bluuebunny/crossref_metadata_2025 huggingface dataset:
A horizontal ground-motion model for crustal and subduction earthquakes in Taiwan
Authors: Chao Shu-Hsien , Chiou Brian , Hsu Chiao-Chu , Lin Po-Shen
Published: March 2020

In this study, a new horizontal ground-motion model is developed for crustal and subduction earthquakes in Taiwan. A novel two-step maximum-likelihood method is used as a regression tool to develop this model. This method simultaneously considers both the correlation between records and the biased sampling because of random truncation. Moreover, additional ground-motion data can be considered to derive more reliable analysis results. The functional form of the proposed ground-motion model is constructed using the response spectrum of the reference ground-motion scenario and different scalings of the source, path, and site to illustrate the ground-motion characteristics. The variabilities in the ground-motion intensity that result from different events, stations, and records are developed individually to derive a single-station sigma. The proposed ground-motion model may be useful for predicting ground-motion intensity and performing site-specific probabilistic seismic hazard analysis in Taiwan.
Late effects after ablative allogeneic stem cell transplantation for adolescent and young adult acute myeloid leukemia
Authors: Lee Catherine J. , Kim Soyoung , Tecca Heather R. , Bo-Subait Stephanie , Phelan Rachel , Brazauskas Ruta , Buchbinder David , Hamilton Betty K. , Battiwalla Minoo , Majhail Navneet S. , Lazarus Hillard M. , Shaw Peter J. , Marks David I. , Litzow Mark R. , Chhabra Saurabh , Inamoto Yoshihiro , DeFilipp Zachariah , Hildebrandt Gerhard C. , Olsson Richard F. , Kasow Kimberly A. , Liesveld Jane L. , Rotz Seth J. , Badawy Sherif M. , Bhatt Neel S. , Yared Jean A. , Page Kristin M. , Arellano Martha L. , Kent Michael , Farhadfar Nosha , Seo Sachiko , Hematti Peiman , Freytes César O. , Rovó Alicia , Ganguly Siddhartha , Nathan Sunita , Burns Linda , Shaw Bronwen E. , Muffly Lori S.
Published: March 2020

There is marked paucity of data regarding late effects in adolescents and young adults (AYAs) who undergo myeloablative conditioning (MAC) allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML). We evaluated late effects and survival in 826 1-year disease-free survivors of MAC HCT for AYA AML, with an additional focus on comparing late effects based upon MAC type (total body irradiation [TBI] vs high-dose chemotherapy only). The estimated 10-year cumulative incidence of subsequent neoplasms was 4% (95% confidence interval [CI], 2%-6%); 10-year cumulative incidence of nonmalignant late effects included gonadal dysfunction (10%; 95% CI, 8%-13%), cataracts (10%; 95% CI, 7%-13%), avascular necrosis (8%; 95% CI, 5%-10%), diabetes mellitus (5%; 95% CI, 3%-7%), and hypothyroidism (3%; 95% CI, 2%-5%). Receipt of TBI was independently associated with a higher risk of cataracts only (hazard ratio [HR], 4.98; P < .0001) whereas chronic graft-versus-host disease (cGVHD) was associated with an increased risk of cataracts (HR, 3.22; P = .0006), avascular necrosis (HR, 2.49; P = .006), and diabetes mellitus (HR, 3.36; P = .03). Estimated 10-year overall survival and leukemia-free survival were 73% and 70%, respectively, and did not differ on the basis of conditioning type. In conclusion, late effects among survivors of MAC HCT for AYA AML are frequent and are more closely linked to cGVHD than type of conditioning.
Unfolded protein response (UPR) integrated signaling networks determine cell fate during hypoxia
Authors: Bartoszewska Sylwia , Collawn James F.
Published: March 2020

During hypoxic conditions, cells undergo critical adaptive responses that include the up-regulation of hypoxia-inducible proteins (HIFs) and the induction of the unfolded protein response (UPR). While their induced signaling pathways have many distinct targets, there are some important connections as well. Despite the extensive studies on both of these signaling pathways, the exact mechanisms involved that determine survival versus apoptosis remain largely unexplained and therefore beyond therapeutic control. Here we discuss the complex relationship between the HIF and UPR signaling pathways and the importance of understanding how these pathways differ between normal and cancer cell models.
Sarcopenia negatively affects hip structure analysis variables in a group of Lebanese postmenopausal women
Authors: Saddik Hayman , Nasr Riad , Pinti Antonio , Watelain Eric , Fayad Ibrahim , Baddoura Rafic , Berro Abdel-Jalil , Al Rassy Nathalie , Lespessailles Eric , Toumi Hechmi , El Hage Rawad
Published: March 2020

Background

The current study’s purpose is to compare hip structural analysis variables in a group of postmenopausal women with sarcopenia and another group of postmenopausal women with normal skeletal muscle mass index. To do so, the current study included 8 postmenopausal women (whose ages ranged between 65 and 84 years) with sarcopenia and 60 age-matched controls (with normal skeletal muscle mass index (SMI)). Body composition and bone parameters were evaluated by dual-energy X-ray absorptiometry (DXA).

Results

Weight, lean mass, body mass index, femoral neck cross-sectional area (FN CSA), FN section modulus (Z), FN cross sectional moment of inertia (CSMI), intertrochanteric (IT) CSA, IT Z, IT CSMI, IT cortical thickness (CT), femoral shaft (FS) CSA, FS Z and FS CSMI were significantly greater (p < 0.05) in women with normal SMI compared to women with sarcopenia. In the whole population, SMI was positively associated with IT CSA, IT Z, IT CSMI, IT CT, FS CSA, FS Z, FS CSMI, FS CT but negatively correlated to IT buckling ratio (BR) and FS BR.

Conclusion

The current study suggests that sarcopenia has a negative effect on hip bone strength indices in postmenopausal women.
Bioelectrical and cytoskeletal patterns correlate with altered axial polarity in the follicular epithelium of the Drosophila mutant gurken
Authors: Schotthöfer Susanne Katharina , Bohrmann Johannes
Published: March 2020

Background

Bioelectrical signals are known to be involved in the generation of cell and tissue polarity as well as in cytoskeletal dynamics. The epithelium ofDrosophilaovarian follicles is a suitable model system for studying connections between electrochemical gradients, patterns of cytoskeletal elements and axial polarity. By interactions between soma and germline cells, the transforming growth factor-α homolog Gurken (Grk) establishes both the anteroposterior and the dorsoventral axis during oogenesis.

Results

In the follicular epithelium of the wild-type (wt) and the polarity mutantgrk, we analysed stage-specific gradients of membrane potentials (Vmem) and intracellular pH (pHi) using the potentiometric dye DiBAC4(3) and the fluorescent pH-indicator 5-CFDA,AM, respectively. In addition, we compared the cytoskeletal organisation in the follicular epithelium of wt andgrkusing fluorescent phalloidin and an antibody against acetylated α-tubulin. Corresponding to impaired polarity ingrk, the slope of the anteroposterior Vmem-gradient in stage S9 is significantly reduced compared to wt.Even more striking differences in Vmem- and pHi-patterns become obvious during stage S10B, when the respective dorsoventral gradients are established in wt but not ingrk. Concurrent with bioelectrical differences, wt andgrkexhibit differences concerning cytoskeletal patterns in the follicular epithelium. During all vitellogenic stages, basal microfilaments ingrkare characterised by transversal alignment, while wt-typical condensations in centripetal follicle cells (S9) and in dorsal centripetal follicle cells (S10B) are absent. Moreover, ingrk, longitudinal alignment of microtubules occurs throughout vitellogenesis in all follicle cells, whereas in wt, microtubules in mainbody and posterior follicle cells exhibit a more cell-autonomous organisation. Therefore, in contrast to wt, the follicular epithelium ingrkis characterised by missing or shallower electrochemical gradients and by more coordinated transcellular cytoskeletal patterns.

Conclusions

Our results show that bioelectrical polarity and cytoskeletal polarity are closely linked to axial polarity in both wt andgrk. When primary polarity signals are altered, both bioelectrical and cytoskeletal patterns in the follicular epithelium change. We propose that not only cell-specific levels of Vmemand pHi, or the polarities of transcellular electrochemical gradients, but also the slopes of these gradients are crucial for cytoskeletal modifications and, thus, for proper development of epithelial polarity.
Inhibition of JAK2/STAT3/SOCS3 signaling attenuates atherosclerosis in rabbit
Authors: Yang Xilan , Jia Jian , Yu Zhen , Duanmu Zheng , He Huiwei , Chen Sen , Qu Chen
Published: March 2020

Background

Previous studies have indicated that the JAK/STAT signaling pathway is involved in modulating arterial adventitia inflammation response. In this study, we designed experiments to further investigate the effect of JAK2/STAT3/SOCS3 signaling in rabbit atherosclerosis process.

Methods

Atherosclerosis was induced in the abdominal arteries of rabbits by balloon injury of the aorta supplemented by the atherogenic diet. Simultaneously, in the process of atherosclerosis, animals underwent either ruxolitinib treatment or not for 12 weeks. At the end of the experimental period, all rabbits were sacrificed. The plaque areas in abdominal artery, the lipid burden of plaque and the calcium burden of plaque were detected by H&E staining, Oil Red O staining and Alizarin Red staining, respectively. In addition, rabbit plasma lipids and inflammatory cytokines were measured by biochemical test kits or ELISA kits. Finally, the expression and phosphorylation levels of JAK2/STAT3/SOCS3 pathway-related proteins were detected by RT-qPCR, western blot and immunohistochemistry assays.

Results

H&E staining and CT scan analysis showed that rabbit atherosclerosis model was constructed successfully. Ruxolitinib, an inhibitor of the Janus kinase 2 (JAK2), substantially reduced the area of atherosclerotic plaques in rabbits treated with high fat diet and balloon injury of the aorta. Moreover, ruxolitinib significantly decreased IL-6, IL-1β, IFN-γ and TNF-α, but increased IL-10 and IL-17 levels in plasma of atherosclerotic rabbits. Additionally, ruxolitinib reduced plasma TC, TG and LDL-C contents and AIP value, while enhanced HDL-C level in atherosclerotic rabbits. Furthermore, we found that JAK2 and STAT3 phosphorylation were up-regulated in rabbits with atherosclerosis when compared with those of the control group, followed by the expression of SOCS3 was also increased due to the activation of JAK2 and STAT3. Interestingly, ruxolitinib could inactivate JAK2 and STAT3 pathway and decrease SOCS3 expression.

Conclusion

Taken together, the inhibition of JAK2/STAT3/SOCS3 signaling pathway may be a novel method for the clinical treatment of artery atherosclerosis.
A novel approach to conducting clinical trials in the community setting: utilizing patient-driven platforms and social media to drive web-based patient recruitment
Authors: Applequist Janelle , Burroughs Cristina , Ramirez Artemio , Merkel Peter A. , Rothenberg Marc E. , Trapnell Bruce , Desnick Robert J. , Sahin Mustafa , Krischer Jeffrey P.
Published: March 2020

Background

Participant recruitment for clinical research studies remains a significant challenge for researchers. Novel approaches to recruitment are necessary to ensure that populations are easier to reach. In the context of rare diseases, social media provides a unique opportunity for connecting with patient groups that have representatively lower diagnosis rates when compared with more common diseases or illness. We describe the implementation of designing a patient-centered approach to message design for the purposes of recruiting patients for clinical research studies for rare disease populations.

Methods

Using an iterative research approach, we analyzed our previous experience of using web-based direct-to-patient recruitment methods to compare these online strategies with traditional center of excellence recruitment strategies. After choosing six research studies for inclusion in the previous study, in-depth, online interviews (n = 37) were conducted with patients represented in each disease category to develop and test recruitment message strategies for social media and a Web-based platform for patients to access study information and pre-screen. Finally, relationships were established with Patient Advocacy Groups representing each rare disease category to ensure further dissemination of recruitment materials via their own social media networks.

Results

Guided by social marketing theory, we created and tested various recruitment message designs. Three key message concepts preferred by patients emerged: (1) infographic; (2) positive emotional messages; and (3) educational information for sharing. A base study website was designed and created based on data from patient interviews. This website includes the option for potential participants to pre-screen and determine their eligibility for the study.

Conclusions

Study participants report wanting to be involved in the design and implementation of recruitment approaches for clinical research studies. The application of the aforementioned methods could aide in the evolution of clinical research practices for the recruitment of both rare and common diseases, where patient-centric approaches can help to create targeted messages designs that participants pre-test and support.
Fecal microbiota characteristics of Chinese patients with primary IgA nephropathy: a cross-sectional study
Authors: Hu Xiaofang , Du Jie , Xie Yuhong , Huang Qiong , Xiao Yi , Chen Juan , Yan Siyuan , Gong Zhicheng , Ouyang Shaxi
Published: March 2020

Background

Growing evidence has shown that the gut-renal connection and gut microbiota dysbiosis play a critical role in immunoglobulin A nephropathy (IgAN). However, the fecal microbiome profile in Chinese patients with IgAN remains unknown. A cross-sectional study was designed for the first time to investigate the fecal microbiota compositions in patients with primary IgAN in China and to evaluate the relationship between the fecal microbiome and IgAN clinical presentation.

Methods

Fecal samples were collected from 17 IgAN patients and 18 age-, sex-, and body mass index-matched healthy controls, and bacterial DNA was extracted for 16S ribosomal RNA gene sequencing targeting the V3-V4 region.

Results

Fecal samples from the IgAN patients and healthy controls showed differences in gut microbiota community richness and compositions. Compared to the healthy controls, IgAN patients at the phylum level had an increased abundance of Fusobacteria, but a decreased abundance of Synergistetes. The significantly increased genera in the IgAN group were Escherichia-Shigella, Hungatella, and Eggerthella, all of which possess pathogenic potential. Furthermore, the genus Escherichia-Shigella was negatively associated with the estimated glomerular filtration rate (eGFR) but was positively associated with the urinary albumin-to-creatinine ratio (uACR). However, the genus rectale_group was present in the IgAN group with a low abundance and was negatively associated with the uACR. Functional analysis disclosed that infection-related pathways were enriched in the IgAN group.

Conclusions

We demonstrate that gut microbiota dysbiosis occurs in patients with IgAN, and that changes in gut bacterial populations are closely related to IgAN clinical features, suggesting that certain specific gut microbiota may be a potential therapeutic target for IgAN.
The impact of physical exercise on the fatigue symptoms in patients with multiple sclerosis: a systematic review and meta-analysis
Authors: Razazian Nazanin , Kazeminia Mohsen , Moayedi Hossein , Daneshkhah Alireza , Shohaimi Shamarina , Mohammadi Masoud , Jalali Rostam , Salari Nader
Published: March 2020

Background

Despite many benefits of the physical activity on physical and mental health of patients with Multiple Sclerosis (MS), the activity level in these patients is still very limited, and they continue to suffer from impairment in functioning ability. The main aim of this study is thus to closely examine exercise’s effect on fatigue of patients with MS worldwide, with particular interest on Iran based on a comprehensive systematic review and meta-analysis.

Methods

The studies used in this systematic review were selected from the articles published from 1996 to 2019, in national and international databases including SID, Magiran, Iranmedex, Irandoc, Google Scholar, Cochrane, Embase, ScienceDirect, Scopus, PubMed and Web of Science (ISI). These databases were thoroughly searched, and the relevant ones were selected based on some plausible keywords to the aim of this study. Heterogeneity index between studies was determined using Cochran’s test and I2. Due to heterogeneity in studies, the random effects model was used to estimate standardized mean difference.

Results

From the systematic review, a meta-analysis was performed on 31 articles which were fulfilled the inclusion criteria. The sample including of 714 subjects was selected from the intervention group, and almost the same sample size of 720 individuals were selected in the control group. Based on the results derived from this meta-analysis, the standardized mean difference between the intervention group before and after the intervention was respectively estimated to be 23.8 ± 6.2 and 16.9 ± 3.2, which indicates that the physical exercise reduces fatigue in patients with MS.

Conclusion

The results of this study extracted from a detailed meta-analysis reveal and confirm that physical exercise significantly reduces fatigue in patients with MS. As a results, a regular exercise program is strongly recommended to be part of a rehabilitation program for these patients.
Correction to: Safety and tolerability of monthly galcanezumab injections in patients with migraine: integrated results from migraine clinical studies
Authors: Bangs Mark E. , Kudrow David , Wang Shufang , Oakes Tina M. , Terwindt Gisela M. , Magis Delphine , Yunes-Medina Laura , Stauffer Virginia L.
Published: March 2020

Following publication of the original article [1], the authors noticed an error in the values for ‘Hypersensitivity SMQ’ and ‘Rash’ in Table 7.
Blepharoptosis among Korean adults: age-related prevalence and threshold age for evaluation
Authors: Paik Ji-Sun , Han Kyungdo , Yang Suk-Woo , Park Yongkyu , Na Kyungsun , Cho Wonkyung , Jung Su-Kyung , Kim Sungeun
Published: March 2020

Background

To evaluate the prevalence of blepharoptosis among Korean adults and the characteristics of blepharoptosis patients, and to determine an appropriate age threshold for recommending blepharoptosis evaluation.

Methods

The Korean National Health and Nutrition Examination Survey (KNHANES-V) was conducted in 2010–2012. We extracted data on 17,878 Korean adults aged more than and equal to 19 years included in KNHANES-V, and determined blepharoptosis prevalence according to age, to determine the cutoff age for recommending blepharoptosis evaluation. We also determined the possible association between blepharoptosis and obesity parameters, such as body mass index (BMI) and waist circumference (WC).

Results

There was astrong association between older age and the prevalence of blepharoptosis. The cutoff age for recommending blepharoptosis evaluation was 63 years for males, 70 years for females, and 66 years for all patients. Patients with a high BMI and large WC had a higher prevalence of blepharoptosis in all age groups except for those aged over 80 years. The association of blepharoptosis with BMI according to age group showed that in the 50–59 and 60–69 years age groups, blepharoptosis prevalence and BMI were higher. However, in the 70–79 and 80–89 years age groups, extremely obese patients (BMI > 30) showed a decreased blepharoptosis prevalence.

Conclusions

Moderate to severe blepharoptosis can result in poor visual function and exacerbate headaches and depression, leading to decreased quality of life. This study proposed an appropriate age threshold for recommending evaluation of patients with blepharoptosis among the general population of Korea.
Do smoking, nutrition, alcohol use, and physical activity vary between regions in Germany? - results of a cross-sectional study
Authors: Atzendorf Josefine , Apfelbacher Christian , de Matos Elena Gomes , Lochbühler Kirsten , Piontek Daniela , Seitz Nicki-Nils , Kraus Ludwig
Published: March 2020

Background

Previous studies on lifestyle risk factors mainly focused on age- or gender-specific differences. However, lifestyle risk factors also vary across regions. Aim of the present study was to examine the extent to which prevalence rates of SNAP (smoking, nutrition, alcohol consumption, physical activity) vary between East and West Germany or North and South Germany.

Methods

Data came from the population-representative 2015 Epidemiological Survey of Substance Abuse (ESA) comprising 9204 subjects aged 18 to 64 years. To assess an east-west or south-north gradient, two binary logistic regression models were carried out for each SNAP factor.

Results

The logistic regression models revealed statistically significant differences with higher rates of at-risk alcohol consumption and lower rates of unhealthy nutrition in East Germany compared to West Germany. Significant differences between North and South Germany were found for at-risk alcohol consumption with higher rates of at-risk alcohol consumption in South Germany. Daily smoking and low physical activity were equally distributed across regions.

Conclusions

The implementation of measures reducing at-risk alcohol consumption in Germany should take the identified east-west and south-north gradient into account. Since the prevalence of unhealthy nutrition was generally high, prevention and intervention measures should focus on Germany as a whole instead of specific regions.
Direct and lost productivity costs associated with avoidable hospital admissions
Authors: Rocha João Victor Muniz , Marques Ana Patrícia , Moita Bruno , Santana Rui
Published: March 2020

Background

Hospitalizations for ambulatory care sensitive conditions are commonly used to evaluate primary health care performance, as the hospital admission could be avoided if care was timely and adequate. Previous evidence indicates that avoidable hospitalizations carry a substantial direct financial burden in some countries. However, no attention has been given to the economic burden on society they represent. The aim of this study is to estimate the direct and lost productivity costs of avoidable hospital admissions in Portugal.

Methods

Hospitalizations occurring in Portugal in 2015 were analyzed. Avoidable hospitalizations were defined and their associated costs and years of potential life lost were calculated. Direct costs were obtained using official hospitalization prices. For lost productivity, there were estimated costs for absenteeism and premature death. Costs were analyzed by components, by conditions and by variations on estimation parameters.

Results

The total estimated cost associated with avoidable hospital admissions was €250 million (€2515 per hospitalization), corresponding to 6% of the total budget of public hospitals in Portugal. These hospitalizations led to 109,641 years of potential life lost. Bacterial pneumonia, congestive heart failure and urinary tract infection accounted for 77% of the overall costs. Nearly 82% of avoidable hospitalizations were in patients aged 65 years or older, therefore did not account for the lost productivity costs. Nearly 84% of the total cost comes from the direct cost of the hospitalization. Lost productivity costs are estimated to be around €40 million.

Conclusion

The age distribution of avoidable hospitalizations had a significant effect on costs components. Not only did hospital admissions have a substantial direct economic impact, they also imposed a considerable economic burden on society. Substantial financial resources could potentially be saved if the country reduced avoidable hospitalizations.
A heat-sensitive Osh protein controls PI4P polarity
Authors: Omnus Deike J. , Cadou Angela , Thomas Ffion B. , Bader Jakob M. , Soh Nathaniel , Chung Gary H. C. , Vaughan Andrew N. , Stefan Christopher J.
Published: March 2020

Background

Phosphoinositide lipids provide spatial landmarks during polarized cell growth and migration. Yet how phosphoinositide gradients are oriented in response to extracellular cues and environmental conditions is not well understood. Here, we elucidate an unexpected mode of phosphatidylinositol 4-phosphate (PI4P) regulation in the control of polarized secretion.

Results

We show that PI4P is highly enriched at the plasma membrane of growing daughter cells in budding yeast where polarized secretion occurs. However, upon heat stress conditions that redirect secretory traffic, PI4P rapidly increases at the plasma membrane in mother cells resulting in a more uniform PI4P distribution. Precise control of PI4P distribution is mediated through the Osh (oxysterol-binding protein homology) proteins that bind and present PI4P to a phosphoinositide phosphatase. Interestingly, Osh3 undergoes a phase transition upon heat stress conditions, resulting in intracellular aggregates and reduced cortical localization. Both the Osh3 GOLD and ORD domains are sufficient to form heat stress-induced aggregates, indicating that Osh3 is highly tuned to heat stress conditions. Upon loss of Osh3 function, the polarized distribution of both PI4P and the exocyst component Exo70 are impaired. Thus, an intrinsically heat stress-sensitive PI4P regulatory protein controls the spatial distribution of phosphoinositide lipid metabolism to direct secretory trafficking as needed.

Conclusions

Our results suggest that control of PI4P metabolism by Osh proteins is a key determinant in the control of polarized growth and secretion.
Long noncoding RNA lncARSR promotes nonalcoholic fatty liver disease and hepatocellular carcinoma by promoting YAP1 and activating the IRS2/AKT pathway
Authors: Chi Yuan , Gong Zheng , Xin He , Wang Ziwen , Liu Zhaoyu
Published: March 2020

Background

Nonalcoholic fatty liver disease (NAFLD) is the main cause for hepatocellular carcinoma (HCC). This study was intended to identify the function of long non-coding RNA (lncRNA) lncARSR in NAFLD and its role in human HCC cells (HepG2) proliferation and invasion.

Methods

LncARSR expression was detected both in high fatty acid-treated HepG2 cells and NAFLD mouse model. After gain- and loss-of-function approaches in high fatty acid-treated HepG2 cells and NAFLD mice, lipid accumulation in livers from NAFLD mice and high fatty acid-treated cells was determined by H&E staining, Oil Red-O staining or Nile Red staining respectively. Expression of YAP1, adipogenesis- (Fasn, Scd1 and GPA) and IRS2/AKT pathway-related genes was measured. Cell proliferation was monitored by MTT and soft-agar colony formation assays, cell cycle was analyzed by flow cytometry, and cell invasion was examined by transwell assay. The tumor weight and volume were then measured through in vivo xenograft tumor model after silencing lncARSR.

Results

LncARSR was highly expressed in high fatty diet (HFD)-fed mice and high fatty acid-treated HepG2 cells. LncARSR was observed to bind to YAP1, which inhibited phosphorylation nuclear translocation. LncARSR activated the IRS2/AKT pathway by reducing YAP1 phosphorylation, and further increased lipid accumulation, cell proliferation, invasion and cell cycle. Silencing lncARSR in HFD-fed mice alleviated NAFLD by regulating YAP1/IRS2/AKT axis.

Conclusion

Silencing lncARSR suppressed the IRS2/AKT pathway, consequently reducing HCC cell proliferation and invasion and inhibiting lipid accumulation in NAFLD mice by downregulating YAP1, which suggests a clinical application in treating NAFLD.
Mechanical ventilation weaning issues can be counted on the fingers of just one hand: part 1
Authors: Vetrugno Luigi , Guadagnin Giovanni Maria , Brussa Alessandro , Orso Daniele , Garofalo Eugenio , Bruni Andrea , Longhini Federico , Bove Tiziana
Published: March 2020

Although mechanical ventilation may be a patient’s vital ally during acute illness, it can quickly transform into an enemy during chronic conditions. The weaning process is the fundamental phase that enables the resumption of physiological respiratory function; however, it is also associated with a number of life-threatening complications, and a large percentage of critically ill patients never achieve airway device removal or require the resumption of mechanical ventilation just a few days post-weaning. Indeed, the weaning process is, at present, more of an art than a science. As such, there is urgent need for novel contributions from the scientific literature to abate the growing rates of morbidity and mortality associated with weaning failure. The physician attempting to wean a patient must integrate clinical parameters and common-sense criteria. Numerous studies have striven to identify single predictive factors of weaning failure and sought to standardize the weaning process, but the results are characterized by remarkable heterogeneity. Despite the lack of benchmarks, it is clear that the analysis of respiratory function must include a detailed overview of the five situations described below rather than a single aspect. The purpose of this two-part review is to provide a comprehensive description of these situations to clarify the “arena” physicians are entering when weaning critically ill patients from mechanical ventilation.
Mechanical load-induced H2S production by periodontal ligament stem cells activates M1 macrophages to promote bone remodeling and tooth movement via STAT1
Authors: He Danqing , Liu Fuliang , Cui Shengjie , Jiang Nan , Yu Huajie , Zhou Yanheng , Liu Yan , Kou Xiaoxing
Published: March 2020

Background

Tooth movement is a unique bone remodeling process induced by mechanical stimulation. Macrophages are important in mediating inflammatory processes during mechanical load-induced tooth movement. However, how macrophages are regulated under mechanical stimulation remains unclear. Mesenchymal stem cells (MSCs) can modulate macrophage polarization during bone remodeling. Hydrogen sulfide (H2S) can be produced by MSCs and have been linked to bone homeostasis. Therefore, this study aimed to investigate whether H2S contributed to periodontal ligament stem cell (PDLSC)-regulated macrophage polarization and bone remodeling under mechanical stimulation.

Methods

An experimental mechanical load-induced tooth movement animal model was established. Changes in cystathionine-β-synthase (CBS), markers of M1/M2 macrophages, tooth movement distance, and the number of osteoclasts were examined. The conditioned medium of PDLSCs with or without mechanical loading was utilized to treat THP-1 derived macrophages for 24 h to further investigate the effect of PDLSCs on macrophage polarization. Different treatments with H2S donor, CBS inhibitor, or the inhibitor of STAT1 were used to investigate the related mechanism. Markers of M1/M2 polarization and STAT1 pathway expression were evaluated in macrophages.

Results

Mechanical load promoted tooth movement and increased the number of M1-like macrophages, M1-associated pro-inflammatory cytokines, and the expression of CBS on the compression side of the periodontal ligament. The injection of CBS inhibitor or H2S donor could further repress or increase the number of M1-like macrophages, tartrate-resistant acid phosphatase-positive osteoclasts and the distance of tooth movement. Mechanistically, load-induced PDLSCs enhanced H2S production, which increased the expression of M1-associated cytokines in macrophages. These effects could be blocked by the administration of CBS inhibitor. Moreover, load-induced H2S steered M1 macrophage polarization via the STAT1 signaling pathway.

Conclusions

These data suggest a novel mechanism indicating that mechanical load-stimulated PDLSCs produce H2S to polarize macrophages toward the M1 phenotype via the STAT1 signaling pathway, which contributes to bone remodeling and tooth movement process. These results provide new insights into the role of PDLSCs in regulating macrophage polarization and mediating bone remodeling under mechanical stimulation, and indicate that appropriate H2S supplementation may accelerate tooth movement.
Genome-wide identification of long noncoding RNAs and their competing endogenous RNA networks involved in the odontogenic differentiation of human dental pulp stem cells
Authors: Chen Zhao , Zhang Kaiying , Qiu Wei , Luo Yifei , Pan Yuhua , Li Jianjia , Yang Yeqing , Wu Buling , Fang Fuchun
Published: March 2020

Background

Long noncoding RNAs (lncRNAs) play an important role in the multiple differentiations of mesenchymal stem cells (MSCs). However, few studies have focused on the regulatory mechanism of lncRNAs in the odontogenic differentiation of human dental pulp stem cells (hDPSCs).

Methods

hDPSCs were induced to differentiate into odontoblasts in vitro, and the expression profiles of lncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) in differentiated and undifferentiated cells were obtained by microarray. Bioinformatics analyses including Gene Ontology (GO) analysis, pathway analysis, and binding site prediction were performed for functional annotation of lncRNA. miRNA/odontogenesis-related gene networks and lncRNA-associated ceRNA networks were constructed. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to verify the expression of selected genes. RNA fluorescence in situ hybridization (FISH), qRT-PCR, and western blot analysis were used to explore the location and function of lncRNA-G043225. Dual-luciferase reporter assay was performed to confirm the binding sites of miR-588 with G043225 and Fibrillin 1 (FBN1).

Results

We identified 132 lncRNAs, 114 miRNAs, and 172 mRNAs were differentially expressed. GO analysis demonstrated that regulation of the neurogenic locus notch homolog (Notch), Wnt, and epidermal growth factor receptor (ERBB) signaling pathways and activation of mitogen-activated protein kinase (MAPK) activity were related to odontogenic differentiation. Pathway analysis indicated that the most significant pathway was the forkhead box O (FoxO) signaling pathway, which is related to odontogenic differentiation. Two odontogenesis-related gene-centered lncRNA-associated ceRNA networks were successfully constructed. The qRT-PCR validation results were consistent with the microarray analysis. G043225 mainly locating in cytoplasm was proved to promote the odontogenic differentiation of hDPSCs via miR-588 and FBN1.

Conclusion

This is the first study revealing lncRNA-associated ceRNA network during odontogenic differentiation of hDPSCs using microarray, and it could provide clues to explore the mechanism of action at the RNA-RNA level as well as novel treatments for dentin regeneration based on stem cells.
A secondary bile acid from microbiota metabolism attenuates ileitis and bile acid reduction in subclinical necrotic enteritis in chickens
Authors: Bansal Mohit , Fu Ying , Alrubaye Bilal , Abraha Mussie , Almansour Ayidh , Gupta Anamika , Liyanage Rohana , Wang Hong , Hargis Billy , Sun Xiaolun
Published: March 2020

Background

Clostridium perfringens-induced chicken necrotic enteritis (NE) is responsible for substantial economic losses worldwide annually. Recently, as a result of antibiotic growth promoter prohibition, the prevalence of NE in chickens has reemerged. This study was aimed to reduce NE through titrating dietary deoxycholic acid (DCA) as an effective antimicrobial alternative.

Materials and methods

Day-old broiler chicks were assigned to six groups and fed diets supplemented with 0 (basal diet), 0.8, 1.0 and 1.5 g/kg (on top of basal diet) DCA. The birds were challenged with Eimeria maxima (20,000 oocysts/bird) at d 18 and C. perfringens (109 CFU/bird per day) at d 23, 24, and 25 to induce NE. The birds were sacrificed at d 26 when ileal tissue and digesta were collected for analyzing histopathology, mRNA accumulation and C. perfringens colonization by real-time PCR, targeted metabolomics of bile acids, fluorescence in situ hybridization (FISH), or terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.

Results

At the cellular level, birds infected with E. maxima and C. perfringens developed subclinical NE and showed shortening villi, crypt hyperplasia and immune cell infiltration in ileum. Dietary DCA alleviated the NE-induced ileal inflammation in a dose-dependent manner compared to NE control birds. Consistent with the increased histopathological scores, subclinical NE birds suffered body weight gain reduction compared to the uninfected birds, an effect attenuated with increased doses of dietary DCA. At the molecular level, the highest dose of DCA at 1.5 g/kg reduced C. perfringens luminal colonization compared to NE birds using PCR and FISH. Furthermore, the dietary DCA reduced subclinical NE-induced intestinal inflammatory gene expression and cell apoptosis using PCR and TUNEL assays. Upon further examining ileal bile acid pool through targeted metabolomics, subclinical NE reduced the total bile acid level in ileal digesta compared to uninfected birds. Notably, dietary DCA increased total bile acid and DCA levels in a dose-dependent manner compared to NE birds.

Conclusion

These results indicate that DCA attenuates NE-induced intestinal inflammation and bile acid reduction and could be an effective antimicrobial alternative against the intestinal disease.
Do epigenetic changes caused by commensal microbiota contribute to development of ocular disease? A review of evidence
Authors: Nayyar Ashima , Gindina Sofya , Barron Arturo , Hu Yan , Danias John
Published: March 2020

There is evidence that genetic polymorphisms and environmentally induced epigenetic changes play an important role in modifying disease risk. The commensal microbiota has the ability to affect the cellular environment throughout the body without requiring direct contact; for example, through the generation of a pro-inflammatory state. In this review, we discuss evidence that dysbiosis in intestinal, pharyngeal, oral, and ocular microbiome can lead to epigenetic reprogramming and inflammation making the host more susceptible to ocular disease such as autoimmune uveitis, age-related macular degeneration, and open angle glaucoma. Several mechanisms of action have been proposed to explain how changes to commensal microbiota contribute to these diseases. This is an evolving field that has potentially significant implications in the management of these conditions especially from a public health perspective.
Health related behaviors among HIV-infected people who are successfully linked to care: an institutional-based cross-sectional study
Authors: Xu Jun-Fang , Wang Pei-Cheng , Cheng Feng
Published: March 2020

Background

By the end of October 2019, there were 958 thousand people were reported living with HIV/AIDS in China. Unhealthy lifestyle factors, such as smoking, drinking alcohol, using illicit drugs and no physical activity have been found to mitigate the positive impact of antiretroviral therapy (ART) on viral load and HIV-related quality of life. Moreover, risky sexual behavior among HIV-positive persons places their partners at risk for HIV transmission and other sexually transmitted infections. The aim of the study is to determine the prevalence of unhealthy behavior of people living with HIV/AIDS and related influencing factors, particularly those that are closely connected with HIV infection and ART effects.

Methods

An institutional based cross-sectional study design was used to collect data from people living with HIV/AIDS (PLWHA) in Beijing and Yunnan Province. The following information was included in the questionnaire survey: social-demographic characteristics, health behavior information, sexual risk behaviors. Binary logistic regression model was conducted to analyze the influencing factors of unhealthy general health behaviors and risky sexual behaviors.

Results

In total, 2575 PLWHA were included in the study and 78.3% (2017/2575) were male. For the general health behaviors, 34.2% (987/2544) smoke; 33.8% (870/2575) drank alcohol and 2.3% (49/2134) reported the use of illicit drugs in the previous 6 months. From the sexual behaviors perspective, 59.0% (1519/2575) had sex in the previous 6 months. Among people who had sex, 92.0% (1398/1519) had fixed sexual partners. Among those with no fixed sexual partner, 38.0% (46/121) had more than three partners. Among men who had sex, 34.7% (448/1292) reported having sex with men in the previous 6 months and 16.7% (75/448) of these had group sexual activity. Among participants, 72.2% (1053/1458) used condoms every time they had sex while 6.4% (94/1458) of people never used condom. Male people living with HIV/AIDS were more likely to have sexual risk behaviors (adjusted odds ratio [OR] = 2.208, 95% confidence interval [CI]: 1.147–4.252) and unhealthy general health behaviors (adjusted OR = 2.029, 95% CI: 1.480–2.783). The odds of higher risk sexual behaviors was 1.546 times (95% CI: 1.302–1.827, P = 0.001) greater among participants who drank alcohol compared with their non-drinking counterparts.

Conclusions

PLWHA is a group that is vulnerable to problematic health behaviors, especially for men who were more likely to drink alcohol, have more sexual partners, more sexual risk behaviors including group sexual activity, not using condoms and using drugs. Therefore, interventions focusing on gender-specific risk behaviors reduction for people living with HIV/AIDS are now necessary to control the spread of HIV infection and improve the efficacy of antiviral treatment.
Histological correlates of postmortem ultra-high-resolution single-section MRI in cortical cerebral microinfarcts
Authors: Yilmazer-Hanke Deniz , Mayer Theresa , Müller Hans-Peter , Neugebauer Hermann , Abaei Alireza , Scheuerle Angelika , Weis Joachim , Forsberg Karin M. E. , Althaus Katharina , Meier Julia , Ludolph Albert C. , Del Tredici Kelly , Braak Heiko , Kassubek Jan , Rasche Volker
Published: March 2020

The identification of cerebral microinfarctions with magnetic resonance imaging (MRI) and histological methods remains challenging in aging and dementia. Here, we matched pathological changes in the microvasculature of cortical cerebral microinfarcts to MRI signals using single 100 μm-thick histological sections scanned with ultra-high-resolution 11.7 T MRI. Histologically, microinfarcts were located in superficial or deep cortical layers or transcortically, compatible with the pattern of layer-specific arteriolar blood supply of the cerebral cortex. Contrary to acute microinfarcts, at chronic stages the core region of microinfarcts showed pallor with extracellular accumulation of lipofuscin and depletion of neurons, a dense meshwork of collagen 4-positive microvessels with numerous string vessels, CD68-positive macrophages and glial fibrillary acidic protein (GFAP)-positive astrocytes. In MRI scans, cortical microinfarcts at chronic stages, called chronic cortical microinfarcts here, gave hypointense signals in T1-weighted and hyperintense signals in T2-weighted images when thinning of the tissue and cavitation and/or prominent iron accumulation were present. Iron accumulation in chronic microinfarcts, histologically verified with Prussian blue staining, also produced strong hypointense T2*-weighted signals. In summary, the microinfarct core was occupied by a dense microvascular meshwork with string vessels, which was invaded by macrophages and astroglia and contained various degrees of iron accumulation. While postmortem ultra-high-resolution single-section imaging improved MRI-histological matching and the structural characterization of chronic cortical cerebral microinfarcts, miniscule microinfarcts without thinning or iron accumulation could not be detected with certainty in the MRI scans. Moreover, string vessels at the infarct margin indicate disturbances in the microcirculation in and around microinfarcts, which might be exploitable in the diagnostics of cortical cerebral microinfarcts with MRI in vivo.
CMT2Q-causing mutation in the Dhtkd1 gene lead to sensory defects, mitochondrial accumulation and altered metabolism in a knock-in mouse model
Authors: Luan Chun-jie , Guo Wenting , Chen Lei , Wei Xi-wei , He Yimin , Chen Yan , Dang Su-ying , Prior Robert , Li Xihua , Kuang Ying , Wang Zhu-gang , Van Den Bosch Ludo , Gu Ming-min
Published: March 2020

Charcot-Marie-Tooth disease (CMT) is a group of inherited neurological disorders of the peripheral nervous system. CMT is subdivided into two main types: a demyelinating form, known as CMT1, and an axonal form, known as CMT2. Nearly 30 genes have been identified as a cause of CMT2. One of these is the ‘dehydrogenase E1 and transketolase domain containing 1’ (DHTKD1) gene. We previously demonstrated that a nonsense mutation [c.1455 T > G (p.Y485*)] in exon 8 of DHTKD1 is one of the disease-causing mutations in CMT2Q (MIM 615025). The aim of the current study was to investigate whether human disease-causing mutations in the Dhtkd1 gene cause CMT2Q phenotypes in a mouse model in order to investigate the physiological function and pathogenic mechanisms associated with mutations in the Dhtkd1 gene in vivo. Therefore, we generated a knock-in mouse model with the Dhtkd1Y486* point mutation. We observed that the Dhtkd1 expression level in sciatic nerve of knock-in mice was significantly lower than in wild-type mice. Moreover, a histopathological phenotype was observed, reminiscent of a peripheral neuropathy, including reduced large axon diameter and abnormal myelination in peripheral nerves. The knock-in mice also displayed clear sensory defects, while no abnormalities in the motor performance were observed. In addition, accumulation of mitochondria and an elevated energy metabolic state was observed in the knock-in mice. Taken together, our study indicates that the Dhtkd1Y486* knock-in mice partially recapitulate the clinical phenotypes of CMT2Q patients and we hypothesize that there might be a compensatory effect from the elevated metabolic state in the knock-in mice that enables them to maintain their normal locomotor function.
Young refugees and locals living under the same roof: intercultural communal living as a catalyst for refugees’ integration in European urban communities?
Authors: Mahieu Rilke , Van Caudenberg Rut
Published: March 2020

In various European cities urban authorities and local stakeholders are exploring ways to tackle challenges arising from recent refugee flows. A central concern is the social integration of refugees: how to connect this particular category of newcomers – and especially the most vulnerable ones – durably with local communities? In this article, we discuss an urban programme that offers young unaccompanied refugees (aged 17–23) cohabitation with young locals (aged 20–30) during a period of one to 2 years in Antwerp (Belgium) in small-scale collective housing units. The programme’s assumption is that this mixed, intercultural communal living will promote regular, informal and meaningful social encounters between refugees and locals, which in turn will strengthen the independence and social inclusion of the young refugees.

In this article, we investigate the opportunities top-down organized intercultural communal living creates for refugee integration. We draw on interviews and observations collected among locals and refugees living together to gain insights into both groups of participants’ experiences with collective living and the actual social dynamics emerging in such a setting. Our findings suggest that intercultural communal living can be conceptualized as an environment where various informal forms of social support and mutual learning emerge. As such, we contribute to the conceptualization of the impact of intercultural communal living on newcomer integration.