bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of TDP-43 proteinopathy, cerebral amyloid angiopathy, and Lewy bodies with cognitive impairment in individuals with or without Alzheimer’s disease neuropathology
Authors: Thomas David X. , Bajaj Sumali , McRae-McKee Kevin , Hadjichrysanthou Christoforos , Anderson Roy M. , Collinge John 
Published: September 2020

AbstractAlzheimer’s disease patients typically present with multiple co-morbid neuropathologies at autopsy, but the impact of these pathologies on cognitive impairment during life is poorly understood. In this study, we developed cognitive trajectories for patients with common co-pathologies in the presence and absence of Alzheimer’s disease neuropathology. Cognitive trajectories were modelled in a Bayesian hierarchical regression framework to estimate the effects of each neuropathology on cognitive decline as assessed by the mini-mental state examination and the clinical dementia rating scale sum of boxes scores. We show that both TDP-43 proteinopathy and cerebral amyloid angiopathy associate with cognitive impairment of similar magnitude to that associated with Alzheimer’s disease neuropathology. Within our study population, 63% of individuals given the ‘gold-standard’ neuropathological diagnosis of Alzheimer’s disease in fact possessed either TDP-43 proteinopathy or cerebral amyloid angiopathy of sufficient severity to independently explain the majority of their cognitive impairment. This suggests that many individuals diagnosed with Alzheimer’s disease may actually suffer from a mixed dementia, and therapeutics targeting only Alzheimer’s disease-related processes may have severely limited efficacy in these co-morbid populations.
Micromorphological details and identification of chitinous wall structures in Rapana venosa (Gastropoda, Mollusca) egg capsules
Authors: Schröder Verginica , Rău Ileana , Dobrin Nicolae , Stefanov Constanţa , Mihali Ciprian-Valentin , Pădureţu Carla-Cezarina , Apetroaei Manuela Rossemary 
Published: September 2020

AbstractThe present study evaluated the structural and ultrastructural characteristics of Rapana venosa egg capsules, starting from observations of their antifouling activity and mechanical resistance to water currents in mid-shore habitats. Optical microscopy, epifluorescence, and electron microscopy were used to evaluate the surface and structure of the R. venosa egg capsules. These measurements revealed an internal multilamellar structure of the capsule wall with in-plane distributions of layers with various orientations. It was found that the walls contained vacuolar structures in the median layer, which provided the particular characteristics. Mechanical, viscoelastic and swelling measurements were also carried out. This study revealed the presence and distribution of chitosan in the capsule of R. venosa. Chitosan identification in the egg capsule wall structure was carried out through SEM–EDX measurements, colorimetric assays, FT-IR spectra and physical–chemical tests. The biopolymer presence in the capsule walls may explain the properties of their surfaces as well as the mechanical resistance of the capsule and its resistance to chemical variations in the living environment.
miRNALoc: predicting miRNA subcellular localizations based on principal component scores of physico-chemical properties and pseudo compositions of di-nucleotides
Authors: Meher Prabina Kumar , Satpathy Subhrajit , Rao Atmakuri Ramakrishna 
Published: September 2020

AbstractMicroRNAs (miRNAs) are one kind of non-coding RNA, play vital role in regulating several physiological and developmental processes. Subcellular localization of miRNAs and their abundance in the native cell are central for maintaining physiological homeostasis. Besides, RNA silencing activity of miRNAs is also influenced by their localization and stability. Thus, development of computational method for subcellular localization prediction of miRNAs is desired. In this work, we have proposed a computational method for predicting subcellular localizations of miRNAs based on principal component scores of thermodynamic, structural properties and pseudo compositions of di-nucleotides. Prediction accuracy was analyzed following fivefold cross validation, where ~ 63–71% of AUC-ROC and ~ 69–76% of AUC-PR were observed. While evaluated with independent test set, > 50% localizations were found to be correctly predicted. Besides, the developed computational model achieved higher accuracy than the existing methods. A user-friendly prediction server “miRNALoc” is freely accessible athttp://cabgrid.res.in:8080/mirnaloc/, by which the user can predict localizations of miRNAs.
Deciphering the secretome of leukocyte-platelet rich fibrin: towards a better understanding of its wound healing properties
Authors: Hermida-Nogueira Lidia , Barrachina María N. , Morán Luis A. , Bravo Susana , Diz Pedro , García Ángel , Blanco Juan 
Published: September 2020

AbstractLeukocyte-platelet rich fibrin (L-PRF) is extensively used in the dentistry field and other clinical scenarios due to its regeneration properties. The goal of the present study was to depict the L-PRF secretome and how it changes over time. We obtained L-PRF membranes and cultured them in DMEM. The secretome was collected at days 3, 7 and 21. The secretome at day 3 was analysed by LC–MS/MS and differences over time were analysed by Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH). Overall, 705 proteins were identified in the secretome of L-PRF membranes after 3 days of culture, including growth factors (EGF, PDGFA) and proteins related to platelet and neutrophil degranulation. A total of 202 differentially secreted proteins were quantified by SWATH when comparing secretomes at days 3, 7 and 21. Most of them were enriched at day 3 such as MMP9, TSP1 and CO3. On the contrary, fibrinogen and CATS were found down-regulated at day 3. Growth factor and western blotting analysis corroborated the proteomic results. This is the most detailed proteome analysis of the L-PRF secretome to date. Proteins and growth factors identified, and their kinetics, provide novel information to further understand the wound healing properties of L-PRF.
Differences between young and older adults in physiological and subjective responses to emotion induction using films
Authors: Fernández-Aguilar Luz , Latorre José M. , Martínez-Rodrigo Arturo , Moncho-Bogani José V. , Ros Laura , Latorre Pablo , Ricarte Jorge J. , Fernández-Caballero Antonio 
Published: September 2020

AbstractEmotional response in aging is typically studied using the dimensional or the discrete models of emotion. Moreover, it is typically studied using subjective or physiological variables but not using both perspectives simultaneously. Additionally, tenderness is neglected in emotion induction procedures with older adults, with the present work being the first to include the study of physiological tenderness using film clips. This study integrated two separate approaches to emotion research, comparing 68 younger and 39 older adults and using a popular set of film clips to induce tenderness, amusement, anger, fear, sadness and disgust emotions. The direction of subjective emotional patterns was evaluated with self-reports and that of physiological emotional patterns was evaluated with a wearable emotion detection system. The findings suggest a dual-process framework between subjective and physiological responses, manifested differently in young and older adults. In terms of arousal, the older adults exhibited higher levels of subjective arousal in negative emotions and tenderness while young adults showed higher levels of physiological arousal in these emotions. These findings yield information on the multidirectionality of positive and negative emotions, corroborating that emotional changes in the adult lifespan appear to be subject to the relevance of the emotion elicitor to each age group.
Benefits of tunnel handling persist after repeated restraint, injection and anaesthesia
Authors: Henderson Lindsay J. , Dani Bridgette , Serrano Esme M. N. , Smulders Tom V. , Roughan Johnny V. 
Published: September 2020

AbstractMillions of mice are used every year for scientific research, representing the majority of scientific procedures conducted on animals. The standard method used to pick up laboratory mice for general husbandry and experimental procedures is known as tail handling and involves the capture, elevation and restraint of mice via their tails. There is growing evidence that, compared to non-aversive handling methods (i.e. tunnel and cup), tail handling increases behavioural signs of anxiety and induces anhedonia. Hence tail handling has a negative impact on mouse welfare. Here, we investigated whether repeated scruff restraint, intraperitoneal (IP) injections and anaesthesia negated the reduction in anxiety-related behaviour in tunnel compared with tail handled BALB/c mice. We found that mice which experienced repeated restraint spent less time interacting with a handler compared to mice that were handled only. However, after repeated restraint, tunnel handled mice showed increased willingness to interact with a handler, and reduced anxiety in standard behavioural tests compared with tail handled mice. The type of procedure experienced (IP injection or anaesthesia), and the duration after which behaviour was measured after a procedure affected the willingness of mice to interact with a handler. Despite this, compared with tail handling, tunnel handling reduced anxiety in standard behavioural tests and increased willingness to interact with a handler within hours after procedures. This suggests that the welfare benefits of tunnel handling are widely applicable and not diminished by the use of other putatively more invasive procedures that are frequently used in the laboratory. Therefore, the simple refinement of replacing tail with tunnel handling for routine husbandry and procedures will deliver a substantial improvement for mouse welfare and has the potential for improving scientific outcomes.
Keratin 17-positive Civatte bodies in oral lichen planus—distribution variety, diagnostic significance and histopathogenesis
Authors: Abé Tatsuya , Kitagawa Norio , Yoshimoto Shohei , Maruyama Satoshi , Yamazaki Manabu , Inai Tetsuichiro , Hashimoto Shuichi , Saku Takashi 
Published: September 2020

AbstractAlthough emergence of keratin 17 (K17) and reciprocal loss of K13 are immunohistochemical hallmarks for oral mucosal malignancy, we report here findings of K17-positive (+) speckles, possibly equivalent to Civatte bodies, in benign oral lichen planus. Sixty-two biopsy samples from oral lichen planus cases were subjected to immunohistochemical examinations to analyze the distribution as well as histopathogenesis of Civatte bodies. K17 was irregularly positive among oral lichen planus-affected epithelial cells, and K17-positive (+) filamentous structures were irregularly distributed within the cytoplasm in confocal images. K17+ speckles were identified as Civatte bodies, and they were mainly distributed in the interface between epithelial cells and lymphocytic infiltrates (type A, 52.8%), followed by distribution within the epithelial layer (type B, 24.7%) or within the lamina propria with lymphocytic infiltration (type C, 22.5%). Apoptotic figures were often engulfed by macrophages and clearly distinguished from Civatte bodies by the presence TUNEL signals. These results indicate that K17 is a sensitive immunohistochemical marker for Civatte bodies and useful for differential diagnosis of oral lichen planus from other oral mucosal lesions. Civatte bodies are generated from denucleation of K17+ epithelial cells during the process of cell death via dyskeratosis, which is possibly related to blood capillary collapse.
Untargeted lipidomics reveals progression of early Alzheimer’s disease in APP/PS1 transgenic mice
Authors: Zhang Xueju , Liu Weiwei , Zan Jie , Wu Chuanbin , Tan Wen 
Published: September 2020

AbstractAlzheimer’s Disease (AD) is closely connected to aberrant lipid metabolism. However, how early AD-like pathology synchronously influences brain and plasma lipidome in AD mice remains unclear. The study of dynamic change of lipidome in early-stage AD mice could be of great interest for the discovery of lipid biomarkers for diagnosis and monitoring of early-stage AD. For the purpose, an untargeted lipidomic strategy was developed for the characterization of lipids (≤ 1,200 Da) perturbation occurring in plasma and brain in early-stage AD mice (2, 3 and 7 months) by ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry. Significant changes were detected in the levels of several lipid species including lysophospholipids, phosphatidylcholines (PCs), phosphatidylethanolamines (PEs) and Ceramides (Cers), as well as other related lipid compounds such as fatty acids (FAs), diacylglycerols (DGs) and triacylglycerols (TGs) in AD mice. In this sense, disorders of lipid metabolism appear to involve in multiple factors including overactivation of phospholipases and diacylglycerol lipases, decreased anabolism of lysophospholipids in plasma and PEs in plasma and brain, and imbalances in the levels of PCs, FAs and glycerides at different ages. We revealed the changing panels of potential lipid biomarkers with the development of early AD. The study raises the possibility of developing lipid biomarkers for diagnosis of early-stage AD.
Fungal attack on archaeological wooden artefacts in the Arctic—implications in a changing climate
Authors: Pedersen Nanna Bjerregaard , Matthiesen Henning , Blanchette Robert A. , Alfredsen Gry , Held Benjamin W. , Westergaard-Nielsen Andreas , Hollesen Jørgen 
Published: September 2020

AbstractClimate change is expected to accelerate the microbial degradation of the many extraordinary well-preserved organic archaeological deposits found in the Arctic. This could potentially lead to a major loss of wooden artefacts that are still buried within the region. Here, we carry out the first large-scale investigation of wood degradation within archaeological deposits in the Arctic. This is done based on wooden samples from 11 archaeological sites that are located along a climatic gradient in Western Greenland. Our results show that Ascomycota fungi are causing extensive soft rot decay at all sites regardless of climate and local environment, but the group is diverse and many of the species were only found once. Cadophora species known to cause soft rot in polar environments were the most abundant Ascomycota found and their occurrence in native wood samples underlines that they are present locally. Basidiomycota fungi were also present at all sites. In the majority of samples, however, these aggressive and potentially very damaging wood degraders have caused limited decay so far, probably due to unfavorable growth conditions. The presence of these wood degrading fungi suggests that archaeological wooden artefacts may become further endangered if climate change leads to more favorable growth conditions.
Suprabasin-null mice retain skin barrier function and show high contact hypersensitivity to nickel upon oral nickel loading
Authors: Nakazawa Shinsuke , Shimauchi Takatoshi , Funakoshi Atsuko , Aoshima Masahiro , Phadungsaksawasdi Pawit , Sakabe Jun-ichi , Asakawa Sanki , Hirasawa Noriyasu , Ito Taisuke , Tokura Yoshiki 
Published: September 2020

AbstractSuprabasin (SBSN) is expressed not only in epidermis but also in epithelial cells of the upper digestive tract where metals such as nickel are absorbed. We have recently shown that SBSN level is decreased in the stratum corneum and serum of atopic dermatitis (AD) patients, especially in intrinsic AD, which is characterized by metal allergy. By using SBSN-null (Sbsn–/–) mice, this study was conducted to investigate the outcome of SBSN deficiency in relation to AD. Sbsn–/– mice exhibited skin barrier dysfunction on embryonic day 16.5, but after birth, their barrier function was not perturbed despite the presence of ultrastructural changes in stratum corneum and keratohyalin granules. Sbsn–/– mice showed a comparable ovalbumin-specific skin immune response to wild type (WT) mice and rather lower contact hypersensitivity (CHS) responses to haptens than did WT mice. The blood nickel level after oral feeding of nickel was significantly higher in Sbsn–/– mice than in WT mice, and CHS to nickel was elevated in Sbsn–/– mice under nickel-loading condition. Our study suggests that the completely SBSN deficient mice retain normal barrier function, but harbor abnormal upper digestive tract epithelium that promotes nickel absorption and high CHS to nickel, sharing the features of intrinsic AD.
Brain mechanisms of eye contact during verbal communication predict autistic traits in neurotypical individuals
Authors: Jiang Jing , von Kriegstein Katharina , Jiang Jiefeng 
Published: September 2020

AbstractAtypical eye contact in communication is a common characteristic in autism spectrum disorders. Autistic traits vary along a continuum extending into the neurotypical population. The relation between autistic traits and brain mechanisms underlying spontaneous eye contact during verbal communication remains unexplored. Here, we used simultaneous functional magnetic resonance imaging and eye tracking to investigate this relation in neurotypical people within a naturalistic verbal context. Using multiple regression analyses, we found that brain response in the posterior superior temporal sulcus (pSTS) and its connectivity with the fusiform face area (FFA) during eye contact with a speaker predicted the level of autistic traits measured by Autism-spectrum Quotient (AQ). Further analyses for different AQ subclusters revealed that these two predictors were negatively associated with attention to detail. The relation between FFA–pSTS connectivity and the attention to detail ability was mediated by individuals’ looking preferences for speaker’s eyes. This study identified the role of an individual eye contact pattern in the relation between brain mechanisms underlying natural eye contact during verbal communication and autistic traits in neurotypical people. The findings may help to increase our understanding of the mechanisms of atypical eye contact behavior during natural communication.
Surgical hand hygiene and febrile urinary tract infections in endourological surgery: a single-centre prospective cohort study
Authors: Unno Rei , Taguchi Kazumi , Fujii Yasuhiro , Unno Naoko , Hamamoto Shuzo , Ando Ryosuke , Nakane Akihiro , Okada Atsushi , Kamiya Hiroyuki , Yasui Takahiro 
Published: September 2020

AbstractSurgical hand hygiene reduces the risk of surgical site infections (SSIs). SSIs are not considered an issue in endourological surgery, whereas febrile urinary tract infections (f-UTIs) and urological sepsis are becoming problematic. We wondered whether surgical hand hygiene is necessary for endourological surgery. Therefore, we aimed to evaluate the influence of surgical hand hygiene on f-UTI onset in endourological surgery by comparing procedures in which surgical hand hygiene with double gloving was used with those in which regular hand hygiene with double gloving was used between April 2016 and July 2020. In this prospective cohort study of 477 patients who underwent endourological surgeries, surgeons in the surgical hand hygiene and regular hygiene groups performed surgery on 259 and 218 patients, respectively. There was no significant difference in patient background, and multivariate analyses revealed no significant differences in f-UTI onset (odds ratio, 0.87; p = 0.74) between the two groups. In conclusion, regular hand hygiene with double gloving may be considered an alternative to surgical hand hygiene to prevent endourological f-UTIs, which could alter operational protocols for endourological surgery. Further studies are needed to validate our findings.
Cost-effectiveness analysis of pre-exposure prophylaxis for the prevention of HIV in men who have sex with men in South Korea: a mathematical modelling study
Authors: Choi Heun , Suh Jiyeon , Lee Woonji , Kim Jun Hyoung , Kim Jung Ho , Seong Hye , Ahn Jin Young , Jeong Su Jin , Ku Nam Su , Park Yoon Soo , Yeom Joon Sup , Kim Changsoo , Kwon Hee-Dae , Smith Davey M. , Lee Jeehyun , Choi Jun Yong 
Published: September 2020

AbstractIn February 2018, the Ministry of Food and Drug Safety in Korea approved tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) co-formulate for use in pre-exposure prophylaxis (PrEP) for the prevention of human immunodeficiency virus (HIV) infection. This study aimed to estimate the cost-effectiveness of PrEP in men who have sex with men (MSM), a major risk group emerging in Korea. A dynamic compartmental model was developed for HIV transmission and progression in MSM aged 15–64 years. With a combined model including economic analysis, we estimated averted HIV infections, changes in HIV prevalence, discounted costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). PrEP was evaluated in both the general MSM and high-risk MSM populations and was assumed to reduce infection risk by 80%. Implementing PrEP in all MSM would avert 75.2% HIV infections and facilitate a gain of 37,372 QALYs at a cost of $274,822 per QALY gained over 20 years relative to the status quo. Initiating PrEP in high-risk MSM with an average of eight partners per year (around 20% of MSM) would improve the cost-effectiveness, averting 78.0% HIV infections and add 29,242 QALYs at a cost of $51,597 per QALY gained, which is within the willingness-to-pay threshold for Korea of $56,000/QALY gained. This result was highly sensitive to annual PrEP costs, quality-of-life for people who are on PrEP, and initial HIV prevalence. Initiating PrEP in a larger proportion of MSM in Korea would prevent more HIV infections, but at an increasing cost per QALY gained. Focusing PrEP on higher risk MSM and any reduction in PrEP cost would improve cost-effectiveness.
Genome-wide association study for circulating fibroblast growth factor 21 and 23
Authors: Chuang Gwo-Tsann , Liu Pi-Hua , Chyan Tsui-Wei , Huang Chen-Hao , Huang Yu-Yao , Lin Chia-Hung , Lin Jou-Wei , Hsu Chih-Neng , Tsai Ru-Yi , Hsieh Meng-Lun , Lee Hsiao-Lin , Yang Wei-shun , Robinson-Cohen Cassianne , Hsiung Chia-Ni , Shen Chen-Yang , Chang Yi-Cheng 
Published: September 2020

AbstractFibroblast growth factors (FGFs) 21 and 23 are recently identified hormones regulating metabolism of glucose, lipid, phosphate and vitamin D. Here we conducted a genome-wide association study (GWAS) for circulating FGF21 and FGF23 concentrations to identify their genetic determinants. We enrolled 5,000 participants from Taiwan Biobank for this GWAS. After excluding participants with diabetes mellitus and quality control, association of single nucleotide polymorphisms (SNPs) with log-transformed FGF21 and FGF23 serum concentrations adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for body mass index (BMI) and a third model additionally adjusted for BMI and estimated glomerular filtration rate (eGFR) were used. A total of 4,201 participants underwent GWAS analysis. rs67327215, located within RGS6 (a gene involved in fatty acid synthesis), and two other SNPs (rs12565114 and rs9520257, located between PHC2-ZSCAN20 and ARGLU1-FAM155A respectively) showed suggestive associations with serum FGF21 level (P = 6.66 × 10–7, 6.00 × 10–7 and 6.11 × 10–7 respectively). The SNPs rs17111495 and rs17843626 were significantly associated with FGF23 level, with the former near PCSK9 gene and the latter near HLA-DQA1 gene (P = 1.04 × 10–10 and 1.80 × 10–8 respectively). SNP rs2798631, located within the TGFB2 gene, was suggestively associated with serum FGF23 level (P = 4.97 × 10–7). Additional adjustment for BMI yielded similar results. For FGF23, further adjustment for eGFR had similar results. We conducted the first GWAS of circulating FGF21 levels to date. Novel candidate genetic loci associated with circulating FGF21 or FGF23 levels were found. Further replication and functional studies are needed to support our findings.