bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of second‐trimester sonographic cervical length on the risk of spontaneous preterm delivery in different risk groups: A prospective observational multicenter study
Authors: Wikström Tove , Hagberg Henrik , Jacobsson Bo , Kuusela Pihla , Wesström Jan , Lindgren Peter , Fadl Helena , Wennerholm Ulla‐Britt , Valentin Lil 
Published: June 2021

AbstractIntroductionThe aim of the study is to compare the effect of cervical length measured with transvaginal ultrasound in the second trimester on the risk of spontaneous preterm delivery (PTD) between different risk groups of asymptomatic women with a singleton pregnancy.Material and methodsThis is a pre‐planned exploratory analysis of the CERVIX study, a prospective blinded multicenter diagnostic accuracy study. Asymptomatic women with a singleton pregnancy were consecutively recruited at their second‐trimester routine ultrasound examination at seven Swedish ultrasound centers. Cervical length was measured with transvaginal ultrasound at 18–20 weeks (Cx1; n = 11 072) and 21–23 weeks (Cx2, optional; n = 6288). The effect of cervical length on the risk of spontaneous PTD and its discriminative ability was compared between women with: (i) previous spontaneous PTD, late miscarriage or cervical conization (high‐risk group; n = 1045); (ii) nulliparae without risk factors (n = 5173); (iii) parae without risk factors (n = 4740). Women with previous indicated PTD were excluded (n = 114). Main outcome measures were: effect of cervical length on the risk of spontaneous PTD expressed as odds ratio per 5‐mm decrease in cervical length with interaction analysis using logistic regression to test whether the effect differed between groups, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, number needed to screen to detect one spontaneous PTD.ResultsThe effect of cervical length at Cx2 on the risk of spontaneous PTD <33 weeks was similar in all groups (odds ratios 2.26–2.58, interaction p value 0.91). The discriminative ability at Cx2 was superior to that at Cx1 and was similar in all groups (AUC 0.69–0.76). Cervical length ≤25 mm at Cx2 identified 57% of spontaneous preterm deliveries <33 weeks in the high‐risk group with number needed to screen 161. The number needed to screen for groups (ii) and (iii) were 1018 and 843.ConclusionsThe effect of cervical length at 21–23 weeks on the risk of spontaneous PTD <33 weeks is similar in high‐ and low‐risk pregnancies. The differences in number needed to screen should be considered before implementing a screening program.
Topical treatment of diabetic retinopathy: a systematic review
Authors: Thagaard Mikkel S. , Vergmann Anna S. , Grauslund Jakob 
Published: June 2021

AbstractDiabetic retinopathy (DR) is the most common microvascular complication in diabetes and may cause severe visual impairment. Until late stages of DR, treatment options are limited. The aim of the present review was to investigate whether changes of DR might be influenced by topical treatment with eye drops. This systematic review included both randomized and non‐randomized human clinical studies on the subject. A systematic search of PubMed Medline, Embase and Scopus databases yielded 710 studies. No inclusion criteria regarding classification of DR were defined. Reference lists as well as first authors were screened for the inclusion of additional studies. Potential bias of the randomized studies was assessed using the Cochrane Risk of Bias tool. Nineteen studies suitable for inclusion were identified. Seven studies were randomized trials. These examined 11 different pharmacological groups of drugs in DR. A favourable effect of corticosteroid eye drops in diabetic macular oedema (DMO) was reported in four studies, and another study reported a positive trend. Eye drops with non‐steroidal anti‐inflammatory drugs were also reported to have a favourable effect in DMO, but not in non‐center involving DMO. Application of neuroprotective agents was found effective in patients with pre‐existing neurodegeneration in three studies. The remaining studies of DMO and DR were heterogeneous in both designs and results. Studies on treatment of DR with topical eye drops vary with regards to patient population, interventional drugs, study design, and outcome measures. Treatment of DR with eye drops was found effective in the aforementioned cases, but there is still a need for further investigations of long‐term, randomized controlled trials in any of the reported pharmacological group.
Methyl CpG binding protein 2 promotes colorectal cancer metastasis by regulating N6‐methyladenosine methylation through methyltransferase‐like 14
Authors: Wang Shuo , Gan Meifu , Chen Chaoyi , Zhang Yi , Kong Jianlu , Zhang Honghe , Lai Maode 
Published: June 2021

AbstractRNA N6‐methyladenosine (m6A) is an emerging regulatory mechanism for tumor progression in several types of cancer. However, the underlying regulation mechanisms of m6A methylation in colorectal cancer (CRC) remain unknown. Although the oncogenic function of methyl CpG binding protein 2 (MeCP2) has been reported, it is still unclear whether MeCP2 could alter RNA m6A methylation state. Here, we systematically identified MeCP2 as a prometastasis gene to regulate m6A methylation in CRC. Interestingly, MeCP2 could bind to methyltransferase‐like 14 (METTL14) to coregulate tumor suppressor Kruppel‐like factor 4 (KLF4) expression through changing m6A methylation modification. Furthermore, insulin‐like growth factor 2 mRNA‐binding protein 2 recognized the unique modified m6A methylation sites to enhance KLF4 mRNA stability. Taken together, these findings highlight the novel function of MeCP2 for regulating m6A methylation and reveal the underlying molecular mechanism for the interaction between MeCP2 and METTL14, which offers a better understanding of CRC progression and metastasis.
An EU budget of states and citizens
Authors: Crowe Richard 
Published: June 2021

AbstractIn a European Union of states and citizens, the budget of the Union continues to function principally as a budget between states. Despite various attempts over the decades to introduce reforms aimed at strengthening the connection with citizens, the budgetary system has shown itself to be resistant to change. However, the landmark agreements of 2020 on the new multiannual financial framework (MFF) 2021–2027, own resources and recovery plan (Next Generation EU [NGEU]) packages potentially open up new possibilities to move beyond the logic of juste retour and promote a more positive vision of European budgetary integration, founded on solidarity between states and citizens and coordinated action at all levels of governance. Building on the developments of 2020, this contribution assesses how the Conference on the Future of Europe might explore options to further strengthen the profile of the Union budget as a ‘budget of citizens’, as well as a ‘budget of states’.
Overcoming the growth–infectivity trade‐off in a bacteriophage slows bacterial resistance evolution
Authors: Zhang Quan‐Guo , Chu Xiao‐Lin , Buckling Angus 
Published: June 2021

AbstractThe use of lytic bacteriophages for treating harmful bacteria (phage therapy) is faced with the challenge of bacterial resistance evolution. Phage strains with certain traits, for example, rapid growth and relatively broad infectivity ranges, may enjoy an advantage in slowing bacterial resistance evolution. Here, we show the possibility for laboratory selection programs (“evolutionary training”) to yield phage genotypes with both high growth rate and broad infectivity, traits between which a trade‐off has been assumed. We worked with a lytic phage that infects the bacterium Pseudomonas fluorescens and adopted three types of training strategies: evolution on susceptible bacteria, coevolution with bacteria, and rotation between evolution and coevolution phases. Overall, there was a trade‐off between growth rate and infectivity range in the evolved phage isolates, including those from the rotation training programs. A small number of phages had both high growth rate and broad infectivity, and those trade‐off‐overcoming phages could slow or even completely prevent resistance evolution in initially susceptible bacterial populations. Our findings show the promise of well‐designed evolutionary training programs, in particular an evolution/coevolution rotation selection regime, for obtaining therapeutically useful phage materials.
Dendritic cell Flt3 – regulation, roles and repercussions for immunotherapy
Authors: Wilson Kayla R , Villadangos Jose A , Mintern Justine D 
Published: June 2021

AbstractDendritic cells (DCs) are essential for initiating immune responses. Depending on the environment, the type of DC and the way in which they interact with T cells, these immune responses can be beneficial or detrimental. DCs can be exploited as cellular vectors for vaccines against infection and cancer. The development and maintenance of DCs is dependent on the FMS‐like tyrosine kinase 3 (Flt3)/Flt3 ligand (Flt3L) signaling cascade. Flt3 is also one of the most commonly mutated genes in acute myeloid leukemia and as such represents an attractive drug target. In this review, Flt3 is discussed with a particular focus on DCs. We detail the lifecycle of Flt3, from transcription to degradation, and interrogate recent studies as to how this pathway can be manipulated for immunotherapy, vaccination and treatment of autoimmune disease.
Change of dental color and temperature through two bleaching agents boosted with light emitted by diodes
Authors: Álvarez‐Quiceno Daniela , Rojas‐Martínez Paola‐Andrea , Cruz‐González Alberto‐Carlos 
Published: June 2021

AbstractIntroductionThe use of light sources during the application of bleaching can reduce the time and improve the results, but at the same time this can increase the dental temperature. The objective of this study was to evaluate the performance of two bleaching agents and the increase in dental temperature with the use of light emitted by diodes (LED)‐unit.Materials and methodsForty third molars were obtained and randomized: the whiteness without lamp (WHN) and Pola office without lamp (PON) groups, two bleaching systems based on 35% hydrogen peroxide were used, according to manufacturer specifications. For the whiteness with lamp (WHL) and Pola office with lamp (POL) groups the same bleaching agents were light boosted. A spectrophotometer and ∆WID equation was used to record and analyzed teeth color. An infrared thermometer was used to record the external and internal temperature. A ∆T was obtained by the difference of the temperature of the groups with and without LED (WHN‐WHL and PON‐POL). For statistical analysis Kruskal‐Wallis test and Anova test were performed.ResultsThe WHN, PON, WHL, and POL groups reported ∆WID values of 4.88 ± 1.08, 9.26 ± 3.27, 5.70 ± 2.48, 12.08 ± 5.44, respectively. The dates of internal temperature were 1.01 and 1.07°C, and for external temperature were 1.61 and 1.15°C respectively.ConclusionsWith the limitations of this study, both bleaching agents reported a significant increase in ∆WID with and without association of light. Significant temperature increases were also observed. The highest average temperature increase was approximately 1.61°C.Clinical significanceBleaching agents boosted with LED may improve the results of bleaching, but it is not essential to obtain good results.
Lipoprotein(a) and SARS‐CoV‐2 infections: Susceptibility to infections, ischemic heart disease and thromboembolic events
Authors: Di Maio Silvia , Lamina Claudia , Coassin Stefan , Forer Lukas , Würzner Reinhard , Schönherr Sebastian , Kronenberg Florian 
Published: June 2021

AbstractBackgroundComorbidities including ischemic heart disease (IHD) worsen outcomes after SARS‐CoV‐2 infections. High lipoprotein(a) [Lp(a)] concentrations are a strong risk factor for IHD and possibly for thromboembolic events. We therefore evaluated whether SARS‐CoV‐2 infections modify the risk of high Lp(a) concentrations for IHD or thromboembolic events during the first 8.5 months follow‐up of the pandemic.MethodCohort study using data from the UK Biobank during the SARS‐CoV‐2 pandemic. Baseline Lp(a) was compared between SARS‐CoV‐2 positive patients and the population controls.ResultsSARS‐CoV‐2 positive patients had Lp(a) concentrations similar to the population controls. The risk for IHD increased with higher Lp(a) concentrations in both, the population controls (n= 435,104) and SARS‐CoV‐2 positive patients (n= 6937). The causality of the findings was supported by a genetic risk score for Lp(a). A SARS‐CoV‐2 infection modified the association with a steeper increase in risk for infected patients (interactionp‐value = 0.03). Although SARS‐CoV‐2 positive patients had a five‐times higher frequency of thromboembolic events compared to the population controls (1.53% vs. 0.31%), the risk was not influenced by Lp(a).ConclusionsSARS‐CoV‐2 infections enforce the association between high Lp(a) and IHD but the risk for thromboembolic events is not influenced by Lp(a).
Low Health Literacy Is Associated With Energy‐Balance‐Related Behaviors, Quality of Life, and BMI Among Rural Appalachian Middle School Students: A Cross‐Sectional Study
Authors: Reid Annie L. , Porter Kathleen J. , You Wen , Kirkpatrick Brittany M. , Yuhas Maryam , Vaught Shannon S. , Zoellner Jamie M. 
Published: June 2021

ABSTRACTBACKGROUNDMany studies document associations between low health literacy (HL) and poor health behaviors and outcomes. Yet, HL is understudied among adolescents, particularly from underserved, rural communities. We targeted rural adolescents in this cross‐sectional study and explored relationships between HL and (1) energy‐balance‐related health behaviors and (2) body mass index (BMI) and quality of life (QOL).METHODSSurveys were administered to 7th graders across 8 middle schools in rural Appalachia. HL was assessed using the Newest Vital Sign. Energy‐balance‐related behaviors and QOL were assessed using validated instruments. Height and weight were objectively measured. Analyses were conducted using the Hodges‐Lehmann nonparametric median difference test.RESULTSOf the 854 adolescent students (mean age = 12; 55% female), 47% had limited HL. Relative to students with higher HL, students with lower HL reported significantly lower frequency of health‐promoting behaviors (water, fruit and vegetable intake, physical activity, sleep), higher frequency of risky health behaviors (sugar‐sweetened beverages, junk food, screen time), and had higher BMI percentiles and lower QOL (all p < .05).CONCLUSIONSLow HL is associated with energy‐balance‐related behaviors, BMI, and QOL among rural, Appalachian adolescents. Findings underscore the relevance of HL among rural middle school students and highlight implications for school health.
Whole‐genome sequencing reveals asymmetric introgression between two sister species of cold‐resistant leaf beetles
Authors: Lukicheva Svitlana , Mardulyn Patrick 
Published: June 2021

AbstractA large number of genetic variation studies have identified cases of mitochondrial genome introgression in animals, indicating that reproductive barriers among closely related species are often permeable. Because of its sheer size, the impact of hybridization on the evolution of the nuclear genome is more difficult to apprehend. Only a few studies have explored it recently thanks to recent progress in DNA sequencing and genome assembly. Here, we analysed whole‐genome sequence variation among multiple individuals of two sister species of leaf beetles inside their hybrid zone, in which asymmetric mitochondrial genome introgression had previously been established. We used a machine learning approach based on computer simulations for training to identify regions of the nuclear genome that were introgressed. We inferred asymmetric introgression of ≈2% of the genome, in the same direction that was observed for the mitochondrial genome. Because a previous study based on a reduced‐representation sequencing approach was not able to detect this introgression, we conclude that whole‐genome sequencing is necessary when the fraction of the introgressed genome is small. We also analysed the whole‐genome sequence of a hybrid individual, demonstrating that hybrids have the capacity to backcross with the species for which virtually no introgression was observed. Our data suggest that one species has recently invaded the range of the other and/or some alleles that where transferred from the invaded into the invading species could be under positive selection and may have favoured the adaptation of the invading species to the Alpine environment.
DNA damage checkpoint activation affects peptidoglycan synthesis and late divisome components in Bacillus subtilis
Authors: Masser Emily A. , Burby Peter E. , Hawkins Wayne D. , Gustafson Brooke R. , Lenhart Justin S. , Simmons Lyle A. 
Published: June 2021

AbstractDuring normal DNA replication, all cells encounter damage to their genetic material. As a result, organisms have developed response pathways that provide time for the cell to complete DNA repair before cell division occurs. In Bacillus subtilis, it is well established that the SOS‐induced cell division inhibitor YneA blocks cell division after genotoxic stress; however, it remains unclear how YneA enforces the checkpoint. Here, we identify mutations that disrupt YneA activity and mutations that are refractory to the YneA‐induced checkpoint. We find that YneA C‐terminal truncation mutants and point mutants in or near the LysM peptidoglycan binding domain render YneA incapable of checkpoint enforcement. In addition, we develop a genetic method which isolated mutations in the ftsW gene that completely bypassed checkpoint enforcement while also finding that YneA interacts with late divisome components FtsL, Pbp2b, and Pbp1. Characterization of an FtsW variant resulted in considerably shorter cells during the DNA damage response indicative of hyperactive initiation of cell division and bypass of the YneA‐enforced DNA damage checkpoint. With our results, we present a model where YneA inhibits septal cell wall synthesis by binding peptidoglycan and interfering with interaction between late arriving divisome components causing DNA damage checkpoint activation.
Bacterial lysate treatment in allergic disease: A systematic review and meta‐analysis
Authors: Li Chengmei , Zhou Hua , Zhang Wei , Che Datian 
Published: June 2021

AbstractObjectiveThe aim of this review was to assess the efficacy of bacterial lysate treatment in patients with allergic disease.MethodRandomized controlled trials (RCTs) of bacterial lysate therapy for patients with allergic diseases (asthma, atopic dermatitis, and allergic rhinitis) were searched using PubMed, EMBASE, Cochrane, China National Knowledge Infrastructure, Chinese Biomedical literature, and Wanfang databases up to March 2020. Based on the guidelines of the Cochrane collaboration, risk of bias was assessed.ResultsThis meta‐analysis based on 19 studies comparing bacterial lysate‐treated patients with a control group showed a 24% (RR: 1.24, 95% CI [1.19, 1.30]) increase in improvement of allergy symptom control. In addition, the improvement of asthma symptom control was 22% (RR: 1.22, 95% CI [1.14, 1.26]) higher in the bacterial lysate treatment group. Moreover, the levels of immunoglobulin (IgA and IgG), T lymphocyte subtype (CD3+, CD4+, CD4+/CD8+, Th1), and cytokines (IFN‐γ, IL‐2, and IL‐12) were increased in the treated group compared with controls. There was no significant difference in adverse event rate between the two groups.ConclusionTreatment with bacterial lysate improves symptom control in patients with allergic diseases on the basis of routine therapy. No adverse risk was found in this meta‐analysis.
Calmodulin‐binding transcription activator AtSR1/CAMTA3 fine‐tunes plant immune response by transcriptional regulation of the salicylate receptor NPR1
Authors: Yuan Peiguo , Tanaka Kiwamu , Poovaiah B. W. 
Published: June 2021

AbstractCalcium (Ca2+) signalling regulates salicylic acid (SA)‐mediated immune response through calmodulin‐meditated transcriptional activators, AtSRs/CAMTAs, but its mechanism is not fully understood. Here, we report an AtSR1/CAMTA3‐mediated regulatory mechanism involving the expression of the SA receptor, NPR1. Results indicate that the transcriptional expression of NPR1 was regulated by AtSR1 binding to a CGCG box in the NPR1 promotor. The atsr1 mutant exhibited resistance to the virulent strain of Pseudomonas syringae pv. tomato (Pst), however, was susceptible to an avirulent Pst strain carrying avrRpt2, due to the failure of the induction of hypersensitive responses. These resistant/susceptible phenotypes in the atsr1 mutant were reversed in the npr1 mutant background, suggesting that AtSR1 regulates NPR1 as a downstream target during plant immune response. The virulent Pst strain triggered a transient elevation in intracellular Ca2+ concentration, whereas the avirulent Pst strain triggered a prolonged change. The distinct Ca2+ signatures were decoded into the regulation of NPR1 expression through AtSR1's IQ motif binding with Ca2+‐free‐CaM2, while AtSR1's calmodulin‐binding domain with Ca2+‐bound‐CaM2. These observations reveal a role for AtSR1 as a Ca2+‐mediated transcription regulator in controlling the NPR1‐mediated plant immune response.
Mosaic de novo SNRPN gene variant associated with Prader-Willi syndrome
Authors: Huang Yue , Grand Katheryn , Kimonis Virginia , Butler Merlin G , Jain Suparna , Huang Alden Yen-Wen , Martinez-Agosto Julian A , Nelson Stanley F , Sanchez-Lara Pedro A 
Published: June 2021

BackgroundPrader-Willi syndrome (PWS) is an imprinting disorder caused by the absence of paternal expressed genes in the Prader-Willi critical region (PWCR) on chromosome 15q11.2-q13. Three molecular mechanisms have been known to cause PWS, including a deletion in the PWCR, uniparental disomy 15 and imprinting defects.ResultsWe report the first case of PWS associated with a single-nucleotide SNRPN variant in a 10-year-old girl presenting with clinical features consistent with PWS, including infantile hypotonia and feeding difficulty, developmental delay with cognitive impairment, excessive eating with central obesity, sleep disturbances, skin picking and related behaviour issues. Whole-exome sequencing revealed a de novo mosaic nonsense variant of the SNRPN gene (c.73C>T, p.R25X) in 10% of DNA isolated from buccal cells and 19% of DNA from patient-derived lymphoblast cells. DNA methylation study did not detect an abnormal methylation pattern in the SNRPN locus. Parental origin studies showed a paternal source of an intronic single-nucleotide polymorphism within the locus in proximity to the SNRPN variant.ConclusionsThis is the first report that provides evidence of a de novo point mutation of paternal origin in SNRPN as a new disease-causing mechanism for PWS. This finding suggests that gene sequencing should be considered as part of the diagnostic workup in patients with clinical suspicion of PWS.