bluuebunny/crossref_metadata_2025 huggingface dataset:
Decomposition Behavior of Triarrhena lutarioriparia Tissues in Dongting Lake Water: A Laboratory Simulation Study
Authors: Zhao Yuanyuan , Xu Youze , Fu Guangyi , Tang Nan , Zhou Shuang
Published: December 2021

Following the overall withdrawal of papermaking enterprises, Triarrhena lutarioriparia, a most abundant macrophyte of Dongting Lake wetland, will remain to be uncut and decay in the lake water. The decomposition dynamics of T. lutarioriparia tissues and the decomposition effects on water quality are investigated in this study. The results show that two main processes are observed during the 90‐day decomposition period of T. lutarioriparia: rapid leaching and gradual biodegradation. During the initial 10‐day leaching process, the initial weight loss of leaves, spikes, and stems reached 13.33%, 12.44%, and 4.67%, respectively; meanwhile, 15.12–32.62% of total nitrogen and 24.16–45.45% of total phosphorus in the tissues are released to the water. The decomposition rate of T. lutarioriparia tissues is in the order: spikes (0.0053 day−1) > leaves (0.0045 day−1) > stems (0.0033 day−1). The T. lutarioriparia decomposition exerted adverse effects on the lake water quality, including the depletion of dissolved oxygen, the increase in concentrations of organic matter and nutrients, especially during the rapid leaching process. Such adverse effects are significantly associated with both the biomass (p < 0.001) and the species of T. lutarioriparia tissues (p < 0.05).
Flush of Nitrous Oxide Emissions from Plastic Greenhouse Soil during Initial Application of Poultry Manure
Authors: Bai Xinlu , Luo Wei , Jiang Yun , Zhang Zhaobei , Chen Zhujun , Zhou Jianbin
Published: December 2021

Poultry manure, which contains abundant water‐soluble organic matter (WSOM), is commonly applied in plastic greenhouse vegetable production. There is little research on whether WSOM stimulates nitrous oxide (N2O) emission after poultry manure application. A 30 day incubation experiment and a field experiment are conducted to investigate the response of the N2O flux after poultry manure or WSOM inputs. The cumulative N2O emissions from soil amended with WSOM in the incubation experiment are two to four times than those from unamended soil. Similarly, in the field experiment, the N2O emissions significantly increased by 225% (to 1.13 kg N ha−1) after poultry manure and irrigation application compared to a control during summer fallow season, accounting for ≈20% of the annual N2O emissions from plastic greenhouse vegetable production. In conclusion, WSOM in poultry manure increases N2O emissions from plastic greenhouse soil during its initial application; moreover, N2O emissions during summer fallow season should be included in the N2O emission inventory of plastic greenhouse vegetable production. Measures for controlling N2O emissions such as avoiding nitrate accumulation and improving water and poultry manure management should be adopted in plastic greenhouse vegetable production.
Biomarkers for respiratory diseases: Present applications and future discoveries
Authors: Liu Xiaojing , Cui Bo , Wang Qian , Ma Yuan , Li Li , Chen Zhihong
Published: December 2021

Biomarkers such as clinical characteristics and laboratory indices have been widely used in many respiratory diseases, such as chronic airway diseases, lung infection, lung cancer and acute respiratory distress syndrome. As such, various non‐invasive and invasive samples, such as blood, urine, induced sputum, bronchoalveolar lavage fluid and lung biopsy are currently being collected. Omics‐based discovery strategies facilitate the identification of next‐generation candidate biomarkers. The identification and integration of multiple omics biomarkers (genomics, epigenomics, proteomics, metabolomics and radiomics) can answer many unsolved questions about respiratory diseases. The ultimate realization of the translation of novel biomarkers into clinical practice is a major challenge because good biomarkers must be sensitive, technically feasible, non‐invasive, non‐expensive and most importantly, validated. The four stages of clinical trial design in the development of biomarkers are also discussed. The concept of systems biology not only focuses on novel molecular biomarkers but also integrates clinical, laboratory and omics information as a whole. Finally, developing multiple biomarker panels is a goal to improve the healthcare of respiratory diseases.
Clinical standardization of metagenomic next generation sequencing (mNGS) in the pathogen diagnosis
Authors: Qian Mengjia , Zhan Yanxia , Wu Duojiao , Ji Lili , Chen Hao , Cheng Yunfeng
Published: December 2021

Background

With the development and advancement of gene sequencing technologies, next generation sequencing, especially metagenomic next generation sequencing (mNGS), has been explored in infectious disease diagnosis.

Aims

To first introduce the standardization of each step of mNGS, the interpretation of positive and negative results and their clinic application in pathogen diagnosis.

Methods

A typical workflow of mNGS includes six main steps: sample collection, nucleic acid extraction, library construction, sequencing ,data analysis and report writing.

Results

Based on our previous work, we introduce the standardization of steps of mNGS in pathogen diagnosis and summarize the interpretation of positve and negative results and their application in clinic settings.

Conclusion

It is believed that this clinical standardization of mNGS could be a routine diagnostic tool for infectious diseases in coming future.
Management of clinical precision medicine
Authors: Chen Hao , Qian Mengjia , Ji Lili , Li Feng , Cheng Yunfeng
Published: December 2021

Precision medicine is an emerging approach for patient treatment as it allows clinicians to select therapies based on the genetic understanding of the disease. The advances of science and technology have greatly speeded up the development of associated applications. Clinical precision medicine is an up‐to‐date resource of precision medicine, an evolving technology and pathway towards optimal clinical performance. Clinical precision medicine adopts the combination of clinical phenotype with gene heterogeneity and carries out targeted therapy per patients gene mutation and heterogeneity. The management of precision medicine in clinical practice is pivotal in this new mode that patients can take the best advantage of precision medicine.
Cholangiocyte organoids from human bile retain a local phenotype and can repopulate bile ducts in vitro
Authors: Roos Floris J. M. , Wu Haoyu , Willemse Jorke , Lieshout Ruby , Albarinos Laura A. Muñoz , Kan Yik‐Yang , Poley Jan‐Werner , Bruno Marco J. , de Jonge Jeroen , Bártfai Richard , Marks Hendrik , IJzermans Jan N. M. , Verstegen Monique M. A. , van der Laan Luc J. W.
Published: December 2021

The well‐established 3D organoid culture method enabled efficient expansion of cholangiocyte‐like cells from intrahepatic (IHBD) and extrahepatic bile duct (EHBD) tissue biopsies. The extensive expansion capacity of these organoids enables various applications, from cholangiocyte disease modelling to bile duct tissue engineering. Recent research demonstrated the feasibility of culturing cholangiocyte organoids from bile, which was minimal‐invasive collected via endoscopic retrograde pancreaticography (ERCP). However, a detailed analysis of these bile cholangiocyte organoids (BCOs) and the cellular region of origin was not yet demonstrated. In this study, we characterize BCOs and mirror them to the already established organoids initiated from IHBD‐ and EHBD‐tissue. We demonstrate successful organoid‐initiation from extrahepatic bile collected from gallbladder after resection and by ERCP or percutaneous transhepatic cholangiopathy from a variety of patients. BCOs initiated from these three sources of bile all show features similar to in vivo cholangiocytes. The regional‐specific characteristics of the BCOs are reflected by the exclusive expression of regional common bile duct genes (HOXB2 and HOXB3) by ERCP‐derived BCOs and gallbladder‐derived BCOs expressing gallbladder‐specific genes. Moreover, BCOs have limited hepatocyte‐fate differentiation potential compared to intrahepatic cholangiocyte organoids. These results indicate that organoid‐initiating cells in bile are likely of local (extrahepatic) origin and are not of intrahepatic origin. Regarding the functionality of organoid initiating cells in bile, we demonstrate that BCOs efficiently repopulate decellularized EHBD scaffolds and restore the monolayer of cholangiocyte‐like cells in vitro. Bile samples obtained through minimally invasive procedures provide a safe and effective alternative source of cholangiocyte organoids. The shedding of (organoid‐initiating) cholangiocytes in bile provides a convenient source of organoids for regenerative medicine.
Biological significance of MYC and CEBPD coamplification in urothelial carcinoma: Multilayered genomic, transcriptional and posttranscriptional positive feedback loops enhance oncogenic glycolysis
Authors: Chan Ti‐Chun , Chen Yi‐Ting , Tan Kien Thiam , Wu Chia‐Ling , Wu Wen‐Jeng , Li Wei‐Ming , Wang Ju‐Ming , Shiue Yow‐Ling , Li Chien‐Feng
Published: December 2021

Background and purpose

The aim of this study is to decipher the underlying mechanisms of CCAAT/enhancer‐binding protein delta (CEBPD)‐enhanced glycolysis as well as the biological significance of CEBPD and MYC coamplification in urothelial carcinoma (UC).

Methods

In vitro analyses were conducted to examine the effects of altered CEBPD or MYC expression on UC cells. The in vivo effects of CEBPD overexpression in a high‐glucose environment on tumour growth were investigated in xenografted induced diabetic severe combined immunodeficiency/beige mice. Data mining was used to cross‐validate the associations between CEBPD and MYC copy number and transcriptional expression, quantitative reverse transcription‐polymerase chain reaction, immunohistochemistry, chromogenic in situ hybridization, and in situ hybridization targeting microRNA were performed on 635 UC patient samples and xenograft samples. UC patient survival in relation to diabetes was validated by using the National Health Insurance Research Database.

Results

CEBPD and MYC coamplification (29.6%) occurred at a high frequency, MYC expression promoted chromosomal instability, facilitating CEBPD copy number gain and expression. CEBPD promoted glucose uptake and lactate production by upregulating SLC2A1 and HK2, leading to mitochondrial fission, increased extracellular acidification rate and decreased oxygen consumption rate to fuel cell growth. CEBPD upregulated HK2 expression through multiple regulation pathways including MYC stabilization, suppression of FBXW7 transactivation and MYC‐independent transcriptional suppression of hsa‐miR‐429. Clinical and xenografted experiments confirmed the growth advantage of CEBPD in relation to glucose metabolic dysregulation and the significant correlations between the expression of these genes.

Conclusions

We confirmed that CEBPD has an oncogenic role in UC by activating AKT signalling and initiating metabolic reprogramming from mitochondrial oxidative phosphorylation to glycolysis to satisfy glucose addiction. These novel CEBPD‐ and MYC‐centric multilayered positive feedback loops enhance cancer growth that could complement theranostic approaches.
Sex influences the effect of adiposity on arterial stiffness and renin‐angiotensin aldosterone system activity in young adults
Authors: Kalenga Cindy Z. , Ramesh Sharanya , Dumanski Sandra M. , MacRae Jennifer M. , Nerenberg Kara , Metcalfe Amy , Sola Darlene Y. , Ahmed Sofia B.
Published: December 2021

Introduction

Sex influences the cardiovascular risk associated with body mass index (BMI) in older adults. Whether this risk differs by sex in younger adults is unknown. We aimed to evaluate the association between measures of adiposity and arterial stiffness and reninangiotensin‐aldosterone system (RAAS) activity in younger adults, stratified by sex.

Methods

Body mass index (BMI), waist circumference (WC), hip circumference (HC), waist‐to‐hip ratio (WHR), waist‐to‐height ratio (WHtR) and fat mass% (FM%) were measured in healthy participants in a fasting, high‐salt state. Arterial stiffness [pulse wave velocity (PWV) and aortic augmentation index (AIx)] were measured at baseline and in response to angiotensin II challenge, a validated marker of RAAS activity. Associations were evaluated using linear regression analysis and stratified by sex.

Results

Ninety‐five healthy, normotensive, non‐diabetic females (n = 67, 37 ± 2 y, BMI 25 ± 1 kg/m2) and males (n = 28, 39 ± 3 y, BMI 27 ± 1 kg/m2) participated in the study. No association was observed between any measure of adiposity and PWV, either at baseline or in response to angiotensin II challenge in premenopausal females. In contrast, all measures of adiposity except HC were associated with PWV at baseline (BMI r = 0.32; WC r = 0.18; WHtR r = 0.34; FM r = 0.21; all values p < .05) and in response to AngII (BMI r = −0.39; WC r = −0.42; WHR r = −0.39; and WHtR r = −0.55) in males. Most adiposity measures were positively associated with baseline AIx (BMI r = 0.33; WC r = 0.27; WHtR r = 0.35; FM% r = 0.25; p < .05) in females, while only WHtR was associated with baseline AIx (r = 0.39; p = .04) in males. All measures of adiposity were positively associated with a blunted Aix response to Ang II (all values p < .001) in females. BMI, WC, WHR and WHtR were associated with a blunted AIx response to Ang II (ΔAIx: BMI r = −0.37; WC r = −0.31; WHR r = −0.16; and WHtR r = −0.22; all values p < .05) in males.

Conclusion

The associations between adiposity measures and cardiovascular risk differ by sex in a young population. These factors should be considered when managing cardiovascular risk.
Spray‐Drying, Oil Blending, and the Addition of Antioxidants Enhance the Storage Stability at Room Temperature of Omega‐3‐Rich Microcapsules Based on Chia Oil
Authors: Bordón María Gabriela , Bodoira Romina Mariana , González Agustín , Piloni Roxana , Ribotta Pablo Daniel , Martínez Marcela Lilian
Published: December 2021

Chia oil (CO) has gained popularity given its α‐linolenic acid content (around 60%). Nonetheless, the susceptibility of polyunsaturated fatty acids toward oxidation represents a challenge for incorporating CO in different products, which justifies the need for exploring stabilization methods. To the best of the authors' knowledge, no reports about powders based on chia oil blends are published. Therefore, the objective of this research is to evaluate the stability at room temperature of microencapsulated CO blends [with virgin sesame (VSO) and wheat germ (WGO) oils] and microencapsulated CO with the addition of tert‐butylhydroquinone (TBHQ). Spray‐drying yielded powders with a better encapsulation efficiency, flowability, and stability, compared with freeze‐drying. After a storage test performed during 3 months, the highest hydroperoxide content (>100 meq.O2 kg−1 oil) is observed for the microencapsulated CO/WGO 80/20 blend, despite its α and β‐tocopherol contents and its antioxidant activity (>90% inhibition of DPPH radical). Notwithstanding, bulk and microencapsulated CO‐TBHQ, CO/VSO 80/20, and 20/80 showed hydroperoxide contents <8 meq.O2 kg−1 oil. By the end of the test, the highest induction period is observed for the microencapsulated CO/VSO 20/80 blend (19.85 ± 0.18 h). Finally, the drying method and the core formulation greatly affect the stability of microcapsules.

Practical Applications: Addition of antioxidants, oil blending and microencapsulation are technological solutions for the preservation of omega‐3‐rich oils, which are popular among healthy food consumers. This research studies and compares the microencapsulation processes by spray or freeze‐drying in order to preserve chia oil blends (with virgin sesame and wheat germ oils) and chia oil with the addition of antioxidants, thereby taking the advantages of the three technological solutions mentioned above. Stable omega‐3‐rich powders, with a higher oxidative stability than pure chia oil, can be obtained as ingredients for the food industry. This ultimately allows the incorporation of the oil into different food products developed to satisfy specific market tendencies.
Transcriptome profiling of guinea pig skin exposed to a high‐power terahertz source
Authors: Zhou Chengxia , Xiong Lidan , Zhou Xun , Li Li , Yan Qiang
Published: December 2021

Terahertz (THz) radiation has a wide range of applications including use in medicine. However, effects of high‐power THz radiation have not been clearly elucidated. We used a 2.52 THz self‐made optically pumped gas THz laser, the low‐ and high‐energy group, to irradiate the backs of Hartley guinea pigs. RNA‐sequencing was done to explore global transcriptional responses in the irradiated skin. Gene Ontology analysis revealed that differentially expressed genes (DEGs) between the unexposed and low‐energy exposed groups were associated with skin development, skin barrier establishment, and multicellular organismal water homeostasis or water loss regulation via the skin. On the other hand, comparison between the unexposed and high‐energy exposed groups showed that the DEGs mediated monocarboxylic acid metabolism, blood vessel morphogenesis, establishment of skin barrier, blood vessel development, or angiogenesis. Our analyses demonstrate the potential effects of high‐power THz source on the skin and sets the basis for further studies on the safety and application of the high‐power THz in dermatology.
Influence of phase change material encapsulation shape on performance of energy‐efficient roof design
Authors: Nagaraju Dora , Preetham Meruva Venkata Surya Murali Vijay , Mohammad Abdul Razack , Satyanarayana Munukurthi Rama Surya , Kolla Narendra Kumar
Published: December 2021

The design of passive cooling systems is part of the energy‐efficient building since population growth and indoor requirements in various dwellings are paramount. As a part of passive designs, modifying the conventional roof with phase change materials (PCM) is one of the techniques to control the abnormal changes of the inner surface temperature of the roof. In this aspect, a numerical investigation has been carried out by incorporating the PCM encapsulated pipes in the RCC (reinforced concrete), and a comprehensive analysis has been carried out. Three different shapes are chosen, namely circular, oval, and rectangular oval, to encapsulate the PCM. Diurnal outside changes are considered to envisage the inner surface temperature of the roof. Validation of the literature's experimental results is done before developing a numerical model for the current study. The effect of encapsulated shape on PCM's average temperature, liquid fraction and energy storage has been studied. The inner surface temperature is reduced drastically with the roof consisting of elliptical encapsulated PCM than other designs such as circular and rectangular oval encapsulated PCM. Moreover, the performance of PCM is sensitive to encapsulated shape and location within the system.
The organic geochemical characteristics from the Palaeogene lacustrine source rock in the Nyima Basin, Central Tibet, and their geological significance
Authors: Chen Yun , Yi Haisheng , Xia Guoqing , Yi Fan , Tang Wenqiang , Li Gaojie , Wu Xinhe , Shi Yuxiang
Published: December 2021

The Lunpola Basin is a fault‐depression type residual Palaeogene continental basin, and it is the only basin located in Tibet in which industrial oil has been discovered. In recent years, as research has progressed, quantities of oil shale and asphalt were discovered in the adjacent Nyima Basin, which shows a good prospect for exploration. In this study, the organic geochemistry, n‐alkanes, biomarkers, and maturity parameters of the samples were analysed using gas chromatography (GC) and mass spectrometry (MS). The organic geochemistry revealed that the Niubao Formation has a high organic matter abundance (total organic carbon content of 0.15–8.43 wt% and hydrogen index of 31.25–1721.15) and is dominated by type I–II2 kerogen. The GC and MS analyses indicate that the oil shales of the Nyima Basin have a high organic matter abundance and a good hydrocarbon production potential, and the main organic matter sources were aquatic algae and terrestrial plants, as evidenced from the unimodal/bimodal distributions of the n‐alkanes. Besides, the high phytoalkane, gammacerane, homohopane, and gypsiferous mudstone contents in the Nyima Basin indicate a deep, hypoxic, well‐stratified, saline lacustrine sedimentary environment. Under warm climatic conditions, accelerated continental weathering increased nutrient input, leading to water‐mass eutrophication and algal blooms in the water column, while arid conditions and intensified evaporation induced saline stratification, leading to enhanced preservation of organic matter and the formation of high‐quality source rock layers in this lake basin. Therefore, the Eocene global greenhouse effect may have been the main reason for the formation of the large sets of oil shales in the Nyima Basin.
Zircon U–Pb ages and Hf isotopes of I‐type granite from western Arunachal Himalaya, NE India: Implications for the continental arc magmatism in the Palaeoproterozoic supercontinent Columbia
Authors: Bikramaditya R. K. , Chung Sun‐Lin , Singh Athokpam Krishnakanta , Lee Hao‐Yang , Lemba Leiphrakpam
Published: December 2021

We present integrated in situ zircon U–Pb and Hf isotope data, along with whole‐rock and mineral chemistry data for the Salari granite of western Arunachal Himalaya to constrain its emplacement age, origin, and geodynamic evolution. The investigated Salari granites are high Fe2O3, CaO, and Nb, and low SiO2 and Rb/Sr ratio with fractionated rare earth element patterns ((Ce/Yb)N = 9.90–20.24) and minor negative Eu anomaly (Eu/Eu* = 0.69–0.94). They are metaluminous (molar A/CNK = 0.93–1.07) and have relatively similar FeOt/MgO ratio in biotite (1.58–1.60) to Mg‐biotite, indicating their affinity with I‐type granites. The enrichment of large‐ion lithophile elements with highly depleted negative Nb anomalies is consistent with their origin in a subduction‐related environment. Our zircon U–Pb ages suggest that the magmatic emplacement of the Salari granite took place between 1,791 and 1,768 Ma. The zircon grains have mostly negative εHf(t) values up to −5.5 and yield crustal Hf model ages from 2.4 to 2.8 Ga, suggesting the occurrence of a major crustal growth event in the Neoarchean and re‐melting of the crust during the Palaeoproterozoic. Our new results, that is, zircon U–Pb age and Hf isotope data, in conjunction with the field observations and petro‐mineralogical and geochemical characteristics, suggest that the Salari granite of eastern Himalaya was produced by partial melting of older metabasaltic/metatonalitic rocks in a continental arc setting of the supercontinent Columbia during the Palaeoproterozoic.
Low‐temperaturethermochronological insights into the Mesozoic–Cenozoic exhumation history of the Taihang–Lvliangshan region: A review
Authors: Huang Xiao , Wang Yannan , Zhang Jin , Wu Fuzhu , Yang Yanli
Published: December 2021

The Taihang–Lvliangshan region is located in the central part of the North China Craton (NCC), which has undergone significant reactivation and reconstruction during the Mesozoic–Cenozoic period. Documenting its long‐term uplift and exhumation history is critical for accurately characterizing the reformation extent of the NCC. In order to further reveal the Mesozoic and Cenozoic exhumation stages and spatial exhumation pattern of the Taihang–Lvliangshan, we present a comprehensive low‐temperature thermochronometric datasets from the region. The compilation revealed five distinct rapid exhumation episodes within the Taihang–Lvliangshan, including the Middle‐Late Jurassic (~160–150 Ma), Early Cretaceous (~120–110 Ma), Late Cretaceous (~100–60 Ma), Eocene (~50–40 Ma), and Late Oligocene–Early Miocene (~30–20 Ma). During the Middle–Late Jurassic, the Taihang–Lvliangshan underwent a strong thrusting deformation caused by the synthesis of northwestward subduction of the Palaeo‐Pacific Plate and southward subduction/collision of the Mongol–Okhotsk suture zone. Subsequently, rapid exhumation under an extensional tectonic environment occurred during the Early Cretaceous primarily owing to the subduction of the Palaeo‐Pacific Plate. During the Late Cretaceous, the collision between the Okhotomorsk Block and East Asia resulted in the regional northwest–southeast shortening and uplift of the Taihang–Lvliangshan. During the Eocene, normal fault activations were occurring throughout the range, likely owing to the change in the convergence rate and direction between the Palaeo‐Pacific Plate and East Asia. Another important exhumation event occurred during the Late Oligocene–Early Miocene period, which was likely attributed to the result of combined effects from both the India–Eurasia collision and Pacific Plate subduction. Furthermore, differential exhumation of the Taihang–Lvliangshan were clearly revealed according to the five separate E–W elevation–distance profiles of the Taihang–Lvliangshan. They displayed greater exhumation thicknesses at the southern regions than those along the northern regions, which can be explained by the development of the Shanxi Rift that began to form following the Oligocene–Miocene period.
Ultrasensitive and affordable assay for early detection of primary liver cancer using plasma cell‐free DNA fragmentomics
Authors: Zhang Xiangyu , Wang Zheng , Tang Wanxiangfu , Wang Xinyu , Liu Rui , Bao Hua , Chen Xin , Wei Yulin , Wu Shuyu , Bao Hairong , Wu Xue , Shao Yang , Fan Jia , Zhou Jian
Published: December 2021

Background and Aims

Early detection of primary liver cancer (PLC), including HCC, intrahepatic cholangiocarcinoma (ICC), and combined HCC‐ICC (cHCC‐ICC), is essential for patients’ survival. This study aims to develop an accurate and affordable method for PLC early detection and differentiating ICC from HCC using plasma cell‐free DNA (cfDNA) fragmentomic profiles.

Approach and Results

Whole‐genome sequencings (WGS) were performed using plasma cfDNA samples from 192 patients with PLC (159 HCC, 26 ICC, 7 cHCC‐ICC) and 170 noncancer controls (including 53 liver cirrhosis [LC] or HBV‐positive) enrolled in the training cohort. An ensembled stacked model for PLC detection was constructed using the training cohort. The model performance was assessed in an independent test cohort (189 patients with PLC [157 HCC, 26 ICC, 6 cHCC‐ICC], 164 noncancer controls [including 51 LC/HBV]). Our model showed excellent performance for cancer detection in the test cohort (AUC: 0.995, 96.8% sensitivity at 98.8% specificity). It showed excellent sensitivities in detecting early‐stage PLC (I: 95.9%, II: 97.9%), small tumors (≤3 cm: 98.2%), and HCC (96.2%) or ICC (100%). The AUC for distinguishing PLC from LC/HBV reached 0.985 (96.8% specificity at 96.1% specificity). Promisingly, our model maintained consistent performances during the downsampling process, even using 1X coverage data (AUC: 0.994, 93.7% sensitivity at 98.8% specificity). A separate model showed potential for distinguishing ICC from HCC (AUC: 0.776).

Conclusions

Our model, outperforming previous reports at a lower cost by solely using low‐coverage WGS data, exhibits excellent clinical potential for ultrasensitive and affordable detection of PLC and its subtypes.
Plasma-Soluble Biomarkers for Fibrodysplasia Ossificans Progressiva (FOP) Reflect Acute and Chronic Inflammatory States
Authors: Pignolo Robert J , McCarrick-Walmsley Ruth , Wang Haitao , Qiu Shirley , Hunter Jeffrey , Barr Sharon , He Kevin , Zhang Hui , Kaplan Frederick S
Published: December 2021

Fibrodysplasia ossificans progressiva (FOP) is a progressive, debilitating genetic disease in which skeletal muscle and connective tissue is episodically replaced by heterotopic bone. Discovery of surrogate biomarkers of disease (genotype)-related and flare-up-associated activity of FOP in a readily accessible matrix, such as plasma, would facilitate an understanding of the complex pathophysiology of FOP, aid patient care, and provide a valuable tool for the development and monitoring of potential therapeutics. In a case–control study, using a carefully collected and curated set of plasma samples from 40 FOP patients with the classic ACVR1R206H mutation and 40 age- and sex-matched controls, we report the identification of disease-related and flare-up-associated biomarkers of FOP using a multiplex analysis of 113 plasma-soluble analytes. Adiponectin (implicated in hypoxia, inflammation, and heterotopic ossification) as well as tenascin-C (an endogenous activator of innate immune signaling through the TLR4 pathway and a substrate for kallikrein-7) were highly correlated with FOP genotype, while kallikrein-7 was highly correlated with acute flare-up status. Plasma-soluble biomarkers for FOP support a flare-up-related acute inflammatory phase of disease activity superimposed on a genotypic background of chronic inflammation. © 2021 American Society for Bone and Mineral Research (ASBMR).
Efficacy of Zoledronic Acid in the Treatment of Nonmalignant Painful Bone Marrow Lesions: A Triple-Blind, Randomized, Placebo-Controlled Phase III Clinical Trial (ZoMARS)
Authors: Seefried Lothar , Genest Franca , Baumann Jasmin , Heidemeier Anke , Meffert Rainer , Jakob Franz
Published: December 2021

Bone marrow lesions (BML) represent areas of deteriorated bone structure and metabolism characterized by pronounced water-equivalent signaling within the trabecular bone on magnetic resonance imaging (MRI). BML are associated with repair mechanisms subsequent to various clinical conditions associated with inflammatory and non-inflammatory injury to the bone. There is no approved treatment for this condition. Bisphosphonates are known to improve bone stability in osteoporosis and other bone disorders and have been used off-label to treat BML. A randomized, triple-blind, placebo-controlled phase III trial was conducted to assess efficacy and safety of single-dose zoledronic acid (ZOL) 5 mg iv with vitamin D 1000 IU/d as opposed to placebo with vitamin D 1000 IU/d in 48 patients (randomized 2:1) with BML. Primary efficacy endpoint was reduction of edema volume 6 weeks after treatment as assessed by MRI. After treatment, mean BML volume decreased by 64.53% (±41.92%) in patients receiving zoledronic acid and increased by 14.43% (±150.46%) in the placebo group (p = 0.007). A decrease in BML volume was observed in 76.5% of patients receiving ZOL and in 50% of the patients receiving placebo. Pain level (visual analogue scale [VAS]) and all categories of the pain disability index (PDI) improved with ZOL versus placebo after 6 weeks but reconciled after 6 additional weeks of follow-up. Six serious adverse events occurred in 5 patients, none of which were classified as related to the study drug. No cases of osteonecrosis or fractures occurred. Therefore, single-dose zoledronic acid 5 mg iv together with vitamin D may enhance resolution of bone marrow lesions over 6 weeks along with reduction of pain compared with vitamin D supplementation only. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Novel domino synthesis of 2‐(2,3.4‐substituted phenyl) quinazolin‐4‐amine
Authors: Fathalla Walid , Pazdera Pavel , Khalifa Mohamed E. , Ali Ibrahim A. I. , El Rayes Samir M.
Published: December 2021

Convenient domino protocol was developed for the synthesis of 2‐arylquinazolin‐4‐amines by the reaction of N‐(2‐cyanophenyl) substituted benzimidoyl isothiocyanates with isopropyl amine. The major advantages of this protocol are short reaction times, mild conditions, simple work up, high yields, and pure products. The efficacy of this protocol owes to the competence of synthesis, pure isolation of imidoyl isothiocyanates, and the unique structure conformation of the corresponding intermediate thiourea derivatives.
The confounder matrix: A tool to assess confounding bias in systematic reviews of observational studies of etiology
Authors: Petersen Julie M. , Barrett Malcolm , Ahrens Katherine A. , Murray Eleanor J. , Bryant Allison S. , Hogue Carol J. , Mumford Sunni L. , Gadupudi Salini , Fox Matthew P. , Trinquart Ludovic
Published: December 2021

Systematic reviews and meta‐analyses are essential for drawing conclusions regarding etiologic associations between exposures or interventions and health outcomes. Observational studies comprise a substantive source of the evidence base. One major threat to their validity is residual confounding, which may occur when component studies adjust for different sets of confounders, fail to control for important confounders, or have classification errors resulting in only partial control of measured confounders. We present the confounder matrix—an approach for defining and summarizing adequate confounding control in systematic reviews of observational studies and incorporating this assessment into meta‐analyses. First, an expert group reaches consensus regarding the core confounders that should be controlled and the best available method for their measurement. Second, a matrix graphically depicts how each component study accounted for each confounder. Third, the assessment of control adequacy informs quantitative synthesis. We illustrate the approach with studies of the association between short interpregnancy intervals and preterm birth. Our findings suggest that uncontrolled confounding, notably by reproductive history and sociodemographics, resulted in exaggerated estimates. Moreover, no studies adequately controlled for all core confounders, so we suspect residual confounding is present, even among studies with better control. The confounder matrix serves as an extension of previously published methodological guidance for observational research synthesis, enabling transparent reporting of confounding control and directly informing meta‐analysis so that conclusions are drawn from the best available evidence. Widespread application could raise awareness about gaps across a body of work and allow for more valid inference with respect to confounder control.
Hyperfluorescence™: Excel the performance, create the future
Authors: Cheng Shuo‐Hsien , Endo Ayataka , Kakizoe Hayato , Otsu Shinya , Suzuki Yoshitake , Yamashita Masataka , Adachi Junji
Published: December 2021

Hyperfluorescence™ (HF), known as the most advanced OLED emitting technology, combines TADF and fluorescence mechanisms enabling 100% internal quantum efficiency (IQE) and narrowband emission. Based on in silico simulation, HF is not only more outperformed than the modern OLED emitting technologies but also feasible for the RGB definition of BT.2020. Of the green top‐emission HF device, the device performance is manifold increased than that of the bottom‐emission, where this effect is more amplified than that in phosphorescence system. An efficiency improvement approach to reach market requirements was illustrated to show our vision in pursuing excellent performance.
A Systematic Review and Meta‐Analysis: Timing of Elective Removal of Tympanostomy Tubes
Authors: Tan Grace X. , Hamilton Andrew , MacArthur Carol J.
Published: December 2021

Objective(s)

Tympanostomy tube (TT) placement is the most common surgical procedure in children. Less than 10% of TT do not self‐extrude. This study is a systematic review (SR) on elective TT removal in the pediatric population: timing, perforation rates, and role of simultaneous repair. A PICOTS (population, intervention, comparison, outcome, timing, setting) question was formulated: In pediatric patients who have retained TT, what is the preferred time to elective removal of such tubes, and what are the outcomes in terms of perforation rates? Does an intervention at the time of TT removal improve perforation rates?

Study Design

Systematic review and meta‐analysis.

Methods

We searched four major electronic databases: EMBASE, MEDLINE, CDSR, CCRCT for articles published prior to 02/19/20. EndNote® was used to gather references, review abstracts, and obtain full text articles. Inclusion criteria were studies reporting patients aged 0 to 18 years undergoing elective TT removal with follow‐up greater than 3 months. Exclusion criteria included patients >18 years, duplicate patient series, or case series with fewer than five patients. Articles that were not available in English, not available in full text, and those that only addressed long‐acting TT were excluded.

Data were pooled and meta‐analysis was conducted to examine how timing of TT removal, patching of the tympanic membrane, or any TM intervention at TT removal affected outcomes.

Results

A total of 1,064 references were found. We identified 63 unique studies for full text review. Of these, 17 were selected for SR. MINORS (Methodological Index for Nonrandomized Studies) scores were low‐revealing high bias among the studies. Reported perforation rates after elective TT removal ranged from 0% to 57%. Four studies had data suitable for comparative meta‐analysis, which showed a significant increase in perforation rates after elective removal of TT after 3 years compared to removal prior to 3 years (OR 2.89; CI 1.78–4.69). No difference in perforation rates were identified when TM intervention vs. no intervention at time of TT removal was performed (six studies: OR 1.21; CI 0.71–2.07). No difference in perforation rates was identified when the type of TM intervention was compared, including freshening of TM edges, to patching with various materials (paper, fat, gelfoam®/gelfilm®, Trichloroacetic acid) (three studies: OR 1.07; CI 0.52–2.19).

Conclusion

From the data reviewed in this SR and meta‐analysis, elective TT removal at or prior to 3 years' retention showed decreased perforation rates. However, TM intervention at the time of TT removal was not shown to lower perforation rates. In the absence of tube complications such as granuloma formation, nonfunctional tube, or chronic tube otorrhea, it may be reasonable to wait up to 3 years to electively remove a retained TT. Laryngoscope, 132:2063–2070, 2022
Clinical Value of Surveillance Biopsies in Pediatric Liver Transplantation
Authors: Rocque Brittany , Zaldana Aaron , Weaver Carly , Huang Julia , Barbetta Arianna , Shakhin Victoria , Goldbeck Cameron , Yanni George , Zielsdorf Shannon , Kwon Yong , Etesami Kambiz , Genyk Yuri , Zhou Shengmei , Kohli Rohit , Emamaullee Juliet
Published: December 2021

Although pediatric liver transplantation (LT) results in excellent long‐term outcomes, a high incidence of early acute cellular rejection and late graft fibrosis persists. Routine measurement of allograft enzymes may not reliably detect rejection episodes, identify candidates for immunosuppression minimization, or indicate allograft fibrosis. Surveillance biopsies (SBs) can provide valuable information in this regard, but their role in pediatric LT is not fully established. A retrospective cohort of 236 pediatric LT recipients from a high‐volume center was studied to characterize the risks and benefits of SB versus for‐cause biopsies (FCBs). The study population was 47.1% male and 54.7% Hispanic, and 31% received living donor grafts. Our data suggest that patients in the SB group had better transplant outcomes (rejection‐free, graft, and patient survival) compared with patients who had FCBs or who never underwent biopsy. Among 817 biopsies obtained from 236 patients, 150 (18.4%) were SBs. Only 6 patients had a biopsy‐related complication, and none were observed in the SB subset. Graft biochemical blood tests did not accurately predict rejection severity on biopsy, with aspartate aminotransferase area under the receiver operating characteristic curve (AUROC) 0.66, alanine aminotransferase AUROC 0.65 (very poor predictions), and gamma‐glutamyltransferase AUROC 0.58 (no prediction). SBs identified subclinical rejection in 18.6% of biopsies, whereas 63.3% of SBs had evidence of fibrosis. SBs prompted changes in immunosuppression including dose reduction. Our experience suggests that SB in pediatric LT is safe, offers valuable information about subclinical rejection episodes, and can guide management of immunosuppression, including minimization. Improved outcomes with SB were likely multifactorial, potentially relating to a more favorable early posttransplant course and possible effect of management optimization through SB. Further multicenter studies are needed to examine the role of SBs on long‐term outcomes in pediatric LT.
Assessing the accuracy of electronic portal imaging device (EPID)‐based dosimetry: II. Evaluation of a dosimetric uncertainty budget and development of a new film‐in‐EPID absorbed dose calibration methodology
Authors: Renaud James , Muir Bryan
Published: December 2021

Purpose

The aim of this study is to reduce the uncertainty associated with determining dose‐to‐water using an amorphous silicon electronic portal imaging detector (EPID) under reference conditions by developing a direct calibration formalism based on radiochromic film measurements made within the EPID panel and detailed Monte Carlo simulations. To our knowledge, this is the first EPID‐based dosimetry study reporting an uncertain budget

Methods

Pixel sensitivity and relative off‐axis response were mapped by simultaneously irradiating film contained within the imager panel and acquiring an EPID image set. The detector panel was disassembled for the purpose of modeling the EPID in detail using the EGSnrc DOSXYZnrc usercode, which was in turn used to calculate dose‐to‐film in the EPID and dose‐to‐water in water conversion factors

Results

A direct comparison of the two correction methodologies investigated in this work, the previously established empirical method and the proposed simultaneous measurement approach involving in‐EPID film dosimetry, produced an agreement with an RMS deviation of 1.4% overall. A combined standard relative uncertainty of 3.3% (k = 1) was estimated for the determination of absorbed dose to water at the position of the EPID using the proposed calibration methodology

Conclusions

This work describes a direct method of calibrating EPID response in terms of absorbed dose to water requiring fewer measurements than other empirical approaches, and without 2D spatial interpolation of correction factors.
Assessment of breast cancer response to neoadjuvant chemotherapy based on ultrasound backscattering envelope statistics
Authors: Klimonda Ziemowit , Karwat Piotr , Dobruch‐Sobczak Katarzyna , Piotrzkowska‐Wróblewska Hanna , Litniewski Jerzy
Published: December 2021

Purpose

Neo‐adjuvant chemotherapy (NAC) is used in breast cancer before tumor surgery to reduce the size of the tumor and the risk of spreading. Monitoring the effects of NAC is important because in a number of cases the response to therapy is poor and requires a change in treatment. A new method that uses quantitative ultrasound to assess tumor response to NAC has been presented. The aim was to detect NAC unresponsive tumors at an early stage of treatment.

Methods

The method assumes that ultrasound scattering is different for responsive and nonresponsive tumors. The assessment of the NAC effects was based on the differences between the histograms of the ultrasound echo amplitude recorded from the tumor after each NAC dose and from the tissue phantom, estimated using the Kolmogorov–Smirnov statistics (KSS) and the symmetrical Kullback–Leibler divergence (KLD). After therapy, tumors were resected and histopathologically evaluated. The percentage of residual malignant cells was determined and was the basis for assessing the tumor response. The data set included ultrasound data obtained from 37 tumors. The performance of the methods was assessed by means of the area under the receiver operating characteristic curve (AUC).

Results

For responding tumors, a decrease in the mean KLD and KSS values was observed after subsequent doses of NAC. In nonresponding tumors, the KLD was higher and did not change in subsequent NAC courses. Classification based on the KSS or KLD parameters allowed to detect tumors not responding to NAC after the first dose of the drug, with AUC equal 0.830.06 and 0.840.07, respectively. After the third dose, the AUC increased to 0.900.05 and 0.910.04, respectively.

Conclusions

The results indicate the potential usefulness of the proposed parameters in assessing the effectiveness of the NAC and early detection of nonresponding cases.
An exact solution method for home health care scheduling with synchronized services
Authors: Qiu Huaxin , Wang Dujuan , Yin Yunqiang , Cheng T. C. Edwin , Wang Yanzhang
Published: December 2021

We study the home health care scheduling problem that considers the synchronized services of multiskilled caregivers necessitated by the simultaneous service requirements of patients. A characteristic feature of the problem is that there is a threshold on the maximum difference between the start times of the pairwise synchronized services at a patient, which enables flexible imposition of various synchronization constraints. We first derive some structural properties of the problem, based on which we provide a set‐partitioning formulation of the problem and devise a branch‐and‐price‐and‐cut solution algorithm. We develop a column generation scheme to obtain lower bounds for the problem, in which we design a labeling algorithm together with some enhancement strategies to address the pricing subproblems, and use the 2‐path inequalities and limited‐node‐memory subset row inequalities to strengthen the lower bounds. To test the algorithm, we apply it to solve the instances generated according to the well‐known Solomon's benchmark data set and real‐world instances. The results demonstrate that the algorithm can find the optimal solutions in most situations within reasonable computational times, confirming its efficacy. Finally, we perform sensitivity analysis of the optimal solution to some key model parameters and discuss the management implications of the results.
A Fragile Points Method, with an interface debonding model, to simulate damage and fracture of U‐notched structures
Authors: Wang Kailei , Shen Baoying , Li Mingjing , Dong Leiting , Atluri Satya N.
Published: December 2021

Notched components are commonly used in engineering structures, where stress concentration may easily lead to crack initiation and development. The main goal of this work is to develop a simple numerical method to predict the strength and crack‐growth‐path of U‐notched specimens made of brittle materials. For this purpose, the Fragile Points Method (FPM), as previously proposed by the authors, has been augmented by an interface debonding model at the interfaces of the FPM domains, to simulate crack initiation and development. The formulations of FPM are based on a discontinuous Galerkin weak form where point‐based piece‐wise‐continuous polynomial test and trial functions are used instead of element‐based basis functions. In this work, the numerical fluxes introduced across interior interfaces between subdomains are postulated as the tractions acting on the interface derived from an interface debonding model. The interface damage is triggered when the numerical flux reaches the interface strength, and the process of crack‐surface separation is governed by the fracture energy. In this way, arbitrary crack initiation and propagation can be naturally simulated without the need for knowing the fracture‐patch before‐hand. Additionally, a small penalty parameter is sufficient to enforce the weak‐form continuity condition before damage initiation, without causing problems such as artificial compliance and numerical ill‐conditioning. As validations, the proposed FPM method with the interface debonding model is used to predict fracture strength and crack‐growth trajectories of U‐notched structures made of brittle materials, which is useful but challenging in engineering structural design practices.