bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reliability analysis of exonic-breakpoint fusions identified by DNA sequencing for predicting the efficacy of targeted therapy in non-small cell lung cancer
Authors: Li Weihua , Wan Rui , Guo Lei , Chang Geyun , Jiang Dong , Meng Lin , Ying Jianming 
Published: May 2022

Abstract
Background
Diverse genomic breakpoints of fusions that localize to intronic, exonic, or intergenic regions have been identified by DNA next-generation sequencing (NGS), but the role of exonic breakpoints remains elusive. We investigated whether exonic-breakpoint fusions could predict matched targeted therapy efficacy in non-small cell lung cancer (NSCLC).

Methods
NSCLC samples were analyzed by DNA NGS, RNA NGS, immunohistochemistry (IHC), and fluorescence in situ hybridization.

Results
Using DNA NGS, kinase fusions were identified in 685 of 7148 (9.6%) NSCLCs, with 74 harboring exonic-breakpoint fusions, mostly anaplastic lymphoma kinase (ALK) fusions. RNA NGS and IHC revealed that 11 of 55 (20%) exonic-breakpoint fusions generated no aberrant transcript/protein, possibly due to open reading frame disruption or different gene transcriptional orientations. Four cases of genomic-positive but RNA/protein-negative fusions were treated with matched targeted therapy, but progressive disease developed within 2 months. Nevertheless, 44 of 55 (80%) exonic-breakpoint fusions produced chimeric transcripts/proteins, possibly owing to various alternative splicing patterns, including exon skipping, alternative splice site selection, and intron retention. Most of these genomic- and RNA/protein-positive fusion cases showed a clinical response to matched targeted therapy. Particularly, there were no differences in objective response rate (P = 0.714) or median progression-free survival (P = 0.500) between intronic-breakpoint (n = 56) and exonic-breakpoint ALK fusion subtypes (n = 11) among ALK RNA/protein-validated patients who received first-line crizotinib.

Conclusions
Exonic-breakpoint fusions may generate in-frame fusion transcripts/proteins or not, and thus are unreliable for predicting the efficacy of targeted therapy, which highlights the necessity of implementing RNA or protein assays for functional validation in exonic-breakpoint fusion cases.
Molecular cloning, characterization, and functional analysis of the uncharacterized C11orf96 gene
Authors: Yang Hongzao , Zhu Jie , Guo Hongyuan , Tang Aoxing , Chen Shaoyu , Zhang Da , Yuan Ligang , Liu Guangqing 
Published: May 2022

Abstract
Background
The mammalian genome encodes millions of proteins. Although many proteins have been discovered and identified, a large part of proteins encoded by genes are yet to be discovered or fully characterized. In the present study, we successfully identified a host protein C11orf96 that was significantly upregulated after viral infection.

Results
First, we successfully cloned the coding sequence (CDS) region of the cat, human, and mouse C11orf96 gene. The CDS region of the C11orf96 gene is 372 bp long, encodes 124 amino acids, and is relatively conserved in different mammals. From bioinformatics analysis, we found that C11orf96 is rich in Ser and has multiple predicted phosphorylation sites. Moreover, protein interaction prediction analysis revealed that the protein is associated with several transmembrane family proteins and zinc finger proteins. Subsequently, we found that C11orf96 is strictly distributed in the cytoplasm. According to the tissue distribution characteristics, C11orf96 is distributed in all tissues and organs, with the highest expression levels in the kidney. These results indicate that C11orf96 may play a specific biological role in the kidney.

Conclusions
Summarizing, these data lay the foundation for studying the biological functions of C11orf96 and for exploring its role in viral replication.
The ultrasound-guided funicular block in cats undergoing orchiectomy: ropivacaine injection into the spermatic cord to improve intra and postoperative analgesia
Authors: Cicirelli Vincenzo , Matteo Burgio , Di Bella Caterina , Lacalandra Giovanni Michele , Aiudi Giulio 
Published: May 2022

Abstract
Background
The orchiectomy in cats is a common surgical procedure with medium level of pain and for this reason requires intra and postoperative analgesia management. The aim of this study was to compare intra and postoperative pain in two groups of cats undergoing orchiectomy. Sixty healthy cats were randomly assigned in two groups (n = 30) to receive pre surgery ropivacaine hydrochloride (0.2 mL/kg at 0.5%) (R Group) or NaCl 0.9% (C group) into the spermatic cord. The intraoperative evaluation was carried out using the cardiorespiratory stability parameters and eventually administration of rescue analgesia. A rescue analgesia (fentanyl 2 µg/kg) was administered during orchiectomy in case of considerable increase of blood pressure, heart rate or respiratory rate. The postoperative evaluation was been done using scores following a UNESP-Botucatu multimodal scale for 6 h post-surgery.

Results
As result, cats in R group responded better to surgical procedure, maintaining lower postoperative pain scores than C group.

Conclusions
The ultrasound-guided funicular block used in this study, as already demonstrated in dogs, is a good method to protect the cats from surgical pain and ensure a good level of surgical analgesia.
De novo biosynthesis of p-coumaric acid and caffeic acid from carboxymethyl-cellulose by microbial co-culture strategy
Authors: Cai Miao , Liu Jiayu , Song Xiaofei , Qi Hang , Li Yuanzi , Wu Zhenzhou , Xu Haijin , Qiao Mingqiang 
Published: May 2022

Abstract
Background
Aromatic compounds, such as p-coumaric acid (p-CA) and caffeic acid, are secondary metabolites of various plants, and are widely used in diet and industry for their biological activities. In addition to expensive and unsustainable methods of plant extraction and chemical synthesis, the strategy for heterologous synthesis of aromatic compounds in microorganisms has received much attention. As the most abundant renewable resource in the world, lignocellulose is an economical and environmentally friendly alternative to edible, high-cost carbon sources such as glucose.

Results
In the present study, carboxymethyl-cellulose (CMC) was utilized as the sole carbon source, and a metabolically engineered Saccharomyces cerevisiae strain SK10-3 was co-cultured with other recombinant S. cerevisiae strains to achieve the bioconversion of value-added products from CMC. By optimizing the inoculation ratio, interval time, and carbon source content, the final titer of p-CA in 30 g/L CMC medium was increased to 71.71 mg/L, which was 155.9-fold higher than that achieved in mono-culture. The de novo biosynthesis of caffeic acid in the CMC medium was also achieved through a three-strain co-cultivation. Caffeic acid production was up to 16.91 mg/L after optimizing the inoculation ratio of these strains.

Conclusion
De novo biosynthesis of p-CA and caffeic acid from lignocellulose through a co-cultivation strategy was achieved for the first time. This study provides favorable support for the biosynthesis of more high value-added products from economical substrates. In addition, the multi-strain co-culture strategy can effectively improve the final titer of the target products, which has high application potential in the field of industrial production.
Dairy food intake is not associated with spinal trabecular bone score in men and women: the Framingham Osteoporosis Study
Authors: Millar Courtney L. , Kiel Douglas P. , Hannan Marian T. , Sahni Shivani 
Published: May 2022

Abstract
Background
Previous studies reported that dairy foods are associated with higher areal bone mineral density (BMD) in older adults. However, data on bone texture are lacking. We determined the association of dairy food intake (milk, yogurt, cheese, milk + yogurt and milk + yogurt + cheese) with spinal trabecular bone score (TBS).

Methods
In this cross-sectional study, a validated semi-quantitative food frequency questionnaire was used to assess dairy food intake (servings/wk). TBS, an analysis of bone texture, was calculated from dual energy X-ray absorptiometry (DXA) scans. Sex-specific multivariable linear regression was used to estimate the association of dairy food intake (energy adjusted via residual methods) with each bone measure adjusting for covariates.

Results
Mean age of 4,740 participants was 49 (SD: 13) years and mean milk + yogurt + cheese intake was 10.1 (SD: 8.4) servings/week in men and 10.9 (SD: 8.0) servings/week in women. There were no associations between dairy food intake and spinal TBS in adjusted models.

Conclusions
In this cohort of primarily healthy adults, dairy intake was not associated with bone texture.
A multimodal analytical method to simultaneously determine monoacetyldiacylglycerols, medium and long chain triglycerides in biological samples during routine lipidomics
Authors: Manful Charles F. , Pham Thu H. , Spicer Heather , Thomas Raymond H. 
Published: May 2022

Abstract
Background
Monoacetyldiglycerides (MAcDG), are acetylated triglycerides (TG) and an emerging class of bioactive or functional lipid with promising nutritional, medical, and industrial applications. A major challenge exists when analyzing MAcDG from other subclasses of TG in biological matrices, limiting knowledge on their applications and metabolism.

Methods
Herein a multimodal analytical method for resolution, identification, and quantitation of MAcDG in biological samples was demonstrated based on thin layer chromatography-flame ionization detection complimentary with C30-reversed phase liquid chromatography-high resolution accurate mass tandem mass spectrometry. This method was then applied to determine the MAcDG molecular species composition and quantity in E. solidaginis larvae. The statistical method for analysis of TG subclass composition and molecular species composition of E. solidaginis larvae was one-way analysis of variance (ANOVA).

Results
The findings suggest that the proposed analytical method could simultaneously provide a fast, accurate, sensitive, high throughput analysis of MAcDG from other TG subclasses, including the fatty acids, isomers, and molecular species composition.

Conclusion
This method would allow for MAcDG to be included during routine lipidomics analysis of biological samples and will have broad interests and applications in the scientific community in areas such as nutrition, climate change, medicine and biofuel innovations.

Graphical abstract
The impact of body mass index on short-term and long-term surgical outcomes of laparoscopic hepatectomy in liver carcinoma patients: a retrospective study
Authors: Zhao Lei , Wang Jiangang , Kong Jingxia , Zheng Xing , Yu Xin 
Published: May 2022

Abstract
Background
It was generally accepted that obesity could increase the morbidity and mortality of surgical patients. However, the influence of body mass index (BMI) on short-term and long-term surgical outcomes of laparoscopic hepatectomy (LH) for patients with liver carcinoma remains unclear. The aim of this study was to evaluate the influence of BMI on surgical outcomes.

Methods
From August 2003 to April 2016, 201 patients with liver carcinoma who underwent LH were enrolled in our study. Based on their BMI in line with the WHO’s definition of obesity for the Asia-Pacific region, patients were divided into three groups: underweight (BMI< 18.5 kg/m2), normal weight (18.5≤BMI< 23 kg/m2), and overweight (BMI≥ 23 kg/m2). Demographics and surgical outcomes of laparoscopic hepatectomy were compared in different BMI stratification. We investigated overall survival and relapse-free survival across the BMI categories.

Results
Of the 201 patients, 23 (11.44%) were underweight, 96 (47.76%) were normal weight, and 82 (40.80%) were overweight. The overall complication rate in the underweight group was much higher than that in the normal weight and overweight groups (p=0.048). Postoperative complications, underweight patients developed grade III or higher Clavien-Dindo classifications (p=0.042). Among the three BMI groups, there were no significant differences in overall and relapse-free survival with Kaplan-Meier analysis (p=0.104 and p=0.190, respectively). On the other hand, gender, age, liver cirrhosis, bile leak, ascites, and Clavien classification (III-IV) were not independent risk factors for overall and relapse-free survival in multivariable Cox proportional hazards models.

Conclusions
BMI status does not affect patients with liver carcinoma long-term surgical outcomes concerned to overall survival and relapse-free survival after laparoscopic hepatectomy. However, being underweight was associated with an increased perioperative complication rate, and perioperative careful monitoring might be required after hepatectomy for underweight with liver carcinoma.
The “Great Debate” at Melanoma Bridge 2021, December 2nd–4th, 2021
Authors: Ascierto Paolo A. , Warner Allison Betof , Blank Christian , Caracò Corrado , Demaria Sandra , Gershenwald Jeffrey E. , Khushalani Nikhil I. , Long Georgina V. , Luke Jason J. , Mehnert Janice M. , Robert Caroline , Rutkowski Piotr , Tawbi Hussein A. , Osman Iman , Puzanov Igor 
Published: May 2022

AbstractThe Great Debate session at the 2021 Melanoma Bridge virtual congress (December 2–4) featured counterpoint views from experts on seven important issues in melanoma. The debates considered the use of adoptive cell therapy versus use of bispecific antibodies, mitogen-activated protein kinase (MAPK) inhibitors versus immunotherapy in the adjuvant setting, whether the use of corticosteroids for the management of side effects have an impact on outcomes, the choice of programmed death (PD)-1 combination therapy with cytotoxic T-lymphocyte-associated antigen (CTLA)-4 or lymphocyte-activation gene (LAG)-3, whether radiation is needed for brain metastases, when lymphadenectomy should be integrated into the treatment plan and then the last debate, telemedicine versus face-to-face. As with previous Bridge congresses, the debates were assigned by meeting Chairs and positions taken by experts during the debates may not have necessarily reflected their respective personal view. Audiences voted both before and after each debate.
Aluminium oxide nanoparticles compromise spatial memory performance and proBDNF-mediated neuronal function in the hippocampus of rats
Authors: Sun Wei , Li Jia , Li Xiaoliang , Chen Xiao , Mei Yazi , Yang Yang , An Lei 
Published: May 2022

AbstractBackgroundAlumina nanoparticles (aluminaNPs), which are widely used in a range of daily and medical fields, have been shown to penetrate blood-brain barrier, and distribute and accumulate in different brain areas. Although oral treatment of aluminaNPs induces hippocampus-dependent learning and memory impairments, characteristic effects and exact mechanisms have not been fully elucidated. Here, male adult rats received a single bilateral infusion of aluminaNPs (10 or 20 µg/kg of body weight) into the hippocampal region, and their behavioral performance and neural function were assessed.ResultsThe results indicated that the intra-hippocampus infusions at both doses of aluminaNPs did not cause spatial learning inability but memory deficit in the water maze task. This impairment was attributed to the effects of aluminaNP on memory consolidation phase through activation of proBDNF/RhoA pathway. Inhibition of the increased proBDNF by hippocampal infusions of p75NTRantagonist could effectively rescue the memory impairment. Incubation of aluminaNPs exaggerated GluN2B-dependent LTD induction with no effects on LTD expression in hippocampal slices. AluminaNP could also depress the amplitude of NMDA-GluN2B EPSCs. Meanwhile, increased reactive oxygen specie production was reduced by blocking proBDNF-p75NTRpathway in the hippocampal homogenates. Furthermore, the neuronal correlate of memory behavior was drastically weakened in the aluminaNP-infused groups. The dysfunction of synaptic and neuronal could be obviously mitigated by blocking proBDNF receptor p75NTR, implying the involvement of proBDNF signaling in aluminaNP-impaired memory process.ConclusionsTaken together, our findings provide the first evidence that the accumulation of aluminaNPs in the hippocampus exaggeratedly activates proBDNF signaling, which leads to neural and memory impairments.
A novel protein encoded by ZCRB1-induced circHEATR5B suppresses aerobic glycolysis of GBM through phosphorylation of JMJD5
Authors: Song Jian , Zheng Jian , Liu Xiaobai , Dong Weiwei , Yang Chunqing , Wang Di , Ruan Xuelei , Zhao Yubo , Liu Libo , Wang Ping , Zhang Mengyang , Liu Yunhui 
Published: May 2022

Abstract
Background
RNA-binding proteins (RBPs) and circular RNAs (circRNAs) play important roles in glioblastoma multiforme (GBM). Aerobic glycolysis is a metabolic characteristic of GBM. However, the roles of RBPs and circRNAs in aerobic glycolysis in GBM remain unclear. The aim of this study is to explore the mechanisms by which RBPs and circRNAs regulate aerobic glycolysis in GBM cells.

Methods
RNA sequencing and circRNA microarray analysis were performed to identify RBPs and circRNAs for further study. Mass spectrometry validated the encoded protein and its interacting proteins. Quantitative reverse transcription PCR and western blot assays were used to determine the mRNA and protein expression, respectively. Furthermore, immunofluorescence and fluorescence in situ hybridization assays were used to determine the protein and RNA localization, respectively. Glucose and lactate measurement assays, Seahorse XF glycolysis stress assays and cell viability assays were conducted to investigate the effects on glycolysis and proliferation in GBM cells.

Results
We selected zinc finger CCHC-type and RNA-binding motif 1 (ZCRB1) and circRNA HEAT repeat containing 5B (circHEATR5B) as candidates for this study. These genes were expressed at low levels in GBM tissues and cells. Both ZCRB1 and circHEATR5B overexpression suppressed aerobic glycolysis and proliferation in GBM cells. ZCRB1 overexpression promoted the Alu element-mediated formation of circHEATR5B. In addition, circHEATR5B encoded a novel protein HEATR5B-881aa which interacted directly with Jumonji C-domain-containing 5 (JMJD5) and reduced its stability by phosphorylating S361. JMJD5 knockdown increased pyruvate kinase M2 (PKM2) enzymatic activity and suppressed glycolysis and proliferation in GBM cells. Finally, ZCRB1, circHEATR5B and HEATR5B-881aa overexpression inhibited GBM xenograft growth and prolonged the survival time of nude mice.

Conclusions
This study reveals a novel mechanism of regulating aerobic glycolysis and proliferation in GBM cells through the ZCRB1/circHEATR5B/HEATR5B-881aa/JMJD5/PKM2 pathway, which can provide novel strategies and potential targets for GBM therapy.
Acute glycemic variability and mortality of patients with acute stroke: a meta-analysis
Authors: Lin Jinbo , Cai Chunsheng , Xie Yituan , Yi Li 
Published: May 2022

Abstract
Background
Increased glucose fluctuation has been related to poor prognosis in patients with critical illnesses, while its prognostic role in patients with acute stroke remains unknown. The meta-analysis aimed to evaluate the association between the acute glycemic variation (GV) and mortality risk in patients with acute stroke.

Methods
Cohort studies were obtained by searching Medline, Web of Science, Embase, Wanfang and CNKI databases. A random-effect model which incorporates the intra-study heterogeneity was chosen to pool the results.

Results
Ten cohort studies with 1433 patients were included, and 280 (19.5%) of them died within 90 days of disease onset. Results of the meta-analyses showed that a higher acute GV was associated with an increased risk of early mortality in patients with acute stroke, as indicated by GV measured with the coefficient of variation of blood glucose (CVBG, odds ratio [OR]: 2.24, 95% CI 1.40 to 3.58, p < 0.001, I2 = 73%), the standard deviation of blood glucose (SDBG, OR: 2.31, 95% CI 1.70 to 3.13, p < 0.001, I2 = 50%), and the mean amplitude of glycemic excursion (OR: 3.57, 95% CI 1.44 to 8.85, p = 0.006, I2 = 23%). For acute GV measured with CVBG and SDBG, subgroup analyses showed consistent results in patients with acute ischemic and hemorrhagic stroke, and for studies reporting 28-day and 90-day all-cause mortality (p for subgroup analysis all > 0.05).

Conclusions
Higher acute GV may be an independent risk factor of early mortality in patients with acute stroke.
FirmiData: a set of 40 genomes of Firmicutes with a curated annotation of ICEs and IMEs
Authors: Guédon Gérard , Lao Julie , Payot Sophie , Lacroix Thomas , Chiapello Hélène , Leblond-Bourget Nathalie 
Published: May 2022

Abstract
Objectives
‘Integrative and Conjugative Elements’ (ICEs) and ‘Integrative and Mobilizable Elements’ (IMEs) are two classes of mobile genetic elements that are complex to detect and delineate. Therefore, they are yet poorly annotated in bacterial genomes. FirmiData provides to the scientific community of microbiologists and bioinformaticians a reference resource of annotated ICEs and of IMEs from Firmicutes. It illustrates their prevalence and their diversity but also gives information on their organization.
FirmiData was designed to assist the scientific community in identifying and annotating these elements by using the sequences of these ICEs and IMEs for the identification of related elements in other genomes of Firmicutes. Therefore, Firmidata meets the needs of the scientific community.

Data description
Firmidata provides a manually curated annotation of 98 ICEs and 148 IMEs identified in 40 chromosomes of Firmicutes. The delineation at the nucleotide level of almost all of these elements allows for the characterization of the genes they carry.
Brazilian spatial, demographic, and socioeconomic data from 1996 to 2020
Authors: Fernandes Santos Alves Ronaldo , de Moraes Mello Boccolini Patricia , Baroni Lais Ribeiro , de Almeida Relvas-Brandt Laís , de Abreu Junqueira Gritz Raquel , Siqueira Boccolini Cristiano 
Published: May 2022

Abstract
Objectives
We present a database on Brazilian spatial, demographic, and socioeconomic characteristics from 1996 to 2020. This database aims for integration and harmonization with epidemiological data from two major studies. It can also be a valuable database for designing and conducting various types of epidemiologic research, such as health inequality studies, ecological studies (mapping and time-trends), and multi-level analysis.

Data description
The database gathers official information obtained via open sources from the Brazilian Institute of Geography and Statistics, the Institute for Applied Economic Research, and the Ministry of Health. It includes 139,153 observations and 26 attributes aggregated by years and policy-relevant geographic units on geocoding of municipality centroids, total population size, child population by age-group, birth and mortality measures, Brazilian Municipal Human Development Index, Gini coefficient, Gross Domestic Product, and sanitation. We automated all data processing and curation in the free and open software R.