bluuebunny/crossref_metadata_2025_split huggingface dataset:
N‐glycan fingerprint predicts alpha‐fetoprotein negative hepatocellular carcinoma: A large‐scale multicenter study
Authors: Huang Chenjun , Fang Meng , Feng Huijuan , Liu Lijuan , Li Ya , Xu Xuewen , Wang Hao , Wang Ying , Tong Lin , Zhou Lin , Gao Chunfang 
Published: March 2021

AbstractAlpha‐fetoprotein (AFP)‐negative hepatocellular carcinoma (ANHCC) patients account for more than 30% of the whole entity of HCC patients and are easily misdiagnosed. This three‐phase study was designed to find and validate new ANHCC N‐glycan markers which identified from The Cancer Genome Atlas (TCGA) database and noninvasive detection. Differentially expressed genes (DEGs) of N‐glycan biosynthesis and degradation related genes were screened from TCGA database. Serum N‐glycan structure abundances were analyzed using N‐glycan fingerprint (NGFP) technology. Totally 1340 participants including ANHCC, chronic liver diseases and healthy controls were enrolled after propensity score matching (PSM). The Lasso algorithm was used to select the most significant N‐glycan structures abundances. Three machine learning models [random forest (RF), support vector machine (SVM) and logistic regression (LR)] were used to construct the diagnostic algorithms. All 13N‐glycan structure abundances analyzed by NGFP demonstrated significant and was enrolled by Lasso. Among the three machine learning models, LR algorithm demonstrated the best diagnostic performance for identifying ANHCC in training cohort (LR: AUC: 0.842, 95%CI: 0.784‐0.899; RF: AUC: 0.825, 95%CI: 0.766‐0.885; SVM: AUC: 0.610, 95%CI: 0.527‐0.684). This LR algorithm achieved a high diagnostic performance again in the independent validation (AUC: 0.860, 95%CI: 0.824‐0.897). Furthermore, the LR algorithm could stratify ANHCC into two distinct subgroups with high or low risks of overall survival and recurrence in follow‐up validation. In conclusion, the biomarker panel consisting of 13N‐glycan structures abundances using the best‐performing algorithm (LR) was defined and indicative as an effective tool for HCC prediction and prognosis estimate in AFP negative subjects.
Introducing longitudinal cumulative dose to describe chemotherapy patterns over time: Case study of a colon cancer trial
Authors: Webster‐Clark Michael , Keil Alexander P. , Sanoff Hanna K. , Stürmer Til , Westreich Daniel , Lund Jennifer L. 
Published: March 2021

AbstractAdjuvant chemotherapy regimens take months to complete. Despite this, studies evaluate chemotherapy adherence via measures assessed at the end of treatment (eg, number of patients missing any dose, relative dose intensity [RDI]). This approach ignores information like the timing of treatment delays. We propose longitudinal cumulative dose (LCD) to integrate impacts of dose reductions, missed doses and dose delays over time. We obtained data from the 2246 participants in the MOSAIC trial randomized to FOLFOX (all three agents) or 5‐FU/LV (only 5‐fluorouracil and leucovorin). We evaluated proportions of patients stopping treatment early and reducing, missing or delaying a dose in each arm for each chemotherapy agent at each cycle. We calculated LCD, the fraction of the final standard dose a participant reached by a given day, for each participant and each agent and compared it over time and at 24 weeks between treatment arms. Participants randomized to FOLFOX were more likely to stop treatment, reduce doses, miss doses or delay cycles; these differences increased over time. Median LCD for oxaliplatin in the FOLFOX arm at 24 weeks was 77%. The LCD for 5‐fluorouracil differed between arms (FOLFOX arm median: 81%; 5‐FU/LV arm median: 96%). Visualizing LCD highlighted the timing of deviations from standard administration in a way RDI could not, with major differences in 5‐fluorouracil LCD across treatment arms beginning after the sixth dose. Further evaluation of LCD and its impacts on clinical outcomes may clarify mechanisms for heterogeneous patient outcomes.
Classification of high‐grade cervical intraepithelial neoplasia by p16ink4a, Ki‐67, HPV E4 and FAM19A4/miR124‐2 methylation status demonstrates considerable heterogeneity with potential consequences for management
Authors: Vink Frederique J. , Dick Stèfanie , Heideman Daniëlle A. M. , De Strooper Lise M. A. , Steenbergen Renske D. M. , Lissenberg‐Witte Birgit I. ,   DNTP Group, Floore Arno , Bonde Jesper H. , Oštrbenk Valenčak Anja , Poljak Mario , Petry Karl U. , Hillemanns Peter , van Trommel Nienke E. , Berkhof Johannes , Bleeker Maaike C. G. , Meijer Chris J. L. M. 
Published: March 2021

AbstractHigh‐grade cervical intraepithelial neoplasia (CIN2 and CIN3) represents a heterogeneous disease with varying cancer progression risks. Biomarkers indicative for a productive human papillomavirus (HPV) infection (HPV E4) and a transforming HPV infection (p16ink4a, Ki‐67 and host‐cell DNA methylation) could provide guidance for clinical management in women with high‐grade CIN. This study evaluates the cumulative score of immunohistochemical expression of p16ink4a (Scores 0‐3) and Ki‐67 (Scores 0‐3), referred to as the “immunoscore” (IS), in 262 CIN2 and 235 CIN3 lesions derived from five European cohorts in relation to immunohistochemical HPV E4 expression and FAM19A4/miR124‐2 methylation in the corresponding cervical scrape. The immunoscore classification resulted in 30 lesions within IS group 0‐2 (6.0%), 151 lesions within IS group 3‐4 (30.4%) and 316 lesions within IS group 5‐6 (63.6%). E4 expression decreased significantly from CIN2 to CIN3 (P < .001) and with increasing immunoscore group (Ptrend < .001). Methylation positivity increased significantly from CIN2 to CIN3 (P < .001) and with increasing immunoscore group (Ptrend < .001). E4 expression was present in 9.8% of CIN3 (23/235) and in 12.0% of IS group 5‐6 (38/316). Notably, in a minority (43/497, 8.7%) of high‐grade lesions, characteristics of both transforming HPV infection (DNA hypermethylation) and productive HPV infection (E4 expression) were found simultaneously. Next, we stratified all high‐grade CIN lesions, based on the presumed cancer progression risk of the biomarkers used, into biomarker profiles. These biomarker profiles, including immunoscore and methylation status, could help the clinician in the decision for immediate treatment or a “wait and see” policy to reduce overtreatment of high‐grade CIN lesions.
Identification of known and novel familial cancer genes in Swedish colorectal cancer families
Authors: Helgadottir Hafdis T. , Thutkawkorapin Jessada , Rohlin Anna , Nordling Margareta , Lagerstedt‐Robinson Kristina , Lindblom Annika 
Published: March 2021

AbstractIdentifying new candidate colorectal cancer (CRC) genes and mutations are important for clinical cancer prevention as well as in cancer care. Genetic counseling is already implemented for known high‐risk variants; however, the majority of CRC are of unknown causes. In our study, 110 CRC patients in 55 Swedish families with a strong history of CRC but unknown genetic causes were analyzed with the aim of identifying novel candidate CRC predisposing genes. Exome sequencing was used to identify rare and high‐impact variants enriched in the families. No clear pathogenic variants were found in known CRC predisposing genes; however, potential pathogenic variants in novel CRC predisposing genes were identified. Over 3000 variants with minor allele frequency (MAF) <0.01 and Combined Annotation Dependent Depletion (CADD) > 20 were seen aggregating in the CRC families. Of those, 27 variants with MAF < 0.001 and CADD>25 were considered high‐risk mutations. Interestingly, more than half of the high‐risk variants were detected in three families, suggesting cumulating contribution of several variants to CRC. In summary, our study shows that despite a strong history of CRC within families, identifying pathogenic variants is challenging. In a small number of families, few rare mutations were shared by affected family members. This could indicate that in the absence of known CRC predisposing genes, a cumulating contribution of mutations leads to CRC observed in these families.
A randomized, double‐blind, placebo‐controlled pilot study of the comparative effects of dienogest and the combined oral contraceptive pill in women with endometriosis
Authors: Mehdizadeh Kashi Abolfazl , Niakan Gelareh , Ebrahimpour Majid , Allahqoli Leila , Hassanlouei Babak , Gitas Georgios , Alkatout Ibrahim 
Published: March 2021

AbstractObjectiveTo compare the effects of dienogest and a combined oral contraceptive pill (COCP) after laparoscopic surgery on pain and quality of life in women with severe endometriosis.MethodsA randomized double‐blind pilot study was conducted from March 2018 to March 2020 in women with severe endometriosis confirmed by laparoscopic surgery. A total of 108 patients who had undergone laparoscopic surgery received dienogest, COCP, or placebo daily for 6 months. Primary and secondary outcomes were compared between the three groups.ResultsTreatment with dienogest or COCP was associated with improved self‐reported pain after 6 months of treatment, as evidenced by significantly lower scores for pelvic pain and dyspareunia compared with placebo (P < 0.05). Significant differences in overall quality of life score were observed over 6 months in the dienogest, COCP, and placebo groups (mean difference 22.00, 23.45, and 6.45 points, respectively; P < 0.001). Post‐hoc analysis revealed a significant difference in overall quality of life score between the placebo group and the dienogest (P < 0.001) and COCP groups (P = 0.004).ConclusionPostoperative administration of dienogest or COCP reduced endometriosis‐associated pain and improved quality of life in women with severe endometriosis.Clinical trials registration: https://en.irct.ir/trial/43070.
Pattern of non‐communicable diseases during pregnancy and their effect on feto‐maternal outcome: A prospective observational study
Authors: Kumari Neha , Kathirvel Soundappan , Arora Aashima , Jain Vanita , Sikka Pooja 
Published: March 2021

AbstractObjectiveTo assess patterns of non‐communicable diseases (NCDs) and pregnancy outcomes of women in a tertiary care hospital.MethodsThis was a prospective observational study, conducted over 1 year. All NCDs in women who delivered or aborted were studied. Maternal and neonatal outcomes were noted.ResultsIn all, 1003 NCDs occurred in 894 women. Chronic hypertension was the commonest, involving 309 (30.8%) women. Others included cardiovascular (159, 15.9%), neurological (142, 14.2%), endocrine (115, 11.5%), autoimmune (76, 7.6%), chronic kidney (48, 4.8%), and chronic respiratory (43, 4.3%) diseases, psychiatric disorders (38, 3.8%), cancers (20, 2.0%), and chronic liver disease (18, 1.8%). Most (599, 67.0%) were diagnosed before pregnancy and 145 (16.2%), 81 (9.1%), and 69 (7.7%) were diagnosed in the first, second, and third trimesters, respectively. Maternal deaths occurred in 6 (0.7%) women and near miss in 19 (2.1%) women. Only 9 (1.5%) women with NCD diagnosed before pregnancy had maternal near miss or death, compared with 16 (5.4%) diagnosed during pregnancy (P < 0.001). Of live births, 281 (35.3%) were low birth weight, 49 (6.1%) were very low birth weight, and 24 (3.0%) were extremely low birth weight.ConclusionChronic hypertension was the commonest NCD, which along with cardiovascular and neurological disorders constituted around 60% of all NCDs. One‐third of NCDs were initially diagnosed during pregnancy. Maternal morbidity was lower if NCDs were diagnosed before pregnancy.
WillCOVID‐19‐related economic worries superimpose health worries, reducing nonpharmaceutical intervention acceptance in Germany? A prospective pre‐registered study
Authors: Rosman Tom , Kerwer Martin , Steinmetz Holger , Chasiotis Anita , Wedderhoff Oliver , Betsch Cornelia , Bosnjak Michael 
Published: March 2021

Nonpharmaceutical interventions (NPI) such as stay‐at‐home orders aim at curbing the spread of the novel coronavirus, SARS‐COV‐2. In March 2020, a large proportion of the German population supported such interventions. In this article, we analyse whether the support for NPI dwindle with economic worries superimposing virus‐related worries in the months to follow. We test seven pre‐registered1hypotheses using data from the German COSMO survey (Betsch, Wieler, Habersaat, et al. 2020), which regularly monitors behavioural and psychological factors related to the pandemic. The present article covers the period from March 24, 2020 to July 7, 2020 (Ntotal = 13,094), and, in addition, includes a validation study providing evidence for the reliability and validity of the corresponding COSMO measures (N = 612). Results revealed that virus‐related worries decreased over time, whereas economic worries remained largely constant. Moreover, the acceptance of NPIs considerably decreased over time. Virus‐related worries were positively associated with acceptance of NPIs, whereas this relationship was negative regarding economic worries (albeit smaller and less consistent). Unexpectedly, no interactions between virus‐related worries and economic worries were found. We conclude that individual differences in virus‐related and economic threat perceptions related to COVID‐19 play an important role in the acceptance of NPIs.
Pro‐angiogenic decellularized vessel matrix gel modified by silk fibroin for rapid vascularization of tissue engineering scaffold
Authors: Fu Qiang , Xia Bin , Huang Xiang , Wang Fuping , Chen Zhongmin , Chen Guobao 
Published: March 2021

AbstractCurrent pro‐angiogenic methods in the fields of tissue engineering always aim to enrich the vascular network but neglect to provide an appropriate environment for cells, which may lead to incomplete endothelium or thrombosis. Decellularized matrix gels derived from specific tissue are expected to be suitable for targeted tissue regeneration because they preserve the biochemical properties of the native tissue. Decellularized vascular matrix gel (DVMG) has shown promise for rapid vascularization. However, DVMG is difficult to directly apply due to its weak mechanical properties and rapid degradation. In this work, silk fibroin (SF) was introduced to the DVMG to improve the physical properties of the hybrid scaffolds. The performances of the SF/DVMG scaffolds were characterized, and the results showed that SF effectively improved the overall mechanical properties of the scaffold and decreased the degradation rate. SF/DVMG scaffolds also showed good cell growth promotion effects in vitro. After the scaffolds were subcutaneously implanted in the dorsa of rats, more CD34‐positive endothelial cells were expressed in the DVMG‐containing scaffolds, and the number of vascular loops significantly increased compared to that of the pure SF scaffold control. The development of DVMG creates more possibilities for the rapid vascular network generation of clinically engineered scaffolds.
Joint Associations of Prevalent Radiographic Vertebral Fracture and Abdominal Aortic Calcification With Incident Hip, Major Osteoporotic, and Clinical Vertebral Fractures
Authors: Schousboe John T , Langsetmo Lisa , Szulc Pawel , Lewis Joshua R , Taylor Brent C , Kats Allyson M , Vo Tien N , Ensrud Kristine E 
Published: March 2021

ABSTRACT
Prevalent vertebral fractures (PVFx) and abdominal aortic calcification (AAC) are both associated with incident fractures and can be ascertained on the same lateral spine images, but their joint association with incident fractures is unclear. Our objective was to estimate the individual and joint associations of PVFx and AAC with incident major osteoporotic, hip, and clinical vertebral fractures in 5365 older men enrolled in the Osteoporotic Fractures in Men (MrOS) Study, using Cox proportional hazards and Fine and Gray subdistribution hazards models to account for competing mortality. PVFx (Genant SQ grade 2 or 3) and 24-point AAC score were ascertained on baseline lateral spine radiographs. Self-reports of incident fractures were solicited every 4 months and confirmed by review of clinical radiographic reports. Compared with men without PVFx and AAC-24 score 0 or 1, the subdistribution hazard ratio (SHR) for incident major osteoporotic fracture was 1.38 (95% confidence interval [CI] 1.13–1.69) among men with AAC-24 score ≥2 alone, 1.71 (95% CI 1.37–2.14) for men with PVFx alone, and 2.35 (95% CI 1.75–3.16) for men with both risk factors, after accounting for conventional risk factors and competing mortality. Wald statistics showed improved prediction model performance by including both risk factors compared with including only AAC (chi-square = 17.3, p &lt; .001) or including only PVFx (chi-square = 8.5, p = .036). Older men with both PVFx and a high level of AAC are at higher risk of incident major osteoporotic fracture than men with either risk factor alone. Assessing prevalent radiographic vertebral fracture and AAC on the same lateral spine images may improve prediction of older men who will have an incident major osteoporotic fracture, even after accounting for traditional fracture risk factors and competing mortality. © 2021 American Society for Bone and Mineral Research (ASBMR).
The competition and cooperativity of hydrogen/halogen bond and π‐hole bond involving the heteronuclear ethylene analogues
Authors: Shen Shaojie , Jing Xinyue , Zhang Xueying , Li Xiaoyan , Zeng Yanli 
Published: March 2021

AbstractThe noncovalent interactions involving heteronuclear ethylene analogues H2CEH2(E = Si, Ge and Sn) have been studied by the Møller–Plesset perturbation theory to investigate the competition and cooperativity between the hydrogen/halogen bond and π‐hole bond. H2CEH2has a dual role of being a Lewis base and acid with the region of π‐electron accumulation above the carbon atom and the region of π‐electron depletion (π‐hole) above the E atom to participate in the NCX···CE (X = H and Cl) hydrogen/halogen bond and CE···NCY (Y = H, Cl, Li and Na) π‐hole bond, respectively. When HCN/ClCN interacts with H2CEH2by two sites, the strength of hydrogen bond/halogen bond is stronger than that of π‐hole bond. The π‐hole bond becomes obviously stronger when the metal substituent of YCN (Y = Li and Na) interacting with H2CEH2, showing the character of partial covalent, its strength is much greater than that of hydrogen/halogen bond. In the ternary complexes, both hydrogen/halogen bond and π‐hole bond are simultaneously strengthened compared to those in the binary complexes, especially in the systems containing alkali metal.
The current landscape of genetic test stewardship: A multi‐center prospective study
Authors: Kieke Michele C. , Conta Jessie H. , Riley Jacquelyn D. , Zetzsche Lindsay H. 
Published: March 2021

AbstractGenetic counselors (GCs) play a pivotal role in selecting clinically appropriate and cost‐effective genetic testing. Several single‐institution reports over the past decade provide evidence of the value GCs bring to this stewardship role across diverse settings in healthcare, including hospital laboratories, commercial laboratories, and insurance companies. This multi‐center, prospective, and quantitative study describes the outcomes of GC review of genetic test requests over a four‐week period at six hospital laboratories and three commercial laboratories, thus expanding our understanding of this emerging specialty in the genetic counseling field. This study also highlights the added value of utilizing GC expertise in stewardship efforts, namely selecting the most appropriate genetic testing and realizing significant cost savings. GC review of genetic test requests led to an average order modification rate of 22%–25%. It also resulted in significant cost savings to institutions. The projected average annual savings after GC review of genetic test requests approximated $665,600 for hospital laboratories and $1,651,000 for commercial laboratories. These study findings demonstrate the significant value of GC‐led genetic test stewardship programs, allow for comparisons across institutions currently performing genetic test stewardship, and support the implementation of a GC‐led stewardship program at institutions who currently do not have one.
Bone Marrow Fat Measured by a Chemical Shift‐Encoded Sequence (IDEAL‐IQ) in Patients With and Without Metabolic Syndrome
Authors: Ma Qiang , Cheng Xiaoyue , Hou Xinmeng , Yang Zhenghan , Ma Daqing , Wang Zhenchang 
Published: March 2021

BackgroundMetabolic syndrome increases the risk of chronic diseases such as cardiovascular disease and diabetes. Metabolic syndrome also has an impact on bone mineral density. However, the relationship between metabolic syndrome and bone marrow fat is unclear.PurposeTo determine factors associated with bone marrow fat concentration in subjects with and without metabolic syndrome.Study TypeRetrospective.PopulationOne hundred and one women with metabolic syndrome (31.0 years ±5.1) and 96 female living liver transplant donors (32.0 years ±3.7). Our institutional review board approved the study. Each subject signed written informed consent.Field Strength/Sequence3.0 T MRI system and a commercially available chemical shift‐encoded 3D sequence (Iterative Decomposition of water and fat with Echo asymmetry and Least Square Estimation).AssessmentProton density fat fraction (PDFF) in liver, vertebral body, and paraspinal muscle (erector spinae) were measured from a single acquisition by a 15‐year‐experience orthopedic radiologist. The factors associated with PDFF were acquired.Statistical TestsThe analysis of covariance test, after adjustment for body mass index and age, was used to analyze the differences between metabolic syndrome and non‐metabolic syndrome groups. A stepwise multiple regression analysis was used to determine which variables were independently associated with PDFF.ResultsMean vertebral PDFF and alanine aminotransferase (ALT) were significantly lower in donors than subjects with metabolic syndrome (both P < 0.05). Serum vitamin D concentration, ferritin, and high‐density lipoprotein (HDL) cholesterol were significantly higher in donors than subjects with metabolic syndrome (all P < 0.05). Multiple regression analysis revealed antidiabetic medicine, higher serum vitamin D concentration, lower waist circumference, lower ferritin, lower HDL, absence of metabolic syndrome, and lower ALT were significantly associated with lower vertebral PDFF (all P < 0.05).Data ConclusionMultiple factors affect bone marrow fat concentration in subjects with metabolic syndrome. Serum vitamin D concentration and antidiabetic medicine are associated with low bone marrow fat, whereas waist circumference, serum ferritin, metabolic syndrome, imbalanced lipid metabolism, and abnormal liver function are associated with high bone marrow fat.Level of Evidence Level3Technical Efficacy Stage1