bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atypical Charles Bonnet syndrome secondary to frontal meningioma: a case report
Authors: Diana Lomelín-López , Carmona-Huerta Jaime , Patiño J. Guillermo , Alejandro Aldana-López , Sol Durand-Arias 
Published: July 2021

Abstract
Background
Charles Bonnet Syndrome (CBS) is a rare clinical entity that is classically composed of visual hallucinations in the context of an altered optic pathway with preservation of reality judgment. This case aims to present the association of visual hallucinations with complex alterations of the nervous structures adjacent to the visual pathway and an atypical clinical presentation, thus explaining the possible mechanisms involved in the generation of these symptoms.

Case presentation
A 43-year-old man presents seeking care due to visual hallucinations with partial preservation of reality judgment and symptoms compatible with a major depressive disorder, including irritability and diminished hygiene habits. He has a history of complete gradual loss of vision and hyposmia. Due to poor treatment response during hospitalization, an MRI was obtained, which showed a frontal tumor lesion with meningioma characteristics adjacent to the olfactory groove and compression of the optic chiasm. He underwent surgical resection of the lesion, which remitted the psychotic symptoms, but preserving the visual limitation and depressive symptoms.

Conclusions
The presence of visual hallucinations, without other psychotic features as delusions, is a focus of attention for basic structural pathologies in the central nervous system. Affection at any level of the visual pathway can cause CBS. When finding atypical symptoms, a more in-depth evaluation should be made to allow optimization of the diagnosis and treatment.
Development of a novel denture care agent with highly active enzyme, arazyme
Authors: Kim Jong-Hoon , Lee Ha-Neul , Bae Seong-Kyeong , Shin Dong-Ha , Ku Bon-Hwan , Park Ho-Yong , Jeong Tae-Sook 
Published: July 2021

Abstract
Background
The importance of efficient denture deposit removal and oral hygiene has been further underscored by the continuous increase of denture wearers. Denture hygiene management has also become an important aspect associated with denture-induced stomatitis. This study aims to evaluate the denture cleaning effect of arazyme, the metalloprotease produced from the Serratia proteamaculans HY-3. We performed growth inhibition tests against oral opportunistic pathogens to be used as a potential oral health care agent.

Methods
The proteolytic activities of arazyme was evaluated over broad ranges of temperature, pH, and denture components compared to those of subtilisin in commercially available denture cleansers. The washing effects of arazyme were also measured by using homogeneously soiled EMPA 105 cottons. To investigate the denture cleaning capability of arazyme, artificially contaminated dentures were treated with arazyme, subtilisin (Everlase 6.0T), and Polident®, respectively. The growth kinetics of Candida albicans, Enterococcus faecalis, Staphylococcus epidermis, and Streptococcus mutans were evaluated in the presence of different concentrations of arazyme to estimate the prevention effects of arazyme against major oral opportunistic pathogens.

Results
Arazyme showed strong proteolytic activities over wide temperature and pH ranges compared with the serine protease of the subtilisin family. Arazyme demonstrated efficient removal and decomposition of artificially contaminated dentures and showed explicit washing effects against soiled cottons. Moreover arazyme inhibited the growth of oral opportunistic pathogens, including C. albicans, E. faecalis, S. epidermis, and S. mutans, with more than 80% inhibition against C. albicans, the major cause of denture stomatitis, with 250 mg/mL arazyme.

Conclusions
Arazyme shows promise as a biological oral health care agent with effective cleaning and antimicrobial activities and is a potential source for developing novel denture care agents.
Bromide toxicosis (bromism) secondary to a decreased chloride intake after dietary transition in a dog with idiopathic epilepsy: a case report
Authors: Fantinati Marco , Priymenko Nathalie , Debreuque Maud 
Published: July 2021

AbstractBackgroundBromide is a halide ion of the element bromine usually administered in the form of potassium salt as monotherapy or add-on treatment in epileptic dogs. It is excreted unchanged in the urine and undergoes tubular reabsorption in competition with chloride. Thus, dietary chloride content affects serum bromide concentrations. This is the first published clinical report of bromide toxicosis secondary to a dietary modification of chloride content in an epileptic dog treated with potassium bromide.Case presentationA 3-year-old 55-kg neutered male Tibetan Mastiff was evaluated because of a 1-month history of progressive signs including ataxia, lethargy and behaviour changes. The dog was successfully treated for idiopathic epilepsy since the age of 1-year-old with phenobarbital and potassium bromide. Two months prior to presentation, the owners decided to change the dog’s diet without veterinary advice. Physical examination was unremarkable. A 12-kg weight gain was recorded since last follow-up (8 months). Neurological examination revealed severe symmetric 4-limbs ataxia with altered vigilance and intermittent episodes of hyperactivity and aggressive behaviour without significant abnormality of cranial nerves. Serum bromide concentration was high and increased by 103 % since last follow-up. Nutritional evaluation revealed a 53 % decrease of chloride content in the diet before and after dietary transition. Bromide toxicosis was suspected, due to bromide reduced clearance secondary to the decreased dietary chloride content. Potassium bromide treatment was lowered by 15 % without further dietary changes. Neurologic signs progressively improved over the next month, without any seizure. After two months, the serum bromide concentration lowered to the same level measured before dietary modification. After four months, neurological examination was unremarkable.ConclusionsDietary chloride content can directly influence serum bromide concentrations, therefore affecting seizure control or contributing to unexpected adverse effects. In the present case, a reduction in chloride intake markedly increased serum bromide concentrations causing bromism. Dietary changes should be avoided in dogs treated with potassium bromide to maintain stable serum bromide levels.
Crystal structure and functional characterization of an oligosaccharide dehydrogenase from Pycnoporus cinnabarinus provides insights into fungal breakdown of lignocellulose
Authors: Cerutti Gabriele , Gugole Elena , Montemiglio Linda Celeste , Turbé-Doan Annick , Chena Dehbia , Navarro David , Lomascolo Anne , Piumi François , Exertier Cécile , Freda Ida , Vallone Beatrice , Record Eric , Savino Carmelinda , Sciara Giuliano 
Published: July 2021

Abstract
Background
Fungal glucose dehydrogenases (GDHs) are FAD-dependent enzymes belonging to the glucose-methanol-choline oxidoreductase superfamily. These enzymes are classified in the “Auxiliary Activity” family 3 (AA3) of the Carbohydrate-Active enZymes database, and more specifically in subfamily AA3_2, that also includes the closely related flavoenzymes aryl-alcohol oxidase and glucose 1-oxidase. Based on sequence similarity to known fungal GDHs, an AA3_2 enzyme active on glucose was identified in the genome of Pycnoporus cinnabarinus, a model Basidiomycete able to completely degrade lignin.

Results
In our work, substrate screening and functional characterization showed an unexpected preferential activity of this enzyme toward oligosaccharides containing a β(1→3) glycosidic bond, with the highest efficiency observed for the disaccharide laminaribiose. Despite its sequence similarity to GDHs, we defined a novel enzymatic activity, namely oligosaccharide dehydrogenase (ODH), for this enzyme. The crystallographic structures of ODH in the sugar-free form and in complex with glucose and laminaribiose unveiled a peculiar saccharide recognition mechanism which is not shared with previously characterized AA3 oxidoreductases and accounts for ODH preferential activity toward oligosaccharides. The sugar molecules in the active site of ODH are mainly stabilized through CH-π interactions with aromatic residues rather than through hydrogen bonds with highly conserved residues, as observed instead for the fungal glucose dehydrogenases and oxidases characterized to date. Finally, three sugar-binding sites were identified on ODH external surface, which were not previously observed and might be of importance in the physiological scenario.

Conclusions
Structure–function analysis of ODH is consistent with its role as an auxiliary enzyme in lignocellulose degradation and unveils yet another enzymatic function within the AA3 family of the Carbohydrate-Active enZymes database. Our findings allow deciphering the molecular determinants of substrate binding and provide insight into the physiological role of ODH, opening new perspectives to exploit biodiversity for lignocellulose transformation into fuels and chemicals.
Mobilization of the nonconjugative virulence plasmid from hypervirulent Klebsiella pneumoniae
Authors: Xu Yanping , Zhang Jianfeng , Wang Meng , Liu Meng , Liu Guitian , Qu Hongping , Liu Jialin , Deng Zixin , Sun Jingyong , Ou Hong-Yu , Qu Jieming 
Published: July 2021

Abstract
Background
Klebsiella pneumoniae, as a global priority pathogen, is well known for its capability of acquiring mobile genetic elements that carry resistance and/or virulence genes. Its virulence plasmid, previously deemed nonconjugative and restricted within hypervirulent K. pneumoniae (hvKP), has disseminated into classic K. pneumoniae (cKP), particularly carbapenem-resistant K. pneumoniae (CRKP), which poses alarming challenges to public health. However, the mechanism underlying its transfer from hvKP to CRKP is unclear.

Methods
A total of 28 sequence type (ST) 11 bloodstream infection-causing CRKP strains were collected from Ruijin Hospital in Shanghai, China, and used as recipients in conjugation assays. Transconjugants obtained from conjugation assays were confirmed by XbaI and S1 nuclease pulsed-field gel electrophoresis, PCR detection and/or whole-genome sequencing. The plasmid stability of the transconjugants was evaluated by serial culture. Genetically modified strains and constructed mimic virulence plasmids were employed to investigate the mechanisms underlying mobilization. The level of extracellular polysaccharides was measured by mucoviscosity assays and uronic acid quantification. An in silico analysis of 2608 plasmids derived from 814 completely sequenced K. pneumoniae strains available in GenBank was performed to investigate the distribution of putative helper plasmids and mobilizable virulence plasmids.

Results
A nonconjugative virulence plasmid was mobilized by the conjugative plasmid belonging to incompatibility group F (IncF) from the hvKP strain into ST11 CRKP strains under low extracellular polysaccharide-producing conditions or by employing intermediate E. coli strains. The virulence plasmid was mobilized via four modes: transfer alone, cotransfer with the conjugative IncF plasmid, hybrid plasmid formation due to two rounds of single-strand exchanges at specific 28-bp fusion sites or homologous recombination. According to the in silico analysis, 31.8% (242) of the putative helper plasmids and 98.8% (84/85) of the virulence plasmids carry the 28-bp fusion site. All virulence plasmids carry the origin of the transfer site.

Conclusions
The nonconjugative virulence plasmid in ST11 CRKP strains is putatively mobilized from hvKP or E. coli intermediates with the help of conjugative IncF plasmids. Our findings emphasize the importance of raising public awareness of the rapid dissemination of virulence plasmids and the consistent emergence of hypervirulent carbapenem-resistant K. pneumoniae (hv-CRKP) strains.
Overweight and obesity in type 1 diabetes is not associated with higher ghrelin concentrations
Authors: Özcan Behiye , Delhanty Patric J. D. , Huisman Martin , Visser Jenny A. , Neggers Sebastian J. , van der Lely Aart Jan 
Published: July 2021

Abstract
Background
Several studies have demonstrated suppressed levels of acylated (AG) and unacylated ghrelin (UAG) in patients with type 2 diabetes. However, the role of these hormones in type 1 diabetes has not been extensively studied. This study assessed the relationship between AG and UAG levels and body composition in patients with type 1 diabetes.

Methods
We selected eighteen patients with type 1 diabetes and divided them into two groups: non-obese (BMI < 25 kg/m2) and overweight (BMI ≥ 25 kg/m2). Demographics, parameters of body composition and serum parameters including AG and UAG, were assessed.

Results
The patients with a BMI ≥ 25 kg/m2 were older and had a longer duration of diabetes. AG and UAG levels were not significantly different between non-obese and overweight groups (mean AG non-obese ± SD: 44.5 ± 29.4 pg/ml and mean UAG non-obese 42.4 ± 20.7 pg/ml vs mean AG overweight ± SD: 46.1 ± 29.6 pg/ml and mean UAG overweight 47.2 ± 18.2 pg/ml). AG/UAG ratios did not discriminate between these groups. There was a positive association of insuline dose/kg bodyweight with BMI (r2 = 0.45, p = 0.002).

Conclusions
Surprisingly, unlike non-diabetics and in T2D, we did not observe a difference in plasma levels of AG and UAG between normal weight and overweight adult type 1 diabetics. However, we did observe a positive correlation between BMI and insuline dose/kg bodyweight, suggesting that exogenous insulin is more important than the ghrelin system in the development of obesity in type 1 diabetes.
Chronic stress and poor sleeping habits are associated with self-reported IBS and poor psychological well-being in the general population
Authors: Zejnelagic Jasmin , Ohlsson Bodil 
Published: July 2021

AbstractObjectiveThe present population-based study aimed to examine the association of chronic stress and sleeping difficulties with self-reported irritable bowel syndrome (IBS), gastrointestinal (GI) symptoms past 2 weeks, and psychological well-being.ResultsThe Malmö Offspring Study included subjects from the general population to complete a questionnaire regarding sociodemographic factors, lifestyle factors, and medical health. Experience of chronic stress during the past or past 5 years was reported. Sleeping patterns included sleeping quality, sleeping hours per day, sleeping onset difficulties, and wake-up frequency. The severity of GI symptoms was measured with the visual analog scale for IBS. Associations of stress and sleeping habits with IBS and GI symptoms were calculated by logistic regression and generalized linear model, adjusted for sociodemographic and lifestyle factors. After exclusion of organic GI disorders or missing values, 2648 participants remained. Participants with self-reported IBS (n = 316) and GI symptoms (n = 459) were often women and smokers. After full adjustment, chronic stress past year was associated with GI symptoms (OR: 1.347; 95% CI 1.030–1.762), whereas stress past 5 years (OR: 1.415; 95% CI 1.058–1.892) and sleeping onset difficulties ≥ 3 times weekly (OR: 2.153: 95% CI 1.228–3.774) were associated with IBS. Stress, poor sleeping quality, sleeping onset difficulties, and IBS/GI symptoms were all associated with poor psychological well-being (p < 0.001).
Genome-wide DNA methylome analysis identifies methylation signatures associated with survival and drug resistance of ovarian cancers
Authors: Chan David W. , Lam Wai-Yip , Chen Fushun , Yung Mingo M. H. , Chan Yau-Sang , Chan Wai-Sun , He Fangfang , Liu Stephanie S. , Chan Karen K. L. , Li Benjamin , Ngan Hextan Y. S. 
Published: July 2021

AbstractBackgroundIn contrast to stable genetic events, epigenetic changes are highly plastic and play crucial roles in tumor evolution and development. Epithelial ovarian cancer (EOC) is a highly heterogeneous disease that is generally associated with poor prognosis and treatment failure. Profiling epigenome-wide DNA methylation status is therefore essential to better characterize the impact of epigenetic alterations on the heterogeneity of EOC.MethodsAn epigenome-wide association study was conducted to evaluate global DNA methylation in a retrospective cohort of 80 mixed subtypes of primary ovarian cancers and 30 patients with high-grade serous ovarian carcinoma (HGSOC). Three demethylating agents, azacytidine, decitabine, and thioguanine, were tested their anti-cancer and anti-chemoresistant effects on HGSOC cells.ResultsGlobal DNA hypermethylation was significantly associated with high-grade tumors, platinum resistance, and poor prognosis. We determined that 9313 differentially methylated probes (DMPs) were enriched in their relative gene regions of 4938 genes involved in small GTPases and were significantly correlated with the PI3K-AKT, MAPK, RAS, and WNT oncogenic pathways. On the other hand, global DNA hypermethylation was preferentially associated with recurrent HGSOC. A total of 2969 DMPs corresponding to 1471 genes were involved in olfactory transduction, and calcium and cAMP signaling. Co-treatment with demethylating agents showed significant growth retardation in ovarian cancer cells through differential inductions, such as cell apoptosis by azacytidine or G2/M cell cycle arrest by decitabine and thioguanine. Notably, azacytidine and decitabine, though not thioguanine, synergistically enhanced cisplatin-mediated cytotoxicity in HGSOC cells.ConclusionsThis study demonstrates the significant association of global hypermethylation with poor prognosis and drug resistance in high-grade EOC and highlights the potential of demethylating agents in cancer treatment.Graphic abstract
Immediate hypersensitivity reaction followed by successful oral desensitization to ursodiol
Authors: Lee Erika Yue , Song Christine 
Published: July 2021

Abstract
Background
Immediate hypersensitivity reaction to ursodiol is rare and there is no previously published protocol on ursodiol desensitization.

Case presentation
A 59-year-old woman with primary biliary cholangitis (PBC) developed an immediate hypersensitivity reaction to ursodiol—the first-line treatment for PBC. When she switched to a second-line treatment, her PBC continued to progress. As such, she completed a novel 12-step desensitization protocol to oral ursodiol. She experienced recurrent pruritus after each dose following desensitization, which subsided after a month of being on daily ursodiol.

Conclusion
Immediate hypersensitivity reaction to ursodiol is uncommon. Our case demonstrated that this novel desensitization protocol to ursodiol could be safely implemented when alternative options are not available or have proven inferior in efficacy.
Extracellular vesicles derived from mesenchymal stromal cells mediate endogenous cell growth and migration via the CXCL5 and CXCL6/CXCR2 axes and repair menisci
Authors: Kawata Kazumasa , Koga Hideyuki , Tsuji Kunikazu , Miyatake Kazumasa , Nakagawa Yusuke , Yokota Takanori , Sekiya Ichiro , Katagiri Hiroki 
Published: July 2021

Abstract
Background
Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are promising candidates for tissue regeneration therapy. However, the therapeutic efficacy of MSC-EVs for meniscus regeneration is uncertain, and the mechanisms underlying MSC-EV-mediated tissue regeneration have not been fully elucidated. The aims of this study were to evaluate the therapeutic efficacy of intra-articular MSC-EV injection in a meniscus defect model and elucidate the mechanism underlying MSC-EV-mediated tissue regeneration via combined bioinformatic analyses.

Methods
MSC-EVs were isolated from human synovial MSC culture supernatants via ultrafiltration. To evaluate the meniscus regeneration ability, MSC-EVs were injected intra-articularly in the mouse meniscus defect model immediately after meniscus resection and weekly thereafter. After 1 and 3 weeks, their knees were excised for histological and immunohistochemical evaluations. To investigate the mechanisms through which MSC-EVs accelerate meniscus regeneration, cell growth, migration, and chondrogenesis assays were performed using treated and untreated chondrocytes and synovial MSCs with or without MSC-EVs. RNA sequencing assessed the gene expression profile of chondrocytes stimulated by MSC-EVs. Antagonists of the human chemokine CXCR2 receptor (SB265610) were used to determine the role of CXCR2 on chondrocyte cell growth and migration induced by MSC-EVs.

Results
In the meniscus defect model, MSC-EV injection accelerated meniscus regeneration and normalized the morphology and composition of the repaired tissue. MSC-EVs stimulated chondrocyte and synovial MSC cell growth and migration. RNA sequencing revealed that MSC-EVs induced 168 differentially expressed genes in the chondrocytes and significantly upregulated CXCL5 and CXCL6 in chondrocytes and synovial MSCs. Suppression of CXCL5 and CXCL6 and antagonism of the CXCR2 receptor binding CXCL5 and CXCL6 negated the influence of MSC-EVs on chondrocyte cell growth and migration.

Conclusions
Intra-articular MSC-EV administration repaired meniscus defects and augmented chondrocyte and synovial MSC cell growth and migration. Comprehensive transcriptome/RNA sequencing data confirmed that MSC-EVs upregulated CXCL5 and CXCL6 in chondrocytes and mediated the cell growth and migration of these cells via the CXCR2 axis.
EGFL6 regulates angiogenesis and osteogenesis in distraction osteogenesis via Wnt/β-catenin signaling
Authors: Shen Junjie , Sun Yi , Liu Xuanzhe , Zhu Yu , Bao Bingbo , Gao Tao , Chai Yimin , Xu Jia , Zheng Xianyou 
Published: July 2021

Abstract
Background
Osteogenesis is tightly coupled with angiogenesis during bone repair and regeneration. However, the underlying mechanisms linking these processes remain largely undefined. The present study aimed to test the hypothesis that epidermal growth factor-like domain-containing protein 6 (EGFL6), an angiogenic factor, also functions in bone marrow mesenchymal stem cells (BMSCs), playing a key role in the interaction between osteogenesis and angiogenesis.

Methods
We evaluated how EGFL6 affects angiogenic activity of human umbilical cord vein endothelial cells (HUVECs) via proliferation, transwell migration, wound healing, and tube-formation assays. Alkaline phosphatase (ALP) and Alizarin Red S (AR-S) were used to assay the osteogenic potential of BMSCs. qRT-PCR, western blotting, and immunocytochemistry were used to evaluate angio- and osteo-specific markers and pathway-related genes and proteins. In order to determine how EGFL6 affects angiogenesis and osteogenesis in vivo, EGFL6 was injected into fracture gaps in a rat tibia distraction osteogenesis (DO) model. Radiography, histology, and histomorphometry were used to quantitatively evaluate angiogenesis and osteogenesis.

Results
EGFL6 stimulated both angiogenesis and osteogenic differentiation through Wnt/β-catenin signaling in vitro. Administration of EGFL6 in the rat DO model promoted CD31hiEMCNhi type H-positive capillary formation associated with enhanced bone formation. Type H vessels were the referred subtype involved during DO stimulated by EGFL6.

Conclusion
EGFL6 enhanced the osteogenic differentiation potential of BMSCs and accelerated bone regeneration by stimulating angiogenesis. Thus, increasing EGFL6 secretion appeared to underpin the therapeutic benefit by promoting angiogenesis-coupled bone formation. These results imply that boosting local concentrations of EGFL6 may represent a new strategy for the treatment of compromised fracture healing and bone defect restoration.