bluuebunny/crossref_metadata_2025_split huggingface dataset:
A review on the new age methodologies for early detection of Alzheimer's and Parkinson's disease
Authors: Ghosh Nabanita , Sinha Krishnendu , Sil Parames C. 
Published: March 2024

AbstractBackgroundsNeurodegenerative diseases (NDDs) such as Alzheimer's (AD) and Parkinson's (PD) are often diagnosed late, impeding effective treatment; therefore, early detection is imperative. Modern methodologies can serve a pivotal role in fulfilling the crucial need for timely detection and intervention in this context.ObjectivesEvaluate early detection's significance and summarize key technologies (biomarkers, neuroimaging, AI/ML, genetics, digital health) for enhanced diagnostic strategies in AD and PD.MethodsThis study employs a focused descriptive review approach, encompassing analysis of peer‐reviewed articles and clinical trials from existing literature, to provide a nuanced exploration of the subject matter.FindingsThis review underscores the efficacy of non‐invasive biomarkers, biosensors and emerging promising technologies for advancing early diagnosis of AD and PD.ConclusionThe landscape of early NDD detection has been reshaped by technology, yet challenges persist, encompassing the domains of validation and ethics. A collaborative effort between medical professionals, researchers and technologists is imperative to effectively address and combat NDDs.
I help, therefore, I am? – A registered report on longitudinal inter‐relations of the three‐dimensional moral self‐concept and prosocial behaviours in preschool children
Authors: Söldner Lena , Paulus Markus 
Published: March 2024

AbstractChildren's moral self‐concept (MSC) has been proposed to relate to prosocial behaviour. However, systematic assessments of their inter‐relations are scarce. Therefore, this longitudinal study investigated the development, structure and inter‐relation of prosocial behaviours and the MSC in childhood, using three measurement points at ages 4, 5 and 6 years. We assessed children's MSC and helping, sharing and comforting behaviours in a laboratory setting. Confirmatory factor analyses revealed a three‐dimensional MSC structure at 5 and 6 years, but not at 4 years. There was inconsistent stability across time points regarding prosocial behaviour and MSC. For the comforting domain, but not the other domains, cross‐lagged relations between self‐concept and behaviour were present. Moreover, helping behaviour and self‐concept were inter‐related at 6 years. Results provide support for reciprocal associations between MSC and prosocial behaviour, albeit only in the comforting domain. They highlight the importance of distinguishing between types of prosocial behaviour and corresponding dimensions of the self‐concept, as different developmental trajectories and associations emerge.
Alix‐normalized exosomal programmed death‐ligand 1 analysis in urine enables precision monitoring of urothelial cancer
Authors: Woo Hyun‐Kyung , Park Juhee , Kim Kyung Hwan , Ku Ja Yoon , Ha Hong Koo , Cho Yoon‐Kyoung 
Published: March 2024

AbstractAnti‐programmed death‐ligand 1 (PD‐L1) Ab‐based therapies have demonstrated potential for treating metastatic urothelial cancer with high PD‐L1 expression. Urinary exosomes are promising biomarkers for liquid biopsy, but urine's high variability requires normalization for accurate analysis. This study proposes using the PD‐L1/Alix ratio to normalize exosomal PD‐L1 signal intensity with Alix, an internal exosomal protein less susceptible to heterogeneity concerns than surface protein markers. Extracellular vesicles were isolated using ExoDisc and characterized using various methods, including ExoView to analyze tetraspanins, PD‐L1, and Alix on individual exosomes. On‐disc ELISA was used to evaluate PD‐L1 and Alix‐normalized PD‐L1 in 15 urothelial cancer patients during the initial treatment cycle with Tecentriq. Results showed that Alix signal range was relatively uniform, whereas tetraspanin marker intensity varied for individual exosome particles. On‐disc ELISA was more reliable for detecting exosomal PD‐L1 expression than standard plate ELISA‐based measurement. Using exosomal Alix expression for normalization is a more reliable approach than conventional methods for monitoring patient status. Overall, the study provides a practical and reliable method for detecting exosomal PD‐L1 in urine samples from patients with urothelial cancer.
Upregulation of HLA‐II related to LAG‐3+CD4+ T cell infiltration is associated with patient outcome in human glioblastoma
Authors: Guo Wenli , Peng Daijun , Liao Yuee , Lou Lei , Guo Moran , Li Chen , Yu Wangyang , Tian Xiaoxi , Wang Guohui , Lv Ping , Zuo Jing , Shen Haitao , Li Yuehong 
Published: March 2024

AbstractGlioblastoma (GBM) is the most common malignant diffuse glioma of the brain. Although immunotherapy with immune checkpoint inhibitors (ICIs), such as programmed cell death protein (PD)‐1/PD ligand‐1 inhibitors, has revolutionized the treatment of several cancers, the clinical benefit in GBM patients has been limited. Lymphocyte‐activation gene 3 (LAG‐3) binding to human leukocyte antigen‐II (HLA‐II) plays an essential role in triggering CD4+ T cell exhaustion and could interfere with the efficiency of anti‐PD‐1 treatment; however, the value of LAG‐3–HLA‐II interactions in ICI immunotherapy for GBM patients has not yet been analyzed. Therefore, we aimed to investigate the expression and regulation of HLA‐II in human GBM samples and the correlation with LAG‐3+CD4+ T cell infiltration. Human leukocyte antigen‐II was highly expressed in GBM and correlated with increased LAG‐3+CD4+ T cell infiltration in the stroma. Additionally, HLA‐IIHighLAG‐3High was associated with worse patient survival. Increased interleukin‐10 (IL‐10) expression was observed in GBM, which was correlated with high levels of HLA‐II and LAG‐3+ T cell infiltration in stroma. HLA‐IIHighIL‐10High GBM associated with LAG‐3+ T cells infiltration synergistically showed shorter overall survival in patients. Combined anti‐LAG‐3 and anti‐IL‐10 treatment inhibited tumor growth in a mouse brain GL261 tumor model. In vitro, CD68+ macrophages upregulated HLA‐II expression in GBM cells through tumor necrosis factor‐α (TNF‐α). Blocking TNF‐α‐dependent inflammation inhibited tumor growth in a mouse GBM model. In summary, T cell–tumor cell interactions, such as LAG‐3–HLA‐II, could confer an immunosuppressive environment in human GBM, leading to poor prognosis in patients. Therefore, targeting the LAG‐3–HLA‐II interaction could be beneficial in ICI immunotherapy to improve the clinical outcome of GBM patients.
FAXC interacts with ANXA2 and SRC in mitochondria and promotes tumorigenesis in cholangiocarcinoma
Authors: Fujimori Haruna , Shima‐Nakamura Mao , Kanno Shin‐Ichiro , Shibuya‐Takahashi Rie , Mochizuki Mai , Mizuma Masamichi , Unno Michiaki , Wakui Yuta , Abue Makoto , Iwai Wataru , Fukushi Daisuke , Satoh Kennich , Yamaguchi Kazunori , Shindo Norihisa , Yasuda Jun , Tamai Keiichi 
Published: March 2024

AbstractCholangiocarcinoma (CCA) is one of the most difficult malignancies to treat as the therapeutic options are limited. Although several driver genes have been identified, most remain unknown. In this study, we identified a failed axon connection homolog (FAXC), whose function is unknown in mammals, by analyzing serially passaged CCA xenograft models. Knockdown of FAXC reduced subcutaneous tumorigenicity in mice. FAXC was bound to annexin A2 (ANXA2) and c‐SRC, which are tumor‐promoting genes. The FAXC/ANXA2/c‐SRC complex forms in the mitochondria. FAXC enhances SRC‐dependent ANXA2 phosphorylation at tyrosine‐24, and the C‐terminal amino acid residues (351–375) of FAXC are required for ANXA2 phosphorylation. Transcriptome data from a xenografted CCA cell line revealed that FAXC correlated with epithelial–mesenchymal transition, hypoxia, and KRAS signaling genes. Collectively, these findings advance our understanding of CCA tumorigenesis and provide candidate therapeutic targets.
Quality of life of families and siblings of children and adolescents with meningomyelocele
Authors: Dias Bruno Leonardo Scofano , de Rodrigues Maura Calixto Cecherelli , Duarte José Luiz Muniz Bandeira 
Published: March 2024

AbstractBackgroundChildren with meningomyelocele may require continuous care. Consequently, there is a risk for caregiver burden and impact on family quality of life (QoL), including siblings' QoL. Some studies analysed caregivers' burden and family QoL separately. However, none of these studies evaluated siblings' QoL and the associations between these three dimensions. This study investigated the associations between caregivers' burden, family QoL and siblings' QoL in Brazilian families of children with meningomyelocele and its correlations with sociodemographic, functional and clinical variables. Siblings' QoL was specifically assessed using as a parameter the QoL of typically developed Brazilian children.MethodsOne hundred and fifty families, 150 caregivers and 68 siblings completed the Family Quality of Life Scale, Burden Interview, KIDSCREEN‐27 Child and Adolescent Version and Parents Version questionnaires.ResultsMost families and caregivers reported a high family QoL and a low caregiver burden. Family QoL was significantly lower as caregivers' burden increased. Caregiver's burden was significantly lower with increasing family QoL levels. Self‐reported siblings' QoL was significantly worse than that of typically developed peers. There were no significant differences between self and parent‐reported siblings' QoL. Self‐reported siblings' QoL was significantly worse as their age increased and better with increasing family QoL levels. Parent‐reported siblings' QoL was significantly worse with increasing levels of caregiver's burden and significantly better as family QoL increased. There were no significant associations with functional and clinical variables.ConclusionsDespite the cross‐sectional nature of the available data precludes any statements of causality, our results reinforce the relevance of knowing the factors that influence the QoL of families and siblings of children and adolescents with meningomyelocele and the relevance of actions aimed at reducing caregivers' burden, improving family QoL and meeting siblings' individual needs. Future multicenter studies may validate the generalizability of our findings.
Colon cancer: feeling the imbalance?
Authors: Ballal Devesh S. , Saklani Avanish P. 
Published: March 2024

AbstractWhile neoadjuvant chemotherapy has become the standard of care for rectal cancers in most centres, there is much interest in neoadjuvant chemotherapy in colon cancer after the recent publication of the FOxTROT trial. The management of colon cancers seems to be heading down the same path as rectal cancer, where the radicality of surgery is replaced by chemotherapy intensification. The role of demanding procedures such as complete mesocolic excision with central venous ligation in this new paradigm of upfront chemotherapy remains uncertain and uninvestigated.
Hydrochlorothiazide and increased risk of atypical fibroxanthoma and pleomorphic dermal sarcoma
Authors: Kuntz Thomas , Grimm Alexander , Hofmann Silke C. , Michalowitz Alena‐Lioba , Schaller Jörg , Hellmich Martin , Assaf Chalid , Oellig Frank , Kreuter Alexander 
Published: March 2024

SummaryBackground and ObjectivesPrevious work has demonstrated that hydrochlorothiazide (HCTZ) is a risk factor for squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) due to pro‐photocarcinogenic effects. Atypical fibroxanthoma (AFX) and pleomorphic sarcoma (PDS), both ultraviolet‐induced cancers, display a rare but rising cutaneous tumor entity. This study aimed to evaluate if the use of HCTZ is higher in patients with AFX/PDS than in patients with SCC/BCC and subsequently may be a risk factor for AFX/PDS‐development.Patients and MethodsIn a retrospective study of four German skin cancer centers, AFX/PDS cases and SCC/BCC controls were sex and age matched (1:3) over a time‐period of 7 years (2013–2019) to evaluate the use of HCTZ, immunosuppressive medication, second malignancies, and presence of diabetes mellitus.ResultsOverall, 146 AFX/PDS and 438 controls (SCC/BCC) were included in the study. The use of HCTZ was significantly higher in patients with AFX/PDS (44.5%) compared to patients with SCC/BCC (25.3%). Additionally, the presence of diabetes mellitus was significantly higher in AFX/PDS patients.ConclusionsThis study demonstrates a significantly higher use of HCTZ in patients with AFX/PDS compared to SCC/BCC. This result suggests that HCTZ may be a risk factor for AFX/PDS. Additionally, diabetes mellitus or its comorbidities may be associated with an increased risk for AFX/PDS.
Angiotensin II involvement in the development and persistence of amphetamine‐induced sensitization: Striatal dopamine reuptake implications
Authors: Basmadjian Osvaldo M. , Occhieppo Victoria B. , Montemerlo Antonella E. , Rivas Gustavo A. , Rubianes María D. , Baiardi Gustavo , Bregonzio Claudia 
Published: March 2024

AbstractAmphetamine (AMPH) exposure induces behavioural and neurochemical sensitization observed in rodents as hyperlocomotion and increased dopamine release in response to a subsequent dose. Brain Angiotensin II modulates dopaminergic neurotransmission through its AT1 receptors (AT1‐R), positively regulating striatal dopamine synthesis and release. This work aims to evaluate the AT1‐R role in the development and maintenance of AMPH‐induced sensitization. Also, the AT1‐R involvement in striatal dopamine reuptake was analysed. The sensitization protocol consisted of daily AMPH administration for 5 days and tested 21 days after withdrawal. An AT1‐R antagonist, candesartan, was administered before or after AMPH exposure to evaluate the participation of AT1‐R in the development and maintenance of sensitization, respectively. Sensitization was evaluated by locomotor activity and c‐Fos immunostaining. Changes in dopamine reuptake kinetics were evaluated 1 day after AT1‐R blockade withdrawal treatment, with or without the addition of AMPH in vitro. The social interaction test was performed as another behavioural output. Repeated AMPH exposure induced behavioural and neurochemical sensitization, which was prevented and reversed by candesartan. The AT1‐R blockade increased the dopamine reuptake kinetics. Neither the AMPH administration nor the AT1‐R blockade altered the performance of social interaction. Our results highlight the AT1‐R's crucial role in AMPH sensitization. The enhancement of dopamine reuptake kinetics induced by the AT1‐R blockade might attenuate the neuroadaptive changes that lead to AMPH sensitization and its self‐perpetuation. Therefore, AT1‐R is a prominent candidate as a target for pharmacological treatment of pathologies related to dopamine imbalance, including drug addiction and schizophrenia.
A rights‐based approach to the choice of forum in climate displacement litigation: Lessons from the Americas
Authors: Gouritin Armelle 
Published: March 2024

AbstractFew studies address climate litigation and climate forced mobility together, and the link between climate litigation and internal forced climate displacement remains poorly addressed. This article aims to participate in filling this void. We focus on climate displacement litigation argued before regional human rights courts (the Inter‐American Court) and national human rights protection bodies (the Mexican Commission) to determine the adequacy of each from the perspective of potential litigants. We address institutional, procedural and positive law within the context of water scarcity. We find that while institutional and procedural aspects reveal the potential of the Inter‐American Court in ruling on climate displacement cases, the application of the positive obligations doctrine by the Mexican National Human Rights Commission is more disaggregated and a priori suitable to ground the course of action of potential litigants.
Early developmental carry‐over effects on exploratory behaviour and DNA methylation in wild great tits (Parus major)
Authors: Sepers Bernice , Verhoeven Koen J. F. , van Oers Kees 
Published: March 2024

AbstractAdverse, postnatal conditions experienced during development are known to induce lingering effects on morphology, behaviour, reproduction and survival. Despite the importance of early developmental stress for shaping the adult phenotype, it is largely unknown which molecular mechanisms allow for the induction and maintenance of such phenotypic effects once the early environmental conditions are released. Here we aimed to investigate whether lasting early developmental phenotypic changes are associated with post‐developmental DNA methylation changes. We used a cross‐foster and brood size experiment in great tit (Parus major) nestlings, which induced post‐fledging effects on biometric measures and exploratory behaviour, a validated personality trait. We investigated whether these post‐fledging effects are associated with DNA methylation levels of CpG sites in erythrocyte DNA. Individuals raised in enlarged broods caught up on their developmental delay after reaching independence and became more explorative as days since fledging passed, while the exploratory scores of individuals that were raised in reduced broods remained stable. Although we previously found that brood enlargement hardly affected the pre‐fledging methylation levels, we found 420 CpG sites that were differentially methylated between fledged individuals that were raised in small versus large sized broods. A considerable number of the affected CpG sites were located in or near genes involved in metabolism, growth, behaviour and cognition. Since the biological functions of these genes line up with the observed post‐fledging phenotypic effects of brood size, our results suggest that DNA methylation provides organisms the opportunity to modulate their condition once the environmental conditions allow it. In conclusion, this study shows that nutritional stress imposed by enlarged brood size during early development associates with variation in DNA methylation later in life. We propose that treatment‐associated DNA methylation differences may arise in relation to pre‐ or post‐fledging phenotypic changes, rather than that they are directly induced by the environment during early development.
Diagnosis and treatment of von Willebrand disease in 2024 and beyond
Authors: James Paula , Leebeek Frank , Casari Caterina , Lillicrap David 
Published: March 2024

AbstractManuscript background and aimThe diagnosis and clinical care of patients with von Willebrand disease (VWD) has continued to evolve since the characterization of the von Willebrand factor (VWF) gene in 1985. This condition is almost certainly the most common inherited bleeding disorder, and the major symptomatic burden of the disease is experienced by females during their reproductive years. Diagnosis relies on the identification of a personal and family history of excessive mucocutaneous bleeding, and laboratory features consistent with quantitative and/or qualitative abnormalities of VWF. This review focuses on three aspects of VWD management, with current updates and a look into the future.Manuscript themesFirst, we will address the role of genetics in the diagnosis and possible therapies for VWD. With current technologies, VWD genetic diagnosis is usually confined to the confirmation of type 2 subtypes of the disease and type 3 VWD analysis for family planning. While type 3 VWD is a potential candidate for the application of gene therapy, no treatments are currently close to entering the clinic. Second, the peri‐procedural management of patients with VWD remains an important element of care. The choice of product, its dose and schedule all require careful consideration depending upon the type and disruptive nature of the planned procedure. Lastly, in addition to gene therapy, several other novel therapeutic interventions are also being developed for bleeding and prophylaxis in VWD. These include a VWF aptamer interfering with VWF clearance and bioengineered forms of VWF.
Phylogeography of the Iberian endemic butterfly Erebia palarica Chapman, 1905 (Lepidoptera: Nymphalidae): An integrative approach
Authors: Torrado‐Blanco Laura , Eberle Jonas , Romo Helena , Mortera Hugo , Vila Marta 
Published: March 2024

Abstract
Montane biodiversity is particularly vulnerable to rapid oscillations in environmental conditions. Recent modelling showed that only three of the 19 butterfly species of Erebia (Nymphalidae, Satyrinae) currently present in Iberia would persist in a worst‐case scenario for 2070. One of them is Erebia palarica, endemic to Northwest Spain. We combined genetics, morphometrics and ecological niche modelling to reconstruct its evolutionary history.
First, sequences of the cytochrome oxidase I (COI) mitochondrial gene obtained from 305 specimens revealed a double star‐like network that suggests a demographic expansion from two ancestral populations. This finding is congruent with the larger and disjunct putative distribution revealed by climatic modelling during the Last Glacial Maximum.
Second, genotyping of 262 samples with seven microsatellite markers produced a large cluster at the centre‐East of the Cantabrian range, mostly affected by isolation by distance, and revealed different levels of structure in the western localities.
Lastly, we reviewed the intraspecific taxonomy of the species. The westernmost site (Queixa) stands as a clearly separated unit according to genetic and morphometric analyses, which further supports its vague former description as subspecies E. p. castroviejoi.
Altogether, the case of E. palarica exemplifies the complexity that narrow endemics can show and highlights that understanding the evolutionary history of species is crucial for designing adequate conservation strategies.
Phase purifying and dielectric improvement in Zn2SiO4 ceramics via simply controlling the particle size of SiO2
Authors: Xing Zhuo , Song Julong , Pan Hong 
Published: March 2024

AbstractThe zinc orthosilicate, Zn2SiO4 ceramics, exhibit great potential as microwave dielectric materials due to their low dielectric constant and ultrahigh quality factor. The solid‐state synthesis of Zn2SiO4 ceramics often results in the presence of a secondary phase of ZnO, however, leading to significantly lower Q×f values. Cold‐isostatic‐pressing (CIP) and nonstoichiometry have been proven effective in purifying the Zn2SiO4 but need elaborate process and composition manipulation. In this work, it was found that the particle size of SiO2 plays a crucial role in purifying the Zn2SiO4 phase. Specially, nano‐sized SiO2 particles (15 and 30 nm) led to the formation of a ZnO secondary phase in synthesized Zn2SiO4 ceramics, while micro‐sized (2 and 10 µm) resulted in pure‐phase Zn2SiO4 with excellent microwave properties. Notably, when prepared with 10 µm SiO2 and sintered at 1 340°C, the resulting Zn2SiO4 exhibited outstanding microwave performances with a Q×f value of 122 570 GHz, a temperature coefficient of frequency τf of −51.9 ppm/°C, and a dielectric constant (εr) of 6.5. These findings highlight the importance of controlling particle size during synthesis to achieve desired material properties such as purity and excellent microwave performances.