bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety studies and viral shedding of intramuscular administration of oncolytic vaccinia virus TG6002 in healthy beagle dogs
Authors: Béguin Jérémy , Nourtier Virginie , Gantzer Murielle , Cochin Sandrine , Foloppe Johann , Balloul Jean-Marc , Laloy Eve , Tierny Dominique , Klonjkowski Bernard , Quemeneur Eric , Maurey Christelle , Erbs Philippe 
Published: August 2020

Abstract
Background
Cancer is a leading cause of mortality for both humans and dogs. As spontaneous canine cancers appear to be relevant models of human cancers, developing new therapeutic approaches could benefit both species. Oncolytic virotherapy is a promising therapeutic approach in cancer treatment. TG6002 is a recombinant oncolytic vaccinia virus deleted in the thymidine kinase and ribonucleotide reductase genes and armed with the suicide gene FCU1 that encodes a protein which catalyses the conversion of the non-toxic 5-fluorocytosine into the toxic metabolite 5-fluorouracil. Previous studies have shown the ability of TG6002 to infect and replicate in canine tumor cell lines, and demonstrated its oncolytic potency in cell lines, xenograft models and canine mammary adenocarcinoma explants. Moreover, 5-fluorouracil synthesis has been confirmed in fresh canine mammary adenocarcinoma explants infected with TG6002 with 5-fluorocytosine. This study aims at assessing the safety profile and viral shedding after unique or repeated intramuscular injections of TG6002 in seven healthy Beagle dogs.

Results
Repeated intramuscular administrations of TG6002 at the dose of 5 × 107 PFU/kg resulted in no clinical or biological adverse effects. Residual TG6002 in blood, saliva, urine and feces of treated dogs was not detected by infectious titer assay nor by qPCR, ensuring the safety of the virus in the dogs and their environment.

Conclusions
These results establish the good tolerability of TG6002 in healthy dogs with undetectable viral shedding after multiple injections. This study supports the initiation of further studies in canine cancer patients to evaluate the oncolytic potential of TG6002 and provides critical data for clinical development of TG6002 as a human cancer therapy.
A novel two-step, direct-to-PCR method for virus detection off swabs using human coronavirus 229E
Authors: Morehouse Zachary P. , Proctor Caleb M. , Ryan Gabriella L. , Nash Rodney J. 
Published: August 2020

Abstract
Background
Currently, one of the most reliable methods for viral infection detection are polymerase chain reaction (PCR) based assays. This process is time and resource heavy, requiring multiple steps of lysis, extraction, purification, and amplification procedures. Herein, we have developed a method to detect virus off swabs using solely shaker-mill based mechanical lysis and the transfer of the viral lysate directly to a PCR assay for virus detection, bypassing the substantial reagent and time investments required for extraction and purification steps.

Methods
Using Human Coronavirus 229E (HCoV-229E) as a model system, we spiked swabs in vitro for proof-of-concept testing. Swabs were spiked in serial dilutions from 1.2 × 106 to 1.2 × 101 copies/mL and then placed in 2 mL tubes with viral transport media (VTM) to mimic the specimen collection procedures in the clinic prior to processing via shaker-mill homogenization. After homogenization, 1 μL of lysate was processed using RT-qPCR for amplification of the nucleocapsid (N) gene, qualifying viral detection.

Results
HCoV-229E in vitro spiked swabs were processed in a novel two-step, direct-to-PCR methodology for viral detection. After running 54 swabs, we confidently determined our limit of detection to be 1.2 × 103 viral copies/mL with 96.30% sensitivity.

Conclusion
We have proven that the shaker-mill homogenization-based two-step, direct-to-PCR procedures provides sufficient viral lysis off swabs, where the resulting lysate can be used directly in PCR for the detection of HCoV-229E. This finding allows for reductions in the time and resources required for PCR based virus detection in comparison to the traditional extraction-to-PCR methodology.
Clinical application of chromosomal microarray analysis for fetuses with craniofacial malformations
Authors: Xu Chenyang , Xiang Yanbao , Xu Xueqin , Zhou Lili , Li Huanzheng , Dong Xueqin , Tang Shaohua 
Published: August 2020

Abstract
Background
The potential correlations between chromosomal abnormalities and craniofacial malformations (CFMs) remain a challenge in prenatal diagnosis. This study aimed to evaluate 118 fetuses with CFMs by applying chromosomal microarray analysis (CMA) and G-banded chromosome analysis.

Results
Of the 118 cases in this study, 39.8% were isolated CFMs (47/118) whereas 60.2% were non-isolated CFMs (71/118). The detection rate of chromosomal abnormalities in non-isolated CFM fetuses was significantly higher than that in isolated CFM fetuses (26/71 vs. 7/47, p = 0.01). Compared to the 16 fetuses (16/104; 15.4%) with pathogenic chromosomal abnormalities detected by karyotype analysis, CMA identified a total of 33 fetuses (33/118; 28.0%) with clinically significant findings. These 33 fetuses included cases with aneuploidy abnormalities (14/118; 11.9%), microdeletion/microduplication syndromes (9/118; 7.6%), and other pathogenic copy number variations (CNVs) only (10/118; 8.5%).We further explored the CNV/phenotype correlation and found a series of clear or suspected dosage-sensitive CFM genes including TBX1, MAPK1, PCYT1A, DLG1, LHX1, SHH, SF3B4, FOXC1, ZIC2, CREBBP, SNRPB, and CSNK2A1.

Conclusion
These findings enrich our understanding of the potential causative CNVs and genes in CFMs. Identification of the genetic basis of CFMs contributes to our understanding of their pathogenesis and allows detailed genetic counselling.
Protein delivery in intermittent and continuous enteral nutrition with a protein-rich formula in critically ill patients—a protocol for the prospective randomized controlled proof-of-concept Protein Bolus Nutrition (Pro BoNo) study
Authors: Reinhold Simona , Yeginsoy Desirée , Hollinger Alexa , Todorov Atanas , Tintignac Lionel , Sinnreich Michael , Kiss Caroline , Gebhard Caroline E. , Kovács Balázs , Gysi Bianca , Imwinkelried Lara , Siegemund Martin 
Published: August 2020

AbstractBackgroundCritically ill patients rapidly develop muscle wasting resulting in sarcopenia, long-term disability and higher mortality. Bolus nutrition (30–60 min period), whilst having a similar incidence of aspiration as continuous feeding, seems to provide metabolic benefits through increased muscle protein synthesis due to higher leucine peaks.To date, clinical evidence on achievement of nutritional goals and influence of bolus nutrition on skeletal muscle metabolism in ICU patients is lacking. The aim of the Pro BoNo study (Protein Bolus Nutrition) is to compare intermittent and continuous enteral feeding with a specific high-protein formula. We hypothesise that target quantity of protein is reached earlier (within 36 h) by an intermittent feeding protocol with a favourable influence on muscle protein synthesis.MethodsPro BoNo is a prospective randomised controlled study aiming to compare the impact of intermittent and continuous enteral feeding on preventing muscle wasting in 60 critically ill patients recruited during the first 48 h after ICU admission. The primary outcome measure is the time until the daily protein target (≥ 1.5 g protein/kg bodyweight/24 h) is achieved. Secondary outcome measures include tolerance of enteral feeding and evolution of glucose, urea and IGF-1. Ultrasound and muscle biopsy of the quadriceps will be performed.DiscussionThe Basel Pro BoNo study aims to collect innovative data on the effect of intermittent enteral feeding of critically ill patients on muscle wasting.Trial registrationClinicalTrials.govNCT03587870. Registered on July 16, 2018. Swiss National Clinical Trials Portal SNCTP000003234. Last updated on July 24, 2019.
Lower peripheral helper T cell levels in the synovium are associated with a better response to anti-TNF therapy in rheumatoid arthritis
Authors: Julià Antonio , Ávila Gabriela , Celis Raquel , Sanmartí Raimon , Ramírez Julio , Marsal Sara , Cañete Juan D. 
Published: August 2020

AbstractBackgroundThe mechanisms by which only some rheumatoid arthritis (RA) patients respond favorably to TNF blockade are still poorly characterized. The goal of this study was to identify biological features that explain this differential response using a multilevel transcriptome analysis of the synovial membrane.MethodsSynovial samples from 11 patients on anti-TNF therapy were obtained by arthroscopy at baseline and week 20. Analysis of the synovial transcriptome was performed at the gene, pathway, and cell-type levels. Newly characterized pathogenic cell types in RA, peripheral helper T cells (TPH), and CD34-THY1+ fibroblasts were estimated using a cell-type deconvolution approach. TPHassociation was validated using immunofluorescence. External validation was performed on an independent dataset.ResultsAfter multiple-test correction, 16 and 4 genes were differentially expressed at baseline and week 20, respectively. At the pathway level, 86 and 17 biological processes were significantly enriched at baseline and week 20, respectively. Longitudinal expression changes were associated with a drastic decrease of innate immune activity (P < 5e−30), and an activation of the bone and cartilage regeneration processes (P < 5e−10). Cell-type deconvolution revealed a significant association between low TPHcells at baseline and a better response (P = 0.026). Lower TPHcells were maintained in good responders up to week 20 (P = 0.032). Immunofluorescent analyses confirmed the accuracy of the cell-type estimation (r2 = 0.58,P = 0.005) and an association with response. TPHassociation with anti-TNF response was validated in an independent sample of RA patients (P = 0.0040).ConclusionsA lower abundance in the synovial membrane of the pathogenic T cell type newly associated with RA, peripheral helper T lymphocyte, is associated with a good response to anti-TNF therapy. Major changes in the myeloid cell compartment were also observed in response to therapy. The results of this study could help develop more effective therapies aimed at treating the pathogenic mechanisms in RA that are currently not well targeted by anti-TNF agents.
Furosemide and spironolactone doses and hyponatremia in patients with heart failure
Authors: Velat Ivan , Bušić Željko , Jurić Paić Marina , Čulić Viktor 
Published: August 2020

Abstract
Background
Hyponatremia, a marker of disease severity and prognosis, has been associated with various clinical factors and drug use, especially diuretics.

Methods
This observational prospective cohort study enrolled patients hospitalized at the University Hospital Center Split because of heart failure (HF). We investigated the association of clinical variables and cardiovascular drugs, including furosemide, hydrochlorothiazide, spironolactone, and their doses, with the presence of hyponatremia at admission.

Results
Of the 565 included patients, 32.4% were hyponatremic, 62.6% were males, and the mean age was 73.1 ± 10.6 years. In the univariate analysis, hyponatremic patients were more often current smokers (p = 0.01), alcohol consumers (p = 0.01), receiving spironolactone (p = 0.004) or combination of furosemide and spironolactone (p = 0.003). Patients who received 50 and 100 mg of spironolactone, compared to those receiving 25 mg (p < 0.0001), as well as patients who received 250 to 500 mg of furosemide compared to ≤240 mg (p = 0.001), were significantly more often hyponatremic. In the multivariate analysis, when diuretic doses were accounted for, furosemide doses of 250 to 500 mg (p = 0.009), spironolactone doses of 50 to 100 mg (p = 0.0003), increasing age (p = 0.03), diabetes mellitus (p = 0.02) and alcohol consumption (p = 0.04) were independently associated with hyponatremia.

Conclusion
High doses of furosemide and spironolactone, or concomitant use of these diuretics, seem to be an important cause of hyponatremia in HF patients, particularly in combination with advanced age, diabetes and alcohol consumption. Diuretic dose reduction may help avoid hyponatremia and improve clinical status and prognosis in such patients.
New somatic TERT promoter variants enhance the Telomerase activity in Glioblastoma
Authors: Pierini Tiziana , Nardelli Carlotta , Lema Fernandez Anair Graciela , Pierini Valentina , Pellanera Fabrizia , Nofrini Valeria , Gorello Paolo , Moretti Martina , Arniani Silvia , Roti Giovanni , Giovenali Paolo , Lupattelli Marco , Metro Giulio , Molica Carmen , Castrioto Corrado , Corinaldesi Rodolfo , Laurenti Maria Elena , Ascani Stefano , Mecucci Cristina , La Starza Roberta 
Published: August 2020

AbstractThe catalytic activity of human Telomerase Reverse Transcriptase (TERT) compensates for the loss of telomere length, eroded during each cell cycle, to ensure a correct division of stem and germinal cells. In human tumors, ectopic TERT reactivation, most frequently due to hotspot mutations in the promoter region (TERTp), i.e. c.1-124 C > T, c.1-146 C > T, confers a proliferative advantage to neoplastic cells. In gliomas, TERTp mutations (TERTpmut) mainly occur in oligodendroglioma and glioblastoma. We screened, for TERTp hotspot mutations, 301 adult patients with gliomas and identified heterozygous mutations in 239 cases: 94% of oligodendroglioma, 85% of glioblastoma, and 37.5% of diffuse/anaplastic astrocytoma. Besides the recurrent c.1-124 C > T and c.1-146 C > T, two cases of glioblastoma harbored novel somatic TERTp variants, which consisted of a tandem duplications of 22 nucleotides, i.e. a TERTp c.1-100_1-79dup and TERTp c.1-110_1-89, both located downstream c.1-124 C > T and c.1-146 C > T. In silico analysis predicted the formation of 119 and 108 new transcription factor’s recognition sites for TERTp c.1-100_1-79dup and TERTp c.1-110_1-89, respectively. TERTp duplications (TERTpdup) mainly affected the binding capacity of two transcription factors’ families, i.e. the members of the E-twenty-six and the Specificity Protein/Krüppel-Like Factor groups. In fact, these new TERTpdup significantly enhanced the E-twenty-six transcription factors’ binding capacity, which is also typically increased by the two c.1-124 C > T/c.1-146 C > T hotspot TERTpmut. On the other hand, they were distinguished by enhanced affinity for the Krüppel proteins. The luciferase assay confirmed that TERTpdup behaved as gain-of-function mutations causing a 2,3-2,5 fold increase of TERT transcription. The present study provides new insights into TERTp mutational spectrum occurring in central nervous system tumors, with the identification of new recurrent somatic gain-of-function mutations, occurring in 0.8% of glioblastoma IDH-wildtype.
Aluminum tanning of hide powder and skin pieces under microwave irradiation
Authors: Liu Yue , Song Bin , Zhang Jinwei , Gaidau Carmen , Gu Haibin 
Published: August 2020

Abstract
The application and mechanism study of microwave irradiation in traditional industries have attracted considerable attention owing to the unique thermal and athermal effects that could lead to unexpected benefits in high-efficiency and clean production. Herein, we report the investigation of the aluminum tanning under microwave irradiation upon using hide powder and skin pieces, respectively, as simulants of real hide or skin. The aluminum tanning process and the tanned products under microwave heating (MWH) were studied and compared with those of conventional water bath heating (WBH) as the controls. For the tanning system of hide powder, the tanning effluents were analyzed in terms of pH, conductivity, dielectric constant and aluminum content, and the tanned powder was investigated by differential scanning calorimetry (DSC), thermogravimetric (TG) analysis, and FT-IR spectroscopy. For the skin piece system, the pH and aluminum content of tanning effluents were also determined, and at the same time, DSC, TG, SEM, FT-IR and shrinkage temperature were used to illustrate the actions of microwaves on the structure and properties of the tanned pieces. The results show that aluminum reactivity in the penetration and binding process of collagen fibers in hide powder and skin pieces improved using microwave treatment. The residual aluminum content was greatly reduced by microwave heating action, and the increased amount of aluminum with evener distribution was observed in the tanned products. Microwave irradiation also resulted in the tanned products with better thermal stability and thermal decomposition resistance. This work further promotes application of microwave treatments for aluminum-based tanning in leather industry.

Graphical abstract
PET/CT in restaging, prognosis, and recurrence in patients with malignant melanoma
Authors: El-Shourbagy Kholoud H. , Mashaly Emad M. , Khodair Sameh A. , Houseni Mohamed M. , Abou Khadrah Rania S. 
Published: August 2020

Abstract
Background
Cutaneous malignant melanoma (CMM) is a highly aggressive tumor with high tendency of return despite complete surgical removal. It has a high risk of dissemination to regional lymph nodes and visceral organs. The prognosis is highly dependent on lymph node involvement and distant metastases. Positron Emission Tomography with Computed Tomography (PET/CT) is a valuable non-invasive tool for the diagnosis and staging of patients with MM. The purpose of the present study was to evaluate the role of integrated (PET/CT) in staging, restaging, prognosis, and prediction of recurrence in patients with malignant melanoma.

Results
Fifty malignant melanoma patients with age ranged from 28 to74 years (mean age 55.94 + 13.40 years) were 28 males (mean age 56.71 + 12.82) and 22 females (mean age 54.95 + 14.34). All our patients were histopathologically proven to have malignant melanoma. Twenty-one patients came for initial staging by 18F-FDG PET/CT. Their findings were compared with the reference standards and showed the sensitivity of 93.33%, specificity of 60%, and accuracy of 85.71% for primary staging. 18F-FDG PET/CT scan in 11 clinical suspicion patients of relapse after treatment showed the sensitivity of 100%, specificity of 66.66%, positive predictive value of 88.88%; negative predictive value of 100%; and accuracy of 90.90%. FDG-PET/CT of whole body scan in 18 cases of stage IV melanoma showed sensitivity of 100%, specificity of 66.66%, and overall accuracy of 94.44% for detection of distant metastases. SUVmean and SUVmax in all studied groups were significantly higher in true positive more than true negative or false-positive patients diagnosed by PET/CT with high sensitivity (82.88–100%).

Conclusion
PET/CT imaging enhanced diagnostic performance in detection of the primary malignancy, in follow-up of high-risk patients and patients with suspected or known local or distant recurrence, and in restaging of patients with known distant metastatic disease to assess tumor response.
Upper GI series in infants and children with vomiting: insights into ACR appropriateness criteria
Authors: Mohammad Shaimaa AbdelSattar , Hamed Eman Ahmed , Shalaby Mennatallah Hatem , Eldieb Leila M. Rawash 
Published: August 2020

Abstract
Background
Although upper gastrointestinal series (UGI) series are frequently requested in pediatric radiology department, there are few articles investigating its value in children with vomiting. The purpose of this study was to review imaging findings perceived during UGI series in infants and children presented with vomiting in correlation to their symptoms based on the ACR appropriateness criteria. This was to identify clinical scenarios with higher diagnostic yield.

Results
A cross-sectional study including UGI series of 76 patients presented with vomiting (1 month–17 years) was performed. Patients were grouped according to their age into 5 groups and stratified according to the type of vomiting into 3 groups (bilious vomiting, new-onset nonbilious vomiting, intermittent nonbilious vomiting since birth). Associated symptoms were described with calculation of a novel clinical score. Radiological abnormalities in different age groups were described in relation to the type of vomiting. All patients with bilious vomiting or nonbilious vomiting associated with melena or dysphagia had abnormal findings. Gastroesophageal reflux was detected in 25% of cases. Patients with normal and abnormal study were compared according to their clinical score. The clinical score was significantly higher in the group of patients with abnormal findings (p < .001). Patients with recurrent chest symptoms and loss of weight had significantly higher rate of abnormal findings.

Conclusion
UGI series had a higher diagnostic yield in patients with bilious vomiting, children with nonbilious vomiting with higher clinical scores when associated with recurrent chest symptoms, loss of weight, dysphagia, or GIT bleeding especially melena.
Religion and psychiatry: research, prayer and clinical practice
Authors: Cook Christopher C. H. 
Published: August 2020

SUMMARYReligious concerns, manifested in thought and behaviour, have a complex, bidirectional and sometimes conceptually overlapping relationship with mental health and mental disorder. Psychiatry, concerning itself with what is measurable in research, and with the relief of distress in clinical practice, has a different perspective on these complex interrelationships than does theology or religion. That which is transcendent, and therefore not measurable, is often important to patients, and sometimes distress may (theologically) be a sign of human well-being. The giving of careful attention to transcendence and distress may variously be conceived of as prayer, religious coping or clinical care. Applications of research to clinical practice, addressing as they do a sensitive and controversial boundary between psychiatry and religion, must therefore be patient centred and culturally sensitive.
Access to specialist community alcohol treatment in England, and the relationship with alcohol-related hospital admissions: qualitative study of service users, service providers and service commissioners
Authors: Roberts Emmert , Hillyard Miriam , Hotopf Matthew , Parkin Stephen , Drummond Colin 
Published: August 2020

Background
Since 2012 England has seen year-on-year reductions in people accessing specialist community alcohol treatment, and year-on-year increases in alcohol-related hospital admissions.

Aims
We examined perceived barriers to accessing specialist treatment, and perceived reasons behind hospital admission increases.

Method
We conducted focus groups (n = 4) with service users and semi-structured interviews (n = 16) with service providers and service commissioners at four specialist community alcohol services in England, which experience either high or low rates of alcohol dependence prevalence and treatment access. Themes and subthemes were generated deductively drawing upon Rhodes’ risk environment thesis. Data were organised using the framework approach.

Results
Data reveal a treatment sector profoundly affected at all levels by changes implemented in the Health and Social Care Act (HSCA) 2012. Substantial barriers to access exist, even in services with high access rates. Concerns regarding funding cuts and recommissioning processes are at the forefront of providers’ and commissioners’ minds. The lack of cohesion between community and hospital alcohol services, where hospital services exist, has potentially created an environment enabling the reduced numbers of people accessing specialist treatment.

Conclusions
Our study reveals a treatment sector struggling with a multitude of problems; these pervade despite enaction of the HSCA, and are present at the national, service provider and individual service level. Although we acknowledge the problems are varied and multifaceted, their existence is echoed by the united voices of service users, service providers and service commissioners.