Hejlesencrane0787

6%) did not provide access to complete and unmodified data sets, all 229/232 (98.7%) failed to provide step-by-step analysis scripts and 228/232 (98.3%) did not provide access to complete study protocols.

The presentation of studies published in cardiology journals would make reproducing study outcomes challenging, at best. Solutions to increase the reproducibility and transparency of publications in cardiology journals is needed. Moving forward, addressing inadequate sharing of materials, raw data and key methodological details might help to better the landscape of reproducible research within the field.

The presentation of studies published in cardiology journals would make reproducing study outcomes challenging, at best. Solutions to increase the reproducibility and transparency of publications in cardiology journals is needed. Moving forward, addressing inadequate sharing of materials, raw data and key methodological details might help to better the landscape of reproducible research within the field.

In this report, we determine the cumulative incidence of symptomatic cardiac ischaemia and its risk factors among European 5-year childhood cancer survivors (CCS) participating in the PanCareSurFup study.

Eight data providers (France, Hungary, Italy (two cohorts), the Netherlands, Slovenia, Switzerland and the UK) participating in PanCareSurFup ascertained and validated symptomatic cardiac events among their 36 205 eligible CCS. Data on symptomatic cardiac ischaemia were graded according to the Criteria for Adverse Events V.3.0 (grade 3-5). We calculated cumulative incidences, both overall and for different subgroups based on treatment and malignancy, and used multivariable Cox regression to analyse risk factors.

Overall, 302 out of the 36 205 CCS developed symptomatic cardiac ischaemia during follow-up (median follow-up time after primary cancer diagnosis 23.0 years). KY 12420 cell line The cumulative incidence by age 60 was 5.4% (95% CI 4.6% to 6.2%). Men (7.1% (95% CI 5.8 to 8.4)) had higher rates than women (3.4% (95% CI 2.4 to 4.4)) (p<0.0001). Of importance is that a significant number of patients (41/302) were affected as teens or young adults (14-30 years). Treatment with radiotherapy/chemotherapy conferred twofold risk (95% CI 1.5 to 3.0) and cases in these patients appeared earlier than in CCS without treatment/surgery only (15% vs 3% prior to age 30 years, respectively (p=0.04)).

In this very large European childhood cancer cohort, we found that by age 60 years, 1 in 18 CCS will develop a severe, life-threatening or fatal cardiac ischaemia, especially in lymphoma survivors and CCS treated with radiotherapy and chemotherapy increases the risk significantly.

In this very large European childhood cancer cohort, we found that by age 60 years, 1 in 18 CCS will develop a severe, life-threatening or fatal cardiac ischaemia, especially in lymphoma survivors and CCS treated with radiotherapy and chemotherapy increases the risk significantly.

Procalcitonin expression is thought to be stimulated by bacteria and suppressed by viruses via interferon signalling. Consequently, during respiratory viral illness, clinicians often interpret elevated procalcitonin as evidence of bacterial coinfection, prompting antibiotic administration. We sought to evaluate the validity of this practice and the underlying assumption that viral infection inhibits procalcitonin synthesis.

We conducted a retrospective cohort study of patients hospitalised with pure viral infection (n=2075) versus bacterial coinfection (n=179). The ability of procalcitonin to distinguish these groups was assessed. In addition, procalcitonin and interferon gene expression were evaluated in murine and cellular models of influenza infection.

Patients with bacterial coinfection had higher procalcitonin than those with pure viral infection, but also more severe disease and higher mortality (p<0.001). After matching for severity, the specificity of procalcitonin for bacterial coinfection dty and is not suppressed by interferon signalling, in contrast to prior models of procalcitonin regulation. Applied clinically, our data suggest that procalcitonin represents a better indicator of disease severity than bacterial coinfection during viral respiratory infection.

To validate the use of a brief suicide risk screening tool, the Ask Suicide-Screening Questions (ASQ) instrument, in pediatric inpatient medical and surgical settings.

Pediatric patients (10-21 years) hospitalized on inpatient medical and surgical units were recruited through convenience sampling for participation in a cross-sectional instrument validation study. The Suicidal Ideation Questionnaire was used as a standard criterion to validate the ASQ. Patient opinions about screening and parent consent to enroll in a suicide risk screening study were assessed to determine the feasibility of administering the ASQ in this venue.

A total of 600 pediatric medical inpatients were screened. Compared with the gold standard, the ASQ had strong psychometric properties, with a sensitivity of 96.67% (95% confidence interval [CI] 82.78 to 99.92), a specificity of 91.05% (95% CI 88.40 to 93.27), a negative predictive value of 99.81% (95% CI 98.93 to 99.99), and an area under curve of 0.94 (95% CI 0.90 to 0.97). Only 3 participants (0.5%) had acute positive screen results on the ASQ, endorsing current suicidal ideation, whereas 77 participants (12.8%) screened nonacute positive, and 48 participants (8.0%) reported a past suicide attempt.

The brief 4-item ASQ is a valid tool to detect elevated suicide risk in pediatric medical and surgical inpatients. Our findings also reveal that screening is feasible in terms of detection of suicidal thoughts and behaviors and is acceptable to parents and patients.

The brief 4-item ASQ is a valid tool to detect elevated suicide risk in pediatric medical and surgical inpatients. Our findings also reveal that screening is feasible in terms of detection of suicidal thoughts and behaviors and is acceptable to parents and patients.The recent outbreak of COVID-19 has emerged as a major global health concern. Although susceptible to infection, recent evidence indicates mostly asymptomatic or mild presentation of the disease in infants, children, and adolescents. Similar observations were made for acute respiratory infections caused by other coronaviruses (severe acute respiratory syndrome and Middle East respiratory syndrome). These observations suggest that the immune system behaves differently in children than adults. Recent developments in the field demonstrated fundamental differences in the neonatal immune system as compared with adults, whereby infants respond to microorganisms through biased immune tolerance rather than resistance strategies. Similarly, more frequent/recent vaccinations in children and younger populations may result in trained immunity. Therefore, the physiological abundance of certain immunosuppressive cells, a tightly regulated immune system, and/or exposure to attenuated vaccines may enhance trained immunity to limit excessive immune reaction to COVID-19 in the young.The innate immune system is the first line of defense against bacterial and viral infections. The recognition of pathogen-associated molecular patterns by the RIG-I-like receptors, TLRs, and cGAS leads to the induction of IFN-I by activating the transcription factor IRF-3. Although the mechanism of IRF-3 activation has been extensively studied, the structural basis of IRF-3 activation upon phosphorylation is not fully understood. In this study, we determined the crystal structures of phosphorylated human and mouse IRF-3 bound to CREB-binding protein (CBP), which reveal that phosphorylated IRF-3 forms a dimer via pSer386 (pSer379 in mouse IRF-3) and a downstream pLxIS motif. Size-exclusion chromatography and cell-based studies show that mutations of key residues interacting with pSer386 severely impair IRF-3 activation and IFN-β induction. link2 By contrast, phosphorylation of Ser396 within the pLxIS motif of human IRF-3 only plays a moderate role in IRF-3 activation. The mouse IRF-3/CBP complex structure reveals that the mechanism of mouse IRF-3 activation is similar but distinct from human IRF-3. These structural and functional studies reveal the detailed mechanism of IRF-3 activation upon phosphorylation.The coronavirus pandemic has presented a new set of challenges for the frontline National Health Service staff. It is not only the long working hours but also the uncertainty and increase in patient mortality that has affected mental health and staff well-being. Hospitals all around the country have rightly responded with various well-being initiatives to help their staff such as wobble rooms and developing online resources. Our vision was to set up a safe space for staff away from clinical noise to enable and encourage mindfulness and psychological resilience through a calm and serene environment. We used the continuous quality improvement methodology and administered an initial needs assessment survey to see if our trust staff will be interested in having such a space. Within our team, we managed to secure a place, and used donations to hospital charity and set up a space within a week. link3 Since opening the hub, we have had excellent feedback from various staff groups. Immediate feedback was obtained using emoji stickers asking for feelings before and after visit. A mood board was put up allowing anonymous expression of feelings. Delayed feedback was requested using a repeat survey. We believe that while there is a lot of talk about well-being and an increasing number of resources being offered electronically, the need for a neat and quiet space cannot be overlooked. We collect feedback on a weekly basis and adapt the space to meet the needs of staff. Long-term impact of such spaces will be reassessed at a later stage.Resistance to therapeutic drugs is a major challenge in the treatment of cancers, including breast cancer. Long noncoding RNAs (lncRNA) are known to have diverse physiologic and pathophysiologic functions, including in cancer. In searching for lncRNA responsible for cancer drug resistance, we identified an intergenic lncRNA ERINA (estrogen inducible lncRNA) as a novel lncRNA highly expressed in multiple cancer types, especially in estrogen receptor-positive (ER+) breast cancers. Expression of ERINA was inversely correlated with survival of patients with ER+ breast cancer and sensitivity to CDK inhibitor in breast cancer cell lines. Functional characterization established ERINA as an oncogenic lncRNA, as knockdown of ERINA in breast cancer cells inhibited cell-cycle progression and tumor cell proliferation in vitro and xenograft tumor growth in vivo. In contrast, overexpression of ERINA promoted cell growth and cell-cycle progression. ERINA promoted cell-cycle progression by interacting with the E2F transcription factor 1 (E2F1), which prevents the binding of E2F1 to the tumor suppressor retinoblastoma protein 1 (RB1). ERINA also functioned as an estrogen and ER-responsive gene, and an intronic ER-binding site was identified as an enhancer that mediates the transactivation of ERINA. In summary, ERINA is an estrogen-responsive oncogenic lncRNA that may serve as a novel biomarker and potential therapeutic target in breast cancer. SIGNIFICANCE These findings identify ERINA as an estrogen-responsive, oncogenic lncRNA, whose elevated expression may contribute to drug resistance and poor survival of patients with ER+ breast cancer.