bluuebunny/crossref_metadata_2025_split huggingface dataset:
m7GHub: deciphering the location, regulation and pathogenesis of internal mRNA N7-methylguanosine (m7G) sites in human
Authors: Song Bowen , Tang Yujiao , Chen Kunqi , Wei Zhen , Rong Rong , Lu Zhiliang , Su Jionglong , de Magalhães João Pedro , Rigden Daniel J , Meng Jia 
Published: March 2020

Abstract

Motivation
Recent progress in N7-methylguanosine (m7G) RNA methylation studies has focused on its internal (rather than capped) presence within mRNAs. Tens of thousands of internal mRNA m7G sites have been identified within mammalian transcriptomes, and a single resource to best share, annotate and analyze the massive m7G data generated recently are sorely needed.

Results
We report here m7GHub, a comprehensive online platform for deciphering the location, regulation and pathogenesis of internal mRNA m7G. The m7GHub consists of four main components, including: the first internal mRNA m7G database containing 44 058 experimentally validated internal mRNA m7G sites, a sequence-based high-accuracy predictor, the first web server for assessing the impact of mutations on m7G status, and the first database recording 1218 disease-associated genetic mutations that may function through regulation of m7G methylation. Together, m7GHub will serve as a useful resource for research on internal mRNA m7G modification.

Availability and implementation
m7GHub is freely accessible online at www.xjtlu.edu.cn/biologicalsciences/m7ghub.

Contact
kunqi.chen@liverpool.ac.uk

Supplementary information
Supplementary data are available at Bioinformatics online.
Geographic Shifts in Antibacterial Drug Clinical Trial Enrollment: Implications for Generalizability
Authors: Bart Stephen M , Farley John J , Bala Shukal , Amini Thushi , Cox Edward 
Published: March 2020

Abstract

Background
As drug development has globalized, trials have increasingly enrolled participants from all parts of the world rather than just the United States and Western Europe. For antibacterial drug trials, understanding enrollment trends and regional differences is important for generalizability considerations.

Methods
We retrospectively analyzed 42 phase 3 trials submitted to the US Food and Drug Administration after 2001 for complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), community-acquired bacterial pneumonia (CABP), and acute bacterial skin and skin structure infection (ABSSSI) (n = 29 282 participants). Enrollment numbers, demographics, clinical characteristics, and microbiological data were compared to identify temporal and geographic trends.

Results
For cUTI, cIAI, and CABP trials, Eastern European enrollment greatly increased over the study period. For ABSSSI trials, North American enrollment increased. Demographic characteristics and regional microbiology among regions were broadly similar with several exceptions. For cIAI trials, Eastern European participants had the lowest proportion of participants with prior antibacterial drug therapy. For ABSSSI trials, North American participants more commonly reported intravenous drug use. Microbiological differences relative to North America included a greater proportion of Klebsiella pneumoniae among Asian cIAI isolates (17.8% vs 9.0%, P = .0057), a higher proportion of cephalosporin resistance in South American Enterobacteriaceae cUTI isolates (26.8% vs 15.7%, P = .044), and a lower proportion of Staphylococcus aureus in Eastern European ABSSSI isolates (43.7% vs 61.9%, P &lt; .0001).

Conclusions
Geographic trends in recruitment for recent antibacterial clinical trials differ by indication. Regional similarities in demographic characteristics and microbiology across regions lessen concerns regarding generalizability due to shifting enrollment trends.
Prognosis of Lymphoma in Patients With Known Inflammatory Bowel Disease: A French Multicentre Cohort Study
Authors: Severyns T , Kirchgesner J , Lambert J , Thieblemont C , Amiot A , Abitbol V , Treton X , Cazals-Hatem D , Malamut G , Coppo P , Galicier L , Walter-Petrich A , Deau-Fischer B , Besson C , Aparicio T , Beaugerie L , Allez M , Gornet J M 
Published: March 2020

Abstract

Background and Aims
The prognosis of lymphoma that occurs in patients with inflammatory bowel disease [IBD] is poorly known.

Methods
A multicentre retrospective cohort analysis was done in seven French tertiary centres from 1999 to 2019. Only lymphoma occurring in patients with previous established diagnosis of IBD were analysed. The primary outcome was progression-free survival at 3 years.

Results
A total of 52 patients [male 65%, Crohn’s disease 79%, median age 48.3 years, median duration of IBD 10.1 years] were included, of whom 37 had been previously exposed to immunosuppressants and/or biologics for at least 3 months and 20 had primary intestinal lymphomas. The lymphoma histological types were: diffuse large B cell lymphomas [N = 17], Hodgkin lymphomas [N = 17], indolent B cell lymphomas [N = 12], and others including T cell lymphomas, mantle cell lymphomas, and unclassifiable B cell lymphoma [N = 6]. The median follow-up after lymphoma was 5.1 years (interquartile range [IQR] 4–7.8). Progression-free survival at 3 years was 85% in the overall population (95% confidence interval [CI] 75%–96%) with no significant difference between the exposed and unexposed group, 79% for patients exposed to immunosuppressants and/or biologics [95% CI 67%–94%], and 83% for patients diagnosed with primary intestinal lymphoma [95% CI 67%–100%]. No relapse of IBD has been observed during chemotherapy. The IBD relapse rate at the end of the last chemotherapy cycle was 23% at 3 years [95% CI 11%-39%] in the overall population.

Conclusions
In this large cohort, the prognosis for lymphomas occurring in IBD appears to be good and similar to what is expected, irrespective of the exposure to biologics and/or immunosuppressants.
Intermittent hypoxia retards mandibular growth and alters RANKL expression in adolescent and juvenile rats
Authors: Hong Haixin , Hosomichi Jun , Maeda Hideyuki , Lekvijittada Kochakorn , Oishi Shuji , Ishida Yuji , Usumi-Fujita Risa , Kaneko Sawa , Suzuki Jun-ichi , Yoshida Ken-ichi , Ono Takashi 
Published: March 2020

SummaryObjectivesChronic intermittent hypoxia (IH), a common state experienced in obstructive sleep apnoea (OSA), retards mandibular growth in adolescent rats. The aim of this study was to elucidate the differential effects of IH on mandibular growth in different growth stages.Materials and methodsThree-week-old (juvenile stage) and 7-week-old (adolescent stage) male Sprague–Dawley rats underwent IH for 3 weeks. Age-matched control rats were exposed to room air. Mandibular growth was evaluated by radiograph analysis, micro-computed tomography, real-time polymerase chain reaction and immunohistology. Tibial growth was evaluated as an index of systemic skeletal growth.ResultsIH had no significant impact on the general growth of either the juvenile or adolescent rats. However, it significantly decreased the total mandibular length and the posterior corpus length of the mandible in the adolescent rats and the anterior corpus length in the juvenile rats. IH also increased bone mineral density (BMD) of the condylar head in adolescent rats but did not affect the BMD of the tibia. Immunohistological analysis showed that the expression level of receptor activation of nuclear factor-κB ligand significantly decreased (in contrast to its messenger ribonucleicacid level) in the condylar head of adolescent rats with IH, while the number of osteoprotegerin-positive cells was comparable in the mandibles of adolescent IH rats and control rats.LimitationsThe animal model could not simulate the pathological conditions of OSA completely and there were differences in bone growth between humans and rodents.ConclusionsThese results suggest that the susceptibility of mandibular growth retardation to IH depends on the growth stage of the rats.
Triglycerides and remnant cholesterol associated with risk of aortic valve stenosis: Mendelian randomization in the Copenhagen General Population Study
Authors: Kaltoft Morten , Langsted Anne , Nordestgaard Børge G 
Published: March 2020

Abstract

Aims
We tested the hypothesis that higher levels of plasma triglycerides and remnant cholesterol are observationally and genetically associated with increased risk of aortic valve stenosis.

Methods and results
We included 108 559 individuals from the Copenhagen General Population Study. Plasma triglycerides, remnant cholesterol (total cholesterol minus low-density lipoprotein and high-density lipoprotein cholesterol), and 16 genetic variants causing such increased or decreased levels were determined. Incident aortic valve stenosis occurred in 1593 individuals. Observationally compared to individuals with triglycerides &lt;1 mmol/L (&lt;89 mg/dL), the multifactorially adjusted hazard ratio for aortic valve stenosis was 1.02 [95% confidence interval (CI) 0.87–1.19] for individuals with triglycerides of 1.0–1.9 mmol/L (89–176 mg/dL), 1.22 (1.02–1.46) for 2.0–2.9 mmol/L (177–265 mg/dL), 1.40 (1.11–1.77) for 3.0–3.9 mmol/L (266–353 mg/dL), 1.29 (0.88–1.90) for 4.0–4.9 mmol/L (354–442 mg/dL), and 1.52 (1.02–2.27) for individuals with triglycerides ≥5 mmol/L (≥443 mg/dL). By age 85, the cumulative incidence of aortic valve stenosis was 5.1% for individuals with plasma triglycerides &lt;2.0 mmol/L (77 mg/dL), 6.5% at 2.0–4.9 mmol/L (177–442 mg/dL), and 8.2% for individuals with plasma triglycerides ≥5.0 mmol/L (443 mg/dL). The corresponding values for remnant cholesterol categories were 4.8% for &lt;0.5 mmol/L (19 mg/dL), 5.6% for 0.5–1.4 mmol/L (19–57 mg/dL), and 7.4% for ≥1.5 mmol/L (58 mg/dL). Genetically, compared to individuals with allele score 13–16, odds ratios for aortic valve stenosis were 1.30 (95% CI 1.20–1.42; Δtriglycerides +12%; Δremnant cholesterol +11%) for allele score 17–18, 1.41 (1.31–1.52; +25%; +22%) for allele score 19–20, and 1.51 (1.22–1.86; +51%; +44%) for individuals with allele score 21–23.

Conclusion
Higher triglycerides and remnant cholesterol were observationally and genetically associated with increased risk of aortic valve stenosis.
Adherence to ESC cardiac resynchronization therapy guidelines: findings from the ESC CRT Survey II
Authors: Normand Camilla , Linde Cecilia , Blomström-Lundqvist Carina , Stellbrink Christoph , Gasparini Maurizio , Anker Stefan D , Plummer Chris , Sarigul Nedim Umutay , Papiashvili Giorgi , Iovev Svetoslav , Dickstein Kenneth 
Published: March 2020

AbstractAimsCardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with heart failure (HF) and electrical dyssynchrony. The European Society of Cardiology (ESC) Guidelines provide evidence-based recommendations indicating optimal patient selection for CRT implantation in both the 2013 European Heart Rhythm Association (EHRA) and the 2016 Heart Failure Association (HFA) Guidelines. We assessed the adherence to guidelines and identified factors associated with guideline adherence.Methods and resultsIn 2016, the HFA and EHRA conducted the CRT Survey II in 42 ESC countries. The data collected were sufficient to evaluate adherence to guidelines in 8021 patients. Of these, 67% had a Class I guideline indication for CRT implantation, which was significantly correlated with female gender (1.70, P &lt; 0.0001), age &lt;75 years (1.55, P &lt; 0.0001), non-ischaemic HF aetiology (1.22, P &lt; 0.0001), and elective admission (1.87, P &lt; 0.0001). A further 26% of implants had a Class IIa indication, 5% IIb and only 2% a contraindication to CRT—a Class III indication. Patients implanted under Level IIa indications were much more likely to have more comorbidities than patients implanted under Level I indications. However, there were large variations in guideline adherence between ESC countries.ConclusionImplanters in ESC member states demonstrate a high degree of adherence to ESC guidelines with 98% of implants having a documented Class I, IIa or IIb indication. Cardiac resynchronization therapy implantation without a Class I indication was more likely in men, patients age ≥75 years, with HF of ischaemic origin and in patients admitted to hospital acutely.
A potential post-perovskite province in D″ beneath the Eastern Pacific: evidence from new analysis of discrepant SKS–SKKS shear-wave splitting
Authors: Asplet Joseph , Wookey James , Kendall Michael 
Published: March 2020

SUMMARY
Observations of seismic anisotropy in the lowermost mantle—D″—are abundant. As seismic anisotropy is known to develop as a response to plastic flow in the mantle, constraining lowermost mantle anisotropy allows us to better understand mantle dynamics. Measuring shear-wave splitting in body wave phases which traverse the lowermost mantle is a powerful tool to constrain this anisotropy. Isolating a signal from lowermost mantle anisotropy requires the use of multiple shear-wave phases, such as SKS and SKKS. These phases can also be used to constrain azimuthal anisotropy in D″: the ray paths of SKS and SKKS are nearly coincident in the upper mantle but diverge significantly at the core–mantle boundary. Any significant discrepancy in the shear-wave splitting measured for each phase can be ascribed to anisotropy in D″. We search for statistically significant discrepancies in shear-wave splitting measured for a data set of 420 SKS–SKKS event–station pairs that sample D″ beneath the Eastern Pacific. To ensure robust results, we develop a new multiparameter approach which combines a measure derived from the eigenvalue minimization approach for measuring shear-wave splitting with an existing splitting intensity method. This combined approach allows for easier automation of discrepant shear-wave splitting analysis. Using this approach we identify 30 SKS–SKKS event–station pairs as discrepant. These predominantly sit along a backazimuth range of 260°–290°. From our results we interpret a region of azimuthal anisotropy in D″ beneath the Eastern Pacific, characterized by null SKS splitting, and mean delay time of $1.15 \, \mathrm{ s}$ in SKKS. These measurements corroborate and expand upon previous observations made using SKS–SKKS and S–ScS phases in this region. Our preferred explanation for this anisotropy is the lattice-preferred orientation of post-perovskite. A plausible mechanism for the deformation causing this anisotropy is the impingement of subducted material from the Farallon slab at the core–mantle boundary.
Human Cytomegalovirus (HCMV)-Specific Antibody Response and Development of Antibody-Dependent Cellular Cytotoxicity Against HCMV After Lung Transplantation
Authors: Vietzen Hannes , Görzer Irene , Honsig Claudia , Jaksch Peter , Puchhammer-Stöckl Elisabeth 
Published: March 2020

Abstract

Background
Human cytomegalovirus (HCMV) may cause severe infections in lung transplant recipients (LTRs). The impact of the host antibody (AB)-dependent cytotoxicity (ADCC) on HCMV is still unclear. Therefore, we analyzed the AB-response against HCMV glycoprotein B (gB) and the pentameric complex (PC) and the ADCC response in HCMV-seropositive (R+) LTRs and in seronegative recipients of positive organs (D+/R−).

Methods
Plasma samples were collected from 35 R+ and 28 D+/R− LTRs for 1 (R+) or 2 (D+/R−) years posttransplantation and from 114 healthy control persons. The PC- and gB-specific ABs were assessed by enzyme-linked immunosorbent assay. The ADCC was analyzed by focal expansion assay and CD107 cytotoxicity assay.

Results
In R+ LTRs, significantly higher gB-specific AB levels developed within 1 year posttransplantation than in controls (immunoglobulin [Ig]G1, P &lt; .001; IgG3, P &lt; .001). In addition, higher levels of ADCC were observed by FEA and CD107 assay in R+ patients compared with controls (P &lt; .001). In 23 D+R− patients, HCMV-specific ABs developed. Antibody-dependent cytotoxicity became detectable 3 months posttransplantation in these, with higher ADCC observed in viremic patients. Depletion of gB- and PC-specific ABs revealed that, in particular, gB-specific Abs were associated with the ADCC response.

Conclusions
We show that a strong ADCC is elicited after transplantation and is especially based on gB-specific ABs.
Genomic characterization of 16S rRNA methyltransferase-producing Escherichia coli isolates from the Parisian area, France
Authors: Caméléna François , Morel Florence , Merimèche Manel , Decousser Jean-Winoc , Jacquier Hervé , Clermont Olivier , Darty Mélanie , Mainardis Mary , Cambau Emmanuelle , Tenaillon Olivier , Denamur Erick , Berçot Béatrice ,   the IAME Resistance Group, Rousseau Clotilde , Poncin Thibaut , Braille Aymeric , Amara Marlène , Mammeri Hedi , Armand-Lefevre Laurence , Kumanski Sylvain , Royer Guilhem , Bialek Suzanne , Landraud Luce , Branger Catherine , Carbonnelle Etienne , Bonacorsi Stéphane 
Published: March 2020

Abstract

Background
The resistance to all aminoglycosides (AGs) conferred by 16S rRNA methyltransferase enzymes (16S-RMTases) is a major public health concern.

Objectives
To characterize the resistance genotype, its genetic environment and plasmid support, and the phylogenetic relatedness of 16S-RMTase-producing Escherichia coli from France.

Methods
We screened 137 E. coli isolates resistant to all clinically relevant AGs from nine Parisian hospitals for 16S-RMTases. WGS was performed on clinical isolates with high-level AG resistance (MIC ≥256 mg/L) and their transformants.

Results
Thirty of the 137 AG-resistant E. coli produced 16S-RMTases: 11 ArmA, 18 RmtB and 1 RmtC. The 16S-RMTase producers were also resistant to third-generation cephalosporins (90% due to a blaCTX-M gene), co-trimoxazole, fluoroquinolones and carbapenems (blaNDM and blaVIM genes) in 97%, 83%, 70% and 10% of cases, respectively. Phylogenomic diversity was high in ArmA producers, with 10 different STs, but a similar genetic environment, with the Tn1548 transposon carried by a plasmid closely related to pCTX-M-3 in 6/11 isolates. Conversely, RmtB producers belonged to 12 STs, the most frequent being ST405 and ST complex (STc) 10 (four and four isolates, respectively). The rmtB gene was carried by IncF plasmids in 10 isolates and was found in different genetic environments. The rmtC gene was carried by the pNDM-US plasmid.

Conclusions
ArmA and RmtB are the predominant 16S-RMTases in France, but their spread follows two different patterns: (i) dissemination of a conserved genetic support carrying armA in E. coli with high levels of genomic diversity; and (ii) various genetic environments surrounding rmtB in clonally related E. coli.
Hospice Utilization in Elderly Patients With Brain Metastases
Authors: Mehanna Elie K , Catalano Paul J , Cagney Daniel N , Haas-Kogan Daphne A , Alexander Brian M , Tulsky James A , Aizer Ayal A 
Published: March 2020

Abstract

Background
Brain metastases are associated with considerable morbidity and mortality. Integration of hospice at the end of life offers patients symptom relief and improves quality of life, particularly for elderly patients who are less able to tolerate brain-directed therapy. Population-level investigations of hospice utilization among elderly patients with brain metastases are limited.

Methods
Using the Surveillance, Epidemiology and End Results–Medicare database for primary cancer sites that commonly metastasize to the brain, we identified 50 148 patients (aged 66 years and older) diagnosed with brain metastases between 2005 and 2016. We calculated the incidence, timing, and predictors of hospice enrollment using descriptive techniques and multivariable logistic regression. All statistical tests were 2-sided.

Results
The incidence of hospice enrollment was 71.4% (95% confidence interval [CI] = 71.0 to 71.9; P &lt; .001), a rate that increased over the study period (P &lt; .001). The odds of enrollment for black (odds ratio [OR] = 0.76, 95% CI = 0.71 to 0.82; P &lt; .001), Hispanic (OR = 0.80, 95% CI = 0.72 to 0.87; P &lt; .001), and Asian patients (OR = 0.52, 95% CI = 0.48 to 0.57; P &lt; .001) were substantially lower than white patients; men were less likely to be enrolled in hospice than women (OR = 0.78, 95% CI = 0.74 to 0.81; P &lt; .001). Among patients enrolled in hospice, 32.6% (95% CI = 32.1 to 33.1; P &lt; .001) were enrolled less than 7 days prior to death, a rate that was stable over the study period.

Conclusions
Hospice is used for a majority of elderly patients with brain metastases although a considerable percentage of patients die without hospice services. Many patients enroll in hospice late and, concerningly, statistically significant sociodemographic disparities exist in hospice utilization. Further investigations to facilitate targeted interventions addressing such disparities are warranted.
Reconstruction of an upper lip and intraoral defect following resection of an upper lip melanoma using a lower lip musculomucosal flap combined with a tongue flap
Authors: Yoshioka Yukio , Hayashido Yasutaka , Ito Yoku , Toratani Shigeaki , Okamoto Tetsuji 
Published: March 2020

Abstract
Restoring the cosmetic and functional aspects of the lip after tumor resection is challenging. We report a case of reconstruction for a defect due to resection of a melanoma using a lower lip musculomucosal flap combined with a tongue flap. A 20-year-old man was referred to our hospital and diagnosed with malignant melanoma with metastatic right submaxillary lymph nodes. We excised the tumor with neck dissection. We excised not only the right upper lip mucosa but also the gum, including some orbicularis oris muscle and alveolar bone from the right canine tooth to the left central incisor tooth. The defect was simultaneously reconstructed using both, a lower lip musculomucosal flap and a tongue flap. Revisional operation to remove contraction of a postoperative scar and the right vermillion border collection was performed at 3 months after the initial operation. There had been no functional and cosmetic trouble of the upper lip.
Autologous chondrocyte implantation with a Reveille cartilage processor for articular cartilage injury: a case report
Authors: Igarashi Tadashi , Kaneko Takao , Yoshizawa Shu , Takada Kazutaka , Matsu-ura Yu-uki , Ikegami Hiroyasu , Musha Yoshiro 
Published: March 2020

Abstract
Autologous chondrocyte implantation (ACI) is an important operative option when repairing cartilage defects of the knee. This report introduces a new product development with one-stage ACI using a Reveille Cartilage Processor (Reveille CP) as well as the assessment of MRI and clinical results at a 1-year follow-up. The report compared cases between a 42-year-old female who underwent ACI surgery using Reveille CP and a 51-year old female who received treatment with two-stage ACI of tissue-engineered cartilage-like tissue (J-TEC Autologous Chondrocyte Cultured Cartilage [JACC]). One year after JACC, magnetic resonance imaging (MRI) showed signal intensity area in the grafted area, while patients with Reveille CP showed greater thickness than the surrounding healthy cartilage. The Lysholm, pain and QOL scores of Knee Injury and Osteoarthritis Outcome (KOOS) at one 1 year after surgery with Reveille CP were higher than JACC.