bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein kinase C eta is activated in reactive astrocytes of an Alzheimer's disease mouse model: Evidence for its immunoregulatory function in primary astrocytes
Authors: Muraleedharan Amitha , Rotem‐Dai Noa , Strominger Itai , Anto Nikhil Ponnoor , Isakov Noah , Monsonego Alon , Livneh Etta 
Published: October 2020

AbstractAlzheimer's disease (AD) is the primary cause of age‐related dementia. Pathologically, AD is characterized by synaptic loss, the accumulation of β‐amyloid peptides and neurofibrillary tangles, glial activation, and neuroinflammation. Whereas extensive studies focused on neurons and activation of microglia in AD, the role of astrocytes has not been well‐characterized. Protein kinase C (PKC) was also implicated in AD; however, its role in astrocyte activation was not elucidated. Using the 5XFAD mouse model of AD, we show that PKC‐eta (PKCη), an astrocyte‐specific stress‐activated and anti‐apoptotic kinase, plays a role in reactive astrocytes. We demonstrate that PKCη staining is highly enriched in cortical astrocytes in a disease‐dependent manner and in the vicinity of amyloid‐β peptides plaques. Moreover, activation of PKCη, as indicated by its increased phosphorylation levels, is exhibited mainly in cortical astrocytes derived from adult 5XFAD mice. PKCη activation was associated with elevated levels of reactive astrocytic markers and upregulation of the pro‐inflammatory cytokine interleukin 6 (IL‐6) compared to littermate controls. Notably, inhibiting the kinase activity of PKCη in 5XFAD astrocyte cultures markedly increased the levels of secreted IL‐6—a phenomenon that was also observed in wild‐type astrocytes stimulated by inflammatory cytokines (e.g., TNFα, IL‐1). Similar increase in the release of IL‐6 was also observed upon inhibition of either the mammalian target of rapamycin (mTOR) or the protein phosphatase 2A (PP2A). Our findings suggest that the mTOR‐PKCη‐PP2A signaling cascade functions as a negative feedback loop of NF‐κB‐induced IL‐6 release in astrocytes. Thus, we identify PKCη as a regulator of neuroinflammation in AD.
Intrinsic DNA damage repair deficiency results in progressive microglia loss and replacement
Authors: Zhang Xiaoming , Heng Yang , Kooistra Susanne M. , van Weering Hilmar R. J. , Brummer Maaike L. , Gerrits Emma , Wesseling Evelyn M. , Brouwer Nieske , Nijboer Tjalling W. , Dubbelaar Marissa L. , Boddeke Erik W. G. M. , Eggen Bart J. L. 
Published: October 2020

AbstractThe DNA excision repair protein Ercc1 is important for nucleotide excision, double strand DNA break, and interstrand DNA crosslink repair. In constitutive Ercc1‐knockout mice, microglia display increased phagocytosis, proliferation and an enhanced responsiveness to lipopolysaccharide (LPS)‐induced peripheral inflammation. However, the intrinsic effects of Ercc1‐deficiency on microglia are unclear. In this study, Ercc1 was specifically deleted from Cx3cr1‐expressing cells and changes in microglia morphology and immune responses at different times after deletion were determined. Microglia numbers were reduced with approximately 50% at 2–12 months after Ercc1 deletion. Larger and more ramified microglia were observed following Ercc1 deletion both in vivo and in organotypic hippocampal slice cultures. Ercc1‐deficient microglia were progressively lost, and during this period, microglia proliferation was transiently increased. Ercc1‐deficient microglia were gradually replaced by nondeficient microglia carrying a functional Ercc1 allele. In contrast to constitutive Ercc1‐deficient mice, microglia‐specific deletion of Ercc1 did not induce microglia activation or increase their responsiveness to a systemic LPS challenge. Gene expression analysis suggested that Ercc1 deletion in microglia induced a transient aging signature, which was different from a priming or disease‐associated microglia gene expression profile.
Sex‐differences in network level brain dynamics associated with pain sensitivity and pain interference
Authors: Kim Junseok A. , Bosma Rachael L. , Hemington Kasey S. , Rogachov Anton , Osborne Natalie R. , Cheng Joshua C. , Dunkley Benjamin T. , Davis Karen D. 
Published: October 2020

AbstractNeural dynamics can shape human experience, including pain. Pain has been linked to dynamic functional connectivity within and across brain regions of the dynamic pain connectome (consisting of the ascending nociceptive pathway (Asc), descending antinociceptive pathway (Desc), salience network (SN), and the default mode network (DMN)), and also shows sex differences. These linkages are based on fMRI‐derived slow hemodynamics. Here, we utilized the fine temporal resolution of magnetoencephalography (MEG) to measure resting state functional coupling (FCp) related to individual pain perception and pain interference in 50 healthy individuals (26 women, 24 men). We found that pain sensitivity and pain interference were linked to within‐ and cross‐network broadband FCp across the Asc and SN. We also identified sex differences in these relationships: (a) women exhibited greater within‐network static FCp, whereas men had greater dynamic FCp within the dynamic pain connectome; (b) relationship between pain sensitivity and pain interference with FCp in women was commonly found in theta, whereas in men, these relationships were predominantly in the beta and low gamma bands. These findings indicate that dynamic interactions of brain networks underlying pain involve fast brain communication in men but slower communication in women.
Ipsilateral radiation for squamous cell carcinoma of the tonsil: American Radium Society appropriate use criteria executive summary
Authors: Tsai C. Jillian , Galloway Thomas J. , Margalit Danielle N. , Bakst Richard L. , Beadle Beth M. , Beitler Jonathan J. , Chang Steven , Chen Allen , Cooper Jay , Koyfman Shlomo A. , Ridge John A. , Robbins Jared , Truong Minh Tam , Yom Sue S. , Siddiqui Farzan 
Published: October 2020

AbstractBackgroundWe conducted the current systemic review to provide up‐to‐date literature summary and optimal evidence‐based recommendations for ipsilateral radiation for squamous cell carcinoma of the tonsil.MethodsWe performed literature search of peer‐reviewed journals through PubMed. The search strategy and subject‐specific keywords were developed based on the expert panel's consensus. Articles published from January 2000 to May 2020 with full text available on PubMed and restricted to the English language and human subjects were included. Several prespecified search terms were used to identify relevant publications and additional evidence published since the initial American College of Radiology Appropriateness Criteria Ipsilateral Tonsil Radiation recommendation was finalized in 2012. The full bibliographies of identified articles were reviewed and irrelevant studies were removed.ResultsThe initial search and review returned 46 citations. The authors added three citations from bibliographies, websites, or books not found in the literature search. Of the 49 citations, 30 citations were retained for further detailed review, and 14 of them were added to the evidence table. Articles were removed from the bibliography if they were not relevant or generalizable to the topic, or focused on unknown primary disease. Several commonly encountered clinical case variants were created and panelists anonymously rated each treatment recommendation. The results were reviewed and disagreements discussed.ConclusionsThe panel provided updated evidence and recommendations for ipsilateral radiation for squamous cell carcinoma of the tonsil in the setting of primary radiation‐based therapy and postoperative adjuvant radiotherapy. This committee did not reach agreements for some case variants due to a lack of strong evidence supporting specific treatment decisions, indicating a further need for research in these topics.
Lysyl Oxidase‐Like 4 Fosters an Immunosuppressive Microenvironment During Hepatocarcinogenesis
Authors: Tan Hor‐Yue , Wang Ning , Zhang Cheng , Chan Yau‐Tuen , Yuen Man‐Fung , Feng Yibin 
Published: October 2020

Background and Aims
Lysyl oxidase‐like 4 (LOXL4) is an amine oxidase that is primarily involved in extracellular matrix remodeling and is highly expressed in HCC tissues, but its functional role in mediating liver carcinogenesis is poorly understood. Therefore, we aimed to investigate the role of LOXL4 in hepatocarcinogenesis.

Approach and Results
Here, we demonstrate that hepatic LOXL4 expression was increased during the liver carcinogenesis in mice concomitantly fed a choline‐deficient, l‐amino acid–defined diet. LOXL4 was secreted by the neoplastic cells and primarily localized within hepatic macrophages through exosome internalization. Supplementation of LOXL4 had minimal effect on neoplastic cells. In vitro exposure of macrophages to LOXL4 invoked an immunosuppressive phenotype and activated programmed death ligand 1 (PD‐L1) expression, which further suppressed the function of CD8+ T cells. Injection of LOXL4 promoted macrophages infiltration into the liver and accelerated tumor growth, which was further abolished by adoptive T‐cell transfer or PD‐L1 neutralization. Label‐free proteomics analysis revealed that the immunosuppressive function of LOXL4 on macrophages primarily relied on interferon (IFN)‐mediated signal transducer and activator of transcription–dependent PD‐L1 activation. Hydrogen peroxide scavenger or copper chelation on macrophages abolished the IFN‐mediated PD‐L1 presentation by LOXL4. In human HCC tissue, expression of LOXL4 in CD68+ cells was positively correlated with PD‐L1 level. High expression of LOXL4 in CD68+ cells and low expression of CD8A in tumor tissue cooperatively predict poor survival of patients with HCC.

Conclusions
LOXL4 facilitates immune evasion by tumor cells and leads to hepatocarcinogenesis. Our study unveils the role of LOXL4 in fostering an immunosuppressive microenvironment during hepatocarcinogenesis.
Food community: Understanding community needs for a food security website to support rural and remote Western Australians
Authors: Rewa Johanna , Devine Amanda , Godrich Stephanie 
Published: October 2020

AbstractObjectiveThe South West Food Community (SWFC) project (2018) was implemented to identify initiatives working to enhance healthy food availability, access and use in the South West region of Western Australia (SWWA); and enhance how they functioned as a system. The SWFC project participants included government and community members. This study aimed to understand how a tailored food security website could be developed as a support mechanism to increase understanding of food security, connect participants and enhance the effectiveness of SWFC initiatives.MethodsInitiative leaders from the SWFC project (n = 46) were invited to participate in semi‐structured telephone interviews which sought to understand needs for a food security website. Fifteen stakeholders completed the interviews (32% response rate). Data relating to desirable and undesirable website components were analysed thematically using QSR NVivo 12.ResultsParticipants requested the website to include concise content, food security resources, inviting/useful images and information about initiatives. Undesirable features included academic literature, difficult‐to‐use functions, discussion boards and hard‐to‐view images.ConclusionA tailored, co‐designed website that is monitored, user‐friendly and functional were key stakeholder requirements.Implications for Public HealthA tailored, co‐designed food security website that promotes partnership development, builds networks, increases understanding and communication about food security and implementation strategies is needed.
Applying the Mandala of Health in the Anthropocene
Authors: Langmaid Georgia , Patrick Rebecca , Kingsley Jonathan , Lawson Justin 
Published: October 2020

AbstractIssue addressedThe Anthropocene is a new era in which human activity has been the dominant influence on climate and the environment. The negative impact humans have on the earth's systems pose significant threats to human health. Health promotion is a discipline well placed to respond to planetary health challenges of the Anthropocene. The overarching aim of this paper is to describe the elements of 21st century socio‐ecological health and apply them in a revised socio‐ecological framework for health promotion.MethodsA qualitative description study design was employed to explore the significance of ecological and cultural determinants of health and review models in contemporary health promotion to inform the development of a revised Mandala of Health. Purposeful sampling was used to recruit ten experts from across Australia including academics and practitioners working at the nexus of health promotion, environmental management and sustainability. Data were analysed thematically, using deductive and inductive methods.ResultsA revised Mandala of Health could address existing gaps in health promotion theory and practice. Ecological and cultural determinants of health were considered essential components of health promotion that is often lacking in socio‐ecological frameworks. Indigenous Knowledge Systems were considered immensely important when addressing ecological and cultural determinants of health.ConclusionsA revised Mandala of Health could encourage development of contemporary health models, assisting health promotion to evolve with the health and environmental issues of the Anthropocene. This study highlights the need for more theoretical development and empirical research regarding ecological and cultural determinants of health in a health promotion context.So what?In the context of the Anthropocene, this study highlights the potential gaps in health promotion theory and practice in terms of the natural environment and health and emphasises the need of a paradigm shift to embed ecological and cultural determinants with other determinants of health.
Antibiotic treatment of amniotic fluid “sludge” in patients during the second or third trimester with uterine contraction
Authors: Jin Wan Hu , Ha Kim Yoon , Kim Jong Woon , Kim Tae Young , Kim Ami , Yang Yoonmi 
Published: October 2020

AbstractObjectiveTo assess the effectiveness of antibiotic treatment in patients with amniotic fluid (AF) “sludge” during the second or third trimester with uterine contractions and intact membranes.MethodsA retrospective cohort study was conducted of women at 15–32 weeks of pregnancy with uterine contractions and intact membranes. Women with AF “sludge” were treated with an antibiotic regimen of ceftriaxone, clarithromycin, and metronidazole. Based on changes in AF “sludge,” patients were divided into group A (disappearance of “sludge”) and group B (persistent “sludge”).ResultsWomen in group A (n=30) delivered later than those in group B (n=28). Group A showed a smaller initial size of “sludge” than group B (all P<0.05). Women in group A had a lower rate of preterm birth within 7 days, and before 28, 32, and 34 weeks of pregnancy, and composite neonatal morbidity and perinatal death than group B (all P<0.05).ConclusionThe administration of antibiotics may eradicate AF “sludge” in women in the second or third trimester with uterine contractions and intact membranes, which are associated with the initial size of “sludge.” Patients with disappearing “sludge” had more favorable pregnancy and neonatal outcomes than those with persistent “sludge.”
Development and clinical application of a rapid SARS‐CoV‐2 antibody test strip: A multi‐center assessment across China
Authors: Liao Mengting , Yan Jiawei , Wang Xinfeng , Qian Huimin , Wang Chao , Xu Dan , Wang Bin , Yang Bo , Liu Shaohui , Zhou Mao , Gao Qian , Zhou Qian , Luo Jiquan , Li Zongxiang , Liu Wenen 
Published: October 2020

AbstractBackgroundThe ongoing coronavirus disease 19 (COVID‐19) is posing a threat to the public health globally. Serological test for SARS‐CoV‐2 antibody can improve early diagnosis of COVID‐19 and serves as a valuable supplement to RNA detection.MethodA SARS‐CoV‐2 IgG/IgM combined antibody test strip based on colloidal gold immunochromatography assay was developed, with both spike protein and nucleocapsid protein of SARS‐CoV‐2 antigen used for antibody detection. From 3 medical institutions across China, serum or plasma of 170 patients with confirmed COVID‐19 diagnosis and 300 normal controls were collected and tested with the strip. Sensitivity, specificity, kappa coefficient, receiver operating characteristic (ROC) curve, and area under the curve (AUC) were analyzed. Positive rates in different medical centers, age group, gender, and different disease course were compared.Results158 out 170 samples from confirmed COVID‐19 patients had positive results from the test, and 296 out of 300 samples from normal controls had negative results. The kit was 92.9% sensitive and 98.7% specific. The positive rate was 77.3% during the first week after disease onset, but reached 100% since day 9. AUC and kappa coefficient were 0.958 and 0.926, respectively, which showed the consistency of the test results with the standard diagnosis. Age or gender caused little variations in the kit sensitivity.ConclusionThe rapid, easy‐to‐use SARS‐CoV‐2 IgG/IgM combined antibody test kit has a superior performance, which can help with accurate diagnosis and thus timely treatment and isolation of COVID‐19 patients, that contributes to the better control of the global pandemic.
Thromboelastography (TEG) in normal pregnancy and its diagnostic efficacy in patients with gestational hypertension, gestational diabetes mellitus, or preeclampsia
Authors: Xie Xin , Wang Meng , Lu Yifan , Zeng Jiazi , Wang Jing , Zhang Chunhong , Zhu Hongyuan , Song Yujie , Han Lican , Liu Ying , Zhang Jingnan , Li Lei , Chen Lu , Zhai Yanhong , Cao Zheng 
Published: October 2020

AbstractBackgroundThromboelastography (TEG) provides global assessment of hemostatic function and has been recommended to monitor potential coagulopathies during pregnancy in which hypercoagulable state is favored. In present study, we established the reference intervals (RIs) of the TEG parameters (R, K, MA, and α‐angle) with Chinese pregnant women of third trimester. In addition, we examined the diagnostic efficacies of the TEG parameters in the patients diagnosed of gestational hypertension (GH), gestational diabetes mellitus (GDM), or preeclampsia (PE).MethodsWith specified including and excluding criteria, non‐pregnant controls, healthy pregnant women, and pregnant women with GH, GDM, or PE had their venous blood drawn at Beijing Obstetrics and Gynecology Hospital, followed by TEG tests performed in the clinical laboratory.ResultsThe RIs determined with the healthy pregnant women (in third trimester) for R, K, MA, and α‐angle were 4.0‐7.7, 1.2‐3.2, 51.9‐70.1, and 41.4‐74.4, respectively. When compared with the healthy pregnancy group, the K value was significantly decreased in GH patients but increased in PE patients; MA was significantly lower in the PE group. In the receiver operating characteristic curve (ROC) analyses, K value was able to efficiently distinguish normal pregnancy from the GH patients, with an AUC of 0.86 which is far better than those of R (AUC = 0.57) and MA (AUC = 0.56). For the PE patients, the AUC of MA (0.69) was significantly greater than that of R (0.50).ConclusionsThromboelastography may provide more accurate experimental basis for monitoring coagulation functions especially in pregnant women with complications of GH and PE.
Quantitative analyses of high‐angular resolution diffusion imaging (HARDI)‐derived long association fibers in children with sensorineural hearing loss
Authors: Shiohama Tadashi , Chew Brianna , Levman Jacob , Takahashi Emi 
Published: October 2020

AbstractSensorineural hearing loss (SNHL) is the most common developmental sensory disorder due to a loss of function within the inner ear or its connections to the brain. While successful intervention for auditory deprivation with hearing amplification and cochlear implants during a sensitive early developmental period can improve spoken‐language outcomes, SNHL patients can suffer several cognitive dysfunctions including executive function deficits, visual cognitive impairment, and abnormal visual dominance in speaking perception even after successful intervention. To evaluate whether long association fibers are involved in the pathogenesis of impairment on the extra‐auditory cognitive process in SNHL participants, we quantitatively analyzed high‐angular resolution diffusion imaging (HARDI) tractography‐derived fibers in participants with SNHL. After excluding cases with congenital disorders, perinatal brain damage, or premature birth, we enrolled 17 participants with SNHL aged under 10 years old. Callosal pathways (CP) and six types of cortico‐cortical association fibers (arcuate fasciculus [AF], inferior longitudinal fasciculus [ILF], inferior fronto‐occipital fasciculus [IFOF], uncinate fasciculus [UF], cingulum fasciculus [CF], and fornix [Fx]) in both hemispheres were identified and visualized. The ILF and IFOF were partly undetected in three profound SNHL participants. Compared to age‐ and gender‐matched neurotypical controls (NC), decreased volumes, increased lengths, and high apparent diffusion coefficient (ADC) values without difference in fractional anisotropy (FA) values were identified in multiple types of fibers in the SNHL group. The impairment of long association fibers in SNHL may partly be related to the association of cognitive dysfunction with SNHL.
Not deconstructing serial homology, but instead, the a priori assumption that it generally involves ancestral anatomical similarity: An answer to Kuznetsov's paper
Authors: Diogo Rui 
Published: October 2020

AbstractI am very thankful to Kuznetsov for his comments on our recent paper about serial structures published in this journal. I hope this is just the beginning of a much wider, and holistic, discussion on the evolution of serial homologous structures, and of so‐called “serial structures” in general, whether they are truly serial homologs or the secondary result of homoplasy. Strangely, Kuznetsov seems to have missed the main point of our paper, what is particularly puzzling as this point is clearly made in the very title of our paper. For instance, he states that “Siomava et al. claim that the serial homologues are false because they are ancestrally anisomeric (dissimilar)' and that” Siomava et al., (Siomava et al., Journal of Morphology, 2020, 281, 1110–1132) expected that if serial homology was true, then the serial homologs would be identical at the start and then only diverge. “ However, our paper clearly did not state this. Instead, we stated that (a) serial homology is a real phenomenon, and (b) ancestral dissimilarity is actually likely the norm, and not the exception, within serial homology. In particular, our paper showed that, as clearly stated in its title and abstract, within the evolution of serial homologues these structures “many times display trends toward less similarity while in many others display trends toward more similarity, that is, one cannot say that there is a clear, overall trend to anisomerism.” Serial homology is therefore a genuine and much widespread phenomenon within the evolution of life in this planet. It is clearly one of the most important issues—and paradoxically one of the less understood, precisely because of the a priori acceptance of long‐standing assumptions that have never been empirically tested, some of them repeated in Kuznetsov's paper—within macroevolution and comparative anatomy.