bluuebunny/crossref_metadata_2025 huggingface dataset:
Experiences of participants in the co-design of a community-based health service for people with high healthcare service use
Authors: McGowan Deirdre , Morley Claire , Hansen Emily , Shaw Kelly , Winzenberg Tania
Published: March 2024

Background

Incorporating perspectives of health consumers, healthcare workers, policy makers and stakeholders through co-design is essential to design services that are fit for purpose. However, the experiences of co-design participants are poorly understood. The aim of this study is to explore the experiences and perceptions of people involved in the co-design of a new service for people with high healthcare service utilisation.

Methods

A methodology informed by the principles of grounded theory was used in this qualitative study to evaluate the experiences and perceptions of co-design participants. Participants were healthcare professionals, health managers and leaders and health consumers involved in the co-design of the new service in Tasmania, Australia. Semi-structured interviews were conducted, and data were iteratively and concurrently collected and analysed using constant comparative analysis. Audio/audio-visual recordings of interviews were transcribed verbatim. Transcripts, memos, and an audit trail were coded for experiences and perspectives of participants.

Results

There were thirteen participants (5 health professionals, 6 health managers and leaders, and 2 health consumers). Codes were collapsed into six sub-themes and six themes. Themes were bureaucracy hinders co-design, importance of consumers and diversity, importance of a common purpose, relationships are integral, participants expectations inform their co-design experience and learning from co-design.

Conclusion

Most participants reported positive aspects such as having a common purpose, valuing relationships, and having a personal motivation for participating in co-design. However, there were factors which hindered the adaptation of co-design principles and the co-design process. Our research highlights that bureaucracy can hinder co-design, that including people with lived experience is essential and the need to consider various types of diversity when assembling co-design teams. Future co-design projects could use these findings to improve the co-design experience for participants, and ultimately the outcome for communities.
Influential upregulation of KCNE4: Propelling cancer associated fibroblasts-driven colorectal cancer progression
Authors: Zhang Zizhen , Liu Shengde , Wang Zhenghang , Wang Shuo , Jiang Lei , Wang Xicheng , Li Jian , Shen Lin
Published: March 2024

Background

Colorectal cancer (CRC) is a malignancy of remarkable heterogeneity and heightened morbidity. Cancer associated fibroblasts (CAFs) are abundant in CRC tissues and are essential for CRC growth. Here, we aimed to develop a CAF-related classifier for predicting the prognosis of CRC and identify critical pro-tumorigenic genes in CAFs.

Method

The mRNA expression and clinical information of CRC samples were sourced from two comprehensive databases, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Using a weighted gene co-expression network analysis (WGCNA) approach, CAF-related genes were identified and a CAF risk signature was developed through the application of univariate analysis and the least absolute shrinkage and selection operator (LASSO) Cox regression model. EdU cell proliferation assay, and transwell assay were performed to detect the oncogenic role of KCNE4 in CAFs.

Results

We constructed a prognostic CAF model consisting of two genes (SFRP2 and KCNE4). CRC patients were classified into low- and high-CAF-risk groups using the median CAF risk score, and patients in the high-CAF-risk group had worse prognosis. Meanwhile, a higher risk score for CAFs was associated with greater stromal and CAF infiltrations, as well as higher expression of CAF markers. Furthermore, TIDE analysis indicated that patients with a high CAF risk score are less responsive to immunotherapy. Our further experiments had confirmed the strong correlation between KCNE4 and the malignant phenotypes of CAFs. Moreover, we had shown that KCNE4 could actively promote tumor-promoting phenotypes in CAFs, indicating its critical role in cancer progression.

Conclusion

The two-gene prognostic CAF signature was constructed and could be reliable for predicting prognosis for CRC patients. Moreover, KCNE4 may be a promising strategy for the development of novel anti-cancer therapeutics specifically directed against CAFs.
Roles and mechanisms of aberrant alternative splicing in melanoma — implications for targeted therapy and immunotherapy resistance
Authors: Chen Wanxian , Geng Deyi , Chen Jiasheng , Han Xiaosha , Xie Qihu , Guo Genghong , Chen Xuefen , Zhang Wancong , Tang Shijie , Zhong Xiaoping
Published: March 2024

Background

Despite advances in therapeutic strategies, resistance to immunotherapy and the off-target effects of targeted therapy have significantly weakened the benefits for patients with melanoma.

Main body

Alternative splicing plays a crucial role in transcriptional reprogramming during melanoma development. In particular, aberrant alternative splicing is involved in the efficacy of immunotherapy, targeted therapy, and melanoma metastasis. Abnormal expression of splicing factors and variants may serve as biomarkers or therapeutic targets for the diagnosis and prognosis of melanoma. Therefore, comprehensively integrating their roles and related mechanisms is essential. This review provides the first detailed summary of the splicing process in melanoma and the changes occurring in this pathway.

Conclusion

The focus of this review is to provide strategies for developing novel diagnostic biomarkers and summarize their potential to alter resistance to targeted therapies and immunotherapy.
MicroRNAs as regulators of immune checkpoints in cancer immunotherapy: targeting PD-1/PD-L1 and CTLA-4 pathways
Authors: Zabeti Touchaei Arefeh , Vahidi Sogand
Published: March 2024

Immunotherapy has revolutionized cancer treatment by harnessing the power of the immune system to eliminate tumors. Immune checkpoint inhibitors (ICIs) block negative regulatory signals that prevent T cells from attacking cancer cells. Two key ICIs target the PD-1/PD-L1 pathway, which includes programmed death-ligand 1 (PD-L1) and its receptor programmed death 1 (PD-1). Another ICI targets cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). While ICIs have demonstrated remarkable efficacy in various malignancies, only a subset of patients respond favorably. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, play a crucial role in modulating immune checkpoints, including PD-1/PD-L1 and CTLA-4. This review summarizes the latest advancements in immunotherapy, highlighting the therapeutic potential of targeting PD-1/PD-L1 and CTLA-4 immune checkpoints and the regulatory role of miRNAs in modulating these pathways. Consequently, understanding the complex interplay between miRNAs and immune checkpoints is essential for developing more effective and personalized immunotherapy strategies for cancer treatment.

Graphical Abstract
A proof-of-concept study on bioorthogonal-based pretargeting and signal amplify radiotheranostic strategy
Authors: Yang Hongzhang , Zeng Xinying , Liu Jia , Li Jingchao , Li Yun , Zhang Qinglin , Shu Linlin , Liu Huanhuan , Wang Xueqi , Liang Yuanyuan , Hu Ji , Huang Lumei , Guo Zhide , Zhang Xianzhong
Published: March 2024

Background

Radiotheranostics differs from the vast majority of other cancer therapies in its capacity for simultaneous imaging and therapy, and it is becoming more widely implemented. A balance between diagnostic and treatment requirements is essential for achieving effective radiotheranostics. Herein, we propose a proof-of-concept strategy aiming to address the profound differences in the specific requirements of the diagnosis and treatment of radiotheranostics.

Results

To validate the concept, we designed an s-tetrazine (Tz) conjugated prostate-specific membrane antigen (PSMA) ligand (DOTA-PSMA-Tz) for 68Ga or 177Lu radiolabeling and tumor radiotheranostics, a trans-cyclooctene (TCO) modified Pd@Au nanoplates (Pd@Au-PEG-TCO) for signal amplification, respectively. We then demonstrated this radiotheranostic strategy in the tumor-bearing mice with the following three-step procedures: (1) i.v. injection of the [68Ga]Ga-PSMA-Tz for diagnosis; (2) i.v. injection of the signal amplification module Pd@Au-PEG-TCO; (3) i.v. injection of the [177Lu]Lu-PSMA-Tz for therapy. Firstly, this strategy was demonstrated in 22Rv1 tumor-bearing mice via positron emission tomography (PET) imaging with [68Ga]Ga-PSMA-Tz. We observed significantly higher tumor uptake (11.5 ± 0.8%ID/g) with the injection of Pd@Au-PEG-TCO than with the injection [68Ga]Ga-PSMA-Tz alone (5.5 ± 0.9%ID/g). Furthermore, we validated this strategy through biodistribution studies of [177Lu]Lu-PSMA-Tz, with the injection of the signal amplification module, approximately five-fold higher tumor uptake of [177Lu]Lu-PSMA-Tz (24.33 ± 2.53% ID/g) was obtained when compared to [177Lu]Lu-PSMA-Tz alone (5.19 ± 0.26%ID/g) at 48 h post-injection.

Conclusion

In summary, the proposed strategy has the potential to expand the toolbox of pretargeted radiotherapy in the field of theranostics.

Graphical Abstract
ANGPTL3 is a novel HDL component that regulates HDL function
Authors: Yang Longyan , Wang Yan , Xu Yongsong , Li Kun , Yin Ruili , Zhang Lijie , Wang Di , Wei Lingling , Lang Jianan , Cheng Yanan , Wang Lu , Ke Jing , Zhao Dong
Published: March 2024

Background

Angiopoietin-like protein 3 (ANGPTL3) is secreted by hepatocytes and inhibits lipoprotein lipase and endothelial lipase activity. Previous studies reported the correlation between plasma ANGPTL3 levels and high-density lipoprotein (HDL). Recently ANGPTL3 was found to preferentially bind to HDL in healthy human circulation. Here, we examined whether ANGPTL3, as a component of HDL, modulates HDL function and affects HDL other components in human and mice with non-diabetes or type 2 diabetes mellitus.

Methods

HDL was isolated from the plasma of female non-diabetic subjects and type-2 diabetic mellitus (T2DM) patients. Immunoprecipitation, western blot, and ELISA assays were used to examine ANGPTL3 levels in HDL. Db/m and db/db mice, AAV virus mediated ANGPTL3 overexpression and knockdown models and ANGPTL3 knockout mice were used. The cholesterol efflux capacity induced by HDL was analyzed in macrophages preloaded with fluorescent cholesterol. The anti-inflammation capacity of HDL was assessed using flow cytometry to measure VCAM-1 and ICAM-1 expression levels in TNF-α-stimulated endothelial cells pretreated with HDL.

Results

ANGPTL3 was found to bind to HDL and be a component of HDL in both non-diabetic subjects and T2DM patients. Flag-ANGPTL3 was found in the HDL of transgenic mice overexpressing Flag-ANGPTL3. ANGPLT3 of HDL was positively associated with cholesterol efflux in female non-diabetic controls (r = 0.4102, p = 0.0117) but not in female T2DM patients (r = − 0.1725, p = 0.3224). Lower ANGPTL3 levels of HDL were found in diabetic (db/db) mice compared to control (db/m) mice and were associated with reduced cholesterol efflux and inhibition of VCAM-1 and ICAM-1 expression in endothelial cells (p < 0.05 for all). Following AAV-mediated ANGPTL3 cDNA transfer in db/db mice, ANGPTL3 levels were found to be increased in HDL, and corresponded to increased cholesterol efflux and decreased ICAM-1 expression. In contrast, knockdown of ANGPTL3 levels in HDL by AAV-mediated shRNA transfer led to a reduction in HDL function (p < 0.05 for both). Plasma total cholesterol, total triglycerides, HDL-c, protein components of HDL and the cholesterol efflux function of HDL were lower in ANGPTL3−/− mice than ANGPTL3+/+ mice, suggesting that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL.

Conclusion

ANGPTL3 was identified as a component of HDL in humans and mice. ANGPTL3 of HDL regulated cholesterol efflux and the anti-inflammatory functions of HDL in T2DM mice. Both the protein components of HDL and cholesterol efflux capacity of HDL were decreased in ANGPTL3−/− mice. Our findings suggest that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. Our study contributes to a more comprehensive understanding of the role of ANGPTL3 in lipid metabolism.
Exosomal circRNAs in the plasma serve as novel biomarkers for IPF diagnosis and progression prediction
Authors: Gan Wenhua , Song Wenwen , Gao Yujuan , Zheng Xuexue , Wang Fengjuan , Zhang Zirui , Zen Ke , Liang Hongwei , Yan Xin
Published: March 2024

Background

Idiopathic Pulmonary Fibrosis (IPF) is a type of chronic interstitial pneumonia, often fatal, with elusive causes and a bleak prognosis. Its treatment options are limited and largely ineffective. Early detection and precise diagnosis are pivotal in managing the disease effectively and enhancing patient survival rates. Recently, the quest for trustworthy biomarkers for IPF has gained momentum. Notably, emerging studies indicate that circular RNAs (circRNAs) found in exosomes may hold significant potential as valuable diagnostic markers.

Methods

In this study, we initially explored the expression profile of circRNAs in exosomes sourced from the blood of IPF patients and healthy volunteers, employing a human circRNA microarray. We then utilized RT-qPCR to corroborate the dysregulated circRNAs identified by the microarray during the training phase. Next, the circRNAs that displayed a significant increase during the training phase were selected for further validation in a larger cohort encompassing 113 IPF patients and 76 healthy volunteers. Ultimately, the expression level and function of hsa_circ_0044226 were substantiated through a series of in vivo and in vitro experiments.

Results

Utilizing a human circRNA microarray, we identified 11 dysregulated circRNAs in the exosomes derived from the blood of IPF patients and control volunteers. Subsequent RT-qPCR analysis revealed significant increases in three circRNAs (hsa_circ_0044226, hsa_circ_0004099, hsa_circ_0008898) within the IPF patients. Notably, hsa_circ_0044226 was markedly elevated in patients experiencing acute exacerbation of IPF (AE-IPF) compared to those with stable IPF (S-IPF). Additionally, an upregulation of hsa_circ_0044226 was observed in the blood exosomes derived from a bleomycin-induced IPF mouse model.

Conclusion

The expression levels of hsa_circ_0044226, hsa_circ_0004099, and hsa_circ_0008898 in plasma exosomes introduce a new paradigm of biomarkers for the diagnosis and progression of IPF.
Caregiver experiences and observations of intrathecal idursulfase-IT treatment in a phase 2/3 trial in pediatric patients with neuronopathic mucopolysaccharidosis II
Authors: Yee Karen S. , Lewis Sandy , Evans Emily , Romano Carla , Alexanderian David
Published: March 2024

Background

Approximately two-thirds of patients with mucopolysaccharidosis II (MPS II) have a severe, neuronopathic phenotype, characterized by somatic, cognitive, and behavioral issues. Current standard of care for the treatment of MPS II is enzyme replacement therapy with intravenous recombinant human iduronate-2-sulfatase (idursulfase). To target cognitive manifestations of MPS II, idursulfase has been formulated for intrathecal administration into the cerebrospinal fluid (idursulfase-IT). In accordance with recommendations for patient-focused drug development, semi-structured interviews were conducted to assess caregiver experiences and observations in a 52-week phase 2/3 trial of idursulfase-IT, in addition to intravenous idursulfase in pediatric patients with neuronopathic MPS II, or a substudy which enrolled patients younger than 3 years old, all of whom received idursulfase-IT.

Results

Overall, 46 caregivers providing care for 50 children (mean [range] age 7.9 [3–17] years at interview) took part in a single 60-min exit interview; six of these children had participated in the substudy. Qualitative and quantitative data were obtained demonstrating the burden of MPS II experienced by caregivers and their families. Following participation in the trials, 39 (78%) of the children were reported by their caregivers to have experienced improvements in the symptoms and impact of disease. Of those with improvements, 37 (95%) experienced cognitive improvements and 26 (67%) experienced emotional/behavioral improvements. Overall, 43 children (86%) were rated by caregivers as having moderate or severe symptoms before the trials; after the trials, 28 children (56%) were considered to have mild or no symptoms. For the six children who participated in the substudy, these proportions were 83% and 100%, respectively. Caregivers’ qualitative descriptions of trial experiences suggested improvements in children’s verbal and non-verbal functioning and spatial and motor skills, as well as a positive impact on family life.

Conclusions

This study revealed caregiver-reported improvements in children’s MPS II symptoms and the impact of the disease on patients and their families. There was a trend for cognitive improvement and a reduction in severity of MPS II symptoms. After many years of extensive review and regulatory discussions of idursulfase-IT, the clinical trial data were found to be insufficient to meet the evidentiary standard to support regulatory filings.
Neurobehavioral and developmental profiles: genotype–phenotype correlations in individuals with Cornelia de Lange syndrome
Authors: Ng Rowena , O’Connor Julia , Summa Deirdre , Kline Antonie D.
Published: March 2024

Background

Cornelia de Lange (CdLS) is a rare genetic disorder that affects most body systems. Variants in multiple genes including NIPBL and SMC1A, can cause the syndrome. To date, literature on genotype–phenotype associations in individuals with CdLS is extremely limited, although studies suggest some differences in clinical phenotype severity across variants. This study aimed to examine and compare neurobehavioral differences and developmental variability across CdLS genes, specifically NIPBL and SMC1A, and identify genotype–phenotype correlations.

Participants and methods

This patient-reported outcomes study included accessing data from the Coordination of Rare Diseases registry at Sanford. Parents of a total of 26 children/adults with CdLS and a known variant in NIPBL (Mean age = 20.46 years, SD = 11.21) and 12 with a known variant in SMC1A (Mean age = 11.08 years, SD = 9.04) completed a series of questionnaires regarding their child’s developmental history. This included attainment of common language and motor milestones, intervention history, and behavior functioning. Developmental history and reported behavior regulation difficulties were compared across variant groups.

Results

Overall, individuals with a pathogenic variant in NIPBL or SMC1A were similarly delayed across motor and language milestones with about 70% not using phrase speech and 30–50% not walking by 5 years of age. However, those with NIPBL variants showed more severity in behavioral phenotype, namely with more repetitive behaviors, tantrums, and withdrawn behaviors. In addition, these individuals were more likely than those with SMC1A variants to demonstrate self-injurious behaviors, and anxiety. Both groups yielded a similar proportion of participants who participated in speech and occupational therapy, however those with SMC1A variants were more likely to engage in physical therapy. Both clinical groups report low rate of communicative or assistive device use despite a large proportion of participants never mastering single word or sentence use.

Conclusions

Study results are consistent with recent investigations highlighting more severe behavioral phenotype, particularly autistic features, anxiety, and behavior regulation challenges, among those with NIPBL variants albeit comparable developmental milestones. Both groups endorsed very elevated attention problems. Findings highlight importance of early interventions, including behavioral health services.
MAL expression downregulation through suppressive H3K27me3 marks at the promoter in HPV16-related cervical cancers is prognostically relevant and manifested by the interplay of novel MAL antisense long noncoding RNA AC103563.8, E7 oncoprotein and EZH2
Authors: Sinha Abarna , Ghosh Abhisikta , Ghosh Arnab , Mathai Sonia , Bhaumik Jaydip , Mukhopadhyay Asima , Maitra Arindam , Biswas Nidhan K. , Sengupta Sharmila
Published: March 2024

Background

MAL (T-lymphocyte maturation-associated protein) is highly downregulated in most cancers, including cervical cancer (CaCx), attributable to promoter hypermethylation. Long noncoding RNA genes (lncGs) play pivotal roles in CaCx pathogenesis, by interacting with human papillomavirus (HPV)-encoded oncoproteins, and epigenetically regulating coding gene expression. Hence, we attempted to decipher the impact and underlying mechanisms of MAL downregulation in HPV16-related CaCx pathogenesis, by interrogating the interactive roles of MAL antisense lncRNA AC103563.8, E7 oncoprotein and PRC2 complex protein, EZH2.

Results

Employing strand-specific RNA-sequencing, we confirmed the downregulated expression of MAL in association with poor overall survival of CaCx patients bearing HPV16, along with its antisense long noncoding RNA (lncRNA) AC103563.8. The strength of positive correlation between MAL and AC103563.8 was significantly high among patients compared to normal individuals. While downregulated expression of MAL was significantly associated with poor overall survival of CaCx patients bearing HPV16, AC103563.8 did not reveal any such association. We confirmed the enrichment of chromatin suppressive mark, H3K27me3 at MAL promoter, using ChIP-qPCR in HPV16-positive SiHa cells. Subsequent E7 knockdown in such cells significantly increased MAL expression, concomitant with decreased EZH2 expression and H3K27me3 marks at MAL promoter. In silico analysis revealed that both E7 and EZH2 bear the potential of interacting with AC103563.8, at the same binding domain. RNA immunoprecipitation with anti-EZH2 and anti-E7 antibodies, respectively, and subsequent quantitative PCR analysis in E7-silenced and unperturbed SiHa cells confirmed the interaction of AC103563.8 with EZH2 and E7, respectively. Apparently, AC103563.8 seems to preclude EZH2 and bind with E7, failing to block EZH2 function in patients. Thereby, enhanced EZH2 expression in the presence of E7 could potentially inactivate the MAL promoter through H3K27me3 marks, corroborating our previous results of MAL expression downregulation in patients.

Conclusion

AC103563.8-E7-EZH2 axis, therefore, appears to crucially regulate the expression of MAL, through chromatin inactivation in HPV16-CaCx pathogenesis, warranting therapeutic strategy development.
A gene signature linked to fibroblast differentiation for prognostic prediction of mesothelioma
Authors: Liu Jun , Lu Yuwei , Liu Yifan , Zhang Wei , Xian Shuyuan , Wang Siqiao , Zheng Zixuan , Lin Ruoyi , Jin Minghao , Zhang Mengyi , Qian Weijin , Tang Jieling , Lu Bingnan , Yang Yiting , Liu Zichang , Qu Mingyu , Ma Haonan , Wu Xinru , Chang Zhengyan , Zhang Jie , Zhang Yuan
Published: March 2024

Background

Malignant mesothelioma is a type of infrequent tumor that is substantially related to asbestos exposure and has a terrible prognosis. We tried to produce a fibroblast differentiation-related gene set for creating a novel classification and prognostic prediction model of MESO.

Method

Three databases, including NCBI-GEO, TCGA, and MET-500, separately provide single-cell RNA sequencing data, bulk RNA sequencing profiles of MESO, and RNA sequencing information on bone metastatic tumors. Dimensionality reduction and clustering analysis were leveraged to acquire fibroblast subtypes in the MESO microenvironment. The fibroblast differentiation-related genes (FDGs), which were associated with survival and subsequently utilized to generate the MESO categorization and prognostic prediction model, were selected in combination with pseudotime analysis and survival information from the TCGA database. Then, regulatory network was constructed for each MESO subtype, and candidate inhibitors were predicted. Clinical specimens were collected for further validation.

Result

A total of six fibroblast subtypes, three differentiation states, and 39 FDGs were identified. Based on the expression level of FDGs, three MESO subtypes were distinguished in the fibroblast differentiation-based classification (FDBC). In the multivariate prognostic prediction model, the risk score that was dependent on the expression level of several important FDGs, was verified to be an independently effective prognostic factor and worked well in internal cohorts. Finally, we predicted 24 potential drugs for the treatment of MESO. Moreover, immunohistochemical staining and statistical analysis provided further validation.

Conclusion

Fibroblast differentiation-related genes (FDGs), especially those in low-differentiation states, might participate in the proliferation and invasion of MESO. Hopefully, the raised clinical subtyping of MESO would provide references for clinical practitioners.
Membrane-associated RING-CH 7 inhibits stem-like capacities of bladder cancer cells by interacting with nucleotide-binding oligomerization domain containing 1
Authors: Zhuang Junlong , Zhang Lingli , Zhang Siyuan , Zhang Zhongqing , Xie Tianlei , Zhao Wei , Liu Yantao
Published: March 2024

Background

Cancer stem-like capacities are major factors contributing to unfavorable prognosis. However, the associated molecular mechanisms underlying cancer stem-like cells (CSCs) maintain remain unclear. This study aimed to investigate the role of the ubiquitin E3 ligase membrane-associated RING-CH 7 (MARCH7) in bladder cancer cell CSCs.

Methods

Male BALB/c nude mice aged 4–5 weeks were utilized to generate bladder xenograft model. The expression levels of MARCHs were checked in online databases and our collected bladder tumors by quantitative real-time PCR (q-PCR) and immunohistochemistry (IHC). Next, we evaluated the stem-like capacities of bladder cancer cells with knockdown or overexpression of MARCH7 by assessing their spheroid-forming ability and spheroid size. Additionally, we conducted proliferation, colony formation, and transwell assays to validate the effects of MARCH7 on bladder cancer CSCs. The detailed molecular mechanism of MARCH7/NOD1 was validated by immunoprecipitation, dual luciferase, and in vitro ubiquitination assays. Co-immunoprecipitation experiments revealed that nucleotide-binding oligomerization domain-containing 1 (NOD1) is a substrate of MARCH7.

Results

We found that MARCH7 interacts with NOD1, leading to the ubiquitin–proteasome degradation of NOD1. Furthermore, our data suggest that NOD1 significantly enhances stem-like capacities such as proliferation and invasion abilities. The overexpressed MARCH7 counteracts the effects of NOD1 on bladder cancer CSCs in both in vivo and in vitro models.

Conclusion

Our findings indicate that MARCH7 functions as a tumor suppressor and inhibits the stem-like capacities of bladder tumor cells by promoting the ubiquitin–proteasome degradation of NOD1. Targeting the MARCH7/NOD1 pathway could be a promising therapeutic strategy for bladder cancer patients.
A scalable and cost-efficient rRNA depletion approach to enrich RNAs for molecular biology investigations
Authors: Singh Amrita , Xue Amy , Tai Justin , Mbadugha Faith , Obi Prisca , Mascarenhas Romario , Tyagi Antariksh , Siena Adamo , Chen Y. Grace
Published: March 2024

Transcriptomics analyses play pivotal roles in understanding the complex regulatory networks that govern cellular processes. The abundance of rRNAs, which account for 80-90% of total RNA in eukaryotes, limits the detection and investigation of other transcripts. While mRNAs and long non-coding RNAs have polyA(+) tails that are often used for positive selection, investigations of polyA(-) RNAs, such as circular RNAs, histone mRNAs, and small RNAs, typically require the removal of the abundant rRNAs for enrichment. Current approaches to deplete rRNAs for downstream molecular biology investigations are hampered by restrictive RNA input masses and high cost. To address these challenges, we developed rRNA Removal by RNase H (rRRR), a method to efficiently deplete rRNA from a wide range of human, mouse, and rat RNA inputs and qualities at a cost 10-20-fold cheaper than other approaches. We employed probe-based hybridization and enzymatic digestion to selectively target and remove rRNA molecules while preserving the integrity of non-rRNA transcripts. Comparison between rRRR to two commercially available approaches found that they had similar efficiencies at depleting rRNAs and comparable off-target effects. Our developed method provides researchers with a valuable tool for investigating gene expression and regulatory mechanisms across a wide range of biological systems at an affordable price that increases the accessibility for researchers to enter the field, ultimately advancing our understanding of cellular processes.
Najstarsze miasto rycerzy zakonu krzyżackiego w Ziemi Chełmińskiej. Nowe źródła i perspektywy badań trzynastowiecznego Chełmna
Authors: Wiewióra Marcin , Momot Agata
Published: March 2024

W artykule omówiono wyniki najnowszych badań archeologicznych przeprowadzonych w 2022 r. w Starogrodzie – najstarszym mieście rycerzy zakonu krzyżackiego w ziemi chełmińskiej. W 2017 r. w trakcie realizacji projektu Castra Terrae Culmensis, podczas badań nieinwazyjnych na terenie niewielkiej wsi dokonano niezwykłego odkrycia – zarejestrowano wyraźne anomalie magnetyczne, będące pozostałością dawnej zabudowy. Przeprowadzone dwukrotnie prace wykopaliskowe, w 2018 i 2022 r. potwierdziły, że jest to zaginione, najstarsze miasto rycerzy zakonu krzyżackiego, założone w 1232. r. Badania nieinwazyjne oraz prospekcja LIDAR, zrealizowana w latach 2016-2017, potwierdził przekazy kronikarskie Piotra z Dusburga. Unikatowy obiekt składa się z zachowanego układu przestrzennego planowanego miasta, reliktów budynków wraz z zawartością materialną. Celem badań jest podjęcie kompleksowych, interdyscyplinarnych studiów nad najstarszą fazą urbanizacji ziemi chełmińskiej, rekonstrukcja kultury materialnej mieszkańców, rozpoznanie układu przestrzennego miasta, powstającego tuż obok drewniano-ziemnych fortyfikacji, a także znaczenia napływu nowych idei wraz z osadnikami przybywającymi z terenów dzisiejszych Niemiec i Śląska.
Dłubanka z jeziora Mełno, pow. grudziądzki
Authors: Kurzyńska Małgorzata
Published: March 2024

Pod koniec 1984 roku w jeziorze Mełno na terenie powiatu grudziądzkiego zlokalizowano łódź jednopienną. Informacje o odkryciu pojawiły się w prasie lokalnej i centralnej, ale nie znalazły się w obiegu naukowym. W tym samym jeziorze, ale na początku lat 90. XX wieku, Koło Naukowe Instytutu Archeologii i Etnologii UMK w Toruniu zarejestrowało łódź przy zachodnim brzegu półwyspu w Boguszewie, na którym znajduje się grodzisko łużyckie. Wzmiankę o tym odkryciu zamieścili Leszek Kucharski, badacz wspomnianego grodziska, oraz Waldemar Ossowski zajmujący się badaniem łodzi jednopiennych z terenówPolski.
55 lat od wydania pierwszego tomu uniwersyteckiej „Archeologii”
Authors: Gackowski Jacek , Markiewicz Małgorzata
Published: March 2024

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EFL students’ strategies in learning grammar online
Authors: Irdani Nadya , Fatimah Nur , Triyoga Arilia
Published: March 2024

Students' learning strategies are part of teaching and learning success concerns, including in the online grammar class. The research objectives are to describe students' strategies in learning grammar through online grammar classes and to find out the students' problems and solutions in learning grammar online. This research is mixed-method where the data are collected through questionnaires and interviews. One hundred twenty-three students completed the questionnaire, and twelve students were involved in the interview sessions. All respondents are from the English Education Department. The result shows that the students used all learning strategies; memory, cognitive, compensation, metacognitive, affective, and social strategies). However, the highest percentage of the learning strategy employed by the students is cognitive strategies (18.30%), while the least is affective strategies (14.76%). Moreover, students learning grammar online face various problems; an unstable internet connection, having no friends to practice together, difficulty in vocabulary, the lecturer's teaching methods, and punctuality issues.
Considerações decoloniais sobre a opressão sistêmica aos corpos dissidentes na música da Belle Époque de Fortaleza
Authors: Rios Martins Ana Luiza , Fernandes Emílio Albuquerque
Published: March 2024

Este artigo tem como objetivo debater a opressão sistêmica aos corpos dissidentes por meio da disseminação da ideia de cultura popular propagada na música da Belle Époque de Fortaleza. Acreditamos que essa prática se configura como uma forma de silenciamento mais sofisticada vinculada à colonialidade do poder, que passa pelo processo de julgamento e tentativa de tutela do outro para destituí-lo de um locus próprio de enunciação e de autoridade epistêmica para a elaboração de suas próprias experiências históricas. Usamos como referências as músicas que foram registradas em partituras e discos de 78 rpm dos acervos de Miguel Ângelo de Azevedo e da Banda de Música da Polícia Militar do Ceará; correspondências, livros de música, coletâneas de crônicas e periódicos. Compreendemos, antes de mais nada, a Belle Époque como um discurso que opera dentro da lógica da colonialidade, impondo um padrão de dominação desenvolvido pela modernidade que, por sua vez, incide na realidade dos corpos colocados em dissidência em relação às estruturas de poder. Nesse sentido, refletimos sobre essas questões com base no pensamento decolonial. Acreditamos que esse tipo de análise funciona como uma provocação que tenciona e enriquece a nossa agenda de problemas da Teoria da História e da História da Historiografia.
Guided implant surgery: principles and practice
Authors: Javed Faizan , Hindu Karshma Devi , Ghafoor Robia
Published: March 2024

For dentists who were trained without computers and planning software, the introduction of any sort of digital technology can be met with reservation. Clinicians had to weigh the benefits of a new technique versus the cost and time involved in making it an effective investment. In low- and middle-income countries, the introduction of guided implant surgery is still in a nascent state. The procedures that fall into this category merge patients' data, both clinical and radiographic, to better visualize and guide access to the target site. Guided implant surgery is a minimally invasive, reproducible technique that substantially reduces the risk of injuring critical anatomical structures. Previously published data on guided implant surgery are limited and contain outdated methodology. In this review, the authors introduce the benefits, general principles and updated clinical workflow for guided dental implant surgery.

CPD/Clinical Relevance: Guided implant surgery is a reproducible technique that results in predictable implant placement.
The impact of COVID-19 on trial participants' engagement with IBD-BOOST: a digital cognitive behavioural intervention
Authors: Honzlova Zora , Stagg Imogen , Miller Laura , Norton Christine , Moss-Morris Rona , Sweeney Louise , Wileman Vari
Published: March 2024

Background/Aims:

The COVID-19 pandemic coincided with a randomised-controlled trial of an online-supported self-management intervention for fatigue, pain and urgency in inflammatory bowel disease (IBD). The aim of the present study was to investigate how the pandemic affected engagement with the IBD-BOOST programme.

Methods:

Intervention participants were invited to complete an online survey at 6-month follow-up, including both pre-defined and open-ended questions. A mixed methods quantitative and qualitative analyses were conducted. People who had participated in the online intervention (n= 354) were invited to answer questions about the impact of COVID-19 on their ability to engage with the online intervention

Results:

A total of 171 (48.31%) responded to the survey, with their experiences of the pandemic encompassing both negative and positive impacts on their engagement, as well as those who felt that the pandemic had no impact. For those who reported negative impact (19.30%): the pandemic created additional work and home-life responsibilities, the pandemic-induced emotional and psychological burden contributed to decreased participation, and engagement was reduced due to direct COVID-19 infection. For those who reported a positive impact (9.94%): the pandemic allowed for increased time availability due to pandemic-induced lifestyle changes. For those who felt the pandemic had no impact (50.29%): adaptability helped to maintain their engagement. The remaining 20.47% of participants reported that they were uncertain, or that their involvement varied.

Conclusion:

For some participants, the pandemic negatively impacted their engagement. However, 60% reported that the pandemic had either no or a positive impact on their engagement with IBD-BOOST, indicating the resilience of online delivery of behavioural interventions.
Eski Türkler Yemek Çubukları Kullanıyor muydu?
Authors: KARADAVUT Arda
Published: March 2024

MS I. yüzyıldan itibaren Çin’de buğdayın daha çok tüketilmesi, buğdaydan elde edilen erişte, makarna, mantı gibi yiyeceklerin çeşitlenmesi ve bunları kaşıkla yemenin zor olması yemek çubuklarının kullanım alanlarını genişletmiştir. III. yüzyılda değirmen taşının sadece buğday öğütmede kullanılan bir alet olmadığını fark eden Çinliler kanolayı da öğütüp yağını elde etmişlerdir. Kanola yağının elde edilmesiyle yeni bir pişirme yöntemi ortaya çıkmıştır: Kızartma. Yağda kızartılan yiyecekler lokma büyüklüğünde kesildiğinden bunların yemek çubuklarıyla yenmesi daha da kolaylaşmış ve çubuk kullanımı zaman içerisinde gittikçe artış göstermiştir. Bugün Asya’nın her yerinde bulunan yemek çubukları özellikle Uzak Doğu’da önemli kültürel değere sahiptir. Günümüzde Çin’e yakın coğrafyalarda ve Çin sınırları içerisinde yer alan Uygurlar ve Salarlar gibi Türk boylarının da yemek çubukları kullandıkları bilinmektedir. Bu durum, beraberinde “eski Türkler yemek çubukları kullanıyor muydu?” sorusunu sordurmaktadır. Kullanmışlarsa yemek çubuklarını hangi sözcükle ifade etmişlerdir? Bu sözcük Türkçe kökenli midir yoksa alıntı bir sözcük müdür? Yemek çubuklarının herhangi bir kültürel değeri var mıdır? Bu çalışmada bu soruların cevabı aranacaktır.
Sharing Experiences in Selecting Clinical Outcome and Approving Validated Questionnaires : Insights from an Elderly Registry Study
Authors: Cho Nahyun , Jun Hyungsun , Ha Won-Bae , Lee Junghan , Ko Mi Mi , Kim Young-Eun , Jung Jeeyoun , Leem Jungtae
Published: March 2024

Objectives: Underpinned by the context of a Korean traditional medicine cohort study on healthy aging, this research primarily aims to guide the selection of Clinical Outcome Assessments (COAs) for elderly healthy aging patient registry research, offering insights into the selection process; and secondly, to streamline the resource-intensive process of obtaining permissions for validated COAs, benefiting future traditional Korean medicine clinical researchers.Methods : In this study, we identified outcomes through a review of previous studies, followed by a process involving expert consultations to select the final outcomes. Subsequently, for the selected outcomes that were Clinical Outcome Assessments (COAs) developed tools, we searched in commercial databases to confirm the availability of Korean versions and the necessity of obtaining permissions. Finally, we obtained permissions for their utilization and, when needed, acquired the original instrument questionnaire through payment.Results: Through a literature review of existing observational studies, a total of 57 outcomes were selected, with 19 of them identified as COA instruments. Upon verifying usage permissions for these 19 instruments, it was found that 17 required author-specific permissions, and among these, 2 needed a purchase as they were commercially available.Conclusion: This study provides a detailed overview of outcome selection and permission acquisition for elderly patient registry research. It underscores the importance of Clinical Outcome Assessment (COA) tools and the rigorous approval process, aiming to enhance research reliability. Continuous verification of COA information is essential, and future research should explore Core Outcome Set (COS) development through consensus-building approaches like Delphi studies.
The Effect of Laser Therapy for Stroke Patients : A Systematic Review and Meta-analysis
Authors: An Da-young , Sun Seung-ho
Published: March 2024

Objectives: This study is purposed to investigate the effect and safety of laser therapy for stroke patients by systematic review and meta-analysis of the randomized controlled trials (RCTs).Methods: RCTs on the treatment of laser therapy for stroke patients were selected among the literature published from January 2000 to June 2022 in twelve domestic and foreign databases. The quality of the literature was evaluated using the Cochrane's Risk of Bias tool and RevMan 5.4 was used for the synthesis of results.Results: Total 2,598 patients with stroke were finally selected from 18 RCTs. Meta-analysis showed that laser therapy was effective in significantly improving activities of daily living (MBI), motor function (effective rate), upper motor function (FMA-UE), shoulder pain related factors (CGRP, ET-1, BK). Overall, the risk of bias was uncertain or low in the quality assessment of the literature.Conclusions: Although it is unclear that laser therapy is more effective than sham laser, laser therapy might be more effective in improving symptoms than conventional rehabilitation alone. Furthermore, no serious adverse events were founded in laser therapy studies. However, the quality of the selected literature was generally low. Therefore, further studies with high methodological quality on laser therapy for stroke patients would be required in the future.
Gamitaeeumjowee-tang for Weight Loss in Post-Menopausal Obese Women: A Retrospective Chart Review
Authors: Lee Yun-Jin , Kang Jeong-In , Kim Yun-Ha , Min Eun-Chae , Lim Young-Woo , Kim Eunjoo
Published: March 2024

Objectives: The purpose of this study is to evaluate weight change and analyze adverse events in post-menopausal obese women with Gamitaeeumjowee-tang for weight loss.Methods: A retrospective chart review was conducted for medical records of 115 post-menopausal obese women (body mass index, BMI≥25 kg/m2) who were administered with Gamitaeeumjowee-tang for 12 weeks for the purpose of weight loss. Weight, skeletal muscle ratio and BMI changes were compared before and after the program. Adverse events were evaluated by causality, severity and system-organ classes.Results: A total of 115 patients were included in this study. The average total weight loss in post-menopausal women was 5.72±2.04kg(p<0.001) and the average weight loss rate was 8.06±2.70%(p<0.001). After the 12-week program, the body fat rate was significantly decreased(3.76±2.20%)(p<0.001) and the skeletal muscle ratio was significantly increased(2.07±1.24%)(p<0.001). There were no significant differences in weight loss, skeletal muscle ratio change and body fat rate change depending on the number of hospital visits. Insomnia was frequently reported throughout the period, and no serious adverse events were reported.Conclusions: This study showed the potential that weight management treatment with Gamitaeeumjowee-tang could be a good way to lose weight of post-menopausal obese women without serious adverse events. Continuous well designed clinical studies are needed.
Network pharmacology-based prediction of efficacy and mechanism of Myrrha acting on Allergic Rhinitis
Authors: Lim Yebin , Kweon Bitna , Kim Dong-Uk , Bae Gi-Sang
Published: March 2024

Objectives: Network pharmacology is an analysis method that explores drug-centered efficacy and mechanism by constructing a compound-target-disease network based on system biology, and is attracting attention as a methodology for studying herbal medicine that has the characteristics for multi-compound therapeutics. Thus, we investigated the potential functions and pathways of Myrrha on Allergic Rhinitis (AR) via network pharmacology analysis and molecular docking.Methods: Using public databases and PubChem database, compounds of Myrrha and their target genes were collected. The putative target genes of Myrrha and known target genes of AR were compared and found the correlation. Then, the network was constructed using STRING database, and functional enrichment analysis was conducted based on the Gene Ontology (GO) Biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways. Binding-Docking stimulation was performed using CB-Dock.Results: The result showed that total 3 compounds and 55 related genes were gathered from Myrrha. 33 genes were interacted with AR gene set, suggesting that the effects of Myrrha are closely related to AR. Target genes of Myrrha are considerably associated with various pathways including ‘Fc epsilon RI signaling pathway’ and ‘JAK-STAT signaling pathway’. As a result of blinding docking, AKT1, which is involved in both mechanisms, had high binding energies for abietic acid and dehydroabietic acid, which are components of Myrrha.Conclusion: Through a network pharmacological method, Myrrha was predicted to have high relevance with AR by regulating AKT1. This study could be used as a basis for studying therapeutic effects of Myrrha on AR.
The Potential of Yangdorak Diagnosis Application of Gallstone
Authors: Han Gyu Eon
Published: March 2024

Objectives: The aim of the study was to investigate the potential of Yangdorak diagnosis application against gallstone scanned by Ultrasound diagnosis.Method: For this aim, among 97 patients who had visited Julip Korean Medicine Clinic from July 2016 to June 2023, 30 patients with no gallstone as a control group and 67 patients with gallstone and diagnosed by ultrasonography, were subjected to Yangdorak diagnosis. Then, the changes in Gallbladder Meridian (GB) value as F5 AVE(average of left and right GB value) by Yangdorak were comparatively analyzed between gallstone and non-gallstone groups and statistical significance was evaluated by Tukey's multiple comparison test using Prism software.Results: After all subjects were evaluated by the Yangdorak and ultrasonography to assess the potential of the Yangdorak diagnosis for gallstone, it was noteworthy that the Yangdorak values relevant to F5 AVE of female gallstone group(N=36) were significantly (p<0.001) decreased compared to the control group (N=30), while there was no significance in male gallstone group(N=31). Also, it was recognized significant difference between male and female groups.Conclusion: Based on these results, if the Yangdorak value can be estimated from a decrease with clinical symptom in female patient, it is recommended to follow up the ultrasonography test for diagnosing the gallstone.