bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet-derived growth factor signaling in pericytes promotes hypothalamic inflammation and obesity
Authors: Okekawa Akira , Wada Tsutomu , Onogi Yasuhiro , Takeda Yuki , Miyazawa Yuichiro , Sasahara Masakiyo , Tsuneki Hiroshi , Sasaoka Toshiyasu 
Published: February 2024

Abstract
Background
Pericytes are a vital component of the blood–brain barrier, and their involvement in acute inflammation was recently suggested. However, it remains unclear whether pericytes contribute to hypothalamic chronic inflammation and energy metabolism in obesity. The present study investigated the impact of pericytes on the pathophysiology of obesity by focusing on platelet-derived growth factor (PDGF) signaling, which regulates pericyte functions.

Methods
Tamoxifen-inducible systemic conditional PDGF receptor β knockout mice (Pdgfrb∆SYS-KO) and Calcium/calmodulin-dependent protein kinase type IIa (CaMKIIa)-positive neuron-specific PDGF receptor β knockout mice (Pdgfrb∆CaMKII-KO) were fed a high-fat diet, and metabolic phenotypes before and 3 to 4 weeks after dietary loading were examined. Intracellular energy metabolism and relevant signal transduction in lipopolysaccharide- and/or platelet-derived growth factor-BB (PDGF-BB)-stimulated human brain pericytes (HBPCs) were assessed by the Seahorse XFe24 Analyzer and Western blotting. The pericyte secretome in conditioned medium from HBPCs was studied using cytokine array kit, and its impact on polarization was examined in bone marrow-derived macrophages (BMDMs), which are microglia-like cells.

Results
Energy consumption increased and body weight gain decreased after high-fat diet loading in Pdgfrb∆SYS-KO mice. Cellular oncogene fos (cFos) expression increased in proopiomelanocortin (POMC) neurons, whereas microglial numbers and inflammatory gene expression decreased in the hypothalamus of Pdgfrb∆SYS-KO mice. No significant changes were observed in Pdgfrb∆CaMKII-KO mice. In HBPCs, a co-stimulation with lipopolysaccharide and PDGF-BB shifted intracellular metabolism towards glycolysis, activated mitogen-activated protein kinase (MAPK), and modulated the secretome to the inflammatory phenotype. Consequently, the secretome showed an increase in various proinflammatory chemokines and growth factors including Epithelial-derived neutrophil-activating peptide 78 (C-X-C motif chemokine ligand (CXCL)5), Thymus and activation-regulated chemokine (C–C motif chemokine (CCL)17), Monocyte chemoattractant protein 1 (CCL2), and Growth-regulated oncogene α (CXCL1). Furthermore, conditioned medium from HBPCs stimulated the inflammatory priming of BMDMs, and this change was abolished by the C-X-C motif chemokine receptor (CXCR) inhibitor. Consistently, mRNA expression of CXCL5 was elevated by lipopolysaccharide and PDGF-BB treatment in HBPCs, and the expression was significantly lower in the hypothalamus of Pdgfrb∆SYS-KO mice than in control Pdgfrbflox/flox mice (FL) following 4 weeks of HFD feeding.

Conclusions
PDGF receptor β signaling in hypothalamic pericytes promotes polarization of macrophages by changing their secretome and contributes to the progression of obesity.
Validity and reliability of Arabic version of pediatric migraine disability assessment scale (Child Self-Report versus Parent Proxy-Report): a multi-center study
Authors: Magdy Rehab , Hassan Amr , Mohammed Zeinab , Abdeltwab Mohamed A. , Ghaffar Nawal F. Abdel , Hussein Mona 
Published: February 2024

Abstract
Background
Pediatric Migraine Disability Assessment (PedMIDAS) is one of the most frequently used questionnaires to assess disability from migraine in pediatric patients. This work aimed to evaluate the validity and test–retest reliability of the Arabic version of the child self-report versus the parent proxy report PedMIDAS. We also aimed to test the agreement between children's and parents' reports of the scale.

Methods
PedMIDAS was subjected to translation and back-translation, then applied to 112 pediatric patients fulfilling the migraine diagnostic criteria. This cross-sectional study was conducted on two visits, one week apart. At visit 1, the following data were obtained from the included pediatric patients: disease duration, migraine type, current treatment regimen, monthly migraine days (MMD) during the last month preceding the enrollment, and migraine intensity using the visual analogue scale. Then, each child and his parent were independently asked to fill out PedMIDAS and Child Self-Report of the Pediatric Quality of Life Inventory™ 4.0 (PedsQL™) to test the convergent validity of PedMIDAS. At visit 2, each child was requested to complete PedMIDAS again, and so was the parent to evaluate test–retest reliability.

Results
Cronbach’s alpha was estimated to be 0.94 for each instrument. For the child-self report PedMIDAS, the average measure intraclass correlation coefficient (ICC) value was 0.992 (95%CI = 0.989–0.995), while it was estimated to be 0.990 for the parent-proxy report with 95%CI = 0.985–0.993, indicating excellent test–retest reliability for both instruments. The child-self report and the parent-proxy report PedMIDAS scores were significantly correlated with MMD, VAS, and all domains of the corresponding PedsQL, supporting convergent validity for both instruments. Agreement between parent and child on disability grading categories of PedMIDAS was substantial (κ = 0.644).

Conclusion
The Arabic version of PedMIDAS was a valid and reliable instrument to assess disability from migraine in Arabic-speaking pediatric patients with migraine. Parent reports can be valuable as a complement to child reports for a comprehensive assessment of migraine.
Arterial hypertension in the chronic evolution of migraine: bystander or risk factor? An overview
Authors: Mazzacane Federico , Vaghi Gloria , Cotta Ramusino Matteo , Perini Giulia , Costa Alfredo 
Published: February 2024

Abstract
Background
Several risk factors are associated with the chronic evolution of migraine. Clinical and preclinical studies have provided data about the role of hypertension (HT) as one of the potential modifiable risk factors of chronic migraine (CM). This review is focused on the biological and clinical evidence supporting common mechanisms underlying HT and migraine and the potential role of HT in the transition from episodic to chronic migraine.

Methods
We conducted a narrative review from a literature search covering the available evidence from studies investigating: i) the role of HT in the transition to CM in clinical practice; ii) the biological mechanisms potentially underpinning the association between HT and evolution to CM; iii) the role of antihypertensive medications in migraine prophylaxis.

Results
HT proved to be at the base of multiple mechanisms underlying migraine and migraine chronicization. Endothelial dysfunction, blood–brain barrier alterations, calcitonin gene-related peptide signaling, and renin–angiotensin–aldosterone system dysregulation are involved in the worsening effect of HT on migraine frequency, and the role of HT in the transition to CM is supported by clinical observations.

Conclusions
The observed evidence supports HT contribution to CM evolution due to shared pathophysiologic mechanisms. While a bidirectional influence appears to be ascertained, data are still lacking about the one-way role of HT as direct risk factor for CM transition. Further research is needed to confirm a causal role of HT in this process.
Dynamic changes in glymphatic function in reversible cerebral vasoconstriction syndrome
Authors: Wu Chia-Hung , Kuo Yu , Ling Yu-Hsiang , Wang Yen-Feng , Fuh Jong-Ling , Lirng Jiing-Feng , Wu Hsiu-Mei , Wang Shuu-Jiun , Chen Shih-Pin 
Published: February 2024

Abstract
Background
The pathophysiology of the reversible cerebral vasoconstriction syndrome (RCVS) remains enigmatic and the role of glymphatics in RCVS pathophysiology has not been evaluated. We aimed to investigate RCVS glymphatic dynamics and its clinical correlates.

Methods
We prospectively evaluated the glymphatic function in RCVS patients, with RCVS subjects and healthy controls (HCs) recruited between August 2020 and November 2023, by calculating diffusion-tensor imaging along the perivascular space (DTI-ALPS) index under a 3-T MRI. Clinical and vascular (transcranial color-coded duplex sonography) investigations were conducted in RCVS subjects. RCVS participants were separated into acute (≤ 30 days) and remission (≥ 90 days) groups by disease onset to MRI interval. The time-trend, acute stage and longitudinal analyses of the DTI-ALPS index were conducted. Correlations between DTI-ALPS index and vascular and clinical parameters were performed. Bonferroni correction was applied to vascular investigations (q = 0.05/11).

Results
A total of 138 RCVS patients (mean age, 46.8 years ± 11.8; 128 women) and 42 HCs (mean age, 46.0 years ± 4.5; 35 women) were evaluated. Acute RCVS demonstrated lower DTI-ALPS index than HCs (p < 0.001) and remission RCVS (p < 0.001). A continuously increasing DTI-ALPS trend after disease onset was demonstrated. The DTI-ALPS was lower when the internal carotid arteries resistance index and six-item Headache Impact test scores were higher. In contrast, during 50–100 days after disease onset, the DTI-ALPS index was higher when the middle cerebral artery flow velocity was higher.

Conclusions
Glymphatic function in patients with RCVS exhibited a unique dynamic evolution that was temporally coupled to different vascular indices and headache-related disabilities along the disease course. These findings may provide novel insights into the complex interactions between glymphatic transport, vasomotor control and pain modulation.
Dual-targeted nano-encapsulation of neonatal porcine islet-like cell clusters with triiodothyronine-loaded bifunctional polymersomes
Authors: Lee Sang Hoon , Kim Minse , Lee Eun-Jin , Ahn Sun Mi , Ahn Yu-Rim , Choi Jaewon , Kang Jung-Taek , Kim Hyun-Ouk 
Published: February 2024

AbstractThere is growing evidence that neonatal porcine islet-like cell clusters (NPCCs) isolated from piglets can be used to treat type 1 diabetes in humans. However, graft rejection is a common complication in humans owing to the prevalence of xenoantigens in porcine. Therefore, researchers have investigated various islet encapsulation techniques that could protect against these antigens. To this end, this study presents a robust nano-encapsulation method based on bifunctional polymersomes (PSomes), in which N-hydroxysuccinimide (NHS) and maleimide (Mal) groups conjugated to the PSomes terminal interact with the amine and thiol groups on the surface of NPCCs to induce dual targeting via two covalent bonds. The findings indicate that the ratio of NHS to Mal on PSomes is optimal for dual targeting. Moreover, triiodothyronine (T3) is known to promotes pancreatic islet maturation and differentiation of endocrine cells into beta cells. T3 encapsulated in PSomes is shown to increase the glucose sensitivity of NPCCs and enhance insulin secretion from NPCCs. Furthermore, improvements in the nano-encapsulation efficiency and insulin-secreting capability of NPCCs through dual targeting via dual-Psomes are demonstrated. In conclusion, the proposed nano-encapsulation technique could pave the way for significant advances in islet nano-encapsulation and the imprevement of NPCC immaturity via T3 release.
Personnel adjustments during the Covid-19 pandemic: did co-determination make a difference?
Authors: Fackler Daniel , Schnabel Claus , Stegmaier Jens 
Published: February 2024

AbstractUsing a unique dataset of establishments in Germany surveyed during the Covid-19 pandemic, this study investigates whether personnel adjustments during the crisis differed between establishments with and without a works council. Our regression analyses show that the hiring and dismissal rate as well as the churning rate were lower in establishments with a works council. In contrast, the net employment growth rate over the pandemic and the implementation of short-time work did not differ significantly between establishments with and without a works council. We conclude that worker co-determination did indeed make a difference in terms of higher employment stability for the incumbent workforce during the pandemic.
Modulation of long-term potentiation following microdoses of LSD captured by thalamo-cortical modelling in a randomised, controlled trial
Authors: Murphy Robin J. , Godfrey Kate , Shaw Alexander D. , Muthukumaraswamy Suresh , Sumner Rachael L. 
Published: February 2024

Abstract
Background
Microdosing psychedelics is a phenomenon with claimed cognitive benefits that are relatively untested clinically. Pre-clinically, psychedelics have demonstrated enhancing effects on neuroplasticity, which cannot be measured directly in humans, but may be indexed by non-invasive electroencephalography (EEG) paradigms. This study used a visual long-term potentiation (LTP) EEG paradigm to test the effects of microdosed lysergic acid diethylamide (LSD) on neural plasticity, both acutely while on the drug and cumulatively after microdosing every third day for six weeks. Healthy adult males (n = 80) completed the visual LTP paradigm at baseline, 2.5 h following a dose of 10 µg of LSD or inactive placebo, and 6 weeks later after taking 14 repeated microdoses. Visually induced LTP was used as indirect index of neural plasticity. Surface level event-related potential (ERPs) based analyses are presented alongside dynamic causal modelling of the source localised data using a generative thalamocortical model (TCM) of visual cortex to elucidate underlying synaptic circuitry.

Results
Event-related potential (ERP) analyses of N1b and P2 components did not show evidence of changes in visually induced LTP by LSD either acutely or after 6 weeks of regular dosing. However modelling the complete timecourse of the ERP with the TCM demonstrated changes in laminar connectivity in primary visual cortex. This primarily included changes to self-gain and inhibitory input parameters acutely. Layer 2/3 to layer 5 excitatory connectivity was also different between LSD and placebo groups. After regular dosing only excitatory input from layer 2/3 into layer 5 and inhibitory input into layer 4 were different between groups.

Conclusions
Without modulation of the ERPs it is difficult to relate the findings to other studies visually inducing LTP. It also indicates the classic peak analysis may not be sensitive enough to demonstrate evidence for changes in LTP plasticity in humans at such low doses. The TCM provides a more sensitive approach to assessing changes to plasticity as differences in plasticity mediated laminar connectivity were found between the LSD and placebo groups.
Trial registration: ANZCTR registration number ACTRN12621000436875; Registered 16/04/2021 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381476.
Risk factors for gastroesophageal reflux disease: a population-based study
Authors: Sadafi Sepehr , Azizi Ali , Pasdar Yahya , Shakiba Ebrahim , Darbandi Mitra 
Published: February 2024

Abstract
Background
Gastroesophageal reflux disease (GERD) in the long term reduces the quality of life, leading to digestive diseases. The present study aims to determine the risk factors for GERD.

Method
This study was conducted on 9,631 adults aged 35–65 years. The demographic characteristics, behavioral habits, nutritional intake, physical activity, anthropometric indices, and GERD data were extracted from the databank related to the Ravansar non-communicable diseases (RaNCD). Statistical analysis was performed using logistic regression models.

Results
The prevalence of GERD was 10.99% (n = 1,058). The GERD was higher among older age and women. After adjusting for age and sex, the odds of GERD among current smokers was 23% higher than non-smokers. Drinking increased odds of GERD (OR: 1.51; 95% CI: 1.13, 1.99). The odds of GERD among depressed individuals were 46% higher than non-depressed. In addition, a significant relationship was observed between the high intake of sweets and desserts with increased GERD (OR: 1.02, 95% CI: 1.01, 1.03). Further, high intake of fiber (OR: 0.98, 95% CI: 0.97, 0.99) and dairy (OR: 0.99, 95% CI: 0.98, 0.99) was related to reducing the odds of GERD. Furthermore, a significant relationship was reported between the waist hip ratio (WHR) and visceral fat area (VFA) with increased odds of GERD. Finally, the physical activity level was inversely related to GERD.

Conclusion
Based on the results, smoking, alcohol, inactivity, high intake of sweets and desserts, low intake of fiber, depression, visceral fat, and obesity are considered as risk factors for GERD. Modifying lifestyle and behavioral habits prevent GERD.
The use of a multi-disciplinary geriatric telemedicine service (TELEG) and its acceptance at a tertiary care centre in Malaysia
Authors: Ting Chuo Yew , Abdul Halim Nur Hidayati , Ling Jia Nee , Tiong Ing Khieng , Ahmad Shauki Nor Izzah H. J. , Lee Yew Fong , Osman Nor Anizah , Chai Gin Wei , Ung Shin Han , Ang Melinda 
Published: February 2024

AbstractBackgroundThe COVID-19 pandemic has fueled the widespread adoption of telemedicine in healthcare, particularly in Sarawak, Malaysia. This study investigates the use and acceptance of Sarawak’s inaugural multidisciplinary geriatric telemedicine service, TELEG.MethodsThis cross-sectional study took place at the Sarawak Heart Centre’s geriatric department from July 1, 2021, to April 30, 2022. Convenient sampling included all TELEG-enrolled patients during this period, to achieve minimum sample size of 148. TELEG’s utilization was assessed in terms of medication therapy and treatment plan optimization, as well as enhanced healthcare accessibility. Participants’ acceptance of TELEG was measured using the Service User Technology Acceptability Questionnaire (SUTAQ) administered through Google Forms. Descriptive statistics percentages illustrated the proportion of participants who found TELEG moderately to highly acceptable. Associations between baseline characteristics and overall acceptance were explored through bivariate analyses, including Pearson’s correlation test, independent t-test, and ANOVA. The influence of six SUTAQ dimensions on overall acceptance, multivariable linear regression using enter method was employed. Statistical significance was determined by p-values less than 0.5.ResultsAmong 180 geriatric patients enrolled in TELEG during the study period, 149 agreed to participate. TELEG led to medication therapy optimization for 88.6% of participants, primarily involving dose adjustment (44.7%), de-prescribing (31.8%), and prescribing (15.9%). Additionally, 53.8% received treatment plan optimization, predominantly in the form of self-care education (56.3%), referrals for further treatment (33.8%), additional laboratory investigations (29.6%), and increased monitoring (26.8%). Among those educated in self-care (n = 40), dietary intake (27.5%), lower limb exercise (25.0%), and COVID-19 vaccination (12.5%) were the most common topics. All participants expressed moderate to high acceptance of TELEG (mean = 4.9, SD = 0.65, on a scale of 1 to 6). Notably, care personnel concern (B = 0.256;p < 0.001) had the most significant impact on overall acceptance.ConclusionThis pioneering study evaluates the utilization and user acceptance of a geriatric telemedicine service in the region, providing valuable insights to support its expansion. Follow-up surveys or interviews to gain insights into users’ experiences are crucial to further enhance acceptance.
Prevalence of celiac-related antibodies and its impact on metabolic control in Egyptian children with type 1 diabetes mellitus
Authors: Baseer Khaled A. Abdel , Mohammed Abdallah E. , Elwafa Aya Mohamed Abo , Sakhr Hala M. 
Published: February 2024

Abstract
Objective
The simultaneous presence of celiac disease and type 1 diabetes (T1DM) is coupled with more hazards of comorbidities and complications. This current study aimed to screen for celiac disease in Egyptian children with type 1 diabetes and evaluate its impact on glycemic control.

Methods
A cross-sectional study was verified with 200 Egyptian children diagnosed with T1DM and having a diabetic duration of less than five years. Testing for anti-tissue transglutaminase IgA (tTG-IgA), anti-tissue transglutaminase IgG (tTG-IgG), anti-Endomysial IgA (EMA), and Hb A1c levels were done.

Results
The serological screening revealed that 11 cases (5.5%) tested positive; 8 children with T1DM (4.0%) showed tTG-IgA antibodies ≥ 10 times the upper limit of normal (ULN) with at least one symptom; and 3 cases (1.5%) had levels between 20 and 50 IU/ml (considering a cut-off point of 10 U/ML for positive results). Intestinal biopsy was performed for these three cases, with one case detected to have subtotal villous atrophy, resulting in an overall prevalence of celiac disease in T1DM as 4.5%. Children with positive screening exhibited a higher insulin dose, a higher HbA1c, an increased frequency of hypoglycemic attacks, and recurrent DKA compared to negative cases. A negative correlation was detected between tTG-IgA antibodies with height Z score and hemoglobin level, while a positive correlation was found between tTG-IgA antibodies and HbA1c level.

Conclusion
Undiagnosed celiac disease in children with T1DM negatively impacted metabolic control and affected their general health.
Hair cortisol and self-perceived stress in adolescents with multi-system functional somatic disorders
Authors: Nyengaard Rebecca , Kallesøe Karen Hansen , Rimvall Martin Køster , Ørnbøl Eva , Wellnitz Kaare Bro , Olsen Else Marie , Wyller Vegard Bruun Bratholm , Rask Charlotte Ulrikka 
Published: February 2024

Abstract
Background
Long-term stress causing altered hypothalamic–pituitary–adrenal (HPA) axis dynamics with cortisol dysfunction may be involved in the pathophysiology of functional somatic disorders (FSD), but studies on adolescents with multi-system FSD are lacking. Therefore, we investigated: 1) whether hair cortisol concentration (HCC) differentiates adolescents with multi-system FSD from a) a population-based sample and b) a subgroup derived from the sample reporting a high physical symptom load, and 2) whether FSD population HCC is associated with primary symptom presentations and self-perceived stress.

Methods
We used data from a clinical sample with multi-system FSD (N = 91, age 15–19 years) and a population-based sample (N = 1,450, age 16–17 years) including a subgroup with top 10% total scores on physical symptoms (N = 147). Density plots and multiple linear regression were applied to compare HCC between groups. In the clinical sample, multiple linear regression was employed to assess the association between HCC and primary symptom clusters and self-perceived stress.

Results
Median HCC was lower in the clinical sample than in the population-based sample (β = 0.80 (95%CI: 0.66, 0.97)), but not significantly different from median HCC in the derived subgroup (β = 0.84 (95%CI: 0.66, 1.07)). In the clinical sample, HCC was not significantly associated with primary symptom clusters (F(2, 82) = 0.13, p = 0.88) or self-perceived stress (F(4, 83) = 1.18, p = 0.33).

Conclusion
Our findings indicate that HCC is lowered in adolescents with multi-system FSD but not significantly associated with primary symptom presentations or self-perceived stress. Future studies including multiple measures of HPA axis dynamics alongside psychological measures may further elucidate the role of long-term stress in FSD.

Trial registration
The AHEAD study was pre-registered at ClinicalTrials.gov (NCT02346071), 26/01/2015