bluuebunny/crossref_metadata_2025 huggingface dataset:
Delivering clinical tutorials to medical students using the Microsoft HoloLens 2: A mixed-methods evaluation
Authors: Connolly Murray , Iohom Gabriella , O’Brien Niall , Volz James , O’Muircheartaigh Aogán , Serchan Paschalitsa , Biculescu Agatha , Gadre Kedar Govind , Soare Corina , Griseto Laura , Shorten George
Published: May 2024

Background

Mixed reality offers potential educational advantages in the delivery of clinical teaching. Holographic artefacts can be rendered within a shared learning environment using devices such as the Microsoft HoloLens 2. In addition to facilitating remote access to clinical events, mixed reality may provide a means of sharing mental models, including the vertical and horizontal integration of curricular elements at the bedside. This study aimed to evaluate the feasibility of delivering clinical tutorials using the Microsoft HoloLens 2 and the learning efficacy achieved.

Methods

Following receipt of institutional ethical approval, tutorials on preoperative anaesthetic history taking and upper airway examination were facilitated by a tutor who wore the HoloLens device. The tutor interacted face to face with a patient and two-way audio-visual interaction was facilitated using the HoloLens 2 and Microsoft Teams with groups of students who were located in a separate tutorial room. Holographic functions were employed by the tutor. The tutor completed the System Usability Scale, the tutor, technical facilitator, patients, and students provided quantitative and qualitative feedback, and three students participated in semi-structured feedback interviews. Students completed pre- and post-tutorial, and end-of-year examinations on the tutorial topics.

Results

Twelve patients and 78 students participated across 12 separate tutorials. Five students did not complete the examinations and were excluded from efficacy calculations. Student feedback contained 90 positive comments, including the technology’s ability to broadcast the tutor’s point-of-vision, and 62 negative comments, where students noted issues with the audio-visual quality, and concerns that the tutorial was not as beneficial as traditional in-person clinical tutorials. The technology and tutorial structure were viewed favourably by the tutor, facilitator and patients. Significant improvement was observed between students’ pre- and post-tutorial MCQ scores (mean 59.2% Vs 84.7%, p < 0.001).

Conclusions

This study demonstrates the feasibility of using the HoloLens 2 to facilitate remote bedside tutorials which incorporate holographic learning artefacts. Students’ examination performance supports substantial learning of the tutorial topics. The tutorial structure was agreeable to students, patients and tutor. Our results support the feasibility of offering effective clinical teaching and learning opportunities using the HoloLens 2. However, the technical limitations and costs of the device are significant, and further research is required to assess the effectiveness of this tutorial format against in-person tutorials before wider roll out of this technology can be recommended as a result of this study
Lipocalin-2 as a prognostic marker in patients with acute exacerbation of idiopathic pulmonary fibrosis
Authors: Tanahashi Hiroki , Iwamoto Hiroshi , Yamaguchi Kakuhiro , Sakamoto Shinjiro , Horimasu Yasushi , Masuda Takeshi , Nakashima Taku , Ohshimo Shinichiro , Fujitaka Kazunori , Hamada Hironobu , Hattori Noboru
Published: May 2024

Background

Lipocalin-2 (LCN2) is a secretory glycoprotein upregulated by oxidative stress; moreover, patients with idiopathic pulmonary fibrosis (IPF) have shown increased LCN2 levels in bronchoalveolar lavage fluid (BALF). This study aimed to determine whether circulatory LCN2 could be a systemic biomarker in patients with IPF and to investigate the role of LCN2 in a bleomycin-induced lung injury mouse model.

Methods

We measured serum LCN2 levels in 99 patients with stable IPF, 27 patients with acute exacerbation (AE) of IPF, 51 patients with chronic hypersensitivity pneumonitis, and 67 healthy controls. Further, LCN2 expression in lung tissue was evaluated in a bleomycin-induced lung injury mouse model, and the role of LCN2 was investigated using LCN2-knockout (LCN2 -/-) mice.

Results

Serum levels of LCN2 were significantly higher in patients with AE-IPF than in the other groups. The multivariate Cox proportional hazards model showed that elevated serum LCN2 level was an independent predictor of poor survival in patients with AE-IPF. In the bleomycin-induced lung injury mouse model, a higher dose of bleomycin resulted in higher LCN2 levels and shorter survival. Bleomycin-treated LCN2 -/- mice exhibited increased BALF cell and protein levels as well as hydroxyproline content. Moreover, compared with wild-type mice, LCN2-/- mice showed higher levels of circulatory 8-isoprostane as well as lower Nrf-2, GCLC, and NQO1 expression levels in lung tissue following bleomycin administration.

Conclusions

Our findings demonstrate that serum LCN2 might be a potential prognostic marker of AE-IPF. Moreover, LCN2 expression levels may reflect the severity of lung injury, and LCN2 may be a protective factor against bleomycin-induced acute lung injury and oxidative stress.
Combinatorial metabolic engineering of Streptomyces sp. CB03234-S for the enhanced production of anthraquinone-fused enediyne tiancimycins
Authors: Zhuang Zhoukang , Kong Wenping , Wen Zhongqing , Tong Nian , Lin Jing , Zhang Fan , Fan Zhiying , Yi Liwei , Huang Yong , Duan Yanwen , Yan Xiaohui , Zhu Xiangcheng
Published: May 2024

Background

Anthraquinone-fused enediynes (AFEs) are excellent payloads for antibody-drug conjugates (ADCs). The yields of AFEs in the original bacterial hosts are extremely low. Multiple traditional methods had been adopted to enhance the production of the AFEs. Despite these efforts, the production titers of these compounds are still low, presenting a practical challenge for their development. Tiancimycins (TNMs) are a class of AFEs produced by Streptomyces sp. CB03234. One of their salient features is that they exhibit rapid and complete cell killing ability against various cancer cell lines.

Results

In this study, a combinatorial metabolic engineering strategy guided by the CB03234-S genome and transcriptome was employed to improve the titers of TNMs. First, re-sequencing of CB03234-S (Ribosome engineered mutant strains) genome revealed the deletion of a 583-kb DNA fragment, accounting for about 7.5% of its genome. Second, by individual or combined inactivation of seven potential precursor competitive biosynthetic gene clusters (BGCs) in CB03234-S, a double-BGC inactivation mutant, S1009, was identified with an improved TNMs titer of 28.2 ± 0.8 mg/L. Third, overexpression of five essential biosynthetic genes, including two post-modification genes, and three self-resistance auxiliary genes, was also conducted, through which we discovered that mutants carrying the core genes, tnmE or tnmE10, exhibited enhanced TNMs production. The average TNMs yield reached 43.5 ± 2.4 mg/L in a 30-L fermenter, representing an approximately 360% increase over CB03234-S and the highest titer among all AFEs to date. Moreover, the resulting mutant produced TNM-W, a unique TNM derivative with a double bond instead of a common ethylene oxide moiety. Preliminary studies suggested that TNM-W was probably converted from TNM-A by both TnmE and TnmE10.

Conclusions

Based on the genome and transcriptome analyses, we adopted a combined metabolic engineering strategy for precursor enrichment and biosynthetic pathway reorganization to construct a high-yield strain of TNMs based on CB03234-S. Our study establishes a solid basis for the clinical development of AFE-based ADCs.
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

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

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

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

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

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

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

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

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

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.
Detailed analysis of agro-industrial byproducts/wastes to enable efficient sorting for various agro-industrial applications
Authors: Priyanka Govindegowda , Singiri Jeevan R. , Adler-Agmon Zachor , Sannidhi Sasank , Daida Spurthi , Novoplansky Nurit , Grafi Gideon
Published: May 2024

Agriculture-based industries generate huge amounts of byproducts/wastes every year, which are not exploited or disposed efficiently posing an environmental problem with implications to human and animal health. Finding strategies to increase the recycling of agro-industrial byproducts/wastes (AIBWs) is a primary objective of the current study. A thorough examination of AIBWs in conjunction with experimental research is proposed to facilitate sorting for various agro-industrial applications and consequently increasing byproduct/waste utilization. Accordingly, two sustainable, locally available sources of AIBWs, namely, wheat bran (WB) and garlic straw and peels (GSP) were studied in detail including content and composition of proteins, phytohormones and nutritional elements, as well as the effect of AIBW extracts on plant and microbial growth. Hundreds of proteins were recovered from AIBW mainly from WBs, including chaperons, metabolite and protein modifying enzymes, and antimicrobial proteins. In-gel assays showed that WB and GSP possess high protease and nuclease activities. Conspicuously, phytohormone analysis of AIBWs revealed the presence of high levels of strigolactones, stimulants of seed germination of root parasitic weeds, as well as indole acetic acid (IAA) and abscisic acid (ABA). Garlic straw extract strongly inhibited germination of the weed Amaranthus palmeri but not of Abutilon theophrasti and all examined AIBWs significantly affected post-germination growth. Bacterial growth was strongly inhibited by garlic straw, but enhanced by WBs, which can be used at least partly as a bacterial growth medium. Thus, an in-depth examination of AIBW characteristics will enable appropriate sorting for diverse agro-industrial applications, which will increase their utilization and consequently their economic value.
General regulatory factors exert differential effects on nucleosome sliding activity of the ISW1a complex
Authors: Oyarzún-Cisterna Andrea , Gidi Cristián , Raiqueo Fernanda , Amigo Roberto , Rivas Camila , Torrejón Marcela , Gutiérrez José L.
Published: May 2024

Background

Chromatin dynamics is deeply involved in processes that require access to DNA, such as transcriptional regulation. Among the factors involved in chromatin dynamics at gene regulatory regions are general regulatory factors (GRFs). These factors contribute to establishment and maintenance of nucleosome-depleted regions (NDRs). These regions are populated by nucleosomes through histone deposition and nucleosome sliding, the latter catalyzed by a number of ATP-dependent chromatin remodeling complexes, including ISW1a. It has been observed that GRFs can act as barriers against nucleosome sliding towards NDRs. However, the relative ability of the different GRFs to hinder sliding activity is currently unknown.

Results

Considering this, we performed a comparative analysis for the main GRFs, with focus in their ability to modulate nucleosome sliding mediated by ISW1a. Among the GRFs tested in nucleosome remodeling assays, Rap1 was the only factor displaying the ability to hinder the activity of ISW1a. This effect requires location of the Rap1 cognate sequence on linker that becomes entry DNA in the nucleosome remodeling process. In addition, Rap1 was able to hinder nucleosome assembly in octamer transfer assays. Concurrently, Rap1 displayed the highest affinity for and longest dwell time from its target sequence, compared to the other GRFs tested. Consistently, through bioinformatics analyses of publicly available genome-wide data, we found that nucleosome occupancy and histone deposition in vivo are inversely correlated with the affinity of Rap1 for its target sequences in the genome.

Conclusions

Our findings point to DNA binding affinity, residence time and location at particular translational positions relative to the nucleosome core as the key features of GRFs underlying their roles played in nucleosome sliding and assembly.
Radiation nanomedicines for cancer treatment: a scientific journey and view of the landscape
Authors: Reilly Raymond M. , Georgiou Constantine J. , Brown Madeline K. , Cai Zhongli
Published: May 2024

Background

Radiation nanomedicines are nanoparticles labeled with radionuclides that emit α- or β-particles or Auger electrons for cancer treatment. We describe here our 15 years scientific journey studying locally-administered radiation nanomedicines for cancer treatment. We further present a view of the radiation nanomedicine landscape by reviewing research reported by other groups.

Main body

Gold nanoparticles were studied initially for radiosensitization of breast cancer to X-radiation therapy. These nanoparticles were labeled with 111In to assess their biodistribution after intratumoural vs. intravenous injection. Intravenous injection was limited by high liver and spleen uptake and low tumour uptake, while intratumoural injection provided high tumour uptake but low normal tissue uptake. Further, [111In]In-labeled gold nanoparticles modified with trastuzumab and injected iintratumourally exhibited strong tumour growth inhibition in mice with subcutaneous HER2-positive human breast cancer xenografts. In subsequent studies, strong tumour growth inhibition in mice was achieved without normal tissue toxicity in mice with human breast cancer xenografts injected intratumourally with gold nanoparticles labeled with β-particle emitting 177Lu and modified with panitumumab or trastuzumab to specifically bind EGFR or HER2, respectively. A nanoparticle depot (nanodepot) was designed to incorporate and deliver radiolabeled gold nanoparticles to tumours using brachytherapy needle insertion techniques. Treatment of mice with s.c. 4T1 murine mammary carcinoma tumours with a nanodepot incorporating [90Y]Y-labeled gold nanoparticles inserted into one tumour arrested tumour growth and caused an abscopal growth-inhibitory effect on a distant second tumour. Convection-enhanced delivery of [177Lu]Lu-AuNPs to orthotopic human glioblastoma multiforme (GBM) tumours in mice arrested tumour growth without normal tissue toxicity. Other groups have explored radiation nanomedicines for cancer treatment in preclinical animal tumour xenograft models using gold nanoparticles, liposomes, block copolymer micelles, dendrimers, carbon nanotubes, cellulose nanocrystals or iron oxide nanoparticles. These nanoparticles were labeled with radionuclides emitting Auger electrons (111In, 99mTc, 125I, 103Pd, 193mPt, 195mPt), β-particles (177Lu, 186Re, 188Re, 90Y, 198Au, 131I) or α-particles (225Ac, 213Bi, 212Pb, 211At, 223Ra). These studies employed intravenous or intratumoural injection or convection enhanced delivery. Local administration of these radiation nanomedicines was most effective and minimized normal tissue toxicity.

Conclusions

Radiation nanomedicines have shown great promise for treating cancer in preclinical studies. Local intratumoural administration avoids sequestration by the liver and spleen and is most effective for treating tumours, while minimizing normal tissue toxicity.
Polar code-based secure transmission with higher message rate combining channel entropy and computational entropy
Authors: An Chen , Huang Mengjie , Lu Xianhui , Bi Lei , Li Weijie
Published: May 2024

The existing physical layer security schemes, which are based on the key generation model and the wire-tap channel model, achieve security by utilizing channel reciprocity entropy and noise entropy, respectively. In contrast, we propose a novel secure transmission framework that combines noise entropy with reciprocity entropy, achieved by inserting reciprocity entropy into the frozen bits of polar codes. Note that in real-world scenarios, when eavesdroppers employ polynomial-time attacks, the bit error rate (BER) increases due to the introduction of computational entropy. To achieve indistinguishability security, we convert the practical physical layer security metric, BER, into the average min-entropy, a widely accepted concept in cryptography. The simulation results demonstrate that the eavesdropper’s BER can be significantly increased without compromising the communication performance of the legitimate receiver. Under concrete parameters we selected, when compared to the joint scheme of physical layer key generation and one time pad, the modular semantically-secure scheme based on the wire-tap channel model, and the simple channel entropy combination scheme, our scheme achieves a message rate approximately 1.2 times, 3.8 times, and 1.4 times better, respectively. Experimental testing validates the feasibility of our scheme.
Accuracy of machine learning to predict the outcomes of shoulder arthroplasty: a systematic review
Authors: Karimi Amir H. , Langberg Joshua , Malige Ajith , Rahman Omar , Abboud Joseph A. , Stone Michael A.
Published: May 2024

Background

Artificial intelligence (AI) uses computer systems to simulate cognitive capacities to accomplish goals like problem-solving and decision-making. Machine learning (ML), a branch of AI, makes algorithms find connections between preset variables, thereby producing prediction models. ML can aid shoulder surgeons in determining which patients may be susceptible to worse outcomes and complications following shoulder arthroplasty (SA) and align patient expectations following SA. However, limited literature is available on ML utilization in total shoulder arthroplasty (TSA) and reverse TSA.

Methods

A systematic literature review in accordance with PRISMA guidelines was performed to identify primary research articles evaluating ML’s ability to predict SA outcomes. With duplicates removed, the initial query yielded 327 articles, and after applying inclusion and exclusion criteria, 12 articles that had at least 1 month follow-up time were included.

Results

ML can predict 30-day postoperative complications with a 90% accuracy, postoperative range of motion with a higher-than-85% accuracy, and clinical improvement in patient-reported outcome measures above minimal clinically important differences with a 93%–99% accuracy. ML can predict length of stay, operative time, discharge disposition, and hospitalization costs.

Conclusion

ML can accurately predict outcomes and complications following SA and healthcare utilization. Outcomes are highly dependent on the type of algorithms used, data input, and features selected for the model.

Level of Evidence

III
Plastic behavior and shakedown limit of defected pressurized pipe under cyclic bending moment
Authors: Youssef Mark Nassef Naguib , Megahed Mohammad Mohammad , Saleh Chahinaz Abdel Rahman , Mohammed Sahour Nabil Sayed
Published: May 2024

Pipelines subjected to thermal or mechanical loads may fail due to plastic strain accumulation which leads to ratcheting. In this research, cyclic plastic behavior and shakedown limit are investigated experimentally and numerically for a defected pressurized pipe under cyclic bending moment. In the numerical model, the combined isotropic/kinematic hardening model based on the Chaboche model is adopted to represent the cyclic plastic flow of the material. The hardening parameters are determined experimentally and used in the finite element (FE) model. A four-point bending test rig is manufactured to test a pressurized API 5L steel pipe under cyclic bending. An elliptical defect is created by machining to depict corrosion pits in pipes. The plastic strains are measured experimentally and the results are used to tune the parameters of the FE model. The shakedown limit of the defected pipe is determined numerically by tracking the critical points behavior and the results are verified experimentally. Furthermore, the plastic work dissipated energy (PWD) is estimated within the defective structure to study the behavior of the pipe. By running this compatible model, it is found that the yield and the shakedown limits are lowered by mean values of 55% and 25% respectively due to the presence of metal loss defect occupying almost half of the pipe thickness.
Distribution and conservation of the narrow sub-endemic shrub, Lonicera paradoxa in Pamir-Alay, Central Asia
Authors: DAMINOVA NAZOKAT , NOSIROV SOBITJON , AKBAROV FERUZ , TOJIBAEV KOMILJON , TEMIROV ELDOR
Published: May 2024

Abstract. Daminova N, Nosirov S, Akbarov F, Tojibaev K, Temirov E. 2024. Distribution and conservation of the narrow sub-endemic shrub, Lonicera paradoxa in Pamir-Alay, Central Asia. Biodiversitas 25: 439-448. Lonicera paradoxa Pojark. (Lonicera ser. Alpigenae Pojark. ex A.Byalt) is a shrub with a geographically limited range. This species is included in the national red book lists of Uzbekistan, Kyrgyzstan, and Tajikistan and is considered one of the rare species in danger of extinction in nature. The species grows in a significant elevation from 1600 to 3200 m on the Northern slopes of the Alay Range, Central Asia. In this study, we investigated the geographic distribution of L. paradoxa based on scientific literature, herbarium data collections, and field surveys. We then modeled the current and potential future geographic distribution using Maxent. We also conducted a propagation study for its conservation under laboratory and greenhouse conditions. Our fieldwork in 2021-2022 found new records of L. paradoxa in Uzbekistan and Kyrgyzstan. We calculated the Extent of Occurrence (EOO) and Area of Occupancy (AOO) of the species, which were 5.08 km2 (VU) and 28 km2 (EN), respectively. Therefore, based on the IUCN Red List and Criteria, we recommend the conservation status of L. paradoxa as endangered (EN) in categories B2 ab (ii, iii, iv) + D. Our modeling prediction suggested that compared to the current, suitable habitat of L. paradoxa to reduce significantly in the future with very suitable habitats are expected to expand to the south and high mountain areas. For the first time, the conservation measures of L. paradoxa were carried out at the Tashkent Botanical Garden. The conducted research made it possible to preserve L. paradoxa in ex-situ conditions. The results of this research can be helpful in determining and planning measures for the protection of L. paradoxa in the territory of the Kyrgyz and Tajikistan Republics, both now and in the future.
Chemotaxonomy in the Etlingera Genus from Sulawesi, Indonesia: Design and molecular docking of antioxidant marker
Authors: HAMSIDI RINI , KARMILAH KARMILAH , DAUD NUR SAADAH , MALAKA MUHAMMAD HAJRUL , YODHA AGUNG WIBAWA MAHATVA , MUSDALIPAH MUSDALIPAH , ARFAN ARFAN , SAHIDIN SAHIDIN
Published: May 2024

Abstract. Hamsidi R, Karmilah, Daud NS, Malaka MH, Yodha AWM, Musdalipah, Arfan, Sahidin. 2024. Chemotaxonomy in the Etlingera Genus from Sulawesi, Indonesia: Design and molecular docking of antioxidant marker. Biodiversitas 25: 449-457. Etlingera is one of the important genera in the Zingiberaceae family because of its potential uses. Several studies have been conducted on the Genus Etlingera as nutraceuticals and drugs. Recently new species have been found in the Sulawesi Region, Indonesia, namely E. canaria A.D.Poulsen and E. echinulate A.D.Poulsen. Based on literature review through sciencedirect and springer link, both species unknown for their chemical and pharmacological content, so it is necessary to continue to reveal the deeper potential. The fruits of E. calophrys (K.Schum.) A.D.Poulsen, E. canaria and E. echinulate were extracted with methanol by maceration method. The chemical content of each extract was analyzed using a Liquid Chromatography Mass Spectrometer (LCMS). Antioxidant activity was tested based on the 1,1-Diphenyl-2-Picrylhydrazyl (DPPH) method. The ability as an antioxidant is proven by the molecular interactions of marker compounds in inhibiting xanthine oxidase. The secondary metabolites contained in the fruit extracts of E. calophrys, E. canaria and E. echinulate are E-p-Coumatic acid, 1,5-Dimethyl citrate, Trimethyl citrate, Crocetin, Tanshinone IIA, Ethinyl Estradiol, Yakuchinone B, Anisalacetone, Yakuchinone A, Nobilin, ?-Estradiol, Momor-cerebroside I, Spinasterone, 12-Hydroxy-methyl abietate, Spinasterol, 2,3-Dihydroxypropyl oleate, 11-Octadecenoate acid methyl ester, Stigmastan-3,6-dione, b-Sitosterol- 3-O-b-D-glucopyranoside, Trilaurin, 28-O-Hexahydrophthalate and Fasciculol C. Yakuchinone A and Yakuchinone B are chemotaxonomic marker compounds identified in all species. The antioxidant properties of each extract of 42.27±0.53, 46.59±0.81 and 35.66±0.73 mg/L have been proven by the molecular interactions of the marker compounds in their ability to act as xanthine oxidase inhibitors. The compounds Yakuchinone A and Yakuchinone B are thought to be responsible for the pharmacological activity of the species E. calophrys, E. canaria and E. echinulate. Yakuchinone A and Yakuchinone B are marker compounds because they are distributed in all samples.