bluuebunny/crossref_metadata_2025_split huggingface dataset:
CICAFAST: comparison of a biological dressing composed of fetal fibroblasts and keratinocytes on a split-thickness skin graft donor site versus a traditional dressing: a randomized controlled trial
Authors: Poinas Alexandra , Perrot Pierre , Lorant Judith , Nerrière Olivier , Nguyen Jean-Michel , Saiagh Soraya , Frenard Cécile , Leduc Audrey , Malard Olivier , Espitalier Florent , Duteille Franck , Chiffoleau Anne , Vrignaud Florence , Khammari Amir , Dréno Brigitte 
Published: October 2019

AbstractBackgroundWound repair is one of the most complex biological processes of human life. Allogeneic cell-based engineered skin substitutes provide off-the-shelf temporary wound coverage and act as biologically active dressings, releasing growth factors, cytokines and extracellular matrix components essential for proper wound healing. However, they are susceptible to immune rejection and this is their major weakness.Thanks to their low immunogenicity and high effectiveness in regeneration, fetal skin cells represent an attractive alternative to the commonly used autologous and allogeneic skin grafts.Methods/designWe developed a new dressing comprising a collagen matrix seeded with a specific ratio of active fetal fibroblasts and keratinocytes. These produce a variety of healing growth factors and cytokines which will increase the speed of wound healing and induce an immunotolerant state, with a slight inflammatory reaction and a reduction in pain.The objective of this study is to demonstrate that the use of this biological dressing for wound healing at the split-thickness skin graft (STSG) donor site, reduces the time to healing, decreases other co-morbidities, such as pain, and improves the appearance of the scar.This investigation will be conducted as part of a randomized study comparing our new biological dressing with a conventional treatment in a single patient, thus avoiding the factors that may influence the healing of a graft donor site.DiscussionThis clinical trial should enable the development of a new strategy for STSG donor-wound healing based on a regenerative dressing. The pain experienced in the first few days of STSG healing is well known due to the exposure of sensory nerve endings. Reducing this pain will also reduce analgesic drug intake and the duration of sick leave.Our biological dressing will meet the essential need of surgeons to “re-crop” from existing donor sites, e.g., for thermal-burn patients. By accelerating healing, improving the appearance of the scar and reducing pain, we hope to improve the conditions of treatment for skin grafts.Trial registrationClinicalTrials.gov, ID:NCT03334656. Registered on 7 November 2017.
Association between cognitive impairment patient with solid cancer and insulin resistance
Authors: Gonda Kenji , Yaginuma Kenji , Rokkaku Yuichi , Horita Shoichiro , Maejima Yuko , Shimomura Kenju 
Published: October 2019

Abstract

Objectives
In an aging population, an increase in the number of elderly cancer patients with cognitive impairment is expected. The possible association between cancer and cognitive impairment is important to elucidate, because it can have a serious impact on quality of life. Here, we focused on glucose metabolism as a factor that links cancer and cognitive impairment.

Results
Thirteen subjects with solid cancers and cognitive impairment were recruited. As a control group, 14 subjects with cognitive impairment alone and 8 subjects with cancer alone were recruited. A Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and that of β-cell function (HOMA-B) were used. In comparison with patients with solid cancer alone, those with cognitive impairment alone and those with both cancer and cognitive impairment had increased HOMA-IR values. Insulin resistance was increased in patients with cognitive impairment alone and those with both cognitive impairment and solid cancer than in patients without cognitive impairment; however, β-cell function was not affected. The present data indicated that elderly cancer patients with high HOMA-IR score may be at a relatively high risk for developing cognitive impairment. Furthermore, early treatment to reduce insulin sensitivity may prevent cognitive impairment.
Evaluation of bacterial and fungal contamination of kitchens of Birjand University of Medical Sciences
Authors: Rahimi Seyyedeh Masoomeh , Ebrahimi Maryam , Barikbin Behnam , Zeinali Tayebeh 
Published: October 2019

Abstract

Objective
This study aims to evaluate the total bacterial and fungal count of tools, devices and surfaces of kitchens of the centers affiliated to Birjand University of Medical Sciences. In this study, 200 samples from four kitchens of Birjand University of Medical Sciences were obtained. After the preparation of serial dilutions, samples were cultured in plate count agar (PCA) plates and Sabouraud dextrose agar (SDA). After incubation at 37 and 25 °C for 24–48 and 72–96 h respectively, the microbial and fungal colonies were counted.

Results
The mean bacterial and fungal count of kitchens was 7.7 * 107 and 7.6 * 104, respectively. The highest and lowest levels of bacterial contamination were related to tools/devices and cover of tools/work clothes and the highest and lowest levels of fungal count were related to forks and spoons and the tools and devices of the storage site. The rate of contamination in the kitchens of Birjand University of Medical Sciences was relatively high. Thus, serious, continuous and accurate monitoring of the units, training of people working in all stages of cooking and disinfection the tools and devices are essential for control and prevention of disease transmission.
The dental complications of canine tooth bud removal in 2–12 years old children in Northwest Ethiopia
Authors: Teshome Amare , Assefa Berihun 
Published: October 2019

Abstract

Objective
Canine tooth bud removal is a process of gouging out an infant’s canine tooth buds, using unsterile tools such as Sharpe blade, garlic, or knitting needle, without anesthesia. The aim of the study was to reveal dental complications of canine tooth bud removal among children who visited the dental clinic of the University of Gondar hospital. This study was an institution-based cross-sectional conducted from January 2015 to September 2016 at the University of Gondar hospital on 2–12 years children. The tooth was assessed for whether it had previously oral mutilated or not. In addition to this, the oral cavity was evaluated for the presence of missed, malformed or normal canine.

Results
A group of 355 children aged 2–12 years was examined clinically. The mean age of the children was 7.32 ± 3.12 (SD). The prevalence of canine tooth bud removal was 86.8% which was high in 6–9 years old (54.87%) and first position children (40.26%). The most common dental complications were; malformed enamel (hypoplastic) canine (48.5%) and missed/unerupted canine (38.6%).
Selective demethylation of two CpG sites causes postnatal activation of the Dao gene and consequent removal of d-serine within the mouse cerebellum
Authors: Cuomo Mariella , Keller Simona , Punzo Daniela , Nuzzo Tommaso , Affinito Ornella , Coretti Lorena , Carella Massimo , de Rosa Valeria , Florio Ermanno , Boscia Francesca , Avvedimento Vittorio Enrico , Cocozza Sergio , Errico Francesco , Usiello Alessandro , Chiariotti Lorenzo 
Published: October 2019

Abstract

Background
Programmed epigenetic modifications occurring at early postnatal brain developmental stages may have a long-lasting impact on brain function and complex behavior throughout life. Notably, it is now emerging that several genes that undergo perinatal changes in DNA methylation are associated with neuropsychiatric disorders. In this context, we envisaged that epigenetic modifications during the perinatal period may potentially drive essential changes in the genes regulating brain levels of critical neuromodulators such as d-serine and d-aspartate. Dysfunction of this fine regulation may contribute to the genesis of schizophrenia or other mental disorders, in which altered levels of d-amino acids are found. We recently demonstrated that Ddo, the d-aspartate degradation gene, is actively demethylated to ultimately reduce d-aspartate levels. However, the role of epigenetics as a mechanism driving the regulation of appropriate d-ser levels during brain development has been poorly investigated to date.

Methods
We performed comprehensive ultradeep DNA methylation and hydroxymethylation profiling along with mRNA expression and HPLC-based d-amino acids level analyses of genes controlling the mammalian brain levels of d-serine and d-aspartate. DNA methylation changes occurring in specific cerebellar cell types were also investigated. We conducted high coverage targeted bisulfite sequencing by next-generation sequencing and single-molecule bioinformatic analysis.

Results
We report consistent spatiotemporal modifications occurring at the Dao gene during neonatal development in a specific brain region (the cerebellum) and within specific cell types (astrocytes) for the first time. Dynamic demethylation at two specific CpG sites located just downstream of the transcription start site was sufficient to strongly activate the Dao gene, ultimately promoting the complete physiological degradation of cerebellar d-serine a few days after mouse birth. High amount of 5′-hydroxymethylcytosine, exclusively detected at relevant CpG sites, strongly evoked the occurrence of an active demethylation process.

Conclusion
The present investigation demonstrates that robust and selective demethylation of two CpG sites is associated with postnatal activation of the Dao gene and consequent removal of d-serine within the mouse cerebellum. A single-molecule methylation approach applied at the Dao locus promises to identify different cell-type compositions and functions in different brain areas and developmental stages.
Type Va extrahepatic bile duct duplication: a case report
Authors: Banjade Bharat Mani , Rajbhandari Ashish , Koirala Rabin , Shah Tuhin , Bhattachan Chitra Lal 
Published: October 2019

Abstract

Background
Extrahepatic bile duct duplication is an extremely rare congenital anomaly in which two common bile ducts exist. There are five different types of this anomaly and we present an unusual variant of duplication of an extrahepatic biliary system of type Va variety.

Case presentation
This case report describes a 63-year-old women from rural Nepal who presented with type Va of duplicated extrahepatic bile duct, with chronic calculous cholecystitis and choledocholithiasis. She was managed with cholecystectomy with hepatic ductoplasty and hepaticojejunostomy.

Conclusion
A rare case of double common bile duct (type Va) complicated by choledocholithiasis, cholangitis, and chronic cholecystitis is reported here. Rare cases are sometimes overlooked by modern diagnostic techniques. Correct diagnosis helps appropriate surgical intervention.
Measuring the impact of screening automation on meta-analyses of diagnostic test accuracy
Authors: Norman Christopher R. , Leeflang Mariska M. G. , Porcher Raphaël , Névéol Aurélie 
Published: October 2019

AbstractBackgroundThe large and increasing number of new studies published each year is making literature identification in systematic reviews ever more time-consuming and costly. Technological assistance has been suggested as an alternative to the conventional, manual study identification to mitigate the cost, but previous literature has mainly evaluated methods in terms of recall (search sensitivity) and workload reduction. There is a need to also evaluate whether screening prioritization methods leads to the same results and conclusions as exhaustive manual screening. In this study, we examined the impact of one screening prioritization method based on active learning on sensitivity and specificity estimates in systematic reviews of diagnostic test accuracy.MethodsWe simulated the screening process in 48 Cochrane reviews of diagnostic test accuracy and re-run 400 meta-analyses based on a least 3 studies. We compared screening prioritization (with technological assistance) and screening in randomized order (standard practice without technology assistance). We examined if the screening could have been stopped before identifying all relevant studies while still producing reliable summary estimates. For all meta-analyses, we also examined the relationship between the number of relevant studies and the reliability of the final estimates.ResultsThe main meta-analysis in each systematic review could have been performed after screening an average of 30% of the candidate articles (range 0.07 to 100%). No systematic review would have required screening more than 2308 studies, whereas manual screening would have required screening up to 43,363 studies. Despite an average 70% recall, the estimation error would have been 1.3% on average, compared to an average 2% estimation error expected when replicating summary estimate calculations.ConclusionScreening prioritization coupled with stopping criteria in diagnostic test accuracy reviews can reliably detect when the screening process has identified a sufficient number of studies to perform the main meta-analysis with an accuracy within pre-specified tolerance limits. However, many of the systematic reviews did not identify a sufficient number of studies that the meta-analyses were accurate within a 2% limit even with exhaustive manual screening, i.e., using current practice.
Debate on the compositions of influenza B in northern hemisphere seasonal influenza vaccines
Authors: He Guozhong , Yang Pengfei , Yan Qingli , Xiong Chenglong 
Published: October 2019

Abstract

Background
Annual influenza vaccination is the most effective way to prevent influenza. Influenza vaccines have traditionally included the hemagglutinins (HA) and neuraminidases (NA) from the two A viruses (H1N1 and H3N2) and either B Yamagata or B Victoria. Mismatches between circulating isolates of influenza B and the vaccines are very common. Taking 2017/2018 winter in northern hemisphere as an example, this study was designed to find out the reasons for mismatch between the trivalent influenza vaccine (TIV) and most of the epidemic isolates at that time, and to discuss if there are some optimized programs for seasonal influenza vaccines.

Methods
HA and NA sequences of the seasonal isolates circulating from December 1, 2017 to February 28, 2018, and in the previously other 7 winters in northern hemisphere from Global Initiative on Sharing All Influenza Data (GISAID) and the influenza database of National Center for Biotechnology Information (NCBI). Phylogenetic trees and genetic distances were constructed or calculated by using MAFFT and MEGA 6.0 software.

Results
Influenza B composition in the TIV recommendation mismatched most of circulating viruses in 2017/2018 winter; the vaccine strain was from the B/Victoria lineage, while most of epidemic isolates were from the B/Yamagata lineage. The epidemic lineage of influenza B reached its peak a little late in the previous winter might be responsible for this mismatch. During 2010–2018, the mean genetic distances between epidemic isolates of influenza A (H1N1 and H3N2) and the vaccines were no higher than 0.02375 ± 0.00341 in both HA and NA. However, concerning influenza B virus, when forecasting done well, the mean genetic distances between epidemic isolates and the vaccines were no higher than 0.02368 ± 0.00272; otherwise, the distances could reach 0.13695 ± 0.00238.

Conclusion
When applying quadrivalent influenza vaccines (QIVs) for vaccination, the recommendations of compositions for influenza B could be altered and assessed once in 3 or 4 years; when economic burden was considered intensively and TIVs were utilized, the recommended compositions for influenza B could be announced in April or May, rather than in February or March as now.
Tumors diagnosed as cerebellar glioblastoma comprise distinct molecular entities
Authors: Reinhardt Annekathrin , Stichel Damian , Schrimpf Daniel , Koelsche Christian , Wefers Annika K. , Ebrahimi Azadeh , Sievers Philipp , Huang Kristin , Casalini M. Belén , Fernández-Klett Francisco , Suwala Abigail , Weller Michael , Gramatzki Dorothee , Felsberg Joerg , Reifenberger Guido , Becker Albert , Hans Volkmar H. , Prinz Marco , Staszewski Ori , Acker Till , Dohmen Hildegard , Hartmann Christian , Paulus Werner , Heß Katharina , Brokinkel Benjamin , Schittenhelm Jens , Buslei Rolf , Deckert Martina , Mawrin Christian , Hewer Ekkehard , Pohl Ute , Jaunmuktane Zane , Brandner Sebastian , Unterberg Andreas , Hänggi Daniel , Platten Michael , Pfister Stefan M. , Wick Wolfgang , Herold-Mende Christel , Korshunov Andrey , Reuss David E. , Sahm Felix , Jones David T. W. , Capper David , von Deimling Andreas 
Published: October 2019

Abstract
In this multi-institutional study we compiled a retrospective cohort of 86 posterior fossa tumors having received the diagnosis of cerebellar glioblastoma (cGBM). All tumors were reviewed histologically and subjected to array-based methylation analysis followed by algorithm-based classification into distinct methylation classes (MCs). The single MC containing the largest proportion of 25 tumors diagnosed as cGBM was MC anaplastic astrocytoma with piloid features representing a recently-described molecular tumor entity not yet included in the WHO Classification of Tumours of the Central Nervous System (WHO classification). Twenty-nine tumors molecularly corresponded to either of 6 methylation subclasses subsumed in the MC family GBM IDH wildtype. Further we identified 6 tumors belonging to the MC diffuse midline glioma H3 K27 M mutant and 6 tumors allotted to the MC IDH mutant glioma subclass astrocytoma. Two tumors were classified as MC pilocytic astrocytoma of the posterior fossa, one as MC CNS high grade neuroepithelial tumor with BCOR alteration and one as MC control tissue, inflammatory tumor microenvironment. The methylation profiles of 16 tumors could not clearly be assigned to one distinct MC. In comparison to supratentorial localization, the MC GBM IDH wildtype subclass midline was overrepresented, whereas the MCs GBM IDH wildtype subclass mesenchymal and subclass RTK II were underrepresented in the cerebellum. Based on the integration of molecular and histological findings all tumors received an integrated diagnosis in line with the WHO classification 2016. In conclusion, cGBM does not represent a molecularly uniform tumor entity, but rather comprises different brain tumor entities with diverse prognosis and therapeutic options. Distinction of these molecular tumor classes requires molecular analysis. More than 30% of tumors diagnosed as cGBM belong to the recently described molecular entity of anaplastic astrocytoma with piloid features.
Deep morphological analysis of muscle biopsies from type III glycogenesis (GSDIII), debranching enzyme deficiency, revealed stereotyped vacuolar myopathy and autophagy impairment
Authors: Laforêt Pascal , Inoue Michio , Goillot Evelyne , Lefeuvre Claire , Cagin Umut , Streichenberger Nathalie , Leonard-Louis Sarah , Brochier Guy , Madelaine Angeline , Labasse Clemence , Hedberg-Oldfors Carola , Krag Thomas , Jauze Louisa , Fabregue Julien , Labrune Philippe , Milisenda Jose , Nadaj-Pakleza Aleksandra , Sacconi Sabrina , Mingozzi Federico , Ronzitti Giuseppe , Petit François , Schoser Benedikt , Oldfors Anders , Vissing John , Romero Norma B. , Nishino Ichizo , Malfatti Edoardo 
Published: October 2019

Abstract
Glycogen storage disorder type III (GSDIII), or debranching enzyme (GDE) deficiency, is a rare metabolic disorder characterized by variable liver, cardiac, and skeletal muscle involvement. GSDIII manifests with liver symptoms in infancy and muscle involvement during early adulthood. Muscle biopsy is mainly performed in patients diagnosed in adulthood, as routine diagnosis relies on blood or liver GDE analysis, followed by AGL gene sequencing. The GSDIII mouse model recapitulate the clinical phenotype in humans, and a nearly full rescue of muscle function was observed in mice treated with the dual AAV vector expressing the GDE transgene.
In order to characterize GSDIII muscle morphological spectrum and identify novel disease markers and pathways, we performed a large international multicentric morphological study on 30 muscle biopsies from GSDIII patients. Autophagy flux studies were performed in human muscle biopsies and muscles from GSDIII mice. The human muscle biopsies revealed a typical and constant vacuolar myopathy, characterized by multiple and variably sized vacuoles filled with PAS-positive material. Using electron microscopy, we confirmed the presence of large non-membrane bound sarcoplasmic deposits of normally structured glycogen as well as smaller rounded sac structures lined by a continuous double membrane containing only glycogen, corresponding to autophagosomes. A consistent SQSTM1/p62 decrease and beclin-1 increase in human muscle biopsies suggested an enhanced autophagy. Consistent with this, an increase in the lipidated form of LC3, LC3II was found in patients compared to controls. A decrease in SQSTM1/p62 was also found in the GSDIII mouse model.
In conclusion, we characterized the morphological phenotype in GSDIII muscle and demonstrated dysfunctional autophagy in GSDIII human samples.
These findings suggest that autophagic modulation combined with gene therapy might be considered as a novel treatment for GSDIII.
Phosphorylated TDP-43 aggregates in skeletal and cardiac muscle are a marker of myogenic degeneration in amyotrophic lateral sclerosis and various conditions
Authors: Mori Fumiaki , Tada Mari , Kon Tomoya , Miki Yasuo , Tanji Kunikazu , Kurotaki Hidekachi , Tomiyama Masahiko , Ishihara Tomohiko , Onodera Osamu , Kakita Akiyoshi , Wakabayashi Koichi 
Published: October 2019

Abstract

Background
Amyotrophic lateral sclerosis (ALS) is characterized pathologically by the occurrence of phosphorylated TDP-43 (pTDP-43)-immunoreactive neuronal and glial inclusions in the central nervous system. Recent studies have shown that pTDP-43 aggregates also occur in the skeletal muscles in a certain proportion of ALS patients.

Aim
The aim of this study was to clarify the distribution and incidence of pTDP-43 aggregates in the skeletal and cardiac muscles of patients with ALS, and also those of patients with neuromuscular diseases (NMDs) and non-NMDs.

Material and methods
Five regions of muscle (tongue, cervical muscle, diaphragm, iliopsoas muscle and heart) were examined histologically and immunohistochemically in patients with ALS (n = 30), NMDs (n = 13) and non-NMDs (n = 7).

Results
Two types of pTDP-43 aggregates were distinguishable morphologically: dense filamentous and short linear inclusions. These inclusions were found in at least one of the five muscle regions in all 30 cases of ALS; skeletal muscles in 28 cases and myocardium in 12. pTDP-43 aggregates were also found in 9 of 13 patients with NMDs, including myositis, muscular dystrophy and mitochondrial myopathy, as well as in 3 of 7 patients with non-NMDs. In ALS, pTDP-43 aggregates were most frequent in the diaphragm (19 cases). The mean density of pTDP-43 aggregates in ALS was significantly higher than that in NMDs and non-NMDs. In contiguous sections stained with hematoxylin and eosin and anti-pTDP-43, muscle fibers with dense filamentous inclusions demonstrated single-fiber atrophy with vacuolar degeneration.

Conclusion
The present findings indicate that pTDP-43 aggregates in skeletal and cardiac muscle are a myogenic pathological marker in multiple diseases including ALS.