bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated serum HbA1c level, rather than previous history of diabetes, predicts the disease severity and clinical outcomes of acute pancreatitis
Authors: Han Fei , Shi Xiao-lei , Pan Jia-jia , Wu Ke-yan , Zhu Qing-tian , Yuan Chen-chen , Xiao Wei-ming , Ding Yan-bing , Yu Xiao-ping , Jiao Xiu-ping , Hu Liang-hao , Lu Guo-tao , Li Wei-qin 
Published: February 2023

IntroductionThe aim of our study is to explore the value of serum glycosylated hemoglobin A1c (HbA1c) in disease severity and clinical outcomes of acute pancreatitis (AP).Research design and MethodsPatients with AP were included from January 2013 to December 2020, retrospectively, dividing into normal serum HbA1c level (N-HbA1c) group and high serum HbA1c level (H-HbA1c) group according to the criteria HbA1c <6.5%. We compared patient characteristics, biochemical parameters, disease severity, and clinical outcomes of patients with AP in two groups. Besides, we evaluated the efficacy of serum HbA1c to predict organ failure (OF) in AP patients by receiver operating curve (ROC).ResultsWe included 441 patients with AP, including 247 patients in N-HbA1c group and 194 patients in H-HbA1c group. Serum HbA1c level was positively correlated with Atlanta classification, systemic inflammatory response syndrome, local complication, and OF (all p<0.05). Ranson, BISAP (bedside index of severity in acute pancreatitis), and CT severity index scores in patients with H-HbA1c were markedly higher than those in patients with N-HbA1c (all p<0.01). ROC showed that the best critical point for predicting the development of OF in AP with serum HbA1c is 7.05% (area under the ROC curve=0.79). Logistic regression analysis showed H-HbA1c was the independent risk factor for the development of OF in AP. Interestingly, in patients with presence history of diabetes and HbA1c <6.5%, the severity of AP was significantly lower than that in H-HbA1c group. Besides, there was no significant difference between with and without history of diabetes in N-HbA1c group.ConclusionsGenerally known, diabetes is closely related to the development of AP, and strict control of blood glucose can improve the related complications. Thus, the level of glycemic control before the onset of AP (HbA1c as an indicator) is the key to poor prognosis of AP, rather than basic history of diabetes. Elevated serum HbA1c level can become the potential indicator for predicting the disease severity of AP.
Digitally deployed, GP remote consultation video intervention that aims to reduce opioid prescribing in primary care: protocol for a mixed-methods evaluation
Authors: Fu Yu , Allen Ben , Batterham Alan M , Price Christopher , Jones Niki , Martin Denis , Hex Nick , Maule Ewan , Finch Tracy , Newton Julia L , Ryan Cormac G 
Published: February 2023

IntroductionOpioid prescribing rates are disproportionately high in the North of England. In addition to patients’ complex health needs, clinician prescribing behaviour is also a key driver. Although strategies have been initiated to reduce opioid prescribing nationally, the COVID-19 pandemic has interrupted service provision and created challenges for the system and health professionals to tackle this complex issue. A pilot intervention using smartphone video messaging has been developed to remotely explain the rationale for opioid reduction and facilitate self-initiation of support. The aim of this study is to evaluate the potential benefits, risks and economic consequences of ‘at scale’ implementation.Methods and analysisThis will be a mixed-methods study comprising a quasi-experimental non-randomised before-and-after study and qualitative interviews. The intervention arm will comprise 50 General Practitioner (GP) Practices using System 1 (a clinical computer system hosting the intervention) who will deliver the video to their patients via text message. The control arm will comprise 50 practices using EMIS (a different computer system) who will continue usual care. Monthly practice level prescribing and consultation data will be observed for 6 months postintervention. A general linear model will be used to estimate the association between the exposure and the main outcome (opioid prescribing; average daily quantity (ADQ)/1000 specific therapeutic group age-sex related prescribing unit). Semi-structured interviews will be undertaken remotely with purposively selected participants including patients who received the video, and health professionals involved in sending out the videos and providing additional support. Interviews will be audio recorded, transcribed and analysed thematically.Ethics and disseminationEthics approval has been granted by the NHS Health Research Authority Research Ethics Committee (22/PR/0296). Findings will be disseminated to the participating sites, participants, and commissioners, and in peer-reviewed journals and academic conferences.Trial registration numberNCT05276089.
Exploring nurses’ experiences of a tailored intervention to increase MMR vaccine acceptance in a Somali community in Stockholm, Sweden: a qualitative interview study
Authors: Appelqvist Emma , Jama Asha , Kulane Asli , Roth Adam , Lindstrand Ann , Godoy-Ramirez Karina 
Published: February 2023

ObjectivesTo explore nurses’ experiences of a tailored intervention that supported them with knowledge and tools to use during encounters and dialogue with parents with low vaccine acceptance.DesignA qualitative study with in-depth interviews conducted in 2017. Data were analysed using thematic analysis.SettingThis study was part of a multicomponent intervention targeting Somali parents and the nurses at child health centres in the Rinkeby and Tensta neighbourhoods of Stockholm. An area with documented low measles, mumps and rubella (MMR) vaccination coverage. Previous research has revealed that Somali parents in the community delayed MMR vaccination due to fear of autism despite lack of scientific evidence. The interventions were implemented in 2015–2017.ParticipantsEleven nurses employed at the child health centres involved in the intervention participated in interviews. The tailored intervention targeting nurses included a series of seminars, a narrative film and an information card with key messages for distribution to parents.ResultsThe qualitative analysis revealed an overarching theme: perception of improved communication with parents. Two underlying themes were identified: (1) feeling more confident to address parents’ MMR vaccine concerns and (2) diverse tools as useful support to dispel myth and reduce language barriers.ConclusionFrom the nurses’ perspective, the tailored intervention was useful to improve communication with parents having vaccine concerns. Nurses have a crucial role in vaccine uptake and acceptance. Interventions aiming to strengthen their communication with parents are therefore essential, especially in areas with lower vaccine acceptance.
Effectiveness of physical and mental health interventions for young people with heart conditions: protocol for a systematic review and meta-analysis
Authors: Capobianco Lora , Adewusi Joy , Cooper Beth , Belcher Andrew , Wells Adrian 
Published: February 2023

IntroductionCardiovascular disease is among the most common of non-communicable diseases, affecting 13.9 million children and young people (CYP) globally. Survival rates for CYP with heart conditions are rising, however, support for adjusting to life with a heart condition is lacking, as such it is unsurprising that one in three suffer from anxiety, depression or adjustment disorder. The proposed review aims to identify and assess the effectiveness of physical and mental health interventions across physical and mental health outcomes in young people with cardiac conditions using narrative synthesis and meta-analysis if appropriate.Methods and analysisEmbase, Medline, PubMed, PsycINFO, Cochrane Databases, Web of Science and reference lists of relevant publications will be searched from 1980 to June 2022 for articles published in English or Italian. Screening, data extraction, intervention coding and risk of bias will be performed by two independent reviewers using an extraction checklist. Intervention content and features will be identified and reported using the Template for Intervention Description and Replication checklist. A narrative review of the included studies will be conducted. If possible and appropriate, a random-effects model meta-analysis will be conducted to calculate the pooled within-group and between-group effect sizes for the primary outcome measures. If sufficient data are available, a subgroup meta-analysis will investigate whether specific intervention types are associated with different levels of intervention effectiveness.Ethics and disseminationThis systematic review does not directly involve the use of human beings, therefore, there is no requirement for ethical approval. Findings will be disseminated through peer-reviewed publication and in various media, such as conferences, congresses or symposia.PROSPERO registration numberCRD42022330582.
Scoping review protocol on the impact of antimicrobial resistance on cancer management and outcomes
Authors: Bratti Vanessa F , Wilson Brooke E , Fazelzad Rouhi , Pabani Aliyah , Zurn Shalini J , Johnson Sonali , Sung Lillian , Rodin Danielle 
Published: February 2023

IntroductionAntimicrobial resistance (AMR) is a growing global public health concern and is becoming a significant challenge in the management of patients with cancer. Due to the immunosuppressive nature of cancer treatment, infection is a common complication and the necessary high usage of antibiotics increases the risk of AMR. Failure to adequately prevent and treat infection in patients with cancer as a result of AMR can increase the morbidity and mortality of the disease. The objective of this scoping review is to understand the relationship between AMR and cancer in order to develop effective antimicrobial stewardship in this patient population and minimise the detrimental effects of AMR on cancer outcomes.Methods and analysisThis scoping review will follow the Arksey and O’Malley methodology framework. An exploratory review of the literature on antibiotic resistance in cancer care will help to define the research questions (stage 1). A broad range of electronic databases (MEDLINE ALL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Embase) and search terms will be used to retrieve relevant articles published between 2000 and 2021 (stage 2). Studies will be systematically selected based on the eligibility criteria by two independent reviewers (stage 3). The titles and abstracts will be appraised to determine whether articles meet the eligibility criteria. This will be followed by screening of the full texts and only relevant publications will be retrieved. Data will then be extracted, collated and charted (stage 4); and the summary of aggregated results will be presented (stage 5).Ethics and disseminationAs this scoping review will collect and synthesise data from publicly available sources, no ethics review is required. When data collection and summarisation is completed, results will be disseminated through peer-reviewed publication and the key findings of the review will be presented at relevant conferences.
Mediating role of psychological distress and domestic violence in the association of fear of COVID-19 with marital satisfaction and sexual quality of life among women of reproductive age: An Iranian cross-sectional study
Authors: Alimoradi Zainab , Bahrami Nasim , Khodaparast Samaneh , Griffiths Mark D , Pakpour Amir H 
Published: February 2023

ObjectivesThis study aimed to determine the mediating role of psychological distress and domestic violence in the association of fear of COVID-19 with marital satisfaction and sexual quality of life (QoL) among Iranian women of reproductive age.MethodsA cross-sectional study comprising 324 married women was conducted. Online convenience sampling was used to collect data. SPSS PROCESS macro was used for the mediation analysis. The direct and indirect effects of the fear of COVID-19 on sexual QoL and marital satisfaction were estimated comprising a 95% CI using 5000 bootstrap samples. Pairwise comparisons between the mediators were calculated by Hayes’ macros.ResultsA positive/negative or suspected history of COVID-19 infection had marginally significant relationship with marital satisfaction (p=0.049). The total effect of fear of COVID-19 on sexual QoL was significant (b=−1.31, SE=0.20, p<0.001). Fear of COVID-19 had no significant direct effect on sexual QoL (b=−0.22, SE=0.19, p=0.24) but it had an indirect effect on sexual QoL via mediation of psychological distress (b=−0.34, SE=0.09, 95% CI: −0.53 to −0.19) and domestic violence (b=−0.75, SE=0.18, 95% CI: −1.12 to −0.40). The total effect of fear of COVID-19 on marital satisfaction was significant (b=−1.91, SE=0.32, p<0.001). Fear of COVID-19 had no significant direct effect (b=0.20, SE=0.25, p=0.42) on marital satisfaction but it had an indirect effect on marital satisfaction via mediation of psychological distress (b=−0.59, SE=0.13, 95% CI: −0.86 to −0.36) and domestic violence (b=−1.51, SE=0.29, 95% CI: −2.08 to −0.92).ConclusionThe fear of COVID-19 during the pandemic indirectly decreased women’s marital satisfaction and sexual QoL via increased psychological distress and domestic violence. Consequently, in critical situations such as the COVID-19 pandemic, improving couples’ psychological health and reducing domestic violence are likely to improve women’s sexual QoL and marital satisfaction.
Spatial analysis and factors associated with transcatheter aortic valve implantation in Portugal: a retrospective analysis from 2015 to 2017
Authors: Avelar Fernando Genovez , Emmerick Isabel , Alves Joana 
Published: February 2023

ObjectivesTo identify the factors associated with transcatheter aortic valve implantation (TAVI) use of TAVI in inpatients with aortic stenosis (AS) in Portugal and its geographical distribution.MethodsA quantitative, observational and retrospective study using the Portuguese National Health Service inpatient discharge database from 2015 to 2017. Surgical aortic valve replacement (SAVR) and TAVI procedures were selected using the International Classification of Diseases. First, we mapped the yearly age-standardised rate for each procedure using QGIS. Then, we performed χ2tests, independent t-tests and logistic regressions to study the factors associated with TAVI use.ResultsFrom 2015 to 2017, 8398 hospitalisations were selected, 88.5% SAVR and 11.5% TAVI. From 2015 to 2017, SAVR use increased in the Northern region and decreased in the Lisbon region, while the opposite was observed for TAVI. TAVI was performed among the most complex (p<0.001) and older patients (the mean (SD) age for SAVR was 70 (±11) years old and 81 (±7) years old for TAVI, p<0.001). The results for the logistic regressions showed that, more recent hospitalisations, being older, living in the Lisbon region and having a higher Charlson Comorbidity Index was associated with an increased likelihood of undergoing TAVI (p<0.001).ConclusionsTAVI increased over the years. TAVI is more often performed in more severe patients as an alternative to SAVR with similar discharge outcomes. These results suggest the existence of geographic disparities in the availability and access to healthcare services and technologies.
Intratumoral IFN-γ or topical TLR7 agonist promotes infiltration of melanoma metastases by T lymphocytes expanded in the blood after cancer vaccine
Authors: Tran Christine A , Lynch Kevin T , Meneveau Max O , Katyal Priya , Olson Walter C , Slingluff, Craig L 
Published: February 2023

BackgroundImmune-mediated melanoma regression relies on melanoma-reactive T cells infiltrating tumor. Cancer vaccines increase circulating melanoma-reactive T cells, but little is known about vaccine-induced circulating lymphocytes (viCLs) homing to tumor or whether interventions are needed to enhance infiltration. We hypothesized that viCLs infiltrate melanoma metastases, and intratumoral interferon (IFN)-γ or Toll-like receptor 7 (TLR7) agonism enhances infiltration.MethodsPatients on two clinical trials (Mel51 (NCT00977145), Mel53 (NCT01264731)) received vaccines containing 12 class I major histocompatibility complex-restricted melanoma peptides (12MP). In Mel51, tumor was injected with IFN-γ on day 22, and biopsied on days 1, 22, and 24. In Mel53, dermal metastases were treated with topical imiquimod, a TLR7 agonist, for 12 weeks, and biopsied on days 1, 22, and 43. For patients with circulating T-cell responses to 12MP by IFN-γ ELISpot assays, DNA was extracted from peripheral blood mononuclear cells (PBMCs) pre-vaccination and at peak T-cell response, and from tumor biopsies, which underwent T-cell receptor sequencing. This enabled identification of clonotypes induced in PBMCs post-vaccination (viCLs) and present in tumor post-vaccination, but not pre-vaccination.ResultsSix patients with T-cell responses post-vaccination (Mel51 n = 4, Mel53 n = 2) were evaluated for viCLs and vaccine-induced tumor infiltrating lymphocytes (viTILs). All six patients had viCLs, five of whom were evaluable for viTILs in tumor post-vaccination alone. Mel51 patients had viTILs identified in day 22 tumors, post-vaccination and before IFN-γ (median = 2, range = 0–24). This increased in day 24 tumors after IFN-γ (median = 30, range = 4–74). Mel53 patients had viTILs identified in day 22 tumors, post-vaccination plus imiquimod (median = 33, range = 2–64). Three of five evaluable patients across both trials had viTILs with vaccination alone. All five had enhancement of viTILs with tumor-directed therapy. viTILs represented 0.0–2.9% of total T cells after vaccination alone, which increased to 0.6–8.7% after tumor-directed therapy.ConclusionCancer vaccines induce expansion of new viCLs, which infiltrate melanoma metastases in some patients. Our findings identify opportunities to combine vaccines with tumor-directed therapies to enhance T-cell infiltration and T cell-mediated tumor control. These combinations hold promise in improving the therapeutic efficacy of antigen-specific therapies for solid malignancies.
COVID-19 vaccination in patients with cancer receiving immune checkpoint inhibitors: a systematic review and meta-analysis
Authors: Ruiz Juan Ignacio , Lopez-Olivo Maria Angeles , Geng Yimin , Suarez-Almazor Maria E 
Published: February 2023

BackgroundImmune checkpoint inhibitors (ICI) can cause off-target inflammatory and immune-related adverse events (irAE). Conceivably, COVID-19 vaccination could trigger an inflammatory and immune response that could induce or aggravate irAE.MethodsThe objective of this systematic review is to appraise the efficacy and safety of COVID-19 vaccination in patients with cancer treated with ICI. The literature search was performed in PubMed and Embase in English from December 2019 to February 2022. The review included clinical trials, observational cohort studies, case series, and case reports reporting on the clinical efficacy and safety of COVID-19 vaccines on patients with cancer treated with ICI. Outcomes of interest included seroconversion, SARS-CoV-2 infection rate, severe COVID-19, COVID-19 mortality rate. Incidence of ICI irAEs was also ascertained as well as vaccine adverse events. A meta-analysis was conducted to estimate the pooled effect sizes of the outcomes when possible, using random effects models.ResultsOverall, 19 studies were included for the analysis (n=10 865 with 2477 receiving ICI). We analyzed 15 cohort studies, 1 cross-sectional study, and 3 case reports. There were no statistically significant differences in seroconversion rates after the second dose of the vaccine when comparing patients with cancer receiving ICI with patients without cancer (risk ratio, RR 0.97, 95% CI 0.92 to 1.03) or with patients with cancer without active treatment (RR 1.00, 95% CI 0.96 to 1.04). There was a higher probability of seroconversion in patients with cancer treated with ICI compared with patients with cancer treated with chemotherapy (RR 1.09, 95% CI 1.00 to 1.18). In a single study in patients receiving ICI, no differences were observed in risk of irAE between those receiving inactivated vaccine and those unvaccinated (pneumonitis RR 0.88, 95% CI 0.33 to 2.3; rash RR 1.03, 95% CI 0.66 to 1.62; arthralgia RR 0.94, 95% CI 0.51 to 1.75). There were no studies for other types of vaccines comparing vaccinated vs not vaccinated in patients treated with ICI. The most common vaccine-related adverse events were local pain or fatigue. Overall, the quality of evidence was rated as very low.ConclusionCOVID-19 vaccination appears to be effective and safe in patients with cancer receiving ICI.
Oncogenic IDH1 Mutation Imparts Therapeutically Targetable Metabolic Dysfunction in Multiple Tumor Types
Authors: Robinson Troy M. , Levine Ross L. 
Published: February 2023

Summary:
In this issue of Cancer Discovery, Thomas and colleagues leverage mass spectrometry metabolomics, stable isotope labeling, and functional studies to explore metabolic vulnerabilities in cancers harboring mutations in isocitrate dehydrogenase (IDH). The authors present compelling data to support the claim that dysregulated lipid synthesis underpins a synthetic lethal target in cancers with IDH1, but not IDH2, mutations.
See related article by Thomas et al., p. 496 (9).
Dysregulated Smooth Muscle Cell BMPR2–ARRB2 Axis Causes Pulmonary Hypertension
Authors: Wang Lingli , Moonen Jan-Renier , Cao Aiqin , Isobe Sarasa , Li Caiyun G. , Tojais Nancy F. , Taylor Shalina , Marciano David P. , Chen Pin-I. , Gu Mingxia , Li Dan , Harper Rebecca L. , El-Bizri Nesrine , Kim Yu-Mee , Stankunas Kryn , Rabinovitch Marlene 
Published: February 2023

Objective:

Mutations in
BMPR2
(bone morphogenetic protein receptor 2) are associated with familial and sporadic pulmonary arterial hypertension (PAH). The functional and molecular link between loss of BMPR2 in pulmonary artery smooth muscle cells (PASMC) and PAH pathogenesis warrants further investigation, as most investigations focus on BMPR2 in pulmonary artery endothelial cells. Our goal was to determine whether and how decreased BMPR2 is related to the abnormal phenotype of PASMC in PAH.

Methods:

SMC-specific

Bmpr2
−/−

mice (

BKO
SMC

) were created and compared to controls in room air, after 3 weeks of hypoxia as a second hit, and following 4 weeks of normoxic recovery. Echocardiography, right ventricular systolic pressure, and right ventricular hypertrophy were assessed as indices of pulmonary hypertension. Proliferation, contractility, gene and protein expression of PASMC from

BKO
SMC

mice, human PASMC with
BMPR2
reduced by small interference RNA, and PASMC from PAH patients with a
BMPR2
mutation were compared to controls, to investigate the phenotype and underlying mechanism.

Results:

BKO
SMC

mice showed reduced hypoxia-induced vasoconstriction and persistent pulmonary hypertension following recovery from hypoxia, associated with sustained muscularization of distal pulmonary arteries. PASMC from mutant compared to control mice displayed reduced contractility at baseline and in response to angiotensin II, increased proliferation and apoptosis resistance. Human PASMC with reduced BMPR2 by small interference RNA, and PASMC from PAH patients with a
BMPR2
mutation showed a similar phenotype related to upregulation of pERK1/2 (phosphorylated extracellular signal related kinase 1/2)-pP38-pSMAD2/3 mediating elevation in ARRB2 (β-arrestin2), pAKT (phosphorylated protein kinase B) inactivation of GSK3-beta, CTNNB1 (β-catenin) nuclear translocation and reduction in RHOA (Ras homolog family member A) and RAC1 (Ras-related C3 botulinum toxin substrate 1). Decreasing ARRB2 in PASMC with reduced BMPR2 restored normal signaling, reversed impaired contractility and attenuated heightened proliferation and in mice with inducible loss of BMPR2 in SMC, decreasing ARRB2 prevented persistent pulmonary hypertension.

Conclusions:
Agents that neutralize the elevated ARRB2 resulting from loss of BMPR2 in PASMC could prevent or reverse the aberrant hypocontractile and hyperproliferative phenotype of these cells in PAH.