bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and prevalence of inflammatory bowel disease in UK primary care: a population-based cohort study
Authors: Pasvol Thomas Joshua , Horsfall Laura , Bloom Stuart , Segal Anthony Walter , Sabin Caroline , Field Nigel , Rait Greta 
Published: July 2020

ObjectivesWe describe temporal trends in the recorded incidence of inflammatory bowel disease (IBD) in UK primary care patients between 2000 and 2018.DesignA cohort study.SettingThe IQVIA Medical Research data (IMRD) primary care database.ParticipantsAll individuals registered with general practices contributing to IMRD during the period 01 January 2000–31 December 2018.Main outcome measuresThe primary outcome was the recorded diagnosis of IBD.Results11 325 025 individuals were included and 65 700 IBD cases were identified, of which 22 560 were incident diagnoses made during the study period. Overall, there were 8077 incident cases of Crohn’s disease (CD) and 12 369 incident cases of ulcerative colitis (UC). Crude incidence estimates of ‘IBD overall’, CD and UC were 28.6 (28.2 to 28.9), 10.2 (10.0 to 10.5) and 15.7 (15.4 to 15.9)/100 000 person years, respectively. No change in IBD incidence was observed for adults aged 17–40 years and children aged 0–9 years. However, for adults aged over 40 years, incidence fell from 37.8 (34.5 to 41.4) to 23.6 (21.3 to 26.0)/100 000 person years (average decrease 2.3% (1.9 to 2.7)/year (p<0.0001)). In adolescents aged 10–16 years, incidence rose from 13.1 (8.4 to 19.5) to 25.4 (19.5 to 32.4)/100 000 person years (average increase 3.0% (1.7 to 4.3)/year (p<0.0001)). Point prevalence estimates on 31 December 2018 for IBD overall, CD and UC were 725, 276 and 397 per 100 000 people, respectively.ConclusionsThis is one of the largest studies ever undertaken to investigate trends in IBD epidemiology. Although we observed stable or falling incidence of IBD in adults, our results are consistent with some of the highest reported global incidence and prevalence rates for IBD, with a 94% rise in incidence in adolescents. Further investigation is required to understand the aetiological drivers.
How does the intensity of physical therapy affect the Gross Motor Function Measure (GMFM-66) total score in children with cerebral palsy? A systematic review protocol
Authors: Rahlin Mary , Duncan Burris , Howe Carol L , Pottinger Heidi L 
Published: July 2020

IntroductionIntensive physical therapy (PT) interventions administered to children with cerebral palsy (CP) have received a significant amount of attention in published literature. However, there is considerable variability in therapy intensity among studies and notable lack of information on optimal intervention dosing. This makes it difficult for clinicians to use evidence to inform practice. Many studies use the Gross Motor Function Measure (GMFM-66) to assess functional progress in children with CP. The purpose of this systematic review will be to identify the GMFM-66 change score reported in published studies, with outcomes based on intervention intensity. Whether the type of PT intervention, child’s age, and Gross Motor Function Classification System level influence the GMFM-66 scores will be also assessed.Methods and analysisThis systematic review protocol was developed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) 2015 checklist. In March 2018, nine databases (PubMed, Ovid MEDLINE, Cochrane Library, Embase, Scopus, Web of Science, CINAHL, ClinicalTrials.gov, and REHABDATA) were searched for controlled clinical trials and single-subject design studies of PT interventions of any kind and intensity that used the GMFM-66 as an outcome measure for children with CP, age up to 18 years. Two authors independently reviewed the titles and abstracts and arrived at consensus on paper selection for a full-text review. The same process was used for a full-text article screening based on further detailed inclusion criteria, with a final selection made for those suitable for data extraction. Prior to commencement of data extraction, all searches will be updated, and new results re-screened.Ethics and disseminationThis study will involve a systematic review of published articles and no primary data collection. Therefore, no ethical approval will be necessary. Results will be disseminated in a peer-reviewed publication and presented at scientific conferences.PROSPERO registration numberCRD42020147669
In situ vaccination at a peripheral tumor site augments response against melanoma brain metastases
Authors: Clark Paul A , Sriramaneni Raghava N , Jin Won Jong , Jagodinsky Justin C , Bates Amber M , Jaquish Abigail A , Anderson Bryce R , Le Trang , Lubin Jonathan A , Chakravarty Ishan , Arthur Ian S , Heinze Clinton M , Guy Emily I , Kler Jasdeep , Klar Kelsey A , Carlson Peter M , Kim Kyung Mann , Kuo John S , Morris Zachary S 
Published: July 2020

BackgroundImmune checkpoint inhibition (ICI) alone is not efficacious for a large number of patients with melanoma brain metastases. We previously established an in situ vaccination (ISV) regimen combining radiation and immunocytokine to enhance response to ICIs. Here, we tested whether ISV inhibits the development of brain metastases in a murine melanoma model.MethodsB78 (GD2+) melanoma ‘primary’ tumors were engrafted on the right flank of C57BL/6 mice. After 3–4 weeks, primary tumors were treated with ISV (radiation (12 Gy, day 1), α-GD2 immunocytokine (hu14.18-IL2, days 6–10)) and ICI (α-CTLA-4, days 3, 6, 9). Complete response (CR) was defined as no residual tumor observed at treatment day 90. Mice with CR were tested for immune memory by re-engraftment with B78 in the left flank and then the brain. To test ISV efficacy against metastases, tumors were also engrafted in the left flank and brain of previously untreated mice. Tumors were analyzed by quantitative reverse transcription-PCR, immunohistochemistry, flow cytometry and multiplex cytokine assay.ResultsISV+α-CTLA-4 resulted in immune memory and rejection of B78 engraftment in the brain in 11 of 12 mice. When B78 was engrafted in brain prior to treatment, ISV+α-CTLA-4 increased survival compared with ICI alone. ISV+α-CTLA-4 eradicated left flank tumors but did not elicit CR at brain sites when tumor cells were engrafted in brain prior to ISV. ISV+α-CTLA-4 increased CD8+and CD4+T cells in flank and brain tumors compared with untreated mice. Among ISV + α-CTLA-4 treated mice, left flank tumors showed increased CD8+infiltration and CD8+:FOXP3+ratio compared with brain tumors. Flank and brain tumors showed minimal differences in expression of immune checkpoint receptors/ligands orMhc-1. Cytokine productions were similar in left flank and brain tumors in untreated mice. Following ISV+α-CTLA-4, production of immune-stimulatory cytokines was greater in left flank compared with brain tumor grafts.ConclusionISV augmented response to ICIs in murine melanoma at brain and extracranial tumor sites. Although baseline tumor-immune microenvironments were similar at brain and extracranial tumor sites, response to ISV+α-CTLA-4 was divergent with reduced infiltration and activation of immune cells in brain tumors. Additional therapies may be needed for effective antitumor immune response against melanoma brain metastases.
Comparison of endoscopic endotracheal intubation and the v‐gel supraglottic airway device for spontaneously ventilating New Zealand white rabbits undergoing ovariohysterectomy
Authors: Comolli Jessica , Schnellbacher Rodney , Beaufrere Hugues , Blas‐Machado Uriel , Quandt Jane , Mayer Jörg , Divers Stephen J 
Published: July 2020

BackgroundDue to the technical difficulties with endotracheal intubation of rabbits, a prospective, randomised, controlled study was performed to compare a rabbit‐specific supraglottic airway device (SGAD), the v‐gel, with endoscopic endotracheal intubation (EEI) in spontaneously breathing rabbits undergoing ovariohysterectomy.MethodsFourteen adult female New Zealand white rabbits were randomly allocated to one of two groups based on the method of airway establishment: EEI or v‐gel SGAD. Anaesthesia was induced with ketamine and xylazine and maintained using isoflurane in 100 per cent oxygen. Comparisons were made between groups based on placement time of endotracheal tube/SGAD, number of attempts and adjustments, the necessity to increase isoflurane concentrations to maintain a surgical plane of anaesthesia, arterial blood gas values, gross laryngeal evaluation, and laryngotracheal histopathology.ResultsBoth techniques resulted in elevated arterial pCO2 levels, but the v‐gel was associated with more elevated pCO2 in comparison with EEI (P=0.045). Airway trauma was histologically present but clinically negligible in both groups, with no statistically significant differences observed between techniques (P>0.05). Placement time of the v‐gel was significantly faster (P=0.003) and required less technical skill than EEI, but was more easily displaced when changing the animal's position (P=0.004).ConclusionThe v‐gel is a practical alternative to EEI for securing the airway of healthy spontaneously ventilating rabbits, provided a capnograph is utilised to ensure continuous placement. Both airway techniques appear safe and effective with few complications, as long as intermittent positive pressure ventilation can be employed to correct hypercapnia.
Is there a novel Einstein–Gauss–Bonnet theory in four dimensions?
Authors: Gürses Metin , Şişman Tahsin Çağrı , Tekin Bayram 
Published: July 2020

AbstractNo! We show that the field equations of Einstein–Gauss–Bonnet theory defined in generic $$D>4$$D>4 dimensions split into two parts one of which always remains higher dimensional, and hence the theory does not have a non-trivial limit to $$D=4$$D=4. Therefore, the recently introduced four-dimensional, novel, Einstein–Gauss–Bonnet theory does not admit an intrinsically four-dimensional definition, in terms of metric only, as such it does not exist in four dimensions. The solutions (the spacetime, the metric) always remain $$D>4$$D>4 dimensional. As there is no canonical choice of 4 spacetime dimensions out of D dimensions for generic metrics, the theory is not well defined in four dimensions.
Gravitational waves in massive conformal gravity
Authors: Faria F. F. 
Published: July 2020

AbstractFirst, we obtain the plane wave solution of the linearized massive conformal gravity field equations. It is shown that the theory has seven physical plane waves. In addition, we investigate the gravitational radiation from binary systems in massive conformal gravity. We find that the theory with large graviton mass can reproduce the orbit of binaries by the emission of gravitational waves.
Redox and mTOR-dependent regulation of plasma lamellar calcium influx controls the senescence-associated secretory phenotype
Authors: Chandrasekaran Akshaya , Lee May Y , Zhang Xuexin , Hasan Shaheen , Desta Habben , Tenenbaum Scott A , Melendez J Andrés 
Published: July 2020

Cellular senescence has evolved as a protective mechanism to arrest growth of cells with oncogenic potential but is accompanied by the often pathologically deleterious senescence-associated secretory phenotype (SASP). Here we demonstrate an H2O2-dependent functional disruption controlling senescence-associated Ca2+ homeostasis and the SASP. Senescent cells fail to respond to H2O2-dependent plasma lamellar Ca2+ entry when compared to pre-senescent cells. Limiting exposure to senescence-associated H2O2 restores H2O2-dependent Ca2+ entry as well as transient receptor potential cation channel subfamily C member 6 (TRPC6) function. SA-TRPC6 and SASP expression is blocked by restoring Ca2+ entry with the TRP channel antagonist SKF-96365 or by the mTOR inhibitors rapamycin and Ku0063794. Together, our findings provide compelling evidence that redox and mTOR-mediated regulation of Ca2+ entry through TRPC6 modulates SASP gene expression and approaches which preserve normal Ca2+ homeostasis may prove useful in disrupting SASP activity. Impact statement Through its ability to evoke responses from cells in a paracrine fashion, the senescence-associated secretory phenotype (SASP) has been linked to numerous age-associated disease pathologies including tumor invasion, cardiovascular dysfunction, neuroinflammation, osteoarthritis, and renal disease. Strategies which limit the amplitude and duration of SASP serve to delay age-related degenerative decline. Here we demonstrate that the SASP regulation is linked to shifts in intracellular Ca2+ homeostasis and strategies which rescue redox-dependent calcium entry including enzymatic H2O2 scavenging, TRP modulation, or mTOR inhibition block SASP and TRPC6 gene expression. As Ca2+ is indispensable for secretion from both secretory and non-secretory cells, it is exciting to speculate that the expression of plasma lamellar TRP channels critical for the maintenance of intracellular Ca2+ homeostasis may be coordinately regulated with the SASP.
Transmembrane protein 16A/anoctamin 1 inhibitor T16Ainh‐A01 reversed monocrotaline‐induced rat pulmonary arterial hypertension
Authors: Xie Jianye , Liu Wenyuan , Lv Wenjing , Han Xiaohua , Kong Qingnuan , Wu Yuhui , Liu Xin , Han Ying , Shi Chunying , Jia Xiujuan 
Published: July 2020

Transmembrane protein 16A was involved in the development of the monocrotaline‐induced pulmonary arterial hypertension model through ERK1/2 activation, and it was considered as potential target for pulmonary arterial hypertension treatment. A pulmonary arterial hypertension rat model was established by intraperitoneal administration of monocrotaline. Noninvasive pulsed‐wave Doppler and histological analysis was performed, and it revealed proliferation and remodeling of pulmonary arterioles and right ventricle hypertrophy. In addition, transmembrane protein 16A, proliferating cell nuclear antigen—a proliferate marker, P‐ERK1/2 increased following monocrotaline treatment. Expression of transmembrane protein 16A in the pulmonary arteries was co‐localized with a specific marker of vascular smooth muscle α‐actin. Then, a specific inhibitor of transmembrane protein 16A‐T16Ainh‐A01 was administered to pulmonary arterial hypertension rats. It was found to alleviate the remodeling of pulmonary arterioles and right ventricle hypertrophy significantly, and decrease the upregulation of proliferating cell nuclear antigen in monocrotaline‐induced pulmonary arteries. In addition, T16Ainh‐A01 could inhibit the activation of ERK1/2 in pulmonary arterial hypertension model. Transmembrane protein 16A mediated the proliferation and remodeling of pulmonary arterioles in the monocrotaline‐induced pulmonary arterial hypertension model. ERK1/2 pathway is one of downstream factors. Long‐term use of T16Ainh‐A01 in vivo could alleviate remodeling and pressure in pulmonary arterial hypertension.
A comprehensive survey of integron-associated genes present in metagenomes
Authors: Buongermino Pereira Mariana , Österlund Tobias , Eriksson K Martin , Backhaus Thomas , Axelson-Fisk Marina , Kristiansson Erik 
Published: July 2020

Abstract
Background
Integrons are genomic elements that mediate horizontal gene transfer by inserting and removing genetic material using site-specific recombination. Integrons are commonly found in bacterial genomes, where they maintain a large and diverse set of genes that plays an important role in adaptation and evolution. Previous studies have started to characterize the wide range of biological functions present in integrons. However, the efforts have so far mainly been limited to genomes from cultivable bacteria and amplicons generated by PCR, thus targeting only a small part of the total integron diversity. Metagenomic data, generated by direct sequencing of environmental and clinical samples, provides a more holistic and unbiased analysis of integron-associated genes. However, the fragmented nature of metagenomic data has previously made such analysis highly challenging.

Results
Here, we present a systematic survey of integron-associated genes in metagenomic data. The analysis was based on a newly developed computational method where integron-associated genes were identified by detecting their associated recombination sites. By processing contiguous sequences assembled from more than 10 terabases of metagenomic data, we were able to identify 13,397 unique integron-associated genes. Metagenomes from marine microbial communities had the highest occurrence of integron-associated genes with levels more than 100-fold higher than in the human microbiome. The identified genes had a large functional diversity spanning over several functional classes. Genes associated with defense mechanisms and mobility facilitators were most overrepresented and more than five times as common in integrons compared to other bacterial genes. As many as two thirds of the genes were found to encode proteins of unknown function. Less than 1% of the genes were associated with antibiotic resistance, of which several were novel, previously undescribed, resistance gene variants.

Conclusions
Our results highlight the large functional diversity maintained by integrons present in unculturable bacteria and significantly expands the number of described integron-associated genes.
An analysis of the “Half-Perc” versus open surgical placement method for a peritoneal dialysis catheter: a non-inferiority cohort study
Authors: Zhang Difei , Peng Yu , Zheng Tingting , Liu Hui , Wu Jianfeng , Li Zewen , Su Jingxu , Xu Yuan , Hu Xiaoxuan , Chen Guowei , Hou Haijing , Zhang La , Wu Liwen , Liu Xusheng , Lu Fuhua 
Published: July 2020

Abstract
Background
Most end-stage renal disease (ESRD) patients undergo open surgical techniques for peritoneal dialysis (PD) catheter placement. An alternative method to PD catheter implantation is the half-percutaneous (“Half-Perc”) technique based on a modified trocar that is performed by a nephrologist. The single-center, retrospective, observational, cohort study presented here aimed to compare the effects of the “Half-Perc” technique with the traditional open surgery on peritoneal catheter insertion.

Methods
From January 2015 to January 2018, 240 ESRD patients who received initial PD catheter placement were divided into two groups based on the “Half-Perc” technique or open surgery. All patients were followed up for 365 days or until loss of initial PD catheter or death. Prism 5 software was used to analyze baseline characteristics, operation-related parameters, mechanical complications and clinical outcomes.

Results
The “Half-Perc” technique showed shorter operation time, shorter incision length, lower postoperative pain scores and quick initiation of the PD program compared to the open surgery. After the 365-day follow-up, the “Half-Perc” group showed a higher rate of catheter dysfunction (4% versus 0.9%) that was corrected by conservative treatment in most patients and a lower rate of peritonitis (4% versus 9.6%) but mechanical complications and clinical outcomes did not differ between the two groups. There was also no significant difference based on overall patient mortality or catheter removal. One-year initial catheter survival and true catheter survival were not statistically different between the groups.

Conclusion
The “Half-Perc” placement of the PD catheter using a modified metal trocar appears to be a non-inferior alternative method and carries minimal invasiveness and risk compared to open surgical placement.
Evaluating the effect of an educational program on increasing cervical cancer screening behavior among rural women in Guilan, Iran
Authors: Eghbal Sedighe Bab , Karimy Mahmood , Kasmaei Parisa , Roshan Zahra Atrkar , Valipour Roghieh , Attari Seyedeh Maryam 
Published: July 2020

Abstract
Background
Cervical cancer is one of the major health problems and the third prevalent cancer in women all around the world. As a simple, inexpensive, and with no side-effects, Pap test is a reliable way to screen cervical cancer. This study aimed to investigate, the effects of educational intervention based on the Health Belief Model (HBM) on doing Pap smear tests among the rural women of the north of Iran.

Methods
In a quasi-experimental study, 160 rural women were randomly divided into control and experimental groups to experience a three-session intervention. The experimental group received the usual educational programs of rural health center and educational programs based on the HBM constructs through personal consultation, asking/answering questions, and an educational pamphlet. The control group, received the usual educational programs of rural health center. The post-test data were collected 2 months after the intervention and analyzed in SPSS-18.

Results
Before the intervention, there was no significant difference between the control and experimental groups regarding the mean score of knowledge, performance and constructs of the HBM. After the intervention, however, there was a significant difference in the mean scores of knowledge performance and all constructs of the HBM in two groups (p < 0.001). Rate of doing the Pap smear test in the experimental group increased from 18.7 to 78.7% in the intervention group.

Conclusion
These findings support the effectiveness of cervical cancer prevention programs based on the HBM. Therefore, conducting similar programs in other regions is recommended.
HPLC-DAD analysis of Hyssopus Cuspidatus Boriss extract and mensuration of its antioxygenation property
Authors: Zhao Lu , Ji Zhihong , Li Keao , Wang Bo , Zeng Ya , Tian Shuge 
Published: July 2020

Abstract
Background
Hyssopus cuspidatus Boriss has been used as an important ethnomedicinal plant for long to eliminate phlegm, relieve cough and as well as having antibacterial, antioxygenation, and antitumor activities. In this study, the polyphenol contents, flavonoid contents, free radical scavenging assay and animal antioxygenation property assay of ethanol extract of H. cuspidatus were measured.

Methods
This study determined the total polyphenol and flavonoid contents in H. cuspidatus by UV-VIS. Caffeic, ferulic, and rosmarinic acids were measured using HPLC-DAD. Free radical scavenging assay of H. cuspidatus was studied by colorimetric method. Animal antioxygenation property assay of H. cuspidatus was studied with mice by biochemical assay kits.

Results
The total polyphenol and flavonoid contents of H. cuspidatus in 2017, 2018, 2019 were determined and the contents of H. cuspidatus in 2019 was the highest. In addition, rosmarinic acid was the phenolic acid with the highest content in H. cuspidatus. Compared with those of DPPH free radical, hydroxyl free radical, and superoxide anion free radical, the scavenging ability of H. cuspidatus of ABTS free radical was stronger, the average IC50 value was 0.0245 mg/mL. In animal antioxygenation property experiment, the model group was successfully established with decreased activities of SOD, CAT, and GSH-px and increased content of MDA. The ethanol extract of H. cuspidatus increased the activities of SOD, CAT, and GSH-px and reduced the content of MDA. Each group of samples and the ascorbic acid positive control group showed significant differences in the results of free radical scavenging and animal antioxygenation property experiments (P < 0.05).

Conclusions
These results suggest that H. cuspidatus exerts an antioxygenation property, which can be attributed to the contents of total polyphenol and flavonoid. Given its strong antioxygenation property, H. cuspidatus can be used as a new natural antioxidant in food preservation and disease treatment.