bluuebunny/crossref_metadata_2025_split huggingface dataset:
The lysosomal β-glucocerebrosidase strikes mitochondria: implications for Parkinson’s therapeutics
Authors: Rubilar Juan Carlos , Outeiro Tiago Fleming , Klein Andrés D 
Published: March 2024

AbstractParkinson’s disease is a neurodegenerative disorder primarily known for typical motor features that arise due to the loss of dopaminergic neurons in the substantia nigra. However, the precise molecular aetiology of the disease is still unclear. Several cellular pathways have been linked to Parkinson’s disease, including the autophagy-lysosome pathway, α-synuclein aggregation and mitochondrial function. Interestingly, the mechanistic link between GBA1, the gene that encodes for lysosomal β-glucocerebrosidase (GCase), and Parkinson’s disease lies in the interplay between GCase functions in the lysosome and mitochondria. GCase mutations alter mitochondria-lysosome contact sites. In the lysosome, reduced GCase activity leads to glycosphingolipid build-up, disrupting lysosomal function and autophagy, thereby triggering α-synuclein accumulation. Additionally, α-synuclein aggregates reduce GCase activity, creating a self-perpetuating cycle of lysosomal dysfunction and α-synuclein accumulation. GCase can also be imported into the mitochondria, where it promotes the integrity and function of mitochondrial complex I. Thus, GCase mutations that impair its normal function increase oxidative stress in mitochondria, the compartment where dopamine is oxidized. In turn, the accumulation of oxidized dopamine adducts further impairs GCase activity, creating a second cycle of GCase dysfunction. The oxidative state triggered by GCase dysfunction can also induce mitochondrial DNA damage which, in turn, can cause dopaminergic cell death. In this review, we highlight the pivotal role of GCase in Parkinson’s disease pathogenesis and discuss promising examples of GCase-based therapeutics, such as gene and enzyme replacement therapies, small molecule chaperones and substrate reduction therapies, among others, as potential therapeutic interventions.
Small fibre integrity and axonal pathology in the rat model of experimental autoimmune neuritis
Authors: Renk Pia , Sgodzai Melissa , Klimas Rafael , Blusch Alina , Grüter Thomas , Motte Jeremias , Pedreiturria Xiomara , Gebel Jeannette , Gobrecht Philipp , Fischer Dietmar , Gold Ralf , Pitarokoili Kalliopi 
Published: March 2024

Abstract
Experimental autoimmune neuritis is a common animal model for acute human immune–mediated polyneuropathies. Although already established in 1955, a number of pathophysiological mechanisms remain unknown. In this study, we extensively characterize experimental autoimmune neuritis progression in Lewis rats, including new insights into the integrity of small nerve fibres, neuropathic pain and macrophage activation. Acute experimental autoimmune neuritis was induced with P253–78 peptide and consequently investigated using the gait analysis system CatWalk XT, electrophysiological and histopathological analyses, quantitative polymerase chain reaction (PCR), dorsal root ganglia outgrowth studies, as well as the von Frey hair and Hargreaves tests. For the longitudinal setup, rats were sacrificed at Day (d) 10 (onset), d15 (peak), d26 (recovery) and d29 (late recovery). We confirmed the classical T-cell and macrophage-driven inflammation and the primarily demyelinating nature of the experimental autoimmune neuritis. The dual role of macrophages in experimental autoimmune neuritis is implicated by the high number of remaining macrophages throughout disease progression. Furthermore, different subpopulations of macrophages based on Cx3-motif chemokine receptor 1 (Cx3cr1), platelet factor 4 (Pf4) and macrophage galactose-type lectin-1 (Mgl1) expressions were identified. In addition, modulation of the sensory system in experimental autoimmune neuritis was detected. An outgrowth of small fibres in the plantar skin at the onset and peak of the experimental autoimmune neuritis was evident parallel to the development of acute hyperalgesia mediated through transient receptor potential vanilloid 1 modulation. Our data depict experimental autoimmune neuritis as a primary demyelinating disease with implicated axonal damage, a small unmyelinated fibre impairment throughout the disease progression course, and underline the pivotal role of macrophages in the effector and during the recovery stage.
In vivo PET classification of tau pathologies in patients with frontotemporal dementia
Authors: Kubota Manabu , Endo Hironobu , Takahata Keisuke , Tagai Kenji , Suzuki Hisaomi , Onaya Mitsumoto , Sano Yasunori , Yamamoto Yasuharu , Kurose Shin , Matsuoka Kiwamu , Seki Chie , Shinotoh Hitoshi , Kawamura Kazunori , Zhang Ming-Rong , Takado Yuhei , Shimada Hitoshi , Higuchi Makoto 
Published: March 2024

Abstract
Frontotemporal dementia refers to a group of neurodegenerative disorders with diverse clinical and neuropathological features. In vivo neuropathological assessments of frontotemporal dementia at an individual level have hitherto not been successful. In this study, we aim to classify patients with frontotemporal dementia based on topologies of tau protein aggregates captured by PET with 18F-florzolotau (aka 18F-APN-1607 and 18F-PM-PBB3), which allows high-contrast imaging of diverse tau fibrils in Alzheimer’s disease as well as in non–Alzheimer’s disease tauopathies. Twenty-six patients with frontotemporal dementia, 15 with behavioural variant frontotemporal dementia and 11 with other frontotemporal dementia phenotypes, and 20 age- and sex-matched healthy controls were included in this study. They underwent PET imaging of amyloid and tau depositions with 11C-PiB and 18F-florzolotau, respectively. By combining visual and quantitative analyses of PET images, the patients with behavioural variant frontotemporal dementia were classified into the following subgroups: (i) predominant tau accumulations in frontotemporal and frontolimbic cortices resembling three-repeat tauopathies (n = 3), (ii) predominant tau accumulations in posterior cortical and subcortical structures indicative of four-repeat tauopathies (n = 4); (iii) amyloid and tau accumulations consistent with Alzheimer’s disease (n = 4); and (iv) no overt amyloid and tau pathologies (n = 4). Despite these distinctions, clinical symptoms and localizations of brain atrophy did not significantly differ among the identified behavioural variant frontotemporal dementia subgroups. The patients with other frontotemporal dementia phenotypes were also classified into similar subgroups. The results suggest that PET with 18F-florzolotau potentially allows the classification of each individual with frontotemporal dementia on a neuropathological basis, which might not be possible by symptomatic and volumetric assessments.
Hypoxia macrophage-derived exosomal miR-26b-5p targeting PTEN promotes the development of keloids
Authors: Dai Siya , Xu Mingyuan , Pang Qianqian , Sun Jiaqi , Lin Xiaohu , Chu Xi , Guo Chunyi , Xu Jinghong 
Published: March 2024

Abstract

Background
Hypoxia is the typical characteristic of keloids. The development of keloids is closely related to the abnormal phenotypic transition of macrophages. However, the role of exosomal microRNAs (miRNAs) derived from hypoxic macrophages in keloids remains unclear. This study aimed to explore the role of hypoxic macrophage-derived exosomes (HMDE) in the occurrence and development of keloids and identify the critical miRNA.

Methods
The expression of CD206+ M2 macrophage in keloids and normal skin tissues was examined through immunofluorescence. The polarization of macrophages under a hypoxia environment was detected through flow cytometry. The internalization of macrophage-derived exosomes in human keloid fibroblasts (HKFs) was detected using a confocal microscope. miRNA sequencing was used to explore the differentially expressed miRNAs in exosomes derived from the normoxic and hypoxic macrophage. Subsequently, the dual-luciferase reporter assay verified that phosphatase and tension homolog (PTEN) was miR-26b-5p’s target. The biological function of macrophage-derived exosomes, miR-26b-5p and PTEN were detected using the CCK-8, wound-healing and Transwell assays. Western blot assay was used to confirm the miR-26b-5p’s underlying mechanisms and PTEN-PI3K/AKT pathway.

Results
We demonstrated that M2-type macrophages were enriched in keloids and that hypoxia treatment could polarize macrophages toward M2-type. Compared with normoxic macrophages-derived exosomes (NMDE), HMDE promote the proliferation, migration and invasion of HKFs. A total of 38 differential miRNAs (18 upregulated and 20 downregulated) were found between the NMDE and HMDE. miR-26b-5p was enriched in HMDE, which could be transmitted to HKFs. According to the results of the functional assay, exosomal miR-26b-5p produced by macrophages facilitated HKFs’ migration, invasion and proliferation via the PTEN-PI3K/AKT pathway.

Conclusions
The highly expressed miR-26b-5p in HMDE promotes the development of keloids via the PTEN-PI3K/AKT pathway.
Experimental study on the effect of micro-carbon additives in vegetable oils for aquifer thermal energy storage
Authors: Suzuki Takashi , Ichiyanagi Mitsuhisa , Yilmaz Emir , Maxwell Archie G K , Anggraini Handoyo Ekadewi 
Published: March 2024

Abstract
Aquifer thermal energy storage is a versatile method for regulating building temperatures, utilizing groundwater as a medium for both summer cooling and winter heating. Water has high thermal conductivity and specific heat but is corrosive, creating a mineral build-up that causes scaling. Additionally, its high freezing point presents operational challenges. Vegetable oils emerge as a promising alternative, owing to their lower freezing points. In light of environmental concerns, researchers are exploring vegetable oils as substitutes for petroleum-derived mineral oils. This paper is intended as an initial study using vegetable oils, i.e. coconut and sunflower oil, as the heat-transfer medium in aquifer thermal energy storage. The experiments assess the heat-transfer coefficient of coconut, sunflower, mineral, and synthetic oils when exposed to the same heat source. The study also evaluates the impact of introducing micro-carbon (graphite and charcoal) to the oils. Results indicate that sunflower oil has the highest heat-transfer coefficient of 374.4 W/m2 K among the oils, making it suitable for aquifer thermal energy storage applications. Furthermore, augmenting sunflower oil with charcoal powder enhances its performance by increasing the heat-transfer coefficient to 474.9 W/m2 K, or a 27% increase. In contrast, coconut oil proves unsuitable for aquifer thermal energy storage deployment because of its low heat-transfer coefficient of 293.7 W/m2 K. The heat-transfer coefficient of synthetic oil increases with graphite powder but decreases with charcoal powder introduction.
Green hydrogen energy production: current status and potential
Authors: Maka Ali O M , Mehmood Mubbashar 
Published: March 2024

Abstract
The technique of producing hydrogen by utilizing green and renewable energy sources is called green hydrogen production. Therefore, by implementing this technique, hydrogen will become a sustainable and clean energy source by lowering greenhouse gas emissions and reducing our reliance on fossil fuels. The key benefit of producing green hydrogen by utilizing green energy is that no harmful pollutants or greenhouse gases are directly released throughout the process. Hence, to guarantee all of the environmental advantages, it is crucial to consider the entire hydrogen supply chain, involving storage, transportation and end users. Hydrogen is a promising clean energy source and targets plan pathways towards decarbonization and net-zero emissions by 2050. This paper has highlighted the techniques for generating green hydrogen that are needed for a clean environment and sustainable energy solutions. Moreover, it summarizes an overview, outlook and energy transient of green hydrogen production. Consequently, its perspective provides new insights and research directions in order to accelerate the development and identify the potential of green hydrogen production.
Toward a better understanding of how a gyrified brain develops
Authors: Barresi Mikaela , Hickmott Ryan Alexander , Bosakhar Abdulhameed , Quezada Sebastian , Quigley Anita , Kawasaki Hiroshi , Walker David , Tolcos Mary 
Published: March 2024

Abstract
The size and shape of the cerebral cortex have changed dramatically across evolution. For some species, the cortex remains smooth (lissencephalic) throughout their lifetime, while for other species, including humans and other primates, the cortex increases substantially in size and becomes folded (gyrencephalic). A folded cortex boasts substantially increased surface area, cortical thickness, and neuronal density, and it is therefore associated with higher-order cognitive abilities. The mechanisms that drive gyrification in some species, while others remain lissencephalic despite many shared neurodevelopmental features, have been a topic of investigation for many decades, giving rise to multiple perspectives of how the gyrified cerebral cortex acquires its unique shape. Recently, a structurally unique germinal layer, known as the outer subventricular zone, and the specialized cell type that populates it, called basal radial glial cells, were identified, and these have been shown to be indispensable for cortical expansion and folding. Transcriptional analyses and gene manipulation models have provided an invaluable insight into many of the key cellular and genetic drivers of gyrification. However, the degree to which certain biomechanical, genetic, and cellular processes drive gyrification remains under investigation. This review considers the key aspects of cerebral expansion and folding that have been identified to date and how theories of gyrification have evolved to incorporate this new knowledge.
Association of left atrial enlargement with heart failure events in non-valvular atrial fibrillation patients with preserved left ventricular ejection fraction
Authors: Hamatani Yasuhiro , Iguchi Moritake , Okamoto Keita , Nakanishi Yumiko , Minami Kimihito , Ishigami Kenjiro , Ikeda Syuhei , Doi Kosuke , Yoshizawa Takashi , Ide Yuya , Fujino Akiko , Ishii Mitsuru , Masunaga Nobutoyo , Esato Masahiro , Tsuji Hikari , Wada Hiromichi , Hasegawa Koji , Abe Mitsuru , Akao Masaharu 
Published: March 2024

Abstract

Aims
Atrial fibrillation (AF) increases the risk of heart failure (HF); however, little is known regarding the risk stratification for incident HF in AF patients, especially with preserved left ventricular ejection fraction (LVEF).

Methods and results
The Fushimi AF Registry is a community-based prospective survey of AF patients. From the registry, 3002 non-valvular AF patients with preserved LVEF and with the data of antero-posterior left atrial diameter (LAD) at enrolment were investigated. Patients were stratified by LAD (&lt;40, 40–44, 45–49, and ≥50 mm) with backgrounds and HF hospitalization incidences compared between groups. Of 3002 patients [mean age, 73.5 ± 10.7 years; women, 1226 (41%); paroxysmal AF, 1579 (53%); and mean CHA2DS2-VASc score, 3.3 ± 1.7], the mean LAD was 43 ± 8 mm. Patients with larger LAD were older and less often paroxysmal AF, with a higher CHA2DS2-VASc score (all P &lt; 0.001). Heart failure hospitalization occurred in 412 patients during the median follow-up period of 6.0 years. Larger LAD was independently associated with a higher HF hospitalization risk [LAD ≥ 50 mm: hazard ratio (HR), 2.36; 95% confidence interval (CI), 1.75–3.18; LAD 45–49 mm: HR, 1.84; 95% CI, 1.37–2.46; and LAD 40–44 mm: HR, 1.34; 95% CI, 1.01–1.78, compared with LAD &lt; 40 mm) after adjustment by age, sex, AF type, and CHA2DS2-VASc score. These results were also consistent across major subgroups, showing no significant interaction.

Conclusion
Left atrial diameter is significantly associated with the risk of incident HF in AF patients with preserved LVEF, suggesting the utility of LAD regarding HF risk stratification for these patients.
Kidney replacement therapy: trends in incidence, treatment, and outcomes of myocardial infarction and stroke in a nationwide Scottish study
Authors: Gallacher Peter J , Yeung David , Bell Samira , Shah Anoop S V , Mills Nicholas L , Dhaun Neeraj 
Published: March 2024

Abstract

Background and Aims
Patients with kidney failure have a higher risk of cardiovascular disease compared with the general population. Whilst temporal trends of myocardial infarction and stroke are declining in the general population, these have not been evaluated in patients with kidney failure. This study aimed to describe national trends in the incidence, treatment, and outcomes of myocardial infarction and stroke in patients with kidney failure (i.e. on dialysis or with a kidney transplant) over a 20-year period, stratified by age and sex.

Methods
In this retrospective national data linkage study, all patients with kidney failure in Scotland (UK) receiving kidney replacement therapy between January 1996 and December 2016 were linked to national hospitalization, prescribing, and death records. The primary outcomes were the incidence of myocardial infarction and stroke, and subsequent cardiovascular death. Generalized additive models were constructed to estimate age-standardized, sex-stratified incidence rates and trends in cardiovascular and all-cause death.

Results
Amongst 16 050 patients with kidney failure [52 (SD 15) years; 41.5% women], there were 1992 [66 (SD 12) years; 34.8% women] and 996 [65 (SD 13) years; 45.1% women] incident myocardial infarctions and strokes, respectively, between January 1996 and December 2016. During this period, the age-standardized incidence of myocardial infarction per 100 000 decreased in men {from 4376 [95% confidence interval (CI) 3998–4785] to 1835 (95% CI 1692–1988)} and women [from 3268 (95% CI 2982–3593) to 1369 (95% CI 1257–1491)]. Similarly, the age-standardized incidence of stroke per 100 000 also decreased in men [from 1978 (95% CI 1795–2175) to 799 (95% CI 729–875)] and women [from 2234 (95% CI 2031–2468) to 903 (95% CI 824–990)]. Compared with the general population, the incidence of myocardial infarction was four- to eight-fold higher in patients with kidney failure, whilst for stroke it was two- to four-fold higher. The use of evidence-based cardioprotective treatment increased over the study period, and the predicted probability of cardiovascular death within 1 year of myocardial infarction for a 66-year-old patient with kidney failure (mean age of the cohort) fell in men (76.6% to 38.6%) and women (76.8% to 38.8%), and also decreased in both sexes following stroke (men, from 63.5% to 41.4%; women, from 67.6% to 45.8%).

Conclusions
The incidence of myocardial infarction and stroke has halved in patients with kidney failure over the past 20 years but remains significantly higher than in the general population. Despite improvements in treatment and outcomes, the prognosis of these patients following myocardial infarction and stroke remains poor.
The Metalinguistic Dimension of Literary Multilingualism: Linguistic Biographies in Italian Fiction
Authors: Ala-Risku Riikka 
Published: March 2024

ABSTRACT
In this article, I argue that a thorough analysis of literary multilingualism and code-switching needs to take their metalinguistic dimension into account. Many scholars have noticed multilingual authors’ tendency to frame code-switches with metalinguistic comments, but they are sometimes treated marginally, or as just one of the many functions of code-switching. My article argues that metalanguage is, in fact, a fundamental characteristic of literary multilingualism, and key to its interpretation. This is particularly evident when we look at how the contemporary Italian writers Laura Pariani, Silvana Grasso and Elena Ferrante construct their characters through linguistic biographies, and how they describe dialect use, bilingualism, language loss and shift and other collective and individual sociolinguistic processes. I also show that metalanguage needs to be analysed together with other tools used by authors to flag multilingualism: namely intratextual translations and peritextual elements (such as glossaries or notes), but also visual cues, such as italics.
The Impact of Type 2 Diabetes on Peripheral and Cerebral Hemodynamic Responses to Active Stand
Authors: Hernández Belinda , Dyer Adam H , Finucane Ciaran , Nipoti Bernardo , Romero-Ortuno Roman , Reilly Richard , Kenny Rose Anne 
Published: March 2024

Abstract

Background
Although type 2 diabetes mellitus (T2DM) is an established risk factor for cognitive impairment, the underlying mechanisms remain poorly explored. One potential mechanism may be through effects of T2DM on cerebral perfusion. The current study hypothesized that T2DM is associated with altered peripheral and central hemodynamic responses to orthostasis, which may in turn be associated with cognitive impairment in T2DM.

Methods
A novel use of function-on-scalar regression, which allows the entire hemodynamic response curve to be modeled, was employed to assess the association between T2DM and hemodynamic responses to orthostasis. Logistic regression was used to assess the relationship between tissue saturation index (TSI), T2DM, and cognitive impairment. All analyses used cross-sectional data from Wave 3 of The Irish Longitudinal Study on Ageing (TILDA).

Results
Of 2 984 older adults (aged 64.3 ± 8.0; 55% female), 189 (6.3%) had T2DM. T2DM was associated with many features that are indicative of autonomic dysfunction including a blunted peak heart rate and lower diastolic blood pressure. T2DM was associated with reduced TSI and also with greater odds of impaired performance on the Montreal Cognitive Assessment (odds ratio [OR]: 1.62; confidence interval [CI: 1.07, 2.56]; p = .019). Greater TSI was associated with lower odds of impaired performance (OR: 0.90, CI [0.81–0.99]; p = .047).

Conclusions
T2DM was associated with impaired peripheral and cerebral hemodynamic responses to active stand. Both T2DM and reduced cerebral perfusion were associated with impaired cognitive performance. Altered cerebral perfusion may represent an important mechanism linking T2DM and adverse brain health outcomes in older adults.
Access to perinatal doula services in Medicaid: a case analysis of 2 states
Authors: Safon Cara B , McCloskey Lois , Estela Maria Guadalupe , Gordon Sarah H , Cole Megan B , Clark Jack 
Published: March 2024

Abstract
Doula services support maternal and child health, but few Medicaid programs reimburse for them. Through qualitative interviews with key policy informants (n = 20), this study explored facilitators and barriers to Medicaid reimbursement through perceptions of doula-related policies in 2 states: Oregon, where doula care is reimbursed, and Massachusetts, where reimbursement is pending. Five themes characterize the inclusion of doula services in Medicaid. In Theme 1, stakeholders recognized an imperative to expand access to doula services. Subsequent themes represent complications in accomplishing that imperative. In Theme 2, perceptions that doula services were not valued by health care providers resulted in conflict between doulas and the health care system. In Theme 3, complex billing processes created friction and impeded reimbursement. In Theme 4, internal conflict presented barriers to policymaking. In Theme 5, structural fragmentation between state government and doula communities was prominent in Massachusetts, presenting tensions during policymaking. Informants reported on problems demanding resolution to establish equitable and robust doula care policies. Medicaid coverage of doula services requires ongoing collaboration with doulas, providers, and health care advocates.