bluuebunny/crossref_metadata_2025_split huggingface dataset:
Remittance dependence, support for taxation and quality of public services in Africa
Authors: Konte Maty , Ndubuisi Gideon 
Published: December 2023

AbstractWe explore the heterogeneous effect of migrant remittances on citizens' support for taxation using a sample comprising 45,000 individuals from the Afrobarometer survey round 7 [2016–2018] across 34 African countries. To correct for unobserved heterogeneity, we endogenously identify latent classes/subtypes of individuals that share similar patterns on how their support for taxation is affected by their unobserved and observed characteristics, including remittance dependency. We apply the finite multilevel mixture of regressions approach, a supervised machine learning method to detect hidden classes in the data without imposinga prioriassumptions on class membership. Our data are best generated by an econometric model with two classes/subtypes of individuals. In class 1 where more than two-thirds of the citizens belong, we do not find any significant evidence that remittance dependence affects support for taxation. However, in class 2 where the remaining one-third of the citizens belong, we find a significant negative effect of remittance dependence on support for taxation. Furthermore, we find that citizens who have a positive appraisal of the quality of the public service delivery have a lower probability of belonging to the class in which depending on remittance reduces support for taxation. The findings emphasize the need for efficient public services provisioning to counteract the adverse effect of remittances on tax morale.
Association Between Dysmenorrhea and Risk of Epilepsy in East Asian Populations: A Bidirectional Two-Sample Mendelian Randomization Study
Authors: Ren Yuehan , Zhang Junning , Chen Tong , Chen Jiaqin , Liao Yan , Liu Tingxiu , Yang Liangliang , Liu Chang , Liu Xinmin , Liu Baoqin 
Published: December 2023

AbstractDysmenorrhea is associated with epilepsy. Existing evidence is mostly limited to observational studies, which are liable to confounding and bias. This study investigated the causal relevance of dysmenorrhea on epilepsy using Mendelian randomization (MR). We extracted instrumental variants for dysmenorrhea and epilepsy from published genomewide association study data, focusing on individuals of East Asian descent. A comprehensive suite of MR estimations and sensitivity analyses was performed to ensure the robustness of the findings. Each outcome database was analyzed separately in both directions. For dysmenorrhea and epilepsy, 7 and 3 genetic variants respectively were selectively extracted as instrumental variants. The results suggest that dysmenorrhea is causally associated with an elevated risk of epilepsy (inverse variance weighted [IVW]: OR = 1.26; 95% CI [1.07, 1.47]; p = 4.42 × 10−3); conversely, no strong evidence was found to corroborate that epilepsy exerts a causal effect on the incidence of dysmenorrhea (IVW: OR = 1.04; 95% CI [0.82, 1.33]; p = .72). These findings provide novel insights into the causal relationship between dysmenorrhea and epilepsy, which may have implications for clinical decision-making in patients with epilepsy and dysmenorrhea.
Comprehensive Multiomics Analysis of Monozygotic Twin Discordant for Double Outlet Right Ventricle
Authors: Liu Zhen , Li Nana , Pan Xiaoyu , Li Jun , Li Shengli , Li Qintong , Li Ping , Deng Ying , Chen Fang , Jiang Hui , Wang Wei , Mu Dezhi , Yu Ping , Zhu Jun 
Published: December 2023

AbstractThe objective of this study was to understand and measure epigenetic changes associated with the occurrence of CHDs by utilizing the discordant monozygotic twin model. A unique set of monozygotic twins discordant for double-outlet right ventricles (DORVs) was used for this multiomics study. The cardiac and muscle tissue samples from the twins were subjected to whole genome sequencing, whole genome bisulfite sequencing, RNA-sequencing and liquid chromatography-tandem mass spectrometry analysis. Sporadic DORV cases and control fetuses were used for validation. Global hypomethylation status was observed in heart tissue samples from the affected twins. Among 36,228 differentially methylated regions (DMRs), 1097 DMRs involving 1039 genes were located in promoter regions. A total of 419 genes, and lncRNA–mRNA pairs involved 30 genes, and 62 proteins were significantly differentially expressed. Multiple omics integrative analysis revealed that five genes, including BGN, COL1A1, COL3A1, FBLN5, and FLAN, and three pathways, including ECM-receptor interaction, focal adhesion and TGF-β signaling pathway, exhibited differences at all three levels. This study demonstrates a multiomics profile of discordant twins and explores the possible mechanism of DORV development. Global hypomethylation might be associated with the risk of CHDs. Specific genes and specific pathways, particularly those involving ECM–receptor interaction, focal adhesion and TGF–β signaling, might be involved in the occurrence of CHDs.
Revealing Elysium Planitia's Young Geologic History: Constraints on Lava Emplacement, Areas, and Volumes
Authors: Voigt J. R. C. , Hamilton C. W. , Steinbrügge G. , Christoffersen M. S. , Nerozzi S. , Kerber L. , Holt J. W. , Carter L. M. 
Published: December 2023

AbstractElysium Planitia includes several outflow channels that were likely carved by aqueous erosion and subsequently infilled by younger lava flows, making Elysium Planitia the youngest volcanic terrain on Mars. Studying this region is critical for constraining the recent hydrological and thermal evolution of the planet. Here, we investigate the lava flow areas, thicknesses, and volumes in Elysium Planitia using Context (CTX) camera images in combination with SHAllow RADar (SHARAD) sounder data. Compiling 1,777 reflectors over an area of 9,126,790 km2 allows us to reconstruct the subsurface landscape evolution over time. Our findings show that Elysium Planitia is composed of material from about 40 episodes of effusive volcanic activity. We report volumes for individual eruptions of 4,000 ± 1,600 km3 infilling Athabasca Valles, 12,200 ± 2,500 km3 in Marte Vallis, and 16,000 ± 4,000 km3 in Rahway Valles for the major flow units and volumes as small as 100 ± 50 km3 in Cerberus Plains. The surface morphologies and inferred dielectric properties of lobe interfaces suggests that the regions consists of basaltic lava. The region also experienced multiple aqueous flooding events. Although, we found evidence of past lava–water interactions, present‐day ground‐ice (if present) is likely limited to local patches. Further, the pre‐eruption landscape reveals that the aqueously carved Marte Vallis is more areal extensive, but shallower than previously suggested, with a likely paleo‐flow direction from northwest to southeast. The channel is most likely sourced from a segment in the northwestern portion of Cerberus Fossae, and is now buried by multiple Late Amazonian lavas with the same lava flow direction.
One Health assessment of persistent organic chemicals and PFAS for consumption of restored anadromous fish
Authors: Melnyk Lisa Jo , Lazorchak James M. , Kusnierz Daniel H. , Perlman Gary D. , Lin John , Venkatapathy Raghuraman , Sundaravadivelu Devi , Thorn Jonathan , Durant James , Pugh Katherine , Stover Michael A. 
Published: December 2023

Abstract
Background
Restoration efforts have led to the return of anadromous fish, potential source of food for the Penobscot Indian Nation, to the previously dammed Penobscot River, Maine.

Objective
U.S. Environmental Protection Agency (EPA), Penobscot Indian Nation’s Department of Natural Resources (PINDNR), and Agency for Toxic Substances and Disease Registry (ATSDR), measured contaminants in six species of anadromous fish. Fish tissue concentrations were then used, along with exposure parameters, to evaluate potential human and aquatic-dependent wildlife risk.

Methods
PINDNR collected, filleted, froze, and shipped fish for analysis of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), dioxins/furans, and per- and polyfluoroalkyl substances (PFAS). Contaminant levels were compared to reference doses (where possible) and wildlife values (WVs).

Results
Chemical concentrations ranged from 6.37 nanogram per gram (ng/g) wet weight (ww) in American Shad roe to 100 ng/g ww in Striped Bass for total PCBs; 0.851 ng/g ww in American Shad roe to 5.92 ng/g ww in large Rainbow Smelt for total PBDEs; and 0.037 ng/g ww in American Shad roe to 0.221 ng/g ww in Striped Bass for total dioxin/furans. PFAS concentrations ranged between 0.38 ng/g ww of PFBA in Alewife to 7.86 ng/g ww of PFUnA in Sea Lamprey. Dioxin/furans and PFOS levels indicated that there are potential human health risks. The WV for mink for total PCBs (72 ng/g) was exceeded in Striped Bass and the WV for Kestrel for PBDEs (8.7 ng/g) was exceeded in large Rainbow Smelt. Mammalian wildlife consuming Blueback Herring, Striped Bass, and Sea Lamprey may be at risk based on PFOS WVs from Canada.

Impact

Anadromous fish returning to the Penobscot River potentially could represent the restoration of a major component of tribal traditional diet. However, information about contaminant levels in these fish is needed to guide the tribe about consumption safety. Analysis of select species of fish and risk calculations demonstrated the need for a protective approach to consumption for both humans and wildlife. This project demonstrates that wildlife can also be impacted by contamination of fish and their risks can be as great or greater than those of humans. A One Health approach addresses this discrepancy and will lead to a healthier ecosystem.
Curation of causal interactions mediated by genes associated with autism accelerates the understanding of gene-phenotype relationships underlying neurodevelopmental disorders
Authors: Iannuccelli Marta , Vitriolo Alessandro , Licata Luana , Lo Surdo Prisca , Contino Silvia , Cheroni Cristina , Capocefalo Daniele , Castagnoli Luisa , Testa Giuseppe , Cesareni Gianni , Perfetto Livia 
Published: December 2023

AbstractAutism spectrum disorder (ASD) comprises a large group of neurodevelopmental conditions featuring, over a wide range of severity and combinations, a core set of manifestations (restricted sociality, stereotyped behavior and language impairment) alongside various comorbidities. Common and rare variants in several hundreds of genes and regulatory regions have been implicated in the molecular pathogenesis of ASD along a range of causation evidence strength. Despite significant progress in elucidating the impact of few paradigmatic individual loci, such sheer complexity in the genetic architecture underlying ASD as a whole has hampered the identification of convergent actionable hubs hypothesized to relay between the vastness of risk alleles and the core phenotypes. In turn this has limited the development of strategies that can revert or ameliorate this condition, calling for a systems-level approach to probe the cross-talk of cooperating genes in terms of causal interaction networks in order to make convergences experimentally tractable and reveal their clinical actionability. As a first step in this direction, we have captured from the scientific literature information on the causal links between the genes whose variants have been associated with ASD and the whole human proteome. This information has been annotated in a computer readable format in the SIGNOR database and is made freely available in the resource website. To link this information to cell functions and phenotypes, we have developed graph algorithms that estimate the functional distance of any protein in the SIGNOR causal interactome to phenotypes and pathways. The main novelty of our approach resides in the possibility to explore the mechanistic links connecting the suggested gene-phenotype relations.
Intranasal oxytocin in a genetic animal model of autism
Authors: Szabó Jakub , Mlynár Matúš , Feješ Andrej , Renczés Emese , Borbélyová Veronika , Ostatníková Daniela , Celec Peter 
Published: December 2023

AbstractAutism spectrum disorder (ASD) is a group of neurodevelopmental disorders mainly characterized by deficient sociability and repetitive behaviors. Effective treatment for the core symptoms of ASD is still lacking. Behavioral interventions show limited effectiveness, while pharmacotherapy focuses on the amelioration of secondary symptomatology. Oxytocin (OXT) is a neuropeptide known for its prosocial impact, making it a candidate drug for ASD treatment. Its alleviating effect has been and still is widely researched, but outcomes reported by clinical studies are ambiguous. We examined the effect of daily intranasal OXT (0.8 IU/kg) administration for 4 weeks on the ASD-like phenotype in Shank3−/− adult mice. Animals treated with OXT spent twice as much time interacting with the social partner as early as after 2 weeks of treatment. Furthermore, OXT-treated mice exhibited reduced explorative behavior by 50%, after 4 weeks of treatment, and a 30% reduction in repetitive behavior, 4 weeks after treatment termination. One-fold higher sociability and 30% reduced exploration due to OXT lasted up to 4 weeks following the treatment termination. However, social disinterest was elevated by roughly 10% as well, indicating a form of social ambivalence. Obtained results support the therapeutic potential of intranasally administered OXT in alleviating social shortfalls in a genetic model of ASD. Subsequent research is necessary to elucidate the benefits and risks of the long-term OXT administration, as well as its applicability in other ASD models and the potential treatment effect on social communication, which was not measured in the present study.
Cerebral organoids with chromosome 21 trisomy secrete Alzheimer’s disease-related soluble aggregates detectable by single-molecule-fluorescence and super-resolution microscopy
Authors: Fertan Emre , Böken Dorothea , Murray Aoife , Danial John S. H. , Lam Jeff Y. L. , Wu Yunzhao , Goh Pollyanna A. , Alić Ivan , Cheetham Matthew R. , Lobanova Evgeniia , Zhang Yu P. , Nižetić Dean , Klenerman David 
Published: December 2023

AbstractUnderstanding the role of small, soluble aggregates of beta-amyloid (Aβ) and tau in Alzheimer’s disease (AD) is of great importance for the rational design of preventative therapies. Here we report a set of methods for the detection, quantification, and characterisation of soluble aggregates in conditioned media of cerebral organoids derived from human iPSCs with trisomy 21, thus containing an extra copy of the amyloid precursor protein (APP) gene. We detected soluble beta-amyloid (Aβ) and tau aggregates secreted by cerebral organoids from both control and the isogenic trisomy 21 (T21) genotype. We developed a novel method to normalise measurements to the number of live neurons within organoid-conditioned media based on glucose consumption. Thus normalised, T21 organoids produced 2.5-fold more Aβ aggregates with a higher proportion of larger (300–2000 nm2) and more fibrillary-shaped aggregates than controls, along with 1.3-fold more soluble phosphorylated tau (pTau) aggregates, increased inflammasome ASC-specks, and a higher level of oxidative stress inducing thioredoxin-interacting protein (TXNIP). Importantly, all this was detectable prior to the appearance of histological amyloid plaques or intraneuronal tau-pathology in organoid slices, demonstrating the feasibility to model the initial pathogenic mechanisms for AD in-vitro using cells from live genetically pre-disposed donors before the onset of clinical disease. Then, using different iPSC clones generated from the same donor at different times in two independent experiments, we tested the reproducibility of findings in organoids. While there were differences in rates of disease progression between the experiments, the disease mechanisms were conserved. Overall, our results show that it is possible to non-invasively follow the development of pathology in organoid models of AD over time, by monitoring changes in the aggregates and proteins in the conditioned media, and open possibilities to study the time-course of the key pathogenic processes taking place.
Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma development and progression
Authors: Chen Liping , Zhu Shihao , Liu Tianyuan , Zhao Xuan , Xiang Tao , Hu Xiao , Wu Chen , Lin Dongxin 
Published: December 2023

AbstractEpithelial-mesenchymal transition (EMT) and proliferation play important roles in epithelial cancer formation and progression, but what molecules and how they trigger EMT is largely unknown. Here we performed spatial transcriptomic and functional analyses on samples of multistage esophageal squamous-cell carcinoma (ESCC) from mice and humans to decipher these critical issues. By investigating spatiotemporal gene expression patterns and cell–cell interactions, we demonstrated that the aberrant epithelial cell interaction via EFNB1-EPHB4 triggers EMT and cell cycle mediated by downstream SRC/ERK/AKT signaling. The aberrant epithelial cell interaction occurs within the basal layer at early precancerous lesions, which expands to the whole epithelial layer and strengthens along the cancer development and progression. Functional analysis revealed that the aberrant EFNB1-EPHB4 interaction is caused by overexpressed ΔNP63 due to TP53 mutation, the culprit in human ESCC tumorigenesis. Our results shed new light on the role of TP53-TP63/ΔNP63-EFNB1-EPHB4 axis in EMT and cell proliferation in epithelial cancer formation.
Eculizumab treatment in paediatric patients diagnosed with aHUS after haematopoietic stem cell transplantation: a HSCT-TMA case series from Japanese aHUS post-marketing surveillance
Authors: Ito Shuichi , Saito Atsuro , Sakurai Ayako , Watanabe Kenichiro , Karakawa Shuhei , Miyamura Takako , Yokosuka Tomoko , Ueki Hideaki , Goto Hiroaki , Yagasaki Hiroshi , Kinoshita Mariko , Ozeki Michio , Yokoyama Norifumi , Teranishi Hirofumi 
Published: December 2023

AbstractHaematopoietic stem-cell transplantation (HSCT)-associated thrombotic microangiopathy (HSCT-TMA) is a serious complication with high mortality. Accumulating evidence suggests that complement dysregulation is potentially involved in the development of HSCT-TMA. We retrospectively analysed the clinical characteristics and outcomes of thirteen paediatric patients who were diagnosed with atypical haemolytic uremic syndrome and treated with eculizumab to manage HSCT-TMA during post-marketing surveillance in Japan. The median time from HSCT to TMA was 31 days (Interquartile range, IQR;21–58) and the median doses of eculizumab was three (IQR;2–5). Seven patients (54%) were alive at the last follow-up while six died due to complications related to HSCT. Six of seven survivors initiated eculizumab after insufficient response to plasma therapy. Following eculizumab treatment, median platelet counts and LDH levels in all survivors significantly improved and renal function improved in 4/7 patients. All survivors possessed potential risk factors of complement overactivation. During the follow-up period after eculizumab discontinuation (median;111.5 days, IQR;95–555), no TMA recurrence was observed. In this analysis, eculizumab showed benefit in over half of this paediatric patient population. Ongoing clinical studies are expected to optimize the treatment regimen of terminal complement pathway inhibitor, and it may become a therapeutic option for paediatric HSCT-TMA in the future.
Pharmacological inhibition of MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1) induces ferroptosis in vascular smooth muscle cells
Authors: Yan Binjie , Belke Darrell , Gui Yu , Chen Yong-Xiang , Jiang Zhi-Sheng , Zheng Xi-Long 
Published: December 2023

AbstractMALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1) is a human paracaspase protein with proteolytic activity via its caspase-like domain. The pharmacological inhibition of MALT1 by MI-2, a specific chemical inhibitor, diminishes the response of endothelial cells to inflammatory stimuli. However, it is largely unknown how MALT1 regulates the functions of vascular smooth muscle cells (SMCs). This study aims to investigate the impact of MALT1 inhibition by MI-2 on the functions of vascular SMCs, both in vitro and in vivo. MI-2 treatment led to concentration- and time-dependent cell death of cultured aortic SMCs, which was rescued by the iron chelator deferoxamine (DFO) or ferrostatin-1 (Fer-1), a specific inhibitor of ferroptosis, but not by inhibitors of apoptosis (Z-VAD-fmk), pyroptosis (Z-YVAD-fmk), or necrosis (Necrostatin-1, Nec-1). MI-2 treatment downregulated the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy polypeptide 1 (FTH1), which was prevented by pre-treatment with DFO or Fer-1. MI-2 treatment also activated autophagy, which was inhibited by Atg7 deficiency or bafilomycin A1 preventing MI-2-induced ferroptosis. MI-2 treatment reduced the cleavage of cylindromatosis (CYLD), a specific substrate of MALT1. Notably, MI-2 treatment led to a rapid loss of contractility in mouse aortas, which was prevented by co-incubation with Fer-1. Moreover, local application of MI-2 significantly reduced carotid neointima lesions and atherosclerosis in C57BL/6J mice and apolipoprotein-E knockout (ApoE−/−) mice, respectively, which were both ameliorated by co-treatment with Fer-1. In conclusion, the present study demonstrated that MALT1 inhibition induces ferroptosis of vascular SMCs, likely contributing to its amelioration of proliferative vascular diseases.
Genetic basis of osteogenesis imperfecta from a single tertiary centre in South Africa
Authors: Coetzer Kimberly Christine , Zöllner Ekkehard , Moosa Shahida 
Published: December 2023

AbstractOsteogenesis imperfecta (OI) is a clinically heterogeneous disorder characterised by skeletal fragility and an increased fracture incidence. It occurs in approximately one in every 15–20,000 births and is known to vary considerably in its severity. This report aimed to use next-generation sequencing (NGS) technology to identify disease genes and causal variants in South African patients with clinical-radiological features of OI. A total of 50 affected individuals were recruited at Tygerberg Hospital’s Medical Genetics clinic. Patients were selected for a gene panel test (n = 39), a single variant test (n = 1) or exome sequencing (ES) (n = 12, 7 singletons, 1 affected duo, and 1 trio), depending on funding eligibility. An in-house genomic bioinformatics pipeline was developed for the ES samples using open-source software and tools. This study’s 100% diagnostic yield was largely attributable to an accurate clinical diagnosis. A causal variant in COL1A1 or COL1A2 was identified in 94% of this patient cohort, which is in line with previous studies. Interestingly, this study was the first to identify the common South African pathogenic FKBP10 variant in a patient of mixed ancestry, adding to what was previously known about this variant in our population. Additionally, a recurrent variant in COL1A2: c.1892G>T was discovered in 27 individuals (25 from three large unrelated families and two further individuals), facilitating the establishment of local testing for this variant in South African patients.