bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Haplotype Diversity in the BADH2 Aroma Gene and Development of a KASP SNP Assay for Predicting Aroma in U.S. Rice
Authors: Addison Christopher K. , Angira Brijesh , Kongchum Manoch , Harrell Dustin L. , Baisakh Niranjan , Linscombe Steven D. , Famoso Adam N. 
Published: July 2020

Abstract
Background
Aroma is an important grain quality trait in rice, controlled by mutations within the BADH2 gene. The trait is simply inherited, and its importance in variety development makes it a practical target for marker-assisted selection in applied breeding programs. The predominant functional mutation within BADH2, an 8-bp indel, can be reliably detected using a PCR-based assay, but the available assays and associated genotyping platforms are insufficient for large-scale applied molecular breeding applications and are not compatible with outsourcing genotyping services.

Results
We first characterized SNP diversity across the BADH2 gene in a collection of 2932 rice varieties to determine the number of gene haplotypes in O. sativa. Using 297 gene-based SNPs, 11 haplotype groups were detected, and subsequently identified a minimal set of nine informative SNPs that uniquely identified the BADH2 haplotypes. These nine SNPs were developed into KASP assays and used to examine a panel of 369 U.S. rice accessions. The panel represented modern breeding germplasm and included all known aroma pedigree sources in U.S. rice. Six haplotypes were detected within the U.S. panel, of which two were found in majority (85%) of varieties. A representative set of 39 varieties from all haplotype groups was evaluated phenotypically to distinguish aromatic from non-aromatic lines.

Conclusion
One haplotype (Hap 6) was found to be perfectly associated with the aromatic phenotype. A single KASP SNP unique to Hap 6 was demonstrated to reliably differentiate aromatic from non-aromatic rice varieties across U.S. germplasm.
Efficient In Vivo Introduction of Point Mutations Using ssODN and a Co-CRISPR Approach
Authors: Levi Tgst , Sloutskin Anna , Kalifa Rachel , Juven-Gershon Tamar , Gerlitz Offer 
Published: July 2020

Abstract
Background
The generation of point mutations is a major tool for evaluating the roles of specific nucleotides or amino acids within the regulatory or functional landscape. However, examination of these mutations in vivo requires the generation of animals carrying only the relevant point mutations at the endogenous genomic loci, which is technically challenging. The CRISPR-Cas9 based genome editing greatly facilitates the generation of such genetically modified animals; however, most of the described methods use double-strand DNA (dsDNA) as the donor template. The dsDNA plasmids frequently undergo undesired integration events into the targeted genomic locus. The use of a single-strand oligodeoxynucleotide (ssODN) as the donor template prevents this complication and is therefore the preferred choice for introducing point mutations, as well as short sequences such as protein tags.

Results
We successfully applied the CRISPR-based white co-conversion strategy with a ssODN template, instead of the originally described dsDNA plasmid, to create genetically modified Drosophila melanogaster strains. We used the technique to easily introduce point mutations in two distinct chromosomes. Using the generated flies, we were able to demonstrate the in vivo importance of the respective mutations. For the Nucleoporin107 (Nup107) gene, the 1090G > A mutation was confirmed to affect ovarian development, while for the tinman (tin) gene, the regulatory role of the downstream core promoter element (DPE) was demonstrated within the developing Drosophila melanogaster embryo.

Conclusions
The described approach has facilitated the successful generation of point mutations in two different chromosomes, by two different labs. Distinct phenotypes associated with the newly-generated genotype were identified, thus exemplifying the importance of investigating the in vivo role of specific nucleotides. In addition, detailed guidelines, recommendations and crossing schemes are provided in order to support the generation of additional genetically modified animals by the scientific community.
The genetic heritage of Alpine local cattle breeds using genomic SNP data
Authors: Senczuk Gabriele , Mastrangelo Salvatore , Ciani Elena , Battaglini Luca , Cendron Filippo , Ciampolini Roberta , Crepaldi Paola , Mantovani Roberto , Bongioni Graziella , Pagnacco Giulio , Portolano Baldassare , Rossoni Attilio , Pilla Fabio , Cassandro Martino 
Published: July 2020

AbstractBackgroundAssessment of genetic diversity and population structure provides important control metrics to avoid genetic erosion, inbreeding depression and crossbreeding between exotic and locally-adapted cattle breeds since these events can have deleterious consequences and eventually lead to extinction. Historically, the Alpine Arc represents an important pocket of cattle biodiversity with a large number of autochthonous breeds that provide a fundamental source of income for the entire regional economy. By using genotype data from medium-density single nucleotide polymorphism (SNP) arrays, we performed a genome-wide comparative study of 23 cattle populations from the Alpine Arc and three cosmopolitan breeds.ResultsAfter filtering, we obtained a final genotyping dataset consisting of 30,176 SNPs for 711 individuals. The local breeds showed high or intermediate values of genetic diversity compared to the highly selected cosmopolitan breeds. Patterns of genetic differentiation, multidimensional scaling, admixture analysis and the constructed phylogenetic tree showed convergence, which indicates the presence of gene flow among the breeds according to both geographic origin and historical background. Among the most differentiated breeds, we identified the modern Brown cattle. In spite of admixture events, several local breeds have preserved distinctive characteristics, which is probably due to differences in genetic origin and geographic location.ConclusionsThis study represents one of the most comprehensive genome-wide analysis of the Alpine cattle breeds to date. Using such a large dataset that includes the majority of the local breeds found in this region, allowed us to expand knowledge on the evaluation and status of Alpine cattle biodiversity. Our results indicate that although many of the analyzed local breeds are listed as endangered, they still harbor a large amount of genetic diversity, even when compared to some cosmopolitan breeds. This finding, together with the reconstruction of the phylogeny and the relationships between these Alpine Arc cattle breeds, provide crucial insights not only into the improvement of genetic stocks but also into the implementation of future conservation strategies.
TRANSTHYRETIN-LIKE and BYPASS1-LIKE co-regulate growth and cold tolerance in Arabidopsis
Authors: Chen Tao , Zhang Wei , Yang Gang , Chen Jia-Hui , Chen Bi-Xia , Sun Rui , Zhang Hua , An Li-Zhe 
Published: July 2020

Abstract
Background
Cold stress inhibits normal physiological metabolism in plants, thereby seriously affecting plant development. Meanwhile, plants also actively adjust their metabolism and development to adapt to changing environments. Several cold tolerance regulators have been found to participate in the regulation of plant development. Previously, we reported that BYPASS1-LIKE (B1L), a DUF793 family protein, participates in the regulation of cold tolerance, at least partly through stabilizing C-REPEAT BINDING FACTORS (CBFs). In this study, we found that B1L interacts with TRANSTHYRETIN-LIKE (TTL) protein, which is involved in brassinosteroid (BR)-mediated plant growth and catalyses the synthesis of S-allantoin, and both proteins participate in modulating plant growth and cold tolerance.

Results
The results obtained with yeast two hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays showed that B1L directly interacted with TTL. Similar to the ttl-1 and ttl-2 mutants, the b1l mutant displayed a longer hypocotyl and greater fresh weight than wild type, whereas B1L-overexpressing lines exhibited a shorter hypocotyl and reduced fresh weight. Moreover, ttl-1 displayed freezing tolerance to cold treatment compared with WT, whereas the b1l mutant and TTL-overexpressing lines were freezing-sensitive. The b1l ttl double mutant had a developmental phenotype and freezing tolerance that were highly similar to those of ttl-1 compared to b1l, indicating that TTL is important for B1L function. Although low concentrations of brassinolide (0.1 or 1 nM) displayed similarly promoted hypocotyl elongation of WT and b1l under normal temperature, it showed less effect to the hypocotyl elongation of b1l than to that of WT under cold conditions. In addition, the b1l mutant also contained less amount of allantoin than Col-0.

Conclusion
Our results indicate that B1L and TTL co-regulate development and cold tolerance in Arabidopsis, and BR and allantoin may participate in these processes through B1L and TTL.
The statistical importance of a study for a network meta-analysis estimate
Authors: Rücker Gerta , Nikolakopoulou Adriani , Papakonstantinou Theodoros , Salanti Georgia , Riley Richard D. , Schwarzer Guido 
Published: July 2020

Abstract
Background
In pairwise meta-analysis, the contribution of each study to the pooled estimate is given by its weight, which is based on the inverse variance of the estimate from that study. For network meta-analysis (NMA), the contribution of direct (and indirect) evidence is easily obtained from the diagonal elements of a hat matrix. It is, however, not fully clear how to generalize this to the percentage contribution of each study to a NMA estimate.

Methods
We define the importance of each study for a NMA estimate by the reduction of the estimate’s variance when adding the given study to the others. An equivalent interpretation is the relative loss in precision when the study is left out. Importances are values between 0 and 1. An importance of 1 means that the study is an essential link of the pathway in the network connecting one of the treatments with another.

Results
Importances can be defined for two-stage and one-stage NMA. These numbers in general do not add to one and thus cannot be interpreted as ‘percentage contributions’. After briefly discussing other available approaches, we question whether it is possible to obtain unique percentage contributions for NMA.

Conclusions
Importances generalize the concept of weights in pairwise meta-analysis in a natural way. Moreover, they are uniquely defined, easily calculated, and have an intuitive interpretation. We give some real examples for illustration.
Risk literacy assessment of general practitioners and medical students using the Berlin Numeracy Test
Authors: Friederichs Hendrik , Birkenstein Roman , Becker Jan C. , Marschall Bernhard , Weissenstein Anne 
Published: July 2020

AbstractBackgroundThe responsibility for helping patients understand potential health benefits and risks, especially regarding screening tests, falls largely to general practitioners (GPs). The Berlin Numeracy Test (BNT) specifically measures risk literacy (i.e., the ability to understand different aspects of statistical numeracy associated with accurate interpretation of information about risks). This study explored the association between risk literacy levels and clinical experience in GPs vs. medical students. Additionally, the effect of GP risk literacy on evaluation of the predictive value of screening tests was examined.MethodsThe participants were 84 GPs and 92 third-year medical students who completed the BNT (total score range 0–4 points). The GPs received an additional case scenario on mammography screening as a simple measure of performance in applying numeracy skills.ResultsDespite having an average of 25.9 years of clinical experience, GPs scored no better than medical students on risk literacy (GPs: 2.33 points, 95% confidence interval [CI] 2.08–2.59; students: 2.34, 95% CI 2.07–2.61;P = .983). Of all GPs, 71.6% (n = 58) greatly overestimated the real predictive value.ConclusionsIn this study, we found no difference in risk literacy between current students and current GPs. GPs lack risk literacy and consequently do not fully understand numeric estimates of probability in routine screening procedures.
Association among cytokine profiles of innate and adaptive immune responses and clinical-virological features in untreated patients with chronic hepatitis B
Authors: Gu Yurong , Lian Yifan , Zheng Qiaolan , Huang Zexuan , Gu Lin , Bi Yanhua , Li Jing , Huang Yanlin , Wu Yuankai , Chen Lubiao , Huang Yuehua 
Published: July 2020

Abstract
Background
Complete clearance of intracellular viruses depends on effector cells of innate and adaptive immune systems. This study aimed to identify the relationships among antiviral cytokines produced by natural killer (NK) and T cells and clinical-virological characteristics in untreated chronic hepatitis B (CHB) patients.

Methods
We measured antiviral cytokines interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2) produced by T, NK and natural killer T (NKT) cells, respectively, in a cohort with chronic hepatitis B virus (HBV) infection (CHB). We also correlated these cytokines with clinical-virological characteristics using a linear regression model.

Results
levels of IFN-γ+ and TNF-α+ CD4+ and CD8+ T cells were significantly higher in immune active (IA) phase than in other phases. Immune tolerant (IT) patients showed the lowest expression of IFN-γ by NK and NKT cells, and TNF-α by NK cells. IFN-γ+, TNF-α+ and IL-2+ CD4+ and CD8+ T cells frequencies were similar between IA and gray zone (GZ) phases. Principal component analysis based on cytokines confirmed that most IT patients significantly differed from inactive carriers (IC) and IA patients, while GZ patients were widely scattered. Multivariate analysis showed both T and NK cells producing IFN-γ and TNF-α, but not IL-2, had significant association with serum alanine aminotransferase (ALT). Moreover, IFN-γ+ NKT cells were associated with HBV DNA, while IFN-γ+ CD4+ and CD8+ T cells were correlated with age.

Conclusion
HBV clinical phases are characterized by distinct cytokine signatures, which showed relationship to viral features in these untreated CHB patients.
Relationship between the temporal course of astrogliosis and symptom improvement in cerebral infarction: report of a case monitored using 18F-THK5351 positron emission tomography
Authors: Ishibashi Kenji , Miura Yoshiharu , Hirata Kosei , Toyohara Jun , Ishii Kenji 
Published: July 2020

Abstract
Background
18F-THK5351 was recently shown to bind to monoamine oxidase B (MAO-B) with high affinity. MAO-B is highly concentrated in astrocytes and increases during astrogliosis. Therefore, 18F-THK5351 accumulates in lesions undergoing astrogliosis. Cerebral infarction causes astrogliosis, which may be beneficial for repairing and regenerating injured cells and tissues in the lesions. Therefore, monitoring the degree of astrogliosis and stroke symptoms is essential for understanding the roles of astrogliosis in cerebral infarction.

Case presentation
A 72-year-old man, complaining of total loss of sensation in the left index finger, was diagnosed with acute cerebral infarction, and underwent 18F-THK5351 positron emission tomography (PET) on two occasions after the stroke. The first PET scan performed on day 27 revealed intense uptake in the infarct lesion located around the right precentral and postcentral gyri. However, the second PET scan on day 391 showed that the uptake had diminished significantly. The sensory deficit in the left index finger had improved by 30 and 70% at the times of the first and second PET scans, respectively.

Conclusions
18F-THK5351 uptake in the infarct lesion evidently changed between days 27 and 391, along with improved sensory deficit in the left index finger. Astrocytes reportedly play a role in restoring neuronal integrity. Therefore, the temporal course of astrogliosis may have been related to improving stroke symptoms in this patient, suggesting that the degree of astrogliosis in the infarct lesion may aid in assessing the prognosis in stroke patients.
Prevalence of human alveolar echinococcosis in China: a systematic review and meta-analysis
Authors: Wang Xuanzhuo , Dai Guodong , Li Min , Jia Wanzhong , Guo Zhongmin , Lu Jiahai 
Published: July 2020

AbstractBackgroundHuman alveolar echinococcosis (HAE), caused by the larvae ofEchinococcus multilocularis,is a severe parasitic disease that is a major public health concern. New HAE cases in China account for 91% of the global HAE burden every year. Although there are a few studies and systematic reviews (SRs) on the prevalence of HAE in China, trends in the prevalence have not been estimated. This study aims to describe the overall variation in the trend of HAE prevalence in China, and provide evidence for preventive measures in the future.MethodsThirty-five eligible studies were retrieved from PubMed, Web of Science, EMBASE, CNKI, Wanfang Data, and VIP, and included in the SR and meta-analysis. An adjusted Agency for Healthcare Research and Quality checklist was used to evaluate study quality. The arcsine transformation was used to adjust the individual reported prevalence, and the pooled HAE prevalence was calculated. Heterogeneity was evaluated using the chi-square test andI2statistic. Forest plots were generated for the meta-analysis, and publication bias of the studies was assessed using the Egger’s test and funnel plots. We conducted subgroup analyses, sensitivity analyses, and meta-regression analyses to analyze the source of heterogeneity and factors potentially influencing the prevalence of HAE.ResultsThe meta-analysis indicated that the pooled HAE prevalence in China was 0.96% (95% CI: 0.71 to 1.25%). Factors potentially influencing HAE prevalence were female sex (OR = 1.60, 95% CI: 1.35 to 1.91,P<0.01), being ≥30 years old (OR = 4.72, 95% CI: 2.29 to 9.75,P<0.01), and being farmers and/or herdsmen (OR = 2.54, 95% CI: 1.60 to 4.02,P<0.01). The results of the meta-regression analysis (R2 = 38.11%,P < 0.01) indicated that HAE prevalence is on a downward trend.ConclusionsHAE prevalence has decreased over time and maintained low levels after 2005 in China. This decline was influenced by the utilization of One Health strategies as intervention measures. Therefore, these One Health strategies should be used as references to formulate future programs for HAE control. More high-quality epidemiological investigations and surveillance programs should be conducted in order to improve HAE control in the future.
Association of job category and occupational activity with breast cancer incidence in Japanese female workers: the JACC study
Authors: Sari Gita Nirmala , Eshak Ehab Salah , Shirai Kokoro , Fujino Yoshihisa , Tamakoshi Akiko , Iso Hiroyasu 
Published: July 2020

Abstract
Background
Breast cancer represented the leading cause of cancer deaths among women in Japan. Although physical activity has been reported protective against breast cancer, scientific evidence is limited on the risk of breast cancer according to job category or occupational activity in Japanese. Our objective was to examine the association of job category and occupational activity with breast cancer incidence in Japanese female workers using the data from the Japan Collaborative Cohort (JACC) Study.

Methods
A prospective cohort study involving 19,041 women aged 40–79 years who have reported their occupational data and followed-up from 1988 to 2009. All variables were assessed by a self-administered questionnaire. Cancer incidence data were obtained from 24 areas of the JACC study through cancer population data registration, or review of hospital records. The Cox proportional hazard models were operated to calculate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs).

Results
There were 138 incident cases of breast cancer during 13.3 years median follow-up period. Office workers compared with manual workers were at a higher risk of breast cancer after adjusting for reproductive health factors and physical activity indicators; the multivariable HR (95% CI) was 1.65 (1.07–2.55). Also, women who had mainly a sitting position during work compared with those moving during work had the higher risk: the multivariable HR (95%CI) of 1.45 (1.01–2.12). The excess risk of breast cancer was observed for office workers when time spent in walking was < 30 min/ day; HR (95% CI) was 1.11 (1.01–1.23), and for women mainly at a sitting position during work when time spent in walking was 30–59 min or < 30 min/day; HRs (95% CIs) were 1.87 (1.07–3.27) and 1.74 (1.07–2.83), respectively.

Conclusion
The job category and occupational activity were associated with risk of breast cancer incidence. A high risk was observed in office workers and in women with a sitting position during work. These observed increased risks were evident in women with less daily walking activity.
Parental awareness and utilization of meningococcal serogroup B vaccines in the United States
Authors: Srivastava Amit , Dempsey Amanda , Galitsky Alex , Fahimi Mansour , Huang Liping 
Published: July 2020

Abstract
Background
Meningococcal serogroup B (MenB) is the most common cause of invasive meningococcal disease (IMD) in the United States. The US Advisory Committee on Immunization Practices (ACIP) recommends vaccination of healthy adolescents against MenB based on shared clinical decision-making (Category B recommendation). This survey assessed factors associated with MenB vaccine awareness, utilization, and interest among parents/guardians of US adolescents.

Methods
Survey participants were identified in 2016 through KnowledgePanel®, an online random sample of US households; population-based weighting methodology was used to ensure data reflected a demographically representative population sample. Adults with ≥1 dependent aged 16–19 years were eligible and completed an online questionnaire. Respondents were grouped in terms of MenB vaccination of their child as: 1) vaccinated, 2) intending to vaccinate, 3) MenB vaccine-unaware, or 4) vaccine-aware but not intending to vaccinate. Univariate and multivariate analyses were used to identify factors influencing MenB vaccine awareness and utilization; univariate analyses used the weighted proportion of each group or weighted means, and multivariate analyses used logistic regression models based on the weighted study sample of each group.

Results
Six hundred nineteen parents/guardians participated, corresponding to 26,266,700 members of the US population after weighting. MenB vaccine awareness was significantly associated with parent race and sex. Specifically, 57% of parents were unaware of MenB vaccines, and there was significantly higher lack of awareness among males and those of Hispanic or non-White ethnicity. In addition, 36% of unaware parents/guardians were interested in and seeking MenB vaccine information from their healthcare provider (HCP), and there was higher interest among parents of Hispanic ethnicity. ‘Vaccinated/intending to vaccinate’ versus ‘not intending to vaccinate’ and ‘vaccinated’ versus ‘intending to vaccinate’ were both strongly associated with whether an HCP had recommended vaccination (odds ratios, 4.81 [95% CI 2.46, 9.35] and 5.66 [95% CI 2.46, 12.87], respectively).

Conclusions
Racial and socioeconomic disparities exist in the awareness and utilization of MenB vaccines among parents/guardians of US adolescents. HCP discussion and recommendation are critical catalysts for MenB vaccination and underscore the need to accurately interpret and implement the shared clinical decision-making (Category B) recommendation.