bluuebunny/crossref_metadata_2025 huggingface dataset:
CAIXAS DE LEITE DE DIFERENTES TIPOS: ENSINANDO VOLUME E ÁREA DE SUPERFÍCIE DE UM PRISMA POR MEIO DE RESOLUÇÃO DE PROBLEMAS
Authors: Hoffmann Luciane Cristina Joenk , Silva Viviane Clotilde
Published: May 2023

O objetivo deste estudo é relatar uma experiência desenvolvida por meio da metodologia de Ensino-Aprendizagem-Avaliação de Matemática através da Resolução de Problemas, de modo a possibilitar o desenvolvimento de uma aprendizagem com compreensão da Matemática em uma prática que envolve o cálculo de medidas de volume e superfície de um prisma, com estudantes do 7° ano do Ensino Fundamental. Ela fez parte de uma pesquisa de mestrado, de modo que foi realizada uma análise qualitativa, com base na observação participante e no diário de campo da professora pesquisadora, registros escritos dos estudantes com a resolução da atividade, seus depoimentos e registros feitos por meio de gravações de áudio e fotografias. Os resultados mostraram que a resolução do problema apresentado por meio dessa metodologia possibilitou que os estudantes compreendessem melhor os conceitos de capacidade, volume e área de superfície de prismas e analisassem qual das formas seria mais vantajosa (lucrativa) considerando apenas a matéria prima utilizada. Além disso, contribuiu para o desenvolvimento da criatividade dos estudantes e, propiciou que a professora pesquisadora analisasse as estratégias de resolução dos estudantes durante o processo e verificasse a compreensão dos conceitos envolvidos e sua importância para essa situação prática.
Proteomic analysis of urinary extracellular vesicles highlights specific signatures for patients with primary aldosteronism
Authors: Bertolone Lorenzo , Castagna Annalisa , Manfredi Marcello , De Santis Domenica , Ambrosani Francesca , Antinori Elisa , Mulatero Paolo , Danese Elisa , Marengo Emilio , Barberis Elettra , Veneri Mariangela , Martinelli Nicola , Friso Simonetta , Pizzolo Francesca , Olivieri Oliviero
Published: May 2023

Background

Urinary extracellular vesicles (uEVs) can be released by different cell types facing the urogenital tract and are involved in cellular trafficking, differentiation and survival. UEVs can be easily detected in urine and provide pathophysiological information “in vivo” without the need of a biopsy. Based on these premises, we hypothesized that uEVs proteomic profile may serve as a valuable tool in the differential characterization between Essential Hypertension (EH) and primary aldosteronism (PA).

Methods

Patients with essential hypertension (EH) and PA were enrolled in the study (EH= 12, PA=24: 11 Bilateral Primary Aldosteronism subtype (BPA) and 13 Aldosterone Producing Adenoma (APA)). Clinical and biochemical parameters were available for all the subjects. UEVs were isolated from urine by ultracentrifugation and analysed by Transmission Electron Microscopy (TEM) and nanotrack particle analysis (NTA). UEVs protein content was investigated through an untargeted MS-based approach. Statistical and network analysis was performed to identify potential candidates for the identification and classification of PA.

Results

MS analysis provided more than 300 protein identifications. Exosomal markers CD9 and CD63 were detected in all samples. Several molecules characterizing EH vs PA patients as well as BPA and APA subtypes were identified after statistical elaboration and filtering of the results. In particular, some key proteins involved in water reabsorption mechanisms, such as AQP1 and AQP2, were among the best candidates for discriminating EH vs PA, as well as A1AG1 (AGP1).

Conclusion

Through this proteomic approach, we identified uEVs molecular indicators that can improve PA characterization and help in the gain of insights of the pathophysiological features of this disease. In particular, PA was characterized by a reduction of AQP1 and AQP2 expression as compared with EH.
Transcriptomic changes in liver transplant recipients with non-alcoholic steatohepatitis indicate dysregulation of wound healing
Authors: Pellegrina Diogo , Prayitno Khairunnadiya , Azhie Amirhossein , Pasini Elisa , Baciu Cristina , Fischer Sandra , Reimand Jüri , Bhat Mamatha
Published: May 2023

Background

Non-alcoholic steatohepatitis (NASH) has become a leading indication for liver transplantation. However, it often recurs in the graft and can also arise de novo in individuals transplanted for other indications. Post-transplant NASH (PT-NASH) is more aggressive and leads to accelerated fibrosis. The mechanistic basis of PT-NASH has not yet been defined and no specific therapeutic strategies are currently available.

Methods

Here, we profiled the transcriptomes of livers with PT-NASH from liver transplant recipients to identify dysregulated genes, pathways, and molecular interaction networks.

Results

Transcriptomic changes in the PI3K-Akt pathway were observed in association with metabolic alterations in PT-NASH. Other significant changes in gene expression were associated with DNA replication, cell cycle, extracellular matrix organization, and wound healing. A systematic comparison with non-transplant NASH (NT-NASH) liver transcriptomes indicated an increased activation of wound healing and angiogenesis pathways in the post-transplant condition.

Conclusion

Beyond altered lipid metabolism, dysregulation of wound healing and tissue repair mechanisms may contribute to the accelerated development of fibrosis associated with PT-NASH. This presents an attractive therapeutic avenue to explore for PT-NASH to optimize the benefit and survival of the graft.
Animal models of the placenta accreta spectrum: current status and further perspectives
Authors: Ma Yongdan , Hu Yongyan , Ma Jingmei
Published: May 2023

Placenta accreta spectrum disorder (PAS) is a kind of disease of placentation defined as abnormal trophoblast invasion of part or all of the placenta into the myometrium, even penetrating the uterus. Decidual deficiency, abnormal vascular remodeling in the maternal–fetal interface, and excessive invasion by extravillous trophoblast (EVT) cells contribute to its onset. However, the mechanisms and signaling pathways underlying such phenotypes are not fully understood, partly due to the lack of suitable experimental animal models. Appropriate animal models will facilitate the comprehensive and systematic elucidation of the pathogenesis of PAS. Due to the remarkably similar functional placental villous units and hemochorial placentation to humans, the current animal models of PAS are based on mice. There are various mouse models induced by uterine surgery to simulate different phenotypes of PAS, such as excessive invasion of EVT or immune disturbance at the maternal–fetal interface, which could define the pathological mechanism of PAS from the perspective of the “soil.” Additionally, genetically modified mouse models could be used to study PAS, which is helpful to exploring the pathogenesis of PAS from the perspectives of both “soil” and “seed,” respectively. This review details early placental development in mice, with a focus on the approaches of PAS modeling. Additionally, the strengths, limitations and the applicability of each strategy and further perspectives are summarized to provide the theoretical foundation for researchers to select appropriate animal models for various research purposes. This will help better determine the pathogenesis of PAS and even promote possible therapy.
Analysis of mRNA-miRNA-lncRNA differential expression in prediabetes/type 2 diabetes mellitus patients as potential players in insulin resistance
Authors: Ali Hebatalla Said , Kamel Marwa Mostafa , Agwa Sara H. A. , Hakeem Mohamed S. Abdel , Meteini Mahmoud Shawky El , Matboli Marwa
Published: May 2023

Introduction

Type 2 diabetes mellitus (T2DM) is a major global health concern. It usually develops gradually and is frequently preceded by undetectable pre-diabetes mellitus (pre-DM) stage. The purpose of this study was to identify a novel set of seven candidate genes associated with the pathogenesis of insulin resistance (IR) and pre-DM, followed by their experimental validation in patients’ serum samples.

Methods

We used the bioinformatics tools and through a two-step process, we first identified and verified two mRNA candidate genes linked to insulin resistance molecular pathogenesis. Second, we identified a non-coding RNAs related to the selected mRNAs and implicated in the insulin resistance molecular pathways followed by pilot study for the RNA panel differential expression in 66 patients with T2DM, 49 individuals with prediabetes and 45 matched controls using real time PCR.

Results

The levels of expression of TMEM173 and CHUK mRNAs, hsa-miR (-611, -5192, and -1976) miRNAs gradually increased from the healthy control group to the prediabetic group, reaching their maximum levels in the T2DM group (p <10-3), whereas the levels of expression of RP4-605O3.4 and AC074117.2 lncRNAs declined gradually from the healthy control group to the prediabetic group, reaching their lowest levels in the T2DM group (p <10-3). TMEM173, CHUK mRNAs, hsa_miR (-611 & -1976) and RP4-605O3.4 lncRNA were useful in distinguishing insulin resistant from insulin sensitive groups. miR_611 together with RP4-605O3.4 exhibited significant difference in good versus poor glycemic control groups.

Discussion

The presented study provides an insight about this RNA based STING/NOD/IR associated panel that could be used for PreDM-T2DM diagnosis and also as a therapeutic target based on the differences of its expression level in the pre-DM and T2DM stages.
Mendelian randomization indicates a causal contribution of type 2 diabetes to retinal vein occlusion
Authors: Huang Jian
Published: May 2023

Background

Retinal vein occlusion (RVO) is a common retinal vascular disease that can cause severe visual impairment. Many observational studies have shown that type 2 diabetes (T2DM) is associated with RVO, but it remains unknown if the association is causal. The present study aimed to perform Mendelian randomization (MR) analyses to evaluate the causal contribution of genetically predicted T2DM to RVO.

Methods

We obtained summary-level data from a genome-wide association study meta-analysis including 48,286 cases and 250,671 controls for T2DM and from a genome wide association study of 372 cases and 182,573 controls in the FinnGen project for RVO. To verify the robustness of the results, an independent validation dataset for T2DM (12,931 cases and 57,196 controls) was used. In addition to the main MR analysis using the inverse variance weighted (fixed effect) approach, sensitivity analyses and multivariable MR adjusting for common risk factors of RVO were conducted.

Results

Genetically predicted T2DM was found to be causally associated with RVO risk (odds ratio (OR)=2.823, 95% confidence interval (CI): 2.072-3.847, P=4.868×10-11). This association was supported by sensitivity analyses using the weighted median (OR=2.415, 95% CI: 1.411-4.132, P=1.294×10-3), weighted mode (OR=2.370, 95% CI: 1.321-4.252, P=5.159×10-3), maximum likelihood (OR=2.871, 95% CI: 2.100-3.924, P=3.719×10-11), MR-PRESSO (OR=2.823, 95% CI: 2.135-3.733, P=5.150×10-10), and MR-Egger (OR=2.441, 95% CI: 1.149-5.184, P=2.335×10-2) methods. In addition, this association persisted in multivariable MR after accounting for common RVO risk factors (OR=1.748, 95% CI: 1.238-2.467, P=1.490×10-3). The MR analyses using the validation dataset obtained consistent results.

Conclusion

This study indicates that genetically predicted T2DM may have a causal contribution to RVO. Future studies are required to elucidate the underlying mechanisms.
Nonalcoholic fatty liver disease and type 2 diabetes: an observational and Mendelian randomization study
Authors: Yu Yuetian , Yu Yuefeng , Wang Yuying , Chen Yi , Wang Ningjian , Wang Bin , Lu Yingli
Published: May 2023

Introduction

Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are both chronic multisystem diseases that cause tremendous health burdens worldwide. Previous epidemiological studies have found a bidirectional relationship between these two diseases; however, their causality remains largely unknown. We aim to examine the causal relationship between NAFLD and T2DM.

Methods

The observational analysis included 2,099 participants from the SPECT-China study and 502,414 participants from the UK Biobank. Logistic regression and Cox regression models were used to examine the bidirectional association between NAFLD and T2DM. Two-sample Mendelian randomization (MR) analyses were conducted to investigate the causal effects of the two diseases using summary statistics of genome-wide association studies from the UK Biobank for T2DM and the FinnGen study for NAFLD.

Results

During the follow-up, 129 T2DM cases and 263 NAFLD cases were observed in the SPECT-China study, and 30,274 T2DM cases and 4,896 NAFLD cases occurred in the UK Biobank cohort. Baseline NAFLD was associated with an increased risk of incident T2DM in both studies (SPECT-China: OR: 1.74 (95% confidence interval (CI): 1.12–2.70); UK Biobank: HR: 2.16 (95% CI: 1.82–2.56)), while baseline T2DM was associated with incident NAFLD in the UK Biobank study only (HR: 1.58). Bidirectional MR analysis showed that genetically determined NAFLD was significantly associated with an increased risk of T2DM (OR: 1.003 (95% CI: 1.002–1.004, p< 0.001)); however, there was no evidence of an association between genetically determined T2DM and NAFLD (OR: 28.1 (95% CI: 0.7–1,143.0)).

Conclusions

Our study suggested the causal effect of NAFLD on T2DM development. The lack of a causal association between T2DM and NAFLD warrants further verification.
Mature primary human osteocytes in mini organotypic cultures secrete FGF23 and PTH1-34-regulated sclerostin
Authors: Knowles Helen J. , Chanalaris Anastasios , Koutsikouni Argyro , Cribbs Adam P. , Grover Liam M. , Hulley Philippa A.
Published: May 2023

Introduction

For decades, functional primary human osteocyte cultures have been crucially needed for understanding their role in bone anabolic processes and in endocrine phosphate regulation via the bone-kidney axis. Mature osteocyte proteins (sclerostin, DMP1, Phex and FGF23) play a key role in various systemic diseases and are targeted by successful bone anabolic drugs (anti-sclerostin antibody and teriparatide (PTH1-34)). However, cell lines available to study osteocytes produce very little sclerostin and low levels of mature osteocyte markers. We have developed a primary human 3D organotypic culture system that replicates the formation of mature osteocytes in bone.

Methods

Primary human osteoblasts were seeded in a fibrinogen / thrombin gel around 3D-printed hanging posts. Following contraction of the gel around the posts, cells were cultured in osteogenic media and conditioned media was collected for analysis of secreted markers of osteocyte formation.

Results

The organoids were viable for at least 6 months, allowing co-culture with different cell types and testing of bone anabolic drugs. Bulk RNAseq data displayed the developing marker trajectory of ossification and human primary osteocyte formation in vitro over an initial 8- week period. Vitamin D3 supplementation increased mineralization and sclerostin secretion, while hypoxia and PTH1-34 modulated sclerostin. Our culture system also secreted FGF23, enabling the future development of a bone-kidney-parathyroid-vascular multi-organoid or organ-on-a-chip system to study disease processes and drug effects using purely human cells.

Discussion

This 3D organotypic culture system provides a stable, long-lived, and regulated population of mature human primary osteocytes for a variety of research applications.
A systemically administered detoxified TLR4 agonist displays potent antitumor activity and an acceptable tolerance profile in preclinical models
Authors: Chettab Kamel , Fitzsimmons Chantel , Novikov Alexey , Denis Morgane , Phelip Capucine , Mathé Doriane , Choffour Pierre Antoine , Beaumel Sabine , Fourmaux Eric , Norca Patrick , Kryza David , Evesque Anne , Jordheim Lars Petter , Perrial Emeline , Matera Eva-Laure , Caroff Martine , Kerzerho Jerome , Dumontet Charles
Published: May 2023

Bacterial lipopolysaccharides (LPS) are potent innate immunostimulants targeting the Toll-like receptor 4 (TLR4), an attractive and validated target for immunostimulation in cancer therapy. Although LPS possess anti-tumor activity, toxicity issues prevent their systemic administration at effective doses in humans. We first demonstrated that LPS formulated in liposomes preserved a potent antitumor activity per se upon systemic administration in syngeneic models, and significantly enhance the antitumor activity of the anti-CD20 antibody rituximab in mice xenografted with the human RL lymphoma model. Liposomal encapsulation also allowed a 2-fold reduction in the induction of pro-inflammatory cytokines by LPS. Mice receiving an intravenous administration demonstrated a significant increase of neutrophils, monocytes and macrophages at the tumor site as well as an increase of macrophages in spleen. Further, we chemically detoxified LPS to obtain MP-LPS that was associated with a 200-fold decrease in the induction of proinflammatory cytokines. When encapsulated in a clinically approved liposomal formulation, toxicity, notably pyrogenicity (10-fold), was limited while the antitumor activity and immunoadjuvant effect were maintained. This improved tolerance profile of liposomal MP-LPS was associated with the preferential activation of the TLR4-TRIF pathway. Finally, in vitro studies demonstrated that stimulation with encapsulated MP-LPS reversed the polarization of M2 macrophages towards an M1 phenotype, and a phase 1 trial in healthy dogs validated its tolerance upon systemic administration up to very high doses (10µg/kg). Altogether, our results demonstrate the strong therapeutic potential of MPLPS formulated in liposomes as a systemically active anticancer agent, supporting its evaluation in patients with cancer.
Cause or consequence? The role of IL-1 family cytokines and receptors in neuroinflammatory and neurodegenerative diseases
Authors: Boraschi Diana , Italiani Paola , Migliorini Paola , Bossù Paola
Published: May 2023

Cytokines and receptors of the IL-1 family are key mediators in innate immune and inflammatory reactions in physiological defensive conditions, but are also significantly involved in immune-mediated inflammatory diseases. Here, we will address the role of cytokines of the IL-1 superfamily and their receptors in neuroinflammatory and neurodegenerative diseases, in particular Multiple Sclerosis and Alzheimer’s disease. Notably, several members of the IL-1 family are present in the brain as tissue-specific splice variants. Attention will be devoted to understanding whether these molecules are involved in the disease onset or are effectors of the downstream degenerative events. We will focus on the balance between the inflammatory cytokines IL-1β and IL-18 and inhibitory cytokines and receptors, in view of future therapeutic approaches.
Inflammatory abrasion of hematopoietic stem cells: a candidate clue for the post-CAR-T hematotoxicity?
Authors: Sun Ting , Li Dengju , Huang Liang , Zhu Xiaojian
Published: May 2023

Chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable effects in treating various hematological malignancies. However, hematotoxicity, specifically neutropenia, thrombocytopenia, and anemia, poses a serious threat to patient prognosis and remains a less focused adverse effect of CAR-T therapy. The mechanism underlying lasting or recurring late-phase hematotoxicity, long after the influence of lymphodepletion therapy and cytokine release syndrome (CRS), remains elusive. In this review, we summarize the current clinical studies on CAR-T late hematotoxicity to clarify its definition, incidence, characteristics, risk factors, and interventions. Owing to the effectiveness of transfusing hematopoietic stem cells (HSCs) in rescuing severe CAR-T late hematotoxicity and the unignorable role of inflammation in CAR-T therapy, this review also discusses possible mechanisms of the harmful influence of inflammation on HSCs, including inflammatory abrasion of the number and the function of HSCs. We also discuss chronic and acute inflammation. Cytokines, cellular immunity, and niche factors likely to be disturbed in CAR-T therapy are highlighted factors with possible contributions to post-CAR-T hematotoxicity.
Diagnostic testing for interstitial lung disease in common variable immunodeficiency: a systematic review
Authors: Bintalib Heba M. , van de Ven Annick , Jacob Joseph , Davidsen Jesper Rømhild , Fevang Børre , Hanitsch Leif G. , Malphettes Marion , van Montfrans Joris , Maglione Paul J. , Milito Cinzia , Routes John , Warnatz Klaus , Hurst John R.
Published: May 2023

Introduction

Common variable immunodeficiency related interstitial lung disease (CVID-ILD, also referred to as GLILD) is generally considered a manifestation of systemic immune dysregulation occurring in up to 20% of people with CVID. There is a lack of evidence-based guidelines for the diagnosis and management of CVID-ILD.

Aim

To systematically review use of diagnostic tests for assessing patients with CVID for possible ILD, and to evaluate their utility and risks.

Methods

EMBASE, MEDLINE, PubMed and Cochrane databases were searched. Papers reporting information on the diagnosis of ILD in patients with CVID were included.

Results

58 studies were included. Radiology was the investigation modality most commonly used. HRCT was the most reported test, as abnormal radiology often first raised suspicion of CVID-ILD. Lung biopsy was used in 42 (72%) of studies, and surgical lung biopsy had more conclusive results compared to trans-bronchial biopsy (TBB). Analysis of broncho-alveolar lavage was reported in 24 (41%) studies, primarily to exclude infection. Pulmonary function tests, most commonly gas transfer, were widely used. However, results varied from normal to severely impaired, typically with a restrictive pattern and reduced gas transfer.

Conclusion

Consensus diagnostic criteria are urgently required to support accurate assessment and monitoring in CVID-ILD. ESID and the ERS e-GLILDnet CRC have initiated a diagnostic and management guideline through international collaboration.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022276337.
ULL-SLAM: underwater low-light enhancement for the front-end of visual SLAM
Authors: Xin Zhichao , Wang Zhe , Yu Zhibin , Zheng Bing
Published: May 2023

Underwater visual simultaneous localization and mapping (VSLAM), which can provide robot navigation and localization for underwater vehicles, is crucial in underwater exploration. Underwater SLAM is a challenging research topic due to the limitations of underwater vision and error accumulation over long-term operations. When an underwater vehicle goes down, it may inevitably enter a low-light environment. Although artificial light sources could help to some extent, they might also cause non-uniform illumination, which may have an adverse effect on feature point matching. Consequently, the capability of feature point extraction-based visual SLAM systems could only sometimes work. This paper proposes an end-to-end network for SLAM preprocessing in an underwater low-light environment to address this issue. Our model includes a low-light enhancement branch specific with a non-reference loss function, which can achieve low-light image enhancement without requiring paired low-light data. In addition, we design a self-supervised feature point detector and descriptor extraction branch to take advantage of self-supervised learning for feature points and descriptors matching to reduce the re-projection error. Unlike other works, our model does not require pseudo-ground truth. Finally, we design a unique matrix transformation method to improve the feature similarity between two adjacent video frames. Comparative experiments and ablation experiments confirm that the proposed method in this paper could effectively enhance the performance of VSLAM based on feature point extraction in an underwater low-light environment.
Porewater exchange drives the dissolved silicate export across the wetland‐estuarine continuum
Authors: Wang Fenfang , Lu Zeyang , Wang Yao , Yan Ruifeng , Chen Nengwang
Published: May 2023

Coastal wetlands are an important hotspot for nutrient cycling and transport from the land to the ocean. Silicon (Si) as a vital biogenic element affects plant growth and health of coastal ecosystems. The understanding of key factors and processes controlling dissolved silicate (DSi) exchange between the wetlands and coastal water has been limited due to the lack of measured data. We carried out intensive investigations of time-series DSi concentrations and porewater exchange across the Sediment-Water Interface (SWI) along a tidal creek with a mangrove-salt marsh gradient during neap and spring tides in 2020. Seasonal observations of surface water in a tidal creek and Zhangjiang Estuary (Fujian Province, China) were conducted from 2017 to 2020. The results showed that there was a net export of DSi from the mangroves to tidal creek with rates of 2.11 and 2.40 mmol m-2 d-1 in neap and spring tides respectively, suggesting the mangroves served as the source of DSi. However, the salt marshes had a net DSi import with one or two orders of magnitude lower than the export from the mangroves. DSi export across the wetland‐estuarine continuum was largely controlled by porewater exchange, groundwater geochemistry (pH, temperature) and plant root uptake. Groundwater in the mangroves has larger ratios of DSi : DIN (dissolved inorganic nitrogen) (2.5 ± 0.6) and DSi : DRP (dissolved reactive phosphorus) (1257 ± 35) compared with surface water. The net export of DSi from mangroves would modify the nutrient stoichiometry and mitigate the effects of reduced river DSi flux caused by damming on coastal ecosystem. This study provides new insights into the wetland Si cycling for sustaining coastal ecosystem health.
Image acquisition as novel colonoscopic quality indicator: a single-center retrospective study
Authors: Zhang Ke , Bile Abdiwahid Mohamed , Feng Xinyi , Xu Yemin , Li Yaoyao , She Qiang , Li Guiqing , Wu Jian , Xiao Weiming , Ding Yanbing , Deng Bin
Published: May 2023

Purpose

In order to reduce the incidence and mortality of colorectal cancer, improving the quality of colonoscopy is the top priority. At present, the adenoma detection rate is the most used index to evaluate the quality of colonoscopy. So, we further verified the relevant factors influencing the quality of colonoscopy and found out the novel quality indicators by studying the relationship between the influencing factors and the adenoma detection rate.

Materials/methods

The study included 3824 cases of colonoscopy from January to December 2020. We retrospectively recorded the age and sex of the subjects; the number, size, and histological features of lesions; withdrawal time and the number of images acquired during colonoscopy. We analyzed the associated factors affecting adenoma and polyp detection, and verified their effectiveness with both univariate and multivariate logistic regression analyses.

Results

Logistic regression analyses showed that gender, age, withdrawal time and the number of images acquired during colonoscopy could serve as independent predictors of adenoma/polyp detection rate. In addition, adenoma detection rate (25.36% vs. 14.29%) and polyp detection rate (53.99% vs. 34.42%) showed a marked increase when the number of images taken during colonoscopy was ≥29 (P<0.001).

Conclusions

Gender, age, withdrawal time and the number of images acquired during colonoscopy are influencing factors for the detection of colorectal adenomas and polyps. And we can gain higher adenoma/polyp detection rate when endoscopists capture more colonoscopic images.
Multimodal analysis of genome-wide methylation, copy number aberrations, and end motif signatures enhances detection of early-stage breast cancer
Authors: Pham Thi Mong Quynh , Phan Thanh Hai , Jasmine Thanh Xuan , Tran Thuy Thi Thu , Huynh Le Anh Khoa , Vo Thi Loan , Nai Thi Huong Thoang , Tran Thuy Trang , Truong My Hoang , Tran Ngan Chau , Nguyen Van Thien Chi , Nguyen Trong Hieu , Nguyen Thi Hue Hanh , Le Nguyen Duy Khang , Nguyen Thanh Dat , Nguyen Duy Sinh , Truong Dinh Kiet , Do Thi Thanh Thuy , Phan Minh-Duy , Giang Hoa , Nguyen Hoai-Nghia , Tran Le Son
Published: May 2023

Introduction

Breast cancer causes the most cancer-related death in women and is the costliest cancer in the US regarding medical service and prescription drug expenses. Breast cancer screening is recommended by health authorities in the US, but current screening efforts are often compromised by high false positive rates. Liquid biopsy based on circulating tumor DNA (ctDNA) has emerged as a potential approach to screen for cancer. However, the detection of breast cancer, particularly in early stages, is challenging due to the low amount of ctDNA and heterogeneity of molecular subtypes.

Methods

Here, we employed a multimodal approach, namely Screen for the Presence of Tumor by DNA Methylation and Size (SPOT-MAS), to simultaneously analyze multiple signatures of cell free DNA (cfDNA) in plasma samples of 239 nonmetastatic breast cancer patients and 278 healthy subjects.

Results

We identified distinct profiles of genome-wide methylation changes (GWM), copy number alterations (CNA), and 4-nucleotide oligomer (4-mer) end motifs (EM) in cfDNA of breast cancer patients. We further used all three signatures to construct a multi-featured machine learning model and showed that the combination model outperformed base models built from individual features, achieving an AUC of 0.91 (95% CI: 0.87-0.95), a sensitivity of 65% at 96% specificity.

Discussion

Our findings showed that a multimodal liquid biopsy assay based on analysis of cfDNA methylation, CNA and EM could enhance the accuracy for the detection of early- stage breast cancer.
A systematic method introduced a common lncRNA-miRNA-mRNA network in the different stages of prostate cancer
Authors: Vahabzadeh Gelareh , Khalighfard Solmaz , Alizadeh Ali Mohammad , Yaghobinejad Mahsa , Mardani Mahta , Rastegar Tayebeh , Barati Mahmood , Roudbaraki Morad , Esmati Ebrahim , Babaei Mohammad , Kazemian Ali
Published: May 2023

Introduction

The present study aimed to investigate the interaction of the common lncRNA-miRNA-mRNA network involved in signaling pathways in different stages of prostate cancer (PCa) by using bioinformatics and experimental methods.

Methods

Seventy subjects included sixty PCa patients in Local, Locally Advanced, Biochemical Relapse, Metastatic, and Benign stages, and ten healthy subjects were entered into the current study. The mRNAs with significant expression differences were first found using the GEO database. The candidate hub genes were then identified by analyzing Cytohubba and MCODE software. Cytoscape, GO Term, and KEGG software determined hub genes and critical pathways. The expression of candidate lncRNAs, miRNAs, and mRNAs was then assessed using Real-Time PCR and ELISA techniques.

Results

4 lncRNAs, 5 miRNAs, and 15 common target genes were detected in PCa patients compared with the healthy group. Unlike the tumor suppressors, the expression levels of common onco-lncRNAs, oncomiRNAs, and oncogenes showed a considerable increase in patients with advanced stages; Biochemical Relapse and Metastatic, in comparison to the primary stages; Local and Locally Advanced. Additionally, their expression levels significantly increased with a higher Gleason score than a lower one.

Conclusion

Identifying a common lncRNA-miRNA-mRNA network associated with prostate cancer may be clinically valuable as potential predictive biomarkers. They can also serve as novel therapeutic targets for PCa patients.
Exploring preferences of different modes of administration of hypomethylating agent treatments among patients with acute myeloid leukemia
Authors: Delmas Audrey , Batchelder Laurie , Arora Ira , Bayet Solene , Bruhn David , Eberhardt Alice , Philpott Stephanie , Rodriguez-Leboeuf Ana Maria
Published: May 2023

Introduction

About half of patients with Acute Myeloid Leukemia (AML) are not eligible for Standard Induction Chemotherapy (SIC). Hypomethylating Agents (HMAs) intravenously (IV) or subcutaneously (SC) in a clinical setting are typically offered as an alternative. However, injectable HMAs may be burdensome for patients given the frequent hospital visits and side effects. This study explored patient treatment preferences for different modes of administration (MOA) and the relative importance of treatment-related characteristics that influence treatment decisions.

Methods

Semi-structured 1:1 interviews were conducted with 21 adult patients with AML in Germany, the United Kingdom, and Spain, who are not eligible for SIC, had experience with HMAs or were scheduled to be treated with HMAs. After discussing their experience of living with AML and its treatments, patients were presented with hypothetical treatment scenarios to explore their preferences, and a ranking exercise to assess the relative importance of treatment characteristics that influence their treatment-decisions for AML.

Results

Most patients reported an overall preference for oral administration over parenteral routes (71%), mostly due to convenience. Those preferring IV or SC routes (24%) reasoned with faster speed of action and onsite monitoring. When presented with a hypothetical situation of a patient having to choose between two AML treatments that were identical except for their MOA, the majority preferred the oral route (76%). Regarding treatment characteristics that influence treatment decisions, patients most frequently reported efficacy (86%) and side effects (62%) as important, followed by mode of administration (29%), daily life impacts (24%) and location of treatment (hospital versus home) (14%). However, only efficacy and side effects were rated as number one deciding factors (67% and 19%, respectively). Patients most frequently rated dosing regimen (33%) as least important.

Conclusion

The insights gained from this study may help support patients with AML who are receiving HMA treatment instead of SIC. A potential oral HMA with similar efficacy and tolerability profiles to injectable HMAs could influence treatment decisions. Furthermore, an oral HMA treatment might decrease the burden of parenteral therapies and improve patients’ overall quality of life. However, the extent of influence MOA has on treatment decisions requires further investigation.
Case Report: First longitudinal study of a patient with CALR positive clonal hematopoiesis of indeterminate potential developing into pre-fibrotic myelofibrosis
Authors: Kjær Lasse , Skov Vibe , Larsen Morten Kranker , Boklund Tobias Idor , Andersen Morten , Kefala Maria , Knudsen Trine A. , Schjellerup Eickhardt-Dalbøge Christina , Stiehl Thomas , Gudmand-Høyer Johanne , Snyder Jordan , Holmström Morten , Andersen Mads H. , Ottesen Johnny T. , Ellervik Christina , Hasselbalch Hans C.
Published: May 2023

Initial diagnosis of overt myeloproliferative neoplasms (MPNs) represents the juncture during clonal evolution when symptoms or complications prompt an afflicted individual to seek medical attention. In 30-40% of the MPN subgroups essential thrombocythemia (ET) and myelofibrosis (MF), somatic mutations in the calreticulin gene (CALR) are drivers of the disease resulting in constitutive activation of the thrombopoietin receptor (MPL). In the current study, we describe a healthy CALR mutated individual during a 12 year follow-up from initial identification of CALR clonal hematopoiesis of indeterminate potential (CHIP) to the diagnosis of pre-MF. The pre-diagnostic exponential development dynamics of the malignant clone demonstrated close correlation with the platelet counts, neutrophil-to-lymphocyte (NLR) ratio, and inversely correlated to hemoglobin and erythrocyte counts. Backward extrapolation of the growth rate indicated the potential for discovery of the malignant clone many years prior to presentation of overt disease, opening a window of opportunity for early treatment intervention. We did not find any additional mutations associated with MPNs and the current case report provides novel information regarding the development of a driver mutation and the association with blood cell counts prior to clinical manifestation of symptoms suggesting that pre-diagnostic dynamics may supplement future diagnostic criteria for early diagnosis and intervention in MPN patients.
Development and internal validation of a novel nomogram for predicting lymph node invasion for prostate cancer patients undergoing extended pelvic lymph node dissection
Authors: Li Zhen , Huang Yixin , Zhao Diwei , Luo Xin , Wu Zeshen , Zheng Xinyi , Xie Ye , Liu Yixuan , Wu Jianwei , Peng Yulu , Li Yonghong , Zhou Fangjian
Published: May 2023

Background

Few studies have focused on the performance of Briganti 2012, Briganti 2017 and MSKCC nomograms in the Chinese population in assessing the risk of lymph node invasion(LNI) in prostate cancer(PCa) patients and identifying patients suitable for extended pelvic lymph node dissection(ePLND). We aimed to develop and validate a novel nomogram based on Chinese PCa patients treated with radical prostatectomy(RP) and ePLND for predicting LNI.

Methods

We retrospectively retrieved clinical data of 631 patients with localized PCa receiving RP and ePLND at a Chinese single tertiary referral center. All patients had detailed biopsy information from experienced uropathologist. Multivariate logistic-regression analyses were performed to identify independent factors associated with LNI. The discrimination accuracy and net-benefit of models were quantified using the area under curve(AUC) and Decision curve analysis(DCA).The nonparametric bootstrapping were used to internal validation.

Results

A total of 194(30.7%) patients had LNI. The median number of removed lymph nodes was 13(range, 11-18). In univariable analysis, preoperative prostate-specific antigen(PSA), clinical stage, biopsy Gleason grade group, maximum percentage of single core involvement with highest-grade PCa, percentage of positive cores, percentage of positive cores with highest-grade PCa and percentage of cores with clinically significant cancer on systematic biopsy differed significantly. The multivariable model that included preoperative PSA, clinical stage, biopsy Gleason grade group, maximum percentage of single core involvement with highest-grade PCa and percentage of cores with clinically significant cancer on systematic biopsy represented the basis for the novel nomogram. Based on a 12% cutoff, our results showed that 189(30%) patients could have avoided ePLND while only 9(4.8%) had LNI missing ePLND. Our proposed model achieved the highest AUC (proposed model vs Briganti 2012 vs Briganti 2017 vs MSKCC model: 0.83 vs 0.8 vs 0.8 vs 0.8, respectively) and highest net-benefit via DCA in the Chinese cohort compared with previous nomograms. In internal validation of proposed nomogram, all variables had a percent inclusion greater than 50%.

Conclusion

We developed and validated a nomogram predicting the risk of LNI based on Chinese PCa patients, which demonstrated superior performance compared with previous nomograms.
Integrin β6 deficiency protects mice from experimental colitis and colitis-associated carcinoma by altering macrophage polarization
Authors: Sun Qi , Lu Zhihua , Ma Lei , Xue Dong , Liu Chang , Ye Changchun , Huang Wenbo , Dang Yueyan , Li Fanni
Published: May 2023

Background

Given the key role of integrins in maintaining intestinal homeostasis, anti-integrin biologics in inflammatory bowel disease (IBD) are being investigated in full swing. However, the unsatisfactory efficacy and safety of current anti-integrin biologics in clinical trials limit their widespread use in clinic. Therefore, it is particularly important to find a target that is highly and specifically expressed in the intestinal epithelium of patients with IBD.

Methods

The function of integrin αvβ6 in IBD and colitis-associated carcinoma (CAC) with the underlying mechanisms has been less studied. In the present study, we detected the level of integrin β6 within inflammation including colitis tissues in human and mouse. To investigate the role of integrin β6 in IBD and CAC, integrin β6 deficient mice were hence generated based on the construction of colitis and CAC model.

Results

We noted that integrin β6 was significantly upregulated in inflammatory epithelium of patients with IBD. Integrin β6 deletion not only reduced infiltration of pro-inflammatory cytokines, but also attenuated disruption of tight junctions between colonic epithelial cells. Meanwhile, lack of integrin β6 affected macrophage infiltration in mice with colitis. This study further revealed that lack of integrin β6 could inhibit tumorigenesis and tumor progression in CAC model by influencing macrophage polarization, which was also involved in attenuating the degree of intestinal symptoms and inflammatory responses in mice suffering from colitis.

Conclusions

The present research provides a potentially new perspective and option for the treatment of IBD and CAC.
Characterization of volatiles in flowers from four Rosa chinensis cultivars by HS-SPME-GC × GC-QTOFMS
Authors: Quan Wenxuan , Jin Jing , Qian Chenyu , Li Chaochan , Zhou Hongying
Published: May 2023

Rosa chinensis cultivars with volatile aromas are important resources in the perfume industry. The four rose cultivars introduced to Guizhou province are rich in volatile substances. In this study, volatiles from four Rosa chinensis cultivars were extracted using headspace-solid phase microextraction (HS-SPME), and analyzed with two-dimensional gas chromatography quadrupole time of flight mass spectrometry (GC × GC-QTOFMS). A total of 122 volatiles were identified; the main compounds in these samples were benzyl alcohol, phenylethyl alcohol, citronellol, beta-myrcene and limonene. A total of 68, 78, 71, and 56 volatile compounds were identified in Rosa ‘Blue River’ (RBR), Rosa ‘Crimson Glory’ (RCG), Rosa ‘Pink Panther’ (RPP), and Rosa ‘Funkuhr’ (RF) samples, respectively. The total volatile contents were in the following order: RBR > RCG > RPP > RF. Four cultivars exhibited similar volatility profiles, with alcohols, alkanes, and esters as the major chemical groups, followed by aldehydes, aromatic hydrocarbons, ketones, benzene, and other compounds. Alcohols and aldehydes were quantitatively the two most abundant chemical groups that included the highest number and highest content of compounds. Different cultivars have different aromas, and RCG had high contents of phenyl acetate, rose oxide, trans-rose oxide, phenylethyl alcohol and 1,3,5-trimethoxybenzene, characterized by floral and rose descriptors. RBR contained a high content of phenylethyl alcohol, and RF contained a high content of 3,5-dimethoxytoluene. Hierarchical cluster analysis (HCA) of all volatiles showed that the three cultivars (RCG, RPP, and RF) had similar volatile characteristics and were significantly different from RBR. Differential metabolites among cultivars were screened based on the OPLS-DA model, and there were six main enriched pathways of differential metabolites: biosynthesis of secondary metabolites, monoterpenoid biosynthesis, metabolic pathways, limonene and pinene degradation, sesquiterpenoid and triterpenoid biosynthesis, and alpha-linolenic acid metabolism. The biosynthesis of secondary metabolites is the most differential metabolic pathway.
Vegetation structure and aboveground biomass of Páramo peatlands along a high-elevation gradient in the northern Ecuadorian Andes
Authors: Suárez Esteban , Hribljan John A. , Chimbolema Segundo , Harvey Katie , Triana Victoria , Zurita Juan E. , Jaramillo Ricardo , Doskocil Lenka G.
Published: May 2023

The high-elevation peatlands of the páramos of the northern Andes constitute a diverse environment that harbors large numbers of species and several types of plant communities along altitudinal, latitudinal, and environmental gradients. However, little is known about the structure and functioning of these ecosystems, including peatland vegetation types and their relative contribution to the production and accumulation of peat soils. In this paper we characterized the structure of peatland plant communities of the humid páramos of northern Ecuador by describing the distribution of plant growth-forms and their aboveground biomass patterns. Along an elevation gradient of 640 m we sampled vegetation in 16 peatlands and aboveground biomass in four peatlands. Three distinct peatland vegetation types were identified: High elevation Cushion peatlands, dominated by Plantago rigida and Distichia muscoides, Sedge and rush peatlands dominated by Carex spp. and Juncus spp., and Herbaceous and shrubby peatlands, with a more heterogenous and structurally complex vegetation. In terms of aboveground biomass, we found an 8-fold reduction in the higher peatlands compared to the lower sites, suggesting that the steep elevational gradients characteristic of Andean environments might be crucial in structuring the physiognomy and composition of peatland vegetation, either through its effects on temperature and other environmental factors, or through its effects on the age and development of soils. Additional studies are needed to evaluate the potential effects of temperature, hydrology, micro-topography, geological setting, and land-use, which are likely to influence vegetation patters in these peatlands.
Current and emerging trends in techniques for plant pathogen detection
Authors: Venbrux Marc , Crauwels Sam , Rediers Hans
Published: May 2023

Plant pathogenic microorganisms cause substantial yield losses in several economically important crops, resulting in economic and social adversity. The spread of such plant pathogens and the emergence of new diseases is facilitated by human practices such as monoculture farming and global trade. Therefore, the early detection and identification of pathogens is of utmost importance to reduce the associated agricultural losses. In this review, techniques that are currently available to detect plant pathogens are discussed, including culture-based, PCR-based, sequencing-based, and immunology-based techniques. Their working principles are explained, followed by an overview of the main advantages and disadvantages, and examples of their use in plant pathogen detection. In addition to the more conventional and commonly used techniques, we also point to some recent evolutions in the field of plant pathogen detection. The potential use of point-of-care devices, including biosensors, have gained in popularity. These devices can provide fast analysis, are easy to use, and most importantly can be used for on-site diagnosis, allowing the farmers to take rapid disease management decisions.