bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulation of operating room crisis management - hypotension training for pre‐clinical students
Authors: Gao Peng , Wang Chenyu , Liu Shijia , Tran Kevin C. , Wen Qingping
Published: January 2021

Background

Simulation training is an essential criterion for medical staff. The majority of residents are trained in operating room crisis management (ORCM), but only a few pre-clinical anesthesia undergraduate students are trained. Anesthesia methodology and technology were studied by the anesthesia undergraduate students in theory, but they were not able to practically resolve all clinical problems scientifically and reasonably. Consequently, there is a need to apply their competencies and bring together their technology knowledge practically. The crisis management of operating room emergencies was a method of choice applied and used over time. Here, we designed the scenarios for comprehensive crisis management to train anesthesia undergraduate students. We tried to establish or identify the problems which occurred during attempts to implement these scenarios.

Methods

Anesthesia undergraduate students initially examined the basic theory, fundamental practice techniques, and case studies before the simulation training program. Subsequently, they participated in comprehensive ORCM training. Training outcomes were evaluated through different viewpoints: understanding the subject, crisis management, nontechnical skills, and a user experience evaluation.

Results

Anesthesia undergraduate students performed significantly better with completion of ORCM, indicated by higher scores in all four tests (P < 0.001), as well as clinical crisis management (P = 0.0016) and nontechnical skills (P = 0.0002). Following the simulation, the students described the experience as helpful in “combining theoretical knowledge with clinical practice”, helpful with memorization, and in “promoting understanding of the subject,” while “learning clinical logic authentically” and “inspiring learning interests.”

Conclusions

This research indicates that ORCM could be implemented as a useful learning tool for pre-clinical anesthesia undergraduate students. The ORCM could be an excellent training method to help improve students’ professional competence in crisis management and nontechnical skills, integrating the knowledge and technology of the field of anesthesiology.
Laboratory test ordering in inpatient hospitals: a systematic review on the effects and features of clinical decision support systems
Authors: Zare Sahar , Meidani Zahra , Shirdeli Mohammad , Nabovati Ehsan
Published: January 2021

Background

Studies have revealed inappropriate laboratory testing as a source of waste. This review aimed at evaluating the effects and features of CDSSs on physicians' appropriate laboratory test ordering in inpatient hospitals.

Method

Medline through PubMed, SCOPUS, Web of Science, and Cochrane were queried without any time period restriction. Studies using CDSSs as an intervention to improve laboratory test ordering as the primary aim were included. The study populations in the included studies were laboratory tests, physicians ordering laboratory tests, or the patients for whom laboratory tests were ordered. The included papers were evaluated for their outcomes related to the effect of CDSSs which were categorized based on the outcomes related to tests, physician, and patients. The primary outcome measures were the number and cost of the ordered laboratory tests. The instrument from The National Heart Lung and Blood Institute (NIH) was used to assess the quality of the included studies. Moreover, we applied a checklist for assessing the quality and features of the CDSSs presented in the included studies. A narrative synthesis was used to describe and compare the designs and the results of included studies.

Result

Sixteen studies met the inclusion criteria. Most studies were conducted based on a quasi-experimental design. The results showed improvement in laboratory test-related outcomes (e.g. proportion and cost of tests) and also physician-related outcomes (e.g. guideline adherence and orders cancellation). Patient-related outcomes (e.g. length of stay and mortality rate) were not well investigated in the included studies. In addition, the evidence about applying CDSS as a decision aid for interpreting laboratory results was rare.

Conclusion

CDSSs increase appropriate test ordering in hospitals through eliminating redundant test orders and enhancing evidence-based practice. Appropriate testing and cost saving were both affected by the CDSSs. However, the evidence is limited about the effects of laboratory test CDSSs on patient-related outcomes.
Mixotrophic chemosynthesis in a deep-sea anemone from hydrothermal vents in the Pescadero Basin, Gulf of California
Authors: Goffredi Shana K. , Motooka Cambrie , Fike David A. , Gusmão Luciana C. , Tilic Ekin , Rouse Greg W. , Rodríguez Estefanía
Published: January 2021

Background

Numerous deep-sea invertebrates, at both hydrothermal vents and methane seeps, have formed symbiotic associations with internal chemosynthetic bacteria in order to harness inorganic energy sources typically unavailable to animals. Despite success in nearly all marine habitats and their well-known associations with photosynthetic symbionts, Cnidaria remain one of the only phyla present in the deep-sea without a clearly documented example of dependence on chemosynthetic symbionts.

Results

A new chemosynthetic symbiosis between the sea anemone Ostiactis pearseae and intracellular bacteria was discovered at ~ 3700 m deep hydrothermal vents in the southern Pescadero Basin, Gulf of California. Unlike most sea anemones observed from chemically reduced habitats, this species was observed in and amongst vigorously venting fluids, side-by-side with the chemosynthetic tubeworm Oasisia aff. alvinae. Individuals of O. pearseae displayed carbon, nitrogen, and sulfur tissue isotope values suggestive of a nutritional strategy distinct from the suspension feeding or prey capture conventionally employed by sea anemones. Molecular and microscopic evidence confirmed the presence of intracellular SUP05-related bacteria housed in the tentacle epidermis of O. pearseae specimens collected from 5 hydrothermally active structures within two vent fields ~ 2 km apart. SUP05 bacteria (Thioglobaceae) dominated the O. pearseae bacterial community, but were not recovered from other nearby anemones, and were generally rare in the surrounding water. Further, the specific Ostiactis-associated SUP05 phylotypes were not detected in the environment, indicating a specific association. Two unusual candidate bacterial phyla (the OD1 and BD1-5 groups) appear to associate exclusively with O. pearseae and may play a role in symbiont sulfur cycling.

Conclusion

The Cnidarian Ostiactis pearseae maintains a physical and nutritional alliance with chemosynthetic bacteria. The mixotrophic nature of this symbiosis is consistent with what is known about other cnidarians and the SUP05 bacterial group, in that they both form dynamic relationships to succeed in nature. The advantages gained by appropriating metabolic and structural resources from each other presumably contribute to their striking abundance in the Pescadero Basin, at the deepest known hydrothermal vents in the Pacific Ocean.
SNORD63 and SNORD96A as the non-invasive diagnostic biomarkers for clear cell renal cell carcinoma
Authors: Shang Xiaoling , Song Xingguo , Wang Kangyu , Yu Miao , Ding Shanshan , Dong Xiaohan , Xie Li , Song Xianrang
Published: January 2021

Background

Increasing evidence has demonstrated that snoRNAs play crucial roles in tumorigenesis of various cancer types. However, researches on snoRNAs in ccRCC were very little. This study mainly aimed to validate the differential expression and the potential diagnostic value of SNORD63 and SNORD96A in ccRCC.

Methods

SnoRNAs expression was downloaded from the SNORic and TCGA database including 516 patients with ccRCC and 71 control cases. SNORD63 and SNORD96A expression were further detected in 54 tumor and adjacent FFPE ccRCC tissues, 55 plasma and 75 urinary sediment of ccRCC patients. Then, differential expression and diagnostic value of SNORD63 and SNORD96A were further calculated.

Results

SNORD63 and SNORD96A expression were significantly increased in ccRCC tissues compared with normal tissues from the TCGA database (both, P < 0.0001). In addition, we found that SNORD63 and SNORD96A localized in plasma and US stably after treating with RNase A. Meanwhile, SNORD63 and SNORD96A in FFPE and US were elevated in ccRCC patients (all, P < 0.0001). However, plasma SNORD63 expression had no significance while SNORD96A significantly increased in plasma of ccRCC patients. Notably, the AUC of SNORD63 in US was 0.7055, by comparison the AUC of plasma SNORD63 was only 0.5161. However, the AUC of plasma SNORD96A was up to 0.8909, by comparison the AUC of SNORD96A in US was 0.6788. Interestingly, the AUC of plasma SNORD96A in early stage ccRCC was highly up to 0.9359.

Conclusions

Our findings revealed that SNORD63 in US and SNORD96A in plasma could act as the promising non-invasive diagnostic biomarkers for ccRCC patients.
Association of nutrient-derived dietary patterns with sarcopenia and its components in community-dwelling older Japanese: a cross-sectional study
Authors: Yokoyama Yuri , Kitamura Akihiko , Seino Satoshi , Kim Hunkyung , Obuchi Shuichi , Kawai Hisashi , Hirano Hirohiko , Watanabe Yutaka , Motokawa Keiko , Narita Miki , Shinkai Shoji
Published: January 2021

Background

Diet is a modifiable factor affecting sarcopenia, and accumulating evidence links dietary factors to muscle mass, strength, and function in older adults. However, few studies have examined the association of dietary patterns with sarcopenia. This study examined the association of dietary patterns derived by reduced-rank regression (RRR) with sarcopenia and its components in community-dwelling older Japanese.

Methods

We conducted a cross-sectional study of 1606 community-dwelling adults aged 65 years or older. Dietary intake was assessed by a validated, self-administered diet history questionnaire. Nutrient-derived dietary patterns were identified by using RRR, with sarcopenia-related nutrients (protein, vitamin D, vitamin C, vitamin E, folate, vitamin K, magnesium, iron, and calcium intakes) as response variables. Sarcopenia was defined by using the algorithm of the Asian Working Group for Sarcopenia 2019. Multivariate regression and logistic regression were used to examine the association of dietary patterns with sarcopenia and its components.

Results

The first RRR dietary pattern was characterized by high intakes of fish, soybean products, potatoes, most vegetables, mushrooms, seaweeds, and fruit and a low intake of rice and was associated with decreased prevalence of sarcopenia: the multivariable-adjusted odds ratio of sarcopenia was 0.57 (95% confidence interval, 0.34–0.94; p for trend=0.022) in the highest versus the lowest tertile of dietary pattern. This dietary pattern was also significantly positively associated with usual gait speed (β: 0.02, p=0.024).

Conclusions

A dietary pattern characterized by high intakes of fish, soybean products, potatoes, most vegetables, mushrooms, seaweeds, and fruits and low rice intake was inversely associated with sarcopenia in community-dwelling older Japanese.
Exploring country-wide equitable government health care facility access in Uganda
Authors: Dowhaniuk Nicholas
Published: January 2021

Background

Rural access to health care remains a challenge in Sub-Saharan Africa due to urban bias, social determinants of health, and transportation-related barriers. Health systems in Sub-Saharan Africa often lack equity, leaving disproportionately less health center access for the poorest residents with the highest health care needs. Lack of health care equity in Sub-Saharan Africa has become of increasing concern as countries enter a period of simultaneous high infectious and non-communicable disease burdens, the second of which requires a robust primary care network due to a long continuum of care. Bicycle ownership has been proposed and promoted as one tool to reduce travel-related barriers to health-services among the poor.

Methods

An accessibility analysis was conducted to identify the proportion of Ugandans within one-hour travel time to government health centers using walking, bicycling, and driving scenarios. Statistically significant clusters of high and low travel time to health centers were calculated using spatial statistics. Random Forest analysis was used to explore the relationship between poverty, population density, health center access in minutes, and time saved in travel to health centers using a bicycle instead of walking. Linear Mixed-Effects Models were then used to validate the performance of the random forest models.

Results

The percentage of Ugandans within a one-hour walking distance of the nearest health center II is 71.73%, increasing to 90.57% through bicycles. Bicycles increased one-hour access to the nearest health center III from 53.05 to 80.57%, increasing access to the tiered integrated national laboratory system by 27.52 percentage points. Significant clusters of low health center access were associated with areas of high poverty and urbanicity. A strong direct relationship between travel time to health center and poverty exists at all health center levels. Strong disparities between urban and rural populations exist, with rural poor residents facing disproportionately long travel time to health center compared to wealthier urban residents.

Conclusions

The results of this study highlight how the most vulnerable Ugandans, who are the least likely to afford transportation, experience the highest prohibitive travel distances to health centers. Bicycles appear to be a “pro-poor” tool to increase health access equity.
Adapting the SPOTLIGHT Virtual Audit Tool to assess food and activity environments relevant for adolescents: a validity and reliability study
Authors: Andersen Oddbjørn Klomsten , O’Halloran Siobhan A. , Kolle Elin , Lien Nanna , Lakerveld Jeroen , Arah Onyebuchi A. , Gebremariam Mekdes K.
Published: January 2021

Background

Physical inactivity and unhealthy diet are key behavioral determinants underlying obesity. The neighborhood environment represents an important arena for modifying these behaviors, and hence reliable and valid tools to measure it are needed. Most existing virtual audit tools have been designed to assess either food or activity environments deemed relevant for adults. Thus, there is a need for a tool that combines the assessment of food and activity environments, and which focuses on aspects of the environment relevant for youth.

Objective

The aims of the present study were: (a) to adapt the SPOTLIGHT Virtual Audit Tool (S-VAT) developed to assess characteristics of the built environment deemed relevant for adults for use in an adolescent population, (b) to assess the tool’s inter- and intra-rater reliability, and (c) to assess its criterion validity by comparing the virtual audit to a field audit.

Methods

The tool adaptation was based on literature review and on results of a qualitative survey investigating how adolescents perceived the influence of the environment on dietary and physical activity behaviors. Sixty streets (148 street segments) in six neighborhoods were randomly selected as the study sample. Two raters assessed the inter- and intra-rater reliability and criterion validity, comparing the virtual audit tool to a field audit. The results were presented as percentage agreement and Cohen’s kappa (κ).

Results

Intra-rater agreement was found to be moderate to almost perfect (κ = 0.44–0.96) in all categories, except in the category aesthetics (κ = 0.40). Inter-rater agreement between auditors ranged from fair to substantial for all categories (κ = 0.24–0.80). Criterion validity was found to be moderate to almost perfect (κ = 0.56–0.82) for most categories, except aesthetics and grocery stores (κ = 0.26–0.35).

Conclusion

The adapted version of the S-VAT can be used to provide reliable and valid data on built environment characteristics deemed relevant for physical activity and dietary behavior among adolescents.
Factors associated with health-related quality of life of military policemen in Salvador, Brazil: cross-sectional study
Authors: Barreto Carla Requião , Carvalho Fernando Martins , Lins-Kusterer Liliane
Published: January 2021

Background

Brazil is a violent society and police officers play a fundamental role in this scenario. Police work is a stressful occupation. Dealing with routine violence, police officers must have high standards of physical and mental health. Patrolling the streets involves several risks and stressful situations that may hamper military policemen's quality of life. The identification of factors associated with health-related quality of life may help in planning and providing adequate care to military policemen. This study aimed to identify factors associated with health-related quality of life of military policemen in Salvador, Brazil.

Methods

A cross-sectional design study investigated a random sample of 329 male military police officers, engaged in patrolling the streets of Salvador, Brazil. A structured questionnaire applied to the policemen collected information about age, education, marital status, income, house ownership, car ownership, police rank, working day, alcohol consumption, smoking, frequency of vigorous physical activity, obesity (body mass index ≥ 30.0), and work ability. Health-related quality of life was evaluated through the 36-Item Short Form Health Survey Questionnaire (SF-36). Work ability was assessed through the Work Ability Index questionnaire. Poor work ability was defined by a 7–27 points score. Multiple linear regression models were used to measure the impact of police officers characteristics on the variation in the Physical Component and Mental Component Summary scores.

Results

Normalised scores were below 50.0% for seven out of the eight SF-36 domains and for the two component summaries. The SF-36 Physical Component Summary was significantly (P < 0.05) associated with poor work ability, while the Mental Component Summary was associated with poor work ability, excessive alcohol consumption, and younger age (24–34 years). Multivariate analysis estimated that the Physical Component Summary was 7.386 units (%) lower among policemen with poor work ability compared to those with moderate/good/excellent work ability. The Mental Component Summary was 12.755 units lower among those with poor work ability, 5.354 units lower among those with excessive alcohol consumption, and 5.532 units higher among those with younger age.

Conclusions

The military police officers investigated presented low health-related quality of life, associated with younger age, excessive alcohol consumption, and poor work ability.
Metabotropic glutamate receptor 5 inhibits α-synuclein-induced microglia inflammation to protect from neurotoxicity in Parkinson’s disease
Authors: Zhang Ya-Nan , Fan Jing-Kai , Gu Li , Yang Hui-Min , Zhan Shu-Qin , Zhang Hong
Published: January 2021

Background

Microglia activation induced by α-synuclein (α-syn) is one of the most important factors in Parkinson’s disease (PD) pathogenesis. However, the molecular mechanisms by which α-syn exerts neuroinflammation and neurotoxicity remain largely elusive. Targeting metabotropic glutamate receptor 5 (mGluR5) has been an attractive strategy to mediate microglia activation for neuroprotection, which might be an essential regulator to modulate α-syn-induced neuroinflammation for the treatment of PD. Here, we showed that mGluR5 inhibited α-syn-induced microglia inflammation to protect from neurotoxicity in vitro and in vivo.

Methods

Co-immunoprecipitation assays were utilized to detect the interaction between mGluR5 and α-syn in microglia. Griess, ELISA, real-time PCR, western blotting, and immunofluorescence assays were used to detect the regulation of α-syn-induced inflammatory signaling, cytokine secretion, and lysosome-dependent degradation.

Results

α-syn selectively interacted with mGluR5 but not mGluR3, and α-syn N terminal deletion region was essential for binding to mGluR5 in co-transfected HEK293T cells. The interaction between these two proteins was further detected in BV2 microglia, which was inhibited by the mGluR5 specific agonist CHPG without effect by its selective antagonist MTEP. Moreover, in both BV2 cells and primary microglia, activation of mGluR5 by CHPG partially inhibited α-syn-induced inflammatory signaling and cytokine secretion and also inhibited the microglia activation to protect from neurotoxicity. We further found that α-syn overexpression decreased mGluR5 expression via a lysosomal pathway, as evidenced by the lysosomal inhibitor, NH4Cl, by blocking mGluR5 degradation, which was not evident with the proteasome inhibitor, MG132. Additionally, co-localization of mGluR5 with α-syn was detected in lysosomes as merging with its marker, LAMP-1. Consistently, in vivo experiments with LPS- or AAV-α-syn-induced rat PD model also confirmed that α-syn accelerated lysosome-dependent degradation of mGluR5 involving a complex, to regulate neuroinflammation. Importantly, the binding is strengthened with LPS or α-syn overexpression but alleviated by urate, a potential clinical biomarker for PD.

Conclusions

These findings provided evidence for a novel mechanism by which the association of α-syn with mGluR5 was attributed to α-syn-induced microglia activation via modulation of mGluR5 degradation and its intracellular signaling. This may be a new molecular target for an effective therapeutic strategy for PD pathology.
Knowledge of and adherence to radiographic guidelines for low back pain: a survey of chiropractors in Newfoundland and Labrador, Canada
Authors: De Carvalho Diana , Bussières André , French Simon D. , Wade Darrell , Brake-Patten Debbie , O’Keefe Lino , Elliott Barbara , Budgell Ken , O’Reilly Sara , To Daphne , Hall Amanda
Published: January 2021

Background

Low back pain (LBP) rarely requires routine imaging of the lumbar spine in the primary care setting, as serious spinal pathology is rare. Despite evidence-based clinical practice guidelines recommending delaying imaging in the absence of red flags, chiropractors commonly order imaging outside of these guidelines. The purpose of this study was to survey chiropractors to determine the level of knowledge, adherence to, and beliefs about, clinical practice guidelines related to the use of lumbar radiography for LBP in Newfoundland and Labrador (NL), Canada.

Methods

A cross-sectional survey of chiropractors in NL (n = 69) was conducted between May and June 2018, including questions on demographics, awareness of radiographic guidelines, and beliefs about radiographs for LBP. We assessed behavioural simulation using clinical vignettes to determine levels of adherence to LBP guideline recommendations.

Results

The response rate was 77% (n = 53). Half of the participants stated they were aware of current radiographic guideline recommendations, and one quarter of participants indicated they did not use guidelines to inform clinical decisions. The majority of participants agreed that x-rays of the lumbar spine are useful for patients with suspected pathology, are indicated when a patient is non-responsive to 4 weeks of conservative treatment for LBP, and when there are neurological signs associated with LBP. However, a small proportion indicated that there is a role for full spine x-rays (~ 21%), x-rays to evaluate patients with acute LBP (~ 13%), and that patient expectations play a role in decision making (4%). Adherence rate to radiographic guidelines measured using clinical vignettes was 75%.

Conclusions

While many chiropractors in this sample reported being unsure of specific radiographic guidelines, the majority of respondents adhered to guideline recommendations measured using clinical vignettes. Nonetheless, a small proportion still hold beliefs about radiographs for LBP that are discordant with current radiographic guidelines. Future research should aim to determine barriers to guideline uptake in this population in order to design and evaluate tailored knowledge translation strategies to reduce unnecessary LBP imaging.
Anemoside B4 ameliorates TNBS-induced colitis through S100A9/MAPK/NF-κB signaling pathway
Authors: Zhang Yong , Zha Zhengxia , Shen Wenhua , Li Dan , Kang Naixin , Chen Zhong , Liu Yanli , Xu Guoqiang , Xu Qiongming
Published: January 2021

Background

Despite the increased morbidity of ulcerative colitis (UC) in the developing countries, available treatments remain unsatisfactory. Therefore, it is urgent to discover more effective therapeutic strategies. Pulsatilla chinensis was widely used for the treatment of inflamed intestinal diseases including UC for thousands of years in China. Anemoside B4, the most abundant triterpenoid saponin isolated from P. chinensis, exerts anti-inflammatory and antioxidant effects and may be the most active compounds, which is responsible for the therapeutic effects. However, the mechanism how anemoside B4 executes its biological functions is still elusive.

Methods

Here, we used the 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rat model to evaluate the therapeutic effect of anemoside B4. Blood samples of colitis rats were collected for hematology analysis. The inflammation-associated factors were investigated by enzyme-linked immunosorbent assay (ELISA). Cell proliferation and apoptosis was determined with EdU cell proliferation assay and TUNEL assay. The proteins regulated by anemoside B4 were identified by label-free quantitative proteomics. The significantly down-regulated proteins were verified by Western blotting analysis. mRNA expression was analyzed by quantitative real-time RT-PCR.

Results

The results showed that anemoside B4 ameliorated TNBS-induced colitis symptoms, including tissue damage, inflammatory cell infiltration, and pro-inflammatory cytokine production, apoptosis and slowed proliferation in colon. Quantitative proteomic analyses discovered that 56 proteins were significantly altered by anemoside B4 in the TNBS-induced rats. These proteins mainly clustered in tricarboxylic acid (TCA) cycle and respiratory electron transport chain. Among the altered proteins, S100A9 is one of the most significantly down-regulated proteins and associated with NF-κB and MAPK signaling pathways in the pathogenesis of UC. Further experiments revealed that anemoside B4 suppressed the expression of S100A9 and its downstream genes including TLR4 and NF-κB in colon. In vitro, anemoside B4 could inhibit the NF-κB signaling pathway induced by recombinant S100A9 protein in human intestinal epithelial Caco-2 cells. Moreover, anemoside B4 inhibits neutrophils recruitment and activation in colon induced by TNBS.

Conclusions

Our results demonstrate that anemoside B4 prevents TNBS-induced colitis by inhibiting the NF-κB signaling pathway through deactivating S100A9, suggesting that anemoside B4 is a promising therapeutic candidate for colitis.
The psychosocial barriers to medication adherence of patients with type 2 diabetes: a qualitative study
Authors: Mostafavi Firoozeh , Alavijeh Fereshteh Zamani , Salahshouri Arash , Mahaki Behzad
Published: January 2021

Background

The adherence of diabetic patients to their medication regimen is associated with many psychosocial factors that are still unknown. Therefore, the present study aims to identify the psychosocial barriers to medication adherence of patients with type2 diabetes (T2D).

Methodology

This descriptive qualitative study was done in Isfahan, Iran by conducting in-depth unstructured interviews with 23 purposively selected patients with T2D and 10 healthcare providers (HCPs). The participants were interviewed face-to-face between November 2017 and June 2018 at the patient’s home, a Health Care Center, or at the diabetes clinic. Data analysis was performed using MAXQDA-10 software and the conventional content analysis.

Results

The analysis of the data led to six categories of perceived psychosocial barriers: 1) fear, concern and distress, 2) exhaustion and burnout, 3) the children’s issues being the priority, 4) poor financial support, 5) communication challenges, and 6) poor work conditions.

Conclusions

This study identified some of the psychosocial barriers to medication adherence of patients with T2D, which will be of great help to researchers and HCPs in designing and implementing effective interventions to overcome these barriers and change patient self-care behaviors and increase their medication adherence.
Neuropilin 1 and Neuropilin 2 gene invalidation or pharmacological inhibition reveals their relevance for the treatment of metastatic renal cell carcinoma
Authors: Dumond Aurore , Brachet Etienne , Durivault Jérôme , Vial Valérie , Puszko Anna K. , Lepelletier Yves , Montemagno Christopher , Pagnuzzi-Boncompagni Marina , Hermine Olivier , Garbay Christiane , Lagarde Nathalie , Montes Matthieu , Demange Luc , Grépin Renaud , Pagès Gilles
Published: January 2021

Background

Despite the improvement of relapse-free survival mediated by anti-angiogenic drugs like sunitinib (Sutent®), or by combinations of anti-angiogenic drugs with immunotherapy, metastatic clear cell Renal Cell Carcinoma (mccRCC) remain incurable. Hence, new relevant treatments are urgently needed. The VEGFs coreceptors, Neuropilins 1, 2 (NRP1, 2) are expressed on several tumor cells including ccRCC. We analyzed the role of the VEGFs/NRPs signaling in ccRCC aggressiveness and evaluated the relevance to target this pathway.

Methods

We correlated the NRP1, 2 levels to patients’ survival using online available data base. Human and mouse ccRCC cells were knocked-out for theNRP1andNRP2genes by a CRISPR/Cas9 method. The number of metabolically active cells was evaluated by XTT assays. Migration ability was determined by wound closure experiments and invasion ability by using Boyden chamber coated with collagen. Production of VEGFA and VEGFC was evaluated by ELISA. Experimental ccRCC were generated in immuno-competent/deficient mice. The effects of a competitive inhibitor of NRP1, 2, NRPa-308, was tested in vitro and in vivo with the above-mentioned tests and on experimental ccRCC. NRPa-308 docking was performed on both NRPs.

Results

Knock-out of theNRP1andNRP2genes inhibited cell metabolism and migration and stimulated the expression of VEGFA or VEGFC, respectively. NRPa-308 presented a higher affinity for NRP2 than for NRP1. It decreased cell metabolism and migration/invasion more efficiently than sunitinib and the commercially available NRP inhibitor EG00229. NRPa-308 presented a robust inhibition of experimental ccRCC growth in immunocompetent and immunodeficient mice. Such inhibition was associated with decreased expression of several pro-tumoral factors. Analysis of the TCGA database showed that the NRP2 pathway, more than the NRP1 pathway correlates with tumor aggressiveness only in metastatic patients.

Conclusions

Our study strongly suggests that inhibiting NRPs is a relevant treatment for mccRCC patients in therapeutic impasses and NRPa-308 represents a relevant hit.
Effects of exogenous adiponectin supplementation in early pregnant PCOS mice on the metabolic syndrome of adult female offspring
Authors: Zuo Meng , Liao Guotao , Zhang Wenqian , Xu Dan , Lu Juan , Tang Manhong , Yan Yue , Hong Chenghao , Wang Yuxia
Published: January 2021

Objective

PCOS is a heterogeneous endocrine disorder with both reproductive and metabolic abnormalities. At present, PCOS has been confirmed to have a certain genetic background. Compared with healthy women, the vast majority of PCOS patients have hyperandrogenemia, and this excessive androgen exposure during pregnancy may affect the development of female fetuses. The aim of the current study was to investigate the effect of adiponectin intervention during early pregnancy of obese mice with PCOS on the metabolic phenotype of adult female offspring.

Methods

After the PCOS model was established, C57BL/6J mice were divided into maternal-control, maternal-PCOS, and maternal-PCOS + APN groups. DHEA-induced PCOS mice were supplemented with adiponectin (10 mg/kg/day) in the early pregnancy in order to eliminate adverse hormone exposure and then traced for endocrine indicators in their adult female offspring, which were observed for metabolism syndrome or endocrine disturbance and exhibited the main effects of APN. To further explore the underlying mechanism, the relative expressions of phosphorylated AMPK, PI3K, and Akt were detected in the ovaries of offspring mice.

Results

The serum testosterone level of the maternal-PCOS + APN group in early pregnancy was significantly lower than that of the maternal-PCOS group (p < 0.01). The serum testosterone level in the offspring-PCOS + APN group was significantly lower than in the offspring-PCOS group (p <0.05), the diestrus time characterized by massive granulocyte aggregation in the estrus cycle was significantly shorter than in the offspring-PCOS group (p<0.05), and the phenotypes of PCOS-like reproductive disorders and metabolic disorders, such as obesity, insulin resistance, impaired glucose tolerance, and hyperlipidemia, were also significantly improved in the offspring-PCOS + APN group (p < 0.05). Compared with the control group, the expression levels of phosphorylated AMPK, PI3K, and Akt in the offspring-PCOS group were significantly decreased (p < 0.05), while those in the offspring-PCOS + APN group were significantly increased (p < 0.05).

Conclusions

APN intervention in early pregnancy significantly reduced the adverse effects of maternal obesity and high androgen levels during pregnancy on female offspring and corrected the PCOS-like endocrine phenotype and metabolic disorders of adult female offspring. This effect may be caused by the activation of the AMPK/PI3K-Akt signaling pathway in PCOS offspring mice.
Coculture with hemicellulose-fermenting microbes reverses inhibition of corn fiber solubilization by Clostridium thermocellum at elevated solids loadings
Authors: Beri Dhananjay , Herring Christopher D. , Blahova Sofie , Poudel Suresh , Giannone Richard J. , Hettich Robert L. , Lynd Lee R.
Published: January 2021

Background

The cellulolytic thermophile Clostridium thermocellum is an important biocatalyst due to its ability to solubilize lignocellulosic feedstocks without the need for pretreatment or exogenous enzyme addition. At low concentrations of substrate, C. thermocellum can solubilize corn fiber > 95% in 5 days, but solubilization declines markedly at substrate concentrations higher than 20 g/L. This differs for model cellulose like Avicel, on which the maximum solubilization rate increases in proportion to substrate concentration. The goal of this study was to examine fermentation at increasing corn fiber concentrations and investigate possible reasons for declining performance.

Results

The rate of growth of C. thermocellum on corn fiber, inferred from CipA scaffoldin levels measured by LC–MS/MS, showed very little increase with increasing solids loading. To test for inhibition, we evaluated the effects of spent broth on growth and cellulase activity. The liquids remaining after corn fiber fermentation were found to be strongly inhibitory to growth on cellobiose, a substrate that does not require cellulose hydrolysis. Additionally, the hydrolytic activity of C. thermocellum cellulase was also reduced to less-than half by adding spent broth. Noting that > 15 g/L hemicellulose oligosaccharides accumulated in the spent broth of a 40 g/L corn fiber fermentation, we tested the effect of various model carbohydrates on growth on cellobiose and Avicel. Some compounds like xylooligosaccharides caused a decline in cellulolytic activity and a reduction in the maximum solubilization rate on Avicel. However, there were no relevant model compounds that could replicate the strong inhibition by spent broth on C. thermocellum growth on cellobiose. Cocultures of C. thermocellum with hemicellulose-consuming partners—Herbinix spp. strain LL1355 and Thermoanaerobacterium thermosaccharolyticum—exhibited lower levels of unfermented hemicellulose hydrolysis products, a doubling of the maximum solubilization rate, and final solubilization increased from 67 to 93%.

Conclusions

This study documents inhibition of C. thermocellum with increasing corn fiber concentration and demonstrates inhibition of cellulase activity by xylooligosaccharides, but further work is needed to understand why growth on cellobiose was inhibited by corn fiber fermentation broth. Our results support the importance of hemicellulose-utilizing coculture partners to augment C. thermocellum in the fermentation of lignocellulosic feedstocks at high solids loading.
The miR-204-5p/FOXC1/GDF7 axis regulates the osteogenic differentiation of human adipose-derived stem cells via the AKT and p38 signalling pathways
Authors: Zhou You , Liu Siyu , Wang Wei , Sun Qiang , Lv Mengzhu , Yang Shude , Tong Shuang , Guo Shu
Published: January 2021

Background

Human adipose-derived stem cells (hADSCs) are stem cells with the potential to differentiate in multiple directions. miR-204-5p is expressed at low levels during the osteogenic differentiation of hADSCs, and its specific regulatory mechanism remains unclear. Here, we aimed to explore the function and possible molecular mechanism of miR-204-5p in the osteogenic differentiation of hADSCs.

Methods

The expression patterns of miR-204-5p, Runx2, alkaline phosphatase (ALP), osteocalcin (OCN), forkhead box C1 (FOXC1) and growth differentiation factor 7 (GDF7) in hADSCs during osteogenesis were detected by qRT-PCR. Then, ALP and alizarin red staining (ARS) were used to detect osteoblast activities and mineral deposition. Western blotting was conducted to confirm the protein levels. The regulatory relationship among miR-204-5p, FOXC1 and GDF7 was verified by dual-luciferase activity and chromatin immunoprecipitation (ChIP) assays.

Results

miR-204-5p expression was downregulated in hADSC osteogenesis, and overexpression of miR-204-5p suppressed osteogenic differentiation. Furthermore, the levels of FOXC1 and GDF7 were decreased in the miR-204-5p mimics group, which indicates that miR-204-5p overexpression suppresses the expression of FOXC1 and GDF7 by binding to their 3′-untranslated regions (UTRs). Overexpression of FOXC1 or GDF7 improved the inhibition of osteogenic differentiation of hADSCs induced by the miR-204-5p mimics. Moreover, FOXC1 was found to bind to the promoter of miR-204-5p and GDF7, promote the deacetylation of miR-204-5p and reduce the expression of miR-204-5p, thus promoting the expression of GDF7 during osteogenic differentiation. GDF7 induced hADSC osteogenesis differentiation by activating the AKT and P38 signalling pathways.

Conclusions

Our results demonstrated that the miR-204-5p/FOXC1/GDF7 axis regulates the osteogenic differentiation of hADSCs via the AKT and p38 signalling pathways. This study further revealed the regulatory mechanism of hADSC differentiation from the perspective of miRNA regulation.
Generic SDE and GA-based workload modeling for cloud systems
Authors: St-Onge Cédric , Benmakrelouf Souhila , Kara Nadjia , Tout Hanine , Edstrom Claes , Rabipour Rafi
Published: January 2021

Workload models are typically built based on user and application behavior in a system, limiting them to specific domains. Undoubtedly, such a practice creates a dilemma in a cloud computing (cloud) environment, where a wide range of heterogeneous applications are running and many users have access to these resources. The workload model in such an infrastructure must adapt to the evolution of the system configuration parameters, such as job load fluctuation. The aim of this work is to propose an approach that generates generic workload models (1) which are independent of user behavior and the applications running in the system, and can fit any workload domain and type, (2) model sharp workload variations that are most likely to appear in cloud environments, and (3) with high degree of fidelity with respect to observed data, within a short execution time. We propose two approaches for workload estimation, the first being a Hull-White and Genetic Algorithm (GA) combination, while the second is a Support Vector Regression (SVR) and Kalman-filter combination. Thorough experiments are conducted on real CPU and throughput datasets from virtualized IP Multimedia Subsystem (IMS), Web and cloud environments to study the efficiency of both propositions. The results show a higher accuracy for the Hull-White-GA approach with marginal overhead over the SVR-Kalman-Filter combination.
Correction to: Disability-adjusted life years and mortality rate attributed to unsafe sex and drug use for AIDS in the Middle East and North Africa countries
Authors: Najafi Farid , Shadmani Fatemeh Khosravi , Ghalandari Mojtaba , Darbandi Mitra
Published: January 2021

An amendment to this paper has been published and can be accessed via the original article.
Bloodstream infections caused by ST2 Acinetobacter baumannii: risk factors, antibiotic regimens, and virulence over 6 years period in China
Authors: Yu Kaihang , Zeng Weiliang , Xu Ye , Liao Wenli , Xu Wenya , Zhou Tieli , Cao Jianming , Chen Lijiang
Published: January 2021

Background

Bloodstream infection (BSI) caused by multidrug-resistant Acinetobacter baumannii (MDR-AB) has been increasingly observed among hospitalized patients. The following study analyzed the epidemiology and microbiological characteristics of MDR-AB, as well as the clinical features, antimicrobial treatments, and outcomes in patients over a six years period in China.

Methods

This retrospective study was conducted in a large tertiary hospital in China between January 2013 and December 2018. The clinical and microbiological data of all consecutive hospitalized patients with MDR-AB induced bloodstream infection were included and analyzed.

Results

A total of 108 BSI episodes were analyzed. All MDR isolates belonged to ST2, a sequence type that has spread all over the world. Overall, ST2 strains showed strong biofilm formation ability, high serum resistance, and high pathogenicity. As for the clinical characteristics of the patient, 30-day mortality was 69.4% (75/108). The three main risk factors included mechanical ventilation, intensive care unit (ICU) stay, and thrombocytopenia; three protective factors included a change of antimicrobial regimen within 48 h after positive blood culture, use of the antibacterial agent combination, and more inpatient days. The most effective antibacterial regimen was the combination of cefoperazone/sulbactam and tigecycline.

Conclusions

BSI caused by ST2 A.baumannii represents a difficult challenge for physicians, considering the high mortality associated with this infection. The combination of cefoperazone/sulbactam and tigecycline may be an effective treatment option.
Riverbank erosion and migration inter-linkage: with special focus on Assam, India
Authors: Dekaraja Dimpal , Mahanta Ratul
Published: January 2021

Background

Riverbank erosion becomes a vulnerable phenomenon in the bank of the Brahmaputra river and its tributaries. Around 17 riverine districts of Assam are affected by riverbank erosion and lost a large plot of land. Due to riverbank erosion the victims’ loss their homestead and crop land as well as their survival strategy in the eroded areas. Moreover, farmers largely affected due to riverbank erosion as they loss their sources of income. This forces the farmer to migrate to another place for their survival. The paper examines the linkage between river bank erosion and migration based on secondary information.

Method

To examine the linkage, information collected from government published sources ‘Census of India’ and ‘Statistical handbook of Assam’. On the basis of the information, 10 indicators constructed from 26 variables and then factor analysis method applied to examine the linkage between riverbank erosion and migration.

Results

Four variables that are agricultural worker, industrial worker, cropped area and livestock population are loaded into the first factor, for which the first factor is labeled as the socio-economic indicator. In case of second factor the two variables i.e. Migrational Growth Index (MGI) and urban population are loaded. On the basis of the loaded variables this factor labeled as demographic indicator. In case of third factor also two variables are loaded that is, Natural Growth Index (NGI) and Literacy rate. The loaded variables indicate that both NGI and Literacy rate are positively related. Two variables are loaded in this fourth factor i.e. river bank eroded area and the district population growth. This factor labeled as environmental indicator on the basis of the variables loaded in this factor. The factor correlation matrix indicates the opposite relation between first and fourth factor.

Conclusion

The results obtained from Factor component analysis reveals that the first and fourth factor component mainly established the linkage between riverbank erosion and migration. Besides this the component correlation matrix also reveals the inter-linkage between the variables. Thus we can say that there is positive relation between riverbank erosion and migration. However, it can be interpret that farmers mostly affected due to riverbank erosion and migrate more, because most of the inhabitants of the floodplain areas are the farmers.
An environmental study of tracheostomy on eight COVID-19 patients
Authors: Xu Kai , Zhang Xin-Hao , Long Xiao-Bo , Lu Xiang , Liu Zheng
Published: January 2021

Background

Tracheostomy, as an aerosol-generating procedure, is considered as a high-risk surgery for health care workers (HCWs) during the coronavirus disease (COVID-19) pandemic. Current recommendations are to perform tracheostomy after a period of intubation of > 14 days, with two consecutive negative throat swab tests, to lower the risk of contamination to HCWs. However, specific data for this recommendation are lacking. Therefore, this study aimed to evaluate viral shedding into the environment, including HCWs, associated with bedside tracheostomy in the intensive care unit.

Methods

Samples obtained from the medical environment immediately after tracheostomy, including those from 19 surfaces, two air samples at 10 and 50 cm from the surgical site, and from the personal protective equipment (PPE) of the surgeon and assistant, were tested for the presence of severe acute respiratory syndrome coronavirus 2 in eight cases of bedside tracheostomy. We evaluated the rate of positive tests from the different samples obtained.

Results

Positive samples were identified in only one of the eight cases. These were obtained for the air sample at 10 cm and from the bed handrail and urine bag. There were no positive test results from the PPE samples. The patient with positive samples had undergone early tracheostomy, at 9 days after intubation, due to a comorbidity.

Conclusions

Our preliminary results indicate that delayed tracheostomy, after an extended period of endotracheal intubation, might be a considerably less contagious procedure than early tracheostomy (defined as < 14 days after intubation).