bluuebunny/crossref_metadata_2025 huggingface dataset:
What matters for health? Public views from eight countries
Authors: Abdalla Salma M , Hernandez Mark , Fazaludeen Koya Shaffi , Rosenberg Samuel B , Robbins Grace , Magana Laura , Nsoesie Elaine Okanyene , Sabin Lora , Galea Sandro
Published: June 2022

Introduction

Despite growing scholarship on the social determinants of health (SDoH), wider action remains in its early stages. Broad public understanding of SDoH can help catalyse such action. This paper aimed to document public perception of what matters for health from countries with broad geographic, cultural, linguistic, population composition, language and income level variation.

Methods

We conducted an online survey in Brazil, China, Germany, Egypt, India, Indonesia, Nigeria and the USA to assess rankings of what respondents thought matters for health and what they perceived decision makers think matters for health. We analysed the percentages of each determinant rated as the most important for good health using two metrics: the top selection and a composite of the top three selections. We used two-tailed χ2test for significance testing between groups.

Results

Of 8753 respondents, 56.2% (95% CI 55.1% to 57.2%) ranked healthcare as the most important determinant of good health using the composite metric. This ranking was consistent across countries except in China where it appeared second. While genetics was cited as the most important determinant by 22.3% (95% CI 21.5% to 23.2%) of the overall sample with comparable rates in most countries, the percentage increased to 33.3% (95% CI 30.5% to 36.3%) in Germany and 35.9% (95% CI 33.0% to 38.8%) in the USA. Politics was the determinant with the greatest absolute difference (18.5%, 95% CI 17.3% to 19.6%) between what respondents considered matters for health versus what they perceived decision makers think matters for health.

Conclusion

The majority of people consider healthcare the most important determinant of health, well above other social determinants. This highlights the need for more investment in communication efforts around the importance of SDoH.
Civil–military cooperation in the management of infectious disease outbreaks: a scoping review
Authors: Janse Jacobine , Kalkman Jori Pascal , Burchell George Louis , Hopperus Buma Adriaan Pieter Cornelis Christiaan , Zuiderent-Jerak Teun , Bollen Myriame Thérèse Isabella Beatrice , Timen Aura
Published: June 2022

Introduction

Civil–military cooperation (CMC) in infectious disease outbreak responses has become more common, and has its own cooperation dynamics. These collaborations fit WHO’s call for multisectoral cooperation in managing health emergencies according to the emergency management cycle (EMC). However, the literature on CMC on this topic is fragmented. The core aim of this review is to understand the breadth and dynamics of this cooperation by using the EMC as a framework and by identifying challenges and opportunities in the management of outbreaks.

Methods

A scoping review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guideline was conducted. A systematic search for peer-reviewed journals was performed in PubMed, Embase, Web of Science and Scopus. Eligible papers addressed substantive contributions to the understanding of CMC. Papers were categorised by EMC phase and relevant information on study characteristics and areas of cooperation were extracted from the data. Recurring themes on challenges and opportunities in cooperation were identified by means of qualitative interpretation analysis.

Results

The search resulted in 8360 papers; 54 were included for analysis. Most papers provided a review of activities or expert opinions. CMC was described in all EMC phases, with the fewest references in the recovery phase (n=1). In total, eight areas of CMC were explored. Regarding the better understanding of cooperative dynamics, the qualitative analysis of the papers yielded five recurring themes covering challenges and opportunities in CMC: managing relations, framework conditions, integrating collective activities, governance and civil–military differences.

Conclusion

Guided by these five themes, successful CMC requires sustainable relations, binding agreements, transparency, a clear operational perspective and acknowledgement of organisational cultural differences. Early and continuous engagement proves crucial to avoid distrust and tension among stakeholders, frequently caused by differences in strategical goals. Original research on this topic is limited.
Relationship between serum insulin-like growth factor 1 levels and ischaemic stroke: a systematic review and meta-analysis
Authors: Li Yangni , Yang Weinan , Li Jinhui , Zhang Yishu , Zhang Lincheng , Chen Simiao , He Lan , Zhang Yuyan
Published: June 2022

Objective

To assess the association of insulin-like growth factor 1 (IGF-1) with the risk of incident ischaemic stroke and outcome after ischaemic stroke.

Design

A systematic review of primary studies.

Setting

Hospitals in Western Sweden, Italy, China and Denmark.

Methods

A search was carried out in eligible studies in electronic databases (PubMed, Scopus, Embase, China National Knowledge Infrastructure and Web of Science) updated to 29 December 2020. The relevant data were extracted in order to conduct the meta-analysis. Review Manager V.5.2 was used to pool data and calculate the mean difference (MD) and its 95% CI. Heterogeneity, subgroup analysis, sensitivity analysis and publication bias were also performed in this meta-analysis.

Results

A total of 2277 patients were included in 17 studies. This meta-analysis indicated that higher serum IGF-1 levels were significantly correlated with less risk of ischaemic stroke (MD=−45.32 95% CI –63.70 to –26.94], p < 0.00001, I2=99%) and better improvement of outcome after ischaemic stroke (MD=27.52, 95% CI 3.89 to 51.14, p=0.02, I2=96%). According to subgroup analysis, heterogeneity comes from country, sample size, male and the time from symptom onset to blood collection. Sensitivity analysis showed that there was no significant influence of any individual study on the pooled MD. The effect of high heterogeneity on result credibility was eliminated when four included studies were merged (MD=−30.32, 95% CI −36.52 to –24.11, p< 0.00001, I2=0%). Moreover, no potential publication bias was discovered in this meta-analysis.

Conclusion

Higher serum IGF-1 was significantly correlated with a lower risk of ischaemic stroke. In view of the high degree of heterogeneity, it may need more studies to confirm the prognostic value of serum IGF-1 levels in ischaemic stroke and explore the sources of heterogeneity.
Levels of blood pressure, cardiovascular biomarkers and their correlations in women with previous pre-eclamptic pregnancy within 7 years postpartum: a cross-sectional study in Thailand
Authors: Sukmanee Jarawee , Rothmanee Penkae , Sriwimol Wilaiwan , Staff Annetine , Liabsuetrakul Tippawan
Published: June 2022

Objective

To assess the levels of blood pressure, cardiovascular biomarkers and their correlations measured within 7 years postpartum in women with previous pre-eclamptic pregnancies compared with women with previous normotensive pregnancies.

Design

Cross-sectional study.

Setting

Two tertiary hospitals in the southern region of Thailand.

Participants

Women with pre-eclamptic and normotensive pregnancies in the past 7 years were enrolled from 1 October 2019 to 30 April 2021. Eligible women were interviewed, examined for body mass index (BMI) and blood pressure, and donated morning spot urine and blood samples.

Primary outcome measures

Serum high-sensitivity C reactive protein, creatinine, fasting blood glucose (FBS), glycated haemoglobin (HbA1c), low-density lipoprotein (LDL) cholesterol, urine microalbumin to creatinine ratio (UACR) and sodium were measured. Group differences in biomarkers were tested using unpaired t-test, Wilcoxon rank-sum test or χ2 test. The levels of blood pressure and biomarkers between the two study groups at <2 years, 2–4 years and >4 years were also compared. The correlations between blood pressure and biomarkers were analysed using Pearson’s correlation and partial correlation methods.

Results

From 206 women included in the analysis, 88 had pre-eclamptic pregnancies and 118 had normotensive pregnancies. Compared with women with previous normotensive pregnancies, women with previous pre-eclamptic pregnancies had significantly increased rates of hypertension (31.8% vs 7.6%, p<0.001) and obesity (55.7% vs 40.7%, p=0.038), as well as higher serum levels of FBS (p<0.001), HbA1c (p<0.001), LDL cholesterol (p=0.03), creatinine (p<0.001) and UACR (p<0.001). Correlation coefficients of BMI, serum creatinine and UACR with blood pressure ranged from 0.27 to 0.31.

Conclusion

The risk of hypertension after a pre-eclamptic pregnancy increased. Blood pressure measurement combined with BMI, serum creatinine and UACR screening at least once during 7 years postpartum is suggested for early detection of cardiovascular risk.
Research priorities for autosomal dominant polycystic kidney disease: a UK priority setting partnership
Authors: Harris Tess , Bridges Hannah R , Brown Wendy D , O’Brien Natasha L , Daly Ann C , Jindal Bharat K , Mundy Gillian S , Ong Albert , Power Albert J , Sandford Richard N , Sayer John , Simms Roslyn J , Wilson Patricia D , Winyard Paul J D , Tarpey Maryrose
Published: June 2022

Objectives

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney condition, accounting for 7%–10% of patients with kidney failure. Fundamental basic science and clinical research on ADPKD is underway worldwide but no one has yet considered which areas should be prioritised to maximise returns from limited future funding. The Polycystic Kidney Disease Charity began a priority setting partnership with the James Lind Alliance (JLA) in the UK in 2019–2020 to identify areas of uncertainty in the ADPKD care pathway and allow patients, carers and healthcare professionals to rank the 10 most important questions for research.

Design

The scope covered ADPKD diagnosis and management, identifying new treatments to prevent/slow disease progression and practical, integrated patient support (https://pkdcharity.org.uk/research/for-researchers/adpkd-research-priorities). We used adapted JLA methodology. Initially, an independent information specialist collated uncertainties in ADPKD care from recent consensus conference proceedings and additional literature. These were refined into indicative questions with Steering Group oversight. Finally, the 10 most important questions were established via a survey and online consensus workshop.

Setting

UK.

Participants

747 survey respondents (76% patients, 13% carers, 11% healthcare professionals); 23 workshop attendees.

Results

117 uncertainties in ADPKD care were identified and refined into 35 indicative questions. A shortlist of 17 questions was established through the survey. Workshop participants reached agreement on the top 10 ranking. The top three questions prioritised by patients, carers and healthcare professionals centred around slowing disease progression, identifying persons for early treatment and organising care to improve outcomes.

Conclusions

Our shortlist reflects the varied physical, psychological and practical challenges of living with and treating ADPKD, and perceived gaps in knowledge that impair optimal care. We propose that future ADPKD research funding takes these priorities into account to focus on the most important areas and to maximise improvements in ADPKD outcomes.
Physical activity behaviour up to 1 year post-rehabilitation among adults with physical disabilities and/or chronic diseases: results of the prospective cohort study ReSpAct
Authors: Brandenbarg Pim , Hoekstra Femke , Krops Leonie A , Seves Bregje L , Hettinga Florentina J , Hoekstra Trynke , Dekker Rienk , van der Woude Lucas H V
Published: June 2022

Background

Little is known of physical activity behaviour among adults with a disability and/or chronic disease during and up to 1 year post-rehabilitation. We aimed to explore (1) dose characteristics of physical activity behaviour among adults with physical disabilities and/or chronic diseases during that period, and (2) the effects of personal characteristics and diagnosis on the development of physical activity over time.

Methods

Adults with physical disabilities and/or chronic diseases (N=1256), enrolled in the Rehabilitation, Sports and Active lifestyle study, were followed with questionnaires: 3–6 weeks before (T0) and 14 (T1), 33 (T2) and 52 (T3) weeks after discharge from rehabilitation. Physical activity was assessed with the adapted version of the Short Questionnaire to ASsess Health enhancing physical activity. Dose characteristics of physical activity were descriptively analysed. Multilevel regression models were performed to assess physical activity over time and the effect of personal and diagnosis characteristics on physical activity over time.

Results

Median total physical activity ranged from 1545 (IQR: 853–2453) at T0 to 1710 (IQR: 960–2730) at T3 min/week. Household (495–600 min/week) and light-intensity (900–998 min/week) activities accrued the most minutes. Analyses showed a significant increase in total physical activity moderate-intensity to vigorous-intensity physical activity and work/commuting physical activity for all time points (T1–T3) compared with baseline (T0). Diagnosis, age, sex and body mass index had a significant effect on baseline total physical activity.

Conclusion

Physical activity is highly diverse among adults with physical disabilities and/or chronic diseases. Understanding this diversity in physical activity can help improve physical activity promotion activities.
Non-invasive prenatal testing in mitigating concerns from invasive prenatal diagnostic testing: retrospective assessment of utility in an academic healthcare system in the US
Authors: Kim Kibum , Craft Linda Kaitlyn
Published: June 2022

Objective

Non-invasive prenatal testing (NIPT) is a front-line screening for fatal chromosomal aneuploidy. In pregnant women with a risk of having fetal congenital disorders, NIPT is anticipated to reduce the needs of invasive prenatal diagnostic test (IPD). The objective of this study was to understand the acceptance of NIPT and the utility of NIPT to mitigate concerns about IPD in the US high-risk pregnancy management.

Design and setting

This was a retrospective observational research using healthcare records obtained from an academic healthcare system in the US. The study consisted of site-level longitudinal analysis and patient-level cross-sectional analysis.

Participant

A total of 5660 new high-risk pregnancies with age ≥35 years were identified for the longitudinal trend analysis. Cross-sectional utility assessment included 2057 pregnant women.

Exposure and outcome measures

Longitudinal trends of NIPT order, IPD procedure and the number of patients diagnosed with high-risk pregnancy were descriptively summarised. In the cross-sectional assessment, we tested the association between the use of NIPT and IPD using multivariable regression.

Results

The rate of increase in the NIPT use exceeded the changes in the number of high-risk pregnancies with age ≥35 years, while the number of annual IPD procedures has fluctuated without specific trends. There was no significant association between the numbers of NIPT and IPD with the adjusted ORs between 0.90 and 1.14 (p>0.1). The order of NIPT was not selected as an independent variable predicting the use of IPD. Clinical characteristics indicating low socioeconomic status and limited healthcare coverage are associated with less use of NIPT and lower clinical utility.

Conclusion

Although prenatal care accepted NIPT over the last decade, the utility of NIPT in mitigating concerns on IPD is unclear and needs further investigation. Limited clinical utility should be addressed in the context of disparity in prenatal care.
Emotional and physical experiences of people with neovascular age-related macular degeneration during the injection process in Germany: a qualitative study
Authors: Thier Anne , Breuning Martina , Wolfram Christian , Zeitz Oliver , Holmberg Christine
Published: June 2022

Objectives

In order to better understand the continued barriers to the provision of vascular endothelial inhibitor therapy, this study aims to investigate patients’ experiences with neovascular age-related macular degeneration (nvAMD) in Germany during the injection process and how they deal with it.

Design and participants

This analysis is part of the qualitative arm of a wider mixed-methods study. We recruited participants all over Germany via ophthalmologists, eye clinics, general practitioners, care bases and support groups between June 2018 and December 2020 and selected a subsample of study participants with nvAMD who were either undergoing or had previously undergone vascular endothelial growth factor inhibitor therapy. We conducted narrative, semistructured, face-to-face interviews at the participants’ homes, which were audio-recorded. The interviews were thematically analysed.

Results

Twenty-two participants were included in this analysis. Experiencing neovascular macular degeneration was dominated by the injection experience. Study participants perceived the treatment with vascular endothelial inhibitor injections as uncomfortable, and they described undergoing varying levels of anxiety during the whole injection process. After some years of receiving multiple injections, the pain and not experiencing any positive effects made participants with significant vision loss want to discontinue therapy. Furthermore, they narrated negative injection experiences in association with their interactions with medical staff and doctors.

Conclusion

Although time in the medical setting is limited, efficient and good doctor-patient relationships seem crucial for satisfying care experiences. A respectful and humane relationship may be one key to achieving treatment adherence.
Steroid use for established bronchopulmonary dysplasia: study protocol for a systematic review and meta-analysis
Authors: Strashun Sabina , Seliga-Siwecka Joanna , Chioma Roberto , Zielińska Kinga , Włodarczyk Krzysztof , Villamor Eduardo , Philip Roy K , Assaf Niazy Al , Pierro Maria
Published: June 2022

Introduction

Postnatal steroids during the first few weeks of life have been demonstrated to be effective in decreasing the incidence of bronchopulmonary dysplasia (BPD), a serious chronic respiratory condition affecting preterm infants. However, this preventive option is limited by the concern of neurological side effects. Steroids are used to treat established BPD in an attempt to reduce mortality, and length of stay and home oxygen therapy, both of which associated with high levels of parental stress and healthcare costs. Moreover, a late timing for steroid treatment may show a more favourable safety profile in terms of neurodevelopment outcomes, considering the added postnatal brain maturation of these infants. Here, we report a protocol for a systematic review, which aims to determine the efficacy and long-term safety of postnatal steroids for the treatment of established BPD in preterm infants.

Methods and analysis

MEDLINE, Embase, Cochrane databases and sources of grey literature for conference abstracts and trial registrations will be searched with no time or language restriction. We will include case–control studies, cohort studies and non-randomised or randomised trials that evaluate postnatal steroids for infants diagnosed with moderate or severe established BPD at 36 weeks’ postmenstrual age. We will pool data from studies that are sufficiently similar to make this appropriate. Data extraction forms will be developed a priori. Observational studies and non-randomised and randomised clinical trials will be analysed separately. We will combine OR with 95% CI for dichotomous outcomes and the mean difference (95% CI) for continuous outcomes. We will account for the expected heterogeneity by using a random-effects model. We will perform subgroup analysis based on the a priori determined covariate of interest.

Ethics and dissemination

Systematic reviews are exempted from approval by an ethics committee. Attempts will be sought to publish all results.

PROSPERO registration number

CRD42021218881.
Effectiveness of interventions for middle-aged and ageing population with neck pain: a systematic review and network meta-analysis protocol
Authors: Boonyapo Uchukarn , Rushton Alison B , Heneghan Nicola R , Dilokthornsakul Piyameth , Phungwattanakul Nattawan , Wiangkham Taweewat
Published: June 2022

Introduction

Neck pain (NP) is a common musculoskeletal complaint and is increasing in prevalence. Current clinical practice guidelines and systematic reviews recommended conservative, pharmacological and invasive interventions for individuals with NP. However, optimal management specifically for those who are middle-aged or older adults (≥45 years) is not available; and important considering our ageing population.

Methods and analysis

A systematic review with network meta-analysis (NMA) will be conducted following the Cochrane guidelines. Eligibility criteria include randomised controlled/clinical trials evaluating any of acute (<3 months) or chronic (≥3 months) non-specific NP, whiplash associated disorders, cervical radiculopathy and cervicogenic headache. Any interventions and outcome measures detailed within The International Classification of Functioning, Disability and Health domains will be included. Two independent reviewers will search key databases (AMED, CENTRAL, CINAHL, Embase, MEDLINE, PEDro and PsycINFO), grey literature, key journals and reference lists in May 2022. Two reviewers will decide eligibility and assess risk of bias (ROB) of included studies. The kappa statistic will be used to evaluate agreement between the reviewers at each stage. Data will be extracted by one reviewer and checked for accuracy by a second reviewer. Descriptive data and ROB will be summarised and tabulated. Traditional pairwise meta-analysis using random-effect model will be performed for all direct comparisons, and NMA using a frequentist random-effect model then performed based on NP classification where possible. A network of traditional pairwise meta-analysis allows comparisons of multiple interventions from both direct and indirect evidence to provide a hierarchal establishment for enhancing decision making of clinical practitioners.

Ethics and dissemination

Ethic approval is not required as the study is a literature review. The findings will be shared with the national and international researchers, healthcare professionals and the general public through publishing in a peer-reviewed journal and presentations at conferences.

PROSPERO registration number

CRD42021284618.
Evaluation of routinely collected records for dementia outcomes in UK: a prospective cohort study
Authors: Hayat Shabina , Luben Robert , Khaw Kay-Tee , Wareham Nicholas , Brayne Carol
Published: June 2022

Objectives

To evaluate the characteristics of individuals recorded as having a dementia diagnosis in different routinely collected records and to examine the extent of overlap of dementia coding across data sources. Also, to present comparisons of secondary and primary care records providing value for researchers using routinely collected records for dementia outcome capture.

Study design

A prospective cohort study.

Setting and participants

A cohort of 25 639 men and women in Norfolk, aged 40–79 years at recruitment (1993–1997) followed until 2018 linked to routinely collected to identify dementia cases. Data sources include mortality from death certification and National Health Service (NHS) hospital or secondary care records. Primary care records for a subset of the cohort were also reviewed.

Primary outcome measure

Diagnosis of dementia (any-cause).

Results

Over 2000 participants (n=2635 individuals) were found to have a dementia diagnosis recorded in one or more of the data sources examined. Limited concordance was observed across the secondary care data sources. We also observed discrepancies with primary care records for the subset and report on potential linkage-related selection bias.

Conclusions

Use of different types of record linkage from varying parts of the UK’s health system reveals differences in recorded dementia diagnosis, indicating that dementia can be identified to varying extents in different parts of the NHS system. However, there is considerable variation, and limited overlap in those identified. We present potential selection biases that might occur depending on whether cause of death, or primary and secondary care data sources are used. With the expansion of using routinely collected health data, researchers must be aware of these potential biases and inaccuracies, reporting carefully on the likely extent of limitations and challenges of the data sources they use.
Safety and performance of oropharyngeal muscle strength training in the treatment of post-stroke dysphagia during oral feeding: protocol for a systematic review and meta-analysis
Authors: Gao Minxing , Wang Ying , Xu Lingyuan , Wang Xin , Wang Heying , Song Jinan , Yang Xiaoqiu , Zhou Fenghua
Published: June 2022

Introduction

Dysphagia is a common functional disorder after stroke. Most patients post-stroke are incapable of oral feeding, which often leads to complications such as malnutrition, aspiration pneumonia and dehydration that seriously affect the quality of life of patients. Oropharyngeal muscle strength training is a major method of swallowing training, and recent studies have focused on healthy adults, elderly persons, and patients with head and neck cancer or neurodegenerative diseases; but there have been few studies on such training in patients with post-stroke dysphagia. Our study aims to systematically review the safety and performance of oropharyngeal muscle strength training in the treatment of post-stroke dysphagia during oral feeding.

Methods and analysis

The Cochrane Library, Web of Science, PubMed, Embase and ClinicalTrials.gov databases will be systematically searched, and all relevant articles in English from the establishment of the databases to January 2022 will be reviewed. The study will be conducted in accordance with the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions and will be reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. The primary outcome measures include the Penetration–Aspiration Scale and the Functional Oral Intake Scale. Two authors will independently screen the articles, extract the data and assess the study quality. Any disagreements during this process will be resolved by discussion or by consultation with a third author. Next, quantitative or qualitative, subgroup and sensitivity analyses of the included literature data will be performed as appropriate.

Ethics and dissemination

Ethical approval is not required for this systematic review as no primary data collection will be required. The results of the present study will be published in a peer-reviewed journal in the field of deglutition disorders.

PROSPERO registration number

CRD42022302471.
Aortic dilation and growth in women with Turner syndrome
Authors: Meccanici Frederike , Schotte Mathilda H , Snoeren Miranda , Bons Lidia R , van den Hoven Allard T , Kardys Isabella , Budde Ricardo P J , van den Bosch Annemien E , Duijnhouwer Anthonie L , Roos-Hesselink Jolien W
Published: June 2022

Objective

Women with Turner syndrome (TS) are at increased risk of aortic dissection, which is a life-threatening event associated with aortic dilation. Knowledge on the development of aortic dilation over time remains limited. This study aims to describe the prevalence of aortic dilation, to find associated factors and to study aortic growth in women with TS.

Methods

In this prospective multicentre cohort study, consecutive adult women with genetically proven TS included between 2014 and 2016 underwent ECG-triggered multiphase CT angiography at baseline and after 3 years. Aortic diameters were measured at seven levels of the thoracic aorta using double oblique reconstruction and indexed for body surface area. Ascending aortic dilation was defined as an aortic size index >20 mm/m2. Aorta-related and cardiovascular events were collected. Statistical analysis included linear and logistic regression and linear mixed effects models.

Results

The cohort consisted of 89 women with a median age of 34 years (IQR: 24–44). Ascending aortic dilation was found in 38.2% at baseline. At baseline, age (OR: 1.08 (95% CI 1.03 to 1.13), p<0.001), presence of bicuspid aortic valve (BAV) (OR: 7.09 (95% CI 2.22 to 25.9), p=0.002) and systolic blood pressure (OR: 1.06 (95% CI 1.02 to 1.11), p=0.004) were independently associated with ascending aortic dilation. During a median follow-up of 3.0 (2.4–3.6) years (n=77), significant aortic growth was found only at the sinotubular junction (0.20±1.92 mm, p=0.021). No aortic dissection occurred, one patient underwent aortic surgery and one woman died.

Conclusions

In women with TS, ascending aortic dilation is common and associated with age, BAV and systolic blood pressure. Aortic diameters were stable during a 3-year follow-up, apart from a significant yet not clinically relevant increase at the sinotubular junction, which may suggest a more benign course of progression than previously reported.
Combination of AKT1 and CDH1 mutations predicts primary resistance to immunotherapy in dMMR/MSI-H gastrointestinal cancer
Authors: Wang Zhenghang , Zhang Qi , Qi Changsong , Bai Yuezong , Zhao Feilong , Chen Hui , Li Zhongwu , Wang Xicheng , Chen Mifen , Gong Jifang , Peng Zhi , Zhang Xiaotian , Cai Jinping , Chen Shiqing , Zhao Xiaochen , Shen Lin , Li Jian
Published: June 2022

Background

Gastrointestinal (GI) cancer is the second most common cancer type with mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) phenotype that is expected to respond to immune-checkpoint inhibitors (ICIs). However, approximately half of the patients with dMMR/MSI-H GI cancer derive no benefit from ICIs. We sought to identify the predictors of primary resistance to ICIs in dMMR/MSI-H GI cancer.

Methods

Three independent cohorts were included: (1) the discovery cohort (65 patients with dMMR/MSI-H GI cancer) with ICI efficacy data and pre-ICIs tissue samples for genomic profile and tumor immune infiltration; (2) the validation cohort (22 patients with dMMR/MSI-H GI cancer) with ICI efficacy data and pre-ICIs plasma samples for genomic profile; and (3) the TCGA (The Cancer Genome Atlas) cohort not receiving ICIs (152 patients with MSI-H GI cancer) with genomic profile and survival data.

Results

AKT1 and CDH1 mutations were identified as independent predictors of poor progression-free survival (PFS) and primary resistance to ICIs in dMMR/MSI-H GI cancer. We combined these two genes as an immuno-oncology therapy predictor (IOpred), which could recognize 52.4% (11/21) of dMMR/MSI-H patients with primary resistance to ICIs with a positive predictive value (PPV) of 91.7% (11/12). Receiver operating characteristic analysis demonstrated IOpred with a good performance in predicting primary resistance (area under the curve 0.751). Patients with IOpred-Mut (mutant AKT1 or CDH1) GI cancer had significantly shorter PFS (HR=8.36, p<0.001) and overall survival (OS, HR=5.17, p<0.001) than IOpred-WT (wild-type for both AKT1 and CDH1) cases upon ICI treatment. The validation cohort also confirmed the correlation between IOpred-mutation and poorer prognosis (PFS, HR=4.68, p=0.004; OS, HR=15.98, p<0.001) in dMMR/MSI-H patients after ICIs. The PPV of IOpred in identifying primary resistance to ICIs was 80% (4/5) in the validation cohort. Additionally, IOpred-WT patients could be further stratified by tumor mutational burden (TMB), wherein TMB-low patients (TMB ≤26.19 mutations per megabase (Mb)) had a significantly higher primary resistance rate to ICIs (34.8% vs 6.7%, p=0.014) and poorer PFS (HR=3.46, p=0.008) and OS (HR=4.42, p=0.047) than TMB-high patients (TMB >26.19 mutations/Mb).

Conclusions

IOpred was identified as a powerful predictor of primary resistance to ICIs in dMMR/MSI-H GI cancer, which might serve as a promising biomarker to help guide immunotherapy decision-making.
Wilms tumor reveals DNA repair gene hyperexpression is linked to lack of tumor immune infiltration
Authors: Higgs Emily F , Bao Riyue , Hatogai Ken , Gajewski Thomas F
Published: June 2022

Background

A T cell-rich tumor microenvironment has been associated with improved clinical outcome and response to immune checkpoint blockade therapies in several adult cancers. Understanding the mechanisms for lack of immune cell infiltration in tumors is critical for expanding immunotherapy efficacy. To gain new insights into the mechanisms of poor tumor immunogenicity, we turned to pediatric cancers, which are generally unresponsive to checkpoint blockade.

Methods

RNA sequencing and clinical data were obtained for Wilms tumor, rhabdoid tumor, osteosarcoma, and neuroblastoma from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database, and adult cancers from The Cancer Genome Atlas (TCGA). Using an 18-gene tumor inflammation signature (TIS) representing activated CD8+T cells, we identified genes inversely correlated with the signature. Based on these results, adult tumors were also analyzed, and immunofluorescence was performed on metastatic melanoma samples to assess the MSH2 relationship to anti-programmed cell death protein-1 (PD-1) efficacy.

Results

Among the four pediatric cancers, we observed the lowest TIS scores in Wilms tumor. TIS scores were lower in Wilms tumors compared with matched normal kidney tissues, arguing for loss of endogenous T cell infiltration. Pathway analysis of genes upregulated in Wilms tumor and anti-correlated with TIS revealed activated pathways involved DNA repair. The majority of adult tumors in TCGA also showed high DNA repair scores associated with low TIS. Melanoma samples from an independent cohort revealed an inverse correlation between MSH2+tumor cells and CD8+T cells. Additionally, melanomas with high MSH2+tumor cell numbers were largely non-responders to anti-PD-1 therapy.

Conclusions

Increased tumor expression of DNA repair genes is associated with a less robust immune response in Wilms tumor and the majority of TCGA tumor types. Surprisingly, the negative relationship between DNA repair score and TIS remained strong across TCGA when correcting for mutation count, indicating a potential role for DNA repair genes outside of preventing the accumulation of mutations. While loss of DNA repair machinery has been associated with carcinogenesis and mutational antigen generation, our results suggest that hyperexpression of DNA repair genes might be prohibitive for antitumor immunity, arguing for pharmacologic targeting of DNA repair as a potential therapeutic strategy.
Active counselling and well-controlled disease result in a higher percentage of women with rheumatoid arthritis that breast feed: results from the PreCARA study
Authors: Kemper Erik , Ghalandari Nafise , Wintjes Hetty , Van Steensel-Boon Anneke , Kranenburg Laura , Mulders Annemarie , Crijns Hubertina , Smeele Hieronymus , Dolhain Radboud J EM
Published: June 2022

Objectives

Previous research has demonstrated that patients with rheumatoid arthritis (RA) are less likely to breast feed their offspring. Treatment options for RA during lactation have expanded and the importance of counselling is recognised. The aim of the current research was to study breast feeding among women with RA who benefit from these developments.

Methods

Patients were derived from the Preconceptional Counselling in Active Rheumatoid Arthritis (PreCARA) cohort. Patients were treated according to a modified treat-to-target approach aimed at remission and received pregnancy counselling, including counselling on breast feeding. Postpartum visits were scheduled at 4–6, 12 and 26 weeks post partum. Prevalence of breast feeding at each postpartum visit was compared with a historical reference cohort (Pregnancy-induced Amelioration of Rheumatoid Arthritis cohort) and the general population.

Results

Data on 171 pregnancies were available for the current analysis. 120 (70.2%) patients with RA initiated breast feeding. 103/171 (60.2%), 68/171 (39.8%) and 45/171 (26.3%) patients with RA breast fed their offspring at 4–6, 12 and 26 weeks post partum, respectively. These percentages were higher at all postpartum visits compared with the historical reference cohort (p<0.001). In comparison with the general population, the rates were similar at each time point.

Conclusion

Patients with RA in the PreCARA cohort were more likely to breast feed their offspring compared with patients with RA in the historical reference cohort. The breastfeeding rates observed were similar to breastfeeding rates among women in the general population. The increase in breast feeding among patients with RA may be due to the extension of lactation-compatible medication and pregnancy counselling.
Heat and lost work in irreversible cycles: the two sides of the same coin
Authors: Anacleto Joaquim
Published: June 2022

We discussed the criterion for usefully comparing an irreversible cycle with a reversible one. Grounded on entropy generation, a new definition of lost work is proposed, which cannot be determined by the usual cycle diagrams, contrary to what has been found in the literature. To better understand the lost work concept and its role in entropy generation, we presented two irreversible cycles, which also instructively reveal that heat and lost work are the two sides of the same coin, this coin being the entropy generation. This study, addressing issues that are virtually absent from the literature, is expected to be not only relevant from a scientific standpoint but also useful for physics teachers and students with a solid background in thermodynamics.
State  control strategy of open quantum systems by reverse engineering: via homodyne-based feedback control
Authors: Xiao Shan , Ke Qiang , Ji Yinghua
Published: June 2022

Quantum state transition is the core content of quantum control. This paper presents a control scheme of the state evolution path based on feedback control and reverse engineering design. To achieve high-precision state transition, we first adopt a homodyne-based feedback control strategy to form a closed-loop system. Then, based on the idea of reverse engineering design, the state evolution path of the system is planned and designed by considering the influence of environment decoherence on the state evolution. Numerical simulation results show that the control pulse based on planning design can drive the system from any initial state to the desired target state, and the coherence of the system is effectively protected during state transition.
Emergence of cosmic space and horizon entropy maximization from Tsallis and Cirto entropy
Authors: Chen Ge-Rui
Published: June 2022

In this note by use of the idea of the emergence of cosmic space suggested by Padmanabhan (Emergence and expansion of cosmic space as due to the quest for holographic equipartition; Res Astro Astrophys 12:891, 2012), we derive the modified Friedmann equation of a Friedmann-Robertson-Walker (FRW) Universe from Tsallis and Cirto entropy in $$(n+1)$$

(
n
+
1
)

dimension with any spatial curvature. We investigate further the consistency of the law of emergence with the maximization of horizon entropy in the context of Tsallis and Cirto horizon entropy. Our results reveal the deep connection between the law of emergence and horizon thermodynamics.
Correlations of mixed systems in confining backgrounds
Authors: Ghodrati Mahdis
Published: June 2022

We show that the entanglement of purification and the critical distance between the two mixed systems is a powerful measure in probing the phase structures of QCD and confining backgrounds, as it can distinguish the scale of chiral symmetry breaking versus the scale of confinement/deconfinement phase transitions. For two symmetric strips with equal and finite width and infinite length, and in the background of several confining geometries, we numerically calculate the critical distance between them where the mutual information vanishes and show that this quantity can probe the very rich phase structures of these backgrounds. The geometries that we study here are AdS-soliton, Witten–Sakai–Sugimoto and deformed Sakai–Sugimoto, Witten-QCD, Klebanov–Strassler, Klebanov–Tseytlin, Klebanov–Witten, Maldacena–Nunez, Nunez–Legramandi metric, and Domain-Wall QCD model. For each background we also present the relation for the entanglement of purification. Finally, we show that the Crofton forms of these geometries also behave in a universal form where a “well” is being observed around the IR wall, and therefore for all confining backgrounds, the Crofton form would also be capable of distinguishing the confining versus conformal backgrounds as it is also a tool in the reconstruction of various bulk geometries.
Einstein–Dirac–Maxwell wormholes: ansatz, construction and properties of symmetric solutions
Authors: Blázquez-Salcedo Jose Luis , Knoll Christian , Radu E.
Published: June 2022

We present a discussion of the traversable wormholes in Einstein–Dirac–Maxwell theory recently reported in e-Print: 2010.07317. This includes a detailed description of the ansatz and junction condition, together with an investigation of the domain of existence of the solutions. In this study, we assume symmetry under interchange of the two asymptotically flat regions of a wormhole. Possible issues and limitations of the approach are also discussed.
Density waves in an improved car-following model under intelligent transportation system environment
Authors: Wang Wen-Jie , Ma Ming-Hui , Liang Shi-Dong , Ma Guang-Yi , Wang Yan-Song
Published: June 2022

The intelligent transportation system (ITS) can effectively utilize the existing transportation facilities and improve traffic safety and efficiency. To study and evaluate the dynamic characteristics of traffic flow, a novel car-following model is proposed based on the two-velocity difference model (TVDM) with connected consideration of headway memory and backward looking effect under ITS environment. The linear stability theory is used to acquire the stability condition of the improved model, which shows that the proposed model can effectively strengthen the traffic flow stability. According to the nonlinear theory, the time-dependent Ginzburg–Landau (TDGL) equation and modified Korteweg–de Vries (mKdV) equation are obtained to exhibit the evolution characteristics of traffic flow density wave. At last, numerical simulation is performed to further validate that the improved model can enhance the traffic flow stability and eliminate traffic congestion.
Multiple and complex codimension-2 bifurcations underlying post-inhibitory rebound spike and excitability transition
Authors: Wang Xianjun , Gu Huaguang , Li Yuye , Lu Bo
Published: June 2022

Neuron exhibits nonlinear dynamics such as excitability transition and post-inhibitory rebound (PIR) spike related to bifurcations, which are associated with information processing, locomotor modulation, or brain disease. PIR spike is evoked by inhibitory stimulation instead of excitatory stimulation, which presents a challenge to the threshold concept. In this paper, 7 codimension-2 or degenerate bifurcations related to 10 codimension-1 bifurcations are acquired in a neuronal model, which presents the bifurcations underlying the excitability transition and PIR spike. Type I excitability corresponds to saddle-node bifurcation on an invariant cycle (SNIC) bifurcation, and type II excitability to saddle-node (SN) bifurcation or sub-critical Hopf (SubH) bifurcation or sup-critical Hopf (SupH) bifurcation. The excitability transition from type I to II corresponds to the codimension-2 bifurcation, Saddle-Node Homoclinic orbit (SNHO) bifurcation, via which SNIC bifurcation terminates and meanwhile big homoclinic orbit (BHom) bifurcation and SN bifurcation emerge. A degenerate bifurcation via which BHom bifurcation terminates and limit point of cycle (LPC) bifurcation emerges is responsible for spiking transition from type I to II, and the roles of other codimension-2 bifurcations (Cusp, Bogdanov-Takens, and Bautin) are discussed. In addition, different from the widely accepted viewpoint that PIR spike is mainly evoked near Hopf bifurcation rather than SNIC bifurcation, PIR spike is identified to be induced near SNIC or BHom or LPC bifurcations, and threshold curves resemble that of Hopf bifurcation. The complex bifurcations present comprehensive and deep understandings of excitability transition and PIR spike, which are helpful for the modulation to neural firing activities and physiological functions.
A novel kind of reduced integrable matrix mKdV equations and their binary Darboux transformations
Authors: Ma Wen-Xiu
Published: June 2022

A novel kind of reduced integrable matrix mKdV equations is generated from a group reduction replacing the spectral parameter [Formula: see text] with [Formula: see text] in the matrix AKNS spectral problems. The traditional replacement in making integrable reductions is to replace the spectral parameter [Formula: see text] with its complex conjugate [Formula: see text]. Binary Darboux transformations are constructed by use of Lax pairs and adjoint Lax pairs, and thus, soliton solutions are presented for the resulting reduced integrable matrix mKdV equations from the zero seed solution.
TAM: A Front-End to an Auto-Parallelizing Compiler
Authors: Sharma Ashish , Badjatiya Mayank , Sahay Aayush , Verma Aryan , Agarwal Ayush , Singal Gaurav , Garg Deepak , Jain Deepak Kumar , Kotecha Ketan
Published: June 2022

The multi-core architecture has revolutionized the parallel computing. Despite this, the modern age compilers have a long way to achieve auto-parallelization. Through this paper, we introduce a language that encouraging the auto-parallelization. We are also introducing Front-End for our auto-parallelizing compiler. Later, we examined our compiler employing a different number of core and verify results based on different metrics based on total compilation time, memory utilization, power utilization and CPU utilization. At last, we learned that parallelizing multiple files engage more CPU resources, memory and energy, but it finishes the task at hand in less time. In this paper, we have proposed a loop code generation technique that makes the generation of nested loop IR code faster by dividing the blocks into some extra code blocks using a modular approach. Our TAM compiler technique speedup by 7.506, 5.283 and 2.509 against sequential compilation when we utilized 8, 4 and 2 cores respectively. We observed that the CPU utilization of the TAM compiler reaches the maximum permissible limit when an optimal parallelizable instance is compiled.
Moneo
Authors: Jiang Yuting , Xiong Yifan , Qu Lei , Luo Cheng Luo , Tian Chen , Cheng Peng , Xiong Yongqiang
Published: June 2022

Cloud-based AI infrastructure is becoming increasingly important, especially on large-scale distributed training. To improve its efficiency and serviceability, real-time monitoring of the infrastructure and workload profiling are proved to be the effective approach empirically. However, cloud environment poses great challenges as service providers cannot interfere with their tenants' workloads or touch user data, thus previous instrumentation-based monitoring approach cannot be applied, nor does the workload trace collection.
One Profile Fits All
Authors: Ugur Muhammed , Jiang Cheng , Erf Alex , Ahmed Khan Tanvir , Kasikci Baris
Published: June 2022

Modern data center applications have multi-megabyte instruc- tion footprints that easily exhaust on-chip cache structures, which typically have a size of only a couple hundred kilobytes. Consequently, today's data center applications suffer from frequent Instruction cache (I-cache) and Instruction Transla- tion Lookaside Buffer (I-TLB) misses, causing performance losses worth millions of dollars. To make matters worse, the multi-megabyte instruction footprint of the Linux kernel pre- cipitates an undue burden on the performance of data center applications.