term plan management of healthcare information to provide a more efficient and reliable shared healthcare plans to people.
Redox signaling and Alzheimer’s disease: from pathomechanism insights to biomarker discovery and therapy strategy
Authors: Chen Yuan-Yuan , Wang Min-Chang , Wang Yan-Ni , Hu He-He , Liu Qing-Quan , Liu Hai-Jing , Zhao Ying-Yong
Published: September 2020

Aging and average life expectancy have been increasing at a rapid rate, while there is an exponential risk to suffer from brain-related frailties and neurodegenerative diseases as the population ages. Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide with a projected expectation to blossom into the major challenge in elders and the cases are forecasted to increase about 3-fold in the next 40 years. Considering the etiological factors of AD are too complex to be completely understood, there is almost no effective cure to date, suggesting deeper pathomechanism insights are urgently needed. Metabolites are able to reflect the dynamic processes that are in progress or have happened, and metabolomic may therefore provide a more cost-effective and productive route to disease intervention, especially in the arena for pathomechanism exploration and new biomarker identification. In this review, we primarily focused on how redox signaling was involved in AD-related pathologies and the association between redox signaling and altered metabolic pathways. Moreover, we also expatiated the main redox signaling-associated mechanisms and their cross-talk that may be amenable to mechanism-based therapies. Five natural products with promising efficacy on AD inhibition and the benefit of AD intervention on its complications were highlighted as well.

Graphical Abstract
The distribution of soil morphological characteristics for landslide-impacted Sumbing Volcano, Central Java - Indonesia
Authors: Noviyanto Amir , Sartohadi Junun , Purwanto Benito Heru
Published: September 2020

Landslides are the second biggest natural disasters in Indonesia, occurring mostly in volcanic area with thick and clay rich soils. Examining the changes of land surface and soil morphology brought about by a particular landslide is usually the first step required for vegetative rehabilitation. Most examinations to date, however, have been based on general characters rather than on soil morphology, including physical and chemical characteristics of the soil, which are usually locally specific. This study investigates the morphological characteristics of soil in a landslide-prone slope region of Sumbing Volcano, in Central Java Province of Indonesia. The field investigations are conducted at three landslides sites. It starts with interpreting small format areal-photographs which have been geo-corrected, followed by the delineation of landslide zones (i.e. crowns, main scarps, heads, bodies and toes) based on morphological analysis of the landslide sites. Finally, identification of morphological, physical and chemical characteristics of the soil in each of the landslide zones are conducted in the field, along with laboratory tests. The results demonstrate that soil morphology is unique for each of the landslide zones. The characters of the undisturbed soil, as indicated by well-defined genetic horizons, are found in the crown zones. Outcrop of high clay content soil material layers are seen in the main scarp zones. Meanwhile pedoturbation processes are evident in the zone of bodies and toes, suggesting that the soil is prone for erosion. If natural erosions in these zones are not controlled and/or unmitigated, the situation will trigger landslide reactivations. We suggest that in studying landslide, one also considers the characters of soil morphology, as this additional information provides a more complete understanding of both land surface morphology and soil morphology to inform landslide vegetative rehabilitation.
Uptake of the child care expense deduction: exploring factors associated with the use of the child care expense deduction among families with a child under 12 years
Authors: Heidinger Loanna , Findlay Leanne C. , Guèvremont Anne
Published: September 2020

The Canadian government implemented the child care expense deduction in 1972, a policy initiative intended to offset the financial cost of child care for eligible families. Although the deduction has now been in place for almost 50 years, and almost half of all families with a child aged 0–14 years use child care (Sinha, 2014), little research has examined the factors associated with claiming the child care expense deduction. The current study examined the uptake and usage of the child care expense deduction among families with at least one child under the age of 12 in 2011. Furthermore, the family demographic and work characteristics of families who have at least one child under the age of 12 in the household were explored in terms of the characteristics associated with a higher likelihood of claiming the child care expense deduction.
A safe, stable, and convenient three-dimensional device for high Le Fort I osteotomy
Authors: Sugahara Keisuke , Koyachi Masahide , Odaka Kento , Matsunaga Satoru , Katakura Akira
Published: September 2020

Background

Le Fort I osteotomy is a highly effective treatment for skeletal jaw deformities and is commonly performed. High Le Fort I osteotomy is a modified surgical procedure performed for improving the depression of the cheeks by setting the osteotomy higher than the conventional Le Fort I osteotomy. Developments in three-dimensional (3D) technology have popularized the use of 3D printers in various institutions, especially in orthognathic surgeries. In this study, we report a safe and inexpensive method of performing a high Le Fort I osteotomy using a novel 3D device and piezosurgery, which prevent tooth root injury without disturbing the operation field for patients with a short midface and long tooth roots.

Results

A 17-year-old woman presented with facial asymmetry, mandibular protrusion, a short midface, and long tooth roots. We planned high Le Fort I osteotomy and bilateral sagittal split ramus osteotomy. Prevention of damage to the roots of the teeth and the infraorbital nerve and accurate determination of the posterior osteotomy line were crucial for clinical success. Le Fort I osteotomy using 3D devices has been reported previously but were particularly large in size for this case. Additionally, setting the fixing screw of the device was difficult, because of the risk of damage to the roots of the teeth. Therefore, a different surgical technique, other than the conventional Le Fort I osteotomy and 3D device, was required. The left and right parts of the 3D device were fabricated separately, to prevent any interference in the surgical field. Further, the 3D device was designed to accurately cover the bone surface from the piriform aperture to the infra-zygomatic crest with two fixation points (the anterior nasal spine and the piriform aperture), which ensured stabilization of the 3D device. The device is thin and does not interfere with the surgical field. Safe and accurate surgical performance is possible using this device and piezosurgery. The roots of the teeth and the infraorbital nerve were unharmed during the surgery.

Conclusions

This device is considerably smaller than conventional devices and is a simple, low-cost, and efficient method for performing accurate high Le Fort I osteotomy.
Minnesota wild hemp: a crucial botanical source in early cannabinoid discovery
Authors: Filer Crist N.
Published: September 2020

Renewed and sustained Cannabis chemistry exploration was initiated by Roger Adams at the University of Illinois Chemistry Department with cooperation from the Treasury Department Narcotics Laboratory in the early 1940’s. This partnership and time investment by both parties made practical sense. Adams was able to explore natural products chemistry and the Narcotics Laboratory began to clarify the chemistry mysteries of Cannabis. Minnesota wild hemp, often viewed as just a roadside weed, was employed as the critical botanical source. Based on its widespread cultivation during World War II, this was also a very pragmatic decision. Although the unique Illinois – Washington D. C. collaboration lasted only a few short years (1939–1942), the stunning results included the isolation and extensive characterization of cannabidiol, the structure elucidation and total synthesis of cannabinol as well as the identification of the tetrahydrocannabinol structure as an intoxicating pharmacophore. Furthermore, this research well prepared many junior chemists for prolific careers in both academia as well as industry, inspired the discoveries of later Cannabis investigators and also provided a successful model of a productive academic-government partnership.
Percutaneous trans-ulnar versus trans-radial arterial approach for coronary angiography and angioplasty, a preliminary experience at an Egyptian cardiology center
Authors: Shafiq Mohammad , Mahmoud Hesham Boushra , Fanous Malak Lamie
Published: September 2020

Background

Trans-ulnar approach was proposed primarily for elective procedures in patients not suitable for trans-radial approach that was introduced two decades ago. The trans-ulnar approach is as safe and effective as the trans-radial approach for coronary angiography and intervention.

Aim

This study’s aim was to assess the feasibility and safety of the trans-ulnar approach in coronary procedures as a preliminary experience for operators experienced in trans-radial approach with no/minimal trans-ulnar approach experience at an Egyptian center.

Results

Vascular access in 120 patients was selected randomly for coronary angiography and angioplasty—80 through radial and 40 through ulnar approach. Patients were examined for local complications and Doppler evaluation to both radial and ulnar arteries a day after the procedure was done. Ulnar approach success was 82.5% versus 93.7% in the radial group; failure of ulnar artery puncture was the only cause of crossover in the ulnar group, while occurrence of persistent spasm was the leading cause of crossover in the radial group followed by radial artery tortuosity. The procedure time of coronary angiography and percutaneous coronary intervention of the ulnar group was significantly higher than that of the radial group (Pvalue = 0.011 and 0.034, respectively). The mean caliber of the right ulnar artery was 2.45 ± 0.38, slightly larger than that of the radial artery 2.33 ± 0.38 at the level of the wrist, but this difference was statistically non-significant.

Conclusion

Our study demonstrated that ulnar access with experienced radial operators and in our patients is a safe and practical approach for coronary angiography or angioplasty, without any major complications. Bearing in mind its high success rate, it can be used when a radial artery is not useful for the catheterization or as a default approach on the expense of slightly longer procedural time.