bluuebunny/crossref_metadata_2025_split huggingface dataset:
p53 activation enhances the sensitivity of non-small cell lung cancer to the combination of SH003 and docetaxel by inhibiting de novo pyrimidine synthesis
Authors: Choi Yu-Jeong , Lee Kangwook , Lee Seo Yeon , Kwon Youngbin , Woo Jaehyuk , Jeon Chan-Yong , Ko Seong-Gyu 
Published: May 2024

Abstract
Background
Identifying molecular biomarkers for predicting responses to anti-cancer drugs can enhance treatment precision and minimize side effects. This study investigated the novel cancer-targeting mechanism of combining SH003, an herbal medicine, with docetaxel in non-small cell lung cancer (NSCLC) cells. Also, the present study aimed to identify the genetic characteristics of cancer cells susceptible to this combination.

Methods
Cell viability was analyzed by WST-8 assay. Apoptosis induction, BrdU incorporation, and cell cycle analysis were performed using flow cytometry. Metabolites were measured by LC–MS/MS analysis. Real-time PCR and western blotting evaluated RNA and protein expression. DNA damage was quantified through immunofluorescence. cBioPortal and GEPIA data were utilized to explore the mutual co-occurrence of TP53 and UMPS and UMPS gene expression in NSCLC.

Results
The combination treatment suppressed de novo pyrimidine nucleotide biosynthesis by reducing the expression of related enzymes. This blockade of pyrimidine metabolism led to DNA damage and subsequent apoptosis, revealing a novel mechanism for inducing lung cancer cell death with this combination. However, some lung cancer cells exhibited distinct responses to the combination treatment that inhibited pyrimidine metabolism. The differences in sensitivity in lung cancer cells were determined by the TP53 gene status. TP53 wild-type lung cancer cells were effectively inhibited by the combination treatment through p53 activation, while TP53 mutant- or null-type cells exhibited lower sensitivity.

Conclusions
This study, for the first time, established a link between cancer cell genetic features and treatment response to simultaneous SH003 and docetaxel treatment. It highlights the significance of p53 as a predictive factor for susceptibility to this combination treatment. These findings also suggest that p53 status could serve as a crucial criterion in selecting appropriate therapeutic strategies for targeting pyrimidine metabolism in lung cancer.
A new long-read mitochondrial-genome protocol (PacBio HiFi) for haemosporidian parasites: a tool for population and biodiversity studies
Authors: Pacheco M. Andreína , Cepeda Axl S. , Miller Erica A. , Beckerman Scott , Oswald Mitchell , London Evan , Mateus-Pinilla Nohra E. , Escalante Ananias A. 
Published: May 2024

Abstract
Background
Studies on haemosporidian diversity, including origin of human malaria parasites, malaria's zoonotic dynamic, and regional biodiversity patterns, have used target gene approaches. However, current methods have a trade-off between scalability and data quality. Here, a long-read Next-Generation Sequencing protocol using PacBio HiFi is presented. The data processing is supported by a pipeline that uses machine-learning for analysing the reads.

Methods
A set of primers was designed to target approximately 6 kb, almost the entire length of the haemosporidian mitochondrial genome. Amplicons from different samples were multiplexed in an SMRTbell® library preparation. A pipeline (HmtG-PacBio Pipeline) to process the reads is also provided; it integrates multiple sequence alignments, a machine-learning algorithm that uses modified variational autoencoders, and a clustering method to identify the mitochondrial haplotypes/species in a sample. Although 192 specimens could be studied simultaneously, a pilot experiment with 15 specimens is presented, including in silico experiments where multiple data combinations were tested.

Results
The primers amplified various haemosporidian parasite genomes and yielded high-quality mt genome sequences. This new protocol allowed the detection and characterization of mixed infections and co-infections in the samples. The machine-learning approach converged into reproducible haplotypes with a low error rate, averaging 0.2% per read (minimum of 0.03% and maximum of 0.46%). The minimum recommended coverage per haplotype is 30X based on the detected error rates. The pipeline facilitates inspecting the data, including a local blast against a file of provided mitochondrial sequences that the researcher can customize.

Conclusions
This is not a diagnostic approach but a high-throughput method to study haemosporidian sequence assemblages and perform genotyping by targeting the mitochondrial genome. Accordingly, the methodology allowed for examining specimens with multiple infections and co-infections of different haemosporidian parasites. The pipeline enables data quality assessment and comparison of the haplotypes obtained to those from previous studies. Although a single locus approach, whole mitochondrial data provide high-quality information to characterize species pools of haemosporidian parasites.
The importance of self-management for better treatment outcomes for HIV patients in a low-income setting: perspectives of HIV experts and service providers
Authors: Dadi Tegene Legese , Tegene Yadessa , Vollebregt Nienke , Medhin Girmay , Spigt Mark 
Published: May 2024

Abstract
Background
Self-management is the most important strategy to improve quality of life in patients with a chronic disease. Despite the increasing number of people living with HIV (PLWH) in low-income countries, very little research on self-management is conducted in this setting. The aim of this research is to understand the perspectives of service providers and experts on the importance of self-management for PLWH.

Methods
A systematizing expert interview type of qualitative methodology was used to gain the perspectives of experts and service providers. The study participants had experience in researching, managing, or providing HIV service in east and southern African (ESA) countries. All the interviews were audio recorded, transcribed, and translated to English. The quality of the transcripts was ensured by randomly checking the texts against the audio record. A thematic analysis approach supported by Atlas TI version 9 software.

Result
PLWH face a variety of multi-dimensional problems thematized under contextual and process dimensions. The problems identified under the contextual dimension include disease-specific, facility-related, and social environment-related. Problems with individual origin, such as ignorance, outweighing beliefs over scientific issues, low self-esteem, and a lack of social support, were mostly highlighted under the process dimensions. Those problems have a deleterious impact on self-management, treatment outcomes, and the quality of life of PLWH. Low self-management is also a result of professional-centered service delivery in healthcare facilities and health service providers’ incapacity to comprehend a patient’s need beyond the medical concerns. Participants in the study asserted that patients have a significant stake in enhancing treatment results and quality of life through enhancing self-management.

Conclusion and recommendation
HIV patients face multifaceted problems beyond their medical issues. The success of medical treatment for HIV is strongly contingent upon patients’ self-management practices and the supportive roles of their family, society, and health service providers. The development and integration of self-management practices into clinical care will benefit patients, their families, and the health system.
Long-read sequencing improves the genetic diagnosis of retinitis pigmentosa by identifying an Alu retrotransposon insertion in the EYS gene
Authors: Fernández-Suárez Elena , González-del Pozo María , Méndez-Vidal Cristina , Martín-Sánchez Marta , Mena Marcela , de la Morena-Barrio Belén , Corral Javier , Borrego Salud , Antiñolo Guillermo 
Published: May 2024

Abstract
Background
Biallelic variants in EYS are the major cause of autosomal recessive retinitis pigmentosa (arRP) in certain populations, a clinically and genetically heterogeneous disease that may lead to legal blindness. EYS is one of the largest genes (~ 2 Mb) expressed in the retina, in which structural variants (SVs) represent a common cause of disease. However, their identification using short-read sequencing (SRS) is not always feasible. Here, we conducted targeted long-read sequencing (T-LRS) using adaptive sampling of EYS on the MinION sequencing platform (Oxford Nanopore Technologies) to definitively diagnose an arRP family, whose affected individuals (n = 3) carried the heterozygous pathogenic deletion of exons 32–33 in the EYS gene. As this was a recurrent variant identified in three additional families in our cohort, we also aimed to characterize the known deletion at the nucleotide level to assess a possible founder effect.

Results
T-LRS in family A unveiled a heterozygous AluYa5 insertion in the coding exon 43 of EYS (chr6(GRCh37):g.64430524_64430525ins352), which segregated with the disease in compound heterozygosity with the previously identified deletion. Visual inspection of previous SRS alignments using IGV revealed several reads containing soft-clipped bases, accompanied by a slight drop in coverage at the Alu insertion site. This prompted us to develop a simplified program using grep command to investigate the recurrence of this variant in our cohort from SRS data. Moreover, LRS also allowed the characterization of the CNV as a ~ 56.4kb deletion spanning exons 32–33 of EYS (chr6(GRCh37):g.64764235_64820592del). The results of further characterization by Sanger sequencing and linkage analysis in the four families were consistent with a founder variant.

Conclusions
To our knowledge, this is the first report of a mobile element insertion into the coding sequence of EYS, as a likely cause of arRP in a family. Our study highlights the value of LRS technology in characterizing and identifying hidden pathogenic SVs, such as retrotransposon insertions, whose contribution to the etiopathogenesis of rare diseases may be underestimated.
A giant peripheral ossifying fibroma of the maxilla with extreme difficulty in clinical differentiation from malignancy: a case report and review of the literature
Authors: Takagi Ryo , Mori Kosei , Koike Takashi , Tsuyuguchi Sayumi , Kanai Kengo , Watanabe Yoshihiro , Okano Mitsuhiro , Noguchi Yoshihiro , Tanaka Aya , Kurihara Kinue , Sato Kazumichi , Ishizaki Ken , Hayashi Yuichiro , Imanishi Yorihisa 
Published: May 2024

Abstract
Background
Peripheral ossifying fibroma is a nonneoplastic inflammatory hyperplasia that originates in the periodontal ligament or periosteum in response to chronic mechanical irritation. Peripheral ossifying fibroma develops more commonly in young females as a solitary, slow-growing, exophytic nodular mass of the gingiva, no more than 2 cm in diameter. While various synonyms have been used to refer to peripheral ossifying fibroma, very similar names have also been applied to neoplastic diseases that are pathologically distinct from peripheral ossifying fibroma, causing considerable nomenclatural confusion. Herein, we report our experience with an unusual giant peripheral ossifying fibroma with a differential diagnostic challenge in distinguishing it from a malignancy.

Case presentation
A 68-year-old Japanese male was referred to our department with a suspected gingival malignancy presenting with an elastic hard, pedunculated, exophytic mass 60 mm in diameter in the right maxillary gingiva. In addition to computed tomography showing extensive bone destruction in the right maxillary alveolus, positron emission tomography with computed tomography revealed fluorodeoxyglucose hyperaccumulation in the gingival lesion. Although these clinical findings were highly suggestive of malignancy, repeated preoperative biopsies showed no evidence of malignancy. Since even intraoperative frozen histological examination revealed no malignancy, surgical resection was performed in the form of partial maxillectomy for benign disease, followed by thorough curettage of the surrounding granulation tissue and alveolar bone. Histologically, the excised mass consisted primarily of a fibrous component with sparse proliferation of atypical fibroblast-like cells, partly comprising ossification, leading to a final diagnosis of peripheral ossifying fibroma. No relapse was observed at the 10-month follow-up.

Conclusions
The clinical presentation of giant peripheral ossifying fibromas can make the differential diagnosis from malignancy difficult. Proper diagnosis relies on recognition of the characteristic histopathology and identification of the underlying chronic mechanical stimuli, while successful treatment mandates complete excision of the lesion and optimization of oral hygiene. Complicated terminological issues associated with peripheral ossifying fibroma require appropriate interpretation and sufficient awareness of the disease names to avoid diagnostic confusion and provide optimal management.
Establishment of human hematopoietic organoids for evaluation of hematopoietic injury and regeneration effect
Authors: Chen Keyi , Li Yunqiao , Wu Xumin , Tang Xuan , Zhang Bowen , Fan Tao , He Lijuan , Pei Xuetao , Li Yanhua 
Published: May 2024

Abstract
Background
Human hematopoietic organoids have a wide application value for modeling human bone marrow diseases, such as acute hematopoietic radiation injury. However, the manufacturing of human hematopoietic organoids is an unaddressed challenge because of the complexity of hematopoietic tissues.

Methods
To manufacture hematopoietic organoids, we obtained CD34+ hematopoietic stem and progenitor cells (HSPCs) from human embryonic stem cells (hESCs) using stepwise induction and immunomagnetic bead-sorting. We then mixed these CD34+ HSPCs with niche-related cells in Gelatin-methacryloyl (GelMA) to form a three-dimensional (3D) hematopoietic organoid. Additionally, we investigated the effects of radiation damage and response to granulocyte colony-stimulating factor (G-CSF) in hematopoietic organoids.

Results
The GelMA hydrogel maintained the undifferentiated state of hESCs-derived HSPCs by reducing intracellular reactive oxygen species (ROS) levels. The established hematopoietic organoids in GelMA with niche-related cells were composed of HSPCs and multilineage blood cells and demonstrated the adherence of hematopoietic cells to niche cells. Notably, these hematopoietic organoids exhibited radiation-induced hematopoietic cell injury effect, including increased intracellular ROS levels, γ-H2AX positive cell percentages, and hematopoietic cell apoptosis percentages. Moreover, G-CSF supplementation in the culture medium significantly improved the survival of HSPCs and enhanced myeloid cell regeneration in these hematopoietic organoids after radiation.

Conclusions
These findings substantiate the successful manufacture of a preliminary 3D hematopoietic organoid from hESCs-derived HSPCs, which was utilized for modeling hematopoietic radiation injury and assessing the radiation-mitigating effects of G-CSF in vitro. Our study provides opportunities to further aid in the standard and scalable production of hematopoietic organoids for disease modeling and drug testing.
Impaired autophagy in myeloid cells aggravates psoriasis-like skin inflammation through the IL-1β/CXCL2/neutrophil axis
Authors: Lee Jinju , Kim Mi-Yeon , Kim Hyo Jeong , Choi Woo Sun , Kim Hun Sik 
Published: May 2024

Abstract
Background
Psoriasis is an inflammatory skin disease characterized by the hyperproliferative epidermal keratinocytes and significant immune cells infiltration, leading to cytokines production such as IL-1β, TNF-α, IL-23, and IL-17. Recent study highlights the critical role of IL-1β in the induction and activation of pathogenic Th17 and IL-17-producing γδ T cells, contributing to psoriasis. However, the mechanism underlying IL-1β dysregulation in psoriasis pathogenesis is unclear. Autophagy regulates IL-1β production and has a pleiotropic effect on inflammatory disorders. Previous studies showed controversial role of autophagy in psoriasis pathogenesis, either pro-inflammatory in autophagy-deficient keratinocyte or anti-inflammatory in pharmacologically autophagy-promoting macrophages. Thus, the direct role of autophagy and its therapeutic potential in psoriasis remains unclear.

Methods
We used myeloid cell-specific autophagy-related gene 7 (Atg7)-deficient mice and determined the effect of autophagy deficiency in myeloid cells on neutrophilia and disease pathogenesis in an imiquimod-induced psoriasis mouse model. We then assessed the pathogenic mechanism focusing on immune cells producing IL-1β and IL-17 along with gene expression profiles associated with psoriasis in mouse model and public database on patients. Moreover, therapeutic potential of IL-1β blocking in such context was assessed.

Results
We found that autophagy deficiency in myeloid cells exacerbated neutrophilic inflammation and disease pathogenesis in mice with psoriasis. This autophagy-dependent effect was associated with a significant increase in IL-1β production from myeloid cells, particularly macrophages, Cxcl2 expression, and IL-17 A producing T cells including γδ T cells. Supporting this, treatment with systemic IL-1 receptor blocking antibody or topical saccharin, a disaccharide suppressing pro-IL-1β expression, led to the alleviation of neutrophilia and psoriatic skin inflammation linked to autophagy deficiency. The pathophysiological relevance of this finding was supported by dysregulation of autophagy-related genes and their correlation with Th17 cytokines in psoriatic skin lesion from patients with psoriasis.

Conclusions
Our results suggest that autophagy dysfunction in myeloid cells, especially macrophages, along with IL-1β dysregulation has a causal role in neutrophilic inflammation and psoriasis pathogenesis.
Protocol for a systematic review of the application of the kidney failure risk equation and Oxford classification in estimating prognosis in IgA nephropathy
Authors: Toal Michael , Fergie Ruth , Quinn Michael , Hill Christopher , O’Neill Ciaran , Maxwell Alexander P. 
Published: May 2024

Abstract
Background
IgA nephropathy (IgAN) is a common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Outcomes are highly variable and predicting risk of disease progression at an individual level is challenging. Accurate risk stratification is important to identify individuals most likely to benefit from treatment. The Kidney Failure Risk Equation (KFRE) has been extensively validated in CKD populations and predicts the risk of ESRD at 2 and 5 years using non-invasive tests; however, its predictive performance in IgAN is unknown. The Oxford classification (OC) describes pathological features demonstrated on renal biopsy that are associated with adverse clinical outcomes that may also inform prognosis. The objective of this systematic review is to compare the KFRE with the OC in determining prognosis in IgAN.

Methods
A systematic review will be conducted and reported in line with PRISMA guidelines (PRISMA-P checklist attached as Additional file 1). Inclusion criteria will be cohort studies that apply the KFRE or OC to determine the risk of CKD progression or ESRD in individuals with IgAN. Multiple databases will be searched in duplicate to identify relevant studies, which will be screened first by title, then by abstract and then by full-text analysis. Results will be collated for comparison. Risk of bias and confidence assessments will be conducted independently by two reviewers, with a third reviewer available if required.

Discussion
Identifying individuals at the highest risk of progression to ESRD is challenging in IgAN, due to the heterogeneity of clinical outcomes. Risk prediction tools have been developed to guide clinicians; however, it is imperative that these aids are accurate and reproducible. The OC is based on observations made by specialist renal pathologists and may be open to observer bias, therefore the utility of prediction models incorporating this classification may be diminished, particularly as in the future novel biomarkers may be incorporated into clinical practice.

Systematic review registration
PROSPERO CRD42022364569
Organoleptic quality and formaldehyde content of mackerel marketed in Dar es Salaam, Tanzania
Authors: Manyanga Vicky Peter , Uledi Mtoke Ahmadi , Makoye Paul Malaba , Daniel Innocent John , Shedafa Raphael , Masota Nelson Enos , Shewiyo Danstan Hipolite , Nyakirang’ani Nzaghi , Sempombe Joseph , Mugoyela Veronica , Kaale Eliangiringa 
Published: May 2024

Abstract
Background
Fish constitutes a nutritious food that deteriorates quickly when poorly preserved. Several biochemicals, including formaldehyde, accumulate naturally in the fish post-mortem. Apart from this natural formaldehyde, reports reveal the deliberate addition of formalin (37% formaldehyde solution) to the stored fish as a preservative. This is risky to consumers since formaldehyde is carcinogenic, genotoxic, and a potentiator of other carcinogens.

Aim
This study aimed to assess both the organoleptic quality and formaldehyde content of mackerels, the most consumed fish in Dar es Salaam, Tanzania.

Methods
A total of 60 mackerel samples were conveniently and equally obtained from the local markets, street vendors, and supermarkets in five districts of the Dar es Salaam region. Organoleptic quality was evaluated based on organoleptic characteristics. Formaldehyde analysis was done by High-Performance Liquid Chromatography (HPLC). Analysis of variance was subsequently run to test the variation of formaldehyde content in mackerel by outlet type and district.

Results
All analyzed mackerel samples had acceptable levels of organoleptic quality (2.46 ± 0.50) and a mean formaldehyde concentration of 10.89 ± 2.44 mg/kg. On average, the samples from supermarkets had the highest level of organoleptic quality (2.20 ± 0.21) but were also the most contaminated with formaldehyde (16.07 ± 4.68 mg/kg), while those from local markets were the least contaminated (3.91 ± 1.86 mg/kg) (p = 0.000). Moreover, 0% (n = 0), 20% (n = 4), and 35% (n = 7) of samples from local markets, street vendors, and supermarkets, respectively, had formaldehyde concentrations above 20 mg/kg, the previously estimated highest concentration for naturally formed formaldehyde in fish.

Conclusion
Mackerels marketed in Dar es Salaam have acceptable organoleptic quality but are substantially contaminated with formaldehyde. Whether this is natural or artificial formaldehyde, our findings are inconclusive given the conflicting global standards. Nonetheless, the findings reveal the potential exposure of fish consumers to formaldehyde. Future research should explore the dynamics of the accumulation of natural formaldehyde in marketed fish and accurately assess the risk associated with the exposure of consumers to the formaldehyde in fish. The emanating findings will ultimately guide the development of local guidelines for natural and permissible formaldehyde concentrations in fish and fish products in Tanzania.