bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shank3 deficiency elicits autistic-like behaviors by activating p38α in hypothalamic AgRP neurons
Authors: Wu Shanshan , Wang Jing , Zhang Zicheng , Jin Xinchen , Xu Yang , Si Youwen , Liang Yixiao , Ge Yueping , Zhan Huidong , peng Li , Bi Wenkai , Luo Dandan , Li Mengzhu , Meng Bo , Guan Qingbo , Zhao Jiajun , Gao Ling , He Zhao 
Published: April 2024

Abstract
Background
SH3 and multiple ankyrin repeat domains protein 3 (SHANK3) monogenic mutations or deficiency leads to excessive stereotypic behavior and impaired sociability, which frequently occur in autism cases. To date, the underlying mechanisms by which Shank3 mutation or deletion causes autism and the part of the brain in which Shank3 mutation leads to the autistic phenotypes are understudied. The hypothalamus is associated with stereotypic behavior and sociability. p38α, a mediator of inflammatory responses in the brain, has been postulated as a potential gene for certain cases of autism occurrence. However, it is unclear whether hypothalamus and p38α are involved in the development of autism caused by Shank3 mutations or deficiency.

Methods
Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and immunoblotting were used to assess alternated signaling pathways in the hypothalamus of Shank3 knockout (Shank3−/−) mice. Home-Cage real-time monitoring test was performed to record stereotypic behavior and three-chamber test was used to monitor the sociability of mice. Adeno-associated viruses 9 (AAV9) were used to express p38α in the arcuate nucleus (ARC) or agouti-related peptide (AgRP) neurons. D176A and F327S mutations expressed constitutively active p38α. T180A and Y182F mutations expressed inactive p38α.

Results
We found that Shank3 controls stereotypic behavior and sociability by regulating p38α activity in AgRP neurons. Phosphorylated p38 level in hypothalamus is significantly enhanced in Shank3−/− mice. Consistently, overexpression of p38α in ARC or AgRP neurons elicits excessive stereotypic behavior and impairs sociability in wild-type (WT) mice. Notably, activated p38α in AgRP neurons increases stereotypic behavior and impairs sociability. Conversely, inactivated p38α in AgRP neurons significantly ameliorates autistic behaviors of Shank3−/− mice. In contrast, activated p38α in pro-opiomelanocortin (POMC) neurons does not affect stereotypic behavior and sociability in mice.

Limitations
We demonstrated that SHANK3 regulates the phosphorylated p38 level in the hypothalamus and inactivated p38α in AgRP neurons significantly ameliorates autistic behaviors of Shank3−/− mice. However, we did not clarify the biochemical mechanism of SHANK3 inhibiting p38α in AgRP neurons.

Conclusions
These results demonstrate that the Shank3 deficiency caused autistic-like behaviors by activating p38α signaling in AgRP neurons, suggesting that p38α signaling in AgRP neurons is a potential therapeutic target for Shank3 mutant-related autism.
Efficacy and safety of mesenchymal stem cell therapy for ovarian ageing in a mouse model
Authors: Pei Wendi , Fu Lin , Guo Wenhuan , Wang Yibo , Fan Yong , Yang Rui , Li Rong , Qiao Jie , Yu Yang 
Published: April 2024

Abstract
Background
Ovarian ageing is one of the major issues that impacts female fertility. Mesenchymal stem cell (MSC)-based therapy has made impressive progress in recent years. However, the efficacy and safety of MSCs, as nonautologous components, remain to be further verified.

Methods
Two common sources of MSCs, umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (AD-MSCs), were orthotopically transplanted into a mouse model of ovarian ageing to evaluate their therapeutic effects. The safety of the treatment was further evaluated, and RNA sequencing was performed to explore the underlying mechanisms involved.

Results
After orthotopic transplantation of MSCs into the ovary, the oestrous cycle, ovarian weight, number and proportion of primary follicles, granulosa cell proliferation, and angiogenesis were improved. The effects of AD-MSCs were superior to those of UC-MSCs in several indices, such as post-transplant granulosa cell proliferation, ovarian weight and angiogenesis. Moreover, the tumorigenesis, acute toxicity, immunogenicity and biodistribution of MSCs were evaluated, and both AD-MSCs and UC-MSCs were found to possess high safety profiles. Through RNA sequencing analysis, enhancement of the MAPK cascade was observed, and long-term effects were mainly linked to the activation of immune function.

Conclusions
Orthotopic transplantation of MSCs displays significant efficacy and high safety for the treatment of ovarian ageing in mice.
Sex differences and sex-specific regulation of motivated behavior by Melanin-concentrating hormone: a short review
Authors: Kuebler Isabel R. K. , Suárez Mauricio , Wakabayashi Ken T. 
Published: April 2024

AbstractRecent preclinical research exploring how neuropeptide transmitter systems regulate motivated behavior reveal the increasing importance of sex as a critical biological variable. Neuropeptide systems and their central circuits both contribute to sex differences in a range of motivated behaviors and regulate sex-specific behaviors. In this short review, we explore the current research of how sex as a biological variable influences several distinct motivated behaviors that are modulated by the melanin-concentrating hormone (MCH) neuropeptide system. First, we review how MCH regulates feeding behavior within the context of energy homeostasis differently between male and female rodents. Then, we focus on MCH’s role in lactation as a sex-specific process within the context of energy homeostasis. Next, we discuss the sex-specific effects of MCH on maternal behavior. Finally, we summarize the role of MCH in drug-motivated behaviors. While these topics are traditionally investigated from different scientific perspectives, in this short review we discuss how these behaviors share commonalities within the larger context of motivated behaviors, and that sex differences discovered in one area of research may impact our understanding in another. Overall, our review highlights the need for further research into how sex differences in energy regulation associated with reproduction and parental care contribute to regulating motivated behaviors.
Orthoceratoid and coleoid cephalopods from the Middle Triassic of Switzerland with an updated taxonomic framework for Triassic Orthoceratoidea
Authors: Pohle Alexander , Klug Christian 
Published: April 2024

AbstractOrthoconic cephalopods are subordinate, but persistent, widespread and regionally abundant components of Triassic marine ecosystems. Here, we describe unpublished specimens from the Anisian (Middle Triassic) Besano Formation at Monte San Giorgio, Switzerland. They can be assigned to two major but unrelated lineages, the Coleoidea and the Orthoceratoidea. The orthoceratoids belong toTrematoceras elegans(Münster, 1841) and occur regularly within the Besano Formation, are uniform in size, and have few available morphological characters. In contrast, coleoids are more diverse and appear to be restricted to shorter intervals. A new coleoid is described asTicinoteuthis chuchichaeschtligen. et sp. nov. To better put the orthoceratoids of the Besano Formation into perspective, we also synthesise the current taxonomy of Triassic orthoceratoids on a global scale. The currently used scheme is largely outdated, with very little taxonomic progress in the past 100 years. Despite previous research showing the distinctness of Triassic orthoceratoids from Palaeozoic taxa, they are still commonly labelled as “Orthoceras” or “Michelinoceras”, which are confined to the Palaeozoic. We show that Triassic orthoceratoids probably belong to a single lineage, the Trematoceratidae, which can be assigned to the Pseudorthocerida based on the embryonic shell and endosiphuncular deposits. Many Triassic species can probably be assigned toTrematoceras, but there are at least two additional Triassic orthoceratoid genera,ParatrematocerasandPseudotemperoceras. Finally, we review the palaeobiogeographic and stratigraphic distribution of the group and outline possible future research directions.
Ground state normalized solutions to the Kirchhoff equation with general nonlinearities: mass supercritical case
Authors: Wang Qun , Qian Aixia 
Published: April 2024

AbstractWe study the following nonlinear mass supercritical Kirchhoff equation: $$ - \biggl(a+b \int _{\mathbb{R}^{N}} \vert \nabla u \vert ^{2} \biggr) \triangle u+ \mu u=f(u) \quad \text{in } {\mathbb{R}^{N}}, $$
−

(
a
+
b

∫

R
N

|
∇
u

|
2

)

△
u
+
μ
u
=
f
(
u
)

in

R
N

,
where $a ,b,m>0$
a
,
b
,
m
>
0
are prescribed, and the normalized constrain $\int _{\mathbb{R}^{N}}|u|^{2}\,dx =m$

∫

R
N

|
u
|

2

d
x
=
m
is satisfied in the case $1\leq N\leq 3$
1
≤
N
≤
3
. The nonlinearity f is more general and satisfies weak mass supercritical conditions. Under some mild assumptions, we establish the existence of ground state when $1\leq N\leq 3$
1
≤
N
≤
3
and obtain infinitely many radial solutions when $2\leq N\leq 3$
2
≤
N
≤
3
by constructing a particular bounded Palais–Smale sequence.
Psychometric properties of the cannabis abuse screening test (CAST) in a sample of Moroccans with cannabis use
Authors: El Malki Hicham , Moutawakkil Salma Ghofrane , El-Ammari Abdelfettah , Ragala Mohammed El Amine , El Hilaly Jaouad , El Gnaoui Samir , El Houari Fatima , El Rhazi Karima , Zarrouq Btissame 
Published: April 2024

Abstract
Background
The Cannabis Abuse Screening Test (CAST) is a widely used screening tool for identifying patterns of cannabis use that have negative health or social consequences for both the user and others involved. This brief screening instrument has been translated into multiple languages, and several studies examining its psychometric properties have been published. However, studies on the factorial validity and psychometric properties of a Moroccan version of the CAST are not yet available. The objective of this study is to validate the CAST, translated, and adapted to the Moroccan Arabic dialect among persons with cannabis use.

Methods
A total of 370 participants from an addictology center in Fez City, were selected over two phases to form the study sample. First, in phase I, exploratory factor analysis was employed to evaluate the factor structure in the pilot sample (n1 = 150). Subsequently, in the second phase (Phase II), confirmatory factor analysis was utilized to confirm this structure in the validation sample (n2 = 220). All statistical analyses were carried out using the R program.

Results
The CFA unveiled a three-factor structure that showed a good overall fit (χ2/df = 2.23, RMSEA = 0.07, SRMR = 0.02, CFI = 0.99, NFI = 0.98) and satisfactory local parameters (standardized factor loadings between 0.72 and 0.88). The model demonstrates satisfactory reliability and convergent validity, as evidenced by the acceptable values of composite reliability (CR) (0.76–0.88) and average variance extracted (AVE) (0.62–0.78), respectively. The square roots of the AVE exceeded the correlations of the factor pairs, and the heterotrait-monotrait (HTMT) ratio of the correlation values was below 0.85, indicating acceptable discriminant validity.

Conclusion
The reliability, convergent validity, and discriminant validity tests all demonstrated that the Moroccan version of the CAST performed well and can be considered a valid tool for screening of problematic cannabis use.
Validation of graph sequence clusters through multivariate analysis: application to Rovash scripts
Authors: Hosszú Gábor 
Published: April 2024

Abstract
This paper introduces the concept of pattern systems that evolve, with a focus on scripts, a specific type of pattern system. The study analyses the development of different script systems, known as scriptinformatics, with a focus on the historical Rovash scripts used in the Eurasian steppe. The aim is to assess the traditional classification of historical inscriptions, referred to as script relics, into distinct Rovash scripts. Clustering and ordination techniques were used to perform multivariate analyses on Rovash scripts and inscriptions. The study presents two new measures, the script-specific holophyletic index and the joint holophyletic index, for evaluating trees produced by hierarchical clustering. The results indicate that holophyletic indices can validate the traditional assignment of inscriptions to scripts through phylogenetic tree evaluation. This method can be extended to include pattern systems with evolutionary properties and graph sequences derived from them, as well as additional scripts and inscriptions.
A new ingredient to improve Chinese traditional hydraulic lime and its assessment on stone heritage conservation
Authors: Chen Weichang , Li Li 
Published: April 2024

Abstract
Ginger nut, AGA soil, and shell lime are the primary building limes used in traditional Chinese architectural sites. They have been widely researched and developed for restoring rock and soil heritage over the last decade. Previous studies have shown that these materials are compatible with weathered rock in terms of mechanical properties and environmental adaptability. In this study, metakaolinite was added to Chinese hydraulic limes to improve the mortar abilities. The basic properties and weather abilities of the mortars were evaluated. The characteristics of carbonation and hydration were analyzed over 900 days. The results indicated that the early strength improved and the contracting rate reduced when metakaolinite was added. The shell lime mortar was improved considerably compared with the modified ginger nut and AGA soil. The lime mortar content was determined using the X-ray diffraction results. The carbonation and hydration characteristics revealed that the metakaolinite aided the generation of hydraulic products (Ca2Al2SiO7·nH2O and β-CaSiO3·nH2O), particularly in the early stage. The microstructures were observed by scanning electron microscopy, which revealed more uniform and consolidated structures when metakaolinite was added.
Gene selection via improved nuclear reaction optimization algorithm for cancer classification in high-dimensional data
Authors: El-Mageed Amr A. Abd , Elkhouli Ahmed E. , Abohany Amr A. , Gafar Mona 
Published: April 2024

AbstractRNA Sequencing (RNA-Seq) has been considered a revolutionary technique in gene profiling and quantification. It offers a comprehensive view of the transcriptome, making it a more expansive technique in comparison with micro-array. Genes that discriminate malignancy and normal can be deduced using quantitative gene expression. However, this data is a high-dimensional dense matrix; each sample has a dimension of more than 20,000 genes. Dealing with this data poses challenges. This paper proposes RBNRO-DE (Relief Binary NRO based on Differential Evolution) for handling the gene selection strategy on (rnaseqv2 illuminahiseq rnaseqv2 un edu Level 3 RSEM genes normalized) with more than 20,000 genes to pick the best informative genes and assess them through 22 cancer datasets. The k-nearest Neighbor (k-NN) and Support Vector Machine (SVM) are applied to assess the quality of the selected genes. Binary versions of the most common meta-heuristic algorithms have been compared with the proposed RBNRO-DE algorithm. In most of the 22 cancer datasets, the RBNRO-DE algorithm based on k-NN and SVM classifiers achieved optimal convergence and classification accuracy up to 100% integrated with a feature reduction size down to 98%, which is very evident when compared to its counterparts, according to Wilcoxon’s rank-sum test (5% significance level).
A novel neuroimmune modulation system for the treatment of rheumatoid arthritis
Authors: Bonaz Bruno 
Published: April 2024

AbstractThe vagus nerve has an anti-inflammatory effect through the inflammatory reflex, which inhibits the release of proinflammatory cytokines by macrophages. Recent pilot clinical trials, using implantable bioelectronic devices, have demonstrated the efficacy of vagus nerve stimulation in adult patients with rheumatoid arthritis and inflammatory bowel diseases as an alternative to drugs, which are not devoid of side effects and are costly. In this issue of Bioelectronic Medicine, Peterson et al. report the safety of novel implantable neuroimmune modulation device for treating rheumatoid arthritis (The RESET RA study), which I will discuss in this commentary.
Joint contrastive learning and belief rule base for named entity recognition in cybersecurity
Authors: Hu Chenxi , Wu Tao , Liu Chunsheng , Chang Chao 
Published: April 2024

AbstractNamed Entity Recognition (NER) in cybersecurity is crucial for mining information during cybersecurity incidents. Current methods rely on pre-trained models for rich semantic text embeddings, but the challenge of anisotropy may affect subsequent encoding quality. Additionally, existing models may struggle with noise detection. To address these issues, we propose JCLB, a novel model that Joins Contrastive Learning and Belief rule base for NER in cybersecurity. JCLB utilizes contrastive learning to enhance similarity in the vector space between token sequence representations of entities in the same category. A Belief Rule Base (BRB) is developed using regexes to ensure accurate entity identification, particularly for fixed-format phrases lacking semantics. Moreover, a Distributed Constraint Covariance Matrix Adaptation Evolution Strategy (D-CMA-ES) algorithm is introduced for BRB parameter optimization. Experimental results demonstrate that JCLB, with the D-CMA-ES algorithm, significantly improves NER accuracy in cybersecurity.
The outcome of genetic and non-genetic pediatric cardiomyopathies
Authors: AlAlakhfash Ali , Agati Luciano , Mazzesi Giuseppe , Elhobi Dalia , Alqwaiee Abdullah , Alhory Khalid , Almesned Abdulrahman , Alhasnan Zuhair , Alwadai Abdullah 
Published: April 2024

Abstract
Background
Pediatric cardiomyopathies (CMP) can be familial or idiopathic with increasing detection of genetic mutations. The study is a retrospective single-center review of cardiomyopathy patients from January 2011 to May 2020. Results of the genetic study, as well as the outcome, were reported. Patients were divided according to the type of CMP, age of presentation, and EF at presentation. Univariate and multivariate analysis and ROC and survival curves were done.

Results
We reported 229 patients under 14 years of age with a diagnosis of cardiomyopathy, most commonly DCM (160 patients (70%)) followed by HCM (26.2%). 52% presented at 6 months of age or less and 119 (52%) required ICU admission at presentation. The genetic and or metabolic disorder was confirmed in 21.4% of patients, most commonly VLCAD defect (16, 7%) and ELAC2 gene defect (10, 4.4%). During the disease course, 88 patients (38.4%) died (48 with DCM, 39 with HCM, and 1 with RCM). An EF of 20% or less at presentation and presentation at 6 months of age or less carries a risk for mortality in patients with DCM and HCM, respectively (RR 3.88 and 2.06 and OR of 11.09 and 4.35, respectively). Death was more common among HCM patients especially patients with positive genetic abnormality compared with patients with DCM.

Conclusions
The mortality for CMP in children reaches up to 40%, (30% in DCM and 65% in HCM patients). Mortality was higher in those with HCM, DCM with EF of 20% or less, and HCM presented at 6 months of age or less. Whole-exome and/or whole-genome sequencing is advised for all patients of CMP and at-risk family members.
Design and implementation of a Primary Health Care (PHC) Toolbox for improving the impact of support from Global Development Partners
Authors: Spasenoska Dijana , Grundy John , Omam Lundi-Anne , Chaudhri Irtaza Ahmad , Khalid Faraz , O’Connell Thomas S. , Tampe Tova 
Published: April 2024

AbstractPrimary Health Care (PHC) is the most equitable and cost-effective way to enhance the health of populations and improve health security and is a requirement for achieving universal health coverage (UHC). Vital to advancing the PHC agenda is effective global health partnerships, particularly with Global Health Initiatives (GHIs) which provide financial support for improving population health. Despite progress, GHI support at times remained parallel to rather than embedded in national health strategies. To improve the impact of GHI support, World Health Organization (WHO) member states requested specific guidance to better align GHI support to national health strategies and PHC principles. We present the PHC-GHI Toolbox as a comprehensive set of resources for use by countries to apply the PHC approach to development of plans for securing and optimally utilizing funding received from GHIs, such as Gavi, the Vaccine Alliance; the Global Fund to Fight AIDS, Tuberculosis, and Malaria (GFATM); and the Global Financing Facility (GFF) as well as other donors. The PHC-GHI Toolbox includes a PHC resource database, GHI-specific overviews, a database of health system strengthening (HSS) investments, COVID-19 funding rapid assessment tool, and a focal point database for identifying expert technical assistance. This paper describes the process undertaken for Toolbox development and outlines its potential applications.
PmWebSpec: An Application to Create and Manage CDISC-Compliant Pharmacometric Analysis Dataset Specifications
Authors: Chen Lu , Dombrowsky Erin , Boyle Baylea , Tang Chengke , Thanneer Neelima 
Published: April 2024

AbstractA well-documented pharmacometric (PMx) analysis dataset specification ensures consistency in derivations of the variables, naming conventions, traceability to the source data, and reproducibility of the analysis dataset. Lack of standards in creating the dataset specification can lead to poor quality analysis datasets, negatively impacting the quality of the PMx analysis. Standardization of the dataset specification within an individual organization helps address some of these inconsistencies. The recent introduction of the Clinical Data Interchange Standards Consortium (CDISC) Analysis Data Model (ADaM) Population Pharmacokinetic (popPK) Implementation Guide (IG) further promotes industry-wide standards by providing guidelines for the basic data structure of popPK analysis datasets. However, manual implementation of the standards can be labor intensive and error-prone. Hence, there is still a need to automate the implementation of these standards. In this paper, we present PmWebSpec, an easily deployable web-based application to facilitate the creation and management of CDISC-compliant PMx analysis dataset specifications. We describe the application of this tool through examples and highlight its key features including pre-populated dataset specifications, built-in checks to enforce standards, and generation of an electronic Common Technical Document (eCTD)-compliant data definition file. The application increases efficiency, quality and semi-automates PMx analysis dataset, and specification creation and has been well accepted by pharmacometricians and programmers internally. The success of this application suggests its potential for broader usage across the PMx community.
Graphical Abstract