bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

IntroductionFor 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.MethodsPrimary 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.ResultsThe 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.DiscussionThis 3D organotypic culture system provides a stable, long-lived, and regulated population of mature human primary osteocytes for a variety of research applications.
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

IntroductionCommon 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.AimTo systematically review use of diagnostic tests for assessing patients with CVID for possible ILD, and to evaluate their utility and risks.MethodsEMBASE, MEDLINE, PubMed and Cochrane databases were searched. Papers reporting information on the diagnosis of ILD in patients with CVID were included.Results58 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.ConclusionConsensus 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 registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022276337.
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

PurposeIn 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/methodsThe 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.ResultsLogistic 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&lt;0.001).ConclusionsGender, 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

IntroductionBreast 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.MethodsHere, 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.ResultsWe 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.DiscussionOur 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

IntroductionThe 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.MethodsSeventy 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.Results4 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.ConclusionIdentifying 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

IntroductionAbout 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.MethodsSemi-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.ResultsMost 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.ConclusionThe 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.
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

BackgroundFew 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.MethodsWe 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.ResultsA 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%.ConclusionWe 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

BackgroundGiven 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.MethodsThe 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.ResultsWe 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.ConclusionsThe present research provides a potentially new perspective and option for the treatment of IBD and CAC.
Metabolome analysis reveals flavonoid changes during the leaf color transition in Populus × euramericana ‘Zhonghuahongye’
Authors: Chen Mengjiao , Chang Cuifang , Li Hui , Huang Lin , Zhou Zongshun , Zhu Jingle , Liu Dan 
Published: May 2023

IntroductionTo investigate the mechanism of leaf color change at different stages in Populus × euramericana ‘Zhonghuahongye’ (‘Zhonghong’ poplar).MethodsLeaf color phenotypes were determined and a metabolomic analysis was performed on leaves at three stages (R1, R2 and R3).ResultsThe a*, C* and chromatic light values of the leaves decreased by 108.91%, 52.08% and 113.34%, while the brightness L values and chromatic b* values gradually increased by 36.01% and 13.94%, respectively. In the differential metabolite assay, 81 differentially expressed metabolites were detected in the R1 vs. R3 comparison, 45 were detected in the R1 vs. R2 comparison, and 75 were detected in the R2 vs. R3 comparison. Ten metabolites showed significant differences in all comparisons, which were mostly flavonoid metabolites. The metabolites that were upregulated in the three periods were cyanidin 3,5-O-diglucoside, delphinidin, and gallocatechin, with flavonoid metabolites accounting for the largest proportion and malvidin 3- O-galactoside as the primary downregulated metabolite. The color shift of red leaves from a bright purplish red to a brownish green was associated with the downregulation of malvidin 3-O-glucoside, cyanidin, naringenin, and dihydromyricetin.DiscussionHere, we analyzed the expression of flavonoid metabolites in the leaves of ‘Zhonghong’ poplar at three stages and identified key metabolites closely related to leaf color change, providing an important genetic basis for the genetic improvement of this cultivar.
Analisis Ukuran Perusahaan Dan Leverage Terhadap Nilai Perusahaan Dengan Profitabilitas Sebagai Variabel Intervening Pada Perusahaan Keuangan Sektor Energy A121 Produksi Batu Bara Yang Terdapat Di BEI Periode 2017-2022
Authors: Wati Putri Maulina , Arjuniadi Arjuniadi , Yanti Evi Maulida 
Published: May 2023

Penelitian ini bertujuan untuk menguji analisis variabel ukuran perusahaan, leverage terhadap nilai perusahaan dan profitabilitas sebagai variabel intervening. Populasi dalam penelitian ini adalah seluruh perusahaan sektor energy A121 produksi batu bara yang terdapat di BursaEfek Indonesia (BEI) periode 2017-2022. Teknik yang digunakan untuk pengambilan sampel adalah perusahaan keuangan sektor energy A121 produksi batu bara periode 2017-2022 dan yang menerbitkan laporan keuangan setiap tahunnya. Berdasarkan kriteria yang digunakan maka jumlah sampel yang diambil adalah 16 perusahaan. Penelitian ini menggunakan analisis linear berganda dengan menggunakan aplikasi SPSS ver.25. Hasil penelitian menunjukkan bahwa: 1) Profitabilitas berpengaruh negative tidak signifikan terhadap nilai perusahaan.; 2) Leverage berpengaru negative signifikan terhadap profitabilitas; 3) Profitabilitas berpengaruh positif terhadap signifikan terhadap nilai perusahaan; 4) Ukuran perusahaan berpengaruh positif signifikan terhadap nilai perusahaan; 5) Ukuran perusahaan berpengaruh negative signifikan terhadap nilai perusahaan; 6) Profitabilitas memediasi ukuran perusahaan terhadap nilai perusahaan; 7) Profitabilitas memediasi leverage terhadap nilai perusahaan. Nilai koefisien determinasi persamaan I sebesar 0,402 atau 40,2% dan persamaan II sebesar 0,087 atau 9,7%. Angka tersebut menunjukkan bahwa variabel dependen yaitu ukuran perusahaan,leverage dan profitabilitas, sedangkan sisanya pada persamaan I sebesar 59,8% dan sisa dipersamaan II sebesar 90,3% dijelaskan oleh factor-faktor lain yang tidak dimasukkan kedalam penelitian ini.
EDUKASI POLA PANGAN HARAPAN DALAM MENDUKUNG KETAHANAN PANGAN DI KELURAHAN KAMPUNG SATU
Authors: Mulyani Sekar Inten , Suryana Nia Kurniasih , Wahyuni Etty 
Published: May 2023

Pola Pangan Harapan (PPH) merupakan indikator kinerja di bidang Ketahanan Pangan. Keberhasilan ketahanan pangan dapat dilihat dari ketersediaan pangan yang cukup dan kemudahan masyarakat dalam mengakses panga. Pola Konsumsi Pangan Penduduk Indonesia masih terdapat ketimpangan yaitu masih tingginya konsumsi kelompok padi-padian terutama beras dan masih rendahnya konsumsi pangan hewani dan umbi-umbian serta buah dan sayur. Kualitas konsumsi pangan masyarakat yang ditujukan dengan skor Pola Pangan Harapan (PPH) masih belum mencapai kondisi ideal. Pemanfaatan sumber-sumber pangan lokal seperti umbi, jagung dan sagu masih rendah. Diperlukan upaya untuk penganekaragaman konsumsi pangan masyarakat menuju skor PPH yang ideal agar hidup sehat, aktif dan produktif. Mitra dalam kegiatan pengabdian masyarakat ini adalah ibu-ibu anggota PKK di Kelurahan Kampung Satu. Adapun permasalahan yang dihadapi mitra adalah : 1) Masih tingginya ketergantungan konsumsi pangan rumah tangga pada komoditas beras;2) Keanekaragaman konsumsi pangan lokal yang berasal dari bahan pangan lokal misalnya umbi-umbian dan jagung masih rendah; 3) Pengetahuan mitra mengenai Pola Pangan Harapan masih rendah sehingga keberagaman pangan baik kualitas dan kuantitas masih kurang. Kegiatan ini akan dilaksankan di Kelurahan Kampung Satu pada bulan Juni Sampai Dengan November 2020. Kegiatan yang dilakukan berupa edukasi dan pendampingan pada anggota PKK Kelurahan Kampung Satu dengan partisipasi aktif dari mitra.Hasil kegiatan menunjukan terjadi peningkatan pemahaman masyarakat (96%) terhadap Pola Pangan Harapan dan pentingnya penganekaragaman pangan dalam keluarga guna mencapai ketahanan pangan keluarga, masyarakat sangat antusias daan berpartisipasi aktif dalam kegiatan edukasi, masyarakat mampu secara mandiri memanfaatkan pekarangan untuk memenuhi kebutuhan pangan dan gizi keluarga