bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pathogenic role of circulating Hashimoto's Thyroiditis‐derived TPO‐positive IgG on fetal loss in naïve mice
Authors: Borodina Elena , Katz Itai , Antonelli Alessandro , Gzgzyan Alexander M. , Dzhemlikhanova Liailia Kh , Ostrinski Yuri , Niauri Dariko , Khizroeva Jamilya , Bitsadze Victoria , Makatsariya Alexander , Tincani Angela , Nalli Cecilia , Churilov Leonid P. , Shovman Ora , Halpert Gilad , Blank Miri , Shoenfeld Yehuda , Amital Howard 
Published: September 2020

AbstractProblemAntibody‐mediated autoimmune diseases, such as autoimmune thyroid diseases (ATD), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS), often are associated with recurrent fetal loss. One of the ATD is Hashimoto's thyroiditis which recently showed association with complications of pregnancy with increased levels of circulating autoantibodies reactive with epitopes on thyroid tissue such as thyroid peroxidase (anti‐TPO). In retrospective study of sera analyses in patients with Hashimoto's thyroiditis, all patients had mainly elevated circulating anti‐TPO autoantibodies.AimWe assessed the potential of human anti‐TPO highly positive IgG, derived from patients with Hashimoto's thyroiditis sera associated with complications of pregnancy, to cause directly complications of pregnancy in murine model.Method of studyNaïve ICR female mice, infused intravenously with 100 μg of anti‐TPO‐positive IgG, showed increased fetal loss and embryo small for date (P < .001) in comparison with mice passively transferred with commercial IgG or PBS. Moreover, we observed embryos small for date in the mice passively transferred with anti‐TPO‐positive IgG, exemplified by reduced weight of embryos and placentae (P = .001). Histopathological examination revealed delay in fetal development in 50% cases of anti‐TPO‐positive IgG‐treated mice. Importantly, pathological changes in the transition zone, state of glycogen cells, and significant structural changes in the labyrinth part of placenta were observed in all anti‐TPO‐positive IgG samples.ConclusionThe current study shows in the first time, a direct proof of concept, on the association of human TPO‐positive IgG from Hashimoto's thyroiditis patients on fetal loss induction in murine model.
Interleukin‐4‐loaded hydrogel scaffold regulates macrophages polarization to promote bone mesenchymal stem cells osteogenic differentiation via TGF‐β1/Smad pathway for repair of bone defect
Authors: Zhang Jiankang , Shi Haitao , Zhang Nian , Hu Liru , Jing Wei , Pan Jian 
Published: September 2020

AbstractObjectiveTissue engineering is a promising strategy for repair of large bone defect. However, the immune system reactions to biological scaffold are increasingly being recognized as a crucial factor influencing regeneration efficacy. In this study, a bone‐bioactive hydrogel bead loaded with interleukin‐4 (IL‐4) was used to regulate macrophages polarization and accelerate bone regeneration.MethodsIL‐4‐loaded calcium‐enriched gellan gum (Ca‐GG + IL‐4) hydrogel beads were synthesised. And the effect on cell behaviour was detected. Furthermore, the effect of the Ca‐GG + IL‐4 hydrogel bead on macrophage polarization and the effect of macrophage polarization on bone mesenchymal stem cells (BMSCs) apoptosis and osteogenic differentiation were evaluated in vitro and in vivo.ResultsBMSCs were able to survive in the hydrogel regardless of whether IL‐4 was incorporated. Immunofluorescence staining and qPCR results revealed that Ca‐GG + IL‐4 hydrogel bead could promote M2 macrophage polarization and increase transforming growth factor (TGF)‐β1 expression level, which activates the TGF‐β1/Smad signalling pathway in BMSCs and promotes osteogenic differentiation. Moreover, immunohistochemical analysis demonstrated Ca‐GG + IL‐4 hydrogel bead could promote M2 macrophage polarization and reduce cell apoptosis in vivo. In addition, micro‐CT and immunohistochemical analysis at 12 weeks post‐surgery showed that Ca‐GG + IL‐4 hydrogel bead could achieve superior bone defect repair efficacy in vivo.ConclusionsThe Ca‐GG + IL‐4 hydrogel bead effectively promoted bone defect regeneration via regulating macrophage polarization, reducing cell apoptosis and promoting BMSCs osteogenesis through TGF‐β1/Smad pathway. Therefore, it is a promising strategy for repair of bone defect.
Prevalence of pain and interference with daily activities and sleep in adults with cerebral palsy
Authors: Rodby‐Bousquet Elisabet , Alriksson‐Schmidt Ann , Jarl Johan 
Published: September 2020

AimTo analyse the prevalence of pain, pain sites, pain severity, and pain interfering with work or daily activities and sleep in adults with cerebral palsy (CP).MethodThis was a cross‐sectional study based on data from 1591 adults (16–76y, median age 25y; 879 males, 712 females; Communication Function Classification System [CFCS] levels I–V) in the Swedish Cerebral Palsy Follow‐up Program. Pain severity was rated for several body sites and pain interference with activities/work and sleep was also evaluated. Logistic regression was used to estimate the odds ratios (ORs) of the factors associated with the prevalence of pain and pain interfering with activities/work or sleep.ResultsPain was reported in 1059 of 1591 adults; a higher proportion self‐reported pain (69.9%) compared to proxy‐reported pain (62.4%). More adults classified in CFCS level I (72.5%) reported pain compared to those in CFCS levels II to V (56.5–64.9%). Adults with severe/very severe pain had a sixfold risk of pain interfering with activity/work (OR=6.68; 95% CI 4.99–8.96) and sleep (OR=6.60; 95% CI 4.84–8.98).InterpretationTwo‐thirds of adults with CP experienced pain, which is likely to be underreported in individuals who do not communicate efficiently or rely on proxy reports. Pain strongly interfered with activities and sleep; thus, it must be assessed and treated more effectively.What this paper adds

Two‐thirds of adults with cerebral palsy (CP) experienced pain from a median of three body sites.

Pain is likely to be underreported in adults who do not communicate efficiently or rely on proxy reports.

Adults with CP in severe pain had a sixfold risk of pain interfering with activity/work and sleep.
Buried in the sand: Uncovering the ecological roles and importance of rays
Authors: Flowers Kathryn I. , Heithaus Michael R. , Papastamatiou Yannis P. 
Published: September 2020

AbstractRays (superorder Batoidea) are the most diverse group of elasmobranchs, and many are threatened with extinction. However, there remain areas where research on the ecology of this group is lacking, from trophic interactions to their importance to ecosystem structure and function. Such ecological insights are critical for predicting the potential consequences of changes in their population sizes. Our aim was to synthesize the existing ray ecology literature and identify key knowledge gaps in order to provide a framework for future research. Numerous studies describe ray diets, and the number of studies using biochemical methods to address ray trophic interactions is increasing. The implications of ray predator–prey interactions on population dynamics of prey and how ray foraging might influence ecosystem dynamics through bioturbation remain relatively unexplored, despite claims that rays are ecologically important because they are bioturbators and because of their potential to deplete stocks of commercially important bivalves. Therefore, to better integrate rays in our understanding of marine community dynamics, there is a need to: (i) combine behavioural data with dietary information to describe predator–prey interactions; (ii) understand how ray bioturbation affects biogeochemical cycles and infaunal communities; (iii) elucidate conditions under which rays might initiate or transmit trophic cascades through consumptive and non‐consumptive pathways; and (iv) consider anthropogenic influences on the ecological roles and importance of rays.
Interaction between and impact of IL‐6 genotype and alpha‐tocopherol levels on periodontal condition in aging individuals
Authors: Yoshihara Akihiro , Kaneko Noboru , Miyamoto Akane , Nohno Kaname 
Published: September 2020

AbstractBackground and ObjectivesFew studies have assessed the possible interaction between and impact of IL‐6 variants and serum α‐tocopherol levels on periodontal condition in older individuals. Here, we assessed the relationship between IL‐6 variants and serum α‐tocopherol levels on periodontal condition by considering effect modification.Material and MethodsAmong the study participants, 359 who were 71 years of age underwent a dental examination, biochemical analysis, and interview. After dividing the participants into tertiles based on serum α‐tocopherol levels, we conducted Poisson regression analysis to compare the prevalence rate ratio (PRR) for periodontal disease markers with the IL‐6 genotype (rs1800796) based on each tertile adjusted by the number of teeth present (offset).ResultsThe PRRs of the IL‐6 genotype for periodontal condition (probing pocket depth [PPD], clinical attachment level [CAL], and bleeding on probing [BOP]) which were adjusted by the number of teeth present (offset) were 1.17 (P < .001), 1.37 (P < .001), and 1.08 (P = .048), respectively. In addition, a significant association was found between the reciprocal number of PRRs of the IL‐6 genotype and three serum α‐tocopherol levels. The adjusted PRRs (± standard error) of the IL‐6 genotypes for PPD were 0.48 (0.12) for the first group (P < .001), 1.54 (0.04) for the second group (P < .001), and 2.11 (0.03) for the third group (P < .001); similar tendencies were seen for CAL and BOP.ConclusionThe results of this study suggest a potential association between the IL‐6 genotype and periodontal condition in relation to serum antioxidant concentrations.
Case of “relapsing” COVID‐19 in a kidney transplant recipient
Authors: MA Becky Mingyao , Hung Ivan Fan Ngai , Chan Gary Chi Wang , Tam Anthony Raymond , Chan Samuel Shung Kay , Wong Bonnie Chun Kwan , Fukuda Kenichiro , Ohno Takanori , Yuen Kwok Yung , Chan Tak Mao 
Published: September 2020

AbstractClinical outcomes of COVID‐19 vary considerably between patients. Little was known about the clinical course and optimal management of immunosuppressed patients infected with SARS‐CoV‐2. We report a kidney transplant recipient with COVID‐19 who presented with pneumonitis and acute kidney injury (AKI). She improved after reduction of immunosuppressive treatment and had two consecutive negative reverse transcription polymerase chain reaction (RT‐PCR) tests. Her respiratory tract samples turned positive again afterwards, and she was treated with lopinavir‐ritonavir. She had satisfactory virological and clinical response after a prolonged disease course. This case illustrates the risk of relapse or persisting shedding of SARS‐CoV‐2 in immunosuppressed patients, the important role of viral load monitoring in management, the challenges in balancing the risks of COVID‐19 progression and transplant rejection, and the pharmacokinetic interaction between immunosuppressive and antiviral medications.
Treatment of tinea capitis with topical 1% encapsulated terbinafine hydrochloride gel: A pilot study
Authors: Jerasutus Suthep , Vejjabhinanta Voraphol , Prapapan Ornicha 
Published: September 2020

AbstractBackground/ObjectiveOral antifungal agents are the mainstay of the therapy of pediatric tinea capitis. No approved topical medications for tinea capitis are found. We evaluated the therapeutic efficacy, safety, and tolerability of topical 1% encapsulated terbinafine hydrochloride gel for the treatment of pediatric tinea capitis.MethodsAn open‐label clinical trial was performed on 10 children with clinical and mycologically confirmed diagnosis of tinea capitis. Each child was prescribed topical 1% encapsulated terbinafine hydrochloride gel to be applied twice daily to the full scalp for 4 weeks. Clinical and mycological examinations were assessed 2 weeks after completion of treatment. Monitoring was performed for associated side effects during the treatment and follow‐up periods.ResultsTen male patients were enrolled with a mean age of 10.3 years. A cure rate of 80% (n = 8) was noted 2 weeks after treatment completion. An additional 20% (n = 2) had mycological cure with incomplete, but significant clinical improvement. No significant side effects were reported.ConclusionsThis preliminary study demonstrated that topical 1% encapsulated terbinafine hydrochloride gel was an effective treatment for tinea capitis in children.
METHYLENE BLUE REMOVAL USING COCONUT SHELL BIOCHAR SYNTHESIZED THROUGH MICROWAVE-ASSISTED PYROLYSIS
Authors: Nuryana Dwi , Alim Muhammad Fahrul Rahman , Yahayu Maizatulakmal , Ahmad Muhammad Abbas , Sulong Raja Safazliana Raja , Aziz Muhammad Fakhrul Syukri Abd , Prasetiawan Haniif , Zakaria Zainul Akmar , Kusumaningtyas Ratna Dewi 
Published: September 2020

Indonesia is the world’s second largest producer of coconut. This at the same time resulted in huge generation of coconut shell waste that need to be properly managed to prevent environmental contamination such as water, air and soil pollution. Current techniques of physical and thermal processing are time and energy consuming. This study reports on the conversion of coconut shell biomass into biochar using microwave-assisted pyrolysis (MAP). The MAP processes were carried out at different microwave power (550-650W) and residence time (15-25 minutes). Two of the highest biochar yields were obtained at 550W with the residence times of 15 minutes (91.31 wt%, termed as S1) and 20 minutes (83.88 wt%, termed as S2), respectively. Both values were higher than biochar yield obtained using conventional pyrolysis process i.e. 30.10 wt%. Both S1 and S2 showed considerable capacity to remove 0.6875 mg.g-1 and 0.5165 mg.g-1 methylene blue which had the initial concentration of 25 mg.L-1. The adsorption efficiencies of S1 and S2 biochars were 55.00% and 41.32%, respectively. Results obtained from the FTIR, FESEM and BET analysis also supported the methylene blue removal properties of both S1 and S2, respectively. As a conclusion, coconut shell showed potential as a useful raw material to produce biochar that can be used for methylene blue removal from solution. Nevertheless, more investigation need to be carried out prior to commercialization venture of the coconut-shell based biochar.
Down-regulation of PADI2 prevents proliferation and epithelial-mesenchymal transition in ovarian cancer through inhibiting JAK2/STAT3 pathway in vitro and in vivo, alone or in combination with Olaparib
Authors: Liu Lidong , Zhang Zhiwei , Zhang Guoxiang , Wang Ting , Ma Yingchun , Guo Wei 
Published: September 2020

Abstract
Background
Epithelial ovarian cancer (EOC) is the most lethal disease among female genital malignant tumors. Peptidylarginine deiminase type II(PADI II) has been shown to enhance a variety of cancers carcinogenesis, including ovarian cancer. The purpose of this study was to investigate the biological role of PADI2 in ovarian cancer (OC) and the relative mechanism.

Methods
Gene Expression Profiling Interactive Analysis (GEPIA) (https://gepia.pku.cn/) and ONCOMINE (https://www.oncomine.org/) were used to analyze PADI2 Gene Expression data. The survival curve for the PADI2 gene was generated by using the online Kaplan–Meier mapping site (https://www.kmplot.com/). We conducted MTT assay, cloning formation assay and EdU cell proliferation assay to detect the cell activity of PADI2 knockdown A2780 and SKOV3 ovarian cancer cells treated with Olaparib. Cell migration and invasion were observed by would healing and transwell assay. The pathway changes after the treatment of PADI2 were detected by transcriptome sequencing and western blot. The role of PADI2 combined with Olaparib treatment in vivo was studied in nude mouse model bearing ovarian cancer tumor.

Results
We investigated the role of PADI2 on EOC in vitro and in vivo. PADI2 was upregulated in ovarian cancer samples and high PADI2 expression was correlated with poor outcome. Downregulating PADI2 suppressed colony formation, proliferation, migration and invasion of A2780 and SKOV3 cells. Furthermore, downregulating PADI2 and Olaparib combination treatment attenuated the viability, migration and invasion of A2780 and SKOV3 cells. We identified differentially expressed genes in A2780-shPADI2 and SKOV3-shPADI2 cell by transcriptome sequencing analysis and verified that downregulating PADI2 and Olaparib combination treatment suppresses EMT and JAK2/STAT3 signaling pathway in A2780 and SKOV3 cells in vitro and in vivo.

Conclusions
Downregulation of PADI2 and Olaparib combination treatment attenuated the proliferation, migration and invasion of A2780 and SKOV3 cells by inhibiting the EMT through JAK2/STAT3 signaling pathway.
Novel role of mortalin in attenuating HIV-1 Tat-mediated astrogliosis
Authors: Priyanka  , Wadhwa Renu , Chaudhuri Rituparna , Nag Tapas Chandra , Seth Pankaj 
Published: September 2020

Abstract
Background
In human immunodeficiency virus-1 (HIV-1) infection, activation of astrocytes induces imbalance in physiological functions due to perturbed astrocytic functions that unleashes toxicity on neurons. This leads to inflammatory response finally culminating into neurocognitive dysfunction. In neuroAIDS, HIV-1 protein, transactivator of transcription (Tat) is detected in the cerebrospinal fluid of infected patients. Mortalin, a multifunctional protein, has anti-inflammatory role following its activation in various stress conditions. Recent studies demonstrate downregulation of mortalin in neurodegenerative diseases. Here, we explored the mechanisms of mortalin in modulating HIV-1 Tat-mediated neuroinflammation.

Methods
Expression of mortalin in autopsy section in normal and diseased individuals were examined using immunohistochemistry. To decipher the role of mortalin in HIV-1 Tat-induced activation, human fetal brain-derived astrocytes were transiently transfected with Tat and mortalin using expression vectors. HIV-1 Tat-mediated damage was analyzed using RT-PCR and western blotting. Modulatory role of mortalin was examined by coexpressing it with Tat, followed by examination of mitochondrial morphodynamics using biochemical assay and confocal and electron microscopy. Extracellular ATP release was monitored using luciferase assay. Neuroinflammation in astrocytes was examined using flow cytometry, dye based study, immunocytochemistry, immunoprecipitation, and western blotting. Indirect neuronal damage was also analyzed.

Results
HIV-1 Tat downregulates the expression of mortalin in astrocytes, and this is corroborated with autopsy sections of HIV-1 patients. We found that overexpression of mortalin with Tat reduced inflammation and also rescued astrocytic-mediated neuronal death. Using bioinformatics, we discovered that binding of mortalin with Tat leads to Tat degradation and rescues the cell from neuroinflammation. Blocking of proteosomal pathway rescued the Tat degradation and revealed the ubiquitination of Tat.

Conclusion
Overall, our data demonstrated the protective role of mortalin in combating HIV-1 Tat-mediated damage. We also showed that mortalin could degrade Tat through direct binding with HIV-1 Tat. Overexpression of mortalin in the presence of Tat could significantly reduce cytotoxic effects of Tat in astrocytes. Indirect neuronal death was also found to be rescued. Our in vitro findings were validated as we found attenuated expression of mortalin in the autopsy sections of HIV-1 patients.
Langat virus infection affects hippocampal neuron morphology and function in mice without disease signs
Authors: Cornelius Angela D. A. , Hosseini Shirin , Schreier Sarah , Fritzsch David , Weichert Loreen , Michaelsen-Preusse Kristin , Fendt Markus , Kröger Andrea 
Published: September 2020

Abstract
Background
Tick-borne encephalitis virus (TBEV) is an important human pathogen that can cause the serious illness tick-borne encephalitis (TBE). Patients with clinical symptoms can suffer from severe meningoencephalitis with sequelae that include cognitive disorders and paralysis. While less than 30% of patients with clinical symptoms develop meningoencephalitis, the number of seropositive individuals in some regions indicates a much higher prevalence of TBEV infections, either with no or subclinical symptoms. The functional relevance of these subclinical TBEV infections and their influence on brain functions, such as learning and memory, has not been investigated so far.

Methods
To compare the effect of low and high viral replication in the brain, wildtype and Irf-7−/− mice were infected with Langat virus (LGTV), which belongs to the TBEV-serogroup. The viral burden was analyzed in the olfactory bulb and the hippocampus. Open field, elevated plus maze, and Morris water maze experiments were performed to determine the impact on anxiety-like behavior, learning, and memory formation. Spine density of hippocampal neurons and activation of microglia and astrocytes were analyzed.

Results
In contrast to susceptible Irf-7−/− mice, wildtype mice showed no disease signs upon LGTV infection. Detection of viral RNA in the olfactory bulb revealed CNS infections in wildtype and Irf-7−/− mice. Very low levels of viral replication were detectable in the hippocampus of wildtype mice. Although wildtype mice develop no disease signs, they showed reduced anxiety-like behavior and impaired memory formation, whereas Irf-7−/− mice were not affected. This impairment was associated with a significant decrease in spine density of neurons in the hippocampal CA1 region of wildtype mice. Microglia activation and astrogliosis were detected in the hippocampus.

Conclusion
In this study, we demonstrate that subclinical infections by viruses from the TBEV-serogroup affected anxiety-like behavior. Virus replication in the olfactory bulb induced far-reaching effects on hippocampal neuron morphology and impaired hippocampus-dependent learning and memory formation.