bluuebunny/crossref_metadata_2025 huggingface dataset:
MINI SEED 2 (MIS2) Encodes a Receptor-like Kinase that Controls Grain Size and Shape in Rice
Authors: Chun Yan , Fang Jingjing , Zafar Syed Adeel , Shang Jiangyuan , Zhao Jinfeng , Yuan Shoujiang , Li Xueyong
Published: January 2020

Background

Grain size is a key agronomic trait that is directly associated with grain yield in rice. Although several genes related to grain size in rice have been identified, our understanding of the mechanism of grain development is still limited.

Results

In this study, we reported the characterization of a novel seed size mutant mini seed 2 (mis2), in which the grain showed reduced length, width and thickness along with wrinkled surface. Microscopic analysis revealed that the spikelet epidermal cell size was reduced but the cell number was increased in the mis2 mutant, suggesting that MIS2 controls grain size by coordinately regulating epidermal cell size and cell number. Map-based cloning revealed that MIS2 encodes a receptor-like kinase CRINKLY4 (CR4) which showed the highest expression in developing panicles. The MIS2 protein is localized primarily on the plasma membrane along with the endosome. However, the Arg258Gln mutation located in extracellular domain in the mis2 mutant disturbed its subcellular localization. Additionally, three major haplotypes of MIS2 were identified in the japonica, indica and aus rice cultivars. The 18-bp InDel (insertion and deletion) in the 5′-UTR (untranslated region) caused different expression level of MIS2 in haplotypes.

Conclusions

We reported a key role of OsCR4 in controlling grain size and shape by coordinately regulating epidermal cell size and cell number. The Arg258 in the extracellular seven-repeat domain is essential for the correct subcellular behavior and function of the OsCR4 protein.
Transcriptomic response to three osmotic stresses in gills of hybrid tilapia (Oreochromis mossambicus female × O. urolepis hornorum male)
Authors: Su Huanhuan , Ma Dongmei , Zhu Huaping , Liu Zhigang , Gao Fengying
Published: January 2020

Background

Osmotic stress is a widespread phenomenon in aquatic animal. The ability to cope with salinity stress and alkaline stress is quite important for the survival of aquatic species under natural conditions. Tilapia is an important commercial euryhaline fish species. What’s more tilapia is a good experimental material for osmotic stress regulation research, but the molecular regulation mechanism underlying different osmotic pressure of tilapia is still unexplored.

Results

To elucidate the osmoregulation strategy behind its hyper salinity, alkalinity and salinity-alkalinity stress of tilapia, the transcriptomes of gills in hybrid tilapia (Oreochromis mossambicus ♀ × O. urolepis hornorum ♂) under salinity stress (S: 25‰), alkalinity stress(A: 4‰) and salinity-alkalinity stress (SA: S: 15‰, A: 4‰) were sequenced using deep-sequencing platform Illumina/HiSeq-2000 and differential expression genes (DEGs) were identified. A total of 1958, 1472 and 1315 upregulated and 1824, 1940 and 1735 downregulated genes (P-value < 0.05) were identified in the salt stress, alkali stress and saline-alkali stress groups, respectively, compared with those in the control group. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted in the significant different expression genes. In all significant DEGs, some of the typical genes involved in osmoregulation, including carbonic anhydrase (CA), calcium/calmodulin-dependent protein kinase (CaM kinase) II (CAMK2), aquaporin-1(AQP1), sodium bicarbonate cotransporter (SLC4A4/NBC1), chloride channel 2(CLCN2), sodium/potassium/chloride transporter (SLC12A2 / NKCC1) and other osmoregulation genes were also identified. RNA-seq results were validated with quantitative real-time PCR (qPCR), the 17 random selected genes showed a consistent direction in both RNA-Seq and qPCR analysis, demonstrated that the results of RNA-seq were reliable.

Conclusions

The present results would be helpful to elucidate the osmoregulation mechanism of aquatic animals adapting to saline-alkali challenge. This study provides a global overview of gene expression patterns and pathways that related to osmoregulation in hybrid tilapia, and could contribute to a better understanding of the molecular regulation mechanism in different osmotic stresses.
TaSTP13 contributes to wheat susceptibility to stripe rust possibly by increasing cytoplasmic hexose concentration
Authors: Huai Baoyu , Yang Qian , Wei Xiaobo , Pan Qinglin , Kang Zhensheng , Liu Jie
Published: January 2020

Background

Biotrophic fungi make intimate contact with host cells to access nutrients. Sugar is considered as the main carbon sources absorbed from host cells by pathogens. Partition, exchanges and competition for sugar at plant-pathogen interfaces are controlled by sugar transporters. Previous studies have indicated that the leaf rust resistance (Lr) gene Lr67, a natural mutation of TaSTP13 encoding a wheat sugar transport protein, confers partial resistance to all three wheat rust species and powdery mildew possibly due to weakened sugar transport activity of TaSTP13 by heterodimerization. However, one major problem that remains unresolved concerns whether TaSTP13 participates in wheat susceptibility to rust and mildew.

Results

In this study, expression of TaSTP13 was highly induced in wheat leaves challenged by Puccinia striiformis f. sp. tritici (Pst) and certain abiotic treatments. TaSTP13 was localized in the plasma membrane and functioned as homooligomers. In addition, a functional domain for its transport activity was identified in yeast. Suppression of TaSTP13 reduced wheat susceptibility to Pst by barley stripe mosaic virus-induced gene silencing (VIGS). While overexpression of TaSTP13 promoted Arabidopsis susceptibility to powdery mildew and led to increased glucose accumulation in the leaves.

Conclusions

These results indicate that TaSTP13 is transcriptionally induced and contributes to wheat susceptibility to stripe rust, possibly by promoting cytoplasmic hexose accumulation for fungal sugar acquisition in wheat-Pst interactions.
Impact of glycemic control status on patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention
Authors: Li Yan , Li Xiaowen , Zhang Yinhua , Zhang Leimin , Wu Qingqing , Bai Zhaorun , Si Jin , Zuo Xuebing , Shi Ning , Li Jing , Chu Xi
Published: January 2020

Background

The combined effects of diabetes mellitus (DM), admission plasma glucose (APG), and glycated hemoglobin (HbA1c) levels on predicting long-term clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) are unknown. Therefore, we evaluated their combined effects on long-term clinical outcomes in STEMI patients treated with pPCI.

Methods

In total, 350 consecutive patients with STEMI undergoing pPCI were enrolled. Patients were divided into 3 groups according to DM history and APG and HbA1c levels. The cumulative rates of 24-month all-cause deaths and major adverse cardiac and cerebrovascular events (MACCEs) were calculated.

Results

Both the incidence of all-cause deaths and cumulative rates of MACCEs were significantly the lowest in patients without a DM history and admission HbA1c level < 6.5%. DM patients with poor glycemic control or stress hyperglycemia on admission experienced the highest rates of all-cause deaths, MACCEs, and cardiac deaths. Admission HbA1c levels, Triglyceride (TG) levels, hemoglobin levels, DM history, and admission Killip class > 1 correlated with 24-month all-cause death; HbA1c levels on admission, DM history, APG levels, history of stroke, history of coronary heart disease, and TG levels on admission were significantly associated with MACCEs through the 24-month follow-up. The predictive effects of combining DM and APG and HbA1c levels were such that for STEMI patients undergoing pPCI, DM patients with poor glycemic control or with stress hyperglycemia on admission had worse prognosis than other patients.

Conclusion

Strict control of glycemic status may improve the survival of patients who have both DM and coronary heart diseases.
Breastfeeding practices within the first six months of age in mid-western and eastern regions of Nepal: a health facility-based cross-sectional study
Authors: Dharel Dinesh , Dhungana Ranjan , Basnet Sushma , Gautam Swotantra , Dhungana Animesh , Dudani Rajesh , Bhattarai Asmita
Published: January 2020

Background

The World Health Organization recommends initiation of breastfeeding within 1 hour of birth and exclusive breastfeeding up to 6 months of age. Infant feeding practices, including suboptimal breastfeeding practices, are associated with stunting. Rate of stunting was highest in the Mid-western region and lowest in the Eastern region of Nepal. This study aimed to assess the breastfeeding practices in these two regions, as well as to identify factors associated with partial breastfeeding.

Methods

We conducted a health facility-based cross-sectional study in the Mid-western and Eastern regions of Nepal from December 2017 to May 2018. Investigators administered a pre-tested questionnaire among consecutive 574 mother-infant dyads at different levels of health facilities. We dichotomized the breastfeeding pattern to partial breastfeeding and full (exclusive or predominant) breastfeeding. We conducted multivariable logistic regression to identify factors associated with partial breastfeeding within 6 months of age.

Results

There were 574 infants included in the study, all of which received at least some breastfeeding. Only 23.2% of infants were exclusively breastfed until 6 months, with 28.2% predominantly breastfed and 48.6% partially breastfed. Partial breastfeeding rate was 52.3% in the Mid-western region and 44.4% in the Eastern region. Breastfeeding was initiated within an hour from birth in 67.2% of infants. One-quarter of infants were given pre-lacteal feed, honey being the commonest. Knowledge of the recommended duration of exclusive breastfeeding was inadequate in 16, and 65% of mothers reported breastfeeding problems in the first 6 months. Firstborn and low birth weight infants had a significantly higher rate of partial breastfeeding. Partial breastfeeding was also higher when infants were not breastfed within 1 hour from birth, mothers reported having breastfeeding-related problems or had inadequate knowledge of the duration of exclusive breastfeeding.

Conclusion

Nearly half of the infants were fully breastfed at 6 months of age in Nepal. The rate of partial breastfeeding was higher with inadequate knowledge on duration of exclusive breastfeeding or late initiation of breastfeeding or perceived breastfeeding problems. Hence, programs should address knowledge and practice gaps in breastfeeding practices, particularly among mothers of low birth weight and firstborn infants.
A web application for the design of multi-arm clinical trials
Authors: Grayling Michael J. , Wason James MS.
Published: January 2020

Background

Multi-arm designs provide an effective means of evaluating several treatments within the same clinical trial. Given the large number of treatments now available for testing in many disease areas, it has been argued that their utilisation should increase. However, for any given clinical trial there are numerous possible multi-arm designs that could be used, and choosing between them can be a difficult task. This task is complicated further by a lack of available easy-to-use software for designing multi-arm trials.

Results

To aid the wider implementation of multi-arm clinical trial designs, we have developed a web application for sample size calculation when using a variety of popular multiple comparison corrections. Furthermore, the application supports sample size calculation to control several varieties of power, as well as the determination of optimised arm-wise allocation ratios. It is built using the Shiny package in the R programming language, is free to access on any device with an internet browser, and requires no programming knowledge to use. It incorporates a variety of features to make it easier to use, including help boxes and warning messages. Using design parameters motivated by a recently completed phase II oncology trial, we demonstrate that the application can effectively determine and evaluate complex multi-arm trial designs.

Conclusions

The application provides the core information required by statisticians and clinicians to review the operating characteristics of a chosen multi-arm clinical trial design. The range of designs supported by the application is broader than other currently available software solutions. Its primary limitation, particularly from a regulatory agency point of view, is its lack of validation. However, we present an approach to efficiently confirming its results via simulation.
Genomic subtyping of liver cancers with prognostic application
Authors: Wu Zhenggang , Long Xi , Tsang Shui Ying , Hu Taobo , Yang Jian-Feng , Mat Wai Kin , Wang Hongyang , Xue Hong
Published: January 2020

Background

Cancer subtyping has mainly relied on pathological and molecular means. Massively parallel sequencing-enabled subtyping requires genomic markers to be developed based on global features rather than individual mutations for effective implementation.

Methods

In the present study, the whole genome sequences (WGS) of 110 liver cancers of Japanese patients published with different pathologies were analyzed with respect to their single nucleotide variations (SNVs) comprising both gain-of-heterozygosity (GOH) and loss-of-heterozygosity (LOH) mutations, the signatures of combined GOH and LOH mutations, along with recurrent copy number variations (CNVs).

Results

The results, obtained based on the WGS sequences as well as the Exome subset within the WGSs that covered ~ 2.0% of the WGS and the AluScan-subset within the WGSs that were amplifiable by Alu element-consensus primers and covered ~ 2.1% of the WGS, indicated that the WGS samples could be employed with the mutational parameters of SNV load, LOH%, the Signature α%, and survival-associated recurrent CNVs (srCNVs) as genomic markers for subtyping to stratify liver cancer patients prognostically into the long and short survival subgroups. The usage of the AluScan-subset data, which could be implemented with sub-micrograms of DNA samples and vastly reduced sequencing analysis task, outperformed the usage of WGS data when LOH% was employed as stratifying criterion.

Conclusions

Thus genomic subtyping performed with novel genomic markers identified in this study was effective in predicting patient-survival duration, with cohorts of hepatocellular carcinomas alone and those including intrahepatic cholangiocarcinomas. Such relatively heterogeneity-insensitive genomic subtyping merits further studies with a broader spectrum of cancers.
Oncologic outcomes after immediate breast reconstruction following mastectomy: comparison of implant and flap using propensity score matching
Authors: Ha Jeong Hyun , Hong Ki Yong , Lee Han-Byoel , Moon Hyeong-Gon , Han Wonshik , Noh Dong-Young , Lim Joonho , Yoon Sehoon , Chang Hak , Jin Ung Sik
Published: January 2020

Background

Although immediate breast reconstruction has been reported to be oncologically safe, no affirmative study comparing the two reconstruction methods exists. We investigated breast cancer recurrence rates in two breast reconstruction types; implant reconstruction and autologous flap reconstruction.

Methods

A retrospective cohort study was performed on propensity score-matched (for age, stage, estrogen receptor status) patients who underwent IBR after mastectomy at Seoul National University Hospital between 2010 and 2014. The main outcomes determined were locoregional recurrence-free interval (LRRFI) and disease-free interval (DFI).

Results

We analyzed 496 patients among 731 patients following propensity score matching (Median age 43, 247 implant reconstruction and 249 flap reconstruction). During median follow-up of 58.2 months, DFI was not different between the two groups at each tumor stage. However, flap reconstruction showed inferior DFI compared to implant reconstruction in patients with high histologic grade (p = 0.012), and with high Ki-67 (p = 0.028). Flap reconstruction was related to short DFI in multivariate analysis in aggressive tumor subsets. Short DFI after flap reconstruction in aggressive tumor cell phenotype was most evident in hormone positive/Her-2 negative cancer (p = 0.008). LRRFI, on the other hand, did not show difference according to reconstruction method regardless of tumor cell aggressiveness.

Conclusion

Although there is no difference in cancer recurrence according to reconstruction method in general, flap-based reconstruction showed higher systemic recurrence associated with histologically aggressive tumors.
Current status of the clinical use of PD-1/PD-L1 inhibitors: a questionnaire survey of oncologists in China
Authors: Zhang Bicheng , Song Yuxiao , Fu Yang , Zhu Bo , Wang Baocheng , Wang Jun
Published: January 2020

Background

The purpose of the present study was to obtain information on the use of PD-1/PD-L1 inhibitors by oncologists in China through a national questionnaire survey.

Methods

Between the 7th and 25th of July in 2019, a questionnaire designed by the Chinese Society of Clinical Oncology Immuno-Oncology (CSCO IO) Committee on the current status of the use of PD-1/PD-L1 inhibitors was distributed online and offline to cancer-related medical departments in thirty different provinces and autonomous regions of China. The national questionnaire consisted of three sections as follows: general information, current status of the application of PD-1/PD-L1 inhibitors in the clinic, and oncologists’ concerns regarding utilization.

Results

The valid response rate of the current status survey was 76.3%. The proportion of senior doctors (physician-in-charge or a more superior position for more than 3 years) among the respondents was relatively high (67.0% in 588). Of the respondents, 59.2% had prescribed PD-1/PD-L1 inhibitors during clinical treatment, and the most frequent reason for not prescribing these inhibitors was the choice “do not understand the mechanism and the efficacy of PD-1/PD-L1 inhibitors”. In addition, 77.9% of the prescribers used the medications in an off-label situation, and the most important motivation for this use was the fact that “there were indications abroad but not domestically”. In addition, 77.9% of the prescribers believed that “immunotherapy-related adverse effects could be controlled or intervened through follow-up management”. The prescribers were mostly concerned about “how to identify pseudoprogression and hyperprogression” and “immunity-related adverse effects management”.

Conclusion

The present study highlights the current status of PD-1/PD-L1 inhibitors in China. Increasing numbers of medical oncologists are interested in PD-1/PD-L1 inhibitors, and they are in need of immunotherapy education.
Malapposition of graft-host interface after penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK): an optical coherence tomography study
Authors: Zhao Yujin , Zhuang Hong , Hong Jiaxu , Tian Lijia , Xu Jianjiang
Published: January 2020

Backgroud

Previous studies of internal graft-host malappositions have not dealt with the precise ways in which each malapposition affected post-penetrating keratoplasty (post-PK) visual outcomes. In this study, we reviewed our post-PK and post-deep anterior lamellar keratoplasty (post-DALK) keratoconic patients and used anterior segment optical coherence tomography (AS-OCT) to evaluate the associations between graft-host interface (GHI) characteristics and visual outcomes.

Methods

Novel GHI metrics included: mean graft-host touch (GHT), total prevalence of malapposition proportion (Pm), frequency of apposition (F), size of malapposition (Sm), junctional graft thickness (Tg), junctional host thickness (Th) and the absolute value of difference between Tg and Th (|Tg-Th|). We connected the external and internal junction points of GHI (GHT) and drew a straight line through the central point, perpendicular to both sides of the cornea. Tg and Th were the thicknesses at cross-points 1 mm away from the meeting point on the external side of the graft and host, respectively. Linear regression analysis was used to describe associations between GHI metrics and postsurgical visual outcomes [logarithm of minimum angle of resolution best-corrected visual acuity (logMAR BCVA), spherical equivalent diopter (SE), diopter of spherical power (DS), diopter of cylindrical power (DC) and keratometric astigmatism (Astig value)].

Results

We enrolled 22 post-PK and 23 post-DALK keratoconic patients. Compared with the regular-apposition results, GHT was decreased in step and gape patterns, and increased in hill and tag patterns. SE increased averagely by 6.851, 5.428 and 5.164 diopter per 1% increase in: F (step) [β = 6.851; 95% Confidence interval (CI) = 2.975–10.727; P = 0.001]; F (graft step) [β = 5.428; 95% CI = 1.685–9.171; P = 0.005]; and Pm [β = 5.164; 95%CI = 0.913–9.146; P = 0.018], respectively. SE increased averagely by 0.31 diopter per 10-μm increment in |Tg-Th| [β = 0.031; 95% CI = 0.009–0.054; P = 0.007]. LogMAR BCVA increased (on average) by 0.01 per 10-μm increment in both GHT [β = 0.001; 95% CI = 0–0.002; P = 0.030]. and Tg [β = 0.001; 95% CI = 0.001–0.002; P = 0.001]. Astig value increased on average by 0.17 diopter per 10-μm increment in Sm [β = 0.017; 95% CI = 0–0.033; P = 0.047].

Conclusion

This investigation of GHI characteristics suggests explanations for varied ametropia in keratoconic eyes and has potential significance as a reference for promoting pre-surgical planning and technology for corneal transplantation.
Correction to: Adaptive capacity of 2- to 5-month-old infants to the flow, shape, and flexibility of different teats during bottle feeding: a cross-sectional study
Authors: Lagarde M. L. J. , van Alfen N. , de Groot S. A. F. , Geurts A. C. H. , van den Engel-Hoek L.
Published: January 2020

Following the publication of the article [1], the authors noticed that Fig. 3 used is not the updated version. The correct version is shown below.
Does this lung nodule need urgent review? A discrete choice experiment of Australian general practitioners
Authors: Brownell P. , Piccolo F. , Brims F. , Norman R. , Manners D.
Published: January 2020

Background

Lung cancer is the leading cause of cancer mortality in Australia. Guidelines suggest that patients with suspected lung cancer on thoracic imaging be referred for urgent specialist review. However, the term “suspected” is broad and includes the common finding of lung nodules, which often require periodic surveillance rather than urgent invasive investigation. The British Thoracic Society recommends that a lung nodule with a PanCan risk > 10% be considered for invasive investigation. This study aimed to assess which factors influence general practitioners (GPs) to request urgent review for a lung nodule and if these factors concur with PanCan risk prediction model variables.

Methods

A discrete choice experiment was developed that produced 32 individual case vignettes. Each vignette contained eight variables, four of which form the parsimonious PanCan risk prediction model. Two additional vignettes were created that addressed haemoptysis with a normal chest computed tomography (CT) scan and isolated mediastinal lymphadenopathy. The survey was distributed to 4160 randomly selected Australian GPs and they were asked if the patients in the vignettes required urgent (less than two weeks) specialist review. Multivariate logistic regression identified factors associated with request for urgent review.

Results

Completed surveys were received from 3.7% of participants, providing 152 surveys (1216 case vignettes) for analysis. The factors associated with request for urgent review were nodule spiculation (adj-OR 5.57, 95% CI 3.88–7.99, p < 0.0001), larger nodule size, presentation with haemoptysis (adj-OR 4.79, 95% CI 3.05–7.52, p < 0.0001) or weight loss (adj-OR 4.87, 95% CI 3.13–7.59, p < 0.0001), recommendation for urgent review by the reporting radiologist (adj-OR 4.68, 95% CI 2.86–7.65, p < 0.0001) and female GP gender (adj-OR 1.87, 95% CI 1.36–2.56, p 0.0001). In low risk lung nodules (PanCan risk < 10%), there was significant variability in perceived sense of urgency. Most GPs (83%) felt that a patient with haemoptysis and a normal chest CT scan did not require urgent specialist review but that a patient with isolated mediastinal lymphadenopathy did (75%).

Conclusion

Future lung cancer investigation pathways may benefit from the addition of a risk prediction m9odel to reduce variations in referral behavior for low risk lung nodules.
Surfactant protein A as a biomarker of outcomes of anti-fibrotic drug therapy in patients with idiopathic pulmonary fibrosis
Authors: Yoshikawa Takumi , Otsuka Mitsuo , Chiba Hirofumi , Ikeda Kimiyuki , Mori Yuki , Umeda Yasuaki , Nishikiori Hirotaka , Kuronuma Koji , Takahashi Hiroki
Published: January 2020

Background

Idiopathic pulmonary fibrosis (IPF) is a progressive and fibrosing lung disease with poor prognosis. Pirfenidone and nintedanib are anti-fibrotic drugs used for patients with IPF. These drugs reduce the rate of decline in forced vital capacity (FVC). Serum surfactant protein (SP)-A, SP-D, and Krebs von den Lungen-6 (KL-6) are monitoring and prognostic biomarkers in patients with IPF; however, their relationship with the therapeutic outcomes of anti-fibrotic drugs has not been investigated. We aim to clarify whether serum SP-A, SP-D, and KL-6 reflect therapeutic outcomes of pirfenidone and nintedanib administration in patients with IPF.

Methods

We retrospectively investigated patients with IPF who were initiated on pirfenidone or nintedanib administration between January 2014 and June 2018 at our hospital. Changes in clinical parameters and serum SP-A, SP-D, and KL-6 levels were evaluated. Patients with ≥10% decline in FVC or ≥ 15% decline in diffusing capacity of the lung for carbon monoxide (DLco) from baseline to 6 months were classified as progression group, while the other patients were classified as stable group.

Results

Forty-nine patients were included (pirfenidone, 23; nintedanib, 26). Stable group comprised 32 patients, while progression group comprised 17 patients. In the stable group, changes in SP-A and KL-6 from baseline to 3 and 6 months significantly decreased compared with the progression group (SP-A: 3 months − 6.0% vs 16.7%, 6 months − 10.2% vs 20.2%, KL-6: 3 months − 9.2% vs 6.7%, 6 months − 15.0% vs 12.1%, p < 0.05). Changes in SP-A and SP-D levels showed significant negative correlations with the change in %FVC (r = − 0.46 and r = − 0.39, p < 0.01, respectively) and %DLco (r = − 0.67 and r = − 0.54, p < 0.01, respectively). Similar results were also seen in subgroup analysis for both pirfenidone and nintedanib groups. On logistic regression analysis, decrease in SP-A from baseline to 3 months and 6 months was found to predict the outcomes at 6 months (odds ratios: 0.89 and 0.88, respectively).

Conclusions

Changes in serum SP-A reflected the outcomes of anti-fibrotic drug therapy. Serum SP-A has a potential as a biomarker of therapeutic outcomes of anti-fibrotic drugs.
Effect of air-polishing on surface roughness of composite dental restorative material – comparison of three different air-polishing powders
Authors: Janiszewska-Olszowska Joanna , Drozdzik Agnieszka , Tandecka Katarzyna , Grocholewicz Katarzyna
Published: January 2020

Background

Increased composite roughness enhances bacterial adhesion and discoloration, thus increasing the risk of gingival inflammation and secondary caries. Concerns about detrimental effects of sodium bicarbonate on surface roughness influenced the development of less abrasive powders: a glycine-based powder and an erythritol-based powder, additionally - sodium bicarbonate-based powder of reduced grain size. However, there is limited evidence on effects of these materials on the surface of dental fillings. The aim of the present study was to compare the effects of three air-polishing powders (of a reduced abrasiveness) on surface roughness of microhybrid restorative composite material.

Material and methods

Microhybrid light-cure resin composite samples were placed on 64 plaster cubes and light-cured through polyester strips. Surface roughness was measured using laser confocal microscope (magnification 2160x). The specimens were randomly divided into three groups (n = 20, 20 and 24) and air-polished with: sodium bicarbonate (40 μm), glycine (25 μm) and erythritol (14 μm), respectively. Then surface roughness was remeasured, keeping the same field of observation. Specialized 3D analysis software was used for data processing. Parameters according to ISO 25178: Sa, Sq, Sku, Sp, Sv, Sz, Ssk were used to describe surface roughness.

Results

Sa, Sq, Sp, Sv, Sz increased significantly following air polishing. Ssk was significantly higher, whereas Sku was significantly lower in sodium bicarbonate and erythritol groups than before air polishing. Comparison between the three powders revealed that Sa was significantly higher in sodium bicarbonate group than in glycine group. Sku was significantly higher in glycine and erythritol groups than in sodium bicarbonate group.

Conclusions

Sodium bicarbonate has a stronger detrimental effect on composite surface than glycine or erythritol. No advantage of erythritol comparing to glycine could be found.
Association between water, sanitation, general hygiene and oral hygiene practices of street-involved young people in Southwest Nigeria
Authors: Folayan Morenike Oluwatoyin , Obiyan Mary O. , Olaleye Atinuke O.
Published: January 2020

Background

Oral hygiene practices can be linked to personal hygiene practices, including access to water and other sanitation facilities. The objective of the study was to determine if there is an association between oral hygiene practices and water and sanitation hygiene (WASH) practices among street-involved young people (SIYP).

Methods

A cross-sectional study recruited SIYP age 10–24 years in two States in Nigeria recruited through respondent-driven sampling in December 2018. Interviewer-administered questionnaires were used to collect data on water access, sanitation, personal and oral hygiene. The instruments used for collecting the data were standardized tools for measuring the phenomena studied. The association between knowledge and practice of oral hygiene; oral hygiene and water, sanitation and hygiene (WASH); and indicators of good oral hygiene were determined using binary logistic regression guided by two models.

Results

A total of 845 study participants were recruited. The proportion of SIYP with good knowledge of oral hygiene was low (31.2%), and fewer had good oral hygiene practice (8.9%). There were significant associations between knowledge and practice of tooth cleaning, use of fluoride-containing toothpaste, dental flossing, consumption of sugar between meals, and frequency of dental check-ups (p < 0.001 respectively). Respondents with good water collection and storage practices (AOR: 2.01; 95% CI: 1.24–3.24;P = 0.005) and those residing in Lagos (AOR: 2.85; 95% CI: 1.61–5.06;P = 0.001) had a higher likelihood of having good oral hygiene.

Conclusion

Good oral hygiene practices of SIYP in Nigeria is associated with access to water collection and storage. WASH programs can have an impact on health through improved oral hygiene practices.
Zhenqing recipe attenuates non-alcoholic fatty liver disease by regulating the SIK1/CRTC2 signaling in experimental diabetic rats
Authors: Song Daofei , Yin Lei , Wang Chang , Wen Xiuying
Published: January 2020

Background

As a compound Chinese medicine, Zhenqing Recipe (ZQR) has been shown to ameliorate hyperglycemia, hyperlipidemia, fatty liver and insulin resistance in patients with diabetes and diabetic rats. In this paper, we further examined the effect of ZQR on diabetes complicated by non-alcoholic fatty liver disease (NAFLD) and the underlying molecular mechanisms.

Methods

Diabetic rats with NAFLD were developed by a high-fat diet (HFD) with low-dose streptozotocin (STZ) injection for 4 weeks. These rats were randomly separated into the diabetic model (DM), ZQR, metformin (Met), adenovirus expressing-salt-induced kinase 1 (Ad-SIK1) and adenovirus labeled with green fluorescent protein (Ad-GFP) groups. The effects on hepatic expression of gluconeogenic genes, glycolipid metabolism and pathological changes were subsequently detected.

Results

Serum glucose, triglycerides (TG), total cholesterol (TC) and hepatic TG were reduced in the ZQR group. The histopathological and immunohistochemical changes in the liver and pancreas in the ZQR group were significantly alleviated. The decrease of SIK1 expression was observed in the liver of diabetic rats induced by HFD and STZ. SIK1 overexpression in the liver relieved hyperglycemia, hyperlipidemia and fatty liver. Both the mRNA and protein levels of CREB-regulated transcription co-activator 2 (CRTC2), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in the liver were drastically reduced, whereas those of SIK1 were markedly increased in the ZQR group compared to levels in the DM group. Compared with the DM group, Ser577 phosphorylation of SIK1 was obviously reduced in the liver, while T182 phosphorylation of SIK1 and S171 phosphorylation of CRTC2 were evidently increased in the Ad-SIK1, Met and ZQR groups.

Conclusions

ZQR ameliorates hepatic gluconeogenesis and lipid storage in diabetic rats induced by HFD and STZ by activating the SIK1/CRTC2 signaling pathway. Upregulating hepatic SIK1 by ZQR may represent an efficient strategy for treating diabetes with NAFLD.
Health-related quality of life and symptoms in patients with IPF treated with nintedanib: analyses of patient-reported outcomes from the INPULSIS® trials
Authors: Kreuter Michael , Wuyts Wim A. , Wijsenbeek Marlies , Bajwah Sabrina , Maher Toby M. , Stowasser Susanne , Male Natalia , Stansen Wibke , Schoof Nils , Orsatti Leticia , Swigris Jeffrey
Published: January 2020

Background

In the Phase III INPULSIS® trials, treatment of patients with idiopathic pulmonary fibrosis (IPF) with nintedanib significantly reduced the annual rate of decline in forced vital capacity (FVC) versus placebo, consistent with slowing disease progression. However, nintedanib was not associated with a benefit in health-related quality of life (HRQoL) assessed using the St George’s respiratory questionnaire (SGRQ). We aimed to further examine the impact of IPF progression on HRQoL and symptoms, and to explore the effect of nintedanib on HRQoL in patients from the INPULSIS® trials stratified by clinical factors associated with disease progression.

Methods

Patient-reported outcome (PRO) data from the INPULSIS® trials were included in three post hoc analyses. Two analyses used the pooled data set to examine PRO changes from baseline to week 52 according to 1) decline in FVC and 2) occurrence of acute exacerbations. In the third analysis, patients were stratified based on clinical indicators of disease progression (gender, age and physiology [GAP] stage; FVC % predicted; diffusing capacity of the lung for carbon monoxide [DLCO] % predicted; composite physiologic index [CPI]; and SGRQ total score) at baseline; median change from baseline was measured at 52 weeks and treatment groups were compared using the Wilcoxon two-sample test.

Results

Data from 1061 patients (638 nintedanib, 423 placebo) were analyzed. Greater categorical decline from baseline in FVC % predicted over 52 weeks was associated with significant worsening of HRQoL and symptoms across all PRO measures. Acute exacerbations were associated with deterioration in HRQoL and worsened symptoms. In general, patients with advanced disease at baseline (defined as GAP II/III, FVC ≤ 80%, DLCO ≤ 40%, CPI >  45, or SGRQ > 40) experienced greater deterioration in PROs than patients with less-advanced disease. Among patients with advanced disease, compared with placebo, nintedanib slowed deterioration in several PROs; benefit was most apparent on the SGRQ (total and activity scores).

Conclusions

In patients with advanced IPF, compared with placebo, nintedanib slowed deterioration in HRQoL and symptoms as assessed by several PROs. HRQoL measures have a higher responsiveness to change in advanced disease and may lack sensitivity to capture change in patients with less-advanced IPF.
Using a ‘rich picture’ to facilitate systems thinking in research coproduction
Authors: Conte Kathleen P. , Davidson Seanna
Published: January 2020

Background

In coproduction research, traditional ‘end-users’ are involved in the entire research process. The aim is to facilitate research translation by improving the timeliness and relevance of research. Because end-users often come from multiple sectors and hold diverse perspectives and priorities, involving them in coproduction can be challenging. Tools and approaches are needed to support coproduction teams to successfully navigate divergent viewpoints while producing rigorous but meaningful research outcomes. Rich pictures are a systems thinking tool to help make sense of complexity. In this paper, we describe how we developed and applied a ‘rich picture’ in a coproduction project with policy-level partners.

Methods

Guided by systems thinking principles, we conducted a systemic analysis of ethnographic fieldnotes collected as part of a broader study that examined the dynamics between an IT system and the implementation of the state-wide childhood obesity prevention programmes it was designed to monitor. Translating qualitative themes into metaphor and imagery, we created a visual depiction of the system to reflect the experience of the system’s users (health promotion practitioners) and facilitated a workshop with policy-level programme administrators (i.e. participants, n = 7). Our aim was to increase the transparency of the system for our research partners and to spark new insights to improve the quality of programme implementation.

Results

Guided by provocative questions, participants discussed and challenged each other’s thinking on the current functioning of the system. They identified future lines of inquiry to explore for quality improvement. Participants strongly agreed that the picture was a constructive way to engage with the ethnographic data but were challenged by the information and its implications. The opportunity for participants to co-learn from each other as well as from the picture was an added value.

Conclusion

In the context of the facilitated workshop, the rich picture enabled research partners to engage with complex research findings and gain new insights. Its value was harnessed via the guided participatory process. This demonstrates the importance that, in the future, such tools should be accompanied by practices that enable participants to think with and apply systems thinking concepts and principles.
Safety, tolerability and immunogenicity of V934/V935 hTERT vaccination in cancer patients with selected solid tumors: a phase I study
Authors: Aurisicchio Luigi , Fridman Arthur , Mauro David , Sheloditna Rose , Chiappori Alberto , Bagchi Ansuman , Ciliberto Gennaro
Published: January 2020

Background

Human telomerase reverse transcriptase (hTERT) is an antigen that may represent a target for a novel anti-cancer strategy. A pilot, phase I study tested the safety and feasibility of a prime-boost immunization regimen based on V935, an adenoviral type 6 vector vaccine expressing a modified version of hTERT, administered alone or in combination with V934, a DNA plasmid that also expresses the same antigen and is delivered using the electroporation injection technique.

Methods

Treatments: Group #1 received two doses (low-dose: 0.5 × 109 vg, and high-dose: 0.5 × 1011 vg) of V935 followed by a 4-week observation period. Group #2 received three doses of V934-electroporation and two doses of V935 following a 4-week observation period. Doses were low-dose V934 (0.25 mg of plasmid) with low-dose V935 (0.5 × 109 vg); high-dose V934 (2.5 mg of plasmid) with high-dose V935 (0.5 × 1011 vg). Group #3 received five doses of V934-EP and two doses of V935: V934 was administered IM every 2 weeks for five doses. Following a 4-week observation period, V935 was administered IM every 2 weeks for two doses followed by a 4-week observation period. One (1) dose level was tested in treatment group #3: high-dose V934 (2.5 mg of plasmid), in combination with high-dose V935 (0.5 × 1011 vg). Immunogenicity was measured by ELISPOT assay and three pools of peptides encompassing the sequence of hTERT.

Results

In total, 37 patients affected by solid tumors (prostate cancer in 38%) were enrolled. The safety profile of different regimens was good and comparable across groups, with no severe adverse events, dose-limiting toxicities or treatment discontinuations. As expected, the most common adverse events were local reactions. A significant increase in ELISPOT responses against hTERT peptide pool 2 was observed (p < 0.01), while no evidence of boosting was observed for peptide pools 1 and 3. This was also evident for group #1 and #2 separately. In patients with prostate cancer, there was a significant increase in ELISPOT response against hTERT peptide pool 2 following immunization (p < 0.01), regardless of previous therapy, immunosuppressing agents, or adenoviral type 6 titers at screening.

Conclusion

Our results suggest the safety and feasibility of V934/V935 hTERT vaccination in cancer patients with solid tumors

Trial Registration Name of the registry: ClinicalTrial.gov Trial registration number: NCT00753415 Date of registration: 16 September 2008 Retrospectively registered URL of trial registry record: https://clinicaltrials.gov/ct2/results?cond=&term=NCT00753415&cntry=&state=&city=&dist=
Improved therapeutics of modified mesenchymal stem cells: an update
Authors: Ocansey Dickson Kofi Wiredu , Pei Bing , Yan Yongmin , Qian Hui , Zhang Xu , Xu Wenrong , Mao Fei
Published: January 2020

Background

Mesenchymal stromal cells (MSCs) have attracted intense interest due to their powerful intrinsic properties of self-regeneration, immunomodulation and multi-potency, as well as being readily available and easy to isolate and culture. Notwithstanding, MSC based therapy suffers reduced efficacy due to several challenges which include unfavorable microenvironmental factors in vitro and in vivo.

Body

In the quest to circumvent these challenges, several modification techniques have been applied to the naïve MSC to improve its inherent therapeutic properties. These modification approaches can be broadly divided into two groups to include genetic modification and preconditioning modification (using drugs, growth factors and other molecules). This field has witnessed great progress and continues to gather interest and novelty. We review these innovative approaches in not only maintaining, but also enhancing the inherent biological activities and therapeutics of MSCs with respect to migration, homing to target site, adhesion, survival and reduced premature senescence. We discuss the application of the improved modified MSC in some selected human diseases. Possible ways of yet better enhancing the therapeutic outcome and overcoming challenges of MSC modification in the future are also elaborated.

Conclusion

The importance of prosurvival and promigratory abilities of MSCs in their therapeutic applications can never be overemphasized. These abilities are maintained and even further enhanced via MSC modifications against the inhospitable microenvironment during culture and transplantation. This is a turning point in MSC-based therapy with promising preclinical studies and higher future prospect.
Dynamic changes of angiopoietins and endothelial nitric oxide supply during fluid resuscitation for major gyn-oncological surgery: a prospective observation
Authors: Gehlen Jennifer , Klaschik Sven , Neumann Claudia , Keyver-Paik Mignon-Denise , Mustea Alexander , Soehle Martin , Frede Stilla , Velten Markus , Hoeft Andreas , Hilbert Tobias
Published: January 2020

Background

Despite goal-directed hemodynamic therapy, vascular function may deteriorate during surgery for advanced abdominal tumor masses. Fluid administration has been shown to be associated with distinct changes in serum levels of functional proteins. We sought to determine how serum total protein and angiopoietin (ANG) levels change during major abdominal tumor surgery. In addition, ex vivo endothelial nitric oxide synthase (eNOS) activation as well as NO bioavailability in vivo were assessed.

Methods

30 patients scheduled for laparotomy for late-stage ovarian or uterine cancer were prospectively included. Advanced hemodynamic monitoring as well as protocol-driven goal-directed fluid optimization were performed. Total serum protein, ANG-1, -2, and soluble TIE2 were determined pre-, intra-, and postoperatively. Phosphorylation of eNOS was assessed in microvascular endothelial cells after incubation with patient serum, and microvascular reactivity was determined in vivo by near-infrared spectroscopy and arterial vascular occlusion.

Results

Cardiac output as well as preload gradually decreased during surgery and were associated with a median total fluid intake of 12.8 (9.7–15.4) mL/kg*h and a postoperative fluid balance of 6710 (4113–9271) mL. Total serum protein decreased significantly from baseline (66.5 (56.4–73.3) mg/mL) by almost half intraoperatively (42.7 (36.8–51.5) mg/mL, p < 0.0001) and remained at low level. While ANG-1 showed no significant dilutional change (baseline: 12.7 (11.9–13.9) ng/mL, postop.: 11.6 (10.8 –13.5) ng/mL, p = 0.06), serum levels of ANG-2 were even increased postoperatively (baseline: 2.2 (1.6–2.6) ng/mL vs. postop.: 3.4 (2.3–3.8) ng/mL, p < 0.0001), resulting in a significant shift in ANG-2 to ANG-1 ratio. Ex vivo phosphorylation of eNOS was decreased depending on increased ANG-2 levels and ANG-2/1 ratio (Spearman r = − 0.37, p = 0.007). In vivo, increased ANG-2 levels were associated with impaired capillary recruitment and NO bioavailability (Spearman r = − 0.83, p = 0.01).

Conclusions

Fluid resuscitation-associated changes in serum vascular mediator profile during abdominal tumor surgery were accompanied by impaired eNOS activity ex vivo as well as reduced NO bioavailability in vivo. Our results may explain disturbed microvascular function in major surgery despite goal-directed hemodynamic optimization.
ALK expressed in a gastrointestinal stromal tumor harboring PDGFRA p. D842V mutation:a case report
Authors: Fan Jun , Yang Ming , Huang Bo , Wang Zhenkao , Luo Danju , Zhang Jiwei , Zhang Peng , Shi Heshui , Li Yan , Nie Xiu
Published: January 2020

Background

Gastrointestinal stromal tumors (GISTs) are the most common type of adult mesenchymal neoplasms. The events that drive GIST oncogenesis are primarily KIT or PDGFRA mutations, which lead to the susceptibility of these tumors to small-molecule tyrosine kinase inhibitors such as imatinib and sunitinib. However, previous studies have shown that patients with a PDGFRA D842V mutation in GISTs have a very low rate of response to imatinib treatment. Therefore, novel tyrosine kinase inhibitors (TKIs) are currently being evaluated in clinical trials to treat GISTs harboring a PDGFRA D842V mutation. Anaplastic lymphoma kinase (ALK) overexpression was not expected to be present in the GIST, and it has been used as a biomarker to distinguish GISTs from other types of mesenchymal tumors.

Case presentation

Here, we report a 37-year-old male patient who presented with a large mass in the right upper abdomen and was subsequently diagnosed with a GIST harboring a PDGFRA D842V mutation. We unexpectedly found that the GIST in this patient exhibited simultaneous ALK expression.

Conclusions

This is the first case reported of a GIST with ALK expression. This rare phenomenon suggests that the diagnosis of a GIST cannot be excluded absolutely if a tumor exhibits ALK expression. In addition, ALK may be a potential therapeutic target for patients with imatinib-resistant stromal tumors.