bluuebunny/crossref_metadata_2025 huggingface dataset:
A dose-independent association of triglyceride levels with all-cause mortality among adults population
Authors: Huang Yu-qing , Liu Xiao-cong , Lo Kenneth , Feng Ying-qing , Zhang Bin
Published: October 2020

Background

The relationship between triglyceride (TG) level and the mortality risk of all-cause and cardiovascular disease is not entirely consistent among adults.

Methods

The present analysis included adult participants from National Health and Nutrition Examination Surveys (NHANES) between the periods 1999–2014. The levels of TG were categorized into < 150, 150–199, 200–250 and ≥ 250 mg/dL respectively. Multivariate Cox regression analysis, stratified analysis and generalized additive model were conducted to reveal the correlation between TG and mortality risk. Results were presented in hazard ratio (HRs) and 95% confidence intervals (CIs).

Results

There were 18,781 (9130 males, mean age was 45.64 years) participants being included in the analysis. The average follow-up period was 8.25 years, where 1992 (10.61%) cases of all-cause and 421 (2.24%) cardiovascular death have occurred. In the multivariate Cox model, every 1 mg/dL raise in TG has significantly associated with all-cause mortality (HR: 1.08, 95% CI: 1.02, 1.15) but not cardiovascular mortality (HR: 1.10, 95% CI: 0.97, 1.24). When using TG <  150 mg/dL as reference, TG ≥ 250 mg/dL associated with death from all-cause (HR = 1.34, 95% CI: 1.12, 1.60; P = 0.0016 but not cardiovascular death (HR = 1.26, 95% CI: 0.85, 1.88; P = 0.2517). According to smoothing spline plots, the risk of all-cause was the lowest when TG was approximately 135 mg/dL.

Conclusion

TG might have a dose-independent association with all-cause mortality among adults in United States.
Elevated triglyceride-glucose (TyG) index predicts incidence of Prediabetes: a prospective cohort study in China
Authors: Wen Jing , Wang Anping , Liu Guangxu , Wang Meiping , Zuo Yingting , Li Wei , Zhai Qi , Mu Yiming , Gaisano Herbert Y. , He Yan , Dou Jingtao
Published: October 2020

Background

Prediabetes has become a pandemic. This study aimed to identify a better predictor for the incidence of prediabetes, which we hypothesize to be the triglyceride-glucose (TyG) index, a simplified insulin resistance index. We compared its predictive value with the other common risk factors of prediabetes.

Methods

The participants of this analysis were derived from the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study. A total of 4543 participants without initial prediabetes or diabetes were followed up for 3.25 years. Using multivariate logistic regression model, the associations between baseline obesity, lipid profiles and non-insulin-based insulin resistance indices with the incidence of prediabetes were analyzed. To assess which is better predictor for the incidence of prediabetes, the area under curves (AUCs) calculated from the receiver operating characteristic curve analyses were used to evaluate and compare with the predictive value of the different indices.

Results

During the 3.25 years, 1071 out of the 4543 participants developed prediabetes. Using the logistic regression analysis adjusted for some potential confounders, the risk of incidence of prediabetes increased 1.38 (1.28–1.48) fold for each 1–SD increment of TyG index. The predictive ability (assessed by AUCs) of TyG index for predicting prediabetes was 0.60 (0.58–0.62), which was superior to the indices of obesity, lipid profiles and other non-insulin-based insulin resistance indices. Although the predictive ability of the TyG index was overall similar to fasting plasma glucose (FPG) (P = 0.4340), TyG index trended higher than FPG in females (0.62 (0.59–0.64) vs. 0.59 (0.57–0.61), P = 0.0872) and obese subjects (0.59 (0.57–0.62) vs. 0.57 (0.54–0.59), P = 0.1313). TyG index had superior predictive ability for the prediabetic phenotype with isolated impaired glucose tolerance compared with FPG (P <  0.05) and other indices. Furthermore, TyG index significantly improved the C statistic (0.62 (0.60–0.64)), integrated discrimination improvement (1.89% (1.44–2.33%)) and net reclassification index (28.76% (21.84–35.67%)) of conventional model in predicting prediabetes than other indices.

Conclusions

TyG could be a potential predictor to identify the high risk individuals of prediabetes.
Educational supportive group therapy and the quality of life of hemodialysis patients
Authors: Mansouri Sajad , Jalali Amir , Rahmati Mahmoud , Salari Nader
Published: October 2020

Background

In addition to physical, mental, and social condition, ESRD and hemodialysis affect the quality of life of patients as well. Psychotherapy and non-pharmaceutical interventions are effective measures to add meaning to life, create a goal and motivation in life, and improve the quality of life in chronic patients. The effect of educational and supportive group therapy on the quality of life (QOL) of hemodialysis patients was examined.

Methods

The study was carried out as an interventional quasi-experimental study with the participation of 64 patients who were selected through convenience sampling and based on the patient’s hemodialysis days (Saturday, Monday, and Wednesday patients as an experimental group and Sunday, Tuesday, and Thursday patients as a control group). There were 32 patients in each group. The experimental group received eight 50 min sessions including two sessions per week. The control group received the normal interventions. The participants were assessed using a demographics form and Kidney Disease Quality of Life Short Form before, immediately after, and 1 month after the intervention. The collected data was analyzed using SPSS (v.24).

Results

The mean QOL scores of the experimental group before, immediately after, and 4 weeks after the intervention were 36.99, 43.3, and 44.9 respectively. Those of the control group were 36.39, 37.2, and 37.1 respectively. There was no significant difference between the two groups before the intervention (P > 0.05); however, the difference between the two groups was significant immediately after and 4 weeks after the intervention (P = 0.0001). The trend of score change in the experimental group was also significant (p < 0.05), and Tukey ad-hoc test showed significant differences between the scores before intervention and those immediately after and 4 weeks after the intervention (p < 0.05).

Conclusion

In general, educational and supportive group therapy can expand the interpersonal relationships of hemodialysis patients and positively affect their quality of life.
Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment
Authors: López de Andrés Julia , Griñán-Lisón Carmen , Jiménez Gema , Marchal Juan Antonio
Published: October 2020

Cancer stem cells (CSCs) represent a tumor subpopulation responsible for tumor metastasis and resistance to chemo- and radiotherapy, ultimately leading to tumor relapse. As a consequence, the detection and eradication of this cell subpopulation represent a current challenge in oncology medicine. CSC phenotype is dependent on the tumor microenvironment (TME), which involves stem and differentiated tumor cells, as well as different cell types, such as mesenchymal stem cells, endothelial cells, fibroblasts and cells of the immune system, in addition to the extracellular matrix (ECM), different in composition to the ECM in healthy tissues. CSCs regulate multiple cancer hallmarks through the interaction with cells and ECM in their environment by secreting extracellular vesicles including exosomes, and soluble factors such as interleukins, cytokines, growth factors and other metabolites to the TME. Through these factors, CSCs generate and activate their own tumor niche by recruiting stromal cells and modulate angiogenesis, metastasis, resistance to antitumor treatments and their own maintenance by the secretion of different factors such as IL-6, VEGF and TGF-ß. Due to the strong influence of the CSC secretome on disease development, the new antitumor therapies focus on targeting these communication networks to eradicate the tumor and prevent metastasis, tumor relapse and drug resistance. This review summarizes for the first time the main components of the CSC secretome and how they mediate different tumor processes. Lastly, the relevance of the CSC secretome in the development of more precise and personalized antitumor therapies is discussed.
Comparative transcriptome study of switchgrass (Panicum virgatum L.) homologous autopolyploid and its parental amphidiploid responding to consistent drought stress
Authors: Chen Peilin , Chen Jing , Sun Min , Yan Haidong , Feng Guangyan , Wu Bingchao , Zhang Xinquan , Wang Xiaoshan , Huang Linkai
Published: October 2020

Background

Newly formed polyploids may experience short-term adaptative changes in their genome that may enhance the resistance of plants to stress. Considering the increasingly serious effects of drought on biofuel plants, whole genome duplication (WGD) may be an efficient way to proceed with drought resistant breeding. However, the molecular mechanism of drought response before/after WGD remains largely unclear.

Result

We found that autoploid switchgrass (Panicum virgatum L.) 8X Alamo had higher drought tolerance than its parent amphidiploid 4X Alamo using physiological tests. RNA and microRNA sequencing at different time points during drought were then conducted on 8X Alamo and 4X Alamo switchgrass. The specific differentially expressed transcripts (DETs) that related to drought stress (DS) in 8X Alamo were enriched in ribonucleoside and ribonucleotide binding, while the drought-related DETs in 4X Alamo were enriched in structural molecule activity. Ploidy-related DETs were primarily associated with signal transduction mechanisms. Weighted gene co-expression network analysis (WGCNA) detected three significant DS-related modules, and their DETs were primarily enriched in biosynthesis process and photosynthesis. A total of 26 differentially expressed microRNAs (DEmiRs) were detected, and among them, sbi-microRNA 399b was only expressed in 8X Alamo. The targets of microRNAs that were responded to polyploidization and drought stress all contained cytochrome P450 and superoxide dismutase genes.

Conclusions

This study explored the drought response of 8X and 4X Alamo switchgrass on both physiological and transcriptional levels, and provided experimental and sequencing data basis for a short-term adaptability study and drought-resistant biofuel plant breeding.
Performance of the Kato-Katz method and real time polymerase chain reaction for the diagnosis of soil-transmitted helminthiasis in the framework of a randomised controlled trial: treatment efficacy and day-to-day variation
Authors: Keller Ladina , Patel Chandni , Welsche Sophie , Schindler Tobias , Hürlimann Eveline , Keiser Jennifer
Published: October 2020

Background

Accurate, scalable and sensitive diagnostic tools are crucial in determining prevalence of soil-transmitted helminths (STH), assessing infection intensities and monitoring treatment efficacy. However, assessments on treatment efficacy comparing traditional microscopic to newly emerging molecular approaches such as quantitative Polymerase Chain Reaction (qPCR) are scarce and hampered partly by lack of an established diagnostic gold standard.

Methods

We compared the performance of the copromicroscopic Kato-Katz method to qPCR in the framework of a randomized controlled trial on Pemba Island, Tanzania, evaluating treatment efficacy based on cure rates of albendazole monotherapy versus ivermectin-albendazole against Trichuris trichiura and concomitant STH infections. Day-to-day variability of both diagnostic methods was assessed to elucidate reproducibility of test results by analysing two stool samples before and two stool samples after treatment of 160 T. trichiura Kato-Katz positive participants, partially co-infected with Ascaris lumbricoides and hookworm, per treatment arm (n = 320). As negative controls, two faecal samples of 180 Kato-Katz helminth negative participants were analysed.

Results

Fair to moderate correlation between microscopic egg count and DNA copy number for the different STH species was observed at baseline and follow-up. Results indicated higher sensitivity of qPCR for all three STH species across all time points; however, we found lower test result reproducibility compared to Kato-Katz. When assessed with two samples from consecutive days by qPCR, cure rates were significantly lower for T. trichiura (23.2 vs 46.8%), A. lumbricoides (75.3 vs 100%) and hookworm (52.4 vs 78.3%) in the ivermectin-albendazole treatment arm, when compared to Kato-Katz.

Conclusions

qPCR diagnosis showed lower reproducibility of test results compared to Kato-Katz, hence multiple samples per participant should be analysed to achieve a reliable diagnosis of STH infection. Our study confirms that cure rates are overestimated using Kato-Katz alone. Our findings emphasize that standardized and accurate molecular diagnostic tools are urgently needed for future monitoring within STH control and/or elimination programmes.
TUG1 enhances high glucose-impaired endothelial progenitor cell function via miR-29c-3p/PDGF-BB/Wnt signaling
Authors: Li Yang , Zhi Kangkang , Han Shilong , Li Xue , Li Maoquan , Lian Weishuai , Zhang Haijun , Zhang Xiaoping
Published: October 2020

Background

Diabetes is associated with the dysfunction of endothelial progenitor cells (EPCs), characterized as impaired angiogenesis, a phenomenon thought to be involved in the development of diabetic foot. lncRNA plays an essential role in microvascular dysfunction and signaling pathways in patients with diabetes. lncRNA taurine upregulated gene 1 (TUG1) participates in angiogenesis in various cells. However, the mechanisms of TUG1 activity in EPCs have not been elucidated.

Methods

We isolated and then characterized EPCs from the peripheral blood of mice using immunofluorescence and flow cytometry. Western blot detected the wnt/β-catenin pathway in high glucose-treated EPCs. Bioinformatics analysis predicted a putative binding site for TUG1 on miR-29c-3p. The interactions among TUG1, platelet-derived growth factor-BB (PDGF-BB), and miR-29c-3p were analyzed by luciferase assays. In vivo, diabetic mouse ischemic limb was treated with normal saline or TUG1 overexpression lentiviruses.

Results

We found that EPC migration, invasion, and tube formation declined after treatment with high glucose, but improved with TUG1 overexpression. Mechanically, wnt/β-catenin pathway and autophagy were involved in the function of TUG1 overexpression in high glucose-treated EPCs. Moreover, TUG1 regulates the PDGF-BB/wnt pathway and function of high glucose-treated EPCs via miR-29c-3p. In vivo, injection of TUG1 lentivirus in a diabetic mouse ischemic limb model stimulated angiogenesis.

Conclusions

Our findings suggest that TUG1 restores high glucose-treated EPC function by regulating miR-29c-3p/PDGF-BB/Wnt signaling.
A novel chemical-combination screen in zebrafish identifies epigenetic small molecule candidates for the treatment of Duchenne muscular dystrophy
Authors: Farr Gist H. , Morris Melanie , Gomez Arianna , Pham Thao , Kilroy Elisabeth , Parker Elizabeth U. , Said Shery , Henry Clarissa , Maves Lisa
Published: October 2020

Background

Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder and is one of the most common muscular dystrophies. There are currently few effective therapies to treat the disease, although many small-molecule approaches are being pursued. Certain histone deacetylase inhibitors (HDACi) have been shown to ameliorate DMD phenotypes in mouse and zebrafish animal models. The HDACi givinostat has shown promise for DMD in clinical trials. However, beyond a small group of HDACi, other classes of epigenetic small molecules have not been broadly and systematically studied for their benefits for DMD.

Methods

We used an established animal model for DMD, the zebrafish dmd mutant strain sapje. A commercially available library of epigenetic small molecules was used to treat embryonic-larval stages of dmd mutant zebrafish. We used a quantitative muscle birefringence assay in order to assess and compare the effects of small-molecule treatments on dmd mutant zebrafish skeletal muscle structure.

Results

We performed a novel chemical-combination screen of a library of epigenetic compounds using the zebrafish dmd model. We identified candidate pools of epigenetic compounds that improve skeletal muscle structure in dmd mutant zebrafish. We then identified a specific combination of two HDACi compounds, oxamflatin and salermide, that ameliorated dmd mutant zebrafish skeletal muscle degeneration. We validated the effects of oxamflatin and salermide on dmd mutant zebrafish in an independent laboratory. Furthermore, we showed that the combination of oxamflatin and salermide caused increased levels of histone H4 acetylation in zebrafish larvae.

Conclusions

Our results provide novel, effective methods for performing a combination of small-molecule screen in zebrafish. Our results also add to the growing evidence that epigenetic small molecules may be promising candidates for treating DMD.
[18F]FDG PET/CT for evaluating early response to neoadjuvant chemotherapy in pediatric patients with sarcoma: a prospective single-center trial
Authors: Polverari Giulia , Ceci Francesco , Passera Roberto , Crane Jacquelyn , Du Lin , Li Gang , Fanti Stefano , Bernthal Nicholas , Eilber Fritz C. , Allen-Auerbach Martin , Czernin Johannes , Calais Jeremie , Federman Noah
Published: October 2020

Introduction

This is a prospective, single-center trial in pediatric patients with sarcoma aiming to evaluate [18F]FDG PET/CT as a tool for early response assessment to neoadjuvant chemotherapy (neo-CTX).

Methods

Bone or soft tissue sarcoma patients with (1) baseline [18F]FDG PET/CT within 4 weeks prior to the start of neo-CTX (PET1), (2) early interim [18F]FDG PET/CT (6 weeks after the start of neo-CTX (PET2), (3) evaluation of neo-CTX response by histology or MRI, and (4) definitive therapy after neo-CTX (surgery or radiation) were included. Semiquantitative PET parameters (SUVmax, SUVmean, SUVpeak, MTV and TLG) and their changes from PET1 to PET2 (ΔPET) were obtained. The primary endpoint was to evaluate the predictive value of PET1, PET2 and ΔPET parameters for overall survival (OS) and time to progression (TTP). The secondary outcome was to evaluate if [18F]FDG PET/CT can predict the response to neo-CTX assessed by histopathology or MRI. Primary and secondary outcomes were also evaluated in a subpopulation of patients with bone involvement only.

Results

Thirty-four consecutive patients were enrolled (10 females; 24 males; median age 15.1 years). 17/34 patients (50%) had osteosarcoma, 13/34 (38%) Ewing's sarcoma, 2/34 (6%) synovial sarcoma and 2/34 (6%) embryonal liver sarcoma. Median follow-up was 39 months (range 16–84). Eight of 34 patients (24%) died, 9/34 (27%) were alive with disease, and 17/34 (50%) had no evidence of residual/recurrent disease. Fifteen of 34 (44%) and 19/34 (56%) were responders and non-responders, respectively. PET2-parameters were associated with longer TTP (p < 0.02). ΔMTV was associated with tissue response to neo-CTX (p = 0.047). None of the PET1, PET2 or ΔPET parameters were associated with OS.

Conclusion

[18F]FDG PET/CT performed 6 weeks after the start of neo-CTX can serve as an early interim biomarker for TTP and pathologic response but not for OS in pediatric patients with sarcoma.
Pharmacokinetic and pharmacodynamic integration for optimal dosage of cefquinome against Streptococcus equi subsp. equi in foals
Authors: Lee Dong-Ha , Birhanu Biruk Tesfaye , Lee Eon-Bee , Lee Seung-Jin , Boby Naila , Park Yong-Soo , Park Seung-Chun
Published: October 2020

Cefquinome is administered in horses for the treatment of respiratory infection caused byStreptococcus equisubsp.zooepidemicus, and septicemia caused byEscherichia coli. However, there have been no attempts to use cefquinome againstStreptococcus equisubsp. equi(S. equi), the causative agent of strangles. Hence the objective of this study was to calculate an optimal dosage of cefquinome againstS. equibased on pharmacokinetics and pharmacodynamics integration. Cefquinome (1.0 mg/kg) was administered by intravenous and intramuscular routes to six healthy thoroughbred foals. Serum cefquinome concentrations were determined by high-performance liquid chromatography. The in vitro and ex vivo antibacterial activity were determined from minimum inhibitory concentrations (MIC) and bacterial killing curves. The optimal dosage was calculated from the integration of pharmacokinetic parameters and area under the curve (AUC24h/MIC) values. Total body clearance and volume of distribution of cefquinome after intravenous administration were 0.06 L/h/kg and 0.09 L/kg, respectively. Following intramuscular administration, a maximum concentration of 0.73 μg/mL at 1.52 h (Tmax) and a systemic bioavailability of 37.45% were observed. The MIC of cefquinome againstS. equiwas 0.016 μg/mL. The ex vivo AUC24h/MIC values representing bacteriostatic, and bactericidal activity were 113.11, and 143.14 h, respectively. Whereas the %T > MIC for bactericidal activity was 153.34%. In conclusion, based on AUC24h/MIC values and pharmacokinetic parameters, cefquinome when administered by intramuscularly at a dosage of 0.53 mg/kg every 24 h, would be effective against infection caused byS. equiin foals. Further studies may be necessary to confirm its therapeutic efficacy in a clinical environment.
Beta-catenin inhibits TR4-mediated lipid accumulation in 3T3-L1 adipocytes via induction of Slug
Authors: Choi Hojung , Park Sung-Soo , Kim Seung-Jin , Kim Eungseok
Published: October 2020

Background

TR4, an orphan nuclear receptor plays a key role in glucose and lipid metabolism by regulating the expression of genes involved in energy metabolism. We previously reported that overexpression of TR4 in 3T3-L1 adipocytes promotes lipid accumulation in part by facilitating fatty acid uptake and synthesis, indicating that TR4 tightly regulates lipid homeostasis during adipogenesis. Here, we report that β-catenin suppresses TR4 transcriptional activity and that this inhibition is achieved through induction of Slug gene, a well-known transcription repressor in a variety of cells

Methods

To generate the stable cell line, 3T3-L1 cells were transfected with plasmids then cultured in presence of geneticin and/or blasticidin for 2 weeks. The lipid accumulation was measured by Oil Red O. The TR4-Slug and TR4-β-catenin interactions were checked by GST pull-down and mammalian two-hybrid assay. The TR4 transcriptional activities on various promoters were measured by luciferase activity. To check the binding affinity of TR4, we performed the gel shift and chromatin immunoprecipitation (ChIP) assay. Gene expression was detected by RT-qPCR at the mRNA level and western blotting at the protein level.

Results

Stable overexpression of Slug gene in 3T3-L1 preadipocytes strongly inhibited differentiation of 3T3-L1 preadipocytes. Using GST pull-down, gel shift and ChIP assays, we found that Slug abolished the formation of TR4 homodimers through direct interaction with TR4 and reduced the binding affinity of TR4 for its response elements located in TR4 target gene promoters such as fatty acid transport protein 1 and pyruvate carboxylase. Consistently, Slug inhibited TR4 target gene expression and was accompanied by repression of TR4-induced lipid accumulation in 3T3-L1 adipocytes.

Conclusions

Our results demonstrated that Slug inhibits 3T3-L1 adipogenesis through suppression of TR4 transcriptional activity.
Attracting Israeli nursing students to community nursing
Authors: Sela-Vilensky Yael , Grinberg Keren , Nissanholtz-Gannot Rachel
Published: October 2020

Background

The shift from inpatient care to community patient care has had an essential impact on the nursing profession. Despite the growing demand for community nurses in many countries, their number remains relatively low and many students do not perceive this field as an interesting career to pursue. In this review we aimed to understand if exposure of undergraduate nursing students to various nursing work settings during their studies affects their work setting choices after graduation.

Methods

A literature search of papers relating to work setting preferences of nursing students in Israel and other countries was performed. Israel Ministry of Health, Nursing Administration documents and other related documents were also reviewed, with a focus on the nursing training program in Israel.

Findings

While most first-year nursing students have limited knowledge regarding the profession, in later years, their preferences for post-graduation work settings are affected by their exposure to the various clinical fields through knowledge gained in courses together with clinical practice placements. In Israel, specific classroom courses in community nursing are allocated only 6% of the total time allocated to all classroom courses in nursing, and a single clinical placement in community nursing takes place during the third or fourth year of the nursing program, exposing students to a single aspect of community nursing during their nursing training. Studies in other countries have reported that students’ experience during clinical placement contributes to shaping students’ opinions of nurses’ roles within that field. Nursing students who had a primary healthcare placement showed greater intention for working in this setting after graduation.

Conclusions

The lack of exposure to the various aspects of community nursing during undergraduate studies contributes to a lack of motivation for entering this field. Therefore, a profound change is needed in nursing training programs’ curricula to prepare graduates to face future challenges in community nursing. Whilst both hospital and community nursing are equally important, nursing leaders and policy makers must be made aware of the various factors that contribute to new registered nurses’ preferences of hospital over community nursing and build strategies for directing nurses to work in the community in order to respond to the expected nurse shortage in this setting.
Application of intelligent orienteering based on Internet of things
Authors: Zhang Donghui , Liu Ruijie
Published: October 2020

Orienteering has gradually changed from a professional sport to a civilian sport. Especially in recent years, orienteering has been widely popularized. Many colleges and universities in China have also set up this course. With the improvement of people’s living conditions, orienteering has really become a leisure sport in modern people’s life. The reduced difficulty of sports enables more people to participate, but it also exposes a series of problems. As the existing positioning technology is relatively backward, the progress in personnel tracking, emergency services, and other aspects is slow. To solve these problems, a new intelligent orienteering application system is developed based on the Internet of things. ZigBee network architecture is adopted in the system. ZigBee is the mainstream scheme in the current wireless sensor network technology, which has many advantages such as convenient carrying, low power consumption, and signal stability. Due to the complex communication environment in mobile signal, the collected information is processed by signal amplification and signal anti-interference technology. By adding anti-interference devices, video isolators and other devices, the signal is guaranteed to the maximum extent. In order to verify the actual effect of this system, through a number of experimental studies including the relationship between error and traffic radius and the relationship between coverage and the number of anchor nodes, the data shows that the scheme studied in this paper has a greater improvement in comprehensive performance than the traditional scheme, significantly improving the accuracy and coverage. Especially the coverage is close to 100% in the simulation experiment. This research has achieved good results and can be widely used in orienteering training and competition.
Behavioral modifications by a large-northern herbivore to mitigate warming conditions
Authors: Jennewein Jyoti S. , Hebblewhite Mark , Mahoney Peter , Gilbert Sophie , Meddens Arjan J. H. , Boelman Natalie T. , Joly Kyle , Jones Kimberly , Kellie Kalin A. , Brainerd Scott , Vierling Lee A. , Eitel Jan U. H.
Published: October 2020

Background

Temperatures in arctic-boreal regions are increasing rapidly and pose significant challenges to moose (Alces alces), a heat-sensitive large-bodied mammal. Moose act as ecosystem engineers, by regulating forest carbon and structure, below ground nitrogen cycling processes, and predator-prey dynamics. Previous studies showed that during hotter periods, moose displayed stronger selection for wetland habitats, taller and denser forest canopies, and minimized exposure to solar radiation. However, previous studies regarding moose behavioral thermoregulation occurred in Europe or southern moose range in North America. Understanding whether ambient temperature elicits a behavioral response in high-northern latitude moose populations in North America may be increasingly important as these arctic-boreal systems have been warming at a rate two to three times the global mean.

Methods

We assessed how Alaska moose habitat selection changed as a function of ambient temperature using a step-selection function approach to identify habitat features important for behavioral thermoregulation in summer (June–August). We used Global Positioning System telemetry locations from four populations of Alaska moose (n = 169) from 2008 to 2016. We assessed model fit using the quasi-likelihood under independence criterion and conduction a leave-one-out cross validation.

Results

Both male and female moose in all populations increasingly, and nonlinearly, selected for denser canopy cover as ambient temperature increased during summer, where initial increases in the conditional probability of selection were initially sharper then leveled out as canopy density increased above ~ 50%. However, the magnitude of selection response varied by population and sex. In two of the three populations containing both sexes, females demonstrated a stronger selection response for denser canopy at higher temperatures than males. We also observed a stronger selection response in the most southerly and northerly populations compared to populations in the west and central Alaska.

Conclusions

The impacts of climate change in arctic-boreal regions increase landscape heterogeneity through processes such as increased wildfire intensity and annual area burned, which may significantly alter the thermal environment available to an animal. Understanding habitat selection related to behavioral thermoregulation is a first step toward identifying areas capable of providing thermal relief for moose and other species impacted by climate change in arctic-boreal regions.
Development of chromosome-based T7 RNA polymerase and orthogonal T7 promoter circuit in Escherichia coli W3110 as a cell factory
Authors: Ting Wan-Wen , Tan Shih-I , Ng I-Son
Published: October 2020

Background

Orthogonal T7 RNA polymerase (T7RNAP) and T7 promoter is a powerful genetic element to mediate protein expression in different cells. Among all, Escherichia coli possess advantages of fast growth rate, easy for culture and comprehensive elements for genetic engineering. As E. coli W3110 owns the benefits of more heat shock proteins and higher tolerance to toxic chemicals, further execution of T7-based system in W3110 as cell factory is a conceivable strategy.

Results

Three novel W3110 strains, i.e., W3110:IL5, W3110::L5 and W3110::pI, were accomplished by chromosome-equipped T7RNAP. At first, the LacZ and T7RNAP with isopropyl-β-D-thiogalactopyranoside (IPTG) induction showed higher expression levels in W3110 derivatives than that in BL21(DE3). The plasmids with and without lacI/lacO repression were used to investigate the protein expression of super-fold green fluorescence protein (sfGFP), carbonic anhydrase (CA) for carbon dioxide uptake and lysine decarboxylase (CadA) to produce a toxic chemical cadaverine (DAP). All the proteins showed better expression in W3110::L5 and W3110::pI, respectively. As a result, the highest cadaverine production of 36.9 g/L, lysine consumption of 43.8 g/L and up to 100% yield were obtained in W3110::pI(−) with plasmid pSU-T7-CadA constitutively.

Conclusion

Effect of IPTG and lacI/lacO regulator has been investigated in three chromosome-based T7RNAP E. coli strains. The newly engineered W3110 strains possessed similar protein expression compared to commercial BL21(DE3). Furthermore, W3110::pI displays higher production of sfGFP, CA and CadA, due to it having the highest sensitivity to IPTG, thus it represents the greatest potential as a cell factory.
Antioxidant-rich Tamarindus indica L. leaf extract reduced high-fat diet-induced obesity in rat through modulation of gene expression
Authors: Kuddus Syed Abdul , Bhuiyan Mazharul Islam , Subhan Nusrat , Shohag Md Hasanuzzaman , Rahman Aura , Hossain Muhammad Maqsud , Alam Md Ashraful , Khan Ferdous
Published: October 2020

Background

Different parts of the medicinal plant Tamarindus indica L. are full of phytochemicals that are able to reduce elevated blood pressure, blood sugar and lipids. These pharmacological effects are due to the presence of antioxidant type compounds in those parts of the plant. This study was aimed to explore the molecular mechanism of anti-obesity effects of ethanolic extract of T. indica L. leaves (TILE) through the evaluation of biochemical parameters and gene expression analysis in high-fat diet (HFD) consuming Wistar rats.

Methods

Male Wistar rats were supplied with a standard diet (SD), or HFD, or HFD with 100 mg/kg or 200 mg/kg or 400 mg/kg TILE for 8 weeks. The body weight, liver weight, fat weight, plasma lipids, and oxidative stress-related parameters were measured. The transcript levels of different adipogenesis related transcription factors, lipogenic enzymes, and lipolytic enzymes were also evaluated by quantitative real-time PCR.

Result

Phytochemical analysis demonstrated that TILE is enriched with a substantial level of polyphenols (287.20 ± 9.21 mg GAE/g extract) and flavonoids (107.52 ± 11.12 mg QE/g extract) which might be the reason of significant antioxidant and radical scavenging activities. Feeding of TILE (400 mg/kg/day) to HFD-fed rats increased activity of superoxide dismutase and catalase which is reflected as a significant reduction of oxidative stress markers like nitric oxide and malondialdehyde. TILE (400 mg/kg/day) feeding also down-regulated the mRNA levels of proadipogenic transcription factors including liver X receptor alpha (LXRα), peroxisome proliferator-activated receptor gamma (PPARγ), and sterol regulatory element-binding protein 1c (SREBP1c) in diet-induced obese rats. As a consequence of this, the mRNA level of lipogenic enzymes like acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), diacylglycerol acyltransferase (DGAT), and HMG-CoA reductase was down-regulated with a parallel up-regulation of the transcript level of lipolytic enzyme, hormone-sensitive lipase (HSL).

Conclusion

Observations from this study indicate that antioxidant-rich TILE can reduce HFD-induced body weight, fat weight and liver weight as well as blood lipids through down-regulating the gene expression of proadipogenic transcription factors and lipogenic enzymes with a concerted diminution of the gene expression of lipolytic enzyme, HSL.
Involving research participants in a pan-European research initiative: the EPAD participant panel experience
Authors: Gregory S. , Bunnik E. M. , Callado A. B. , Carrie I. , De Boer C. , Duffus J. , Fauria K. , Forster S. , Gove D. , Knezevic I. , Laquidain A. , Pennetier D. , Saunders S. , Sparks S. , Rice J. , Ritchie C. W. , Milne R.
Published: October 2020

Background

Including participants in patient and public involvement activities is increasingly acknowledged as a key pillar of successful research activity. Such activities can influence recruitment and retention, as well as researcher experience and contribute to decision making in research studies. However, there are few established methodologies of how to set up and manage participant involvement activities. Further, there is little discussion of how to do so when dealing with collaborative projects that run across countries and operate in multiple linguistic and regulatory contexts.

Methods

In this paper we describe the set-up, running and experiences of the EPAD participant panel. The EPAD study was a pan-European cohort study with the aim to understand risks for developing Alzheimer’s disease and build a readiness cohort for Phase 2 clinical trials. Due to the longitudinal nature of this study, combined with the enrolment of healthy volunteers and those with mild cognitive impairments, the EPAD team highlighted participant involvement as crucial to the success of this project. The EPAD project employed a nested model, with local panels meeting in England, France, Scotland, Spain and The Netherlands, and feeding into a central study panel. The local panels were governed by terms of reference which were adaptable to local needs.

Results

The impact of the panels has been widespread, and varies from feedback on documentation, to supporting with design of media materials and representation of the project at national and international meetings.

Conclusions

The EPAD panels have contributed to the success of the project and the model established is easily transferable to other disease areas investigating healthy or at-risk populations.
Serratus anterior plane block in modified radical mastectomy surgery: a case series
Authors: Datu Madonna Damayanthie , Prasetyadhi Jokevin
Published: October 2020

Background

Postoperative breast pain may lead to poorer outcome if left untreated. Common analgesia modalities for postoperative breast pain include opioids and regional anesthesia. However, both of these modalities can cause significant side effects or complications. Serratus anterior plane (SAP) block is a new procedure that is relatively easier to perform and safer, compared with other modalities. Previous studies have reported its usefulness in reducing the need for both intraoperative and postoperative opioids.

Case

We reported 2 patients that underwent SAP block combined with general anesthesia in modified radical mastectomy (MRM). Patient 2 was given rescue analgesia during the intraoperative period. The administration of postoperative opioids did not exceed 24 h in both patients. Pain assessment using numeric rating scale (NRS) showed minimal postoperative pain. No side effects were found during 24-h monitoring period.

Conclusion

SAP block can be used as one of the modalities in managing the pain of MRM surgery.
Wisdom of crowds and collective decision-making in a survival situation with complex information integration
Authors: Hamada Daisuke , Nakayama Masataka , Saiki Jun
Published: October 2020

Background

The wisdom of crowds and collective decision-making are important tools for integrating information between individuals, which can exceed the capacity of individual judgments. They are based on different forms of information integration. The wisdom of crowds refers to the aggregation of many independent judgments without deliberation and consensus, while collective decision-making is aggregation with deliberation and consensus. Recent research has shown that collective decision-making outperforms the wisdom of crowds. Additionally, many studies have shown that metacognitive knowledge of subjective confidence is useful for improving aggregation performance. However, because most of these studies have employed relatively simple problems; for example, involving general knowledge and estimating values and quantities of objects, it remains unclear whether their findings can be generalized to real-life situations involving complex information integration. This study explores the performance and process of the wisdom of crowds and collective decision-making by applying the wisdom of crowds with weighted confidence to a survival situation task commonly used in studies of collective decision-making.

Results

The wisdom of crowds and collective decision-making outperformed individual judgment. However, collective decision-making did not outperform the wisdom of crowds. Contrary to previous studies, weighted confidence showed no advantage from comparison between confidence-weighted and non-weighted aggregations; a simulation analysis varying in group size and sensitivity of confidence weighting revealed interaction between group size and sensitivity of confidence weighting. This reveals that it is because of small group size and not the peculiarity of the survival task that results in no advantage of weighted confidence.

Conclusions

The study’s findings suggest that the wisdom of crowds could be applicable to complex problem-solving tasks, and interaction between group size and sensitivity of confidence weighting is important for confidence-weighted aggregation effects.
C-reactive protein course after classical complication free total knee arthroplasty using navigation
Authors: Nam Jun Ho , Cho Myung Rae , Lee Seo Ho , Song Suk-Kyoon , Choi Won-Kee
Published: October 2020

Purpose

The purpose is to estimate the degree of normalization of C-reactive protein (CRP) at 2 weeks and 4 weeks after uncomplicated total knee arthroplasty (TKA) using computer navigation. We also wish to determine whether the degree of normalization of CRP at 2 and 4 weeks differs after TKA performed in one knee and after TKA performed sequentially in both knees. We also want to analyze the patient factors that may influence the normalization of CRP.

Material and methods

We studied 400 knees who underwent primary computer-navigated TKA for treatment of advanced osteoarthritis: the TKAs were all performed by the same surgeon. We retrospectively analyzed CRP levels during the preoperative period, the early postoperative period (5–7 days), the 2-week postoperative period (12–14 days), and the 4-week postoperative period (25–30 days). We have assumed gender, age, body mass index (BMI), staged bilateral TKA, and preoperative CRP as the potential patient factors associated with CRP normalization.

Results

In unilateral TKA, CRP was normalized in 94 cases (34.3%) and in 219 cases (81.4%) within 2 weeks and 4 weeks after surgery, respectively. In second-knee, staged bilateral TKA, CRP was normalized in 46 cases (35.1%) and in 104 cases (79.4%) within 2 weeks and 4 weeks after surgery, respectively. There were no statistical differences between unilateral TKA and second-knee, staged bilateral TKA during the 2-week postoperative and the 4-week postoperative period. Compared to women, men were 1.99 times less likely to have normalized CRP at 2 weeks after surgery (P = 0.02).

Conclusion

CRP was less likely to normalize during the 2-week postoperative period in men than it is in women, while there was no difference between men and women in the normalization of CRP during the 4-week postoperative period. There were no statistical differences in the course of CRP levels after unilateral TKA and staged bilateral TKA during the 2-week postoperative and the 4-week postoperative period.
Lysinuric protein intolerance: an overlooked diagnosis
Authors: Olgac Asburce , Yenicesu Idil , Ozgul Rıza Köksal , Biberoğlu Gürsel , Tümer Leyla
Published: October 2020

Background

Lysinuric protein intolerance (LPI) is an autosomal recessively inherited inborn error of metabolism (IEM) caused by the defect in the dibasic cationic amino acid transporter found on the basolateral membrane of the lung, small intestine, and kidney due to mutations in the SLC7A7 gene, which encodes the y+LAT1 protein. LPI may present as an acute hyperammonemic episode or as chronic symptoms. Major clinical symptoms are feeding problems, vomiting and diarrhea, failure to thrive, hepatosplenomegaly, and cytopenia. We present a delayed diagnosis of symptomatic LPI with a homozygous mutation in the SLC7A7 gene.

Case presentation

A 15-year-old girl was referred to our clinic due to growth retardation and diarrhea. Physical examination showed short stature, retarded puberty, and hepatosplenomegaly. Laboratory tests showed normal complete blood count and biochemical analyses except elevated aspartate aminotransferase, triglyceride, total cholesterol, and ferritin. Peripheral blood smear and hemoglobin electrophoresis were within normal limits. Bone marrow analysis showed hemophagocytic cells. Postprandial ammonium level was found elevated. Low lysine, arginine, and ornithine and elevated glycine and alanine in plasma amino acid analysis and high amount of lysine and slightly elevated arginine and ornithine excretion in urine were detected. Molecular genetic analysis of the SLC7A7 gene showed a previously reported homozygous mutation. Low protein diet, sodium benzoate, l-carnitine, low-dose l-citrulline, and calcium replacement were initiated. The patient is now in good condition still being followed up in our department.

Conclusions

LPI is a metabolic disorder with multi-systemic involvement that may have severe consequences if left untreated. Initiation of early treatment is essential for the prevention of severe chronic complications. Also, confirmation of the genetic defect may provide the parents to have healthy offsprings in the future with the help of genetic counselling and preimplantation genetics.
Protocol for an economic evaluation and budget impact assessment of a randomised, stepped-wedge controlled trial for practice change support to increase routine provision of antenatal care for maternal alcohol consumption
Authors: Reeves Penny , Szewczyk Zoe , Kingsland Melanie , Doherty Emma , Elliott Elizabeth , Dunlop Adrian , Searles Andrew , Wiggers John
Published: October 2020

Background

Antenatal clinical practice guidelines recommend routine assessment of women’s alcohol consumption during pregnancy. The delivery of advice and referral when necessary are also recommended. However, evidence suggests there are barriers to the uptake of best-care guidelines. Effective, cost-effective and affordable implementation strategies are needed to ensure the intended benefits of guidelines are realised through addressing identified barriers. This paper describes the protocol for evaluating the efficiency and affordability of a practice change intervention compared to the usual practice in an implementation trial.

Methods

The effectiveness of the intervention will be evaluated in a stepped-wedge randomised controlled implementation trial, conducted in an Australian setting. An economic evaluation will be conducted alongside the trial to assess intervention efficiency. A budget impact assessment will be conducted to assess affordability. The prospective trial-based economic evaluation will identify, measure and value key resource and outcome impacts arising from the multi-strategy practice change intervention compared with usual practice. The evaluation will comprise (i) cost-consequence analyses, where a scorecard approach will be used to show the costs and benefits given the multiple primary outcomes included in the trial, and (ii) cost-effectiveness analyses, where the primary outcome will be incremental cost per percent increase in participants reporting receipt of antenatal care for maternal alcohol consumption consistent with the guideline recommendations. Intervention affordability will be evaluated using budget impact assessment and will estimate the financial implications of adoption and diffusion of this implementation strategy from the perspective of relevant fundholders. Results will be extrapolated to estimate the cost and cost-effectiveness of rolling out the model of care.

Discussion

Uptake of clinical guidelines requires practice change support. It is hypothesized that the implementation strategy, if found to be effective, will also be cost-effective, affordable and scalable. This protocol describes the economic evaluation that will address these hypotheses.

Trial registration

Australian and New Zealand Clinical Trials Registry, ACTRN12617000882325. Registered on 16 June 2017