bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering potential causative factors for undiagnosed Waardenburg syndrome through multi-data integration
Authors: Sun Fengying , Xiao Minmin , Ji Dong , Zheng Feng , Shi Tieliu 
Published: June 2024

Abstract
Background
Waardenburg syndrome (WS) is a rare genetic disorder mainly characterized by hearing loss and pigmentary abnormalities. Currently, seven causative genes have been identified for WS, but clinical genetic testing results show that 38.9% of WS patients remain molecularly unexplained. In this study, we performed multi-data integration analysis through protein-protein interaction and phenotype-similarity to comprehensively decipher the potential causative factors of undiagnosed WS. In addition, we explored the association between genotypes and phenotypes in WS with the manually collected 443 cases from published literature.

Results
We predicted two possible WS pathogenic genes (KIT, CHD7) through multi-data integration analysis, which were further supported by gene expression profiles in single cells and phenotypes in gene knockout mouse. We also predicted twenty, seven, and five potential WS pathogenic variations in gene PAX3, MITF, and SOX10, respectively. Genotype-phenotype association analysis showed that white forelock and telecanthus were dominantly present in patients with PAX3 variants; skin freckles and premature graying of hair were more frequently observed in cases with MITF variants; while aganglionic megacolon and constipation occurred more often in those with SOX10 variants. Patients with variations of PAX3 and MITF were more likely to have synophrys and broad nasal root. Iris pigmentary abnormality was more common in patients with variations of PAX3 and SOX10. Moreover, we found that patients with variants of SOX10 had a higher risk of suffering from auditory system diseases and nervous system diseases, which were closely associated with the high expression abundance of SOX10 in ear tissues and brain tissues.

Conclusions
Our study provides new insights into the potential causative factors of WS and an alternative way to explore clinically undiagnosed cases, which will promote clinical diagnosis and genetic counseling. However, the two potential disease-causing genes (KIT, CHD7) and 32 potential pathogenic variants (PAX3: 20, MITF: 7, SOX10: 5) predicted by multi-data integration in this study are all computational predictions and need to be further verified through experiments in follow-up research.
Early onset and liver failure indicating poor prognosis of infant liver failure syndrome type 1
Authors: Li Shu-Yuan , Feng Jia-Yan , Li Zhong-Die , Liu Teng 
Published: June 2024

Abstract
Background
Infantile liver failure syndrome type 1 (ILFS1, OMIM #615,438), caused by leucyl-tRNA synthase 1 (LARS1, OMIM *151,350) deficiency, is a rare autosomal-recessive disorder. The clinical manifestations, molecular-genetic features, and prognosis of LARS1 disease remain largely elusive.

Methods
Three new instances of ILFS1 with confirmed variants in LARS1, encoding LARS1, were identified. Disease characteristics were summarized together with those of 33 reported cases. Kaplan-Meier analysis was performed to assess prognostic factors in ILFS1 patients.

Results
The 3 new ILFS1 patients harbored 6 novel variants in LARS1. Among the 36 known patients, 12 died or underwent liver transplantation. The main clinical features of ILFS1 were intrauterine growth restriction (31/32 patients in whom this finding was specifically described), failure to thrive (30/31), hypoalbuminemia (32/32), microcytic anemia (32/33), acute liver failure (24/34), neurodevelopmental delay (25/30), seizures (22/29), and muscular hypotonia (13/27). No significant correlations were observed between genotype and either presence of liver failure or clinical severity of disease. Kaplan-Meier analysis indicated that age of onset < 3mo (p = 0.0015, hazard ratio = 12.29, 95% confidence interval [CI] = 3.74–40.3), like liver failure (p = 0.0343, hazard ratio = 6.57, 95% CI = 1.96-22.0), conferred poor prognosis.

Conclusions
Early age of presentation, like liver failure, confers poor prognosis in ILFS1. Genotype-phenotype correlations remain to be established.
Understanding the impact of digital therapeutic engagement in promoting mental wellbeing for Pacific youth in Aotearoa New Zealand: an exploration of the literature
Authors: Auva’a-Alatimu Taulaga , Alefaio-Tugia Siautu , Ioane Julia 
Published: June 2024

AbstractThe Pacific population in Aotearoa New Zealand is youthful, with the majority (55%) being under the age of 25 (Statistics New Zealand, 2014). It is vital that youth mental health for Pacific is understood in relation to their overall wellbeing (Paterson et al., 2018). In parallel to this, the World Health Organization (2022) accentuates the need to protect and promote mental wellbeing for young people globally. Specifically, Pacific youth were far more likely than Aotearoa New Zealand European counterparts to have poorer mental health and higher numbers of suicidality and self-harming behaviours (Ataera-Minster & Trowland, 2018; Fa'alili-Fidow et al., 2016). Moreover, research confirms that Pacific people aged 15–24 years have higher levels of psychological distress of 38% compared to 35% of Pacific adults aged 45–64 years (Ataera-Minster & Trowland, 2018). There is a lack of evidence-based psychological approaches that are culturally appropriate and applicable for Pacific people in Aotearoa New Zealand. Considerably, substantial evidence supports the need to provide more accessible resources and interventions that are flexible, culturally adaptable and cost-effective for Pacific youth. This review aims to (1) provide an insight into Pacific people in Aotearoa New Zealand, (2) have an understanding of Pacific worldview & wellbeing, (3) highlight mental health for Aotearoa New Zealand youth & globally (4) identify therapeutic approaches, including digital mental health globally and in Aotearoa New Zealand.Understanding the perspectives of Pacific youth is a significant first step. Therefore, this article will examine the therapeutic approaches, specifically in the digital space, that are proven effective when promoting wellness for Pacific youth.
Adolescent suicidal ideation: dissecting the role of sex in depression and NSSI predictors
Authors: Huang Zi-Ye , Ruan Qian-Nan , Zheng Yawen , Miao Heng , Wu Yu-Wei , Yan Wen-Jing 
Published: June 2024

Abstract
Background
Suicidal ideation (SI) is increasingly prevalent among adolescents, often arising from depression and linked with non-suicidal self-injury (NSSI). Previous studies have noted significant sex differences in the manifestation and predictors of SI, depression, and NSSI.

Aim
This study aims to analyze and compare the relationships between SI, depression, and NSSI among male and female adolescents, examining whether these associations differ based on sex.

Methods
A total of 368 adolescents (M = 15.43, SD = 1.22, about 56.2% female participants), both from clinical and school settings, were assessed for SI, depression, NSSI, and other related variables. Network analysis was utilized to explore the interconnections among these variables, focusing on identifying sex-specific patterns. Logistic regression was used to confirm the findings from the network analysis.

Results
The network analysis revealed significant sex differences in the relationships between SI, depression, and NSSI. In the female network, the edge weights between SI and NSSI (0.93) and between SI and depression (0.31) were much higher compared to the male network (0.29 and 0, respectively). Centrality indices (strength, betweenness, closeness, and expected influence) for SI, NSSI, and depression were also higher in the female network. Logistic regression confirmed these findings, with depression being a potential predictor of SI only in females (OR = 1.349, p = 0.001) and NSSI having a stronger influence on SI in females (OR = 13.673, p < 0.001) than in males (OR = 2.752, p = 0.037).

Conclusion
The findings underscore the necessity of considering sex differences when predicting suicidal ideation from depression and NSSI in adolescents. Intervention and prevention strategies should be tailored to address these distinct patterns in male and female adolescents.
Targeting mTOR and survivin concurrently potentiates radiation therapy in renal cell carcinoma by suppressing DNA damage repair and amplifying mitotic catastrophe
Authors: Rachamala Hari K. , Madamsetty Vijay S. , Angom Ramcharan S. , Nakka Naga M. , Dutta Shamit Kumar , Wang Enfeng , Mukhopadhyay Debabrata , Pal Krishnendu 
Published: June 2024

Abstract
Background
Renal cell carcinoma (RCC) was historically considered to be less responsive to radiation therapy (RT) compared to other cancer indications. However, advancements in precision high-dose radiation delivery through single-fraction and multi-fraction stereotactic ablative radiotherapy (SABR) have led to better outcomes and reduced treatment-related toxicities, sparking renewed interest in using RT to treat RCC. Moreover, numerous studies have revealed that certain therapeutic agents including chemotherapies can increase the sensitivity of tumors to RT, leading to a growing interest in combining these treatments. Here, we developed a rational combination of two radiosensitizers in a tumor-targeted liposomal formulation for augmenting RT in RCC. The objective of this study is to assess the efficacy of a tumor-targeted liposomal formulation combining the mTOR inhibitor everolimus (E) with the survivin inhibitor YM155 (Y) in enhancing the sensitivity of RCC tumors to radiation.

Experimental design
We slightly modified our previously published tumor-targeted liposomal formulation to develop a rational combination of E and Y in a single liposomal formulation (EY-L) and assessed its efficacy in RCC cell lines in vitro and in RCC tumors in vivo. We further investigated how well EY-L sensitizes RCC cell lines and tumors toward radiation and explored the underlying mechanism of radiosensitization.

Results
EY-L outperformed the corresponding single drug-loaded formulations E-L and Y-L in terms of containing primary tumor growth and improving survival in an immunocompetent syngeneic mouse model of RCC. EY-L also exhibited significantly higher sensitization of RCC cells towards radiation in vitro than E-L and Y-L. Additionally, EY-L sensitized RCC tumors towards radiation therapy in xenograft and murine RCC models. EY-L mediated induction of mitotic catastrophe via downregulation of multiple cell cycle checkpoints and DNA damage repair pathways could be responsible for the augmentation of radiation therapy.

Conclusion
Taken together, our study demonstrated the efficacy of a strategic combination therapy in sensitizing RCC to radiation therapy via inhibition of DNA damage repair and a substantial increase in mitotic catastrophe. This combination therapy may find its use in the augmentation of radiation therapy during the treatment of RCC patients.
TMO-Net: an explainable pretrained multi-omics model for multi-task learning in oncology
Authors: Wang Feng-ao , Zhuang Zhenfeng , Gao Feng , He Ruikun , Zhang Shaoting , Wang Liansheng , Liu Junwei , Li Yixue 
Published: June 2024

AbstractCancer is a complex disease composing systemic alterations in multiple scales. In this study, we develop the Tumor Multi-Omics pre-trained Network (TMO-Net) that integrates multi-omics pan-cancer datasets for model pre-training, facilitating cross-omics interactions and enabling joint representation learning and incomplete omics inference. This model enhances multi-omics sample representation and empowers various downstream oncology tasks with incomplete multi-omics datasets. By employing interpretable learning, we characterize the contributions of distinct omics features to clinical outcomes. The TMO-Net model serves as a versatile framework for cross-modal multi-omics learning in oncology, paving the way for tumor omics-specific foundation models.
M2 macrophage-derived exosomes promote angiogenesis and improve cardiac function after myocardial infarction
Authors: Guo Hongzhou , Li Zeya , Xiao Bin , Huang Rongchong 
Published: June 2024

Abstract
Background
Myocardial infarction (MI) is a major cause of mortality and morbidity worldwide. The intercellular communication in post-infarction angiogenesis remains unclear.

Methods
In this study, we explored the role and mechanism of action of M2 macrophage-derived exosomes (M2-exos) in angiogenesis after MI. M2-exos were harvested and injected intramyocardially at the onset of MI. Two distinct endothelial cells (ECs) were cultured with M2-exos to explore the direct effects on angiogenesis.

Results
We showed that M2-exos improved cardiac function, reduced infarct size, and enhanced angiogenesis after MI. Moreover, M2-exos promoted angiogenesis in vitro; the molecules loaded in the vesicles were responsible for its proangiogenic effects. We further validated that higher abundance of miR-132-3p in M2-exos, which recapitulate their functions, was required for the cardioprotective effects exerted by M2-exos. Mechanistically, miR-132-3p carried by M2-exos down-regulate the expression of THBS1 through direct binding to its 3´UTR and the proangiogenic effects of miR-132-3p were largely reversed by THBS1 overexpression.

Conclusion
Our findings demonstrate that M2-exos promote angiogenesis after MI by transporting miR-132-3p to ECs, and by binding to THBS1 mRNA directly and negatively regulating its expression. These findings highlight the role of M2-exos in cardiac repair and provide novel mechanistic understanding of intercellular communication in post-infarction angiogenesis.
Letrozole ovulation regimen for frozen-thawed embryo transfer in women with polycystic ovary syndrome: study protocol for a randomized controlled trial
Authors: Xie Yanqiu , Deng Min , Deng Weifen , Fan Qi , Shi Yuhua 
Published: June 2024

Abstract
Background
Women with polycystic ovary syndrome (PCOS) are usually selected to undergo an ovulation induction regimen or a programmed regimen for endometrial preparation in the frozen-thawed embryo transfer (FET) during their IVF/ICSI treatment. The programmed regimen permits flexible scheduling of embryo transfer but requires long-term usage of exogenous estrogen and higher dosages of luteal support while the letrozole ovulation regimen needs lower dosages of luteal support only. Recently, multiple studies have shown that the letrozole ovulation regimen can improve pregnancy outcomes of FET in women with PCOS compared with the programmed regimen. However, most of these studies are retrospective, and prospective studies are urgently needed the evidence from the perspective study is insufficient.

Methods/design
We are undertaking a multicentre, randomized, controlled clinical trial of an endometrial preparation regimen for FET in women with PCOS. The eligible women are randomly assigned to either the letrozole ovulation regimen or the programmed regimen for endometrial preparation. The primary outcome is the clinical pregnancy rate.

Discussion
The results of this study will provide evidence for whether the letrozole ovulation regimen for endometrial preparation could improve pregnancy outcomes in PCOS women undergoing FET.

Trial registration
Chinese Clinical Trial Registry ChiCTR2200062244. Registered on 31 July 2022.
International assessment results on non-NIOSH approved respirators by the national personal protective technology laboratory (NPPTL): a data note
Authors: Tsui Kwai Yu , Wang Yu , Lam Simon Ching 
Published: June 2024

Abstract
Objectives
Due to the COVID-19 pandemic and the shortage of the National Institute for Occupational Safety & Health (NIOSH)-approved N95 respirators, the Food and Drug Administration granted an Emergency Use Authorization to allow the use of non-NIOSH approved respirators provided that these respirators must undergo tests by a protocol of TEB-APR-STP-0059, similar methods of NIOSH standard testing procedure. This initiative safeguards the quality of respirators and the effectiveness of occupational protection. The dataset of all the testing results could benefit further analysis of COVID-19 infection rates in relation to different types of N95 respirators used and identify potential correlations of various test parameters in the testing system for validation. The analysis enhances understanding of the quality, effectiveness, and performance of N95 respirators in the prevention of respiratory infectious transmission and develops improved occupational safety measures.

Data description
The dataset was transformed, transcribed, and compiled from the official testing data of non-NIOSH-approved N95 respirators reported in the NIOSH website under the Centers for the Disease Control and Prevention in the United States. The dataset included details of 7,413 testing results of N95 respirators (manufacturer, model, and maximum and minimum filtration efficiency) and test parameters (flow rate, initial filter resistance, and initial percent leakage). Supplementary items were added to increase the availability of data analysis and enhance the interpretability of the assessments of the quality of N95 respirators.
An efficient numerical approach for singularly perturbed time delayed parabolic problems with two-parameters
Authors: Daba Imiru Takele , Melesse Wondewosen Gebeyaw , Gelu Fasika Wondimu , Kebede Guta Demisu 
Published: June 2024

Abstract
Objectives
The main objective of this work is to design an efficient numerical scheme is proposed for solving singularly perturbed time delayed parabolic problems with two parameters.

Results
The scheme is constructed via the implicit Euler and non-standard finite difference method to approximate the time and space derivatives, respectively. Besides, to enhance the accuracy and order of convergence of the method Richardson extrapolation technique is employed. Intensive numerical experimentation has been done on some model examples. Further, the layer behavior of the solutions is presented using graphs and observed to agree with the existing theories. Finally, error analysis of the scheme is done and observed that the proposed method is parameter uniform convergent with the order of convergence $$\left( (\Delta t )^2+h^2\right) $$

(
Δ
t
)

2

+

h
2
Consistent cord blood DNA methylation signatures of gestational age between South Asian and white European cohorts
Authors: Deng Wei Q. , Pigeyre Marie , Azab Sandi M. , Wilson Samantha L. , Campbell Natalie , Cawte Nathan , Morrison Katherine M. , Atkinson Stephanie A. , Subbarao Padmaja , Turvey Stuart E. , Moraes Theo J. , Mandhane Piush , Azad Meghan B. , Simons Elinor , Pare Guillaume , Anand Sonia S. 
Published: June 2024

Abstract
Background
Epigenetic modifications, particularly DNA methylation (DNAm) in cord blood, are an important biological marker of how external exposures during gestation can influence the in-utero environment and subsequent offspring development. Despite the recognized importance of DNAm during gestation, comparative studies to determine the consistency of these epigenetic signals across different ethnic groups are largely absent. To address this gap, we first performed epigenome-wide association studies (EWAS) of gestational age (GA) using newborn cord blood DNAm comparatively in a white European (n = 342) and a South Asian (n = 490) birth cohort living in Canada. Then, we capitalized on established cord blood epigenetic GA clocks to examine the associations between maternal exposures, offspring characteristics and epigenetic GA, as well as GA acceleration, defined as the residual difference between epigenetic and chronological GA at birth.

Results
Individual EWASs confirmed 1,211 and 1,543 differentially methylated CpGs previously reported to be associated with GA, in white European and South Asian cohorts, respectively, with a similar distribution of effects. We confirmed that Bohlin’s cord blood GA clock was robustly correlated with GA in white Europeans (r = 0.71; p = 6.0 × 10–54) and South Asians (r = 0.66; p = 6.9 × 10–64). In both cohorts, Bohlin’s clock was positively associated with newborn weight and length and negatively associated with parity, newborn female sex, and gestational diabetes. Exclusive to South Asians, the GA clock was positively associated with the newborn ponderal index, while pre-pregnancy weight and gestational weight gain were strongly predictive of increased epigenetic GA in white Europeans. Important predictors of GA acceleration included gestational diabetes mellitus, newborn sex, and parity in both cohorts.

Conclusions
These results demonstrate the consistent DNAm signatures of GA and the utility of Bohlin’s GA clock across the two populations. Although the overall pattern of DNAm is similar, its connections with the mother's environment and the baby's anthropometrics can differ between the two groups. Further research is needed to understand these unique relationships.
An alternative method for SARS-CoV-2 detection with use modified fluorescent in situ hybridization
Authors: Sroka-Oleksiak Agnieszka , Krawczyk Agnieszka , Talaga-Ćwiertnia Katarzyna , Salamon Dominika , Brzychczy-Włoch Monika , Gosiewski Tomasz 
Published: June 2024

AbstractThe real-time reverse-transcriptase polymerase-chain-reaction (rRT-PCR) tests are the gold standard in detecting SARS-CoV-2 virus infection. However, despite high sensitivity and specificity, they have limitations that in some cases may result in false negative results. Therefore, it is reasonable to search for additional tools that could support microbiological diagnosis of SARS-CoV-2. The aim of the study was to develop a highly specific molecular test capable of detecting and visualizing SARS-CoV-2 infection. A universal probe and a set of 18 specific oligonucleotides with a FLAP sequence attached to them on both sides were designed to visualize SARS-CoV-2 virus infection based on the fluorescence in situ hybridization method (FISH). FISH conditions using the developed kit were standardized on the Vero CCL-81 cell line infected by SARS-CoV-2 virus. The method was tested on 290 nasopharyngeal swabs (collected in a doublet) from patients with clinical symptoms of SARS-CoV-2. Each one swab from the doublet was subjected to RNA isolation and amplification by rRT-PCR. From the second swab, a microscopic preparation was performed for FISH. The use of the rRT-PCR allowed obtaining 200 positive and 90 negative results, while our FISH method allowed for 220 positive results and 70 negative results. The differences obtained using both methods were statistically significant (p = 0.008). The obtained results support the use of FISH as an additional method in microbiological diagnostics of SARS-CoV-2.
Rapid genotyping of Toxoplasma gondii isolates via Nanopore-based multi-locus sequencing
Authors: Koutsogiannis Zisis , Denny Paul W. 
Published: June 2024

AbstractToxoplasma gondii is an obligate intracellular parasite associated with severe disease, especially in the immunosuppressed. It is also a cause of congenital malformation and abortion in both animals and humans and is considered one of the most important foodborne pathogens worldwide with different strains showing variable distribution and differing pathogenicity. Thus, strain-level differentiation of T. gondii isolates is an essential asset in the understanding of parasite’s diversity, geographical distribution, epidemiology and health risk. Here, we designed and implemented an Oxford Nanopore MinION protocol to analyse genomic sequence variation including single nucleotide polymorphisms (SNPs) and insertion/deletion polymorphisms (InDel’s) of four different genomic loci, part of protein coding genes SAG2, SAG3, ROP17 and ROP21. This method provided results with the sequencing depth necessary for accurate differentiation of T. gondii strains and represents a rapid approach compared to conventional techniques which we further validated against environmental samples isolated from wild wood mice. In summary, multi-locus sequence typing (MLST) of both highly conserved and more polymorphic areas of the genome, provided robust data for strain classification in a platform ready for further adaption for other strains and pathogens.