bluuebunny/crossref_metadata_2025_split huggingface dataset:
SomatoSim: precision simulation of somatic single nucleotide variants
Authors: Hawari Marwan A. , Hong Celine S. , Biesecker Leslie G. 
Published: March 2021

Abstract
Background
Somatic single nucleotide variants have gained increased attention because of their role in cancer development and the widespread use of high-throughput sequencing techniques. The necessity to accurately identify these variants in sequencing data has led to a proliferation of somatic variant calling tools. Additionally, the use of simulated data to assess the performance of these tools has become common practice, as there is no gold standard dataset for benchmarking performance. However, many existing somatic variant simulation tools are limited because they rely on generating entirely synthetic reads derived from a reference genome or because they do not allow for the precise customizability that would enable a more focused understanding of single nucleotide variant calling performance.

Results
SomatoSim is a tool that lets users simulate somatic single nucleotide variants in sequence alignment map (SAM/BAM) files with full control of the specific variant positions, number of variants, variant allele fractions, depth of coverage, read quality, and base quality, among other parameters. SomatoSim accomplishes this through a three-stage process: variant selection, where candidate positions are selected for simulation, variant simulation, where reads are selected and mutated, and variant evaluation, where SomatoSim summarizes the simulation results.

Conclusions
SomatoSim is a user-friendly tool that offers a high level of customizability for simulating somatic single nucleotide variants. SomatoSim is available at https://github.com/BieseckerLab/SomatoSim.
Investigating mechanisms underlying genetic resistance to Salmon Rickettsial Syndrome in Atlantic salmon using RNA sequencing
Authors: Moraleda Carolina P. , Robledo Diego , Gutiérrez Alejandro P. , del-Pozo Jorge , Yáñez José M. , Houston Ross D. 
Published: March 2021

Abstract
Background
Salmon Rickettsial Syndrome (SRS), caused by Piscirickettsia salmonis, is one of the primary causes of morbidity and mortality in Atlantic salmon aquaculture, particularly in Chile. Host resistance is a heritable trait, and functional genomic studies have highlighted genes and pathways important in the response of salmon to the bacteria. However, the functional mechanisms underpinning genetic resistance are not yet well understood. In the current study, a large population of salmon pre-smolts were challenged with P. salmonis, with mortality levels recorded and samples taken for genotyping. In parallel, head kidney and liver samples were taken from animals of the same population with high and low genomic breeding values for resistance, and used for RNA-Sequencing to compare their transcriptome profile both pre and post infection.

Results
A significant and moderate heritability (h2 = 0.43) was shown for the trait of binary survival. Genome-wide association analyses using 38 K imputed SNP genotypes across 2265 animals highlighted that resistance is a polygenic trait. Several thousand genes were identified as differentially expressed between controls and infected samples, and enriched pathways related to the host immune response were highlighted. In addition, several networks with significant correlation with SRS resistance breeding values were identified, suggesting their involvement in mediating genetic resistance. These included apoptosis, cytoskeletal organisation, and the inflammasome.

Conclusions
While resistance to SRS is a polygenic trait, this study has highlighted several relevant networks and genes that are likely to play a role in mediating genetic resistance. These genes may be future targets for functional studies, including genome editing, to further elucidate their role underpinning genetic variation in host resistance.
Study on the transcriptome for breast muscle of chickens and the function of key gene RAC2 on fibroblasts proliferation
Authors: Zhang Genxi , Wu Pengfei , Zhou Kaizhi , He Mingliang , Zhang Xinchao , Qiu Cong , Li Tingting , Zhang Tao , Xie Kaizhou , Dai Guojun , Wang Jinyu 
Published: March 2021

Abstract
Background
Growth performance is significant in broiler production. In the growth process of broilers, gene expression varies at different growth stages. However, limited research has been conducted on the molecular mechanisms of muscle growth and development in yellow-feathered male chickens.

Results
In the study, we used RNA-seq to study the transcriptome of the breast muscle of male Jinghai yellow chickens at 4 (M4F), 8 (M8F) and 12 weeks (M12F) of age. The results showed that 4608 differentially expressed genes (DEGs) were obtained by comparison in pairs of the three groups with Fold Change (FC) ≥ 2 and False Discovery Rate (FDR) ≤ 0.05, and 83, 3445 and 3903 DEGs were obtained separately from M4FvsM8F, M4FvsM12F and M8FvsM12F. Six genes were found as co-differentially expressed in the three age groups, namely SNCG, MYH1A, ARHGDIB, ENSGALG00000031598, ENSGALG00000035660 and ENSGALG00000030559. The GO analysis showed that 0, 304 and 408 biological process (BP) were significantly enriched in M4FvsM8F, M4FvsM12F and M8FvsM12F groups, respectively. KEGG pathway enrichment showed that 1, 2, 4 and 4 pathways were significantly enriched in M4FvsM8F, M4FvsM12F, M8FvsM12F and all DEGs, respectively. They were steroid biosynthesis, carbon metabolism, focal adhesion, cytokine-cytokine receptor interaction, biosynthesis of amino acids and salmonella infection. We constructed short hairpin RNA (shRNA) to interfere the differentially expressed gene RAC2 in DF-1 cells and detected mRNA and protein expression of the downstream genes PAK1 and MAPK8. Results of qPCR showed that RAC2, PAK1 and MAPK8 mRNA expression significantly decreased in the shRAC2–2 group compared with the negative control (NC) group. Western Blot (WB) results showed that the proteins of RAC2, PAK1 and MAPK8 also decreased in the shRAC2–2 group. Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2′-deoxyuridine (EdU) assay both showed that the proliferation of DF-1 cells was significantly inhibited after transfection of shRAC2–2.

Conclusions
The results of RNA-seq revealed genes, BP terms and KEGG pathways related to growth and development of male Jinghai yellow chickens, and they would have important guiding significance to our production practice. Further research suggested that RAC2 might regulate cell proliferation by regulating PAKs/MAPK8 pathway and affect growth of chickens.
Prenatal testosterone triggers long-term behavioral changes in male zebra finches: unravelling the neurogenomic mechanisms
Authors: Bentz Alexandra B. , Niederhuth Chad E. , Carruth Laura L. , Navara Kristen J. 
Published: March 2021

AbstractBackgroundMaternal hormones, like testosterone, can strongly influence developing offspring, even generating long-term organizational effects on adult behavior; yet, the mechanisms facilitating these effects are still unclear. Here, we experimentally elevated prenatal testosterone in the eggs of zebra finches (Taeniopygia guttata) and measured male aggression in adulthood along with patterns of neural gene expression (RNA-seq) and DNA methylation (MethylC-Seq) in two socially relevant brain regions (hypothalamus and nucleus taenia of the amygdala). We used enrichment analyses and protein-protein interaction networks to find candidate processes and hub genes potentially affected by the treatment. We additionally identified differentially expressed genes that contained differentially methylated regions.ResultsWe found that males from testosterone-injected eggs displayed more aggressive behaviors compared to males from control eggs. Hundreds of genes were differentially expressed, particularly in the hypothalamus, including potential aggression-related hub genes (e.g., brain derived neurotrophic factor). There were also enriched processes with well-established links to aggressive phenotypes (e.g., somatostatin and glutamate signaling). Furthermore, several highly connected genes identified in protein-protein interaction networks also showed differential methylation, including adenylate cyclase 2 and proprotein convertase 2.ConclusionsThese results highlight genes and processes that may play an important role in mediating the effects of prenatal testosterone on long-term phenotypic outcomes, thereby providing insights into the molecular mechanisms that facilitate hormone-mediated maternal effects.
Association between alcohol consumption and oesophageal microbiota in oesophageal squamous cell carcinoma
Authors: Rao Wenqing , Lin Zheng , Liu Shuang , Zhang Zhihui , Xie Qianwen , Chen Huilin , Lin Xi , Chen Yuanmei , Yang Huimin , Yu Kaili , Hu Zhijian 
Published: March 2021

Abstract
Background
Microbiota has been reported to play a role in cancer patients. Nevertheless, little is known about the association between alcohol consumption and resultant changes in the diversity and composition of oesophageal microbiota in oesophageal squamous cell carcinoma (ESCC).

Methods
We performed a hospital-based retrospective study of 120 patients with pathologically diagnosed primary ESCC. The relevant information for all study participants were collected through a detailed questionnaire. The differences in adjacent tissues between non-drinkers and drinkers were explored using 16S rRNA gene sequencing. Raw sequencing data were imported into QIIME 2 to analyse the diversity and abundance of microbiota. Linear discriminant analysis effect size (LEfSe) and unconditional logistic regression were performed to determine the bacterial taxa that were associated with drinking.

Results
The Shannon diversity index and Bray-Curtis distance of oesophageal microbiota were significantly different among drinkers(P < 0.05). The alcohol-related bacteria were primarily from the orders Clostridiales, Gemellales and Pasteurellales, family Clostridiaceae, Lanchnospiraceae, Helicobacteraceae, Alcaligenaceae, Bacteroidaceae, Pasteurellaceae and Gemellaceae; genus Clostridium, Helicobacter, Catonella, Bacteroides, Bacillus, Moraxella, and Bulleidia; and species B. moorei and longum (genus Bifidobacterium). In addition, the diversity and abundance of these microbiota were observed to be affected by the age, residential districts of the patients, and sampling seasons. Moreover, the higher the frequency and years of alcohol consumption, the lower was the relative abundance of genus Catonella that was observed.

Conclusion
Alcohol consumption is associated with alterations in both the diversity and composition the of the oesophageal microbiota in ESCC patients.
Estimated glomerular filtration rate and postoperative mortality in patients undergoing non-cardiac and non-neuron surgery: a single-center retrospective study
Authors: Luo Xueying , Zheng Sujing , Liu Baoer , Yang Liping , Li Ya , Li Feng , Gao Rui , Hu Haofei , He Jinsong 
Published: March 2021

Abstract
Background
There is limited evidence to clarify the specific relationship between preoperative estimated glomerular filtration rate (preop-eGFR) and postoperative 30-day mortality in Asian patients undergoing non-cardiac and non-neuron surgery. We aimed to investigate details of this relationship.

Methods
We reanalyzed a retrospective analysis of the clinical records of 90,785 surgical patients at the Singapore General Hospital from January 1, 2012 to October 31, 2016. The main outcome was postoperative 30-day mortality.

Results
The average age of these recruited patients was 53.96 ± 16.88 years, of which approximately 51.64% were female. The mean of preop-eGFR distribution was 84.45 ± 38.56 mL/min/1.73 m2. Multivariate logistic regression analysis indicated that preop-eGFR was independently associated with 30-day mortality (adjusted odds ratio: 0.992; 95% confidence interval [CI] 0.990–0.995; P < 0.001). A U-shaped relationship was detected between preop-eGFR and 30-day mortality with an inflection point of 98.688 (P for log likelihood ratio test < 0.001). The effect sizes and confidence intervals on the right and left sides of the inflection point were 1.013 (1.007 to 1.019) [P < 0.0001] and 0.984 (0.981 to 0.987) [P < 0.0001], respectively. Preoperative comorbidities such as congestive heart failure (CHF), type 1 diabetes, ischemic heart disease (IHD), and anemia were associated with the odds ratio of preop-eGFR to 30-day mortality (interaction P < 0.05).

Discussion
The relationship between preop-eGFR and 30-day mortality is U-shaped. The recommended preop-eGFR at which the rate of the 30-day mortality was lowest was 98.688 mL/min/1.73 m2.
Influence of enhanced recovery after surgery (ERAS) on patients receiving lung resection: a retrospective study of 1749 cases
Authors: Wang Chunmei , Lai Yutian , Li Pengfei , Su Jianhuan , Che Guowei 
Published: March 2021

Abstract
Background
The study aimed to evaluate the outcomes following the implementation of enhanced recovery after surgery (ERAS) for patients undergoing lung cancer surgery.

Method
A retrospective cohort study involving 1749 patients with lung cancer undergoing pulmonary resection was conducted. The patients were divided into two time period groups for analysis (routine pathway and ERAS pathway). Logistic regression analysis was performed to assess the risks of developing postoperative pulmonary complications.

Results
Among the 1749 patients, 691 were stratified into the ERAS group, and 1058 in to the routine group. The ERAS group presented with shorter postoperative in-hospital length of stay (LOS) (4.0 vs 6.0, P < 0.001), total LOS (10.0 vs. 13.0 days, P < 0.001), and lower total in-hospital costs (P < 0.001), including material (P < 0.001) and drug expenses (P < 0.001). Furthermore, the ERAS group also presented with a lower occurrence of postoperative pulmonary complications (PPCs) than the routine group (15.2% vs. 19.5%, P = 0.022). Likewise, a significantly lower occurrence of pneumonia (8.4% vs. 14.2%, P < 0.001) and atelectasis (5.9% vs. 9.8%, P = 0.004) was found in the ERAS group. Regarding the binary logistic regression, the ERAS intervention was the sole independent factor for the occurrence of PPCs (OR: 0.601, 95% CI 0.434–0.824, P = 0.002). In addition, age (OR: 1.032, 95% CI 1.018–1.046), COPD (OR: 1.792, 95% CI 1.196–2.686), and FEV1 (OR: 0.205, 95% CI 0.125–0.339) were also independent predictors of PPCs.

Conclusion
Implementation of an ERAS pathway shows improved postoperative outcomes, including shortened LOS, lower in-hospital costs, and reduced occurrence of PPCs, providing benefits to the postoperative recovery of patients with lung cancer undergoing surgical treatment.
The physician-nurse collaboration in truth disclosure: from nurses’ perspective
Authors: Cheng Qinqin , Duan Yinglong , Wang Ying , Zhang Qinghui , Chen Yongyi 
Published: March 2021

Abstract
Background
Collaboration between physicians and nurses is critical. However, a limited number of studies have provided insights into the status of physician–nurse collaboration in truth disclosure.

Methods
A cross-sectional survey was conducted using an electronic questionnaire among Chinese nurses who attended a provincial conference. The Nurse–Physician Collaboration Scale was administered to nurses to assess the collaboration in truth disclosure from their perspective. A multiple-choice question was asked to assess the perceived difficulties in truth disclosure. Descriptive statistics, univariate, and multiple stepwise regression analyses were performed to evaluate physician–nurse collaboration in truth disclosure.

Results
A total of 287 nurses completed the survey, and 279 of them reported that they had carried out truth disclosures among patients. The average score for physician–nurse collaboration in truth disclosure was 3.98 ± 0.72. The majority of nurses (73.1–81%) responded positively to different dimensions of collaboration in truth disclosure. The results of multiple stepwise regression analysis showed that seniority (B = − 0.111, 95% confidence interval [CI] = − 0.167−− 0.055, p < 0.001) and frequency of truth disclosure (B = 0.162, 95%CI = 0.076–0.249, p < 0.001) were the only two factors associated with collaboration in truth disclosure between physicians and nurses. The most common barrier perceived by nurses was fear of patients’ negative emotions or their suicide attempts after truth telling.

Conclusions
Most nurses responded positively to physician–nurse collaboration in truth disclosure. Various difficulties existed in the practice of truth-telling collaboration. Further studies are required to test the potential interventions to promote cooperation between nurses and physicians in truth disclosure.
Comparison of capillary and venous blood for malaria detection using two PCR-based assays in febrile patients in Sierra Leone
Authors: Leski Tomasz A. , Taitt Chris Rowe , Bangura Umaru , Lahai Joseph , Lamin Joseph M. , Baio Victoria , Koroma Mohamed S. , Swaray Abdulai G. , Jacobsen Kathryn H. , Jackson Olivia , Jones Brian W. , Phillips Cynthia L. , Ansumana Rashid , Stenger David A. 
Published: March 2021

Abstract
Background
Rapid and sensitive diagnostics are critical tools for clinical case management and public health control efforts. Both capillary and venous blood are currently used for malaria detection and while diagnostic technologies may not be equally sensitive with both materials, the published data on this subject are scarce and not conclusive.

Methods
Paired clinical samples of venous and capillary blood from 141 febrile individuals in Bo, Sierra Leone, were obtained between January and May 2019 and tested for the presence of Plasmodium parasites using two multiplexed PCR assays: the FilmArray-based Global Fever Panel (GFP) and the TaqMan-based Malaria Multiplex Sample Ready (MMSR) assay.

Results
No significant differences in Plasmodium parasite detection between capillary and venous blood for both assays were observed. The GFP assay was more sensitive than MMSR for all markers that could be compared (Plasmodium spp. and Plasmodium falciparum) in both venous and capillary blood.

Conclusions
No difference was found in malaria detection between venous and capillary blood using two different PCR-based detection assays. This data gives support for use of capillary blood, a material which can be obtained easier by less invasive methods, for PCR-based malaria diagnostics, independent of the platform.
Lung clearance index and diffusion capacity for CO to detect early functional pulmonary impairment in children with rheumatic diseases
Authors: Hildebrandt Julia , Rahn Anja , Kessler Anja , Speth Fabian , Fischer Dagmar-Christiane , Ballmann Manfred 
Published: March 2021

AbstractBackgroundIn adults with rheumatic diseases pulmonary complications are relevant contributors to morbidity and mortality. In these patients diffusion capacity for CO (DLCO) is an established method to detect early pulmonary impairment. Pilot studies using DLCO indicate that early functional pulmonary impairment is present even in children with rheumatic disease albeit not detectable by spirometry and without clinical signs of pulmonary disease.Since the lung clearance index (LCI) is also a non-invasive, feasible and established method to detect early functional pulmonary impairment especially in children and because it requires less cooperation (tidal breathing), we compared LCI versus DLCO (forced breathing and breath-holding manoeuvre) in children with rheumatic diseases.FindingsNineteen patients (age 9–17 years) with rheumatic disease and no clinical signs of pulmonary disease successfully completed LCI and DLCO during annual check-up. In 2 patients LCI and DLCO were within physiological limits. By contrast, elevated LCI combined with physiological results for DLCO were seen in 8 patients and in 9 patients both, the LCI and DLCO indicate early functional pulmonary changes. Overall, LCI was more sensitive than DLCO to detect early functional pulmonary impairment (p = 0.0128).ConclusionsOur findings suggest that early functional pulmonary impairment is already present in children with rheumatic diseases. LCI is a very feasible and non-invasive alternative for detection of early functional pulmonary impairment in children. It is more sensitive and less cooperation dependent than DLCO. Therefore, we suggest to integrate LCI in routine follow-up of rheumatic diseases in children.
METTL3-mediated m6A mRNA modification of FBXW7 suppresses lung adenocarcinoma
Authors: Wu Yingtong , Chang Ning , Zhang Yong , Zhang Xinxin , Xu Leidi , Che Yinggang , Qiao Tianyun , Wu Bin , Zhou Ying , Jiang Jun , Xiong Jie , Zhang Jian , Zhang Jian 
Published: March 2021

Abstract
Background
FBXW7 m6A modification plays an important role in lung adenocarcinoma (LUAD) progression; however, the underlying mechanisms remain unclear.

Methods
The correlation between FBXW7 and various genes related to m6A modification was analyzed using The Cancer Genome Atlas database. The regulatory effects of METTL3 on FBXW7 mRNA m6A modification were examined in a cell model, and the underlying mechanism was determined by methylated RNA immunoprecipitation, RNA immunoprecipitation, luciferase reporter, and mutagenesis assays. In vitro experiments were performed to further explore the biological effects of METTL3-mediated FBXW7 m6A modification on LUAD development.

Results
Decreased FBXW7 expression was accompanied by downregulated METTL3 expression in human LUAD tissues and was associated with a worse prognosis for LUAD in The Cancer Genome Atlas database. m6A was highly enriched in METTL3-mediated FBXW7 transcripts, and increased m6A modification in the coding sequence region increased its translation. Functionally, METTL3 overexpression or knockdown affected the apoptosis and proliferation phenotype of LUAD cells by regulating FBXW7 m6A modification and expression. Furthermore, FBXW7 overexpression in METTL3-depleted cells partially restored LUAD cell suppression in vitro and in vivo.

Conclusions
Our findings reveal that METTL3 positively regulates FBXW7 expression and confirm the tumor-suppressive role of m6A-modified FBXW7, thus providing insight into its epigenetic regulatory mechanisms in LUAD initiation and development.
Survivorship of Anopheles gambiae sensu lato in irrigated sugarcane plantation scheme in Ethiopia
Authors: Hawaria Dawit , Kibret Solomon , Demissew Assalif , Tsegaye Arega , Bitew Denekew , Yan Guiyun , Yewhalaw Delenasaw 
Published: March 2021

Abstract
Background
To ensure food security, sub-Saharan Africa has initiated massive water resource development projects, such as irrigated agriculture, in recent years. However, such environmental modifications affect the survivorship and development of mosquitoes, which are vectors of different diseases. This study aimed at determining the effects of irrigation practices on development and survivorship of Anopheles gambiae s.l. in Ethiopia.

Methods
A life table experiment was conducted to examine the effect of environmental modification on survivorship of both immature and adult An. gambiae s.l. in irrigated and non-irrigated areas. The pupation rate and development time of the immatures and adult longevity and fecundity were compared between the two settings.

Results
The estimated mean survival time of female An. gambiae s.l. in the irrigated and non-irrigated areas was 37.9 and 31.3 days, respectively. A survival analysis showed that adult females of An. gambiae s.l. placed in an irrigated area lived significantly longer than those in a non-irrigated area (χ2 = 18.3, df = 1, P <0.001), and An. gambiae s.l. females lived significantly longer than males in both areas (P < 0.001).

Conclusions
Adult An. gambiae s.l. survivorship was found to be enhanced in the irrigated area compared to non-irrigated area. Longer survival of adult mosquitoes in irrigated areas could have important implications for vectorial capacity and hence malaria transmission.

Graphical Abstract