bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unraveling the genetic architecture of blood unfolded p-53 among non-demented elderlies: novel candidate genes for early Alzheimer's disease
Authors: Yaghoobi Arash , Malekpour Seyed Amir 
Published: May 2024

Abstract
Background
Alzheimer's disease (AD) is a heritable neurodegenerative disease whose long asymptomatic phase makes the early diagnosis of it pivotal. Blood U-p53 has recently emerged as a superior predictive biomarker for AD in the early stages. We hypothesized that genetic variants associated with blood U-p53 could reveal novel loci and pathways involved in the early stages of AD.

Results
We performed a blood U-p53 Genome-wide association study (GWAS) on 484 healthy and mild cognitively impaired subjects from the ADNI cohort using 612,843 Single nucleotide polymorphisms (SNPs). We performed a pathway analysis and prioritized candidate genes using an AD single-cell gene program. We fine-mapped the intergenic SNPs by leveraging a cell-type-specific enhancer-to-gene linking strategy using a brain single-cell multimodal dataset. We validated the candidate genes in an independent brain single-cell RNA-seq and the ADNI blood transcriptome datasets. The rs279686 between AASS and FEZF1 genes was the most significant SNP (p-value = 4.82 × 10–7). Suggestive pathways were related to the immune and nervous systems. Twenty-three candidate genes were prioritized at 27 suggestive loci. Fine-mapping of 5 intergenic loci yielded nine cell-specific candidate genes. Finally, 15 genes were validated in the independent single-cell RNA-seq dataset, and five were validated in the ADNI blood transcriptome dataset.

Conclusions
We underlined the importance of performing a GWAS on an early-stage biomarker of AD and leveraging functional omics datasets for pinpointing causal genes in AD. Our study prioritized nine genes (SORCS1, KIF5C, TMEFF2, TMEM63C, HLA-E, ATAT1, TUBB, ARID1B, and RUNX1) strongly implicated in the early stages of AD.
Metabolomics reveals high fructose-1,6-bisphosphate from fluoride-resistant Streptococcus mutans
Authors: Zhu Laikuan , Li Jiehang , Pan Yueping , Huang Jing , Yao Hui 
Published: May 2024

Abstract
Background
Fluoride-resistant Streptococcus mutans (S. mutans) strains have developed due to the wide use of fluoride in dental caries prevention. However, the metabolomics of fluoride-resistant S. mutans remains unclear.

Objective
This study aimed to identify metabolites that discriminate fluoride-resistant from wild-type S. mutans.

Materials and methods
Cell supernatants from fluoride-resistant and wild-type S. mutans were collected and analyzed by liquid chromatography-mass spectrometry. Principal components analysis and partial least-squares discriminant analysis were performed for the statistical analysis by variable influence on projection (VIP > 2.0) and p value (Mann–Whitney test, p < 0.05). Metabolites were assessed qualitatively using the Human Metabolome Database version 2.0 (http://www.hmdb.ca), or Kyoto Encyclopedia of Genes and Genomes (http://www.kegg.jp), and Metaboanalyst 6.0 (https://www.metaboanalyst.ca).

Results
Fourteen metabolites differed significantly between fluoride-resistant and wild-type strains in the early log phase. Among these metabolites, 5 were identified. There were 32 differential metabolites between the two strains in the stationary phase, 13 of which were identified. The pyrimidine metabolism for S. mutans FR was matched with the metabolic pathway.

Conclusions
The fructose-1,6-bisphosphate concentration increased in fluoride-resistant strains under acidic conditions, suggesting enhanced acidogenicity and acid tolerance. This metabolite may be a promising target for elucidating the cariogenic and fluoride resistant mechanisms of S. mutans.
Integrated phenotypic, transcriptomics and metabolomics: growth status and metabolite accumulation pattern of medicinal materials at different harvest periods of Astragalus Membranaceus Mongholicus
Authors: Li Xiaojie , Mu Yingtong , Hua Mei , Wang Junjie , Zhang Xiaoming 
Published: May 2024

Abstract
Background
Astragalus membranaceus var. mongholicus (Astragalus), acknowledged as a pivotal “One Root of Medicine and Food”, boasts dual applications in both culinary and medicinal domains. The growth and metabolite accumulation of medicinal roots during the harvest period is intricately regulated by a transcriptional regulatory network. One key challenge is to accurately pinpoint the harvest date during the transition from conventional yield content of medicinal materials to high and to identify the core regulators governing such a critical transition. To solve this problem, we performed a correlation analysis of phenotypic, transcriptome, and metabolome dynamics during the harvesting of Astragalus roots.

Results
First, our analysis identified stage-specific expression patterns for a significant proportion of the Astragalus root genes and unraveled the chronology of events that happen at the early and later stages of root harvest. Then, the results showed that different root developmental stages can be depicted by co-expressed genes of Astragalus. Moreover, we identified the key components and transcriptional regulation processes that determine root development during harvest. Furthermore, through correlating phenotypes, transcriptomes, and metabolomes at different harvesting periods, period D (Nov.6) was identified as the critical period of yield and flavonoid content increase, which is consistent with morphological and metabolic changes. In particular, we identified a flavonoid biosynthesis metabolite, isoliquiritigenin, as a core regulator of the synthesis of associated secondary metabolites in Astragalus. Further analyses and experiments showed that HMGCR, 4CL, CHS, and SQLE, along with its associated differentially expressed genes, induced conversion of metabolism processes, including the biosynthesis of isoflavones and triterpenoid saponins substances, thus leading to the transition to higher medicinal materials yield and active ingredient content.

Conclusions
The findings of this work will clarify the differences in the biosynthetic mechanism of astragaloside IV and calycosin 7-O-β-D-glucopyranoside accumulation between the four harvesting periods, which will guide the harvesting and production of Astragalus.
Combined application of arbuscular mycorrhizal fungi and selenium fertilizer increased wheat biomass under cadmium stress and shapes rhizosphere soil microbial communities
Authors: Liu Haiyang , Wang Haoquan , Nie Zhaojun , Tao Zhikang , Peng Hongyu , Shi Huazhong , Zhao Peng , Liu Hongen 
Published: May 2024

Abstract
Background
Selenium (Se) fertilizer and arbuscular mycorrhizal fungi (AMF) are known to modulate cadmium (Cd) toxicity in plants. However, the effects of their co-application on wheat growth and soil microbial communities in Cd-contaminated soil are unclear.

Results
A pot experiment inoculation with two types of AMF and the application of Se fertilizer under Cd stress in wheat showed that inoculation AMF alone or combined with Se fertilizer significantly increased wheat biomass. Se and AMF alone or in combination significantly reduced available Cd concentration in wheat and soil, especially in the Se combined with Ri treatment. High throughput sequencing of soil samples indicated that Se and AMF application had stronger influence on bacterial community compared to fungal community and the bacterial network seemed to have more complex interconnections than the fungal network, and finally shaped the formation of specific microflora to affect Cd availability.

Conclusion
These results indicate that the application of Se and AMF, particularly in combination, could successfully decrease soil Cd availability and relieve the harm of Cd in wheat by modifying rhizosphere soil microbial communities.
Modified diatomite for soil remediation and its implications for heavy metal absorption in Calendula officinalis
Authors: Samani Maryam , Ahlawat Yogesh K. , Golchin Ahmad , Alikhani Hossein Ali , Baybordi Ahmad , Mishra Sadhna 
Published: May 2024

Abstract
Background
Among different adsorbents, natural and inorganic compounds such as diatomite are important and advantageous in terms of high efficiency and cost-effectiveness, and function in stabilizing heavy metals in the environment. Calendula officinalis, a plant known as a high accumulator of heavy metals, was cultivated in soil treated with varying concentrations of modified diatomite to demonstrate the efficiency of modified diatomite in stabilizating of heavy metals in soils,

Results
The modification of diatomite aimed to enhance Calendula officinalis adsorptive properties, particularly towards heavy metals such as lead (Pb), Zinc (Zn), Chromium (Cr), Nickle (Ni), and Copper (Cu), common contaminants in industrial soils. The experimental design included both control and treated soil samples, with assessments at regular intervals. Modified diatomite significantly decreased the bioaccumulation of heavy metals in contaminated soils except Zn, evidenced by decreased DTPA extractable heavy metals in soil and also heavy metal concentrations in plant tissues. Using 10% modified diatomite decreased 91% Pb and Cu, 78% Cr, and 79% Ni concentration of plants compared to the control treatment. The highest concentration of Zn in plant tissue was observed in 2.5% modified diatomite treatment. Remarkably, the application of modified diatomite also appeared to improve the nutrient profile of the soil, leading to enhanced uptake of key nutrients like phosphorus (P) 1.18%, and potassium (K) 79.6% in shoots and 82.3% in roots in Calendula officinalis. Consequently, treated plants exhibited improved growth characteristics, including shoots and roots height of 16.98% and 12.8% respectively, and shoots fresh and dry weight of 48.5% and 50.2% respectively., compared to those in untreated, contaminated soil.

Conclusion
The findings suggest promising implications for using such amendments in ecological restoration and sustainable agriculture, particularly in areas impacted by industrial pollution.
A novel non-negative Bayesian stacking modeling method for Cancer survival prediction using high-dimensional omics data
Authors: Shen Junjie , Wang Shuo , Sun Hao , Huang Jie , Bai Lu , Wang Xichao , Dong Yongfei , Tang Zaixiang 
Published: May 2024

Abstract
Background
Survival prediction using high-dimensional molecular data is a hot topic in the field of genomics and precision medicine, especially for cancer studies. Considering that carcinogenesis has a pathway-based pathogenesis, developing models using such group structures is a closer mimic of disease progression and prognosis. Many approaches can be used to integrate group information; however, most of them are single-model methods, which may account for unstable prediction.

Methods
We introduced a novel survival stacking method that modeled using group structure information to improve the robustness of cancer survival prediction in the context of high-dimensional omics data. With a super learner, survival stacking combines the prediction from multiple sub-models that are independently trained using the features in pre-grouped biological pathways. In addition to a non-negative linear combination of sub-models, we extended the super learner to non-negative Bayesian hierarchical generalized linear model and artificial neural network. We compared the proposed modeling strategy with the widely used survival penalized method Lasso Cox and several group penalized methods, e.g., group Lasso Cox, via simulation study and real-world data application.

Results
The proposed survival stacking method showed superior and robust performance in terms of discrimination compared with single-model methods in case of high-noise simulated data and real-world data. The non-negative Bayesian stacking method can identify important biological signal pathways and genes that are associated with the prognosis of cancer.

Conclusions
This study proposed a novel survival stacking strategy incorporating biological group information into the cancer prognosis models. Additionally, this study extended the super learner to non-negative Bayesian model and ANN, enriching the combination of sub-models. The proposed Bayesian stacking strategy exhibited favorable properties in the prediction and interpretation of complex survival data, which may aid in discovering cancer targets.
The association of depressive symptoms with handgrip strength and gait speed in community-dwelling older adults: data from the baseline phase of Birjand Longitudinal Aging Study
Authors: Nazari Tina , Moodi Mitra , Fakhrzadeh Hossein , Khodabakhshi Huriye , Khorashadizadeh Masoumeh , Arzaghi Seyed Masoud , Shoaee Shervan , Varmaghani Mehdi , Ejtahed Hanieh-Sadat , Sharifi Farshad 
Published: May 2024

Abstract
Background
Depression is a multifaceted condition with a high prevalence and burden to society. Handgrip strength (HGS) and gait speed (GS) are indices of physical health, which is linked to mental health. Previous studies have shown heterogeneity among countries in the association of physical parameters and depression. In this study, we aimed to investigate the association of HGS and GS with depressive symptoms in older adults.

Methods
This is a cross-sectional study analyzing data from the Birjand Longitudinal Aging Study, a cohort of community-dwelling older adults (≥ 60 years old). Depressive symptoms were assessed by the nine-item Patient Health Questionnaire. HGS was measured with a hand dynamometer in a sitting position, and GS was estimated by a 15-foot walk test at usual pace.

Results
Compared to participants in the first quartile, those in the second quartile of HGS had significantly lower odds of suffering from depressive symptoms, while GS was not significantly associated with depressive symptoms. A higher HGS was associated with a lower risk of moderate depressive symptoms, while a higher GS was related to a lower risk of moderately severe and severe symptoms.

Conclusions
Our findings suggest that older people residing in Birjand, Iran with a moderate HGS are less likely to suffer from depressive symptoms than those with lower HGS.
New framework to assess tracing and testing based on South Korea’s response to COVID-19
Authors: Kim Junhyoung , Jo Suyoung , Cho Sung-il 
Published: May 2024

AbstractSouth Korea’s remarkable success in controlling the spread of COVID-19 during the pre-Omicron period was based on extensive contact tracing and large-scale testing. Here we suggest a general criterion for tracing and testing based on South Korea’s experience, and propose a new framework to assess tracing and testing. We reviewed papers on South Korea’s response to COVID-19 to capture its concept of tracing and testing. South Korea expanded its testing capabilities to enable group tracing combined with preemptive testing, and to conduct open testing. According to our proposed model, COVID-19 cases are classified into 4 types: confirmed in quarantine, source known, source unknown, and unidentified. The proportion of the first two case types among confirmed cases is defined as “traced proportion”, and used as the indicator of tracing and testing effectiveness. In conclusion, South Korea successfully suppressed COVID-19 transmission by maintaining a high traced proportion (> 60%) using group tracing in conjunction with preemptive testing as a complementary strategy to traditional contact tracing.
Medullary sponge kidney with IgA nephropathy: a case report and literature review
Authors: Zeng Chuchu , Jin Yunjie , Wang Yanzhe , Zhu Dingyu , Zhang Zhigang , Wang Xiaoxia 
Published: May 2024

Abstract
Background
Medullary sponge kidney (MSK)is rare in association with glomerulonephritis. We report a patient with medullary sponge kidney, and the kidney biopsy revealed a diagnosis of IgA nephropathy.

Case presentation
A 27-year-old female presented with hematuria and proteinuria, and imaging studies indicated the presence of medullary spongy kidney. With appropriate preparation, a kidney biopsy was performed. Considering the patient’s clinical and pathological characteristics, the final diagnosis was determined to be medullary sponge kidney associated by IgA nephropathy. The combination of corticosteroids and angiotensin receptor blockers (ARBs) proved to be significantly effective in reducing proteinuria in the current case. To the best of our knowledge, this is the first reported case that demonstrates the coexistence of MSK and IgA nephropathy.

Conclusions
Administering precise therapy based on renal pathology can potentially enhance outcomes for patients with renal conditions, necessitating the need for clinicians to be vigilant about differential diagnosis in order to reduce the rates of missed diagnoses and misdiagnosis.
Radiation-induced upregulation of FGL1 promotes esophageal squamous cell carcinoma metastasis via IMPDH1
Authors: Huang Shan , Zhang Jiayi , He Pu , Cui Xinyue , Hou Yuzhu , Su Wanghui , Li Fang 
Published: May 2024

Abstract
Background
While radiation therapy remains pivotal in esophageal squamous cell carcinoma (ESCC) treatment, the perplexing phenomenon of post-radiation metastasis presents a formidable clinical challenge. This study investigates the role of fibrinogen-like protein 1 (FGL1) in driving ESCC metastasis following radiation exposure.

Methods
FGL1 expression in post-radiation ESCC cells was meticulously examined using qRT-PCR, western blotting, and immunofluorescence. The impact of FGL1 on ESCC cell invasion and migration was assessed through Transwell and wound healing assays. In vivo, the metastatic potential of ESCC in response to FGL1 was scrutinized using nude mice models. Comprehensive RNA sequencing and functional experiments elucidated the intricate mechanism associated with FGL1.

Results
Radiation induced upregulation of FGL1 in ESCC cells through FOXO4, intensifying ESCC cell invasion and migration. Targeted knockdown of FGL1 effectively alleviated these characteristics both in vitro and in vivo. FGL1 depletion concurrently suppressed IMPDH1 expression. Rescue experiments underscored that IMPDH1 knockdown robustly reversed the pro-invasive effects induced by FGL1 in ESCC cells. ESCC tissues exhibited heightened IMPDH1 mRNA levels, demonstrating a correlation with patient survival.

Conclusions
Radiation-induced upregulation of FGL1 propels ESCC metastasis through IMPDH1, proposing a potential therapeutic target to mitigate post-radiotherapy metastasis in ESCC patients.
Perceptions on support, challenges and needs among parents and caregivers of children with developmental disabilities in Croatia, North Macedonia and Serbia: a cross-sectional study
Authors: Međaković Jelena , Čivljak Antonia , Zorčec Tatjana , Vučić Vesna , Ristić-Medić Danijela , Veselinović Aleksandra , Čivljak Marta , Puljak Livia 
Published: May 2024

Abstract
Background
Parents/caregivers of children with developmental disabilities (CDD) have a wide range of support needs and there are various interventions available. Support, challenges, and needs among parents/caregivers of CDD likely vary in different geographical settings. This study aimed to analyze the perceptions of support, challenges, and needs among parents/caregivers of CDD in Croatia, North Macedonia, and Serbia.

Methods
We conducted a cross-sectional study in March-April 2023 within the Erasmus + SynergyEd project. The eligible participants were parents and caregivers of CDD in Croatia, North Macedonia, and Serbia, who filled out a modified Caregiver Needs Survey online.

Results
Among 953 participants, 542 (57%) were from Croatia, 205 (21%) were from North Macedonia and 206 (22%) were from Serbia. The most common diagnosis of participants’ children was autism spectrum disorder (26%). The child most often received the first diagnosis at the median of 2 years, diagnosed by a team of professionals. More than half (58%) of children attended preschool and public school, while 22% did not attend any schooling. Additional support from the state/city/county was received by 66% of CDD. Most participants declared not participating in association/organization for family support. Participants mostly (68%) used experts who work with the child as a source of information about their child’s condition, followed by the Internet (53%). In the last 12 months, 60% of participants had difficulties with the availability of services in their area or problems getting appointments. The biggest problem in getting support was ensuring the child’s basic rights were protected. Participants stated that ensuring greater rights for CDD was the greatest need for their families.

Conclusion
Parents/caregivers of CDD in Croatia, North Macedonia, and Serbia faced multiple challenges, but most of them were satisfied with the services provided to their children. Future efforts to develop policies and services related to CDD should consider the opinions of their parents/caregivers and disparities in access to services.
Self-reported sexual coercion among in-school young people with disabilities in Ghana
Authors: Seidu Abdul-Aziz , Kumi-Kyereme Akwasi , Darteh Eugene K. M. 
Published: May 2024

Abstract
Background
Sexual coercion is one of the major public health concerns globally. This is even more worrying among young people with disabilities (YPWDs). This study assessed the prevalence and factors associated with sexual coercion among in-school young people with disabilities in Ghana.

Methods
Using a cross-sectional study design, pre-tested questionnaires were used to collect data from 979 YPWDs in 15 special schools for the visually and hearing impaired in Ghana. Sexual coercion was the outcome variable. Both descriptive (frequencies and percentages) and inferential analysis (binary logistic regression) were conducted.

Results
About 68% reported that they had been sexually coerced at some point in their lifetime. This was higher among males (69.9%) compared to females (66.8%). Those aged 15–19 (72.19%) had the highest prevalence compared to those aged 20–24 (61.74%). YPWDs in Junior High School [JHS] [aOR = 1.722; CI = 1.227,2.417], and those in the coastal zone [aOR = 1.616; CI = 1.068,2.443] had higher odds of being coerced. However, those belonging to the Islamic religion [aOR = 0.266; CI = 0.0764,0.928] and the visually impaired [aOR = 0.477; CI = 0.318,0.716] had lower odds of being coerced compared to those with no religion, and the hearing impaired, respectively.

Conclusion
There is a relatively high prevalence of sexual coercion among in- school YPWDs in Ghana. This is significantly associated with level of education, ecological zone, religion, and the type of disability. This calls for a concerted effort by policy makers such as the Ghana Education Service, Ghana Federation of the Disabled, Ministry of Education, Ministry of Gender, Children and Social Protection to intensify sex education and put in pragmatic steps to halt this serious public health issue.