bluuebunny/crossref_metadata_2025_split 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundMulti-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.ResultsTo 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.ConclusionsThe 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.