bluuebunny/crossref_metadata_2025 huggingface dataset:
Metaplastic breast cancer with a unique presentation and complete response to chemotherapy: a case report
Authors: Nahhat Fouad , Doyya Modar , Zabad Kareem , Ksiri Hazem
Published: May 2024

Background

Metaplastic breast carcinomas are a rare variant group of breast carcinomas. They are usually high-grade and triple-negative tumors. They often present with large primary tumor sizes. However, the involvement of axillary lymph nodes is infrequent at the time of diagnosis. Metaplastic breast carcinomas are associated with a worse prognosis and a poorer response to chemotherapy in comparison with other non-metaplastic triple-negative breast cancers. Up until this point, there are no specific treatment recommendations for metaplastic breast carcinomas beyond those intended for invasive breast cancer in general.

Case presentation

A 40-year-old woman complained of a palpable mass in her left axilla. On ultrasonography, the mass was solid, spindle-shaped, hypoechoic with regular borders, and exhibited decreased vascularity. At first, the mass appeared to be of a muscular origin. There was not any clinical nor ultrasonic evidence of a primary breast tumor. On magnetic resonance imaging, the axillary mass was a well-defined with regular borders, measuring 24 × 35 mm. Needle biopsy showed a spindle cell tumor with mild to moderate atypia. The subsequent surgical resection revealed a spindle cell neoplasm within a lymph node, favoring a metastatic origin of the tumor. The tumor cells lacked expression of estrogen, progesterone, and HER2 receptors. PET-CT scan indicated pathological uptake in the left breast. Accordingly, the patient was diagnosed with metaplastic breast cancer that had metastasized to the axillary lymph node. She commenced a combined chemotherapy regimen of doxorubicin and cyclophosphamide. After six treatment cycles, she underwent left modified radical mastectomy with axillary lymph node dissection. Pathological examination of the specimens revealed a total burn-out tumor in the breast due to excellent treatment response. There were no residual tumor cells. All dissected lymph nodes were free of tumor. At the one-year follow-up, the patient showed no signs of tumor recurrence.

Conclusion

This report sheds light on a distinctive presentation of metaplastic breast carcinoma, emphasizing the need for vigilance in diagnosing this rare and aggressive breast cancer variant. In addition, the patient’s remarkable response to chemotherapy highlights potential treatment avenues for metaplastic breast cancer.
Social accountability in a medical school: is it sufficient? A regional medical school curriculum and approaches to equip graduates for rural and remote medical services
Authors: Noya Farah , Carr Sandra , Thompson Sandra
Published: May 2024

Background

Social accountability is increasingly integral to medical education, aligning health systems with community needs. Universitas Pattimura’s Faculty of Medicine (FMUP) enhances this through a curriculum that prepares graduates for rural and remote (RR) medical practice, exceeding national standards. The impact of this curriculum on graduate readiness in actual work settings remains unassessed.

Objective

This study was conducted to capture the perspectives of FMUP medical graduates in a rural-centric curriculum, focusing on the teaching and learning opportunities afforded to them during their medical education. These insights are crucial for evaluating the accountability of regional medical schools in delivering quality service, particularly in underserved areas.

Methods

Semistructured interviews were conducted with nine FMUP graduates employed in the RR areas of Maluku Province. A qualitative analysis was employed to examine graduates’ views on the curriculum concerning medical school accountability.

Results

The FMUP curriculum, informed by social accountability principles, partially prepares graduates to work under Maluku’s RR conditions. However, it was reported by participants that their skills and preparedness often fall short in the face of substandard working environments.

Conclusions

The FMUP curriculum supports the government’s aim to develop an RR medical workforce. However, the curriculum’s social accountability and rural emphasis fall short of addressing community health needs amid inadequate practice conditions. Political investment in standardizing medical facilities and equipment is essential for enhancing graduates’ effectiveness and health outcomes in RR communities.
Navigating the ethical landscape of artificial intelligence in radiography: a cross-sectional study of radiographers’ perspectives
Authors: Aldhafeeri Faten Mane
Published: May 2024

Background

The integration of artificial intelligence (AI) in radiography presents transformative opportunities for diagnostic imaging and introduces complex ethical considerations. The aim of this cross-sectional study was to explore radiographers’ perspectives on the ethical implications of AI in their field and identify key concerns and potential strategies for addressing them.

Methods

A structured questionnaire was distributed to a diverse group of radiographers in Saudi Arabia. The questionnaire included items on ethical concerns related to AI, the perceived impact on clinical practice, and suggestions for ethical AI integration in radiography. The data were analyzed using quantitative and qualitative methods to capture a broad range of perspectives.

Results

Three hundred eighty-eight radiographers responded and had varying levels of experience and specializations. Most (44.8%) participants were unfamiliar with the integration of AI into radiography. Approximately 32.9% of radiographers expressed uncertainty regarding the importance of transparency and explanatory capabilities in the AI systems used in radiology. Many (36.9%) participants indicated that they believed that AI systems used in radiology should be transparent and provide justifications for their decision-making procedures. A significant preponderance (44%) of respondents agreed that implementing AI in radiology may increase ethical dilemmas. However, 27.8%expressed uncertainty in recognizing and understanding the potential ethical issues that could arise from integrating AI in radiology. Of the respondents, 41.5% stated that the use of AI in radiology required establishing specific ethical guidelines. However, a significant percentage (28.9%) expressed the opposite opinion, arguing that utilizing AI in radiology does not require adherence to ethical standards. In contrast to the 46.6% of respondents voicing concerns about patient privacy over AI implementation, 41.5% of respondents did not have any such apprehensions.

Conclusions

This study revealed a complex ethical landscape in the integration of AI in radiography, characterized by enthusiasm and apprehension among professionals. It underscores the necessity for ethical frameworks, education, and policy development to guide the implementation of AI in radiography. These findings contribute to the ongoing discourse on AI in medical imaging and provide insights that can inform policymakers, educators, and practitioners in navigating the ethical challenges of AI adoption in healthcare.
The role of nurses for patients with Parkinson’s disease at home: a scoping review
Authors: Fujita Takako , Iwaki Miho , Hatono Yoko
Published: May 2024

Background

Parkinson’s disease is a neurodegenerative disease, and many patients are cared for at home by nurses. Parkinson’s disease nurse specialists have been certified in several countries. This study aimed to provide an overview of what is known about the role of nurses in the care of patients with Parkinson’s disease at home and to determine the differences between nurses and Parkinson’s disease nurse specialists.

Methods

A scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. PubMed, Scopus, Web of Science, and Cumulative Index to Nursing and Allied Health Literature were searched (keywords: Parkinson’s disease AND nurse AND [community OR home]) for studies published in English up to September 2023 describing the nurse’s role in caring for patients with Parkinson’s disease at home. Studies without abstracts were removed, along with protocols, systematic reviews, and studies concerned with other diseases or including data that were difficult to distinguish from those of other diseases. Roles were described and organized by category.

Results

A total of 26 studies were included. The nurses’ roles were categorized as overall assessment and support, treatment management, safety assessment regarding falls, care for non-motor symptoms, palliative care, support for caregivers, education for care home staff, multidisciplinary collaboration, and provision of information on social resources. Medication management and education of care home staff were identified as roles of nurse specialists.

Conclusions

This study revealed the role of nurses caring for patients with Parkinson’s disease at home. Because of the complexity of the patients’ medication regimens, nurse specialists provide assistance, especially with medication management and the provision of education to care staff. This study will facilitate the preparation of nurses to acquire the knowledge and skills necessary to help patients with Parkinson’s disease, even in countries where Parkinson’s disease nurse specialists are not officially certified, and will help patients feel comfortable with the care they receive.
Preparation and epitope analysis of monoclonal antibodies against African swine fever virus DP96R protein
Authors: Li Chao , Si Xuan-ying , Wang Xiao-ge , Yan Zhi-wei , Hou Hao-yu , You Long-qi , Chen Yin-long , Zhang Ang-ke , Wang Na , Sun Ai-jun , Du Yong-kun , Zhang Gai-ping
Published: May 2024

Background

Many proteins of African swine fever virus (ASFV, such as p72, p54, p30, CD2v, K205R) have been successfully expressed and characterized. However, there are few reports on the DP96R protein of ASFV, which is the virulence protein of ASFV and plays an important role in the process of host infection and invasion of ASFV.

Results

Firstly, the prokaryotic expression vector of DP96R gene was constructed, the prokaryotic system was used to induce the expression of DP96R protein, and monoclonal antibody was prepared by immunizing mice. Four monoclonal cells of DP96R protein were obtained by three ELISA screening and two sub-cloning; the titer of ascites antibody was up to 1:500,000, and the monoclonal antibody could specifically recognize DP96R protein. Finally, the subtypes of the four strains of monoclonal antibodies were identified and the minimum epitopes recognized by them were determined.

Conclusion

Monoclonal antibody against ASFV DP96R protein was successfully prepared and identified, which lays a foundation for further exploration of the structure and function of DP96R protein and ASFV diagnostic technology.
A non-invasive method to determine core temperature for cats and dogs using surface temperatures based on machine learning
Authors: Zhao Zimu , Li Xujia , Zhuang Yan , Li Fan , Wang Weijia , Wang Qing , Su Song , Huang Jiayu , Tang Yong
Published: May 2024

Background

Rectal temperature (RT) is an important index of core temperature, which has guiding significance for the diagnosis and treatment of pet diseases.

Objectives

Development and evaluation of an alternative method based on machine learning to determine the core temperatures of cats and dogs using surface temperatures.

Animals

200 cats and 200 dogs treated between March 2022 and May 2022.

Methods

A group of cats and dogs were included in this study. The core temperatures and surface body temperatures were measured. Multiple machine learning methods were trained using a cross-validation approach and evaluated in one retrospective testing set and one prospective testing set.

Results

The machine learning models could achieve promising performance in predicting the core temperatures of cats and dogs using surface temperatures. The root mean square errors (RMSE) were 0.25 and 0.15 for cats and dogs in the retrospective testing set, and 0.15 and 0.14 in the prospective testing set.

Conclusion

The machine learning model could accurately predict core temperatures for companion animals of cats and dogs using easily obtained body surface temperatures.
Expanding phenotype of MED13-associated syndrome presenting novel de novo missense variant in a patient with multiple congenital anomalies
Authors: Tolmacheva Ekaterina , Bolshakova Anna S. , Shubina Jekaterina , Rogacheva Margarita S. , Ekimov Alexey N. , Podurovskaya Julia L. , Burov Artem A. , Rebrikov Denis V. , Bychenko Vladimir G. , Trofimov Dmitry Yu. , Sukhikh Gennady T.
Published: May 2024

Background

Whole exome sequencing allows rapid identification of causative single nucleotide variants and short insertions/deletions in children with congenital anomalies and/or intellectual disability, which aids in accurate diagnosis, prognosis, appropriate therapeutic interventions, and family counselling. Recently, de novo variants in the MED13 gene were described in patients with an intellectual developmental disorder that included global developmental delay, mild congenital heart anomalies, and hearing and vision problems in some patients.

Results

Here we describe an infant who carried a de novo p.Pro835Ser missense variant in the MED13 gene, according to whole exome trio sequencing. He presented with congenital heart anomalies, dysmorphic features, hydrocephalic changes, hypoplastic corpus callosum, bilateral optic nerve atrophy, optic chiasm atrophy, brain stem atrophy, and overall a more severe condition compared to previously described patients.

Conclusions

Therefore, we propose to expand the MED13-associated phenotype to include severe complications that could end up with multiple organ failure and neonatal death.
A novel disulfide death-related genes prognostic signature identifies the role of IPO4 in glioma progression
Authors: Wu HaoYuan , Yang ZhiHao , Chang ChenXi , Wang ZhiWei , Zhang DeRan , Guo QingGuo , Zhao Bing
Published: May 2024

Background

“Disulfide death,” a form of cellular demise, is triggered by the abnormal accumulation of intracellular disulfides under conditions of glucose deprivation. However, its role in the prognosis of glioma remains undetermined. Therefore, the main objective of this study is to establish prognostic signature based on disulfide death-related genes (DDRGs) and to provide new solutions in choosing the effective treatment of glioma.

Methods

The RNA transcriptome, clinical information, and mutation data of glioma samples were sourced from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), while normal samples were obtained from the Genotype-Tissue Expression (GTEx). DDRGs were compiled from previous studies and selected through differential analysis and univariate Cox regression analysis. The molecular subtypes were determined through consensus clustering analysis. Further, LASSO analysis was employed to select characteristic genes, and subsequently, a risk model comprising seven DDRGs was constructed based on multivariable Cox analysis. Kaplan-Meier survival curves were employed to assess survival differences between high and low-risk groups. Additionally, functional analyses (GO, KEGG, GSEA) were conducted to explore the potential biological functions and signaling pathways of genes associated with the model. The study also explored immune checkpoint (ICP) genes, immune cell infiltration levels, and immune stromal scores. Finally, the effect of Importin-4(IPO4) on glioma has been further confirmed through RT-qPCR, Western blot, and cell functional experiments.

Results

7 genes associated with disulfide death were obtained and two subgroups of patients with different prognosis and clinical characteristics were identified. Risk signature was subsequently developed and proved to serve as an prognostic predictor. Notably, the high-risk group exhibited an immunosuppressive microenvironment characterized by a high concentration of M2 macrophages and regulatory T cells (Tregs). In contrast, the low-risk group showed lower half-maximal inhibitory concentration (IC50) values. Therefore, patients in the high-risk group may benefit more from immunotherapy, while patients in the low-risk group may benefit more from chemotherapy. In addition, in vitro experiments have shown that inhibition of the expression of IPO4 leads to a significant reduction in the proliferation, migration, and invasion of glioma cells.

Conclusion

This study identified two glioma subtypes and constructed a prognostic signature based on DDRGs. The signature has the potential to optimize the selection of patients for immune- and chemotherapy and provided a potential therapeutic target for glioma.
Effects of robot-assisted gait training using the Welwalk on gait independence for individuals with hemiparetic stroke: an assessor-blinded, multicenter randomized controlled trial
Authors: Hirano Satoshi , Saitoh Eiichi , Imoto Daisuke , Ii Takuma , Tsunoda Tetsuya , Otaka Yohei
Published: May 2024

Background

Gait disorder remains a major challenge for individuals with stroke, affecting their quality of life and increasing the risk of secondary complications. Robot-assisted gait training (RAGT) has emerged as a promising approach for improving gait independence in individuals with stroke. This study aimed to evaluate the effect of RAGT in individuals with subacute hemiparetic stroke using a one-leg assisted gait robot called Welwalk WW-1000.

Methods

An assessor-blinded, multicenter randomized controlled trial was conducted in the convalescent rehabilitation wards of eight hospitals in Japan. Participants with first-ever hemiparetic stroke who could not walk at pre-intervention assessment were randomized to either the Welwalk group, which underwent RAGT with conventional physical therapy, or the control group, which underwent conventional physical therapy alone. Both groups received 80 min of physical therapy per day, 7 days per week, while the Welwalk group received 40 min of RAGT per day, 6 days per week, as part of their physical therapy. The primary outcome was gait independence, as assessed using the Functional Independence Measure Walk Score.

Results

A total of 91 participants were enrolled, 85 of whom completed the intervention. As a result, 91 participants, as a full analysis set, and 85, as a per-protocol set, were analyzed. The primary outcome, the cumulative incidence of gait-independent events, was not significantly different between the groups. Subgroup analysis revealed that the interaction between the intervention group and stroke type did not yield significant differences in either the full analysis or per-protocol set. However, although not statistically significant, a discernible trend toward improvement with Welwalk was observed in cases of cerebral infarction for the full analysis and per-protocol sets (HR 4.167 [95%CI 0.914–18.995], p = 0.065, HR 4.443 [95%CI 0.973–20.279], p = 0.054, respectively).

Conclusions

The combination of RAGT using Welwalk and conventional physical therapy was not significantly more effective than conventional physical therapy alone in promoting gait independence in individuals with subacute hemiparetic stroke, although a trend toward earlier gait independence was observed in individuals with cerebral infarction.

Trial registration

This study was registered with the Japan Registry of Clinical Trials (https://jrct.niph.go.jp; jRCT 042180078) on March 3, 2019.
LINC01002 functions as a ceRNA to regulate FRMD8 by sponging miR-4324 for the development of COVID-19
Authors: Kong Xinyi , Wang Qinjin , Wang Xumeng , Yang Kaming , Nie Shuping , Li Yuetong , Lao Wanwen , Yu Xin , Zhang Yanping , Li Zhenlin , Liu Yang , Ning Jie , Wang Yan , Bi Changlong , Wu Chao , Zhai Aixia
Published: May 2024

Background

Syndrome coronavirus-2 (SARS-CoV-2) has developed various strategies to evade the antiviral impact of type I IFN. Non-structural proteins and auxiliary proteins have been extensively researched on their role in immune escape. Nevertheless, the detailed mechanisms of structural protein-induced immune evasion have not been well elucidated.

Methods

Human alveolar basal epithelial carcinoma cell line (A549) was stimulated with polyinosinic-polycytidylic acid (PIC) and independently transfected with four structural proteins expression plasmids, including nucleocapsid (N), spike (S), membrane (M) and envelope (E) proteins. By RT-qPCR and ELISA, the structural protein with the most pronounced inhibitory effects on IFN-β induction was screened. RNA-sequencing (RNA-Seq) and two differential analysis strategies were used to obtain differentially expressed genes associated with N protein inhibition of IFN-β induction. Based on DIANA-LncBase and StarBase databases, the interactive competitive endogenous RNA (ceRNA) network for N protein-associated genes was constructed. By combining single-cell sequencing data (GSE158055), lncRNA-miRNA-mRNA axis was further determined. Finally, RT-qPCR was utilized to illustrate the regulatory functions among components of the ceRNA axis.

Results

SARS-CoV-2 N protein inhibited IFN-β induction in human alveolar epithelial cells most significantly compared with other structural proteins. RNA-Seq data analysis revealed genes related to N protein inhibiting IFNs induction. The obtained 858 differentially expressed genes formed the reliable ceRNA network. The function of LINC01002-miR-4324-FRMD8 axis in the IFN-dominated immune evasion was further demonstrated through integrating single-cell sequencing data. Moreover, we validated that N protein could reverse the effect of PIC on LINC01002, FRMD8 and miR-4324 expression, and subsequently on IFN-β expression level. And LINC01002 could regulate the production of FRMD8 by inhibiting miR-4324.

Conclusion

SARS-CoV-2 N protein suppressed the induction of IFN-β by regulating LINC01002 which was as a ceRNA, sponging miR-4324 and participating in the regulation of FRMD8 mRNA. Our discovery provides new insights into early intervention therapy and drug development on SARS-CoV-2 infection.
Synthetic silica fibers of different length, diameter and shape: synthesis and interaction with rat (NR8383) and human (THP-1) macrophages in vitro, including chemotaxis and gene expression profile
Authors: Białas Nataniel , Rosenkranz Nina , Weber Daniel Gilbert , Kostka Kathrin , Johnen Georg , Winter Aileen , Brik Alexander , Loza Kateryna , Szafranski Katja , Brüning Thomas , Bünger Jürgen , Westphal Götz , Epple Matthias
Published: May 2024

Background

Inhalation of biopersistent fibers like asbestos can cause strong chronic inflammatory effects, often resulting in fibrosis or even cancer. The interplay between fiber shape, fiber size and the resulting biological effects is still poorly understood due to the lack of reference materials.

Results

We investigated how length, diameter, aspect ratio, and shape of synthetic silica fibers influence inflammatory effects at doses up to 250 µg cm-2. Silica nanofibers were prepared with different diameter and shape. Straight (length ca. 6 to 8 µm, thickness ca. 0.25 to 0.35 µm, aspect ratio ca. 17:1 to 32:1) and curly fibers (length ca. 9 µm, thickness ca. 0.13 µm, radius of curvature ca. 0.5 µm, aspect ratio ca. 70:1) were dispersed in water with no apparent change in the fiber shape during up to 28 days. Upon immersion in aqueous saline (DPBS), the fibers released about 5 wt% silica after 7 days irrespectively of their shape. The uptake of the fibers by macrophages (human THP-1 and rat NR8383) was studied by scanning electron microscopy and confocal laser scanning microscopy. Some fibers were completely taken up whereas others were only partially internalized, leading to visual damage of the cell wall. The biological effects were assessed by determining cell toxicity, particle-induced chemotaxis, and the induction of gene expression of inflammatory mediators.

Conclusions

Straight fibers were only slightly cytotoxic and caused weak cell migration, regardless of their thickness, while the curly fibers were more toxic and caused significantly stronger chemotaxis. Curly fibers also had the strongest effect on the expression of cytokines and chemokines. This may be due to the different aspect ratio or its twisted shape.
Cirsilineol inhibits RANKL-induced osteoclast activity and ovariectomy-induced bone loss via NF-κb/ERK/p38 signaling pathways
Authors: Wang Cong , Zeng Rong , Li Yong , He Rongxin
Published: May 2024

Background

Postmenopausal osteoporosis is a chronic metabolic bone disease caused by excessive osteoclast formation and function. Targeting osteoclast differentiation and activity can modulate bone resorption and alleviate osteoporosis. Cirsilineol, an active constituent of Vestita Wall, has shown numerous biological activities and has been used to treat many metabolic diseases. However, whether cirsilineol inhibits osteoclast activity and prevents postmenopausal osteoporosis still remain unknown.

Materials and methods

Primary bone marrow macrophages (BMMs) and RAW264.7 cells were used. Osteoclast activity was measured by TRAP staining, F-actin staining, and bone resorption assay after BMMs were treated with cirsilineol at concentrations of 0, 1, 2.5 and 5 µM. RT-PCR and western blotting were performed to evaluate the expression of osteoclast-related genes. In addition, female C57BL/6 mice underwent OVX surgery and were treated with cirsilineol (20 mg/kg) to demonstrate the effect of cirsilineol on osteoporosis.

Results

Cirsilineol significantly inhibited receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast differentiation in a concentration- and time-dependent manner, respectively. Additionally, cirsilineol inhibited F-actin ring formation, thus reducing the activation of bone resorption ability. Cirsilineol suppressed the expression of osteoclast-related genes and proteins via blocking nuclear factor (NF)-κb, ERK, and p38 signaling cascades. More importantly, cirsilineol treatment in mice with osteoporosis alleviated osteoclasts hyperactivation and bone mass loss caused by estrogen depletion.

Conclusion

In this study, the protective effect of cirsilineol on osteoporosis has been investigated for the first time. In conclusion, our findings prove the inhibitory effect of cirsilineol on osteoclast activity via NF-κb/ERK/p38 signaling pathways and strongapplication of cirsilineol can be proposed as a potential therapeutic strategy.
KAP1 stabilizes MYCN mRNA and promotes neuroblastoma tumorigenicity by protecting the RNA m6A reader YTHDC1 protein degradation
Authors: Yang Yi , Zhang Yingwen , Chen Guoyu , Sun Bowen , Luo Fei , Gao Yijin , Feng Haizhong , Li Yanxin
Published: May 2024

Background

Neuroblastoma (NB) patients with amplified MYCN often face a grim prognosis and are resistant to existing therapies, yet MYCN protein is considered undruggable. KAP1 (also named TRIM28) plays a crucial role in multiple biological activities. This study aimed to investigate the relationship between KAP1 and MYCN in NB.

Methods

Transcriptome analyses and luciferase reporter assay identified that KAP1 was a downstream target of MYCN. The effects of KAP1 on cancer cell proliferation and colony formation were explored using the loss-of-function assays in vitro and in vivo. RNA stability detection was used to examine the influence of KAP1 on MYCN expression. The mechanisms of KAP1 to maintain MYCN mRNA stabilization were mainly investigated by mass spectrum, immunoprecipitation, RIP-qPCR, and western blotting. In addition, a xenograft mouse model was used to reveal the antitumor effect of STM2457 on NB.

Results

Here we identified KAP1 as a critical regulator of MYCN mRNA stability by protecting the RNA N6-methyladenosine (m6A) reader YTHDC1 protein degradation. KAP1 was highly expressed in clinical MYCN-amplified NB and was upregulated by MYCN. Reciprocally, KAP1 knockdown reduced MYCN mRNA stability and inhibited MYCN-amplified NB progression. Mechanistically, KAP1 regulated the stability of MYCN mRNA in an m6A-dependent manner. KAP1 formed a complex with YTHDC1 and RNA m6A writer METTL3 to regulate m6A-modified MYCN mRNA stability. KAP1 depletion decreased YTHDC1 protein stability and promoted MYCN mRNA degradation. Inhibiting MYCN mRNA m6A modification synergized with chemotherapy to restrain tumor progression in MYCN-amplified NB.

Conclusions

Our research demonstrates that KAP1, transcriptionally activated by MYCN, forms a complex with YTHDC1 and METTL3, which in turn maintain the stabilization of MYCN mRNA in an m6A-dependent manner. Targeting m6A modification by STM2457, a small-molecule inhibitor of METTL3, could downregulate MYCN expression and attenuate tumor proliferation. This finding provides a new alternative putative therapeutic strategy for MYCN-amplified NB.
Proteogenomic characterization of difficult-to-treat breast cancer with tumor cells enriched through laser microdissection
Authors: Raj-Kumar Praveen-Kumar , Lin Xiaoying , Liu Tao , Sturtz Lori A. , Gritsenko Marina A. , Petyuk Vladislav A. , Sagendorf Tyler J. , Deyarmin Brenda , Liu Jianfang , Praveen-Kumar Anupama , Wang Guisong , McDermott Jason E. , Shukla Anil K. , Moore Ronald J. , Monroe Matthew E. , Webb-Robertson Bobbie-Jo M. , Hooke Jeffrey A. , Fantacone-Campbell Leigh , Mostoller Brad , Kvecher Leonid , Kane Jennifer , Melley Jennifer , Somiari Stella , Soon-Shiong Patrick , Smith Richard D. , Mural Richard J. , Rodland Karin D. , Shriver Craig D. , Kovatich Albert J. , Hu Hai
Published: May 2024

Background

Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women globally. Despite advances, there is considerable variation in clinical outcomes for patients with non-luminal A tumors, classified as difficult-to-treat breast cancers (DTBC). This study aims to delineate the proteogenomic landscape of DTBC tumors compared to luminal A (LumA) tumors.

Methods

We retrospectively collected a total of 117 untreated primary breast tumor specimens, focusing on DTBC subtypes. Breast tumors were processed by laser microdissection (LMD) to enrich tumor cells. DNA, RNA, and protein were simultaneously extracted from each tumor preparation, followed by whole genome sequencing, paired-end RNA sequencing, global proteomics and phosphoproteomics. Differential feature analysis, pathway analysis and survival analysis were performed to better understand DTBC and investigate biomarkers.

Results

We observed distinct variations in gene mutations, structural variations, and chromosomal alterations between DTBC and LumA breast tumors. DTBC tumors predominantly had more mutations in TP53, PLXNB3, Zinc finger genes, and fewer mutations in SDC2, CDH1, PIK3CA, SVIL, and PTEN. Notably, Cytoband 1q21, which contains numerous cell proliferation-related genes, was significantly amplified in the DTBC tumors. LMD successfully minimized stromal components and increased RNA–protein concordance, as evidenced by stromal score comparisons and proteomic analysis. Distinct DTBC and LumA-enriched clusters were observed by proteomic and phosphoproteomic clustering analysis, some with survival differences. Phosphoproteomics identified two distinct phosphoproteomic profiles for high relapse-risk and low relapse-risk basal-like tumors, involving several genes known to be associated with breast cancer oncogenesis and progression, including KIAA1522, DCK, FOXO3, MYO9B, ARID1A, EPRS, ZC3HAV1, and RBM14. Lastly, an integrated pathway analysis of multi-omics data highlighted a robust enrichment of proliferation pathways in DTBC tumors.

Conclusions

This study provides an integrated proteogenomic characterization of DTBC vs LumA with tumor cells enriched through laser microdissection. We identified many common features of DTBC tumors and the phosphopeptides that could serve as potential biomarkers for high/low relapse-risk basal-like BC and possibly guide treatment selections.
Abrogation of ORF8–IRF3 binding interface with Carbon nanotube derivatives to rescue the host immune system against SARS-CoV-2 by using molecular screening and simulation approaches
Authors: Suleman Muhammad , Murshed Abduh , Imran Kashif , Khan Abbas , Ali Zafar , Albekairi Norah A. , Wei Dong-Qing , Yassine Hadi M. , Crovella Sergio
Published: May 2024

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to over six million deaths worldwide. In human immune system, the type 1 interferon (IFN) pathway plays a crucial role in fighting viral infections. However, the ORF8 protein of the virus evade the immune system by interacting with IRF3, hindering its nuclear translocation and consequently downregulate the type I IFN signaling pathway. To block the binding of ORF8–IRF3 and inhibit viral pathogenesis a quick discovery of an inhibitor molecule is needed. Therefore, in the present study, the interface between the ORF8 and IRF3 was targeted on a high-affinity carbon nanotube by using computational tools. After analysis of 62 carbon nanotubes by multiple docking with the induced fit model, the top five compounds with high docking scores of − 7.94 kcal/mol, − 7.92 kcal/mol, − 7.28 kcal/mol, − 7.19 kcal/mol and − 7.09 kcal/mol (top hit1-5) were found to have inhibitory activity against the ORF8–IRF3 complex. Molecular dynamics analysis of the complexes revealed the high compactness of residues, stable binding, and strong hydrogen binding network among the ORF8-nanotubes complexes. Moreover, the total binding free energy for top hit1-5 was calculated to be − 43.21 ± 0.90 kcal/mol, − 41.17 ± 0.99 kcal/mol, − 48.85 ± 0.62 kcal/mol, − 43.49 ± 0.77 kcal/mol, and − 31.18 ± 0.78 kcal/mol respectively. These results strongly suggest that the identified top five nanotubes (hit1-5) possess significant potential for advancing and exploring innovative drug therapies. This underscores their suitability for subsequent in vivo and in vitro experiments, marking them as promising candidates worthy of further investigation.
A DNA barcode reference library of Croatian mosquitoes (Diptera: Culicidae): implications for identification and delimitation of species, with notes on the distribution of potential vector species
Authors: Bušić Nataša , Klobučar Ana , Landeka Nediljko , Žitko Toni , Vignjević Goran , Turić Nataša , Sudarić Bogojević Mirta , Merdić Enrih , Kučinić Mladen , Bruvo Mađarić Branka
Published: May 2024

Background

Mosquitoes pose a risk to human health worldwide, and correct species identification and detection of cryptic species are the most important keys for surveillance and control of mosquito vectors. In addition to traditional identification based on morphology, DNA barcoding has recently been widely used as a complementary tool for reliable identification of mosquito species. The main objective of this study was to create a reference DNA barcode library for the Croatian mosquito fauna, which should contribute to more accurate and faster identification of species, including cryptic species, and recognition of relevant vector species.

Methods

Sampling was carried out in three biogeographical regions of Croatia over six years (2017–2022). The mosquitoes were morphologically identified; molecular identification was based on the standard barcoding region of the mitochondrial COI gene and the nuclear ITS2 region, the latter to identify species within the Anopheles maculipennis complex. The BIN-RESL algorithm assigned the COI sequences to the corresponding BINs (Barcode Index Number clusters) in BOLD, i.e. to putative MOTUs (Molecular Operational Taxonomic Units). The bPTP and ASAP species delimitation methods were applied to the genus datasets in order to verify/confirm the assignment of specimens to specific MOTUs.

Results

A total of 405 mosquito specimens belonging to six genera and 30 morphospecies were collected and processed. Species delimitation methods assigned the samples to 31 (BIN-RESL), 30 (bPTP) and 28 (ASAP) MOTUs, with most delimited MOTUs matching the morphological identification. Some species of the genera Culex, Aedes and Anopheles were assigned to the same MOTUs, especially species that are difficult to distinguish morphologically and/or represent species complexes. In total, COI barcode sequences for 34 mosquito species and ITS2 sequences for three species of the genus Anopheles were added to the mosquito sequence database for Croatia, including one individual from the Intrudens Group, which represents a new record for the Croatian mosquito fauna.

Conclusion

We present the results of the first comprehensive study combining morphological and molecular identification of most mosquito species present in Croatia, including several invasive and vector species. With the exception of some closely related species, this study confirmed that DNA barcoding based on COI provides a reliable basis for the identification of mosquito species in Croatia.

Graphical Abstract
Dataset of seminal plasma proteome of Nellore bulls with high and low percentage of abnormalities sperm
Authors: Ramirez-Lopez Camilo Jose , Barros Edvaldo , Vidigal Pedro Marcus , Gomes Lidiany Lopes , Baracat-Pereira Maria Cristina , Guimarães Simone Eliza Facioni , Guimarães José Domingos
Published: May 2024

Objectives

Bovine seminal plasma proteins perform several functions related to sperm function. Changes in the expression pattern or abundance of seminal proteins are related to changes in the fertilizing capacity of bulls. Considering the role of seminal plasma proteins in sperm function and animal reproduction, we investigated changes in the protein abundance profile in response to sperm morphological changes using a proteomic approach.

Datadescription

In our present investigation, we employed liquid chromatography coupled with mass spectrometry to elucidate the proteomic composition of seminal plasma obtained from Nellore bulls exhibiting varying percentages of sperm abnormalities. Following semen collection, seminal plasma was promptly isolated from sperm, and proteins were subsequently precipitated, enzymatically digested using porcine trypsin, and subjected to analysis utilizing the Acquity nano UHPLC System in conjunction with a mass spectrometer. This dataset encompasses a total of 297 proteins, marking the inaugural instance in which a comparative profile of seminal plasma proteins in young Nellore bulls, categorized by their sperm abnormality percentages, has been delineated using LC-MS/MS. The comprehensive nature of this dataset contributes pivotal proteomic insights, representing a noteworthy advancement in our understanding of the reproductive biology of the Nellore breed.
In situ ascending aortic thrombus in a patient with metastatic lung adenocarcinoma and no aortic atherosclerosis or cisplatin exposure: a case report
Authors: Mehta Chirag , Raza Fatima
Published: May 2024

Background

An ascending aortic thrombus is exceedingly rare. Two instances have been reported in the setting of lung cancer, but only after cisplatin use, which is associated with hypercoagulability. We present the first case of a patient with lung cancer who developed an ascending aortic thrombus without structural risk factors or chemotherapy use.

Case

A 60-year-old white female with significant smoking history presented with several weeks of malaise. A chest computed tomography scan revealed a 2.2-cm right upper lobe mass. As an outpatient, right hilar lymph node immunohistochemistry (IHC) samples via endobronchial ultrasound confirmed thyroid transcription factor-1 adenocarcinoma. After the procedure, the patient endorsed dyspnea and was advised to go to the emergency department. A chest computed tomography angiography identified a new 2.4 × 1.1 × 1.1 cm thrombus within the proximal aortic arch. No pulmonary emboli or intrapulmonary shunts were identified. A hypercoagulable workup was negative. Transthoracic echocardiogram was without left ventricular thrombus, akinesis or hypokinesis, left atrial dilation, or intracardiac shunts. A lower extremity ultrasound was negative for deep vein thrombosis. Given the procedural risk, thrombectomy was deferred. The patient was transitioned to enoxaparin, and a repeat computed tomography for resolution is in process.

Conclusion

To our knowledge, this is the only case detailing an in situ ascending aortic thrombus in the setting of lung cancer, without structural risk factors, chemotherapy use, or other hypercoagulable comorbidities. Optimal management for an aortic thrombus and malignant disease is less clear. Clinicians should be vigilant for unusual arterial thromboses in patients with high metastatic burden.
The community of inquiry as a tool for measuring student engagement in blended massive open online courses (MOOCs): a case study of university students in a developing country
Authors: Edumadze John Kwame Eduafo , Govender Desmond Welsey
Published: May 2024

While massive open online courses (MOOCs) promise to democratise access to education, the literature reveals a nuanced understanding of engagement in these settings, especially in resource-constrained environments. Blended MOOCs combine MOOCs and physical classroom settings of contents and instructions. This study extends this discourse by focusing on blended MOOCs, which remain under-explored in the context of developing countries. The blended MOOC at the University of Cape Coast (UCC), Ghana, deals with third-party MOOCs as open educational resources (OERs) integrated with campus-based courses. UCC students have been using such blended MOOCs since 2016, when all level 100 students were mandated to enrol in a course entitled Information Technology Skills (ITS101). ITS101 is aligned to courses in a MOOC platform called Alison as an OER. Students' engagement is key to their continued use and satisfaction with online learning, such as MOOCs. However, among all the e-learning modes, students' engagement is the lowest in MOOCs, leading to high dropout rates. Blended MOOCs are one of the techniques recommended to reverse the undesirability of MOOCs, including engagement. However, few studies have been conducted on students' engagement in blended MOOCs, especially among university students in sub-Saharan Africa using MOOCs as OERs. Thus, this paper aims to measure student engagement in blended MOOCs using the revised Community of Inquiry for university students in a developing country. The rationale is to determine whether factors affect engagement positively or negatively. A two-stage cluster sampling technique was used to determine the participants for this study. A list of blended MOOC classes offered at UCC was obtained from the staff's mailing list. In the first stage, academic levels (100, 200, 300 and 800) were randomly selected from the strata using a lottery sampling technique. In the second stage, another simple random selection of blended MOOC courses or classes was used within each selected academic level. All students in the selected classes were then included in the study. Partial Least Squares Structural Equation Modelling was used to validate the model on the predictive relationships existing among the four presences (cognitive, learning, social and teaching) and engagement. Results from the structural model analysis proved a statistically significant predictive relationship among the constructs within the model. Learning presence had the most significant effect on student engagement. Thus, it should be included as one of the presences in the community of inquiry.
MicroRNA-721 regulates gluconeogenesis via KDM2A-mediated epigenetic modulation in diet-induced insulin resistance in C57BL/6J mice
Authors: Kabeer Shaheen Wasil , Sharma Shivam , Sriramdasu Shalemraju , Tikoo Kulbhushan
Published: May 2024

Background

Aberrant gluconeogenesis is considered among primary drivers of hyperglycemia under insulin resistant conditions, with multiple studies pointing towards epigenetic dysregulation. Here we examine the role of miR-721 and effect of epigenetic modulator laccaic acid on the regulation of gluconeogenesis under high fat diet induced insulin resistance.

Results

Reanalysis of miRNA profiling data of high-fat diet-induced insulin-resistant mice model, GEO dataset (GSE94799) revealed a significant upregulation of miR-721, which was further validated in invivo insulin resistance in mice and invitro insulin resistance in Hepa 1–6 cells. Interestingly, miR-721 mimic increased glucose production in Hepa 1–6 cells via activation of FOXO1 regulated gluconeogenic program. Concomitantly, inhibition of miR-721 reduced glucose production in palmitate induced insulin resistant Hepa 1–6 cells by blunting the FOXO1 induced gluconeogenesis. Intriguingly, at epigenetic level, enrichment of the transcriptional activation mark H3K36me2 got decreased around the FOXO1 promoter. Additionally, identifying targets of miR-721 using miRDB.org showed H3K36me2 demethylase KDM2A as a potential target. Notably, miR-721 inhibitor enhanced KDM2A expression which correlated with H3K36me2 enrichment around FOXO1 promoter and the downstream activation of the gluconeogenic pathway. Furthermore, inhibition of miR-721 in high-fat diet-induced insulin-resistant mice resulted in restoration of KDM2A levels, concomitantly reducing FOXO1, PCK1, and G6PC expression, attenuating gluconeogenesis, hyperglycemia, and improving glucose tolerance. Interestingly, the epigenetic modulator laccaic acid also reduced the hepatic miR-721 expression and improved KDM2A expression, supporting our earlier report that laccaic acid attenuates insulin resistance by reducing gluconeogenesis.

Conclusion

Our study unveils the role of miR-721 in regulating gluconeogenesis through KDM2A and FOXO1 under insulin resistance, pointing towards significant clinical and therapeutic implications for metabolic disorders. Moreover, the promising impact of laccaic acid highlights its potential as a valuable intervention in managing insulin resistance-associated metabolic diseases.

Graphical Abstract
Ghana’s path towards eliminating lymphatic filariasis
Authors: Koray Munawar Harun
Published: May 2024

Lymphatic filariasis, also known as elephantiasis, is a debilitating parasitic disease that has been prevalent in various parts of the world, including China and Ghana. This paper explores the historical context of lymphatic filariasis in Ghana and China, as well as the fights towards eliminating the disease in both countries. The review also covered the strategies employed by the Chinese government to eliminate lymphatic filariasis and the key lessons that Ghana can learn from China's success. The discussion highlights the importance of political commitment, multisectoral collaboration, tailoring control strategies to local contexts, adopting a comprehensive approach, and emphasising health education and community mobilisation. By adopting these lessons and fostering a robust national strategy, engaging diverse stakeholders, and ensuring active community involvement, Ghana can work towards achieving lymphatic filariasis elimination, improving public health, and fostering sustainable development.