bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of ignoring Interval censoring in progression-free survival in cancer trials: a systematic review
Authors: Zhang Xiawen , Pullenayegum Eleanor , Chan Kelvin Kar-Wing 
Published: November 2021

Introduction & Objective: From statistical literature, the bias in treatment effect from ignoring interval censoring in Progression-free survival (PFS) is demonstrated. However, the impact on estimators caused by interval censoring is not carefully took account and investigated by researchers in practice. The objective of this study is to examine the impact of accounting for interval censoring in practice among RCTs used to support FDA approvals anti-cancer drugs between the years 2005 and 2019 that used PFS as an endpoint.
Methods: In this systematic review, the differences of hazard ratios between two methods: considering and ignoring interval censoring, are visualized by Kaplan-Meier survival curves and estimated from a Cox proportional hazard model of 87 RCTs. With assumption that these differences and mean differences (bias) follow a normal distribution, limits of agreement of differences and confidence interval of bias are used to represent agreement of two methods.
Results: Limits of agreement of difference range from -0.044 to 0.0615, while confidence intervals for the bias range from 0.0026 to 0.0145, which does not include zero, resulting in estimated treatment effect differs for two methods.
Conclusion: In general, bias caused by interval censoring in treatment effect exists with large sample studies. Focusing on individual clinical trials, limits of agreement can provide more information for researchers to make decision on how to account for interval censoring.
Шляхи удосконалення системи метрологічного забезпечення в сучасних умовах розвитку Збройних Сил України
Authors: Pavlovskyi Oleh , Sova Oleh , Koval Volodymyr 
Published: November 2021

Система метрологічного забезпечення Збройних Сил України призначена здійснювати вимірювання та контроль параметрів зразків озброєння і військової техніки. Метрологічне забезпечення в Збройних Силах України організується і здійснюється службами метрології та стандартизації військових частин, оперативних (повітряних) командувань, Генерального штабу Збройних Сил України, а його вдосконалення є важливою науково-технічною задачею, актуальність якої підтверджується необхідністю підтримання озброєння та військової техніки військ (сил) у боєздатному стані.
В статті проведено аналіз системи метрологічного забезпечення Збройних Сил України та запропоновані шляхи її удосконалення враховуючи поетапний перехід Збройних Сил України на стандарти НАТО, розвиток озброєння та військової техніки, збільшення обсягів вимірювальних параметрів та стрімкий розвиток інформаційних технологій.
Розвиток високоточного озброєння та військової техніки, систем управління ними, впровадження системи логістичного забезпечення вимагає від нас удосконалення й системи метрологічного забезпечення Збройних Сил України для її інтеграції в єдину систему управління забезпеченням військ (сил), що дасть змогу оперативно та ефективно вирішувати питання метрологічного обслуговування озброєння та військової техніки, вчасного укомплектування засобами вимірювальної техніки військового призначення, та адекватного контролю за станом метрологічного забезпечення Збройних Сил України.
Метрологічне забезпечення озброєння та військової техніки на стадіях його життєвого циклу
Authors: Bychenkov Vasуl , Kotsyuruba Vоlоdymyr , Vlasov Igor 
Published: November 2021

Підвищення ефективності виробництва і якості зразків озброєння та військової техніки не можливе без досягнення необхідної достовірності кількісної інформації про значення параметрів, які характеризують зразки озброєння, що розробляються, створюються та експлуатуються. Джерелами такої інформації є вимірювання. Результати вимірювань будуть об'єктивними та достовірними тільки при правильній організації отримання вимірювальної інформації. Цього неможливо досягти без належного метрологічного забезпечення.
В статті викладені загальні принципи метрологічного забезпечення як складової системи контролю якості зразків озброєння, описаний процес метрологічного забезпечення зразків озброєння та військової техніки на різних стадіях їх життєвого циклу, визначені основні цілі та завдання метрологічного забезпечення.
Важливість метрологічного забезпечення не обмежується його роллю щодо підвищення якості озброєння та військової техніки. Вимірювання лежать в основі процесів обліку витрат та раціонального використання матеріальних ресурсів, методів технічної діагностики та моніторингу процесу експлуатації озброєння та військової техніки.
Удосконалена система індикаторів ефективності функціонування системи протиповітряної оборони військового формування тактичного рівня в наступальному бою
Authors: Horbachov Konstiantin 
Published: November 2021

Результати аналізу воєнних конфліктів, що відбулись за останні десятиріччя, особливо досвід проведення Операції об'єднаних сил та антитерористичної операції на території України, вказує, що військові формування тактичного рівня не можуть успішно виконувати бойові завдання в умовах завоювання противником переваги у повітрі.
Зміни способів досягнення мети загальновійськового бою, зокрема наступального, що пов'язані з появою нових засобів повітряного нападу висувають більш жорсткі вимоги до ефективності системи протиповітряної оборони військових формувань.
Зазначене вище, визначає потребу врахування змін якісного складу, масштабу і характеру застосування противником засобів повітряного нападу, зокрема безпілотних, в ході планування наступального бою.
Тому, система індикаторів ефективності функціонування системи протиповітряної оборони, що використовується у військових формуваннях тактичного рівня, потребує удосконалення.
Вирішенню цього актуального наукового завдання й присвячена дана стаття.
Stress and strain analysis using Autodesk Inventor software in soil-cement brick
Authors: Sousa Ana Carolina Cavalcante de , Oliveira Fernanda Souza , Borges Simone Pereira Taguchi 
Published: November 2021

The computational analysis of materials is fundamental for a better understanding of their physical and mechanical properties, achieving more results in a shorter time. It is a cheaper, non-destructive, practical way, and easily adaptable to various types of models and physical influences. This study has the objective of ascertaining the stress and strain analysis in soil-cement brick through the Autodesk Inventor Professional software, which uses the finite element method. Three models of brick were made: two holes, monoblock, and groove, which are the most commonly used shapes. To the two holes model, the maximum first principal stress observed was 1.464x10-1 MPa and the third principal stress was 5.4x10-3 MPa, presenting an insignificant strain of 1.037x10-3 mm. In the monoblock model, the maximum first principal stress was 4.606x10-1 MPa, and the third principal stress was 1.19x10-2 MPa, presenting a strain of 1.611x10-3 mm. The groove model presented the maximum first principal stress at 3.263x10-1 MPa and for the third principal stress was 9.1x10-3 MPa, respectively, presenting a strain of 3.344x10-3 mm. It can also be observed that the models have stress concentrating regions in the sharp edges and notches of the part. Among the three models studied, the one that presented the most favorable stress-strain conditions was the two-hole model. Since it has a larger contact area, the load applied to it was better distributed, presenting higher resistance than the other models with a smaller contact area.
GH Responsiveness in Children With Noonan Syndrome Compared to Turner Syndrome
Authors: Dahlgren Jovanna , Albertsson-Wikland Kerstin 
Published: November 2021

BackgroundDespite different genetic background, Noonan syndrome (NS) shares similar phenotype features to Turner syndrome (TS) such as short stature, webbed neck and congenital heart defects. TS is an entity with decreased growth hormone (GH) responsiveness. Whether this is found in NS is debated.MethodsData were retrieved from combined intervention studies including 25 children diagnosed with NS, 40 diagnosed with TS, and 45 control children (all prepubertal). NS-children and TS-girls were rhGH treated after investigation of the GH/IGFI-axis. GH was measured with poly- and monoclonal antibodies; 24hGH-profile pattern analysed by PULSAR. The NS-children were randomly assigned to Norditropin® 33 or 66 μg/kg/day, and TS-girls were consecutively treated with Genotropin® 33 or 66 μg/kg/day.ResultsHigher PULSAR-estimates of 24h-profiles were found in both NS-children and TS-girls compared to controls: Polyclonal GHmax24h-profile (Mean ± SD) was higher in both groups (44 ± 23mU/L, p&lt;0.01 in NS; 51 ± 47, p&lt;0.001 in TS; compared to 30 ± 23 mU/L in controls) as was GH-baseline (1.4 ± 0.6 mU/L in NS; 2.4 ± 2.4 mU/L in TS, p&lt;0.01 for both, compared to 1.1 ± 1.2 mU/L in controls). Pre-treatment IGFISDS was 2.2 lower in NS-children (-1.7 ± 1.3) compared to TS-girls (0.6 ± 1.8, p&lt;0.0001). GHmax, IGFI/IGFBP3-ratioSDS, and chronological age at start of GH accounted for 59% of the variance in first-year growth response in NS.ConclusionBoth prepubertal NS-children and TS-girls had a high GH secretion, but low IGFI/IGFBP3 levels only in NS-children. Both groups presented a broad individual response. NS-children showed higher response in IGFI and growth, pointing to higher responsiveness to GH treatment than TS-girls.
High Fasting Glycemia Predicts Impairment of Cardiac Autonomic Control in Adults With Type 2 Diabetes: A Case-Control Study
Authors: Silva Lucas Raphael Bento , Gentil Paulo , Seguro Camila Simões , de Oliveira Gabriela Teles , Silva Maria Sebastiana , Zamunér Antônio Roberto , Beltrame Thomas , Rebelo Ana Cristina Silva 
Published: November 2021

IntroductionType 2 diabetes (T2D) is characterized by a metabolic disorder that elevates blood glucose concentration. Chronic hyperglycemia has been associated with several complications in patients with T2D, one of which is cardiac autonomic dysfunction that can be assessed from heart rate variability (HRV) and heart rate recovery (HRR) response, both associated with many aspects of health and fitness, including severe cardiovascular outcomes.ObjectiveTo evaluate the effects of T2D on cardiac autonomic modulation by means of HRV and HRR measurements.Materials and MethodsThis study has an observational with case-control characteristic and involved ninety-three middle-aged adults stratified into two groups (control group - CG, n = 34; diabetes group - DG, n = 59). After signing the free and informed consent form, the patients were submitted to the evaluation protocols, performed biochemical tests to confirm the diagnosis of T2D, collection of R-R intervals for HRV analysis and cardiopulmonary effort test to quantify HRR.ResultsAt rest, the DG showed a reduction in global HRV (SDNN= 19.31 ± 11.72 vs CG 43.09 ± 12.74, p &lt; 0.0001), lower parasympathetic modulation (RMSSD= 20.49 ± 14.68 vs 52.41 ± 19.50, PNN50 = 4.76 ± 10.53 vs 31.24 ± 19.24, 2VD%= 19.97 ± 10.30 vs 28.81 ± 9.77, p &lt; 0.0001 for both indices) and higher HRrest when compared to CG. After interruption of physical exercise, a slowed heart rate response was observed in the DG when compared to the CG. Finally, a simple linear regression showed that fasting glycemia was able to predict cardiac autonomic involvement in volunteers with T2D.ConclusionPatients with T2D presented lower parasympathetic modulation at rest and slowed HRR after physical exercise, which may be associated with higher cardiovascular risks. The findings show the glycemic profile as an important predictor of impaired cardiac autonomic modulation.
Pattern Recognition Receptors (PRRs) in Macrophages Possess Prognosis and Immunotherapy Potential for Melanoma
Authors: Zhao Qihang , Wang Qiang , Wang Tengjiao , Xu Junfang , Li Tingting , Liu Qiuyan , Yao Qinghua , Wang Pin 
Published: November 2021

BackgroundPattern recognition receptors (PRRs) family plays a vital role in the initial stage of innate immune response and the subsequent activation of adaptive immunity. Increasing evidences have indicated that several PRRs play critical roles in the progress of inflammation and tumorigenesis. However, the comprehensive significance of PRRs family in clinical prognosis of different cancers is still elusive.MethodsWe analyzed expression of 20 canonical PRRs in tumor samples from 9502 patients of 33 tumor types. Next, we used expression profiles of PRRs in skin cutaneous melanoma (SKCM) to build a Cox prognosis model. Then, we analyzed immune infiltration features and immune activity of high risk score and low risk score patients. Finally, we analyzed the single-cell sequencing data of different cancers and detected the expression of PRRs in mouse melanoma model to identify PRRs-expressing cell types.ResultsWe found PRRs had a significantly positive correlation with prognosis in SKCM rather than other tumors, and PRR-based Cox model had a much better prognosis potential than any single PRR. Further analysis shows risk score could indicate immunocyte infiltration and immune activity in SKCM. We also found the expressions of some PRR genes were highly correlated with the expression of immune checkpoints molecules in SKCM, indicating they could be indicators for clinical immune therapy. Finally, we found only in SKCM samples, the expression of PRRs is especially high in a subpopulation of macrophages with a trait of CD206 low expression, probably explaining why PRRs have prognosis potential in melanoma.ConclusionsOur study reveals PRR family in macrophages has a positive prognosis potential in melanoma and could be valuable for clinical prognosis and immune therapy.
The Value of 18F-FDG PET/CT and Abdominal PET/MRI as a One-Stop Protocol in Patients With Potentially Resectable Colorectal Liver Metastases
Authors: Zhou Nina , Guo Xiaoyi , Sun Hongwei , Yu Boqi , Zhu Hua , Li Nan , Yang Zhi 
Published: November 2021

PurposeThe aim of this study was to evaluate the clinical value of simultaneous positron emission tomography/computed tomography (PET/CT) and abdominal positron emission tomography/magnet resonance imaging (PET/MRI) in the detection of liver metastases and extrahepatic disease (EHD) in patients with potentially resectable colorectal liver metastases (CLM).MethodsFifty-six patients with CLM underwent conventional imaging (chest and abdomen CT, liver contrast-enhanced CT or MRI) and PET imaging [fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT and subsequent liver PET/MRI] for staging or restaging. Diagnostic ability of PET imaging was compared with conventional imaging. Abnormal findings were correlated with follow-up imaging and/or histology. The influence of the PET imaging findings was categorized for each patient in relation to operability and other significant findings. The clinical management included three modalities (surgery for resectable CLM, unresectable CLM with conversion treatment, and systemic therapy). The clinical impact of the imaging modality was analyzed. The operative histopathological analysis and/or imaging follow-up were performed as the standard of reference.ResultsThis study enrolled a total of 56 patients (median age 60 years, 62.5% were male, 36 with colon cancer and 20 with rectal cancer). For EHD detection, PET/CT detected more EHD than conventional imaging (60.7% vs. 46.4%). PET/CT had different findings in 19 (33.9%) patients, including downstaging in 4 (7.1%) patients and upstaging in 15 (26.8%) patients. For liver lesion detection, PET/MRI showed comparable detection ability with CE-MRI and CE-CT (99.5%, 99.4%, and 86.5%, respectively) based on lesion analysis, much higher than PET/CT (47.5%). PET imaging had a major impact in 10/56 (17.9%) patients (4 from unresectable to resectable, 6 from resectable to unresectable) and a minor impact in 4/56 (7.1%) patients for changing the surgery extent. The therapeutic strategies had been altered in a total of 14/56 patients (25%) after PET/CT and PET/MRI scans.ConclusionThe results of this study indicate that simultaneous 18F-FDG PET/CT and abdominal PET/MRI scans can provide accurate information regarding CLM status and EHD, and can affect the management of 25% of the patients by changing the therapeutic strategies determined by conventional imaging. This new modality may serve as a new one-stop method in patients with potentially resectable CLM.
Does Ethnicity Matter in Multiple Myeloma Risk Prediction in the Era of Genomics and Novel Agents? Evidence From Real-World Data
Authors: Farswan Akanksha , Gupta Anubha , Sriram Krishnamachari , Sharma Atul , Kumar Lalit , Gupta Ritu 
Published: November 2021

IntroductionCurrent risk predictors of multiple myeloma do not integrate ethnicity-specific information. However, the impact of ethnicity on disease biology cannot be overlooked. In this study, we have investigated the impact of ethnicity in multiple myeloma risk prediction. In addition, an efficient and robust artificial intelligence (AI)-enabled risk-stratification system is developed for newly diagnosed multiple myeloma (NDMM) patients that utilizes ethnicity-specific cutoffs of key prognostic parameters.MethodsK-adaptive partitioning is used to propose new cutoffs of parameters for two different datasets—the MMIn (MM Indian dataset) dataset and the MMRF (Multiple Myeloma Research Foundation) dataset belonging to two different ethnicities. The Consensus-based Risk-Stratification System (CRSS) is designed using the Gaussian mixture model (GMM) and agglomerative clustering. CRSS is validated via Cox hazard proportional methods, Kaplan–Meier analysis, and log-rank tests on progression-free survival (PFS) and overall survival (OS). SHAP (SHapley Additive exPlanations) is utilized to establish the biological relevance of the risk prediction by CRSS.ResultsThere is a significant variation in the key prognostic parameters of the two datasets belonging to two different ethnicities. CRSS demonstrates superior performance as compared with the R-ISS in terms of C-index and hazard ratios on both the MMIn and MMRF datasets. An online calculator has been built that can predict the risk stage of a multiple myeloma (MM) patient based on the values of parameters and ethnicity.ConclusionOur methodology discovers changes in the cutoffs with ethnicities from the established cutoffs of prognostic features. The best predictor model for both cohorts was obtained with the new ethnicity-specific cutoffs of clinical parameters. Our study also revealed the efficacy of AI in building a deployable risk prediction system for MM. In the future, it is suggested to use the CRSS risk calculator on a large dataset as the cohort size of the present study is 25% of the cohort used in the R-ISS reported in 2015.
CDT1 Is a Novel Prognostic and Predictive Biomarkers for Hepatocellular Carcinoma
Authors: Cai Chenhui , Zhang Ying , Hu Xu , Hu Wenhui , Yang Sizhen , Qiu Hao , Chu Tongwei 
Published: November 2021

ObjectiveHepatocellular carcinoma (HCC) is one of the most common malignant tumors endangering human health and life in the 21st century. Chromatin licensing and DNA replication factor 1 (CDT1) is an important regulator of DNA replication licensing, which is essential for initiation of DNA replication. CDT1 overexpression in several human cancers reportedly leads to abnormal cell replication, activates DNA damage checkpoints, and predisposes malignant transformation. However, the abnormal expression of CDT1 in HCC and its diagnostic and prognostic value remains to be elucidated.MethodsTCGA, ONCOMINE, UALCAN, HCCDB, HPA, Kaplan-Meier plotter, STRING, GEPIA, GeneMANIA, and TIMER were conducted for bioinformatics analysis. CDT1 protein expression was evaluated by immunohistochemistry in HCC tissues through a tissue microarray. qRT-PCR, western blot and a cohort of functional experiments were performed for in vitro validation.ResultsIn this study, we discovered remarkably upregulated transcription of CDT1 in HCC samples relative to normal liver samples through bioinformatic analysis, which was further verified in clinical tissue microarray samples and in vitro experiments. Moreover, the transcriptional level of CDT1 in HCC samples was positively associated with clinical parameters such as clinical tumor stage. Survival, logistic regression, and Cox regression analyses revealed the significant clinical prognostic value of CDT1 expression in HCC. The receiver operating characteristic curve and nomogram analysis results demonstrated the strong predictive ability of CDT1 in HCC. Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analyses indicated that CDT1 was mainly associated with the cell cycle, DNA repair, and DNA replication. We further demonstrated the significant correlation between CDT1 and minichromosome maintenance (MCM) family genes, revealing abnormal expression and prognostic significance of MCMs in HCC. Immune infiltration analysis indicated that CDT1 was significantly associated with immune cell subsets and affected the survival of HCC patients. Finally, knockdown of CDT1 decreased, whereas overexpression of CDT1 promoted the proliferation, migration, invasion of HCC cells in vitro.ConclusionsOur study findings demonstrate the potential diagnostic and prognostic significance of CDT1 expression in HCC, and elucidate the potential molecular mechanism underlying its role in promoting the occurrence and development of liver cancer. These results may provide new opportunities and research paths for targeted therapies in HCC.
Combined Use of cyclinD1 and Ki67 for Prognosis of Luminal-Like Breast Cancer Patients
Authors: Hao Junmei , Zhang Wenfeng , Lyu Yan , Zou Jiarui , Zhang Yunyun , Lyu Jiahong , Zhang Jianbo , Xie Shuishan , Zhang Cuiping , Zhang Jiandi , Tang Fangrong 
Published: November 2021

BackgroundKi67 is a biomarker of proliferation to be used in immunohistochemistry (IHC)-based surrogate assay to determine the necessity of cytotoxic therapy for Luminal-like breast cancer patients. cyclinD1 is another frequently used biomarker of proliferation. A retrospective study was performed here to investigate if these two biomarkers may be combined to improve the prognosis of Luminal-like patients.MethodsBoth Ki67 and cyclinD1 protein levels were measured absolutely and quantitatively using Quantitative Dot Blot method in 143 Luminal-like specimens. Optimized cutoffs for these two biomarkers were developed to evaluate their prognostic roles using Kaplan–Meier overall survival (OS) analysis.ResultscyclinD1 was found as an independent prognostic factor from Ki67 in univariate and multivariate OS analyses. At optimized cutoffs (cyclinD1 at 0.44 μmol/g and Ki67 at 2.31 nmol/g), the subgroup with both biomarkers below the cutoffs (n = 65) had 10-year survival probability at 90% in comparison to those with both biomarkers above the cutoffs (n = 18) with 8-year survival probability at 26% (log-rank test, p &lt;0.0001). This finding was used to modify the surrogate assay using IHC-based cyclinD1 scores, with p-value decreased from 0.031 to 0.00061 or from 0.1 to 0.02, when the Ki67 score of 14 or 20% was used as cutoff, respectively, in the surrogate assay.ConclusionThe current study supports the prospective investigation of cyclinD1 relevance in the clinic.