bluuebunny/crossref_metadata_2025_split huggingface dataset:
Control of hippocampal prothrombin kringle‐2 (pKr‐2) expression reduces neurotoxic symptoms in five familial Alzheimer's disease mice
Authors: Kim Sehwan , Moon Gyeong Joon , Kim Hyung Jun , Kim Do‐Geun , Kim Jaekwang , Nam Youngpyo , Sharma Chanchal , Leem Eunju , Lee Shinrye , Kim Kyu‐Sung , Ha Chang Man , McLean Catriona , Jin Byung Kwan , Shin Won‐Ho , Kim Dong Woon , Oh Yong‐Seok , Hong Chang‐Won , Kim Sang Ryong 
Published: September 2021

Background and PurposeThere is a scarcity of information regarding the role of prothrombin kringle‐2 (pKr‐2), which can be generated by active thrombin, in hippocampal neurodegeneration and Alzheimer's disease (AD).Experimental ApproachTo assess the role of pKr‐2 in association with the neurotoxic symptoms of AD, we determined pKr‐2 protein levels in post‐mortem hippocampal tissues of patients with AD and the hippocampi of five familial AD (5XFAD) mice compared with those of age‐matched controls and wild‐type (WT) mice, respectively. In addition, we investigated whether the hippocampal neurodegeneration and object memory impairments shown in 5XFAD mice were mediated by changes to pKr‐2 up‐regulation.Key ResultsOur results demonstrated that pKr‐2 was up‐regulated in the hippocampi of patients with AD and 5XFAD mice, but was not associated with amyloid‐β aggregation in 5XFAD mice. The up‐regulation of pKr‐2 expression was inhibited by preservation of the blood–brain barrier (BBB) via addition of caffeine to their water supply or by treatment with rivaroxaban, an inhibitor of factor Xa that is associated with thrombin production. Moreover, the prevention of up‐regulation of pKr‐2 expression reduced neurotoxic symptoms, such as hippocampal neurodegeneration and object recognition decline due to neurotoxic inflammatory responses in 5XFAD mice.Conclusion and ImplicationsWe identified a novel pathological mechanism of AD mediated by abnormal accumulation of pKr‐2, which functions as an important pathogenic factor in the adult brain via blood brain barrier (BBB) breakdown. Thus, pKr‐2 represents a novel target for AD therapeutic strategies and those for related conditions.
Liquid biopsy of cerebrospinal fluid for MYD88 L265P mutation is useful for diagnosis of central nervous system lymphoma
Authors: Yamagishi Yuki , Sasaki Nobuyoshi , Nakano Yoshiko , Matushita Yuko , Omura Takaki , Shimizu Saki , Saito Kuniaki , Kobayashi Keiichi , Narita Yoshitaka , Kondo Akihide , Shiokawa Yoshiaki , Nagane Motoo , Ichimura Koichi 
Published: September 2021

AbstractThe current standard of diagnosing central nervous system (CNS) lymphoma is stereotactic biopsy, however the procedure has a risk of surgical complication. Liquid biopsy of the CSF is a less invasive, non‐surgical method that can be used for diagnosing CNS lymphoma. In this study, we established a clinically applicable protocol for determining mutations in MYD88 in the CSF of patients with CNS lymphoma. CSF was collected prior to the start of chemotherapy from 42 patients with CNS lymphoma and matched tumor specimens. Mutations in MYD88 in 33 tumor samples were identified using pyrosequencing. Using 10 ng each of cellular DNA and cell‐free DNA (cfDNA) extracted from the CSF, the MYD88 L265P mutation was detected using digital PCR. The conditions to judge mutation were rigorously determined. The median Target/Total value of cases with MYD88 mutations in the tumors was 5.1% in cellular DNA and 22.0% in cfDNA. The criteria to judge mutation were then determined, with a Target/Total value of 0.25% as the cutoff. When MYD88 mutations were determined based on these criteria, the sensitivity and specificity were 92.2% and 100%, respectively, with cellular DNA; and the sensitivity and specificity were 100% with cfDNA. Therefore, the DNA yield, mutated allele fraction, and accuracy were significantly higher in cfDNA compared with that in cellular DNA. Taken together, this study highlights the importance of detecting the MYD88 L265P mutation in cfDNA of the CSF for diagnosing CNS lymphoma using digital PCR, a highly accurate and clinically applicable method.
Quantifying the road‐effect zone for a critically endangered primate
Authors: Andrasi Balint , Jaeger Jochen A.G. , Heinicke Stefanie , Metcalfe Kristian , Hockings Kimberley J. 
Published: September 2021

AbstractThe global road network is expanding at an unprecedented rate, threatening the persistence of many species. Yet, even for the most endangered wildlife, crucial information on the distance up to which roads impact species abundance is lacking. Here we use ecological threshold analysis to quantify the road‐effect zone (REZ) for the critically endangered western chimpanzee (Pan troglodytes verus). We found: (1) the REZ extends 5.4 km (95% CI [4.9–5.8 km]) from minor roads and 17.2 km (95% CI [15.8–18.6]) from major roads, the latter being more than three times wider than a previous estimate of the average REZ for mammals; and (2) only 4.3% of the chimpanzees’ range is not impacted by existing roads. These findings reveal the high sensitivity and susceptibility of nonhuman primates to roads across West Africa, a region undergoing rapid development, and can inform the implementation of more effective guidelines to mitigate road impacts.
Safety and clinical efficacy of the double switch from originator infliximab to biosimilars CT‐P13 and SB2 in patients with inflammatory bowel diseases (SCESICS): A multicenter cohort study
Authors: Mazza Stefano , Piazza O. Sed Nicole , Conforti Francesco Simone , Fascì Alberto , Rimondi Alessandro , Marinoni Beatrice , Casini Valentina , Ricci Chiara , Munari Francesca , Pirola Lorena , Invernizzi Pietro , Girelli Carlo , Lupinacci Guido , Pastorelli Luca , Cavallaro Flaminia , Ferraris Luca , Colucci Alice , Amato Arnaldo , Eugenio Tontini Gian , Vecchi Maurizio , Fiorino Gionata , Caprioli Flavio 
Published: September 2021

AbstractData regarding double switching from originator infliximab (IFX) to IFX biosimilars in inflammatory bowel diseases (IBDs) are lacking. The purpose of this study was to evaluate the safety and efficacy of switching from originator IFX to CT‐P13 and subsequently to SB2 (double switch) in patients with IBD. Patients undergoing IFX‐double switch in eight Centers in Lombardy (Italy) from November 2018 to May 2019 were retrospectively analyzed. The IFX discontinuation rate, incidence and type of adverse events (AEs), and clinical remission rate were recorded. A comparison with a control group of patients with IBD single‐switched from originator IFX to CT‐P13 was performed, before and after an inverse probability of treatment weighting (IPTW)‐based propensity score analysis. Fifty‐two double‐switched patients with IBD were enrolled. The 24‐ and 52‐week proportions of patients continuing on IFX therapy following the second switch (CTP13 → SB2) were 98% (95% confidence interval [CI] 94%–100%) and 90% (95% CI 81%–99%), respectively. Four patients experienced a total of five AEs, all graded 1–3 according to Common Terminology Criteria for Adverse Events (CTCAE). No infusion reactions were observed. The 24‐week and follow‐up end clinical remission rates following the second switch were 94% and 88%, respectively. No differences were observed in the safety and efficacy outcomes by comparing the double‐switch group with a single‐switch group of 66 patients with IBD; all these results were confirmed by IPTW‐adjusted analysis. The study suggests both the safety and efficacy of the double switch from originator IFX to CT‐P13 and SB2 in patients with IBD is maintained. This strategy may be associated with potential cost implications.
Pharmacokinetics and pharmacodynamics of itepekimab in healthy adults and patients with asthma: Phase I first‐in‐human and first‐in‐patient trials
Authors: Kosloski Matthew P. , Kalliolias George D. , Xu Christine R. , Harel Sivan , Lai Ching‐Ha , Zheng Wenjun , Davis John D. , Kamal Mohamed A. 
Published: September 2021

AbstractItepekimab is a monoclonal antibody that targets interleukin (IL‐33) and has been shown to reduce airway inflammation and associated tissue damage in preclinical studies. We assessed the safety, tolerability, pharmacokinetics (PKs), and pharmacodynamic profiles of single‐ascending and multiple‐ascending doses of itepekimab in two randomized, double‐blind, placebo‐controlled phase I studies. Healthy adults (N = 40) were randomized to the single‐dose study and patients with moderate asthma (N = 23) to the multiple‐dose study. Itepekimab was administered intravenously (0.3, 1, 3, or 10 mg/kg infusion) or subcutaneously (150 mg) in the single‐dose study and subcutaneously (75 or 150 mg weekly for 4 weeks) in the multiple‐dose study. Itepekimab exhibited linear PKs across studies and dose‐proportional increases in mean maximum concentration in serum and area under the concentration–time curve following single intravenous or multiple subcutaneous doses. Itepekimab demonstrated mean subcutaneous bioavailability of 59–73% and a long terminal half‐life (30.0–31.6 days). IL‐33 concentrations in most healthy participants and patients with asthma were undetectable at baseline. Following administration of itepekimab in both studies, total IL‐33 concentrations increased and blood eosinophils decreased, both with durable effect. Itepekimab was well‐tolerated in both studies with no detection of treatment‐emergent anti‐drug antibody responses.
Urticarial vasculitis: A potential signpost for multisystem inflammatory syndrome in children
Authors: Gosnell Hailey L. , Grider Douglas J. 
Published: September 2021

AbstractMultisystem inflammatory syndrome in children (MIS‐C) is a rare and serious complication of Sars‐Cov‐2 infection. Dermatologic manifestations are present in the majority of patients. Skin lesions found in children with MIS‐C are classified into four categories: morbilliform, reticulated, scarlatiniform, and urticarial lesions. Clinicopathologic characterization within these categories is limited. Thus, we present a clear example of an urticarial lesion in the context of MIS‐C with well‐documented clinicopathologic phenomena. A previously healthy 16‐year‐old female presented with 3 weeks of an itchy, burning rash initially presenting on her right forearm (and lasting greater than 24 hours without migration) before spreading diffusely. She also reported fever, cough, myalgias, nausea, and vomiting of 4 weeks' duration. Physical examination revealed an edematous, maculopapular, nonblanching, erythematous rash covering the patient's upper extremities, abdomen, back, anterior thighs, and face. The patient tested positive for COVID‐19. A low‐grade leukocytoclastic vasculitis was noted along with intraluminal fibrin and rare microthrombi in vessels of the mid to deep dermis. The patient was diagnosed with MIS‐C and urticarial vasculitis. She was treated with steroids and naproxen for subsequent MIS‐C flares. Dapsone treatment was started for the urticarial vasculitis.
Gradients of genetic diversity and differentiation across the distribution range of a Mediterranean coral: Patterns, processes and conservation implications
Authors: Ledoux Jean‐Baptiste , Ghanem Raouia , Horaud Mathilde , López‐Sendino Paula , Romero‐Soriano Valèria , Antunes Agostinho , Bensoussan Nathaniel , Gómez‐Gras Daniel , Linares Cristina , Machordom Annie , Ocaña Oscar , Templado José , Leblois Raphaêl , Ben Souissi Jamila , Garrabou Joaquim 
Published: September 2021

AbstractAimHow historical and contemporary eco‐evolutionary processes shape the patterns of genetic diversity and differentiation across species’ distribution range remains an open question with strong conservation implications. Focusing on the orange stony coral, Astroides calycularis, we (a) characterized the pattern of neutral genetic diversity across the distribution range; (b) gave insights into the underlying processes; and (c) discussed conservation implications with emphasis on a national park located on a hotspot of genetic diversity.LocationSouth Mediterranean Sea and Zembra National Park.MethodsWe combined new data from 12 microsatellites in 13 populations located in the Centre and in the Western Periphery of the distribution range with a published dataset including 16 populations from the Western and Eastern Peripheries. We analysed the relationship among parameters of genetic diversity (He, Ar(g)) and structure (population‐specific FST) and two measures of geographic peripherality. We compared two estimators of pairwise genetic structure (GST, DEST) across the distribution range. The evolutionary and demographic history of the populations following the Last Glacial Maximum was reconstructed using approximate Bayesian computations and maximum‐likelihood analyses. We inferred the contemporary connectivity among populations from Zembra National Park and with the neighbouring area of Cap Bon.ResultsWe demonstrate a decrease in genetic diversity and an increase in genetic differentiation from the Centre to the Eastern and Western Peripheries of the distribution range. Populations from Zembra show the highest genetic diversity reported in the species. We identified a spillover effect towards Cap Bon.Main conclusionsThe patterns of genetic diversity and differentiation are most likely explained by “the postglacial range expansion hypothesis” rather than the “central–peripheral hypothesis.” Enforcement of conservation measures should be considered to protect this genetic diversity pattern, in particular when considering the low effective population size inferred at many sites.
Long‐term outcomes of standardized colonic stenting using WallFlex as a bridge to surgery: Multicenter prospective cohort study
Authors: Kuwai Toshio , Tamaru Yuzuru , Kusunoki Ryusaku , Yoshida Shuntaro , Matsuzawa Takeaki , Isayama Hiroyuki , Maetani Iruru , Shimada Mamoru , Yamada Tomonori , Saito Shuji , Tomita Masafumi , Koizumi Koichi , Shiratori Toshiyasu , Enomoto Toshiyuki , Saida Yoshihisa 
Published: September 2021

ObjectivesThe oncological outcomes, especially high recurrence rate, of bridge‐to‐surgery (BTS) self‐expandable metallic stent (SEMS) placement remain concerning, emphasizing the necessity of standardized SEMS placement. However, its impact on long‐term BTS outcomes is unknown. We investigated the long‐term outcomes of BTS colonic stenting using standardized SEMS placement.MethodsThis prospective, multicenter cohort study conducted at 46 hospitals in Japan (March 2012 to October 2013) included consecutive patients with stage II and III obstructive colorectal cancer managed with BTS SEMS placement. The SEMS placement technique was standardized by information dissemination among the participating hospitals. The primary outcome was overall survival (OS) after SEMS placement, and the secondary outcomes were relapse‐free survival (RFS), recurrence, and short‐term outcomes of SEMS placement and surgery.ResultsThe 1‐, 3‐, and 5‐year OS rates were 94.1%, 77.4%, and 67.4% (Kaplan–Meier), respectively, with high technical success (99.0%, 206/208) and low perforation (1.9%, 4/208) rates. The 1‐, 3‐, and 5‐year RFS rates were 81.6%, 65.6%, and 57.9% (Kaplan–Meier), respectively, and the overall recurrence rate was 31.0% (62/200). The RFS rate was significantly poorer in patients with perforation (n = 4) than in those without perforation (n = 196) (log‐rank P = 0.017); moreover, perforation was identified as an independent factor affecting RFS (hazard ratio 3.31; 95% confidence interval 1.03–10.71, multivariate Cox regression).ConclusionThis large, prospective, multicenter study revealed satisfactory long‐term outcomes of BTS colonic stenting using a standardized SEMS insertion method, which might be specifically due to the reduced perforation rate. (UMIN000007953).
Hyperbaric oxygen via mediating SIRT1‐induced deacetylation of HMGB1 improved cReperfusion inj/reperfusion injury
Authors: Zhao Peng‐Cheng , Xu Shao‐Nian , Huang Zhen‐Shan , Jiang Guo‐Wei , Deng Peng‐Cheng , Zhang Yong‐Ming 
Published: September 2021

AbstractIschemic stroke leads to severe neurological dysfunction in adults. Hyperbaric oxygen (HBO) induces tolerance to cReperfusion inj/reperfusion (I/R) injury. Therefore, our aims were to investigate whether SIRT1 participates in regulatingin the neuro‐protective effect of HBO in a cerebral I/R model and its mechanism. Mice N2a cells were used to construct an oxygen deprivation/reperfusion (OGD/R) model to simulate in vitro brain I/R injury and to evaluate the role of HBO in OGD/R stimulated cells. Cell proliferation was detected using MTT, and apoptosis was determined by flow cytometry. ELISA was used to measure the concentration of TNF‐α, IL‐1β and IL‐6 related inflammatory factors. RT‐qPCR and western blot assays were performed to test the expression of SIRT1. Immunoprecipitation was used to detect acetylation of HMGB1. Expression of SIRT1 was obviously reduced after OGD/R treatment in N2a cells, while SIRT1 was obviously enhanced in HBO treated cells. Moreover, knockdown of SIRT1 induced neuro‐inflammation damage in cells and HBO effectively improved the inflammatory response in OGD/R treated cells by affecting SIRT1 levels. Furthermore, HBO induced the deacetylation of HMGB1 via regulating SIRT1. Interestingly, HBO via regulating the SIRT1‐induced HMGB1 deacetylation and suppressing MMP‐9 improved ischemic brain injury. HBO regulated ischemic brain injury via regulation of SIRT1‐induced HMGB1 deacetylation, making it a potential treatment for ischemic brain injury treatment.
Effect of phosphate sorption on soil pH
Authors: Barrow N. J. , Debnath Abhijit , Sen Arup 
Published: September 2021

AbstractThe effect of reaction between soil and phosphate on pH has not previously been explored or explained. We incubated samples of a soil with calcium carbonate to give a range of from 4.2 to 7.2, and then measured the change in pH when these samples were reacted with phosphate solutions. These solutions were at the same pH as the soil to which they were added. We also measured exchangeable cations and cation exchange capacity. At low pH, reaction with phosphate increased pH; at high pH it decreased it. These effects are a consequence of the way that the charge on the phosphate molecules is distributed. Reaction with phosphate conveys negative charge to the soil. This charge may be located partly on the surface side of the adsorbed phosphorus molecule and partly on the solution side; that is either ‘inside’ or ‘outside’. At low pH the electric potential before reaction is less negative than at higher pH and it is easy to increase the negative charge inside the adsorbed phosphate molecules. Changes in charge inside the phosphorus atom have a large effect on potential; a small amount of charge is required to achieve the necessary electric potential. The charge conveyed to the surface is less than the mean charge of the ions in solution and the pH therefore increases. At high pH, because of the more‐negative potential, it is more difficult to increase the negative charge inside the adsorbed phosphorus atom. A larger fraction of the charge is therefore located outside it. A large amount of charge is required to achieve the necessary electric potential. This charge is greater than the mean charge on the ions in solution and the pH therefore decreases. The cation exchange capacity and the exchangeable cations reflect the charge inside the adsorbed phosphate molecule. At low to medium initial pH, reaction with phosphate did not decrease pH. The decreases in pH that are sometimes observed following application of phosphate are due to ancillary effects.Highlights
The effect of reaction with phosphate on soil pH is not well understood.
At low pH, reaction with phosphate increased soil pH; at high pH, it decreased it.
These effects occur because the distribution of the charge on adsorbed phosphate changes with pH.
These differences occur because of differences in the electrical potential.
Environmental sound classification using convolution neural networks with different integrated loss functions
Authors: Das Joy Krishan , Chakrabarty Amitabha , Piran Md. Jalil 
Published: September 2021

AbstractThe hike in the demand for smart cities has gathered the interest of researchers to work on environmental sound classification. Most researchers' goal is to reach the Bayesian optimal error in the field of audio classification. Nonetheless, it is very baffling to interpret meaning from a three‐dimensional audio and this is where different types of spectrograms become effective. Using benchmark spectral features such as mel frequency cepstral coefficients (MFCCs), chromagram, log‐mel spectrogram (LM), and so on audio can be converted into meaningful 2D spectrograms. In this paper, we propose a convolutional neural network (CNN) model, which is fabricated with additive angular margin loss (AAML), large margin cosine loss (LMCL) and a‐softmax loss. These loss functions proposed for face recognition, hold their value in the other fields of study if they are implemented in a systematic manner. The mentioned loss functions are more dominant than conventional softmax loss when it comes to classification task because of its capability to increase intra‐class compactness and inter‐class discrepancy. Thus, with MCAAM‐Net, MCAS‐Net and MCLCM‐Net models, a classification accuracy of 99.60%, 99.43% and 99.37% is achieved on UrbanSound8K dataset respectively without any augmentation. This paper also demonstrates the benefit of stacking features together and the above‐mentioned validation accuracies are achieved after stacking MFCCs and chromagram on the x‐axis. We also visualized the clusters formed by the embedded vectors of test data for further acknowledgement of our results, after passing it through different proposed models. Finally, we show that the MCAAM‐Net model achieved an accuracy of 99.60% on UrbanSound8K dataset, which outperforms the benchmark models like TSCNN‐DS, ADCNN‐5, ESResNet‐Attention, and so on that are introduced over the recent years.
Scoping review: Facilitators and barriers in the adoption of teledentistry among older adults
Authors: Tan Sharon Hui Xuan , Lee Cheryl Ker Jia , Yong Chee Weng , Ding Yew Yoong 
Published: September 2021

AbstractObjective/BackgroundAccess to oral health care among older adults is a key issue in society, which has been exacerbated by social distancing measures and lockdowns during the COVID‐19 pandemic. Older adults would greatly benefit from teledentistry, yet little information exists on the enablers and challenges of adopting this technology for use with this group. The aim of this scoping review is to summarise the applications and key factors associated with the adoption of teledentistry among older adults.Materials and methodsThis scoping review was developed in accordance with Arksey and O’Malley's five‐stage framework and the Joanna Briggs Institute scoping review protocol guidelines. Publications on teledentistry involving direct clinical services for older adults aged 60 and above were included. Publications that focused solely on teleeducation were excluded. A systematic search was carried out on major electronic databases until 25 August 2020. Out of 1084 articles screened, 25 articles were included. Facilitators and barriers were categorised using the socio‐ecological model.Results/DiscussionTeleconsultation and telediagnosis were the most reported applications of teledentistry among older adults. Reported policy‐level factors were data privacy issues (n = 7) and regulations (n = 17). Community‐level facilitators and barriers included the availability of resources (n = 15) and support (n = 3). Familiar care settings (n = 2) and effective administration (n = 20) were key organisational‐level factors. Staff attitudes and education (n = 23) and individual patient knowledge, attitudes and practices (n = 10) can influence teledentistry adoption while complex medical conditions (n = 8) may pose a challenge.ConclusionKey factors in the uptake of teledentistry among older adults span across policy, community, organisational, interpersonal and individual factors. Commonly reported barriers included technical issues, lack of funding, consent issues and cognitive impairments.