bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL‐17A promotes lung fibrosis through impairing mitochondrial homeostasis in type II alveolar epithelial cells
Authors: Xiao Huijuan , Peng Liang , Jiang Dingyuan , Liu Yuan , Zhu Lili , Li Zhen , Geng Jing , Xie Bingbing , Huang Xiaoxi , Wang Jing , Dai Huaping , Wang Chen 
Published: October 2022

AbstractThe dysfunction of type II alveolar epithelial cells (AECIIs), mainly manifested by apoptosis, has emerged as a major component of idiopathic pulmonary fibrosis (IPF) pathophysiology. A pivotal mechanism leading to AECIIs apoptosis is mitochondrial dysfunction. Recently, interleukin (IL)‐17A has been demonstrated to have a pro‐fibrotic role in IPF, though the mechanism is unclear. In this study, we report enhanced expression of IL‐17 receptor A (IL‐17RA) in AECIIs in lung samples of IPF patients, which may be related to the accumulation of mitochondria in AECIIs of IPF. Next, we investigated this relationship in bleomycin (BLM)‐induced PF murine model. We found that IL‐17A knockout (IL‐17A−/−) mice exhibited decreased apoptosis levels of AECIIs. This was possibly a result of the recovery of mitochondrial morphology from the improved mitochondrial dynamics of AECIIs, which eventually contributed to alleviating lung fibrosis. Analysis of in vitro data indicates that IL‐17A impairs mitochondrial function and mitochondrial dynamics of mouse primary AECIIs, further promoting apoptosis. PTEN‐induced putative kinase 1 (PINK1)/Parkin signal‐mediated mitophagy is an important aspect of mitochondria homeostasis maintenance. Our data demonstrate that IL‐17A inhibits mitophagy and promotes apoptosis of AECIIs by decreasing the expression levels of PINK1. We conclude that IL‐17A exerts its pro‐fibrotic effects by inducing mitochondrial dysfunction in AECIIs by disturbing mitochondrial dynamics and inhibiting PINK1‐mediated mitophagy, thereby leading to apoptosis of AECIIs.
Suramin prevents the development of diabetic kidney disease by inhibiting NLRP3 inflammasome activation in KK‐Ay mice
Authors: Oda Kaori , Miyamoto Satoshi , Kodera Ryo , Wada Jun , Shikata Kenichi 
Published: October 2022

AbstractAims/IntroductionNucleotide‐binding oligomerization domain‐like receptor family pyrin domain containing 3 (NLRP3) inflammasomes produce IL‐18 upon being activated by various stimuli via the P2 receptors. Previously, we showed that serum and urine IL‐18 levels are positively associated with albuminuria in patients with type 2 diabetes, indicating the involvement of inflammasome activation in the pathogenesis of diabetic kidney disease (DKD). In the present study, we investigated whether the administration of suramin, a nonselective antagonist of the P2 receptors, protects diabetic KK.Cg‐Ay/TaJcl (KK‐Ay) mice against DKD progression.Materials and MethodsSuramin or saline was administered i.p. to KK‐Ay and C57BL/6J mice once every 2 weeks for a period of 8 weeks. Mouse mesangial cells (MMCs) were stimulated with ATP in the presence or absence of suramin.ResultsSuramin treatment significantly suppressed the increase in the urinary albumin‐to‐creatinine ratio, glomerular hypertrophy, mesangial matrix expansion, and glomerular fibrosis in KK‐Ay mice. Suramin also suppressed the upregulation of NLRP3 inflammasome‐related genes and proteins in the renal cortex of KK‐Ay mice. P2X4 and P2X7 receptors were significantly upregulated in the isolated glomeruli of KK‐Ay mice and mainly distributed in the glomerular mesangial cells of KK‐Ay mice. Although neither ATP nor suramin affected NLRP3 expression in MMCs, suramin inhibited ATP‐induced NLRP3 complex formation and the downstream expression of caspase‐1 and IL‐18 in MMCs.ConclusionsThese results suggest that the NLRP3 inflammasome is activated in a diabetic kidney and that inhibition of the NLRP3 inflammasome with suramin protects against the progression of early stage DKD.
Decimal reduction value (D) from fraction negative experiments via maximum likelihood estimation: An enabling spreadsheet and its implications on methodology and current standards
Authors: Moruzzi Guido , Lou Yuqian , Fritz Ronald D. 
Published: October 2022

AbstractResistance of biological indicators for sterilization in pharma and food applications is often determined via fraction negative experiments. The ISO 11138 standards prescribe the Holcomb–Spearman–Karber procedure (HSKP) for calculating D value using these methods. However, HSKP imposes limitations on experimental designs. While ISO 11138 requires inactivation kinetics to not significantly deviate from first order, the HSKP does not provide a step to check such departure, or its extent. Maximum likelihood estimation (MLE) is an alternative approach for D value determination from fraction negative experiments. Compared to HSKP, it allows researchers to tailor the experimental design to practical needs, potentially reducing overall sample size in the process. This work presents a development of a 2004 published worksheet for MLE calculation, providing tighter confidence intervals and an improved way for Improbability calculation. Ways to exploit the design flexibility of MLE approach are presented, including simulated experiments and examples on how to optimize experimental design according to various situational needs, also in cases where expected D values are of the order of one or a few seconds as is commonly encountered in the sterilization of aseptic fillers for food. Detection of deviation from first‐order kinetics using the enhanced Improbability methods is discussed; one of the examples provided by ISO 11138‐1 for D value determination by HSKP contains data that deviate significantly from first order.
Association between social integration and risk of dementia: A systematic review and meta‐analysis of longitudinal studies
Authors: Wang Shanshan , Molassiotis Alex , Guo Chunlan , Leung Isaac Sze Him , Leung Angela Yee Man 
Published: October 2022

AbstractBackgroundDementia is an emerging public health issue. Growing evidence emerged on the association between social integration and the risk of dementia. However, the magnitude of the association between different aspects of social integration and the risk of dementia is unclear.MethodsFive databases were systematically searched. Newcastle–Ottawa scale for assessing the quality of the reporting was used for quality appraisal. Longitudinal cohort studies examining the association between social integration and the risk of dementia were analyzed using random effects model. A series of sensitivity analyses was conducted to enhance the robustness of the findings.ResultsForty publications generated from 32 studies/databases were included. The meta‐analysis showed that strong social engagement (overall RR = 0.81, 95% CI = 0.74–0.89, p < 0.001) and frequent social contact (overall RR = 0.86, 95% CI = 0.76–0.97, p = 0.018) were positively associated with decreased risk of dementia. The influence of social support (overall RR = 0.92, 95% CI = 0.80–1.06, p = 0.238) and close social contact (overall RR = 0.74, 95% CI = 0.48–1.13, p = 0.167) was not significant. Loneliness was significantly associated with an increased risk of dementia (overall RR = 1.42, 95% CI = 1.26–1.60, p < 0.001), whereas the influence of social isolation (overall RR = 1.58, 95% CI = 0.80–3.12, p = 0.192) was not significant. A larger social network size (RR = 0.75, 95% CI = 0.59–0.97, p = 0.028) was a promising influencing factor even though the number of studies was insufficient for a meta‐analysis. However, the heterogeneity among studies was generally high even though sensitivity analysis was conducted.ConclusionsOur findings reveal that high social engagement and frequent social contact are significantly associated with a lower risk of dementia, whereas loneliness is associated with a higher risk. The promising impact of large social network size is also identified. Substantial heterogeneity appeared in most of the analysis, making the inference tentative. Nevertheless, the sensitivity analysis provided valuable implications that enhancing social engagement and reducing loneliness may prevent or delay the onset of dementia among middle‐aged and older adults.
Hyperkyphosis and mortality risk in older men: The osteoporotic fractures in men study
Authors: Cours Alexandra , Huang Mei‐Hua , Fink Howard , Ensrud Kristine E. , Schousboe John T. , Katzman Wendy , Schneider Diane , Lane Nancy E. , Cawthon Peggy , Kado Deborah M. 
Published: October 2022

AbstractIntroductionHyperkyphosis commonly affects older people but is not widely acknowledged as a clinically actionable problem, especially in men. There are several techniques to quantify kyphosis including the blocks and Cobb angle measurements. This study includes both kyphosis measures to investigate whether older men with accentuated kyphosis may be at increased mortality risk.MethodsMen aged ≥65 years (N = 5994) were recruited to participate in the MrOS prospective cohort study from 2000 to 2002 (baseline). Our primary cohort included 2931 enrollees (mean age 79.3 years; SD 5.2) who underwent blocks‐measured kyphosis from 2006 to 2009. Our secondary cohort included 2351 participants who underwent radiographic Cobb angle measurements at baseline. Cox proportional hazards analyses were used to determine association between kyphosis and all‐cause mortality while adjusting for prevalent radiographic vertebral fractures, bone mineral density, incident fractures, gait speed, timed chair stands, self‐reported health, alcohol use, medical co‐morbidities, and physical activity.ResultsDuring a mean follow‐up of 8.3 (SD 3.2) years, 1393 participants died in the primary cohort. In this group, compared to men with 0–1 block kyphosis, increasing blocks‐measured kyphosis was associated with increased mortality (HR: 1.26–1.53, p trend <0.001). With addition of prevalent vertebral fracture to adjusted models, the association remained significant in participants with severe kyphosis (3+ blocks‐measured). Similarly, with addition of chair stand performance the association remained significant for 4+ blocks kyphosis. Walking speed did not attenuate the association of kyphosis and mortality. In the secondary cohort, there were no significant associations between radiographic Cobb angle kyphosis and mortality.ConclusionsIncreasing blocks‐measured kyphosis was associated with a greater risk of mortality in older men, indicating that hyperkyphosis identified on physical exam should be considered a clinically significant finding that may warrant further evaluation and treatment.
Low copy numbers for mitochondrial DNA moderates the strength of nuclear–cytoplasmic incompatibility in plants
Authors: Zhang Liguang , Ma Jin , Shen Zhaorui , Wang Bo , Jiang Qingling , Ma Fei , Ju Yan , Duan Guangxing , Zhang Quan , Su Xiaodong , Sodmergen  
Published: October 2022

AbstractPlant cells contain only small amounts of mitochondrial DNA (mtDNA), with the genomic information shared among multiple mitochondria. The biological relevance and molecular mechanism underlying this hallmark of plant cells has been unclear. Here, we report that Arabidopsis thaliana plants exhibited significantly reduced growth and mitochondrial dysfunction when the mtDNA copy number was increased to the degree that each mitochondrion possessed DNA. The amounts of mitochondrion‐encoded transcripts increased several fold in the presence of elevated mtDNA levels. However, the efficiency of RNA editing decreased with this excess of mitochondrion‐encoded transcripts, resulting in impaired assembly of mitochondrial complexes containing mtDNA‐encoded subunits, such as respiratory complexes I and IV. These observations indicate the occurrence of nuclear–mitochondrial incompatibility in the cells with increased amounts of mtDNA and provide an initial answer to the fundamental question of why plant cells have much lower mtDNA levels than animal cells. We propose that keeping mtDNA levels low moderates nuclear–mitochondrial incompatibility and that this may be a crucial factor driving plant cells to restrict the copy numbers of mtDNA.
An assessment of the variation of the intramuscular innervation of the gracilis muscle, with the aim of determining its neuromuscular compartments
Authors: Kurtys Konrad , Podgórski Michał , Gonera Bartosz , Vazquez Teresa , Olewnik Łukasz 
Published: October 2022

AbstractSome muscles present neuromuscular compartments, one of which is the gracilis muscle. The aim of the present study is to determine the number of compartments present within the gracilis muscle based on its intramuscular innervation patterns; such knowledge could be of value in free functional muscle transfer. The study comprised 72 gracilis muscles (38 women, 34 men), fixed in 10% formalin solution. The muscles were removed and then stained using Sihler's method. When sufficient transparency was achieved, some measurements were made. Three different types of intramuscular innervation were distinguished. Type I (70.8%) was featured by at least one direct proximal nerve branch. Type II (23.6%) presented at least one indirect proximal nerve branch. Type III (5.6%) did not possess any proximal nerve branch. The median of descended nerve branches was five. Considerable anatomical variation is possible within the intramuscular innervation of the gracilis muscle. The muscle presents neuromuscular compartments, but the exact number depends on the type of its intramuscular innervation and the number of the main descendent nerve branches. All three types seem to be appropriate for free functional muscle transfer. Our findings may be of great value for surgeons carrying out complex reconstructions with the use of the gracilis muscle.
Natural history of untreated HDV patients: Always a progressive disease?
Authors: Kamal Habiba , Aleman Soo ,   D‐SOLVE Consortium
Published: October 2022

AbstractA severe course has been described in early studies on chronic hepatitis D (CHD), with faster pace towards liver cirrhosis with subsequent high liver‐related morbidity and mortality in the majority of patients. Earlier studies have included risk groups as people using intravenous drugs (PWID) or those with multiple co‐morbidities. During the last decade, the epidemiological landscape of CHD has changed with domestic cases decreasing while increasing cases of CHD consisting of younger persons immigrating from endemic regions to low‐endemic regions. Recently, further insights into the spectrum of the disease with an indolent disease course in a substantial proportion of persons with CHD have been gained. At diagnosis, ≥30%–50% had already established liver cirrhosis. Older age, liver cirrhosis, co‐infection with HIV and lack of interferon (IFN) therapy are the main predictors of worse clinical outcome. The newly introduced and upcoming antivirals against CHD are highly anticipated, considering the historically low virological response rates to antiviral therapy. Further knowledge is needed to fully comprehend the natural course and the spectrum of this severe form of viral hepatitis. This is also to be able to evaluate the long‐term effects of the new antivirals on disease progression.
CARDA: Guiding document analyses in health professions education research
Authors: Cleland Jennifer , MacLeod Anna , Ellaway Rachel H. 
Published: October 2022

AbstractIntroductionDocuments, from policies and procedures to curriculum maps and examination papers, structure the everyday experiences of health professions education (HPE), and as such can provide a wealth of empirical information. Document analysis (DA) is an umbrella term for a range of systematic research procedures that use documents as data.MethodsA meta‐study review was conducted with the aims of describing the current state of DA in HPE, guiding researchers engaging in DA and improving methodological, analytical and reporting rigour. Structured searches were conducted, returns were filtered for inclusion and the 115 remaining articles were critically analysed for their use of DA methods and methodologies.ResultsThere was a significant increase in the number of articles reporting the use of DA over time. Sixty‐three articles were single method (DA only), while the others were mixed methods research (MMR). Overall, there were major lacunae in terms of why documents were used, how documents were identified, what the authors did and what they found from the documents. This was particularly apparent in MMR where DA reporting was typically poorer than the reporting of other methods in the same paper.DiscussionGiven these many lacunae, a framework for reporting on DA research was developed to facilitate rigorous DA research and transparent, complete and accurate reporting of the same, to help readers assess the trustworthiness of the findings from document use and analysis in HPE and, potentially, other domains. It was also noted that there are gaps in HPE knowledge that could be addressed through DA, particularly where documents are conceptualised as more than passive holders of information. Scholars are encouraged to reflect more deeply on the applications and practices of DA, with the ultimate aim of ensuring more substantive and more rigorous use of documents for understanding and constructing meaning in our field.
Axin1: A novel scaffold protein joins the antiviral network of interferon
Authors: Guo Yujie , Bamunuarachchi Gayan , Vaddadi Kishore , Zhu Zhengyu , Gandikota Chaitanya , Ahmed Kainat , Pushparaj Samuel , More Sunil , Xiao Xiao , Yang Xiaoyun , Liang Yurong , Mukherjee Sanjay , Baviskar Pradyumna , Huang Chaoqun , Li Shitao , Oomens Antonius G. P. , Metcalf Jordan Patrick , Liu Lin 
Published: October 2022

AbstractAcute respiratory infection by influenza virus is a persistent and pervasive public health problem. Antiviral innate immunity initiated by type I interferon (IFN) is the first responder to pathogen invasion and provides the first line of defense. We discovered that Axin1, a scaffold protein, was reduced during influenza virus infection. We also found that overexpression of Axin1 and the chemical stabilizer of Axin1, XAV939, reduced influenza virus replication in lung epithelial cells. This effect was also observed with respiratory syncytial virus and vesicular stomatitis virus. Axin1 boosted type I IFN response to influenza virus infection and activated JNK/c‐Jun and Smad3 signaling. XAV939 protected mice from influenza virus infection. Thus, our studies provide new mechanistic insights into the regulation of the type I IFN response and present a new potential therapeutic of targeting Axin1 against influenza virus infection.
Novel insights into the contribution of plastoglobules and reactive oxygen species to chromoplast differentiation
Authors: Morelli Luca , Torres‐Montilla Salvador , Glauser Gaétan , Shanmugabalaji Venkatasalam , Kessler Felix , Rodriguez‐Concepcion Manuel 
Published: October 2022

Summary
Plant tissues can be enriched in phytonutrients not only by stimulating their biosynthesis but also by providing appropriate sink structures for their sequestering and storage. In the case of carotenoids, they accumulate at high levels in chromoplasts naturally found in flowers and fruit. Chromoplasts can also be artificially differentiated from leaf chloroplasts by boosting carotenoid production with the bacterial protein crtB.
Here we used electron and confocal microscopy together with subplastidial fractionation and transcript, protein and metabolite analyses to analyze the structural and biochemical changes occurring in crtB‐induced artificial chromoplasts and their impact on the accumulation of health‐related isoprenoids.
We show that leaf chromoplasts develop plastoglobules (PG) harboring high levels of carotenoids (mainly phytoene and pro‐vitamin A β‐carotene) but also other nutritionally relevant isoprenoids, such as tocopherols (vitamin E) and phylloquinone (vitamin K1). Further promoting PG proliferation by exposure to intense (high) light resulted in a higher accumulation of these health‐related metabolites but also an acceleration of the chloroplast‐to‐chromoplast conversion. We further show that the production of reactive oxygen species (ROS) stimulates chromoplastogenesis.
Our data suggest that carotenoid accumulation and ROS production are not just consequences but promoters of the chromoplast differentiation process.
Obesity and glucose metabolism abnormalities by post‐disaster evacuation
Authors: Kawasaki Yukihiko , Nakano Hironori , Hayashi Fumikazu , Hosoya Mitsuaki , Yasumura Seiji , Ohira Tetsuya , Satoh Hiroaki , Suzuki Hitoshi , Takahashi Atsushi , Sakai Akira , Shimabukuro Michio , Ohto Hitoshi , Kamiya Kenji 
Published: October 2022

AbstractBackgroundThe objectives of this study were to determine the longer‐term trends in childhood obesity and glucose metabolism abnormalities among residents of Fukushima Prefecture 5 years after the Great East Japan Earthquake.MethodsWe evaluated the changes in height, weight, body mass index (BMI), BMI SD score, fasting plasma glucose (FPG) concentration, and hemoglobin A1c (HbA1c) among elementary and junior high school residents who had lived in the evacuation zone between 2011 and 2015.ResultsOf the residents, 11,112 received health checks in 2011, while in 2012, 2013, 2014, and 2015, 5,737, 4522, 4297 and 3405 received health checks, respectively. The mean BMI SD score for all participants in 2011 was 0.149, and this score gradually decreased from 2011 to 2015. FPG levels and HbA1c levels for all participants with a BMI value +2SD or more in 2011 were higher than those in residents with a BMI value of less than +2SD. The frequency of participants with a FPG level of 126 mg/dl or more and the frequency of participants with a HbA1c level of 6.5% or more in 2011 were higher than those in 2012, 2013, and 2015.ConclusionsThese results suggest that a number of pediatric residents suffered from obesity and glucose metabolism abnormalities. However, the longer‐term observations indicated an improvement in obesity and glucose metabolism abnormalities. There was a strong association observed between obesity and glucose metabolism, thus, it is important to continue with health checks for children with obesity and strive to improve their health.
Serving the cause when my organization does not: A self‐affirmation model of employees’ compensatory responses to ideological contract breach
Authors: Deng Hong , Coyle‐Shapiro Jacqueline , Zhu Yanting , Wu Chia‐huei 
Published: October 2022

AbstractTransactional and relational contract breach occur when organizations fail to deliver on promised personal benefits for employees and are associated with negative behaviors reciprocating such mistreatment. However, recent research suggests that ideological contract breach, a unique form of contract breach, may yield constructive behaviors because it is not organizations’ direct personal mistreatment of employees, but organizations’ abandonment of a valued cause to benefit a third party. Such an interesting prediction goes beyond the dominant social‐exchange framework, which mainly forecasts destructive responses to breach. In this research, we develop a novel self‐affirmation model to explain how ideological contract breach results in counterintuitive positive outcomes. In a hospital field study among medical professionals (N = 362) and their supervisors (N = 129), we found that ideological contract breach induces employees’ rumination about the breach, which in turn prompts them to self‐affirm core values at work. This self‐affirmation eventually spurs proactive serving behavior and self‐improvement behavior to compensate for the breached ideology. Professional identification enhances this self‐affirmation process.