bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accurate recognition of colorectal cancer with semi-supervised deep learning on pathological images
Authors: Yu Gang , Sun Kai , Xu Chao , Shi Xing-Hua , Wu Chong , Xie Ting , Meng Run-Qi , Meng Xiang-He , Wang Kuan-Song , Xiao Hong-Mei , Deng Hong-Wen 
Published: November 2021

AbstractMachine-assisted pathological recognition has been focused on supervised learning (SL) that suffers from a significant annotation bottleneck. We propose a semi-supervised learning (SSL) method based on the mean teacher architecture using 13,111 whole slide images of colorectal cancer from 8803 subjects from 13 independent centers. SSL (~3150 labeled, ~40,950 unlabeled; ~6300 labeled, ~37,800 unlabeled patches) performs significantly better than the SL. No significant difference is found between SSL (~6300 labeled, ~37,800 unlabeled) and SL (~44,100 labeled) at patch-level diagnoses (area under the curve (AUC): 0.980 ± 0.014 vs. 0.987 ± 0.008, P value = 0.134) and patient-level diagnoses (AUC: 0.974 ± 0.013 vs. 0.980 ± 0.010, P value = 0.117), which is close to human pathologists (average AUC: 0.969). The evaluation on 15,000 lung and 294,912 lymph node images also confirm SSL can achieve similar performance as that of SL with massive annotations. SSL dramatically reduces the annotations, which has great potential to effectively build expert-level pathological artificial intelligence platforms in practice.
A national and sub-national metaregression of the trend of insufficient physical activity among Iranian adults between 2001 and 2016
Authors: Kamalian Aida , Khosravi Shadmani Fatemeh , Yoosefi Moein , Mohajer Bahram , Mohebi Farnam , Naderimagham Shohreh , Rezaei Negar , Ghasemi Erfan , Rouhifard Khalilabad Mahtab , Hassanmirzaei Bahar , Selk Ghaffari Maryam , Khosravi Afifeh , Kordi Ramin , Farzadfar Farshad 
Published: November 2021

AbstractInsufficient physical activity (IPA) caused approximately 5% of mortalities in 2017 in Iran, almost double its global average. Despite the relatively considerable burden, a knowledge gap exists regarding the trend of IPA in recent years. We described the trend of IPA prevalence utilizing the data from six rounds of STEPwise approach to risk factor Surveillance (STEPS) in Iran. We estimated the physical activity status of Iranian adults from 2006 to 2016 after adjusting for years of schooling, urbanization percentage, and wealth index. We used the spatiotemporal model to interpolate and extrapolate the IPA prevalence for the years in-between the series and from 2001 to 2006, respectively. We used the data of 177,910 participants from six STEPS surveys and found that the national prevalence of IPA had steadily increased over the course of 16 years and had almost doubled in this time period (23.1% in 2001 to 55.4% in 2016). The increase was persistent across all age and gender strata and in every province. Moreover, IPA was more prevalent among women than their male peers regardless of their age category or province of residence. The prevalence of IPA in Khuzestan (highest prevalence) was almost double compared to that in Lorestan (lowest prevalence) in 2016. The IPA prevalence increased considerably and almost doubled in 16 years among Iranian adults, particularly women. Policies need to target IPA as a high priority contributing to the burden of Non-communicable diseases.
Human iPS cell derived RPE strips for secure delivery of graft cells at a target place with minimal surgical invasion
Authors: Nishida Mitsuhiro , Tanaka Yuji , Tanaka Yo , Amaya Satoshi , Tanaka Nobuyuki , Uyama Hirofumi , Masuda Tomohiro , Onishi Akishi , Sho Junki , Yokota Satoshi , Takahashi Masayo , Mandai Michiko 
Published: November 2021

AbstractSeveral clinical studies have been conducted into the practicality and safety of regenerative therapy using hESC/iPSC-retinal pigment epithelium (RPE) as a treatment for the diseases including age-related macular degeneration. These studies used either suspensions of RPE cells or an RPE cell sheet. The cells can be injected using a minimally invasive procedure but the delivery of an intended number of cells at an exact target location is difficult; cell sheets take a longer time to prepare, and the surgical procedure is invasive but can be placed at the target area. In the research reported here, we combined the advantages of the two approaches by producing a quickly formed hiPSC-RPE strip in as short as 2 days. The strip readily expanded into a monolayer sheet on the plate, and after transplantation in nude rats, it showed a potency to partly expand with the correct apical/basal polarity in vivo, although limited in expansion area in the presence of healthy host RPE. The strip could be injected into a target area in animal eyes using a 24G canula tip.
A system for reporting and evaluating adverse drug reactions of herbal medicine in Taiwan from 1998 to 2016
Authors: Chang Hen-Hong , Chiang Su-Yin , Chen Pei-Chun , Tsai Chia-Han , Yang Rong-Chi , Tsai Chiu-Lin , Wu Tsung-hsiu , Hsieh Yow-Wen , Lin Yu-Chun , Kuo Yung-Te , Chen Kuan-Chung , Chu Hsueh-Ting 
Published: November 2021

AbstractThe Taiwan Adverse Drug Reaction Reporting System for Herbal Medicine (TADRRS-HM) has systematically documented suspected adverse events from adverse drug reaction (ADR) reports from 1998 (prior to its formal establishment in 2001) and evaluates safety profiles of herbal medicines. This article describes findings from 2079 ADR reports filed between 1998 and 2016: 941 reports involved single herbs and 87 involved folk herbals; 842 were generated from clinical trials, while 209 ADR reports involving foods, health foods, dietary supplement foods and herbal cuisine were grouped as Other. Severity assessments using the Modified Hartwig and Siegel scale classified 72.4% of ADRs as mild, 17.4% as moderate and 6.5% as severe. System Organ Class classification of the ADRs identified gastrointestinal system disorders as the most common (33.4%), followed by skin and subcutaneous tissue disorders (21.2%). The TADRRS-HM records indicate that herbal medicines may cause a wide range of ADRs. Aconiti Radix, Xiao-Qing-Long-Tang, and Datura suaveolens were the most commonly reported single herb, herbal formula, and folk herbal, respectively. The data indicate that herbal medicines may cause a wide range of ADRs. This system will confer long-term benefits for the development of Taiwan’s herbal medicines adverse reaction database and facilitate epidemiological analysis.
Shorter duration of first-line chemotherapy reflects poorer outcomes in patients with HER2-negative advanced breast cancer: a multicenter retrospective study
Authors: Nakamoto Shogo , Watanabe Junichiro , Ohtani Shoichiro , Morita Satoshi , Ikeda Masahiko 
Published: November 2021

AbstractPost-progression survival affects overall survival (OS) in patients with HER2-negative advanced breast cancer (HER2-ABC); thus, the optimal choice of first-line chemotherapy (1LCT) remains controversial. We investigated patients with HER2-ABC focusing on their sensitivity to 1LCT. We retrospectively analyzed patients with HER2-ABC who received 1LCT between January 2011 and December 2016 in three participating institutions. We identified 149 patients in the shorter and 152 patients in the longer time to treatment failure (TTF) groups. The median OS was significantly longer in the longer TTF group (hazard ratio [HR] 0.44, P < 0.001, log-rank). In the shorter TTF group, OS of patients who received paclitaxel plus bevacizumab (PB) therapy was significantly inferior to that of those who received chemotherapy other than PB (HR 2.57, P < 0.001, log-rank), and subsequent eribulin therapy significantly improved OS from 1LCT initiation (Wilcoxon P < 0.001); multivariate analyses showed that 1LCT PB therapy was an independent risk factor for poorer OS (HR 2.05, P = 0.003), while subsequent eribulin therapy was an independent prognostic factor for better OS (HR 0.56, P = 0.004). OS was significantly poorer in patients with HER2-ABC with a shorter duration of 1LCT, including PB therapy, while subsequent eribulin therapy improved OS.
Accumulating candidate genes for broad-spectrum resistance to rice blast in a drought-tolerant rice cultivar
Authors: Carrillo Maria Gay C. , Martin Federico , Variar Mukund , Bhatt J. C. , L. Perez-Quintero Alvaro , Leung Hei , Leach Jan E. , Vera Cruz Casiana M. 
Published: November 2021

AbstractBiotic stresses, including diseases, severely affect rice production, compromising producers’ ability to meet increasing global consumption. Understanding quantitative responses for resistance to diverse pathogens can guide development of reliable molecular markers, which, combined with advanced backcross populations, can accelerate the production of more resistant varieties. A candidate gene (CG) approach was used to accumulate different disease QTL from Moroberekan, a blast-resistant rice variety, into Vandana, a drought-tolerant variety. The advanced backcross progeny were evaluated for resistance to blast and tolerance to drought at five sites in India and the Philippines. Gene-based markers were designed to determine introgression of Moroberekan alleles for 11 CGs into the progeny. Six CGs, coding for chitinase, HSP90, oxalate oxidase, germin-like proteins, peroxidase and thaumatin-like protein, and 21 SSR markers were significantly associated with resistance to blast across screening sites. Multiple lines with different combinations, classes and numbers of CGs were associated with significant levels of race non-specific resistance to rice blast and sheath blight. Overall, the level of resistance effective in multiple locations was proportional to the number of CG alleles accumulated in advanced breeding lines. These disease resistant lines maintained tolerance to drought stress at the reproductive stage under blast disease pressure.
Auto/paracrine factors and early Wnt inhibition promote cardiomyocyte differentiation from human induced pluripotent stem cells at initial low cell density
Authors: Le Minh Nguyen Tuyet , Takahi Mika , Ohnuma Kiyoshi 
Published: November 2021

AbstractCardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) have received increasing attention for their clinical use. Many protocols induce cardiomyocytes at an initial high cell density (confluence) to utilize cell density effects as hidden factors for cardiomyocyte differentiation. Previously, we established a protocol to induce hiPSC differentiation into cardiomyocytes using a defined culture medium and an initial low cell density (1% confluence) to minimize the hidden factors. Here, we investigated the key factors promoting cardiomyocyte differentiation at an initial low cell density to clarify the effects of cell density. Co-culture of hiPSCs at an initial low cell density with those at an initial high cell density showed that signals secreted from cells (auto/paracrine factors) and not cell–cell contact signals, played an important role in cardiomyocyte differentiation. Moreover, although cultures with initial low cell density showed higher expression of anti-cardiac mesoderm genes, earlier treatment with a Wnt production inhibitor efficiently suppressed the anti-cardiac mesoderm gene expression and promoted cardiomyocyte differentiation by up to 80% at an initial low cell density. These results suggest that the main effect of cell density on cardiomyocyte differentiation is inhibition of Wnt signaling at the early stage of induction, through auto/paracrine factors.
Idiotype vaccines produced with a non-cytopathic alphavirus self-amplifying RNA vector induce antitumor responses in a murine model of B-cell lymphoma
Authors: Casales Erkuden , Martisova Eva , Villanueva Helena , de Cerio Ascensión López Díaz , Inoges Susana , Silva-Pilipich Noelia , Ballesteros-Briones María Cristina , Aranda Alejandro , Bezunartea Jaione , Bendandi Maurizio , Pastor Fernando , Smerdou Cristian 
Published: November 2021

AbstractA promising therapy for patients with B-cell lymphoma is based on vaccination with idiotype monoclonal antibodies (mAbs). Since idiotypes are different in each tumor, a personalized vaccine has to be produced for each patient. Expression of immunoglobulins with appropriate post-translational modifications for human use often requires the use of stable mammalian cells that can be scaled-up to reach the desired level of production. We have used a noncytopathic self-amplifying RNA vector derived from Semliki Forest virus (ncSFV) to generate BHK cell lines expressing murine follicular lymphoma-derived idiotype A20 mAb. ncSFV/BHK cell lines expressed approximately 2 mg/L/24 h of A20 mAb with proper quaternary structure and a glycosylation pattern similar to that of A20 mAb produced by hybridoma cells. A20 mAb purified from the supernatant of a ncSFV cell line, or from the hybridoma, was conjugated to keyhole limpet hemocyanin and used to immunize Balb/c mice by administration of four weekly doses of 25 µg of mAb. Both idiotype mAbs were able to induce a similar antitumor protection and longer survival compared to non-immunized mice. These results indicate that the ncSFV RNA vector could represent a quick and efficient system to produce patient-specific idiotypes with potential application as lymphoma vaccines.
Superior operational stability of immobilized l-asparaginase over surface-modified carbon nanotubes
Authors: Almeida Mafalda R. , Cristóvão Raquel O. , Barros Maria A. , Nunes João C. F. , Boaventura Rui A. R. , Loureiro José M. , Faria Joaquim L. , Neves Márcia C. , Freire Mara G. , Santos-Ebinuma Valéria C. , Tavares Ana P. M. , Silva Cláudia G. 
Published: November 2021

Abstractl-asparaginase (ASNase, EC 3.5.1.1) is an enzyme that catalyzes the l-asparagine hydrolysis into l-aspartic acid and ammonia, being mainly applied in pharmaceutical and food industries. However, some disadvantages are associated with its free form, such as the ASNase short half-life, which may be overcome by enzyme immobilization. In this work, the immobilization of ASNase by adsorption over pristine and modified multi-walled carbon nanotubes (MWCNTs) was investigated, the latter corresponding to functionalized MWCNTs through a hydrothermal oxidation treatment. Different operating conditions, including pH, contact time and ASNase/MWCNT mass ratio, as well as the operational stability of the immobilized ASNase, were evaluated. For comparison purposes, data regarding the ASNase immobilization with pristine MWCNT was detailed. The characterization of the ASNase-MWCNT bioconjugate was addressed using different techniques, namely Transmission Electron Microscopy (TEM), Thermogravimetric Analysis (TGA) and Raman spectroscopy. Functionalized MWCNTs showed promising results, with an immobilization yield and a relative recovered activity of commercial ASNase above 95% under the optimized adsorption conditions (pH 8, 60 min of contact and 1.5 × 10–3 g mL−1 of ASNase). The ASNase-MWCNT bioconjugate also showed improved enzyme operational stability (6 consecutive reaction cycles without activity loss), paving the way for its use in industrial processes.
Uremic serum damages endothelium by provoking excessive neutrophil extracellular trap formation
Authors: Lee Hoi Woul , Nizet Victor , An Jung Nam , Lee Hyung Seok , Song Young Rim , Kim Sung Gyun , Kim Jwa-Kyung 
Published: November 2021

AbstractCardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Endothelial cell (EC) dysfunction is a key CKD-specific risk factor; however, the mechanisms by which uremia harms the endothelium are still unclear. We report a role for excessive neutrophil extracellular trap (NET) formation induced by uremic serum on EC injury. Level of plasma nucleosome and myeloperoxidase-DNA, established in vivo markers of NETs, as well as intracellular adhesion molecule (ICAM)-1 were measured in hemodialysis (HD) patients and healthy volunteers (HV) and their prognostic role evaluated. For in vitro studies, HV-derived neutrophils and differentiated HL-60 cells by retinoic acid were used to determine the effect of uremic serum-induced NETs on human umbilical vein EC (HUVEC). The level of in vivo NETs was significantly higher in incident HD patients compared to HV, and these markers were strongly associated with ICAM-1. Specifically, nucleosome and ICAM-1 levels were independent predictors of a composite endpoint, all-cause mortality, or vascular access failure. In vitro, HD-derived uremic serum significantly increased NET formation both in dHL-60 and isolated neutrophils compared to control serum, and these NETs decreased EC viability and induced their apoptosis. In addition, the level of ICAM-1, E-selectin and von Willebrand factor in HUVEC supernatant was significantly increased by uremic serum-induced NETs compared to control serum-induced NETs. Dysregulated neutrophil activities in the uremic milieu may play a key role in vascular inflammatory responses. The high mortality and CVD rates in ESRD may be explained in part by excessive NET formation leading to EC damage and dysfunction.
miR-146a modulates TLR1/2 and 4 induced inflammation and links it with proliferation and lipid production via the indirect regulation of GNG7 in human SZ95 sebocytes
Authors: Dull Katalin , Fazekas Fruzsina , Deák Dávid , Kovács Dóra , Póliska Szilárd , Szegedi Andrea , Zouboulis Christos C. , Törőcsik Dániel 
Published: November 2021

AbstractActivation of Toll-like receptors (TLR) 1/2 and 4 are central in inducing inflammation in sebocytes by regulating the expression of protein coding mRNAs, however the microRNA (miRNA) profile in response to TLR activation and thus the possible role of miRNAs in modulating sebocyte functions has not been elucidated. In this work we identified miR-146a to have the highest induction in the TLR1/2 and 4 activated SZ95 sebocytes and found that its increased levels led to the down-regulation of IL-8 secretion, decreased the chemoattractant potential and stimulated the proliferation of sebocytes. Assessing the gene expression profile of SZ95 sebocytes treated with a miR-146a inhibitor, the induction of GNG7 was one of the highest, while when cells were treated with a miR-146a mimic, the expression of GNG7 was down-regulated. These findings correlated with our in situ hybridization results, that compared with control, miR-146a showed an increased, while GNG7 a decreased expression in sebaceous glands of acne samples. Further studies revealed, that when inhibiting the levels of GNG7 in SZ95 sebocytes, cells increased their lipid content and decreased their proliferation. Our findings suggest, that miR-146a could be a potential player in acne pathogenesis by regulating inflammation, inducing proliferation and, through the indirect down-regulation of GNG7, promoting the lipid production of sebocytes.
Shape-changing chains for morphometric analysis of 2D and 3D, open or closed outlines
Authors: Li Bingjue , Zhou Shengmin , Murray Andrew Peter , Subsol Gérard 
Published: November 2021

AbstractMorphometrics is a multivariate technique for shape analysis widely employed in biological, medical, and paleoanthropological applications. Commonly used morphometric methods require analyzing a huge amount of variables for problems involving a large number of specimens or complex shapes. Moreover, the analysis results are sometimes difficult to interpret and assess. This paper presents a methodology to synthesize a shape-changing chain for 2D or 3D curve fitting and to employ the chain parameters in stepwise discriminant analysis (DA). The shape-changing chain is comprised of three types of segments, including rigid segments that have fixed length and shape, scalable segments with a fixed shape, and extendible segments with constant curvature and torsion. Three examples are presented, including 2D mandible profiles of fossil hominin, 2D leaf outlines, and 3D suture curves on infant skulls. The results demonstrate that the shape-changing chain has several advantages over common morphometric methods. Specifically, it can be applied to a wide range of 2D or 3D profiles, including open or closed curves, and smooth or serrated curves. Additionally, the segmentation of profiles is a flexible and automatic protocol that can consider both biological and geometric features, the number of variables obtained from the fitting results for statistical analysis is modest, and the chain parameters that characterize the profiles can have physical meaning.
Corrosion mitigation in desalination plants by ammonium-based ionic liquid
Authors: Deyab M. A. , Mohsen Q. 
Published: November 2021

AbstractCuNi (90:10) alloy is widely used in desalination plants. CuNi alloy corrosion in sulfide-containing seawater is the fundamental problem in the desalination industry. Here we have confronted this difficulty by using ammonium-based ionic liquid (Diethyl (2-methoxyethyl)-methyl ammonium Bis(fluorosulfonyl)imide) [DEMEMA][FSI]. The results revealed that the [DEMEMA][FSI] can suppress Cu–Ni alloy corrosion in a solution of (3.5% NaCl + 10 ppm sulphide) with an efficiency of 98.4% at 120 ppm. This has been estimated by electrochemistry and gravimetry. Furthermore, [DEMEMA][FSI] inhibits the growth of sulfate-reducing bacteria SRB in saline water. Surface morphology testing confirmed [DEMEMA][FSI] adsorption on Cu–Ni surface alloys. In addition, quantum calculations have been used to theoretically predict inhibition efficiency [DEMEMA][FSI].
Functional disruption of cell wall invertase inhibitor by genome editing increases sugar content of tomato fruit without decrease fruit weight
Authors: Kawaguchi Kohei , Takei-Hoshi Rie , Yoshikawa Ikue , Nishida Keiji , Kobayashi Makoto , Kusano Miyako , Lu Yu , Ariizumi Tohru , Ezura Hiroshi , Otagaki Shungo , Matsumoto Shogo , Shiratake Katsuhiro 
Published: November 2021

AbstractSugar content is one of the most important quality traits of tomato. Cell wall invertase promotes sucrose unloading in the fruit by maintaining a gradient of sucrose concentration between source leaves and fruits, while invertase inhibitor (INVINH) regulates this process. In this study, knock-out of cell wall INVINH in tomato (SlINVINH1) was performed by genome editing using, CRISPR/Cas9 and Target-AID technologies. Most of the genome-edited lines set higher soluble solid content (SSC) fruit than the original cultivar ‘Suzukoma’, while fruit weight was different among the genome-edited lines. From these genome-edited lines, three lines (193–3, 199–2, and 247–2), whose SSC was significantly higher than ‘Suzukoma’ and fruit weight were almost the same as the original cultivar, were selected. The fruit weight and overall plant growth of the two lines were comparable to those of the original cultivar. In contrast, the fructose and glucose contents in the mature fruits of the two lines were significantly higher than those of the original cultivar. The mature fruits of genome edited line 193–3 showed the highest sugar content, and the fructose and glucose contents were 29% and 36% higher than that of the original cultivar, respectively. Whole genome sequence data showed no off-target mutations in the genome-edited lines. Non-target metabolome analysis of mature fruits revealed that fructose was the highest loading factor in principal component analysis (PCA) between the genome-edited line and the original cultivar, and no unexpected metabolites appeared in the genome-edited line. In this study, we succeeded in producing tomato lines with high sugar content without a decrease in fruit weight and deterioration of plant growth by knock-out of SlINVINH1 using genome editing technology. This study showed that functional disruption of SlINVINH1 is an effective approach to produce tomato cultivars with high sugar content.