bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trajectory research in children on the autism spectrum: a scoping review protocol
Authors: Gentles Stephen , Duku Eric , Kerns Connor , McVey Alana J , Hunsche Michelle C , Ng Cordell Elise C , Bednar E Dmitra , Banfield Laura , Szatmari Peter , Georgiades Stelios 
Published: November 2021

IntroductionLongitudinal trajectory methods, featuring outcome assessments at three or more time points, are increasingly being used as appropriate approaches to understand developmental pathways of people on the autism spectrum across the lifespan. Understanding the scope of this rapidly expanding body of research can help inform future trajectory studies and identify areas for potential meta-analysis as well as key evidence gaps. We present the protocol for a scoping review whose objective is to identify and summarise the scope of research that uses a longitudinal trajectory study design to examine development in children diagnosed with autism. Specifically, we will identify outcome domains and age intervals that have been well characterised, areas where further research is needed and the historical use of various longitudinal trajectory analytical approaches.Methods and analysisWe outline the methods for the proposed scoping review according to the framework outlined by Arksey and O’Malley, with subsequent clarifications and enhancements by other authors. Using a search strategy developed by a medical librarian, we will search six databases for relevant publications. Titles and abstracts will be screened in duplicate, followed by full-text screening. Data extraction fields developed predominantly a priori from a set of guiding subquestions will be used to chart relevant data. The findings will include quantitative aggregate summaries, narrative summaries, and appraisal of trajectory studies according to our methodological subquestions. We will consult autistic self-advocate and parent–caregiver stakeholders to facilitate interpretation of the findings.Ethics and disseminationResearch ethics approval is not required for this scoping review. The results will be presented to researcher, care professional, policy-maker and stakeholder audiences at local and international conferences, other dissemination activities and published in a peer-reviewed journal.
How much of the effect of disability acquisition on mental health is mediated through employment and income? A causal mediation analysis quantifying interventional indirect effects using data from four waves of an Australian cohort study
Authors: Aitken Zoe , Simpson Julie Anne , Bentley Rebecca , Kavanagh Anne Marie 
Published: November 2021

ObjectivesThere is evidence that disability acquisition causes a decline in mental health, but few studies have examined the causal mechanisms through which the effect operates. This study used a novel approach to mediation analysis to quantify interventional indirect effects (IIEs) through employment and income.Design and settingWe used four waves of longitudinal data (2011–2014) from the Household, Income and Labour Dynamics in Australia Survey, a nationally representative survey of Australian households.ParticipantsWorking aged individuals who acquired a disability (n=233) were compared with those who remained disability-free in all four waves (n=5419).Primary outcome measureSelf-reported mental health was measured using the Mental Health Inventory subscale of the Short Form 36 general health questionnaire, which measures symptoms of depression, anxiety and psychological well-being.Statistical analysisWe conducted a causal mediation analysis quantifying IIEs of disability acquisition on mental health operating through two distinct mediators: employment status and income. We used multiple imputation with 50 imputed datasets to account for missing data.ResultsThe total causal effect of disability acquisition on mental health was estimated to be a 4.8-point decline in mental health score (estimated mean difference: −4.8, 95% CI −7.0 to –2.7). The IIE through employment was estimated to be a 0.5-point difference (−0.5, 95% CI −1.0 to 0.0), accounting for 10.6% of the total effect, whereas there was no evidence that income explained any of the effects.ConclusionsThis study estimated that disability-related mental health inequalities could be reduced by 10.6% if employment rates were the same for people with disability as those without disability. The results suggest that employment is implicated in the relationship between disability acquisition and mental health and that more research is needed to understand the influence of other aspects of employment and other socioeconomic characteristics.
Influence of timing of maternal antibiotic administration during caesarean section on infant microbial colonisation: a randomised controlled trial
Authors: Dierikx Thomas , Berkhout Daniel , Eck Anat , Tims Sebastian , van Limbergen Johan , Visser Douwe , de Boer Marjon , de Boer Nanne , Touw Daan , Benninga Marc , Schierbeek Nine , Visser Laura , Knol Jan , Roeselers Guus , de Vries Johanna , de Meij Tim 
Published: November 2021

ObjectiveRevised guidelines for caesarean section (CS) advise maternal antibiotic administration prior to skin incision instead of after umbilical cord clamping, unintentionally exposing the infant to antibiotics antenatally. We aimed to investigate if timing of intrapartum antibiotics contributes to the impairment of microbiota colonisation in CS born infants.DesignIn this randomised controlled trial, women delivering via CS received antibiotics prior to skin incision (n=20) or after umbilical cord clamping (n=20). A third control group of vaginally delivering women (n=23) was included. Faecal microbiota was determined from all infants at 1, 7 and 28 days after birth and at 3 years by 16S rRNA gene sequencing and whole-metagenome shotgun sequencing.ResultsCompared with vaginally born infants, profound differences were found in microbial diversity and composition in both CS groups in the first month of life. A decreased abundance in species belonging to the genera Bacteroides and Bifidobacterium was found with a concurrent increase in members belonging to the phylum Proteobacteria. These differences could not be observed at 3 years of age. No statistically significant differences were observed in taxonomic and functional composition of the microbiome between both CS groups at any of the time points.ConclusionWe confirmed that microbiome colonisation is strongly affected by CS delivery. Our findings suggest that maternal antibiotic administration prior to CS does not result in a second hit on the compromised microbiome. Future, larger studies should confirm that antenatal antibiotic exposure in CS born infants does not aggravate colonisation impairment and impact long-term health.
Irregular erythrocyte antibodies among antenatal women and their neonatal outcome at a tertiary care hospital in Northern India
Authors: Mandal Saikat , Kaur Daljit , Negi Gita , Basu Sriparna , Chaturvedi Jaya , Maji Manideepa , Malhotra Sheetal 
Published: November 2021

AbstractBackgroundRed blood cell alloimmunisation during the pregnancy is a significant cause for neonatal mortality and morbidity. This study was planned to determine the prevalence and specificity of irregular erythrocyte antibodies in antenatal mothers and their neonatal outcome.MethodsIn this observational study, blood grouping and red cell antibody screening of mothers were performed at first visit and after 28 weeks of gestation and positive cases were identified and followed up monthly till delivery by repeating antibody titre and middle cerebral artery—peak systolic velocity. After delivery of alloimmunised mothers, cord blood haemoglobin, bilirubin and direct antiglobulin tests (DAT) were analysed and further outcome of neonate was recorded.ResultsAmong 652 registered antenatal cases, 18 multigravida women were found to be alloimmunised, accounting to prevalence of 2.8%. Most common alloantibody identified was anti D (&gt;70%) followed by anti-Lea, anti-C, anti-Leb, anti-E and anti-Jka. Only 47.7% Rh D negative women received anti-D prophylaxis during previous pregnancies or whenever indicated. DAT was positive in 56.2% of neonates. Among nine DAT positive neonates, two early neonatal deaths due to severe anaemia were observed following birth resuscitation. Four antenatal mothers required intrauterine transfusion in view of fetal anaemia while three neonates received double volume exchange transfusion and top up transfusions after birth.ConclusionsThis study emphasises importance of red cell antibody screening for all multigravida antenatal women at registration of pregnancy and additionally at 28 weeks or later in high-risk cases irrespective of RhD status.
Enhancing cultural food security among the Syilx Okanagan adults with the reintroduction of Okanagan sockeye salmon
Authors: Blanchet Rosanne , Willows Noreen , Johnson Suzanne ,   Okanagan Nation Salmon Reintroduction Initiatives, Batal Malek 
Published: November 2021

For the Syilx Okanagan Nation, food sovereignty is foundational to ensuring their cultural food security and health. Salmon being a central Syilx food, the Nation has worked relentlessly since the 1990s to reintroduce Okanagan sockeye salmon into their traditional territory. This study describes the reach of this initiative and assesses its impact on Syilx households’ income-related and cultural food security status. In total, 265 households participated in the study. Overall, 48.6% of participants ate Okanagan sockeye salmon during the year prior to the survey. Most participants (89.1%) reported that during the prior year their household accessed salmon from a community member or through trade (53.7%), community program (49.8%), a feast or ceremony (35.8%), or household harvest (27.2%). The number of ways that households accessed salmon was associated with a greater frequency of salmon consumption (p < 0.0001). Income-related (46.5%) and cultural (63.1%) food insecurity were prevalent. Households’ access to salmon was significantly associated with cultural food security and the perceived importance of cultural food security. This study suggests Indigenous food sovereignty initiatives can increase traditional food access and consumption, thereby enhancing cultural food security. They should be supported by governments, organizations and corporations. Novelty: Indigenous food sovereignty initiatives can increase traditional food access and consumption, thereby enhancing cultural food security. Indigenous-led wild habitat restoration interventions can help reconcile past social and environmental injustices. This study was conducted on the unceded territory of the Syilx Okanagan People.
Symmetry Finder applied to the 1–3 mass eigenstate exchange symmetry
Authors: Minakata Hisakazu 
Published: November 2021

AbstractIn a previous paper, Symmetry Finder (SF) method is proposed to find the reparametrization symmetry of the state-exchange type in neutrino oscillation in matter. It has been applied successfully to the 1–2 state exchange symmetry in the DMP perturbation theory, yielding the eight symmetries. In this paper, we apply the SF method to the atmospheric-resonance perturbation theory to uncover the 1–3 state relabeling symmetries. The pure 1–3 state symmetry takes the unique position that it is practically impossible to formulate in vacuum under the conventional choice of the flavor mixing matrix. In contrast, our SF method produces the sixteen 1–3 state exchange symmetries in matter. The relationship between the symmetries in the original (vacuum plus matter) Hamiltonian and the ones in the diagonalized system is discussed.
Analysis of the Estrogen Receptor-Associated LncRNA Landscape Identifies a Role for ERLC1 in Breast Cancer Progression
Authors: Yuan Hui , Yan Linlin , Wu Mingming , Shang Yinzhong , Guo Qianying , Ma Xin , Zhang Xiao , Zhu Yong , Wu Zhengsheng , Lobie Peter E. , Zhu Tao 
Published: November 2021

Abstract

Estrogen receptor alpha (ERα) plays a vital role in the development of normal breast tissue and in breast cancer. By cross-analyzing The Cancer Genome Atlas (TCGA) database, ERα-regulated long noncoding RNA 1 (ERLC1) was identified as a long noncoding RNA exhibiting a strong association with ERα signaling and high specificity of expression in breast tissue. ERLC1 was transcriptionally activated by ERα, and ERLC1 stabilized the ESR1 transcript by sequestering miR-129 and tethering FXR1 to maintain a positive feedback loop that potentiated ERα signaling. ERLC1 was elevated in tamoxifen-resistant breast cancer cells, where ERLC1 depletion restored sensitivity to tamoxifen and increased the efficacy of palbociclib or fulvestrant therapy. Collectively, these data warrant further investigation of ERLC1 as a modulator of therapeutic response and potential therapeutic target in ER+ breast cancer.

Significance:
This study identifies an estrogen-regulated lncRNA and the mechanism by which it positively regulates ERα activity, demonstrating a feedback loop that can promote resistance to antiestrogen therapies in ER+ breast cancer.
The Role of Circulating Protein and Metabolite Biomarkers in the Development of Pancreatic Ductal Adenocarcinoma (PDAC): A Systematic Review and Meta-analysis
Authors: Kumar Swati , Santos Ralph J. , McGuigan Andrew J. , Singh Urvashi , Johnson Peter , Kunzmann Andrew T. , Turkington Richard C. 
Published: November 2021

Abstract

Background:
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, and this is attributed to it being diagnosed at an advanced stage. Understanding the pathways involved in initial development may improve early detection strategies. This systematic review assessed the association between circulating protein and metabolite biomarkers and PDAC development.

Methods:
A literature search until August 2020 in MEDLINE, EMBASE, and Web of Science was performed. Studies were included if they assessed circulating blood, urine, or salivary biomarkers and their association with PDAC risk. Quality was assessed using the Newcastle-Ottawa scale for cohort studies. Random-effects meta-analyses were used to calculate pooled relative risk.

Results:
A total of 65 studies were included. Higher levels of glucose were found to be positively associated with risk of developing PDAC [n = 4 studies; pooled relative risk (RR): 1.61; 95% CI: 1.16–2.22]. Additionally, an inverse association was seen with pyridoxal 5′-phosphate (PLP) levels (n = 4 studies; RR: 0.62; 95% CI: 0.44–0.87). Meta-analyses showed no association between levels of C-peptide, members of the insulin growth factor signaling pathway, C-reactive protein, adiponectin, 25-hydroxyvitamin D, and folate/homocysteine and PDAC risk. Four individual studies also reported a suggestive positive association of branched-chain amino acids with PDAC risk, but due to differences in measures reported, a meta-analysis could not be performed.

Conclusions:
Our pooled analysis demonstrates that higher serum glucose levels and lower levels of PLP are associated with risk of PDAC.

Impact:
Glucose and PLP levels are associated with PDAC risk. More prospective studies are required to identify biomarkers for early detection.
Racial/Ethnic Differences in Cancer Diagnosed after Metastasis: Absolute Burden and Deaths Potentially Avoidable through Earlier Detection
Authors: Clarke Christina A. , Patel Alpa V. , Kurian Allison W. , Hubbell Earl , Gomez Scarlett Lin 
Published: November 2021

Abstract

Background:
Racial/ethnic disparities in cancer mortality are well described and are partly attributable to later stage of diagnosis. It is unclear to what extent reductions in the incidence of late-stage cancer could narrow these relative and absolute disparities.

Methods:
We obtained stage- and cancer-specific incidence and survival data from the Surveillance, Epidemiology, and End Results Program for persons ages 50 to 79 years between 2006 and 2015. For eight hypothetical cohorts of 100,000 persons defined by race/ethnicity and sex, we estimated cancer-related deaths if cancers diagnosed at stage IV were detected earlier, by assigning them outcomes of earlier stages.

Results:
We observed a 3-fold difference in the absolute burden of stage IV cancer between the group with the highest rate (non-Hispanic Black males, 337 per 100,000) and the lowest rate (non-Hispanic Asian/Pacific Islander females, 117 per 100,000). Assuming all stage IV cancers were diagnosed at stage III, 32–80 fewer cancer-related deaths would be expected across subgroups, a relative reduction of 13%–14%. Assuming one third of metastatic cancers were diagnosed at each earlier stage (I, II, and III), 52–126 fewer cancer-related deaths would be expected across subgroups, a relative reduction of 21%–23%.

Conclusions:
Across population subgroups, non-Hispanic Black males have the highest burden of stage IV cancer and would have the most deaths averted from improved detection of cancer before metastasis.

Impact:
Detecting cancer before metastasis could meaningfully reduce deaths in all populations, but especially in non-Hispanic Black populations.
See related commentary by Loomans-Kropp et al., p. 512
Concurrent Disruption of the Ras/MAPK and NF-κB Pathways Induces Circadian Deregulation and Hepatocarcinogenesis
Authors: Hanley Kaisa L. , Liang Yan , Wang Gaowei , Lin Xiaoxue , Yang Meixiang , Karin Michael , Fu Wenxian , Feng Gen-Sheng 
Published: November 2021

Abstract

The Ras/Erk and NF-κB pathways play critical roles in cell proliferation and are known to drive oncogenesis when overactivated. Herein we report a gatekeeper function of the two pathways by working in synergy to suppress liver tumorigenesis. Hepatocyte-specific deletion of both Shp2/Ptpn11 and Ikkβ in mice, which promote Ras/Erk and NF-κB signaling, respectively, exacerbated chemical carcinogenesis and even triggered spontaneous development of hepatocellular carcinoma (HCC). We show that the unanticipated severe tumor phenotype was contributed collectively by severe cholestasis, metabolic changes, upregulated cell-cycle progression, and disruption of circadian rhythm in mutant hepatocytes. Remarkably, human HCCs with dysregulated circadian gene expression displayed downregulation of Ras/Erk and NF-κB signaling and poor prognosis. Together, these data indicate that at the ground state, the two central pathways, previously known as oncogenic, cooperate to sustain tumor-suppressive physiologic homeostasis and to prevent hepatic damage. Disruption of this intricate signaling network is carcinogenic in the liver.

Implications:
We demonstrate here that basal levels of the Ras/MAPK and NF-κB pathways, while promoting tumorigenesis if overactivated, are required to maintain physiologic homeostasis and regulate circadian rhythm in the liver, which are antitumorigenic.
Contemporary Management of Cardiogenic Shock: A RAND Appropriateness Panel Approach
Authors: Proudfoot Alastair G. , Kalakoutas Antonis , Meade Susanna , Griffiths Mark J.D. , Basir Mir , Burzotta Francesco , Chih Sharon , Fan Eddy , Haft Jonathan , Ibrahim Nasrien , Kruit Natalie , Lim Hoong Sern , Morrow David A. , Nakata Jun , Price Susanna , Rosner Carolyn , Roswell Robert , Samaan Mark A. , Samsky Marc D. , Thiele Holger , Truesdell Alexander G. , van Diepen Sean , Voeltz Michelle Doughty , Irving Peter M. 
Published: November 2021

Background:
Current practice in cardiogenic shock is guided by expert opinion in guidelines and scientific statements from professional societies with limited high quality randomized trial data to inform optimal patient management. An international panel conducted a modified Delphi process with the intent of identifying aspects of cardiogenic shock care where there was uncertainty regarding optimal patient management.

Methods:
An 18-person multidisciplinary panel comprising international experts was convened. A modified RAND/University of California Los Angeles appropriateness methodology was used. A survey comprising 70 statements was completed. Participants anonymously rated the appropriateness of each statement on a scale of 1 to 9: 1 to 3 inappropriate, 4 to 6 uncertain, and 7 to 9 appropriate. A summary of the results was discussed as a group, and the survey was iterated and completed again before final analysis.

Results:
There was broad alignment with current international guidelines and consensus statements. Overall, 44 statements were rated as appropriate, 19 as uncertain, and 7 as inappropriate. There was no disagreement with a disagreement index <1 for all statements. Routine fluid administration was deemed to be inappropriate. Areas of uncertainty focused panel on pre-PCI interventions, the use of right heart catheterization to guide management, routine use of left ventricular unloading strategies, and markers of futility when considering escalation to mechanical circulatory support.

Conclusions:
While there was broad alignment with current guidance, an expert panel found several aspects of care where there was clinical equipoise, further highlighting the need for randomized controlled trials to better guide patient management and decision making in cardiogenic shock.
Efficacy and Safety of Dapagliflozin in Heart Failure With Reduced Ejection Fraction According to N-Terminal Pro-B-Type Natriuretic Peptide: Insights From the DAPA-HF Trial
Authors: Butt Jawad H. , Adamson Carly , Docherty Kieran F. , de Boer Rudolf A. , Petrie Mark C. , Inzucchi Silvio E. , Kosiborod Mikhail N. , Maria Langkilde Anna , Lindholm Daniel , Martinez Felipe A. , Bengtsson Olof , Schou Morten , O’Meara Eileen , Ponikowski Piotr , Sabatine Marc S. , Sjöstrand Mikaela , Solomon Scott D. , Jhund Pardeep S. , McMurray John J.V. , Køber Lars 
Published: November 2021

Background:
Effective therapies for HFrEF usually reduce NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, and it is important to establish whether new treatments are effective across the range of NT-proBNP.

Methods:
We evaluated both these questions in the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial. Patients in New York Heart Association functional class II to IV with a left ventricular ejection fraction ≤40% and a NT-proBNP level ≥600 pg/mL (≥600 ng/L; ≥400 pg/mL if hospitalized for HF within the previous 12 months or ≥900 pg/mL if atrial fibrillation/flutter) were eligible. The primary outcome was the composite of an episode of worsening HF or cardiovascular death.

Results:

Of the 4744 randomized patients, 4742 had an available baseline NT-proBNP measurement (median, 1437 pg/mL [interquartile range, 857–2650 pg/mL]). Compared with placebo, treatment with dapagliflozin significantly reduced NT-proBNP from baseline to 8 months (absolute least-squares mean reduction, −303 pg/mL [95% CI, −457 to −150 pg/mL]; geometric mean ratio, 0.92 [95% CI, 0.88–0.96]). Dapagliflozin reduced the risk of worsening HF or cardiovascular death, irrespective of baseline NT-proBNP quartile; the hazard ratio for dapagliflozin versus placebo, from lowest to highest quartile was 0.43 (95% CI, 0.27–0.67), 0.77 (0.56–1.04), 0.78 (0.60–1.01), and 0.78 (0.64–0.95);
P
for interaction=0.09. Consistent benefits were observed for all-cause mortality. Compared with placebo, dapagliflozin increased the proportion of patients with a meaningful improvement (≥5 points) in Kansas City Cardiomyopathy Questionnaire total symptom score (
P
for interaction=0.99) and decreased the proportion with a deterioration ≥5 points (
P
for interaction=0.87) across baseline NT-proBNP quartiles.

Conclusions:
In patients with HFrEF, dapagliflozin reduced NT-proBNP by 300 pg/mL after 8 months of treatment compared with placebo. In addition, dapagliflozin reduced the risk of worsening HF and death, and improved symptoms, across the spectrum of baseline NT-proBNP levels included in DAPA-HF.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03036124.