bluuebunny/crossref_metadata_2025 huggingface dataset:
Rum där män möts
Authors: Johnsson Henrik
Published: December 2020

I artikeln analyseras Knut Hamsuns novell ”Hemmelig ve” (1897) ur queer-perspektiv. Artikeln argumenterar för att Hamsuns novell skildrar ett samkönat erotiskt begär mellan berättaren och den man som betecknas som ”den främmande”. Den främmande förstås som berättarens dubbelgångare, och i egenskap av dubbelgångare representerar han berättarens förbjudna begär. Denna tolkning tar som utgångspunkt en jämförelse mellan 1897 års text och den tidigare version av samma novell som gavs ut under titeln ”Underlige Sjæle” (1891), samt genom en närläsning av de båda männens möten. Artikeln avslutas med en diskussion kring Hamsunforskningens förhållande till queerteori.
Knut Hamsuns Sult på scenen
Authors: Domsa Zsófia
Published: December 2020

Artikkelen tar for seg fire sceniske adaptasjoner av Knut Hamsuns Sult. Den teoretiske diskusjonen reflekterer over dramatiseringens vansker og den innfløkte fortellerteknikken i Hamsuns jeg-roman. Med utgangspunkt i moderne adaptasjonsteori som ikke lenger insisterer på foreleggets primat, blir fire ulike sceniske versjoner analysert ut fra hvordan fortellerstemmen, bymiljøet, persongalleriet og kunstnertilværelsen er oversatt fra romanens medium til dramatikk. I artikkelen kommenterer jeg de utvalgte Sult-bearbeidelsene både i sammenligning med det litterære forelegget og på adaptasjonenes egne premisser. Analysen viser at de fleste adaptasjonene har som mål å gestalte Sult-heltens indre monolog på scenen. Skrivesperren og Sult-heltens vandring i storbyen, som er så sentrale motiver i romanen, blir derimot ikke alltid vektlagt. Det overordnede formålet med artikkelen er å høyne den akademiske oppmerksomheten om de tallrike dramatiseringene av Hamsuns romaner.
«Noget af et eksperiment»
Authors: Wærp Lisbeth Pettersen
Published: December 2020

Hamsuns roman er komponert i korte, tilstands- og stemningsorienterte kapitler, har to kontrasterte jegfortellere, fire ulike tidsnivå, vekt på erindring, drøm, ubevisst sjeleliv og det irrasjonelle. Personene, særlig protagonistene Glahn og Edvarda, framstår uten klare motiver, og plotkomposisjonen er vag og åpen. En slik romankomposisjon er utfordrende å adaptere til film og skiller seg kraftig både fra de kunstneriske konvensjonene i samtidens norske bonde- og bygdefilm og fra den framvoksende Hollywood-stilen og det som etterhvert blir den klassiske filmfortellingens ideal. Hovedspørsmålene som stilles i denne artikkelen er derfor hvordan utfordringene er løst, hva som kjennetegner Schwenzens film som adaptasjon av romanen og hvordan adaptasjonen føyer seg inn i norsk filmhistorie og i romanens resepsjons- og tolkningshistorie. Et viktig poeng i artikkelen er at filmen adopterer den modernistiske fortellemåten og formen fra romanen, og gjennom stumfilmsjangerens melodramatiske virkemidler bidrar til å fremme eller forsterke sentrale innovative, modernistiske trekk adoptert fra romanen.
COMPATIBILIDADE FÍSICO-QUÍMICA DE DIFERENTES DOSES E MISTURAS DE HERBICIDAS
Authors: Costa Lilian Lúcia , Santos Thiago Camargo de Melo , Almeida Dieimisson Paulo , Ferreira Marcelo Da Costa , Leão-Araujo Erica Fernades , Timossi Paulo César
Published: December 2020

A manutenção da produtividade de cultivos comerciais é dependente do uso de produtos fitossanitários, mas são restritas as informações sobre a interação entre eles quando usados em mistura. Assim, objetivou-se avaliar as propriedades físico-químicas, a tensão superficial, o ângulo de contato e o espectro de gotas de caldas fitossanitárias contendo diferentes doses e misturas dos herbicidas Glyphosate e Atrazine. Os tratamentos foram constituídos pela combinação de uma formulação do herbicida glyphosate com dois produtos comerciais formulados com o herbicida atrazine. As caldas foram avaliadas pelo método estático de compatibilidade físico-química obtendo-se tabelas descritivas quanto aos aspectos de homogeneidade/heterogeneidade. As medições da tensão superficial e ângulo de contato foram realizados durante um minuto empregando o método da gota pendente para determinar a cinética da tensão superficial e o método da gota séssil para determinar o ângulo de contato. Os atributos avaliados do espectro de gotas produzidos por cada tratamento foram o diâmetro mediano volumétrico, o coeficiente de uniformidade e a porcentagem de volume em gotas com diâmetros menores que 100 μm. É fundamental a agitação constante da calda fitossanitária antes e durante a aplicação para diminuir problemas de incompatibilidade entre os produtos. O espectro de gotas pode variar de acordo com a composição da calda de pulverização e com a dose do produto utilizado.
Assessment of dynamic matrix control controller parameters via estimating Markov parameters of disturbance
Authors: Li Lijuan , Chen Xingyu , Yang Shipin
Published: December 2020

For an industrial control system, controller parameters are important factors that affect the control system performance. This article introduces a controller parameter performance assessment method based on disturbance characteristic variation for a dynamic matrix control system. Assuming that the process model is accurate and the setpoint is constant, disturbance characteristic variation without adjusting controller parameters leads to the degradation of system performance. Hence, the Markov parameters of a disturbance model, which inflect the variation of disturbance characteristics, are used to assess the controller parameter performance. These Markov parameters can be obtained from closed‐loop data using the subspace identification method. The differences between the Markov parameters in an actual running state and those in a well‐regulated state are used to design the assessing index of controller parameters. The simulation results in the Wood–Berry model and TE process show the validity of the proposed index.
A Liquid Metal Based Multimodal Sensor and Haptic Feedback Device for Thermal and Tactile Sensation Generation in Virtual Reality
Authors: Oh Jinhyeok , Kim Suin , Lee Sangyeop , Jeong Seongmin , Ko Seung Hwan , Bae Joonbum
Published: December 2020

Virtual reality (VR) has been widely used for training, gaming, and entertainment, and the value of VR is continually increasing as a contact‐free technology. For an immersive VR experience, measuring finger movements and providing appropriate feedback to the hand are as important as visual information, given the necessity of the hands for activities in daily life. Thus, a hand‐worn VR device with motion sensors and haptic feedback is desirable. In this paper, a multimodal sensing and feedback glove is developed with soft, stretchable, lightweight, and compact sensor and heater sheets manufactured by direct ink writing (DIW) of liquid metal, eutectic gallium‐indium (eGaIn). In the sensor sheet, ten sensors and three vibrators are embedded to measure finger movements and provide vibro‐haptic feedback. The other heater sheet provides thermo‐haptic sensation in accurate and rapid manner via model‐based feedback control even under stretched conditions. The multimodal sensing and feedback glove allows users to feel the contact status and discriminate materials with different temperature. Performance of the proposed multimodal glove is verified under VR environments including touching and pushing two blocks of different materials and grabbing a heated metal ball submerged in hot water.
Atomically Smooth Graphene‐Based Hybrid Template for the Epitaxial Growth of Organic Semiconductor Crystals
Authors: Nguyen Nguyen Ngan , Lee Hyo Chan , Baek Kangkyun , Yoo Min Seok , Lee Hansol , Lim Hyungsub , Choi Shinyoung , Kim Cheol‐Joo , Nam SungWoo , Cho Kilwon
Published: December 2020

Atomically thin 2D materials are good templates to grow organic semiconductor thin films with desirable features. However, the 2D materials typically exhibit surface roughness and spatial charge inhomogeneity due to nonuniform doping, which can affect the uniform assembly of organic thin films on the 2D materials. A hybrid template is presented for preparation of highly crystalline small‐molecule organic semiconductor thin film that is fabricated by transferring graphene onto a highly ordered self‐assembled monolayer. This hybrid graphene template has low surface roughness and spatially uniform doping, and it yields highly crystalline fullerene thin films with grain sizes >300 nm, which is the largest reported grain size for C60 thin films on 2D materials. A graphene/fullerene/pentacene phototransistor fabricated directly on the hybrid template has five times higher photoresponsivity than a phototransistor fabricated on a conventional graphene template supported by a SiO2 wafer.
Tumor Microenvironment Responsive Biodegradable Fe‐Doped MoOx Nanowires for Magnetic Resonance Imaging Guided Photothermal‐Enhanced Chemodynamic Synergistic Antitumor Therapy
Authors: Chen Yusheng , Gao Mengluan , Zhang Lingjian , Ha Enna , Hu Xin , Zou Rujia , Yan Li , Hu Junqing
Published: December 2020

Rational design of nanosystems that target tumor microenvironment have attracted widespread attention. However, it is still a great challenge to make a multifunctional nanoplatform that actively and selectively interacts with tumor microenvironment, without causing toxicity to surrounding normal tissues. Herein, the biodegradable Fe‐doped MoOx (FMO) nanowires are designed as an anti‐tumor nanoreagent that possesses great photothermal conversion ability (48.5%) and magnetic properties for T1 weighted magnetic resonance imaging (MRI). Also, FMO can be used as a chemodynamic therapy (CDT) reagent to effectively catalyze the decomposition of H2O2 and produce hydroxyl radical (·OH). At the same time, the consumption of glutathione will also enhance the CDT effect. More importantly, FMO presents pH‐dependent degradation behavior: rapid degradation at physiological pH, but relatively stable at acidic pH. In vivo anti‐tumor experiment demonstrates that the FMO is able to effectively inhibit the tumor growth with minimal side effects. Generally speaking, these results indicate that the FMO has huge potential for MRI image‐guided cancer therapy and promotes the clinical translation of nanodrugs.
Containerless Bioorganic Reactions in a Floating Droplet by Levitation Technique Using an Ultrasonic Wave
Authors: Matsubara Teruhiko , Takemura Kenjiro
Published: December 2020

To ensure sustainable consumption and production patterns, alternative process design without plastics for chemical and biological reactions will benefit future generations. Reaction flasks used in chemical and biological laboratories have been made from glass, metals, and plastics so far. If containerless processing can be realized, researchers will have a next‐generation reaction process, which will be reactor and plastic‐free, and without risks of unforeseen issues induced by contact with reactions flasks, including contamination and alteration of the reactants. Here, polymerization, click chemistry, and enzymatic reactions can proceed effectively in a floating droplet at a node of standing wave generated by ultrasonic levitation. These results demonstrate that floating droplets levitated by acoustic waves can represent a revolutionary containerless reactor for performing various reactions in the fields of chemistry and biology.
A Scalable Integrated Dopant‐Free Heterostructure to Stabilize Perovskite Solar Cell Modules
Authors: Sha Yongming , Bi Enbing , Zhang Yao , Ru Pengbin , Kong Weiyu , Zhang Peng , Yang Xudong , Chen Han , Han Liyuan
Published: December 2020

Perovskite solar cell (PSC) modules employing a hole transport layer (HTL) without unstable dopants possess high potential for improving operational stability. However, the low efficiencies of the devices greatly limit their commercial applications owing to the lower efficacy of the dopant‐free HTL, introduced by the unintentional n‐doping effect of volatile ions from the halide‐rich perovskite surface. Here, a scalable heterostructure integrated by a methylammonium‐free perovskite film with an iodide‐rich surface, an ultrathin interlayer of bridge‐jointed graphene oxide nanosheets (BJ‐GO), and an HTL without additional ionic dopants is developed. In this heterostructure, the iodide ions are physically immobilized by the compact 2D network, and lead defects are chemically passivated by multiple coordination bonds. Moreover, the BJ‐GO with tunable surface energy enables a highly ordered HTL a considerably improved carrier mobility by an order of magnitude. Finally, the PSC module with an area of 35.80 cm2 employing this heterostructure shows a certified efficiency of 15.3%. The encapsulated PSC modules retain over 91% of initial efficiency after the damp heat test at 85 °C and ≈85% relative humidity for 1000 h, while maintaining 90% of the initial value for 1000 h at the maximum power point under continuous 1‐Sun illumination at 60 °C.
Validation of data quality in a nationwide gastroenterological surgical database: The National Clinical Database site‐visit and remote audits, 2016‐2018
Authors: Hasegawa Hiroshi , Takahashi Arata , Kanaji Shingo , Kakeji Yoshihiro , Marubashi Shigeru , Konno Hiroyuki , Gotoh Mitsukazu , Miyata Hiroaki , Kitagawa Yuko , Seto Yasuyuki
Published: December 2020

Background and Aim

In 2015, the Japanese Society of Gastroenterological Surgery (JSGS) initiated data verification in the gastroenterological section of the National Clinical Database (NCD) and reported high accuracy of data entry. Remote audits were introduced for data validation on a trial basis in 2016 and formally accepted into use in 2017‐2018. The aim of this study was to audit the data quality of the NCD gastroenterological section for 2016‐2018 and to confirm the high accuracy of data in remote audits.

Methods

Each year, 45‐46 hospitals were selected for audit. Twenty cases were randomly selected in each hospital, and the accuracy of patient demographic and surgical outcome data (46 items) was compared with the corresponding medical records obtained by visiting the hospital (site‐visit audit) or by mailing data from the hospital to the JSGS office (remote audit).

Results

A total of 136 hospitals were included, of which 88 (64.7%) had a remote audit, and 124 936 items were evaluated with an overall data accuracy of 98.1%. There was no significant difference in terms of data accuracy between site‐visit audit and remote audit. Accuracy, sensitivity, and specificity of mortality were 99.7%, 89.7%, 100% for site‐visit audits and 99.8%, 97.3%, 100% for remote audits, respectively. Mean time spent on data verification per case of remote audits was shorter than that of site‐visit audits (10.0 minutes vs 13.7 minutes, P < 0.001).

Conclusion

The audits showed that NCD data are reliable and characterized by high accuracy. Remote audits may substitute site‐visit audits.
Asymmetric Hydroesterification of Diarylmethyl Carbinols
Authors: Tian Duanshuai , Xu Ronghua , Zhu Jinbin , Huang Jianxun , Dong Wei , Claverie Jerome , Tang Wenjun
Published: December 2020

An efficient asymmetric hydroesterfication of diarylmethyl carbinols is developed for the first time with a Pd‐WingPhos catalyst, resulting in a series of chiral 4‐aryl‐3,4‐dihydrocoumarins in excellent enantioselectivities and good yields. The method features mild reaction conditions, a broad substrate scope, use of easily accessible starting materials, and low palladium loadings. A plausible stereochemical model is also proposed with the Pd‐WingPhos catalyst. This method has enabled a 4‐step asymmetric synthesis of (R)‐tolterodine from readily available starting materials.
Cross‐sectional survey of the replacement of the Japanese term for dementia: Did it reduce discomfort in family members?
Authors: Yamanaka Katsuo , Todo Naoya , Yoshizawa Mutsumi , Uchida Tatsuji
Published: December 2020

Objectives

Decreasing discrimination and stigma of dementia is an international issue. In 2004, the Japanese government changed the previous Japanese stigmatic term of dementia (“Chiho”) to the present one (“Ninchi‐sho”) a meaning near “neurocognitive disorder.” This study aimed to examine cross‐sectionally if the present term functioned well or not from the viewpoint of families of people with dementia (PWD), and to discover variables influencing their feelings of the term: the feelings about people surrounding PWD, and the family members’ and PWD’s attributes.

Methods

Questions regarding the feelings about the present Japanese term and people surrounding PWD were asked to 155 family members accompanying PWD who visited three hospitals. For analyses, the degree of the discomfort about the present Japanese term was shown descriptively. The relationship of constructs of the feelings extracted by exploratory factor analysis (EFA) and the attributes was analyzed using structural equation modeling (SEM).

Results

71.6% agreed that the present term discomforted them less than the previous one. Only 13.2% thought that the present term was discriminatory. However, about one third of the participants felt discomfort when they used even the present term. Using the constructs extracted by EFA, the analysis of SEM revealed that the negative feelings of the terminology were affected by hesitation to disclose to surrounding people that their family member had dementia, which the attributes of younger family members, wives, husbands, and siblings influenced. Moreover, because of disclosing the dementia, the feelings of support from people alleviated the feelings of hesitation, influenced by sex (female).

Conclusions

It was suggested that overall, the present term successfully reduced discomfort in families, compared with the result of the previous term surveyed by the Ministry of Health, Labour, and Welfare. However, unignorable numbers of family members still feel stigma. New policies are necessary considering the influencing factors.
The role of cultural worldviews in predicating gambling risk perception and behavior in a Chinese sample
Authors: Xue Wen , Zeng Zhonglu , Liu Zuyun , Marks Anthony D. G.
Published: December 2020

Objectives

We investigated the relationships between cultural worldviews, gambling risk perception, and gambling behavior with a sample of tourists in Macao.

Methods

Participants were enrolled at famous landmarks and casinos in Macao, China. Data were collected using several instruments to assess an individual's cultural worldviews, gambling risk perceptions, and gambling intentions.

Results

We found that the three‐dimensional solution was valid for the Chinese version of the gambling expectancy scale. Correlational and mediational analyses revealed that the relationship between an individualistic worldview and gambling intention was fully mediated by gambling risk perception. Respondents with an egalitarian worldview perceived greater risk associated with gambling than those with other worldviews.

Conclusion

These findings demonstrated the important influence of cultural variables on perceived risk and behavior in gambling. Moreover, understanding gamblers’ worldviews could be beneficial for problem gambling interventions. Future research directions and the limitations of the findings were discussed.
225Ac‐labeled CD33‐targeting antibody reverses resistance to Bcl‐2 inhibitor venetoclax in acute myeloid leukemia models
Authors: Garg Ravendra , Allen Kevin J. H. , Dawicki Wojciech , Geoghegan Eileen M. , Ludwig Dale L. , Dadachova Ekaterina
Published: December 2020

Purpose

Despite the availability of new drugs, many patients with acute myeloid leukemia (AML) do not achieve remission and outcomes remain poor. Venetoclax is a promising new therapy approved for use in combination with a hypomethylating agent or with low‐dose cytarabine for the treatment of newly diagnosed older AML patients or those ineligible for intensive chemotherapy. 225Actinium‐lintuzumab (225Ac‐lintuzumab) is a clinical stage radioimmunotherapy targeting CD33 that has shown evidence of single‐agent activity in relapsed/refractory AML. Increased expression of MCL‐1 is a mediator of resistance to venetoclax in cancer.

Experimental design

Here we investigated the potential for 225Ac‐lintuzumab‐directed DNA damage to suppress MCL‐1 levels as a possible mechanism of reversing resistance to venetoclax in two preclinical in vivo models of AML.

Results

We demonstrated that 225Ac‐lintuzumab in combination with venetoclax induced a synergistic increase in tumor cell killing compared to treatment with either drug alone in venetoclax‐resistant AML cell lines through both an induction of double‐stranded DNA breaks (DSBs) and depletion of MCL‐1 protein levels. Further, this combination led to significant tumor growth control and prolonged survival benefit in venetoclax‐resistant in vivo AML models.

Conclusions

There results suggest that the combination of 225Ac‐lintuzumab with venetoclax is a promising therapeutic strategy for the treatment of patients with venetoclax‐resistant AML.

Clinical trial of this combination therapy (NCT03867682) is currently ongoing.
Artificial neural networks for simultaneously predicting the risk of multiple co‐occurring symptoms among patients with cancer
Authors: Xuyi Wenhui , Seow Hsien , Sutradhar Rinku
Published: December 2020

Patients with cancer often exhibit multiple co‐occurring symptoms which can impact the type of treatment received, recovery, and long‐term health. We aim to simultaneously predict the risk of three symptoms: severe pain, moderate‐severe depression, and poor well‐being in order to flag patients who may benefit from pre‐emptive early symptom management. This was a retrospective population‐based cohort study of adults diagnosed with cancer between 2008 and 2015. We developed and tested an Artificial Neural Network (ANN) model to predict the risk of multiple co‐occurring symptoms within 6 months after diagnosis. The ANN model derived from a training cohort was assessed on an independent test cohort for model performance based on sensitivity, specificity, accuracy, AUC, and calibration. The mutually exclusive training and test cohorts consisted of 35,606 and 10,498 patients, respectively. The area under the curve for the risk of experiencing severe pain, moderate‐severe depression, and poor well‐being were 71%, 73%, and 70%, respectively. Patient characteristics at highest risk of simultaneously experiencing these three symptoms included: those with lung cancer, late stage cancer, existing chronic conditions such as osteoarthritis, mood disorder, hypertension, diabetes, and coronary disease. Patients with over a 40% risk of severe pain also had over a 70% risk of depression, and over a 55% risk of poor well‐being. Our ANN model was able to simultaneously predict the risk of pain, depression, and lack of well‐being. Accurate prediction of future symptom burden can serve as an early indicator tool so that providers can implement timely interventions for symptom management, ultimately improving cancer care and quality of life.
Infrastructure Challenges Caused by Industrial Transformation to Achieve Greenhouse Gas Neutrality. Ammonia Production in the Antwerp‐Rotterdam‐Rhine‐Ruhr Area
Authors: Ausfelder Florian , van de Beek Floris , Bhardwaj Rajat , Graf Frank , Meinke‐Hubeny Frank , Lodewijks Pieter , Müller Sabrina Alexandra , Rijkers Monique , Perez Sanchez Diana , Ruf Johannes
Published: December 2020

Several pathways for potentially greenhouse gas neutral production of ammonia have been investigated compared to today's conventional ammonia production at chemical sites in Antwerp, Dormagen, and Geleen. These pathways include on‐site water electrolysis using grid electricity, off‐site production via water electrolysis using renewable electricity and supply of green hydrogen to the site, pyrolysis of natural gas and conventional ammonia production coupled with CO2‐capture on‐site and transport to a storage site. All pathways effectively eliminate scope 1 emissions present in conventional production but continue to emit scope 2 emissions from grid electricity consumption. Eventually, a coordinated industry‐wide and cross‐industry effort is needed to address the transformational changes and develop the common cross‐border infrastructures.
MAFG‐AS1 promotes tumor progression via regulation of the HuR/PTBP1 axis in bladder urothelial carcinoma
Authors: Xiao Mengqing , Liu Jianye , Xiang Liang , Zhao Kai , He Dong , Zeng Qinghai , Zhang Qun , Xie Dan , Deng Minhua , Zhu Yuxing , Zhang Yeyu , Liu Yan , Bo Hao , Liu Xiaoming , Chen Xingyu , Gong Lian , Bao Ying , Hu Yi , Cheng Yaxin , Deng Liping , Zhu Rongrong , Xing Xiaowei , Zhou Ming , Xiong Wei , Zhou Yanhong , Zhou Jianda , Li Xiaohui , Cao Ke
Published: December 2020

Long noncoding RNAs (lncRNAs) play a crucial role in progression of bladder urothelial carcinoma (BUC). However, the molecular mechanisms behind this role have not been elucidated yet. Here, we found that the lncRNA MAFG‐AS1, which is highly expressed in BUC, is correlated with aggressive characteristics and poor prognosis of BUC. We demonstrate that MAFG‐AS1 can promote BUC proliferation, invasion, metastasis, and epithelial‐mesenchymal transition in vitro and in vivo. Mechanistically, MAFG‐AS1 direct binding to Hu antigen R (HuR) could recruit ubiquitin‐specific proteinase 5 (USP5) to prevent HuR from degrading by ubiquitination. We further demonstrate that overexpression of MAFG‐AS1 can upregulate the expression of polypyrimidine tract‐binding protein 1 (PTBP1) through promoting its stability mediated by bound HuR. In conclusion, these findings indicate that MAFG‐AS1 promotes the progression of BUC via regulation of the HUR/PTBP1 axis. Targeting MAFG‐AS1 may provide a novel strategy for individualized therapy and a potential biomarker for prognosis of BUC.
Circulating tumor cell characterization of lung cancer brain metastases in the cerebrospinal fluid through single‐cell transcriptome analysis
Authors: Ruan Haoyu , Zhou Yihang , Shen Jie , Zhai Yue , Xu Ying , Pi Linyu , Huang Ruofan , Chen Kun , Li Xiangyu , Ma Weizhe , Wu Zhiyuan , Deng Xuan , Wang Xu , Zhang Chao , Guan Ming
Published: December 2020

Background

Brain metastases explain the majority of mortality associated with lung cancer, which is the leading cause of cancer death. Cytology analysis of the cerebrospinal fluid (CSF) remains the diagnostic gold standard, however, the circulating tumor cells (CTCs) in CSF (CSF‐CTCs) are not well defined at the molecular and transcriptome levels.

Methods

We established an effective CSF‐CTCs collection procedure and isolated individual CSF cells from five lung adenocarcinoma leptomeningeal metastases (LUAD‐LM) patients and three controls. Three thousand seven hundred ninety‐two single‐cell transcriptomes were sequenced, and single‐cell RNA sequencing (scRNA‐seq) gene expression analysis was used to perform a comprehensive characterization of CSF cells.

Results

Through clustering and expression analysis, we defined CSF‐CTCs at the transcriptome level based on epithelial markers, proliferation markers, and genes with lung origin. The metastatic‐CTC signature genes are enriched for metabolic pathway and cell adhesion molecule categories, which are crucial for the survival and metastases of tumor cells. We discovered substantial heterogeneity in patient CSF‐CTCs. We quantified the degree of heterogeneity and found significantly greater among‐patient heterogeneity compared to among‐cell heterogeneity within a patient. This observation could be explained by spatial heterogeneity of metastatic sites, cell‐cycle gene, and cancer‐testis antigen (CTA) expression profiles as well as the proportion of CTCs displaying mesenchymal and cancer stem cell properties. In addition, our CSF‐CTCs transcriptome profiling allowed us to determine the biomarkers during the progression of an LM patient with cancer of unknown primary site (CUP).

Conclusions

Our results will provide candidate genes for an RNA‐based digital detection of CSF‐CTCs from LUAD‐LM and CUP‐LM cases, and shed light on the therapy and mechanism of LUAD‐LM.
Clinical implications of plasma ctDNA features and dynamics in gastric cancer treated with HER2‐targeted therapies
Authors: Zhang Cheng , Chen Zuhua , Chong Xiaoyi , Chen Yang , Wang Zhenghang , Yu Ruoying , Sun Tingting , Chen Xiaoxi , Shao Yang , Zhang Xiaotian , Gao Jing , Shen Lin
Published: December 2020

Background

Gastric cancer (GC) is confronted with limited options for precision medicine. Human epidermal growth factor receptor 2 (HER2) is the principal druggable target of GC, yet proper biomarkers for response/resistance prediction remain unveiled.

Methods

From 40 GC patients received HER2‐targeted therapy, a total of 327 peripheral blood plasma specimens was collected including baseline and treatment time points. Circulating tumor DNA (ctDNA) was extracted and sequenced with a target panel of 425 genes. Experimental validation of resistant mutations was carried out in NIH‐3T3 cell line.

Results

Genomic features, includingERBB2copy number variation (CNV), total copy number load, and tumor mutation burdens (TMBs), dynamically changed along with the treatment process and correlated with disease progression. Plasma ctDNA‐based diagnosis was more sensitive than conventional computed tomography scanning in 40% of investigated patients, gaining additional time for clinical management. Compared to baseline, new gene alterations were emerged in 12 patients who developed drug resistance during treatment.ERBB2mutations potentially related to Pyrotinib resistance were identified in plasma ctDNA of one patient and functional analysis of their downstream signaling pathways was carried out in NIH‐3T3 cell line. TMB exhibited more power thanERBB2CNV in predicting treatment responses and prognosis for HER2‐targeted therapy in GC patients. Interestingly, survival analysis indicated that patients harboring both HER2 (ERBB2) positivity and high TMB might gain more therapeutic benefits from immune checkpoint inhibitors instead of HER2‐targeted regimens that required further studies and validations

Conclusions

Our work showed that the dynamic surveillance of plasma ctDNA genomic features provided instructive information for the precision medication of GC patients.
Phylogeny and biogeography of the Japanese rhinoceros beetle, Trypoxylus dichotomus (Coleoptera: Scarabaeidae) based on SNP markers
Authors: Yang Huan , You Chong Juan , Tsui Clement K. M. , Tembrock Luke R. , Wu Zhi Qiang , Yang De Po
Published: December 2020

The Japanese rhinoceros beetle Trypoxylus dichotomus is one of the largest beetle species in the world and is commonly used in traditional Chinese medicine. Ten subspecies of T. dichotomus and a related Trypoxylus species (T. kanamorii) have been described throughout Asia, but their taxonomic delimitations remain problematic. To clarify issues such as taxonomy, and the degree of genetic differentiation of Trypoxylus populations, we investigated the genetic structure, genetic variability, and phylogeography of 53 specimens of Trypoxylus species from 44 locations in five Asian countries (China, Japan, Korea, Thailand, and Myanmar). Using specific‐locus amplified fragment sequencing (SLAF‐seq) techniques, we developed 330,799 SLAFs over 114.16M reads, in turn yielding 46,939 high‐resolution single nucleotide polymorphisms (SNPs) for genotyping. Phylogenetic analysis of SNPs indicated the presence of three distinct genetic groups, suggesting that the various subspecies could be treated as three groups of populations. PCA and ADMIXTURE analysis also identified three genetic clusters (North, South, West), which corresponded to their locations, suggesting that geographic factors were important in maintaining within population homogeneity and between population divergence. Analyses of SNP data confirmed the monophyly of certain subspecies on islands, while other subspecies (e.g., T. d. septentrionalis) were found to be polyphyletic and nested in more than one lineage. AMOVA demonstrated high level of differentiation among populations/groups. Also, pairwise FST values revealed high differentiation, particularly between South and West, as well as between North and South. Despite the differentiation, measurable gene flow was inferred between genetic clusters but at varying rates and directions. Our study demonstrated that SLAF‐seq derived markers outperformed 16S and COII sequences and provided improved resolution of the genetic differentiation of rhinoceros beetle populations from a large part of the species’ range.
The influence of nutrient enrichment on riverine food web function and stability
Authors: Canning Adam D. , Death Russell G.
Published: December 2020

Nutrient enrichment of rivers and lakes has been increasing rapidly over the past few decades, primarily because of agricultural intensification. Although nutrient enrichment is known to drive excessive algal and microbial growth, which can directly and indirectly change the ecological community composition, the resulting changes in food web emergent properties are poorly understood. We used ecological network analysis (ENA) to examine the emergent properties of 12 riverine food webs across a nutrient enrichment gradient in the Manawatu, New Zealand. We also derive Keystone Sensitivity Indices to explore whether nutrients change the trophic importance of species in a way that alters the resilience of the communities to further nutrient enrichment or floods. Nutrient enrichment resulted in communities composed of energy inefficient species with high community (excluding microbes) respiration. Community respiration was several times greater in enriched communities, and this may drive hypoxic conditions even without concomitant changes in microbial respiration. Enriched communities exhibited weaker trophic cascades, which may yield greater robustness to energy flow loss. Interestingly, enriched communities were also more structurally and functionally affected by species sensitive to flow disturbance making these communities more vulnerable to floods.
Impact of body mass index on surgical coronary revascularization for ischaemic heart failure: insights from STICHES
Authors: Hendren Nicholas S. , Zhong Lin , Neeland Ian J. , Michelis Katherine C. , Drazner Mark H. , Tang W.H. Wilson , Pandey Ambarish , Grodin Justin L.
Published: December 2020

Aims

Patients with obesity and ischaemic heart failure may counter‐intuitively have better outcomes compared with patients with normal body weight due to an ‘obesity paradox’. This study sought to determine if body mass index (BMI) impacts the treatment effects or safety outcomes of the treatment of ischaemic heart failure with coronary artery bypass grafting (CABG).

Methods and results

We obtained and reviewed the Surgical Treatment of Ischaemic Heart Failure (STICHES) data for 1212 patients. We categorized obesity by the World Health Organization (WHO) classes to define baseline characteristics and test for treatment interactions for the primary and secondary STICHES outcomes by treatment groups. While CABG decreased the risk of death, there was no evidence of treatment interaction by BMI per 5 kg/m2 (P = 0.83) or WHO obesity class. For the overall cohort, there was no interaction by WHO obesity class for the cumulative incidence of death in either the medical therapy or CABG plus medical therapy (P‐interaction = 0.90). There was a non‐significant trend for higher BMI and a lower risk of death [hazard ratio 0.92, 95% confidence interval (CI) 0.85–1.00, P = 0.051]. Increasing body size (per 5 kg/m2) was associated with return to the operating room (odds ratio 2.48, 95% CI 1.45–4.26, P < 0.001) and infectious mediastinitis (odds ratio 2.09, 95% CI 1.10–3.97, P = 0.024) at 30 days but not other 30 day safety outcomes.

Conclusions

The benefit of CABG vs. medical therapy for ischaemic heart failure was consistent regardless of BMI or WHO obesity class for death or secondary clinical outcomes. However, higher BMI was associated with some short‐term post‐CABG complications.
Preserved ejection fraction and structural heart disease in 446 848 patients investigated with echocardiography
Authors: Playford David , Strange Geoffrey , Stewart Simon ,   NEDA Investigators
Published: December 2020

Background

Sex‐specific differences in left ventricular ejection fraction (LVEF) and responses to neurohormonal modulating therapies are relevant to clinical trials of treatment for heart failure with preserved ejection fraction (HFpEF).

Aims

This study aimed to identify the proportion and characteristics of patients presenting with possible or confirmed HFpEF within the National Echo Database of Australia.

Results

A total of 237 046 women (48.1%) and 256 019 men (aged 61.0 ± 18.3 vs. 60.6 ± 17.1 years, respectively) had sex‐specific distributions of LVEF: 94.3% of women had LVEF ≥ 45% (mean LVEF 66.0 ± 8.6%), compared with 87.2% of men (mean LVEF 63.4 ± 8.7%). The presence of structural heart disease (SHD) according to the PARAGON‐HF criteria could be calculated in 93.8% of women and 93.4% of men with an LVEF ≥ 45%. Of these, 64 502 (30.8%) women and 104 344 (50.0%) of men had left ventricular hypertrophy, and 78 948 (35.3%) and 95 846 (42.9%), respectively, had left atrial enlargement. As a result, the proportion of women vs. men fulfilling echocardiographic criteria for HFpEF was very different: 111 497 (53.2%) vs. 146 359 (70.1%). SHD markedly increased with age, associated with a greater increase in women than men. The same signal was observed in those referred for suspected or previously confirmed HFpEF.

Conclusions

Double the number of men than women had LVEF < 45%, and the distribution of SHD had was highly sex specific. Left ventricular hypertrophy and left atrial enlargement were more common in men and becoming more frequent in women with advancing age. The echocardiographic SHD distribution was similar in those referred with suspected or confirmed HFpEF. The findings are relevant to sex‐specific recruitment criteria for future clinical trials.
Epstein Barr virus infection and immune defense related to HLA‐DR15: consequences for multiple sclerosis
Authors: Olsson Tomas
Published: December 2020

MS is a multifactorial disease in which a series of genetic and non‐genetic, environmental factors plays a role in its etiology. In particular, HLA class II alleles, mainly HLADRB1*15:01 (HLA‐DR15), increase the risk for this disease. Out of several environmental factors, and with regard to infections, EBV remains to be a strong candidate, and may synergize with HLA‐DR15 thus increasing the risk for MS. In this issue of the European Journal of Immunology, Zdimerova et al. present highly interesting experimental data using EBV infection in immune‐deficient mice engrafted with human immune cells, either HLA‐DR15+ or HLA‐DRB1*04:01 (HLA DR4), here after denoted as HLA‐DR15−. As a result of EBV infection, the viral load and CD8+ cell expansion were conspicuously higher in mice engrafted with HLA‐DR15+ compared to HLA‐DR15− mice; and myelin basic protein specific T cells emerged in mice engrafted with HLA‐DR15 bearing cells. This study sheds light on how EBV and the class II DR15 haplotype may jointly predispose and synergize in the etiology of MS.
Bis(pyrazolato) Bridged Diiron Complexes: Ferromagnetic Coupling in a Mixed‐Valent HS‐FeII/LS‐FeIII Dinuclear Complex
Authors: Wong Joanne W. L. , Hua Shao‐An , Demeshko Serhiy , Dechert Sebastian , Ye Shengfa , Meyer Franc
Published: December 2020

Using a new bis(tridentate) compartmental pyrazolate‐centered ligand HL, the bis(pyrazolato)‐bridged diiron complex [L2FeII2][OTf]2 (1) and its singly oxidized mixed‐valent congener [L2FeIIFeIII][OTf]3 (2) have been synthesized and structurally characterized. While 1 features two HS‐FeII ions coordinated to two cis‐axial pyridine moieties in a highly distorted octahedral environment, the metal ions in 2 are coordinated by the ligand strand in a trans‐axial configuration. Very different Fe–N bond lengths and distinctly different coordination polyhedra are associated with pronounced valence localization in the case of 2. The electronic structures and magnetic properties of 1 and 2 have been further investigated by Mössbauer spectroscopy and variable temperature magnetic susceptibility measurements. In the case of 1, weak antiferromagnetic coupling is observed between the two HS‐FeII ions (J = –0.6 cm–1), while the HS‐FeII and LS‐FeIII ions in 2 are ferromagnetically coupled (J = +5.2 cm–1) to give an ST = 5/2 ground state with significant zero‐field splitting (DFe(II) = 2.3 cm–1). The findings are rationalized with the help of DFT computations.
Layered Inorganic Cationic Frameworks beyond Layered Double Hydroxides (LDHs): Structures and Applications
Authors: Wang Yunzheng , Wang Shuang , Li Xiaolong , Bai Pu , Yan Wenfu , Yu Jihong
Published: December 2020

Layered double hydroxides (LDHs), a typical layered inorganic cationic material, have been widely studied as ion‐exchanger, catalyst and polymer additives. The past few decades have seen rapidly increasing interest in non‐LDH type 2‐dimensional inorganic cationic frameworks. Their novel properties derived from structural and compositional diversity cast a light on the field where LDHs show limited performance. This minireview will discuss the structure, synthesis and applications including anion‐exchange and catalysis of non‐LDH type 2‐dimensional inorganic cationic frameworks and present the prospective for researchers working on.
PIFA‐Mediated Cross‐Dehydrogenative Coupling of N‐Heteroarenes with Cyclic Ethers: Ethanol as an Efficient Promoter
Authors: Li Xiang , Liu Chaoyang , Guo Shixun , Wang Wei , Zhang Yongqiang
Published: December 2020

Ethanol is typically used in organic synthesis as an environmentally benign solvent. Herein, we report a mild and efficient cross‐dehydrogenative coupling (CDC) reaction of N‐heteroarenes with cyclic ethers by uncovering the new reactivity of ethanol as an efficient promoter in PIFA‐mediated radical process. The reaction proceeds smoothly under the irradiation of visible light and features excellent functional group compatibility, which allows the expedite synthesis of a variety of medicinally valuable Cα‐heteroarylated cyclic ethers in moderate to high yields.
Synthesis of Porphyrins Di‐ and Tetra‐Functionalized with Nucleobases
Authors: Tufenkjian Elsa , Kahlfuss Christophe , Kyritsakas Nathalie , Hosseini Mir Wais , Bulach Véronique
Published: December 2020

A library composed of ten porphyrins bearing nucleobases is prepared, following two strategies: substitution or Sonogashira cross‐coupling reactions. The former strategy led to the synthesis of four porphyrins (T2−Po1, A2−Po1, C2−Po1 and P2−Po1) bearing nucleobases (NBs) at two trans meso‐positions. These 4 porphyrins were obtained by reacting 5,15‐di(4‐(bromomethyl)phenyl)‐10,20‐dimesitylporphyrin (Po1) with thymine (T), adenine (A), cytosine (C) and 2‐amino‐6‐chloropurine (P), a precursor of guanine (G), respectively in the presence of a suitable base. A fifth porphyrin, 5,15‐di(N9‐methylphenylguanine)‐10,20‐dimesitylporphyrin (G2−Po1) was obtained by hydrolysis of P2−Po1. A thymine tetra‐functionalized porphyrin was also synthesized following the same strategy starting from T and 5,10,15,20‐tetrakis[4‐(bromomethyl)phenyl]porphyrin (Po2). The second strategy based on Sonogashira cross‐coupling reactions between 5,15‐dibromo‐10,20‐dipentylporphyrin (Po3) and ethynyl‐substituted nucleobases resulted in four rigid porphyrins (U2−Po3, C2−ZnPo3, A2−ZnPo3, and G2−ZnPo3).
A novel two‐step process to produce high‐quality basil flavoured chicken powder: Effect of ultrasonication followed by microwave vacuum and hot air drying
Authors: Xu Kejing , Zhang Min , Mujumdar Arun S. , Liu Yaping
Published: December 2020

The objective of this experimental investigation was to develop a novel two‐step process for production of high‐quality chicken powder infused with basil. The first step consists of ultrasonication of an aqueous chicken pieces mixed with chopped basil leaves to enhance extraction of basil flavour and also pretreat the chicken microstructure to intensify the drying kinetics in the second step. The drying was carried out using microwave vacuum followed by hot air. The results showed that the drying time of chicken was the shortest (110 minutes) after US 40 minutes. In terms of product quality, the best rehydration (136.18%), the lowest hygroscopicity (3.84%) and the best colour of basil chicken powder were obtained after US 40 minutes. In the aspect of flavour addition, the content of linalool, estragole and eucalyptol in the chicken powder treated by US 40 minutes was the highest, and these three compounds were the main flavour substances of basil. At the same time, the content of some substances with bad smell, such as benzaldehyde, was greatly reduced after adding basil flavour. The overall quality of chicken powder produced by this novel process was found to be superior to that of commercially available spray‐dried chicken powder.
Effectiveness of a Decentralized Hub and Spoke Model for the Treatment of Hepatitis C Virus in a Federally Qualified Health Center
Authors: Rojas Sarah A. , Godino Job G. , Northrup Adam , Khasira Maureen , Tam Aaron , Asmus Lisa , Frenette Catherine , Ramers Christian B.
Published: December 2020

Hepatitis C virus (HCV) is a major cause of cirrhosis, liver cancer, and mortality in the United States. We assessed the effectiveness of decentralized HCV treatment delivered by nurse practitioners (NPs), primary care physicians (PMDs), or an infectious disease physician (ID MD) using direct‐acting antivirals in a Federally Qualified Health Center (FQHC) in urban San Diego, CA. We conducted a cross‐sectional analysis of 1,261 patients who received treatment from six NPs, 10 PMDs, and one ID MD practicing in 10 clinics between January 2014 and January 2020. Care was delivered based on the Extension for Community Healthcare Outcomes (Project ECHO) model with one hub and nine spokes. HCV was deemed cured if a patient had a sustained virologic response (SVR) after 12 weeks of treatment (SVR12). We evaluated differences in the prevalence of cure between provider types and hub or spoke status using Poisson regression. Patients were 34% Latino, 16% black, 63% were aged >50 years, and 59% were homeless; 53% had advanced fibrosis, 69% had genotype 1, and 5% were coinfected with human immunodeficiency virus. A total of 943 patients achieved SVR12 (96% per protocol and 73% intention to treat). Even after adjustment for demographics, resources, and disease characteristics, the prevalence of cure did not differ between the ID MD and PMDs (prevalence ratio [PR], 1.00; 95% confidence interval [CI], 0.95‐1.04) or NPs (PR, 1.01; 95% CI, 0.96‐1.05). Similarly, there were no differences between the hub and spokes (PR, 1.01; 95% CI, 0.98‐1.04). Conclusion: Among a low‐income and majority homeless cohort of patients at urban FQHC clinics, HCV treatment administered by nonspecialist providers was not inferior to that provided by a specialist.