bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of glucocorticoid receptors as potential modulators of parasympathetic and sympathetic neurons within rat intracardiac ganglia
Authors: Mousa Shaaban A. , Dehe Lukas , Aboryag Noureddin , Shaqura Mohammed , Beyer Antje , Schäfer Michael , Treskatsch Sascha 
Published: September 2022

BackgroundEmerging evidences indicate that glucocorticoid receptors (GR) play a regulatory role in cardiac function, particularly with regard to the autonomic nervous system. Therefore, this study aimed to demonstrate the expression and the precise anatomical location of GR in relation to the parasympathetic and sympathetic innervations of the heart.MethodsThe present study used tissue samples from rat heart atria to perform conventional reverse-transcriptase polymerase chain reaction (RT-PCR), Western blot, and double immunofluorescence confocal analysis of GR with the neuronal markers vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), calcitonin gene-related peptide (CGRP) as well as the mineralocorticoid receptor (MR).ResultsDouble immunofluorescence labeling revealed that GRs were co-expressed with VAChT in parasympathetic principal neuronal somata and nerve terminals innervating atrium. Also, GR colocalized with the sympathetic neuronal marker TH in a cluster of small intensely fluorescent (SIF) cells, on intracardiac nerve terminals and in the atrial myocardium. GR immunoreactivity was scarcely identified on CGRP-immunoreactive sensory nerve terminals. Approximately 20% of GR immunoreactive neuronal somata co-localized with MR. Finally, conventional RT-PCR and Western blot confirmed the presence of GR and MR in rat heart atria.ConclusionThis study provides evidence for the existence of GR predominantly on cardiac parasympathetic neurons and TH-immunoreactive SIF cells suggesting a functional role of cardiac GR on cardiovascular function by modulation of the cardiac autonomic nervous system.
Cranial autonomic symptoms and response to monoclonal antibodies targeting the Calcitonin gene-related peptide pathway: A real-world study
Authors: De Matteis Eleonora , Caponnetto Valeria , Casalena Alfonsina , Frattale Ilaria , Gabriele Amleto , Affaitati Giannapia , Giamberardino Maria Adele , Maddestra Maurizio , Viola Stefano , Pistoia Francesca , Sacco Simona , Ornello Raffaele 
Published: September 2022

ObjectiveCranial autonomic symptoms (CAS), including conjunctival injection, tearing, nasal congestion or rhinorrhea, eyelid edema, miosis or ptosis, and forehead or facial sweating ipsilateral to headache, are often reported by patients with migraine during headache attacks. CAS is a consequence of the activation of the trigeminovascular system, which is the target of monoclonal antibodies acting on the CGRP pathway. Therefore, we hypothesized that patients with CAS might have higher trigeminovascular activation than those without CAS leading to a better response to anti-CGRP treatments.MethodsWe performed a prospective analysis including patients with episodic or chronic migraine treated with anti-CGRP monoclonal antibodies (i.e., erenumab, fremanezumab, and galcanezumab) between 2019 and 2021. The observation period included a 12-week baseline before treatment with anti-CGRP antibodies and a 12-week treatment follow-up. We evaluated the prevalence of CAS in our cohort and compared disease characteristics and treatment response (i.e., 12-week monthly headache days and 0–29, 30–49, 50–74, 75–99, and 100% monthly headache days reduction from baseline) among patients with and without CAS using the χ2 test, Kruskal–Wallis test, and Mann–Whitney U-test.ResultsOut of 136 patients, 88 (65%) had CAS. Both patients with and without CAS reported a significant decrease in monthly headache days from baseline. During the 12-week follow-up, the median difference in monthly headache days from baseline was higher in patients with CAS (-10, IQR−15 to−6) than in those without CAS (6, IQR 12 to 3; P = 0.009). However, the proportions of patients with 0 to 29, 30 to 49, 50 to 74, 75 to 99, and 100% response rates did not differ between the two groups.ConclusionsIn our cohort, the presence of CAS was associated with a greater response to monoclonal antibodies targeting the CGRP pathway. CAS could be a clinical marker of trigeminovascular activation and thus be related to a better response to CGRP treatments.
Exclusive color-coded duplex sonography of extracranial vessels reliably confirms brain death: A prospective study
Authors: Lambeck Johann , Strecker Christoph , Niesen Wolf-Dirk , Bardutzky Jürgen 
Published: September 2022

BackgroundTranscranial color-coded duplex sonography (TCCD) can be used as an ancillary test for determining irreversible loss of brain function (ILBF) when demonstration of cerebral circulatory arrest (CCA) is required. However, visualization of the intracranial vessels by TCCD is often difficult, or even impossible, in this patient cohort due to elevated intracranial pressure, an insufficient transtemporal bone window, or warped anatomical conditions. Since extracranial color-coded duplex sonography (ECCD) can be performed without restriction in the aforementioned situations, we investigated the feasibility of omitting TCCD altogether, such that the ILBF examination would be simplified, without compromising on its reliability.MethodsA total of 122 patients were prospectively examined by two experienced neurointensivists for the presence of ILBF from 01/2019-12/2021. Inclusion criteria were (i) the presence of a severe cerebral lesion on cranial CT or MRI, and (ii) brainstem areflexia. Upon standardized clinical examination, 9 patients were excluded due to incomplete brainstem areflexia, and a further 22 due to the presence of factors with a potentially confounding influence on apnea testing, EEG or sonography. A total of 91 patients were enrolled and underwent needle-EEG recording for &gt;30 min (= gold standard), as well as ECCD and TCCD. The sonographer was blinded to the EEG result.ResultsAll patients whose ECCD result was consistent with ILBF had this diagnosis confirmed by EEG (n = 77; specificity: 1). Both ECCD and EEG were not consistent with ILBF in a further 12 patients. In the remaining two patients, ECCD detected reperfusion due to long-lasting cerebral hypoxia; however, ILBF was ultimately confirmed by EEG (sensitivity: 0.975). This yielded a positive predictive value (PPV) of one and a negative predictive value of 0.857 for the validity of ECCD in ILBF confirmation. TCCD was not possible/inconclusive in 31 patients (34%).ConclusionsThe use of ECCD for the confirmation of ILBF is associated with high levels of specificity and a high positive predictive value when compared to needle-electrode EEG. This makes ECCD a potential alternative to the ancillary tests currently used in this setting, but confirmation in a multi-center trial is warranted.Trial registrationhttps://www.drks.de, DRKS00017803.
Experiences and needs of the caregivers of stroke survivors in Malaysia—A phenomenological exploration
Authors: Sidek Norsima Nazifah , Kamalakannan Sureshkumar , Tengku Ismail Tengku Alina , Musa Kamarul Imran , Ibrahim Khairul Azmi , Abdul Aziz Zariah , Papachristou Nadal Iliatha 
Published: September 2022

IntroductionInformal caregivers play a crucial role in supporting the activities of daily living, rehabilitation, and the road to recovery for stroke survivors. However, these informal caregivers are often reported as experiencing neglect and lack of recognition despite their primary contribution to stroke recovery. This study investigated the experiences of the caregivers of stroke survivors and access to stroke care in Malaysia.MethodThis qualitative study with a phenomenological approach utilized in-depth interviews, including ten primary caregivers, one formal caregiver, and stroke healthcare providers as the participants. The interviews were done until the data saturation was achieved, and the data was analyzed using thematic analysis.ResultThree primary themes and 14 subthemes were identified from the interviews. The role of primary caregivers of stroke survivors had tremendous physical, mental and social impact on the caregivers. Caregivers had two primary needs. The need for information about comprehensive stroke care at home and the need for psychological support to themselves. The key internal driver for providing care was identified to be the motivation level of the stroke survivor and the external driver was identified to be the societal support with access to comprehensive stroke care.ConclusionThe role of informal caregivers becomes critical for continuum of stroke care. As caregivers take up the roles and responsibilities of those who contribute to stroke rehabilitation single-handedly soon after hospital discharge. Results of this study highlights the needs for providing systematic support to caregivers for engaging them in effective stroke care, particularly in the community. Stroke service providers, policy makers and program planners must be sensitized to empower caregivers of stroke survivors in effectively supporting stroke survivor in their family on the road of recovery.
Synergetic reorganization of the contralateral structure and function in patients with unilateral frontal glioma
Authors: Ge Honglin , Yan Zheng , Liu Dongming , Qi Wenzhang , Chen Shanshan , Yang Kun , Liu Hongyi , Zou Yuanjie , Hu Xinhua , Liu Yong , Chen Jiu 
Published: September 2022

ObjectiveThis study aimed to investigate the contralateral structural and functional plasticity induced by frontal gliomas.MethodsPatients with left (n = 49) or right (n = 52) frontal diffuse glioma were enrolled along with 35 age- matched healthy controls (HCs). The gray-matter volumes (GMVs) of the contralesional region were measured using the voxel-based morphometry (VBM) analysis. Additionally, the amplitude of low-frequency fluctuation (ALFF) of the contralesional region was calculated via resting state functional magnetic resonance imaging (MRI) to assess functional alterations.ResultThe GMV of the contralateral orbitofrontal cortex of the right or left frontal gliomas was significantly larger than the corresponding GMV in the controls. In the patients with right frontal glioma, the GMV and ALFF in the left inferior frontal gyrus were significantly increased compared with those in the controls.ConclusionGlioma invasion of the frontal lobe can induce contralateral structural compensation and functional compensation, which show synergy in the left inferior frontal gyrus. Our findings explain why patients with unilateral frontal glioma can have functional balance, and offer the possibility of preserving the brain function while maximizing tumor removal.
Functional Connectivity Features of Resting-State Functional Magnetic Resonance Imaging May Distinguish Migraine From Tension-Type Headache
Authors: Wang Yajuan , Wang Yingshuang , Bu Lihong , Wang Shaoyang , Xie Xinhui , Lin Fuchun , Xiao Zheman 
Published: September 2022

BackgroundMigraineurs often exhibited abnormalities in cognition, emotion, and resting-state functional connectivity (rsFC), whereas patients with tension-type headache (TTH) rarely exhibited these abnormalities. The aim of this study is to explore whether rsFC alterations in brain regions related to cognition and emotion could be used to distinguish patients with migraine from patients with TTH.MethodsIn this study, Montreal Cognitive Assessment (MoCA), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and rsFC analyses were used to assess the cognition, anxiety, and depression of 24 healthy controls (HCs), 24 migraineurs, and 24 patients with TTH. Due to their important roles in neuropsychological functions, the bilateral amygdala and hippocampus were chosen as seed regions for rsFC analyses. We further assessed the accuracy of the potential rsFC alterations for distinguishing migraineurs from non-migraineurs (including HCs and patients with TTH) by the receiver operating characteristic (ROC) analysis. Associations between headache characteristics and rsFC features were calculated using a multi-linear regression model. This clinical trial protocol has been registered in the Chinese Clinical Trial Registry (registry number: ChiCTR1900024307, Registered: 5 July 2019-Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=40817).ResultsMigraineurs showed lower MoCA scores (p = 0.010) and higher SAS scores (p = 0.017) than HCs. Migraineurs also showed decreased rsFC in the bilateral calcarine/cuneus, lingual gyrus (seed: left amygdala), and bilateral calcarine/cuneus (seed: left hippocampus) in comparison to HCs and patients with TTH. These rsFC features demonstrated significant distinguishing capabilities and got a sensitivity of 82.6% and specificity of 81.8% with an area under the curve (AUC) of 0.868. rsFC alterations showed a significant correlation with headache frequency in migraineurs (p = 0.001, Pc = 0.020).ConclusionThe rsFC of amygdala and hippocampus with occipital lobe can be used to distinguish patients with migraine from patients with TTH.Clinical Trial Registration[http://www.chictr.org.cn/showproj.aspx?proj=40817], identifier [ChiCTR1900024307].
Association between infection and nutritional status among infants in a cohort study of vitamin A in western Kenya
Authors: Grant Frederick K. , Wanjala Rose , Low Jan , Levin Carol , Cole Donald C. , Okuku Haile S. , Ackatia-Armah Robert , Girard Amy W. 
Published: September 2022

BackgroundInfection is associated with impaired nutritional status, especially for infants younger than 5 years.ObjectivesWe assessed the impact of infection indicated by both acute phase proteins (APP), C-reactive protein (CRP), and α-1-acid-glycoprotein (AGP), and as reported by maternal recall on the nutritional status of infants.Materials and methodsA total of 505 pregnant women were enrolled in a nested longitudinal cohort study of vitamin A (VA). Data from 385 children are reported here. The incidence and severity of respiratory infection and diarrhea (previous 14 days) were assessed by maternal recall; infant/child feeding practices were collected. Infant weight, recumbent length, and heel-prick capillary blood were taken at 9 months postpartum. Indicators of the VA status [retinol binding protein (RBP)], iron status (Hb, ferritin), and subclinical inflammation APP, CRP (&gt;5 mg/L), and AGP (&gt;1 g/L) were determined. Impacts of infection on the infant nutritional status were estimated using logistic regression models.ResultsInfection prevalence, based on elevated CRP and AGP levels, was 36.7%. For diarrhea reported symptoms, 42.4% of infants at 9 months had no indication of infection as indicated by CRP and AGP; for acute respiratory reported symptoms, 42.6% had no indication of infection. There was a significant positive association with infection among VA-deficient (RBP &lt; 0.83 μmol/L) infants based on maternal reported symptoms but not with iron deficiency (ferritin &lt; 12 μg/L). The odds of having infection, based on increased CRP and AGP, in underweight infants was 3.7 times higher (OR: 3.7; 95% CI: 2.3, 4.5;P= 0.019). Infants with iron deficiency were less likely (OR: 0.40; 95% CI: 0.1, 0.7;P= 0.001) to have infection based on CRP and AGP, while infants with VA deficiency were five times more likely (OR: 5.06; 95% CI: 3.2, 7.1;P= 0.0001) to have infection.ConclusionAcute phase proteins are more useful in defining infection in a population than reported symptoms of illness. Not controlling for inflammation in a population while assessing the nutritional status might result in inaccurate prevalence estimation.
Association between omega-3/6 fatty acids and cholelithiasis: A mendelian randomization study
Authors: Sun Qi , Gao Ning , Xia Weiliang 
Published: September 2022

BackgroundOmega-3 and omega-6 may be protective factors for cholelithiasis. However, this relationship has not yet been demonstrated clearly. Therefore, we attempted to identify these causal relationships.Materials and methodsThe omega-3/6 fatty acid discovery dataset was obtained from UK Biobank and contained 114,999 individuals. The validation set was derived from an independent genome-wide association study (GWAS) and contained 13,544 individuals. The cholelithiasis dataset was derived from FinnGen and contained 19,023 cases and 195,144 controls. The inverse variance weighting (IVW) method was used as the main method of analysis in this study. Multiple methods of analysis were also used in the repeated methods, including the MR-Egger, weighted median, MR-pleiotropic residual sum (MR-PRESSO), outliers, and maximum likelihood methods. In addition, we used multiple sensitivity analyses to identify the potential pleiotropy.ResultIn the discovery stage, the results of the random effect IVW analysis showed that higher omega-3 levels were correlated inversely with the risk of cholelithiasis (β = –0.22, 95% CI [–0.32 to –0.12], P = 1.49 × 10–5). When the replication analysis was performed using another set of instrumental variables (IVs), the causal relationship between omega-3 fatty acids and cholelithiasis remained stable (β = –0.42, 95% CI [–0.66 to –0.18], P = 5.49 × 10–4), except for the results obtained using the MR-Egger method, which were not significant. The results of the IVW approach showed that each SD increase in omega-6 levels was associated negatively with the risk of cholelithiasis, both in the discovery (β = –0.21, 95% CI [–0.35 to –0.06], P = 4.37 × 10–3) and the validation phases (β = –0.21, 95% CI [–0.40 to –0.02], P = 3.44 × 10–2).ConclusionThe results of our MR study suggest that omega-3/6 is associated with cholelithiasis risk. Attention to the risk of cholelithiasis in individuals with low serum omega-3/6 levels is necessary.
Identification and immune characteristics of molecular subtypes related to fatty acid metabolism in idiopathic pulmonary fibrosis
Authors: Yang Fan , Ma Zhaotian , Li Wanyang , Kong Jingwei , Zong Yuhan , Wendusu Bilige , Wu Qinglu , Li Yao , Dong Guangda , Zhao Xiaoshan , Wang Ji 
Published: September 2022

BackgroundAlthough fatty acid metabolism has been confirmed to be involved in the pathological process of idiopathic pulmonary fibrosis (IPF), systematic analyses on the immune process mediated by fatty acid metabolism-related genes (FAMRGs) in IPF remain lacking.MethodsThe gene expression data of 315 patients with IPF were obtained from Gene Expression Omnibus database and were divided into the training and verification sets. The core FAMRGs of the training set were identified through weighted gene co-expression network analysis. Then, the fatty acid metabolism-related subtypes in IPF were identified on the basis of k-means unsupervised clustering. The scores of fatty acid metabolism and the expression of the fibrosis biomarkers in different subtypes were compared, and functional enrichment analysis was carried out on the differentially expressed genes between subtypes. A random forest model was used to select important FAMRGs as diagnostic markers for distinguishing between subtypes, and a line chart model was constructed and verified by using other datasets and rat models with different degrees of pulmonary fibrosis. The difference in immune cell infiltration among subtypes was evaluated with CIBERSORT, and the correlation between core diagnostic markers and immune cells were analyzed.ResultsTwenty-four core FAMRGs were differentially expressed between the training set and normal samples, and IPF was divided into two subtypes. Significant differences were observed between the two subtypes in biological processes, such as linoleic acid metabolism, cilium movement, and natural killer (NK) cell activation. The subtype with high fatty acid metabolism had more severe pulmonary fibrosis than the other subtype. A reliable construction line chart model based on six diagnostic markers was constructed, and ABCA3 and CYP24A1 were identified as core diagnostic markers. Significant differences in immune cell infiltration were found between the two subtypes, and ABCA3 and CYP24A1 were closely related to NK cells.ConclusionFatty acid metabolism and the immune process that it mediates play an important role in the occurrence and development of IPF. The analysis of the role of FAMRGs in IPF may provide a new potential therapeutic target for IPF.
Contemporary Chinese dietary pattern: Where are the hidden risks?
Authors: Xiang Hong , Tao Xufeng , Guan Xi , Yin Tianyi , Li Junchen , Dong Deshi , Shang Dong 
Published: September 2022

BackgroundWith the rapid improvement in economy and lifestyle, dietary risk-related diseases have become a public health problem worldwide. However, the health effects of dietary risk over time have not been fully clarified in China. Here, we explored the temporal trends in the death burden of unhealthy dietary habits in China and benchmark dietary risk challenges in China to G20 member states.MethodSex–age-specific burdens due to dietary risk in China were extracted from the Global Burden of Disease (GBD) Study 2019, including annual numbers and age-standardized rates (ASRs) of death, disability-adjusted life years (DALYs), and summary exposure values (SEVs) during 1990–2019. The variation trend of ASRs was evaluated by estimated annual percentage changes (EAPCs).ResultBetween 1990 and 2019, the number of dietary risk-based death and DALYs increased significantly in China with an overall downward trend of ASDR and ASR-DALYs. Ischemic heart disease was the first cause of death from diet, followed by stroke and colon and rectum cancers. Chinese men were at greater risk than women for diet-related death and DALYs. Further analysis showed that a high sodium diet has always been the “No. 1 killer” that threatens the health of Chinese residents. The death burden of dietary risk demonstrated an increasing trend with age, and the peak was reached in people over 75 years. Compared with other G20 countries, Japan and South Korea have the most similar dietary patterns to China with the character of high sodium intake. Notably, decreased whole grain intake, as the primary dietary risk attributable to death and DALYs burden in the United States and European countries, had already ranked second in China's dietary risks.ConclusionChina's dietary burden cannot be ignored. Chinese residents should pay more attention to the collocation of dietary nutrients, especially men and 75+ years (elderly) people. Targeted dietary adjustments can significantly reduce deaths and DALYs in China.