bluuebunny/crossref_metadata_2025 huggingface dataset:
Involving Research Participants in a Pan-European Research Initiative: The EPAD Participant Panel Experience
Authors: Gregory Sarah , Bunnik Eline M , Callado Ana Belén , Carrie Isabelle , De Boer Casper , Duffus Julie , Fauria Karine , Forster Shona , Gove Dianne , Knezevic Iva , Laquidain Alejandro , Pennetier Delphine , Saunders Stina , Sparks Sarah , Rice J. , Ritchie Craig W , Milne Richard
Published: September 2020

Background: Including participants in patient and public involvement activities is increasingly acknowledged as a key pillar of successful research activity. Such activities can influence recruitment and retention, as well as researcher experience and contribute to decision making in research studies. However, there are few established methodologies of how to set up and manage participant involvement activities. Further, there is little discussion of how to do so when dealing with collaborative projects that run across countries and operate in multiple linguistic and regulatory contexts. Methods: In this paper we describe the set-up, running and experiences of the EPAD participant panel. The EPAD study was a pan-European cohort study with the aim to understand risks for developing Alzheimer’s disease and build a readiness cohort for Phase 2 clinical trials. Due to the longitudinal nature of this study, combined with the enrolment of healthy volunteers and those with mild cognitive impairments, the EPAD team highlighted participant involvement as crucial to the success of this project. The EPAD project employed a nested model, with local panels meeting in England, France, Scotland, Spain and The Netherlands, and feeding into a central study panel. The local panels were governed by terms of reference which were adaptable to local needs. Results: The impact of the panels has been widespread, and varies from feedback on documentation, to supporting with design of media materials and representation of the project at national and international meetings. Conclusions: The EPAD panels have contributed to the success of the project and the model established is easily transferable to other disease areas investigating healthy or at-risk populations.
Genetically-regulated transcriptomics & copy number variation of proctitis points to altered mitochondrial and DNA repair mechanisms in individuals of European ancestry
Authors: Pathak Gita A , Polimanti Renato , Silzer Talisa K , Wendt Frank R , Chakraborty Ranajit , Phillips Nicole R
Published: September 2020

BACKGROUND: Proctitis is an inflammation of the rectum and may be induced by radiation treatment for cancer. The genetic heritability of developing radiotoxicity and prior role of genetic variants as being associated with side-effects of radiotherapy necessitates further investigation for underlying molecular mechanisms. In this study, we investigated gene expression regulated by genetic variants, and copy number variation in prostate cancer survivors with radiotoxicity. METHODS: We investigated proctitis as a radiotoxic endpoint in prostate cancer patients who received radiotherapy (n=222). We analyzed the copy number variation and genetically regulated gene expression profiles of whole-blood and prostate tissue associated with proctitis. The SNP and copy number data were genotyped on Affymetrix® Genome-wide Human SNP Array 6.0. Following QC measures, the genotypes were used to obtain gene expression by leveraging GTEx, a reference dataset for gene expression association based on genotype and RNA-seq information for prostate (n= 132) and whole-blood tissue (n=369). RESULTS: In prostate tissue, 62 genes were significantly associated with proctitis, and 98 genes in whole-blood tissue. Six genes - CABLES2, ATP6AP1L, IFIT5, ATRIP, TELO2, and PARD6G were common to both tissues. The copy number analysis identified seven regions associated with proctitis, one of which (ALG1L2) was also associated with proctitis based on transcriptomic profiles in the whole-blood tissue. The genes identified via transcriptomics and copy number variation association were further investigated for enriched pathways and gene ontology. Some of the enriched processes were DNA repair, mitochondrial apoptosis regulation, cell-to-cell signaling interaction processes for renal and urological system, and organismal injury.CONCLUSIONS: We report gene expression changes based on genetic polymorphisms. Integrating gene-network information identified these genes to relate to canonical DNA repair genes and processes. This investigation highlights genes involved in DNA repair processes and mitochondrial malfunction possibly via inflammation. Therefore, it is suggested that larger studies will provide more power to infer the extent of underlying genetic contribution for an individual’s susceptibility to developing radiotoxicity.
Artificial neural networks improve LDCT lung cancer screening: A comparative validation study
Authors: Hsu Yin-Chen , Tsai Yuan-Hsiung , Weng Hsu-Huei , Hsu Li-Sheng , Tsai Ying-Huang , Lin Yu-Ching , Hung Ming-Szu , Fang Yu-Hung , Chen Chien-Wei
Published: September 2020

Background: This study proposes a prediction model for the automatic assessment of lung cancer risk based on an artificial neural network (ANN) with a data-driven approach to the low-dose computed tomography (LDCT) standardized structure report. Methods: This comparative validation study analysed a prospective cohort from Chiayi Chang Gung Memorial Hospital, Taiwan. In total, 836 asymptomatic patients who had undergone LDCT scans between February 2017 and August 2018 were included, comprising 27 lung cancer cases and 809 controls. A derivation cohort of 602 participants (19 lung cancer cases and 583 controls) was collected to construct the ANN prediction model. A comparative validation of the ANN and Lung-RADS was conducted with a prospective cohort of 234 participants (8 lung cancer cases and 226 controls). The areas under the curves (AUCs) of the receiver operating characteristic (ROC) curves were used to compare the prediction models. Results: At the cut-off of category 3, the Lung-RADS had a sensitivity of 12.5%, specificity of 96.0%, positive predictive value of 10.0%, and negative predictive value of 96.9%. At its optimal cut-off value, the ANN had a sensitivity of 75.0%, specificity of 85.0%, positive predictive value of 15.0%, and negative predictive value of 99.0%. The area under the ROC curve was 0.764 for the Lung-RADS and 0.873 for the ANN ( P =0.01). The two most important predictors used by the ANN for predicting lung cancer were the documented sizes of partially solid nodules and ground-glass nodules. Conclusions: Compared to the Lung-RADS, the ANN provided better sensitivity for the detection of lung cancer in an Asian population. In addition, the ANN provided a more refined discriminative ability than the Lung-RADS for lung cancer risk stratification with population-specific demographic characteristics. When lung nodules are detected and documented in a standardized structured report, ANNs may better provide important insights for lung cancer prediction than conventional rule-based criteria.
Determinants of participation in a post-hospitalization physical exercise program for older adults
Authors: Urquiza Miriam , Echeverria Iñaki , Besga Ariadna , Amasene Maria , Labayen Idoia , Rodriguez Ana , Barroso Julia , Aldamiz Mikel , Irazusta Jon
Published: September 2020

BACKGROUND: Older patients often experience a decline in physical function and cognitive status after hospitalization. Although interventions involving physical exercise are effective in improving functional performance, participation in physical exercise interventions among older individuals is low. We aimed to identify factors that contribute to exercise refusal among post-hospitalized older patients.METHODS: A cross-sectional study of recruitment data from a randomized controlled trial was conducted involving 495 hospitalized people ≥70 years old. Sociodemographic and clinical data were obtained from the Basque Public Health System database. We determined physical function with the Short Physical Performance Battery (SPPB), nutritional status with the Mini-Nutritional Assessment, frailty according to the Fried phenotype criteria, and cognitive function with the Short Portable Mental Status Questionnaire (SPMSQ). Student’s t, Mann-Whitney U, or chi-squared tests were applied for bivariate analysis. Parameters significantly associated with participation were introduced in a logistic multivariate regression model.RESULTS: Among the analyzed patients, 88.8% declined participation in the physical exercise program. Multivariate regression revealed that older age (OR: 1.13; 95% CI: 1.07 - 1.19), poor nutritional status (OR: 0.81; 95% CI: 0.69 - 0.95), and reduced home accessibility (OR: 0.27; 95% CI: 0.08 - 0.94) were predictors of participation refusal. Moreover, patients who declined participation had worse performance on the SPPB (P < 0.05) and its tests of balance, leg strength, and walking speed (P < 0.05). No differences were found between groups in other variables. CONCLUSIONS: This study confirms low participation of older adults in a post-hospitalization physical exercise program. Non-participation was associated with increased age, poor nutritional status, and reduced home accessibility. Our findings support the need for intervention design that accounts for these factors to increase older patient participation in beneficial exercise programs.
Cancer in Moroccan elderly: The first multicenter transverse study exploring the sociodemographic characteristics, clinical profile and quality of life of elderly Moroccan cancer patients
Authors: Amzerin Mounia , Laayachi Mohamed , Bazine Aziz , Aassab Rachid , Arifi Samia , Benbrahim Zineb , Khmamouche Mohamed Reda , Kairouani Mouna , Raiss Hanan , Majid Noura , Ouaouch Saloua , Ichou Mohammed , Afqir Said , Mellas Nawfal , Fetohi Mohamed , Razine Rachid , Errihani Hassan
Published: September 2020

Background: Moroccan incidence of cancer is increasing with the lengthening of life expectancy. Data regarding elderly Moroccan cancer patients are lacking. In the context of our project aiming to develop an adapted version of the Comprehensive Geriatric Assessment CGA to the Moroccan population, we launched the first Moroccan multicenter transverse study to explore the characteristics of elderly Moroccan cancer patients.Methods: The study was conducted in nine Moroccan medical oncology departments. Patients were enrolled over 4 months. Inclusion criteria were patients aged 65 years or over with verified solid cancer. The questionnaire included four sections: socio-demographic and economic data, clinical data, vulnerability and EORTC-QLQ C30. We explored the entire included population. Then, we compared the results according to age (65-70 years old and ≥71 years old) and sex. We also explored the correlation between G8 scores and the ability to practice religion as an indicator of fitness level. Results: In total, 164 patients were enrolled. The mean age was 73.18± 6.01 years. The majority of patients were married, lived with their children and received their financial income from them. Fifteen percent of families asked to hide the diagnosis from the patient. Breast (23%), colorectal (15.9%) and lung (14%) cancers were the most frequent, and 83.5% had an abnormal G8. The majority of the patients were independent for basic daily activities. Female patients had poorer social and economic conditions. Abnormal G8 was correlated with religious practice and quality of life scores. Conclusion: This is the first multicenter prospective study designed to collect data on the lifestyle and clinical profiles of elderly Moroccan cancer patients as an Arab and Muslim population. Our study shows that it is a well-cared-for population with strong social ties. However, there is deep economic vulnerability, especially among women, requiring urgent care. Religious practice is an important daily activity for our elderly patients and should be included in the Moroccan CGA.
Role of Circulating Free DNA in Evaluating Clinical Tumor Burden and Predicting Survival in Chinese Metastatic Colorectal Cancer Patients
Authors: xu xiaojing , yu yiyi , shen minna , liu menglin , wu shengchao , liang li , huang fei , zhang chenlu , guo wei , liu tianshu
Published: September 2020

Background: The aim of this study was to explore the utility of circulating free DNA (cfDNA) in the evaluation of clinical tumor burden and survival in Chinese patients with metastatic colorectal cancer (mCRC) and to preliminarily summarize some metastatic characteristics associated with mutational status.Methods: A panel covering a total of 197 hotspot mutations of KRAS, NRAS, BRAF and PIK3CA was used to evaluate the mutational status in plasma by next-generation sequencing (NGS) technology in 126 patients with mCRC. An amplification-refractory mutation system (ARMS) was used to analyze genomic DNA from matched tissue samples. Clinical markers including carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125), neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) in serum and the sum of all tumor diameters on CT or PET/CT were collected to indicate clinical tumor burden. The correlations between cfDNA and clinical tumor burden were analyzed using Pearson correlation and linear regression models. The median progression-free survival (PFS) and 1-year overall survival (OS) rates were calculated by Kaplan-Meier (K-M) survival analysis.Results: If the 126 enrolled patients, patients who were tested positive for mutations in plasma accounted for 45.2% (57/126). Mutations in KRAS, NRAS, BRAF and PIK3CA were detected in 37.3% (47/126), 1.6% (2/126), 3.2% (4/126) and 13.5% (17/126) of patients, respectively. The overall concordance rate of mutational status between plasma and matched tissues was 78.6% (99/126). Sixteen patients had mutations in plasma that were not detected in tissue, including some rare hotspot mutations. The cfDNA concentration was significantly correlated with the levels of clinical markers, especially CEA (P<0.0001, Pearson r = 0.81), LDH (P<0.0001, Pearson r = 0.84) and the sum of tumor diameters (P<0.0001, Pearson r = 0.80). Patients with a high cfDNA concentration (>17.91 ng/ml) had shorter median progression-free survival (6.6 versus 11.7 months, P<0.0001) and lower 1-year overall survival rate (56% versus 94%, P<0.0001) than those with a low cfDNA concentration (≤17.91 ng/ml). The most common metastatic site was the liver (77.8%), followed by the lymph nodes (62.7%), lung (40.5%), peritoneum (14.3%) and bone (10.3%), in all patients. There was no significant difference in metastasis between different mutational statuses.Conclusion: Analyzing mutations in plasma could provide a more comprehensive overview of the mutational landscape than analyzing mutations in tissue. The cfDNA concentration could be a quantitative biomarker of tumor burden and could predict survival in Chinese patients with mCRC.
Characterization of poplar growth-regulating factors and analysis of their function in leaf size control
Authors: Wang Jinnan , Zhou Houjun , Zhao Yanqiu , Sun Pengbo , Tang Fang , Song Xueqin , Lu Mengzhu
Published: September 2020

Background: Growth-regulating factors (GRFs) are plant-specific transcription factors that control organ size. Nineteen GRF genes were identified in the Populus trichocarpa genome and one was reported to control leaf size by regulating cell expansion. In this study, we further characterize the roles of the other poplar GRFs in leaf size control in a similar manner.Results: The 19 poplar GRF genes were clustered into six groups according to their phylogenetic relationship with Arabidopsis GRFs. Bioinformatic analysis, degradome, and transient transcription assays showed that 18 poplar GRFs were regulated by miR396, with GRF12b the only exception. The functions of PagGRF6b (Pag, Populus alba × P. glandulosa), PagGRF7a, PagGRF12a, and PagGRF12b, representing three different groups, were investigated. The results show that PagGRF6b may have no function on leaf size control, while PagGRF7a functions as a negative regulator of leaf size by regulating cell expansion. By contrast, PagGRF12a and PagGRF12b may function as positive regulators of leaf size control by regulating both cell proliferation and expansion, primarily cell proliferation.Conclusions: The diversity of poplar GRFs in leaf size control may facilitate the specific, coordinated regulation of poplar leaf development through fine adjustment of cell proliferation and expansion.
The Axin2-Snail axis promotes bone invasion by activating cancer-associated fibroblasts in oral squamous cell carcinoma
Authors: An Yin-Zhe , Cho Eunae , ling Junqi , Zhang Xianglan
Published: September 2020

Background: In bone-invasive oral squamous cell carcinoma (OSCC), cancer-associated fibroblasts (CAFs) infiltrate into bony tissue ahead of OSCC cells. In the present study, we aimed to investigate the role of the Axin2-Snail axis in the biological behaviour of CAFs and bone invasion in OSCC.Methods: The clinicopathological significance of Axin2 and Snail expression was investigated by immunohistochemistry in an OSCC cohort containing 217 tissue samples from patients with long-term follow-up. The influence of the Axin2-Snail axis on the biological behaviour of OSCC cells and CAFs was further investigated both in vitro and in vivo.Results: Axin2 expression was significantly associated with Snail expression, the desmoplasia status, and bone invasion in patients with OSCC. In multivariate analysis, lymph node metastasis, desmoplasia, Axin2 expression, and Snail expression were independent poor prognostic factors in our cohort. Consistent with these findings, OSCC cells demonstrated attenuated oncogenic activity as well as decreased expression of Snail and various cytokines after Axin2 knockdown in vitro. Among the related cytokines, C-C motif chemokine ligand 5 (CCL5) and interleukin 8 (IL8) demonstrated a strong influence on the biological behaviour of CAFs in vitro. Moreover, both the desmoplastic reaction and osteolytic lesions in the calvaria were predominantly decreased after Axin2 knockdown in OSCC cells in vivo using a BALB/c athymic nude mouse xenograft model.Conclusions: Oncogenic activities of the Axin2-Snail axis are not limited to the cancer cells themselves but rather extend to CAFs via regulation of the cytokine-mediated cancer-stromal interaction, with further implications for bone invasion as well as a poor prognosis in OSCC.
Effect of Transcranial Direct Current Stimulation and Reaction Time Training on Cognition and Choice Reaction Time in Recreational Soccer Players (FAST Trial): A Protocol for A Randomized Clinical Trial
Authors: Neto Eduaro de Moura , Luvizutto Gustavo José , Souza Luciane Aparecida Pascucci Sande de
Published: September 2020

Background: Studies examining the effects of transcranial direct current stimulation (tDCS) and reaction time (RT) training on choice RT in the lower limb during a specific task linked to soccer practice, such as kicking, are lacking. Accordingly, this proposal aimed to evaluate the efficacy and safety of tDCS and RT training in choice RT and cognitive function during recreational soccer. Methods: In this single-center, randomized, placebo-controlled, double-blind, parallel-group study of 30 recreational soccer players, tDCS will be applied in the primary motor cortex (M1). Participants will be divided into (1) anodal tDCS plus RT training and (2) sham tDCS plus RT training. The investigator will be blinded to patient treatment before the first session, last session, and 1 day after the last tDCS session. In total, 15 sessions will be performed using a schedule of three times a week for 5 weeks. The RT training protocol will be delivered during tDCS and will comprise kicking a ball from a platform, placed on either the right or the left side, depending on a light cue, during a 10-min interval (between minute 5 and minute 15 after 20-min stimulation). Changes in choice RT in the upper and lower limbs will be considered primary outcome measures, and changes in Trail Making Test and Digit Span Test will be considered secondary outcome measures. Any adverse effects during the study period will be reported. To detect changes in continuous outcomes, a the anodal tDCS and the sham mode will be compared using a t-test for normal distribution, or the nonparametric Mann-Whitney test for non-normal distribution; changes will be considered significant at p < 0.05. Discussion: The FAST trial is a new proposal that uses a novel method of evaluation and training of choice RT in soccer players through a functional task. The anodal tDCS along with choice RT training with a functional task can be an efficient tool for athletes to prevent injuries. Our findings may be useful for soccer athletes to have enhanced responses during a game, and to improve performances in championships. Trial Registration: Registro Brasileiro de Ensaios Clínicos (Rebec) - RBR-9bjttcDate of registration: 02/28/2020Last Update: 04/20/2020
Bovine adapted transmissible mink encephalopathy is similar to L-BSE after passage through sheep with the VRQ/VRQ genotype but not VRQ/ARQ
Authors: Cassmann E.D. , Moore S.J. , Kokemuller R.D. , Balkema-Buschmann A. , Groschup M. H. , Nicholson Eric M , Greenlee Justin
Published: September 2020

BackgroundTransmissible mink encephalopathy (TME) is a fatal neurologic disease of farmed mink. Evidence indicates that TME and L-BSE are similar and may be linked in some outbreaks of TME. We previously transmitted bovine adapted TME (bTME) to sheep. The present study compared ovine passaged bTME (o-bTME) to C-BSE and L-BSE in transgenic mice expressing wild type bovine prion protein (TgBovXV). To directly compare the transmission efficiency of all prion strains in this study, we considered the attack rates and mean incubation periods. Additional methods for strain comparison were utilized including lesion profiles, fibril stability, and western blotting. ResultsSheep donor genotype elicited variable disease phenotypes in bovinized mice. Inoculum derived from a sheep with the VRQ/VRQ genotype (o-bTMEVV) resulted in an attack rate, incubation period, western blot profile, and neuropathology most similar to bTME and L-BSE. Conversely, donor material from a sheep with the VRQ/ARQ genotype (o-bTMEAV) elicited a phenotype distinct from o-bTMEVV, bTME and L-BSE. The TSE with the highest transmission efficiency in bovinized mice was L-BSE. The tendency to efficiently transmit to TgBovXV mice decreased in the order bTME, C-BSE, o-bTMEVV, and o-bTMEAV. The transmission efficiency of L-BSE was approximately 1.3 times higher than o-bTMEVV and 3.2 times higher than o-bTMEAV.ConclusionsOur findings provide insight on how sheep host genotype modulates strain genesis and influences interspecies transmission characteristics. Given that the transmission efficiencies of L-BSE and bTME are higher than C-BSE, coupled with previous reports of L-BSE transmission to mice expressing the human prion protein, continued monitoring for atypical BSE is advisable in order to prevent occurrences of interspecies transmission that may affect humans or other species.
Medical Students’ Attitudes towards Careers in Primary Care in Singapore
Authors: Zainal Humairah , Smith Helen Elizabeth
Published: September 2020

Background: Singapore needs more family doctors to care for its ageing population and their chronic conditions. While there is a shifting of care from acute care settings to more community care, this has not been reflected in the primary care training in local medical schools. Furthermore, no research has explored how different aspects of the medical school curricula in Singapore influence students’ perceptions of careers in General Practice and Family Medicine- a gap that is filled by this study. Methods: Six focus groups involving 54 students from all three medical schools in Singapore were conducted. Discussions focused on their primary care experience, their professional and career aspirations, and perceptions towards the opportunities and challenges of primary care careers. Qualitative content analysis was used to interpret the data. Results: The respondents shared eight key concerns of pursuing primary care careers including limited professional opportunities, emphasis on lifestyle benefits rather than professional characteristics, need for business acumen, conflicts created by business in clinical care, mundane case mix, lack of continuity of care, limited consultation time, and specialists’ negative attitudes towards family doctors. The positive views articulated included the opportunities for entrepreneurialism and a portfolio career, breadth of clinical problems presented, and an improved future for primary care.Conclusions: Improving students’ perceptions of careers in primary care in Singapore would benefit from a concerted effort from multiple stakeholders; medical schools, healthcare providers, professional and regulatory bodies, and government.
Ultrasound-Guided Erector Spinae Plane Block Versus Thoracic Paravertebral Block on Postoperative Analgesia After Laparoscopic Nephroureterectomy: Study Protocol of A Randomized, Double Blinded, Non-Inferiority Design Trial
Authors: Xu Zhen-Zhen , Li Xue , Zhang Zhen , Liu Zheng-Ye , Song Lin-Lin , Zhang Hong , Li Xue-Ying
Published: September 2020

Introduction: Erector spinae plane block (ESPB) is a novel inter-fascial plane block, which is applied more and more in postoperative pain control, especially in chest surgery. Attention is increasingly paid to its premium analgesia in urological surgery. Therefore, we aimed to explore whether ESPB would have similar analgesia compared with thoracic paravertebral block (TPVB) in laparoscopic nephroureterectomy surgery.Methods and analysis: This prospective, randomized, double-blinded, non-inferiority trial will enroll 166 patients undergoing laparoscopic nephroureterectomy. Participants will be randomly assigned 1:1 into receiving ESPB or TPVB before surgery. Both ultrasound-guided ESPB or TPVB will be performed with an injection of 0.375% ropivacaine 0.4ml/kg before anesthesia induction. Standardized patients controlled intravenous analgesia (PCIA) will be applied for each patient. The primary endpoint is the joint of cumulative 24h opioid (sufentanil) consumption and average pain score via numeric rating scale (NRS) at 24th h after surgery. Secondary endpoints include rescued analgesic demand, cumulative opioid consumption and pain NRS scores at different preset timepoint within 48h after surgery. Other predefined outcomes include clinical features of blockage, quality of recovery, subjective sleep quality, time to ambulation and flatus, and adverse events, as well as length of stay in hospital and anesthesia cost. Discussion: Previous studies investigating the analgesic efficacy of ESPB only concentrated on a single endpoint for postoperative pain evaluation, while studies focusing on the direct comparation between ESPB and TPVB in urological surgery is still lacking. Our study is the first trial in non-inferiority design of comparing ESPB and TPVB in patient undergoing laparoscopic nephroureterectomy surgery, and the primary outcome is the joint endpoint of opioid consumption and pain NRS score.Trial registration: Chinese Clinical Trial Registry, ChiCTR 2000031916. Registered on 14 April 2020. http://www.chictr.org.cn/showproj.aspx?proj=50782
Magnetic resonance imaging of the normal dromedary camel tarsus
Authors: Hagag Usama , Almohamad Zakriya Ali , Tawfiek Mohamed Gomaa , Nahas Ayman El
Published: September 2020

Background: Magnetic resonance imaging (MRI) is the most versatile and informative imaging modality for the diagnosis of locomotor injuries in many animal species; however, veterinary literature describing the MRI of the dromedary camel tarsus is lacking. Our purpose was to describe and compare the MRI images of twelve cadaveric tarsi, examined in a 1.5 Tesla MRI scanner, with their corresponding anatomical gross sections. Turbo spin-echo (TSE) T1-weighted (T1), T2-weighted (T2), proton density-weighted (PD), and short tau inversion recovery (STIR) sequences were obtained in 3 planes. Tarsi were sectioned in sagittal, dorsal, and transverse planes. MRI images from different sequences and planes were described and compared with the anatomical sections.Results: The soft and osseous tissues of the dromedary camel tarsus corresponded extensively with the gross anatomic sections. T1 and PD images provided high anatomical details and the synovial fluid had high signal intensity on T2, PD, and STIR sequences and intermediate signal intensity on T1 images. The tibial cochlea, tarsal bones, and the proximal metatarsus were evaluated in all planes. The sagittal and dorsal images were useful for the evaluation of articular cartilage and subchondral bone. Articular cartilage had homogenous intermediate signal intensity on the T1 images and low signal intensity on the T2 and PD images. The Subchondral and cortical bone had low signal intensity on all sequences, and the cancellous bone expressed heterogeneous signal intensity on PD, T1, and T2 images. The tarsal tendons and ligaments had low signal intensity in all sequences including: the tendons of fibularis tertius, long digital extensor, cranial tibial, fibularis longus, lateral digital extensor muscles; the common tendon of the caudal tibial and lateral digital flexor muscles; the medial digital flexor tendon; the long and short bundles of the medial and lateral collateral ligaments; the superficial and deep digital flexor tendons; and the long plantar ligament. Conclusions: MRI images provided a thorough evaluation of the normal dromedary camel tarsus. Information provided in the current study is expected to serve as a basis for interpretation in clinical situations.
Effectiveness of A Home-Based Telerehabilitation System in Patients After Total Hip Arthroplasty: Study Protocol of A Randomized Controlled Trial
Authors: Busso Chiara , Castorina Gabriele , Monaco Marco Di , Rodriguez Daniel , Mahdavi Hadis , Balocco Simone , Trucco Marco , Conti Marco , Castagna Alessandro , Minetto Marco Alessandro
Published: September 2020

Background: The demand for total hip arthroplasty (THA) is quickly rising given the escalating global incidence of hip osteoarthritis and it is widely accepted that the post-surgery rehabilitation is key to optimize outcomes. The overall objective of this study is to evaluate the effectiveness of a new telerehabilitation solution, ReHub, for the physical function and clinical outcome improvement following THA. The specific aim of this manuscript is to describe the study design, protocol, content of interventions, primary and secondary outcomes and to discuss the clinical rehabilitation impact of the expected experimental results.Methods/design: This prospective, randomized, controlled, parallel-group trial will include 56 patients who had undergone primary THA. Patients are randomized to a control group (standard rehabilitation during the 2-week stay in the rehabilitation clinic followed by 3 weeks of unsupervised home-based rehabilitation) or an experimental group (standard rehabilitation during the 2-week stay in the rehabilitation clinic followed by 3 weeks of home-based ReHub-assisted telerehabilitation). The primary outcome is physical performance assessed through the Timed Up-and-Go (TUG) test. Secondary outcomes include independence level, pain intensity, hip disability, hip range of motion, muscle strength and patient’s perception of clinical improvement.Discussion: Proving the clinical and cost-effectiveness of a home-based telerehabilitation program for physical and muscle function following THA could support its systematic incorporation in post-surgical rehabilitation protocols, that should be tailored to individual and collective needs.Trial registration: ClinicalTrial.gov: NCT04382729. Registered 22 November 2019 - https://clinicaltrials.gov/ct2/show/NCT04176315
Performance of the QPLEXTM Alz plus assay, a novel multiplex kit for screening cerebral amyloid deposition
Authors: Park Jong-Chan , Jung Keum Sim , Kim Jiyeong , Jang Ji Sung , Kwon Sunghoon , Byun Min Soo , Yi Dahyun , Byeon Gihwan , Jung Gijung , Kim Yu Kyeong , Lee Dong Young , Han Sun-Ho , Mook-Jung Inhee
Published: September 2020

Background: Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by the hallmark finding of cerebral amyloid deposition. Many researchers have tried to predict the existence of cerebral amyloid deposition by using easily accessible blood plasma samples, but the effectiveness of such strategies remains controversial.Methods: We developed a new multiplex kit, the QPLEXTM Alz plus assay kit, which uses proteomics-based blood biomarkers to prescreen for cerebral amyloid deposition. A total of 300 participants who underwent Pittsburgh compound B (PiB)-positron emission tomography (PET) which allows imaging of cerebral amyloid deposition were included in this study. We compared the levels of QPLEXTM biomarkers between patients who were classified as PiB-negative or PiB-positive, regardless of their cognitive function. Logistic regression analysis followed by receiver operating characteristic (ROC) curve analysis was performed. The kit accuracy was tested using a randomized sample selection method.Results: The results obtained using our assay kit reached 89.1% area under curve (AUC) with 80.0% sensitivity and 83.0% specificity. Further validation of the QPLEXTM Alz plus assay kit using a randomized sample selection method showed an average accuracy of 81.5%.Conclusions: Our QPLEXTM Alz plus assay kit offers a highly effective way to predict cerebral amyloid deposition through a convenient blood test, and should enable easy prediction of AD in daily life.
Sensory Experiences and Cues among E-Cigarette Users
Authors: Piazza Jennifer Di , Caponnetto Pasquale , Askin Gulce , Christos Paul , Maglia Marilena , Gautam Richa , Roche Samantha , Polosa Riccardo
Published: September 2020

Background and Aims: We characterized the extent and quality of respiratory sensations and sensory related smoking cues associated with e-cigarette use among those who failed to quit combustible tobacco cigarette (CTC) use with traditional FDA approved medications but succeeded in doing so with e-cigarettes. Further, we sought to understand former smokers’ perceptions about the influence of sensory experience with e-cigarette use on CTC cessation outcomes.Methods: A nonrandom purposive sample of 156 participants recruited in the U.S. through the Consumer Advocates for Smoke Free Alternatives Association Facebook page completed an online cross-sectional survey to assess sensory experiences and smoking cues associated with e-cigarette use. Descriptive statistics were calculated, and the ANOVA/Kruskal-Wallis test with post-hoc testing and the two-sample t-test/Wilcoxon rank-sum test, as appropriate based on distribution, were used to assess the association between sample characteristics and sensory experiences and cues using investigator constructed questions, the Modified Cigarette Evaluation Questionnaire (mCEQ) and the Smoking Cue Appeal Survey (SCAS). Results With e-cigarette use, participants reported feeling the vapor in their throats, windpipes, noses, lungs, and on their tongues; reductions in nicotine craving; and enjoyment of their e-cigarette, including tasting, smelling, and seeing the vapor and touching the device. Women had greater craving reduction than men (p=0.023). Those who began smoking at 13 years of age or younger had more smoking satisfaction and had greater sensory enjoyment than those who began smoking at 16-17 years of age (p=0.015 and p=0.026, respectively), as well as greater sensory enjoyment than those who began smoking at 14-15 years of age (p=0.047). There was a significant overall association between the number of years a respondent smoked and e-cigarette sensory enjoyment (p=0.038). Participants 18-34 years old rated e-cigarettes as being more pleasant compared to 45+ year olds, (p=0.012). Eighty four percent of participants reported the sensation of the vapor as important in quitting CTCs, and 91% believed the sensations accompanying e-cigarette use contributed to their smoking cessation success. Conclusions: For those who failed to quit previously using approved cessation medications to stop smoking cigarettes, sensory experiences associated with e-cigarette use may help smokers quit smoking.
Engineering cofactor metabolism for improved protein and glucoamylase production in Aspergillus niger
Authors: Sui Yu-fei , Schütze Tabea , Ouyang Li-Ming , Lu Hong-zhong , Liu Peng , Xiao Xian-zun , Qi Jie , Zhuang Yingping , Meyer Vera
Published: September 2020

Background: Nicotinamide adenine dinucleotide phosphate (NADPH) is an important cofactor ensuring intracellular redox balance, anabolism and cell growth in all living systems. Our recent multi-omics analyses of glucoamylase (GlaA) biosynthesis in the filamentous fungal cell factory Aspergillus niger indicated that low availability of NADPH might be a limiting factor for GlaA overproduction.Results: We thus employed the Design-Build-Test-Learn cycle for metabolic engineering to identify and prioritize effective cofactor engineering strategies for GlaA overproduction. Based on available metabolomics and 13C metabolic flux analysis data, we individually overexpressed seven predicted genes encoding NADPH generation enzymes under the control of Tet-on gene switch in two A. niger recipient strains, one carrying a single and one carrying seven glaA gene copies, respectively, to test their individual effects on GlaA and total protein overproduction. Both strains were selected to understand if a strong pull towards glaA biosynthesis (seven gene copies) mandates a higher NADPH supply compared to the native condition (one gene copy). Detailed analysis of all 14 strains cultivated in shake flask cultures uncovered that overexpression of the gsdA gene (glucose 6-phosphate dehydrogenase), gndA gene (6-phosphogluconate dehydrogenase) and maeA gene (NADP-dependent malic enzyme) supported GlaA production on a subtle (10%) but significant level in the background strain carrying seven glaA gene copies. We thus performed maltose-limited chemostat cultures combining metabolome analysis for these three isolates to characterize metabolic-level fluctuations caused by cofactor engineering. In these cultures, overexpression of either the gndA or maeA gene increased the intracellular NADPH pool by 45% and 66%, and the yield of GlaA by 65% and 30%, respectively. In contrast, overexpression of the gsdA gene had a negative effect on both total protein and glucoamylase production.Conclusions: This data suggests for the first time that increased NADPH availability can indeed underpin protein and especially GlaA production in strains where a strong pull towards GlaA biosynthesis exists. This data also indicates that the highest impact on GlaA production can be engineered on a genetic level by increasing the flux through the pentose phosphate pathway (gndA gene)reverse TCA cycle (maeA gene) followed by engineering the flux through the reverse TCA cycle (maeA gene) pentose phosphate pathway (gndA gene). We thus propose that NADPH cofactor engineering is indeed a valid strategy for metabolic engineering of A. niger to improve GlaA production, a strategy which is certainly also applicable to the rational design of other microbial cell factories.
Primary localized retroperitoneal sarcomas. Report from Slovenian sarcoma referral center.
Authors: Novak Marko , Perhavec Andraz , Povsic Milena Kerin , Arnus Matej , Erzen Darja
Published: September 2020

Background: Sarcoma patients should be treated in high volume referral sarcoma centers. Compartmental resection is proposed as the best treatment option in retroperitoneal sarcoma patients. Methods: Institute of Oncology Ljubljana is the only referral sarcoma center in Slovenia. Having population of 2.1 million poses a unique situation. We manage all sarcoma patients in the country and operate on patients with soft tissue tumors of extremities, trunk and abdomen. Data for all consecutive patients surgically treated from January 1999 to December 2018 for primary localized retroperitoneal sarcoma was extracted from a prospective surgical database. Data about the incidence of sarcoma patients in Slovenia was extracted from the Cancer Registry of Republic of Slovenia. Clinicopathologic variables and the outcome were analyzed.Results: In total 89 patients were included. Median age was 62 years. Dedifferentiated liposarcoma was the most common histology (38.2 %). Median tumor size was 21 cm. Compartmental resection was performed in 47.2 % (42/89). Postoperative complication grade 3a or higher according to Clavien-Dindo classification had 30.3 % (27/89) of patients. The 30-day and 90-day mortality rate was 2.2 % and 5.6 %. Median follow-up was 62.1 months. Corresponding 5-year overall survival was 67.2 %, 5-year disease specific survival was 72.6 % and 5-year local recurrence-free survival was 81.5 %, respectively. Conclusion: Results from our institution show that referral sarcoma centers may achieve very good results in management of retroperitoneal sarcoma patients, despite not meeting the criteria for high volume hospitals, as long as they have multidisciplinary team, appropriate facilities and expertise.
Sex-dependent alterations in the physiology of entorhinal cortex neurons in old heterozygous 3xTg-AD mice
Authors: Arsenault Dany , Tremblay Cyntia , Emond Vincent , Calon Frederic
Published: September 2020

While the higher prevalence of Alzheimer Disease (AD) is clear, studies suggest that biological sex may also influence its pathogenesis. However, mechanisms behind these differences are not clear. To investigate physiological differences between sexes at the cellular level in the brain, we investigated the intrinsic and synaptic properties of entorhinal cortex neurons in heterozygous 3xTg-AD mice of both sexes at the age of 20 months. This brain region was selected because of its early association with AD symptoms. First, we found physiological differences between male and female non-transgenic mice, providing indirect evidence of axonal alterations in old females. Second, we observed a transgene-dependent elevation of the firing activity, post-burst after hyperpolarization (AHP) and spontaneous excitatory postsynaptic current (EPSC) activity, without any effect of sex. Third, the passive properties and the hyperpolarization-activated current (Ih) were altered by transgene expression only in female mice, whereas paired-pulse ratio (PPR) of evoked EPSC was changed only in males. Fourth, both sex and transgene expression were associated with changes in action potential properties. Consistent with previous work, higher levels of Aβ neuropathology were detected in 3xTg-AD females, whereas tau deposition was similar. In summary, our results support the idea that aging and AD neuropathology differentially alter the physiology of entorhinal cortex neurons in males and females.
Attenuated Self-serving Bias in People with Internet Gaming Disorder is Related to Altered Neural Activity in Subcortical-Cortical Midline Structures
Authors: Wang Yifan , Zheng Li , Wang Chenggong , Guo Xiuyan
Published: September 2020

Background: To protect and maintain the positivity of self-concept, normal people usually show a self-serving bias (internal attribution of positive events and external attribution of negative events) by the motives of self-enhancement and self-protection. Additionally, self-serving assessments predominantly activate the subcortical-cortical midline structures (CMS) in healthy individuals. However, little is known about self-serving bias and its underlying neural correlates among individuals with Internet gaming disorder (IGD). Methods: Twenty-four participants with IGD and 25 recreational Internet gaming users (RGUs) were scanned while attributing the causes of positive/negative self- and other-related events that could occur in both the game-world and real-world contexts. Region-of-interest (within CMS regions) and parametric analysis were performed to investigate the neural correlates of self-serving bias in IGD. Results: Behaviorally, the IGD participants attributed more negative and fewer positive events to themselves than RGU participants in both contexts. Neurally, during the attributions of negative events, the IGD participants exhibited increased ventromedial prefrontal cortex (vmPFC) activation in both contexts compared with RGU participants. Higher vmPFC activation was associated with weaker self-protective motivation in the IGD group. Meanwhile, during the attributions of positive events, the IGD participants exhibited decreased precuneus/posterior cingulate cortex activation in the real world compared with RGU participants. Parametric analysis showed a reduced positive correlation between precuneus activation and self-attribution ratings of positive events in the real world in the IGD group relative to the RGU group. Conclusion: These results suggest that individuals with IGD show an attenuated self-serving bias and altered brain activity within CMS regions involved in self-attribution, providing evidence for the negative self-concept and weakened abilities in both self-enhancement and self-protection in IGD.
The Pathogenisis of COVID-19 Myocardial Injury: an Immunohistochemical Study of Postmortem Biopsies 
Authors: Hartmann Camila , Miggiolaro Anna Flavia dos Santos , Junior Jarbas da Silva Motta , Carstens Lucas Baena , De Paula Caroline Busatta Vaz , Grobe Sarah Fagundes , Nunes Larissa Hermann de Souza , Marques Gustavo Lenci , Moura Lidia Zytynski , de Noronha Lucia , Baena Cristina Pellegrino
Published: September 2020

Rationale: Myocardial injury is significantly and independently associated with mortality in COVID-19 patients. However, the pathogenesis of myocardial injury in COVID-19 is still not clear, and cardiac involvement by SARS-CoV-2 remains a major challenge worldwide. Objective: This histopathological and immunohistochemical study seeks to clarify the pathogenesis and propose a mechanism with pathways involved in COVID-19 myocardial injury. Methods and Results: Postmortem minimally invasive autopsies were performed in six patients who died from COVID-19, and the myocardium samples were compared to a control patient. Histopathological analysis was performed using hematoxylin-eosin and toluidine blue staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against the following targets: caspase-1, ICAM-1, TNF-α, IL-4, IL-6, CD163, TGF-β, MMP-9, type 1 and type 3 collagen. The samples were also subjected to a TUNEL assay to detect potential apoptosis. The histopathological analysis showed severe pericellular interstitial edema surrounding each of the cardiomyocytes and higher mast cells count by high-power field in all COVID-19 myocardium samples. The IHC analysis showed increased expression of caspase-1, ICAM-1, IL-4, IL-6, CD163, MMP-9 and type 3 collagen in the COVID-19 patients compared to the control. No difference from the control was observed in expression of TNF-α, TGF-β and type 1 collagen. The TUNEL assay was positive in all the COVID-19 samples confirming the presence of endothelial apoptosis. Conclusions: The pathogenesis of COVID-19 myocardial injury seems to be related with pyroptosis leading to endothelial cell injury and disfunction. The subsequent inflammation with associated interstitial edema could explain the myocardial disfunction and arrythmias in these patients. Our findings also show that COVID-19 myocardial injury may cause myocardial fibrosis in the long term. These patients should be monitored for myocardial dysfunction and arrythmias after the acute phase of COVID-19.