bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organic food consumption during pregnancy and symptoms of neurodevelopmental disorders at 8 years of age in the offspring: the Norwegian Mother, Father and Child Cohort Study (MoBa)
Authors: Instanes Johanne T. , Solberg Berit S. , Kvalvik Liv G. , Klungsøyr Kari , Posserud Maj-Britt R. , Hartman Catharina A. , Haavik Jan 
Published: October 2024

Abstract
Background
Partially driven by public concerns about modern food production practices, organic food has gained popularity among consumers. However, the impact of organic food consumption during pregnancy on offspring health is scarcely studied. We aimed to investigate the association between maternal intake of organic food during pregnancy and symptoms of attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in offspring at 8 years of age.

Methods
This study was based on the Norwegian Mother, Father and Child Cohort Study (MoBa) and the Medical Birth Registry of Norway (MBRN). The total study sample included 40,707 mother–child pairs (children born 2002–2009). Organic food consumption during pregnancy was assessed by six questions from a food frequency questionnaire in mid-pregnancy (sum score 0–18). Symptoms of ADHD and ASD in the offspring aged 8 years were measured by ADHD (0–54) and ASD (0–39) symptom scores based on the Parent/Teacher Rating Scale for Disruptive Behaviour disorders and the Social Communication Questionnaire. Associations between maternal intake of organic food during pregnancy and symptoms of ADHD and ASD in the offspring were analyzed using regression models with adjustment for covariates such as maternal anxiety and depression, including sibling analysis.

Results
Mean ADHD and ASD symptom scores in the offspring differed only slightly by maternal intake of organic food. The covariate-adjusted unstandardized regression coefficient (adjusted(Adj)beta) with 95% confidence interval for the ADHD symptom score with one unit increase in organic food sum score was 0.03 (0.01, 0.05). Similarly, Adjbeta for autism symptom score was 0.07 (0.04, 0.10). For ADHD, the adjusted estimates weakened when adjusting for maternal symptoms of ADHD. The sibling analyses showed no significant results with Adjbeta − 0.07 (− 0.15, 0.01) and − 0.001 (− 0.12, 0.12) for ADHD and ASD outcomes, respectively.

Conclusions
We observed weak positive associations between frequent maternal organic food consumption during pregnancy and offspring ADHD and ASD symptom levels at 8 years of age. This trend weakened or disappeared after adjusting for maternal symptoms of ADHD, and in sibling analyses, suggesting that the associations mainly reflect genetic confounding. Our study indicates that consumption of organic food during pregnancy should neither be considered a risk factor nor protective against symptoms of ADHD and ASD in offspring.
Reducing rehospitalization in cardiac patients: a randomized, controlled trial of a cardiac care management program (“Cardiolotse”) in Germany
Authors: Schüttig Wiebke , Darius Harald , Reber Katrin C. , Coors Marie , Flothow Amelie , Holzgreve Alfred , Karmann Sebastian , Stürtz Anica , Zöller Rebecca , Kropp Saskia , Riesner Petra , Sundmacher Leonie 
Published: October 2024

Abstract
Background
We conducted a prospective, randomized, controlled, two-group parallel trial investigating the effectiveness of a care management program employing cardiac care navigators providing post-discharge support to patients compared to standard care.

Methods
The intervention commenced in 2019/2020 for 2862 patients hospitalized with heart failure, coronary heart disease, or cardiac arrhythmias in departments of cardiology across eight participating sites of a hospital group in Berlin, Germany. We analyzed the results using an intention-to-treat approach. The primary outcome was the all-cause rehospitalization rate after 12 months. Secondary outcomes included rehospitalizations due to one of the qualifying cardiac diagnoses, duration of rehospitalization, mortality, health-related quality of life, and several process indicators.
Trial data were collected from a combination of face-to-face and phone interviews conducted by hospital staff throughout the 12-month follow-up period using standardized questionnaires. Administrative claims data were provided by a large statutory health insurer. Outcomes for the intervention and control groups were compared using logistic regression, generalized linear models (GLMs) with a negative binomial distribution, ordinary least squares, and Cox proportional hazards regression.

Results
Compared to the control group (N = 1294), the intervention group (N = 1256) had a lower rate of all-cause rehospitalizations (62.6% vs. 66.4%, p = 0.05) and shorter lengths of stay (14.49 vs. 16.89 days, p = 0.02) during the 12-month follow-up period. These differences were also present for rehospitalizations due to the cardiac diseases qualifying for study recruitment, with rehospitalization rates for the intervention and control groups being 58.0% vs. 61.4% (p = 0.08) and particularly pronounced for lengths of rehospitalization stay of 12.97 vs. 15.40 days (p = 0.01), respectively. Subgroup analyses indicated positive effects of the intervention for patients 70 years and older (p = 0.05), females (p = 0.06), and those with little or no German language proficiency (p = 0.03). Furthermore, we found positive effects on patients’ adherence to health-related behavioral recommendations (81.91% vs. 73.95%, p = 0.000).

Conclusions
This study adds to the body of evidence indicating that care management interventions supporting patients as they transition from the inpatient to the outpatient sector can lower rehospitalizations, decrease length of rehospitalization stays, and improve adherence to post-discharge recommendations.

Trial registration
German Clinical Trial Register, DRKS00020424. Registered 2020-06-18. (retrospectively registered).
Heart-healthy diets including phytostanol ester consumption to reduce the risk of atherosclerotic cardiovascular diseases. A clinical review
Authors: Simonen Piia , Nylund Lotta , Vartiainen Erkki , Kovanen Petri T. , Strandberg Timo E. , Öörni Katariina , Wester Ingmar , Gylling Helena 
Published: October 2024

AbstractThe risk of atherosclerotic cardiovascular diseases (ASCVDs) can be reduced by lowering low-density lipoprotein cholesterol (LDL-C) concentrations. Nevertheless, ASCVDs still cause most deaths worldwide. Here, we discuss the prevention of ASCVD and the event risk with a focus on heart-healthy diets, i.e., low intakes of saturated and trans-fatty acids and cholesterol, and high intakes of unsaturated fatty acids, viscous fibre, and dietary phytostanols as fatty acid esters, according to international dyslipidaemia treatment guidelines. Calculations based on both FINRISK and Cholesterol Treatment Trialists’ Collaborators regression equations indicate that heart-healthy diets combined with phytostanol ester reduce LDL-C concentrations to such an extent that the 10-year estimated reduction in the incidence of coronary artery disease would be 23%. This information can be used, in particular, to prevent the development of subclinical atherosclerosis in healthy middle-aged populations and the progression of atherosclerosis to ASCVD. The outcome of simple and feasible dietary changes, and, when needed, combined with statins, can be significant: reduced mortality, an increased number of healthy life-years, and reduced healthcare costs.
The signature of extracellular vesicles in hypoxic breast cancer and their therapeutic engineering
Authors: Zhu Baiheng , Xiang Kehao , Li Tanghua , Li Xin , Shi Fujun 
Published: October 2024

AbstractBreast cancer (BC) currently ranks second in the global cancer incidence rate. Hypoxia is a common phenomenon in BC. Under hypoxic conditions, cells in the tumor microenvironment (TME) secrete numerous extracellular vesicles (EVs) to achieve intercellular communication and alter the metabolism of primary and metastatic tumors that shape the TME. In addition, emerging studies have indicated that hypoxia can promote resistance to tumor treatment. Engineered EVs are expected to become carriers for cancer treatment due to their high biocompatibility, low immunogenicity, high drug delivery efficiency, and ease of modification. In this review, we summarize the mechanisms of EVs in the primary TME and distant metastasis of BC under hypoxic conditions. Additionally, we highlight the potential applications of engineered EVs in mitigating the malignant phenotypes of BC cells under hypoxia.
Current understanding of the impact of United States military airborne hazards and burn pit exposures on respiratory health
Authors: Trembley Janeen H. , Barach Paul , Tomáška Julie M. , Poole Jedidah T. , Ginex Pamela K. , Miller Robert F. , Lindheimer Jacob B. , Szema Anthony M. , Gandy Kimberly , Siddharthan Trishul , Kirkness Jason P. , Nixon Joshua P. , Torres Rosie Lopez , Klein Mark A. , Nurkiewicz Timothy R. , Butterick Tammy A. 
Published: October 2024

AbstractMillions of United States (U.S.) troops deployed to the Middle East and Southwest Asia were exposed to toxic airborne hazards and/or open-air burn pits. Burn pit emissions contain particulate matter combined with toxic gasses and heavy metals. Ongoing research has demonstrated that exposures to the airborne hazards from military burn pits have profound and lasting health and wellness consequences. Research on the long-term health consequences of exposure to open burn pits has been limited. Work continues to understand the scope of the health impacts and the underlying pathobiology following exposures and to establish care standards. The U.S. Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics (PACT) Act was signed into law August 2022. This act expands the benefits and services to U.S. Veterans exposed to toxicants, requires the Veterans Health Administration to provide toxic exposure screening, and supports increased research, education, and treatment due to toxic occupational exposures. This review highlights the state of the science related to military burn pit exposures research with an emphasis on pulmonary health. Clinical data demonstrate areas of reduced or delayed pulmonary ventilation and lung pathologies such as small airways scarring, diffuse collagen deposition and focal areas of ossification. Identification and characterization of foreign matter deposition in lung tissues are reported, including particulate matter, silica, titanium oxides, and polycyclic aromatic hydrocarbons. These data are consistent with toxic exposures and with the symptoms reported by post-deployment Veterans despite near-normal non-invasive pulmonary evaluations. On-going work toward new methods for non-invasive pulmonary diagnoses and disease monitoring are described. We propose various studies and databases as resources for clinical and health outcomes research. Pre-clinical research using different burn pit modeling approaches are summarized, including oropharyngeal aspiration, intranasal inhalation, and whole-body exposure chamber inhalation. These studies focus on the impacts of specific toxic substances as well as the effects of short-term and sustained insults over time on the pulmonary systems.
Amyloid-β (Aβ) immunotherapy induced microhemorrhages are linked to vascular inflammation and cerebrovascular damage in a mouse model of Alzheimer’s disease
Authors: Taylor Xavier , Noristani Harun N. , Fitzgerald Griffin J. , Oluoch Herold , Babb Nick , McGathey Tyler , Carter Lindsay , Hole Justin T. , Lacor Pascale N. , DeMattos Ronald B. , Wang Yaming 
Published: October 2024

Abstract
Background
Anti-amyloid-β (Aβ) immunotherapy trials have revealed amyloid-related imaging abnormalities (ARIA) as the most prevalent and serious adverse events linked to pathological changes in cerebral vasculature. Recent studies underscore the critical involvement of perivascular macrophages and the infiltration of peripheral immune cells in regulating cerebrovascular damage. Specifically, Aβ antibodies engaged at cerebral amyloid angiopathy (CAA) deposits trigger perivascular macrophage activation and the upregulation of genes associated with vascular permeability. Nevertheless, further research is needed to understand the immediate downstream consequences of macrophage activation, potentially exacerbating CAA-related vascular permeability and microhemorrhages linked to Aβ immunotherapy.

Methods
This study investigates immune responses induced by amyloid-targeting antibodies and CAA-induced microhemorrhages using RNA in situ hybridization, histology and digital spatial profiling in an Alzheimer's disease (AD) mouse model of microhemorrhage.

Results
In the present study, we have demonstrated that bapineuzumab murine surrogate (3D6) induces profound vascular damage, leading to smooth muscle cell loss and blood–brain barrier (BBB) breakdown. In addition, digital spatial profiling (DSP) reveals that distinct immune responses contribute to vascular damage with peripheral immune responses and perivascular macrophage activation linked to smooth muscle cell loss and vascular fibrosis, respectively. Finally, RNA in situ hybridization identifies two distinct subsets of Trem2+ macrophages representing tissue-resident and monocyte-derived macrophages around vascular amyloid deposits. Overall, these findings highlight multifaceted roles of immune activation and vascular damage in driving the development of microhemorrhage.

Conclusions
In summary, our study has established a significant link between CAA-Aβ antibody immune complex formation, immune activation and vascular damage leading to smooth muscle cell loss. However, the full implications of this cascade on the development of microhemorrhages requires further exploration. Additional investigations are warranted to unravel the precise molecular mechanisms leading to microhemorrhage, the interplay of diverse immune populations and the functional roles played by various Trem2+ macrophage populations in response to Aβ immunotherapy.
A review of the response and the emergency medical team (EMT) deployment following a tanker explosion in Freetown, Sierra Leone
Authors: Oyugi Boniface , Kamara Ibrahim Franklyn , Nuwagira Innocent , Musoke Robert , Lakoh Sulaiman , Jalloh Abdulai , Kamara Rashidatu Fouad , Relan Pryanka , Lajolo Camila , Ndiaye René André Macodou , Niang Babacar , Fall Mouhamadou Mansour , Balde Thierno , Salio Flavio , Kabba Mustapha 
Published: October 2024

Abstract
Background
On 5 November 2021, a fire incident following a tanker explosion occurred in the Wellington PMB Junction east of Freetown, Sierra Leone, injuring and killing people. WHO facilitated the deployment of international emergency medical teams (EMTs) to support the Ministry of Health (MoH) in providing care to the wounded in four hospitals.

Objective
In this study, we document Sierra Leone's experience managing the fire incident and the role of EMTs in responding to it.

Method
This is a cross-sectional After-Action Review (AAR) debrief of the response and deployment, including focus group discussion with WHO and MoH staff (n = 14) in a virtual workshop and document reviews on the response. The results thematically cover the event and the different agencies' responses and a review of EMTs' responses.

Results
At the onset of the emergency, the National Disaster Management Agency (NDMA) instituted a well-coordinated response mechanism in collaboration with the MoH and managed all response actions, such as medical services, informing partners and the public and coordinating all other agencies. WHO facilitated EMT deployments and mobilised medical supplies and equipment, while the MoH provided accommodation, logistics and coordination. The EMTs dispensed their functions with professionalism, adapted to the environment and available resources, and augmented the care the national health workers provided. They offered additional care: reconstructive surgery, pain management, palliative care, wound care, rehabilitation, physiotherapy and psychosocial counselling, which were initially inadequate at the onset of the disaster. 94 out of 157 patients were discharged home at the end. National clinicians acquired additional skills through the capacity-building activities of EMTs. The community appreciated the teams.

Conclusion
The government, partners and EMTs were important in the response and worked with speed and political acceptability using the context experience to provide surge support to the country. This experience brought to focus the idea of developing a national EMT in Sierra Leone, which would be useful to help respond even more swiftly. In collaboration with WHO, there is a need to institute further mechanisms to facilitate rapid response and quality-assured deployment of EMTs at regional and sub-regional levels and strengthen to support future responses.
High-cost users after sepsis: a population-based observational cohort study
Authors: Barrett Kali A. , Sheikh Fatima , Chechulina Victoria , Chung Hannah , Dodek Peter , Rosella Laura , Thavorn Kednapa , Scales Damon C. ,   Sepsis Canada
Published: October 2024

Abstract
Background
High-cost users (HCU) represent important targets for health policy interventions. Sepsis is a life-threatening syndrome that is associated with high morbidity, mortality, and economic costs to the healthcare system. We sought to estimate the effect of sepsis on being a subsequent HCU.

Methods
Using linked health-administrative databases, we conducted a population-based, propensity score-weighted cohort study of adults who survived a hospitalization in Ontario, Canada between January 2016 and December 2017. Sepsis was identified using a validated algorithm. The primary outcome was being a persistent HCU after hospital discharge (in the top 5% or 1% of total health care spending for 90 consecutive days), and the proportion of follow-up time since discharge as a HCU.

Results
We identified 927,057 hospitalized individuals, of whom 79,065 had sepsis. Individuals who had sepsis were more likely to be a top 5% HCU for 90 consecutive days at any time after discharge compared to those without sepsis (OR 2.24; 95% confidence interval [CI] 2.04–2.46) and spent on average 42.3% of their follow up time as a top 5% HCU compared to 28.9% of time among those without sepsis (RR 1.46; 95% CI 1.45–1.48). Individuals with sepsis were more likely to be a top 1% HCU for 90 consecutive days compared to those without sepsis (10% versus 5.1%, OR 2.05 [95% CI 1.99–2.11]), and spent more time as a top 1% HCU (18.5% of time versus 10.8% of time, RR 1.68 [95% CI 1.65–1.70]).

Conclusions
The sequelae of sepsis result in higher healthcare costs with important economic implications. After discharge, individuals who experienced sepsis are more likely to be a HCU and spend more time as a HCU compared to individuals who did not experience sepsis during hospitalization.
Ribosomal S6 kinase (RSK) plays a critical role in DNA damage response via the phosphorylation of histone lysine demethylase KDM4B
Authors: Wu Wenwen , Zhu Jing , Nihira Naoe Taira , Togashi Yukiko , Goda Atsushi , Koike Junki , Yamaguchi Kiyoshi , Furukawa Yoichi , Tomita Takuya , Saeki Yasushi , Johmura Yoshikazu , Nakanishi Makoto , Miyoshi Yasuo , Ohta Tomohiko 
Published: October 2024

Abstract
Background
Epigenetic dysregulation affecting oncogenic transcription and DNA damage response is a hallmark of cancer. The histone demethylase KDM4B, a factor regulating these processes, plays important roles in estrogen receptor-mediated transcription and DNA repair in breast cancer. However, how oncogenic phospho-signal transduction affects epigenetic regulation is not fully understood. Here we found that KDM4B phosphorylation by ribosomal S6 kinase (RSK), a downstream effector of the Ras/MAPK pathway, is critical for the function of KDM4B in response to DNA damage.

Methods
KDM4B-knockout breast cancer cell lines were generated via CRISPR/Cas9-mediated gene editing. Re-expression of wild-type or phospho-site mutated KDM4B in knockout cells was performed by lentivirus-mediated gene transfer. Gene knockdown was achieved by RNA interference. DNA double-strand breaks (DSBs) were induced by ionizing radiation or laser-microirradiation. Protein accumulation at DSB sites was analyzed by immunofluorescence. KDM4B phosphorylation by RSK was assessed by in vitro and in vivo kinase assays. Gene and protein expression levels were analyzed by RT‒PCR and western blotting. The sensitivity of cells to ionizing radiation was examined by a clonogenic survival assay.

Results
RSK phosphorylated KDM4B at Ser666, and inhibition of the phosphorylation by RSK depletion or RSK inhibitors abrogated KDM4B accumulation at the sites of DNA double-strand breaks (DSBs). DSB repair was significantly delayed in KDM4B-knockout cells or cells treated with RSK inhibitors. The replacement of endogenous KDM4B with the phosphomimetic mutant S666D restored KDM4B accumulation and DSB repair that had been inhibited by RSK inhibitors, suggesting a critical role for RSK at the specific serine residue of KDM4B in the effect of RSK inhibitors on DSB repair. As a consequence of these aberrant responses, inhibition of KDM4B phosphorylation increased the sensitivity of the cells to ionizing radiation.

Conclusions
Overall, the present study uncovered a novel function of RSK on the DNA damage response, which provides an additional role of its inhibitor in cancer therapy.
Integrating metabolomics and proteomics to identify novel drug targets for heart failure and atrial fibrillation
Authors: van Vugt Marion , Finan Chris , Chopade Sandesh , Providencia Rui , Bezzina Connie R. , Asselbergs Folkert W. , van Setten Jessica , Schmidt A. Floriaan 
Published: October 2024

Abstract

Background

Altered metabolism plays a role in the pathophysiology of cardiac diseases, such as atrial fibrillation (AF) and heart failure (HF). We aimed to identify novel plasma metabolites and proteins associating with cardiac disease.

Methods
Mendelian randomisation (MR) was used to assess the association of 174 metabolites measured in up to 86,507 participants with AF, HF, dilated cardiomyopathy (DCM), and non-ischemic cardiomyopathy (NICM). Subsequently, we sourced data on 1567 plasma proteins and performed cis MR to identify proteins affecting the identified metabolites as well as the cardiac diseases. Proteins were prioritised on cardiac expression and druggability, and mapped to biological pathways.

Results
We identified 35 metabolites associating with cardiac disease. AF was affected by seventeen metabolites, HF by nineteen, DCM by four, and NCIM by taurine. HF was particularly enriched for phosphatidylcholines (p = 0.029) and DCM for acylcarnitines (p = 0.001). Metabolite involvement with AF was more uniform, spanning for example phosphatidylcholines, amino acids, and acylcarnitines. We identified 38 druggable proteins expressed in cardiac tissue, with a directionally concordant effect on metabolites and cardiac disease. We recapitulated known associations, for example between the drug target of digoxin (AT1B2), taurine and NICM risk. Additionally, we identified numerous novel findings, such as higher RET values associating with phosphatidylcholines and decreasing AF and HF. RET is targeted by drugs such as regorafenib which has known cardiotoxic side-effects. Pathway analysis implicated involvement of GDF15 signalling through RET, and ghrelin regulation of energy homeostasis in cardiac pathogenesis.

Conclusions
This study identified 35 plasma metabolites involved with cardiac diseases and linked these to 38 druggable proteins, providing actionable leads for drug development.