bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and electrochemical characteristics of oligo[{3,4‐diphenyl‐1,1‐di(propan‐2‐yl)‐2,5‐silolene}‐co‐(diphenylsilylene)] for lithium‐ion secondary battery anodes
Authors: Jung Young Min , Park Young Tae
Published: September 2021

The co‐oligomerization of 2,5‐dibromo‐3,4‐diphenyl‐1,1‐di(propan‐2‐yl)‐silole (3) with dichlorodiphenylsilane was carried out using n‐butyllithium at −78°C to synthesize oligo[{3,4‐diphenyl‐1,1‐di(propan‐2‐yl)‐2,5‐silolene}‐co‐(diphenylsilylene)] (5) as yellowish‐white powder, with a mass‐average molar mass of 561, polydispersity of 1.01, λabs,max of 260 and 279 nm, λex,max of 296 nm, λem,max of 391 nm, and thermal stability up to 125°C without any weight loss. The rate performance obtained with oligomer 5 was superior to that obtained with monomer 3. The discharge and charge capacities with 5 were 1234 and 1263 mAhg−1, respectively, with Coulombic efficiency of 97.7% at the 100th cycle. Nyquist plots suggested that the resistance decreases gradually with repeated cycling.
Construction of circRNA‐based ceRNA network and its prognosis‐associated subnet of clear cell renal cell carcinoma
Authors: Zhang Yuwei , Zhang Yuchen , Feng Yangkun , Zhang Nan , Chen Saisai , Gu Chaoqun , Hu Lei , Sheng Jiayi , Xu Bin , Feng Ninghan
Published: September 2021

Circular RNAs (circRNAs) are novel biomarkers of various cancers. CircRNAs can sponge miRNAs and regulate target mRNAs, which was called competing endogenous RNAs (ceRNA). This study was designed to identify circRNAs related to patients with clear cell renal cell carcinoma (ccRCC) and the first to select three independent Gene Expression Omnibus microarrays covering circRNAs, miRNAs, and mRNAs for multiple analyses. The data of clinical cases applied in our study were obtained from The Cancer Genome Atlas. We successfully conducted a circRNA/miRNA/mRNA ceRNA network related to ccRCC patients via R software and Cytoscape including 8 circRNAs, 6 miRNAs, and 49 mRNAs. The prognosis‐associated subnet covered 8 circRNAs, 6 miRNAs, and 22 mRNAs. Quantitative real‐time PCR was applied to measure our prediction in three renal cell lines and 23 pairs of tissues. Small interfering RNA targeting the back‐splice region of hsa_circ_0001167 was further implied to confirm the regulation. Ultimately, hsa_circ_0001167/hsa‐miR‐595/CCDC8 regulatory axis was identified in this study, which may serve as prognostic indicators. Lower levels of hsa_circ_0001167 and CCDC8 were potentially correlated with worse patient survival.
Optimization Strategies for the Anodic Phenol‐Arene Cross‐Coupling Reaction
Authors: Hielscher Maximilian , Oehl Elisabeth K. , Gleede Barbara , Buchholz Julian , Waldvogel Siegfried R.
Published: September 2021

Dehydrogenative phenol‐arene cross‐coupling by direct anodic oxidation is a promising alternative to reductive cross‐coupling, especially for construction of smaller molecules. The reaction pathway via phenoxyl radicals allows for unusual regioselectivity. Nevertheless, the numerous electrolysis parameters pose a challenge for optimization, as they determine the yield and selectivity of the reaction. Using design of experiments, we present optimization strategies for two example reactions to improve the space‐time yield. In particular, coupling reactions with 2,6‐dimethoxyphenol (syringol) were found to be very robust in the electrolysis at high current densities of up to 150 mA/cm2. Cyclic voltammetry was used to classify combinations of phenols and arenes, on the basis of which the various clusters were optimized. Based on this classification, various biaryls were synthesized and isolated in yields of up to 85 %.
Relationship between longitudinal changes in type‐2 inflammation, immunoglobulin E sensitization, and clinical outcomes in young asthmatics
Authors: Tsolakis Nikolaos , Jacinto Tiago , Janson Christer , Borres Magnus , Malinovschi Andrei , Alving Kjell
Published: September 2021

Background

Asthma is a heterogeneous condition where biomarkers may be of considerable advantage in diagnosis and therapy monitoring. However, the changes in asthma biomarkers and immunoglobulin E (IgE) over the course of life has not been extensively investigated.

Objective

To study longitudinal changes in type‐2 inflammatory biomarkers, IgE, and clinical outcomes, and the association between these changes, in young asthmatics.

Methods

Asthmatics (age 10–35 years, n = 253) were examined at baseline and at a follow‐up visit, 43 [23–65] (median [range]) months later. Subjects were analyzed using the multi‐allergen tests Phadiatop and fx5 (ImmunoCAP) and grouped based on the baseline allergen‐specific IgE antibody (sIgE) concentration: <0.10, 0.10–0.34, and ≥0.35 kUA/L. The relationship between changes (Δ values) in type‐2 biomarkers (individualized fraction of exhaled nitric oxide [FeNO%], blood eosinophil [B‐Eos] count, total IgE [tIgE] and sIgE, lung function [% predicted forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC)], and Asthma Control Test [ACT]) score were determined.

Results

At follow up, FEV1 and FEV1/FVC had decreased (93.6% vs. 95.8%, and 93.4% vs. 94.7% of predicted, respectively [p < 0.001 both]), whereas ACT score had increased (21.6 vs. 20.6, p = 0.001). A significant decline in lung function was seen in subjects with sIgE ≥ 0.10 kUA/L, but not in those with undetectable sIgE (<0.10 kUA/L). Furthermore, tIgE and sIgE declined over time (p < 0.001 all) whereas FeNO% and B‐Eos count were not significantly changed. In univariate analysis, significant negative correlations between ∆B‐Eos count and ∆FeNO%, on one hand, and changes in lung function, on the other hand, were seen, and multivariate analysis showed an independent relationship between ΔFeNO%, and ΔFEV1 (p < 0.05) and ΔFEV1/FVC% (p < 0.01). Sex‐specific analysis showed that the independent association between ΔFeNO%, and ΔFEV1 remained only in females (p = 0.005), and there was a significant interaction with sex (p = 0.02).

Conclusion

In young asthmatics, IgE levels declined over 43 months, whereas FeNO and B‐Eos remained unchanged. In spite of improved asthma control, an accelerated lung function decline was seen in patients with detectable sIgE at baseline, and the decline correlated with changes in type‐2 biomarkers. Particularly, the increase in individualized FeNO associated independently with decline in FEV1 in females.
A Versatile Compact Parahydrogen Membrane Reactor
Authors: TomHon Patrick M. , Han Suyong , Lehmkuhl Sören , Appelt Stephan , Chekmenev Eduard Y. , Abolhasani Milad , Theis Thomas
Published: September 2021

We introduce a Spin Transfer Automated Reactor (STAR) that produces continuous parahydrogen induced polarization (PHIP), which is stable for hours to days. We use the PHIP variant called signal amplification by reversible exchange (SABRE), which is particularly well suited to produce continuous hyperpolarization. The STAR is operated in conjunction with benchtop (1.1 T) and high field (9.4 T) NMR magnets, highlighting the versatility of this system to operate with any NMR or MRI system. The STAR uses semipermeable membranes to efficiently deliver parahydrogen into solutions at nano to milli Tesla fields, which enables 1H, 13C, and 15N hyperpolarization on a large range of substrates including drugs and metabolites. The unique features of the STAR are leveraged for important applications, including continuous hyperpolarization of metabolites, desirable for examining steady‐state metabolism in vivo, as well as for continuous RASER signals suitable for the investigation of new physics.
A 1‐Hydroxy‐1H‐imidazole ESIPT Emitter Demonstrating anti‐Kasha Fluorescence and Direct Excitation of a Tautomeric Form
Authors: Shekhovtsov Nikita A. , Nikolaenkova Elena B. , Berezin Alexey S. , Plyusnin Victor F. , Vinogradova Katerina A. , Naumov Dmitry Yu. , Pervukhina Natalia V. , Tikhonov Alexsei Ya. , Bushuev Mark B.
Published: September 2021

The ability of 1‐hydroxy‐1H‐imidazoles to exist in the form of two prototropic tautomers, the N‐hydroxy and the N‐oxide forms, can be utilized in the design of new types of ESIPT‐fluorophores (ESIPT=excited state intramolecular proton transfer). Here we report the first example of 1‐hydroxy‐1H‐imidazole‐based ESIPT‐fluorophores, 1‐hydroxy‐5‐methyl‐2,4‐di(pyridin‐2‐yl)‐1H‐imidazole (HL), featuring a short intramolecular hydrogen bond O−H⋅⋅⋅N (O⋅⋅⋅N 2.56 Å) as a pre‐requisite for ESIPT. The emission of HL originates from the anti‐Kasha S2→S0 fluorescence in the N‐oxide form as a result of a large S2–S1 energy gap slowing down the S2→S1 internal conversion. Due to an energy barrier between the N‐hydroxy and N‐oxide forms in the ground state, the HL molecules can be trapped and photoexcited in the N‐oxide form leading to the Stokes shift of ca. 60 nm which is the smallest among known ESIPT‐fluorophores.
Multidomain modeling of nonlinear electromagnetic circuits using wave digital filters
Authors: Giampiccolo Riccardo , Bernardini Alberto , Gruosso Giambattista , Maffezzoni Paolo , Sarti Augusto
Published: September 2021

Accurate models of electromagnetic systems can be derived by coupling electric and magnetic equivalent circuits together. The different nature of such physical domains constitutes a big challenge that puts a continuous strain on software simulators. To face this problem, a simulation approach based on Wave Digital Filters (WDFs) is proposed in this manuscript. The method is employed to solve nonlinear electromagnetic systems containing complex magnetic equivalent circuits while maintaining the modularity of the electric and magnetic subsystems. The nonlinearities can be locally handled, enabling the possibility to choose a dedicated model for each one of them. The proposed algorithm is a hierarchical generalization of the Scattering Iterative Method, which has shown, over the past few years, promising performance for the simulation of large nonlinear circuits. In addition, the method constitutes a further step towards the development of novel general‐purpose circuit simulators based on WDF principles. In a comparison with mainstream circuit simulation software, the proposed approach turns out to be considerably faster and thus particularly promising for parametric analyses of electromagnetic systems.
Compact closed‐slot eight‐antenna system for 5G laptops with a metal back cover
Authors: Chen Shu‐Chuan , Zhu Jia‐Le , Hsu Chung‐I G.
Published: September 2021

This paper presents the design of a compact closed‐slot sub‐6‐GHz dual‐band eight‐antenna system on a 5G laptop with a metal back cover. The antenna system is installed in a 277 × 2 mm2 clearance area that is 3 mm below the upper edge of the metal back cover of the laptop. Each single closed‐slot antenna element measures 32 × 2 mm2 and features an inverted‐C feeding section and a crossover path consisting of a meandered section and a series chip capacitor. The crossover path can help generate a resonance mode at high frequencies while adjusting the frequency location of the low‐frequency mode, allowing the closed‐slot antenna to support the 3300‐ to 3600‐ and 4800‐ to 5000‐MHz dual‐band operation required for sub‐6‐GHz 5G. The eight closed‐slot antenna elements are oriented in the same direction and aligned in the same axis with a 3‐mm separation between any two adjacent antenna elements. Without the help of any isolation elements, the resultant eight‐element multi‐input multi‐output (MIMO) antenna system possesses measured isolations of larger than 10 dB. The envelope correlation coefficients (ECCs) calculated from the measured complex radiation patterns are all less than 0.105, and the measured antenna efficiencies are over 40%. These results indicate that the proposed MIMO antenna system is ideal for use in laptop devices with a metal back cover and a large screen‐to‐body ratio.
Endoscopic diagnosis of chronic diarrhea
Authors: Kinoshita Yoshikazu , Ariyoshi Ryusuke , Fujigaki Seiji , Tanaka Katsuhide , Morikawa Teruhisa , Sanuki Tsuyoshi
Published: September 2021

The prevalence of chronic diarrhea in the general population is reported to be 4%–5%. Since various pathological conditions cause diarrheal symptoms, etiological diagnosis of chronic diarrhea is difficult in many cases. Medical history taking, physical examinations, and laboratory testing are not adequately sensitive or specific, thus a colonoscopic investigation is frequently employed for etiological evaluation. However, for cases with non‐bloody chronic diarrhea, the diagnostic yield of a colonoscopy procedure is reported to be not high enough. Furthermore, endoscopically identifiable findings are not adequately specific for the diagnosis of diarrheal disease, except for inflammatory bowel disease, while microscopic colitis, amyloidosis, eosinophilic gastroenteritis, celiac disease, and bile acid diarrhea are difficult to definitively diagnose using endoscopic findings. Thus, a histopathological examination of biopsy samples obtained with endoscopy is critically important. Endoscopists should consider obtaining biopsy samples from even normal‐appearing gastrointestinal mucosa for chronic diarrhea diagnosis.
Experimental verification of bidirectional modular multilevel cascaded converter suitable for applying 120‐degree discontinuous pulse width modulation maximum
Authors: Oi Kazunobu , Urushibata Shota , Tadano Yugo , Sato Yukihiko
Published: September 2021

Modular multilevel cascaded converters (MMCCs) have advantages in the application of high or medium voltage without transformers. They can also generate high‐quality voltage with fewer harmonics. Their unique merits make them leading technology candidates for high/medium voltage applications. However, a concern still exists that the number of parts may be increased. In this study, an MMCC topology using high‐voltage IGBT (HV‐IGBT) with snubber capacitor connected in parallel as a cell module arm is proposed, by which the number of cells can be halved and conduction loss can be significantly reduced owing to the output current flowing through the HV‐IGBT in one‐third of the cycle. Meanwhile, the proposed control stratagem can control the cell capacitor voltage, suppress the HV‐IGHT surge voltage, and avoid short‐circuiting of the snubber capacitor by circulating current. This study reports the evaluation results of capacitors and the experimental results of bidirectional active power conversion operation.
Limitations and Benefits of MAX Phases in Electroanalysis
Authors: Tesař Jan , Muñoz Jose , Pumera Martin
Published: September 2021

MAX phases are a group of layered 2D materials made of early transition metal, A‐group element (e.g., Al, Sn or Si), and C or N. These nanolaminated carbides and nitrides combine many attractive characteristics of metals and ceramics such as excellent electric and thermal conductivity and high chemical resistance. Although MAX phases have shown promising electrochemical results in the field of energy conversion, their use for electroanalytical approaches is nowadays an unexplored field. Herein, the potential use of MAX phases for electroanalytical approaches has been investigated. For this aim, seven different MAX phases (Cr2AlC, Mo2AlC, Ta2AlC, Ti2AlN, Ti2SnC, Ti3AlC2, Ti3SiC2, and V2AlC) have been drop‐casted upon a conventional glassy‐carbon electrode and tested at different pH media, also providing their potential towards the determination of different analytes. Overall, our findings elucidate the limitations and benefits of using MAX phases for electroanalysis, demonstrating that a proper combination of both MAX phases and electrolyte media is a must to direct efficient performances as electrode for electroanalysis. Accordingly, this work provides new knowledge about the electrochemical behaviour of MAX phases and their potential in the field of electronic devices.
The mechanism exploration of the non‐colonic toxicity and obesity inhibition of food‐grade κ‐carrageenan by transcriptome
Authors: Zhang Hui , Cao Wanxiu , Liu Fang , Gao Yuan , Chang Yaoguang , Xue Changhu , Tang Qingjuan
Published: September 2021

Previous study has suggested the colonic nontoxicity and obesity inhibition of food‐grade κ‐carrageenan in obese mice. Further study using transcriptome is important to provide further understanding on the gene expressions of inflammation and obesity. Here, the obese mice without any treatment (HFD) or with 5% food‐grade κ‐carrageenan diet intervention (H5%) were used to perform colonic transcriptome sequencing. The results showed that genes involved in the inflammatory pathways or tight junction protein encoding were not significantly dysregulated by 5% carrageenan. However, the expression of lipid metabolism genes meaningfully changed as evidenced by the decreased gene levels of adipocytokines, lipogenesis, lipid absorption and transport, and the increased adipolysis and oxidation. In addition, the carrageenan metabolism experiments by toluidine blue (TB) staining of colon and high‐performance size exclusion chromatography (HPSEC) of feces supernatant showed that the food‐grade κ‐carrageenan was not absorbed or significantly degraded in the digestive tract of obese mice. Hence, the fact that food‐grade κ‐carrageenan was not significantly metabolized by the organism and did not cause obvious dysregulation of colonic inflammatory genes provided evidences for its noncolonic toxicity in obese mice. An anti‐obesity potential of food‐grade κ‐carrageenan was probably mediated by the regulation of lipids metabolism‐related genes.
Use of high‐frequency data to evaluate the performance of dynamic hedging strategies
Authors: Lai Yu‐Sheng
Published: September 2021

The hedging performance results of generalized autoregressive conditional heteroskedasticity models are mixed; we address this herein by adopting an asymptotic setting to determine the relative performance of competing hedge ratios. The proxy variable is constructed through precise realized measures rather than through noisy squared returns because the substitution of the latent true hedged portfolio variance with a noisy proxy renders the loss function incapable of ranking forecasts consistently. The merits of allowing some features in modeling the spot–futures distribution are assessed. Empirical comparisons suggest that hedgers may favor the wrong model when the quality of the proxy variable deteriorates.
A Skellam market model for loan prime rate options
Authors: Chen Zhanyu , Zhang Kai , Zhao Hongbiao
Published: September 2021

This paper documents vanilla interest‐rate options newly introduced in China. The underlying rates are the RMB loan prime rates (LPRs), the foremost interest rates that matter to almost all businesses and households in China. They are digital with a tick size of five basis points, and the changes only occur monthly at predetermined announcement times. We propose a novel continuous‐time discrete‐state market model based on the integer‐valued Skellam distribution, and derive arbitrage‐free pricing formulas in closed forms. We advocate that it is more meaningful to quote LPR option prices in terms of implied intensity rather than implied volatility.
Do enhanced derivative disclosures work? An informational perspective
Authors: He Guanming , Ren Helen Mengbing , Taffler Richard
Published: September 2021

Firms use derivatives both for hedging and nonhedging purposes. The Statement of Financial Accounting Standards No. 161 (SFAS 161) requires firms to disclose the purposes of their derivatives usage, thereby helping investors to evaluate the effects of derivatives usage on firm performance. Using a hand‐collected sample of US listed firms and a difference‐in‐differences research design, we find that, compared with nonderivative‐users, derivative‐users compliant with SFAS 161 experience a significantly greater reduction in stock illiquidity and the probability of informed trading in the post‐SFAS 161 period, and such impact is evident only for firms with a high degree of investor attention.
Identifying individuals with Alzheimer's disease‐like brains based on structural imaging in the Human Connectome Project Aging cohort
Authors: Li Binyin , Jang Ikbeom , Riphagen Joost , Almaktoum Randa , Yochim Kathryn Morrison , Ances Beau M. , Bookheimer Susan Y. , Salat David H. ,   For the Alzheimer's Disease Neuroimaging Initiative
Published: September 2021

Given the difficulty in factoring out typical age effects from subtle Alzheimer's disease (AD) effects on brain structure, identification of very early, as well as younger preclinical “at‐risk” individuals has unique challenges. We examined whether age‐correction procedures could be used to better identify individuals at very early potential risk from adults who did not have any existing cognitive diagnosis. First, we obtained cross‐sectional age effects for each structural feature using data from a selected portion of the Human Connectome Project Aging (HCP‐A) cohort. After age detrending, we weighted AD structural deterioration with patterns quantified from data of the Alzheimer's Disease Neuroimaging Initiative. Support vector machine was then used to classify individuals with brains that most resembled atrophy in AD across the entire HCP‐A sample. Additionally, we iteratively adjusted the pipeline by removing individuals classified as AD‐like from the HCP‐A cohort to minimize atypical brain structural contributions to the age detrending. The classifier had a mean cross‐validation accuracy of 94.0% for AD recognition. It also could identify mild cognitive impairment with more severe AD‐specific biomarkers and worse cognition. In an independent HCP‐A cohort, 8.8% were identified as AD‐like, and they trended toward worse cognition. An “AD risk” score derived from the machine learning models also significantly correlated with cognition. This work provides a proof of concept for the potential to use structural brain imaging to identify asymptomatic individuals at young ages who show structural brain patterns similar to AD and are potentially at risk for a future clinical disorder.
Experimental investigation of hot AISI 304 steel plate with very‐high mass‐flux varying water temperature spray
Authors: Kumar Prashant , Chakraborty Sudipto
Published: September 2021

The spray cooling is investigated for very high mass‐flux coolants at different temperatures. First, the intended spray is characterized for its role in the cooling enhancement, which reveals that droplet detachment frequency, droplet residence time, liquid film, and vapor film wavelength influence heat‐transfer performance for high‐temperature very‐high mass‐flux spray. After that, the furnace heated 6‐mm thick steel plate at 1030°C is quenched using spray possessing average impingement density (231 kg/m2s) and coolant temperatures (30°C, 40°C, and 50°C). The heat transfer performance is analyzed using inverse heat conduction analysis, wherein temperature‐dependent steel thermophysical properties are considered. The heat transfer performance assessment through parameters such as cooling rate, surface heat flux, and heat transfer coefficient curves shows improvement in cooling performance. For 50°C coolant temperature, we observed the maximum improvement in cooling rate, 141°C/s, and critical heat flux, 3.64 MW/m2. The efficiency analysis reveals that coolant at the highest temperature is the most efficient. Also, an approximate cost assessment suggests enhanced coolant temperature as an economical alternative for heat transfer enhancement than additives‐based coolant.
Interleukin‐6 receptor alpha and CD27 discriminate intratumoral T helper 17 subpopulations with distinct functional properties in a mouse lung cancer model
Authors: Liu Chong , Xiong Fei , Wang Lingying , Chen Kang , Wu Pingshang , Hua Li , Zhang Zhuo
Published: September 2021

Background

T helper 17 (Th17) cells actively participate in the tumor immune response in lung cancer. However, the heterogeneity and plasticity of intratumoral Th17 cells in lung cancer remain elusive. In this study, Th17 subpopulations were characterized in a mouse lung cancer model.

Methods

Urethane was administered to induce lung cancer in interleukin (IL)‐17‐EGFP transgenic mice. Flow cytometry was used to analyze the phenotypes, signaling status, and functions of Th17 subpopulations either in vivo or in vitro. The adoptive transfer assay and real‐time polymerase chain reaction were applied to analyze the plasticity of Th17 subpopulations.

Results

IL‐6RαhighCD27− Th17 and IL‐6RαlowCD27+ Th17 were identified in intratumoral Th17 cells. The two subpopulations expressed equivalent RORγt. However, the former expressed higher T‐bet but lower Foxp3, more IL‐17A and IFN‐γ but less IL‐10 than the latter. Furthermore, IL‐6RαhighCD27− Th17 moderately inhibited the proliferation of lung cancer cells while IL‐6RαlowCD27+ Th17 could not. IL‐6RαhighCD27− Th17 exhibited weaker Jun N‐terminal kinases (JNK) signaling but stronger signal transducer and activator of transcription 3 (Stat3) signaling than IL‐6RαlowCD27+ Th17. The adoptive transfer assay indicated that both subpopulations downregulated RORγt in recipients' spleens but maintained RORγt in recipients' lungs. Meanwhile, IL‐6RαhighCD27− Th17 expressed higher T‐bet and IFN‐γ than IL‐6RαlowCD27+ Th17 in the recipients. IL‐6RαlowCD27+ Th17 expressed Foxp3 and IL‐10 in recipients' spleens but not lungs.

Conclusions

This study reveals intratumoral Th17 subpopulations with distinct functional properties and signaling patterns, thus offering valuable insight into Th17 heterogeneity and plasticity in lung cancer.
Immunogenomic characterization in gastric cancer identifies microenvironmental and immunotherapeutically relevant gene signatures
Authors: Han Xiao , Lu Heyue , Tang Xiaojun , Zhao Yao , Liu Hongxue
Published: September 2021

Background

Multiple molecular subtypes with distinct clinical outcomes in gastric cancer have been identified. Nonetheless, the immunogenomic subtypes of gastric cancer and its mediated tumor microenvironment (TME) characterizations have not been fully understood.

Methods

Six gastric cancer cohorts with 1506 samples were obtained. Unsupervised methods were used to perform immunogenomic phenotype clustering. The least absolute shrinkage and selection operator regression method was used to construct immunogenomic characterization score (IGCS).

Results

Three distinct immunogenomic phenotypes were determined. We observed a prominent survival difference between three phenotypes. The TME cell‐infiltrating characteristics under these three phenotypes were highly consistent with three immune subtypes of tumors. Cluster 1, was characterized by the “immune‐desert” phenotype, with relatively lower cell infiltration level (type 1 “cold tumor”); Cluster 2, characterized by “immune‐inflamed” phenotype, with abundant innate and adaptive immune cell infiltration (“hot tumor”); Cluster 3, characterized by “immune‐excluded” phenotype, with significant stromal activation and inactivated immune cell infiltration (type 2 “cold tumor”). We demonstrated IGCS signature was significantly correlated with TME inflammation and stroma activity, molecular subtypes, genetic variation, microsatellite instability, immune checkpoint molecules, and patient prognosis. High IGCS subtype, with poorer survival and enhanced stromal activity, presented an immune‐exclusion and non‐inflamed TME characterization. Low IGCS, related to increased mutation/neoantigen load and microsatellite instability, showed enhanced responses to anti‐checkpoint immunotherapy. Four immunotherapy cohorts confirmed patients with low IGCS exhibited prominently enhanced clinical responses and treatment advantages.

Conclusions

This study demonstrated the immunogenomic characterizations could play a crucial role in shaping the complexity and diversity of tumor microenvironment. Targeting tumor immunogenomic characteristic in order for changing adverse phenotypes may contribute to exploiting the novel immunotherapy combination strategies or novel immunotherapeutic drugs, and promoting the advance of tumor personalized immunotherapy.
Interpretability of deep neural networks used for the diagnosis of Alzheimer's disease
Authors: Pohl Tomáš , Jakab Marek , Benesova Wanda
Published: September 2021

Alzheimer's disease (AD) is a chronic brain disorder and is the most common cause of dementia. Patients suffering from AD experience memory loss, confusion, and other cognitive and behavioral complications. As the disease progresses, these symptoms become severe enough to interfere with the patient's daily life. Since AD is an irreversible disease and existing treatments can only slow down its progress, early diagnosis of AD is a key moment in fighting this disease. In this article, we propose a novel approach for diagnosing AD via deep neural networks from magnetic resonance imaging images. Additionally, we propose three new propagation rules for the layer‐wise relevance propagation (LRP) method, which is a method used for visualizing evidence in deep neural networks to obtain a better understanding of the network's behavior. We also propose various rule configurations for the LRP to achieve better interpretability of the network. Our proposed classification method achieves a 92% accuracy when classifying AD versus healthy controls, which is comparable to state‐of‐the‐art approaches and could potentially aid doctors in AD diagnosis and reduce the occurrence of human error. Our proposed visualization approaches also show improvements in evidence visualization, which helps the spread of computer‐aided diagnosis in the medical domain by eliminating the “black‐box” nature of the neural networks.
Modelling of potential groundwater artificial recharge in the transboundary Algero‐Tunisian Basin (Tebessa‐Gafsa): The application of stable isotopes and hydroinformatics tools*
Authors: Hamed Younes , Hadji Riheb , Ncibi Kaouther , Hamad Amor , Ben Sâad Amina , Melki Achraf , Khelifi Faten , Mokadem Naziha , Mustafa Eissa
Published: September 2021

Water resource overuse is a considerable challenge in areas with diverse activities and mixed climate. An area with deteriorated water quality (salinity higher than 5 g/L), typical of the transboundary Algero‐Tunisian area of the Tebessa‐Gafsa Basin in North Africa, was selected to investigate the spatial distribution of groundwater recharge and the water resources management. Several data including soil type, hydrogeologic characteristics, geomorphologic parameters, and climatic settings were used. Seasonal and early groundwater recharge and evapotranspiration were evaluated by applying the physical WetSpass model (Water and Energy Transfer between Soil, Plants, and Atmosphere Under quasi‐Steady State) model‐based geographic information system during 44 years. Results indicate spatio‐temporal changes in the recharge values. The highest values (13.3 mm) were recorded to the north of the study area during the wet season, while the lowest values, which reached −0.5 mm, were recorded to the south during the dry season. The recharge period of these transboundary aquifers, dated using isotopic tools (3H, 2H, and 18O), coincides with the Late Pleistocene and the Early Holocene humid periods. This Pleistocene and Holocene period could be responsible for the groundwater recharge in the Middle East and North Africa regions. Then, management and geovalorization of unconventional water processes promoting better water resource use have been proposed by applying artificial groundwater recharge.
Development and characterization of matrix‐derived microcarriers from decellularized tissues using electrospraying techniques
Authors: Kornmuller Anna , Flynn Lauren E.
Published: September 2021

Stirred bioreactor systems integrating microcarriers represent a promising approach for therapeutic cell manufacturing. While a variety of microcarriers are commercially available, current options do not integrate the tissue‐specific composition of the extracellular matrix (ECM), which can play critical roles in directing cell function. The current study sought to generate microcarriers comprised exclusively of ECM from multiple tissue sources. More specifically, porcine decellularized dermis, porcine decellularized myocardium, and human decellularized adipose tissue were digested with α‐amylase to obtain ECM suspensions that could be electrosprayed into liquid nitrogen to generate 3D microcarriers that were stable over a range of ECM concentrations without the need for chemical crosslinking or other additives. Characterization studies confirmed that all three microcarrier types had similar soft and compliant mechanical properties and were of a similar size range, but that their composition varied depending on the native tissue source. In vivo testing in immunocompetent mice revealed that the microcarriers integrated into the host tissues, supporting the infiltration of host cells including macrophages and endothelial cells at 2 weeks post‐implantation. In vitro cell culture studies validated that the novel microcarriers supported the attachment of tissue‐specific stromal cell populations under dynamic culture conditions within spinner flasks, with a significant increase in live cell numbers observed over 1 week on the dermal‐ and adipose‐derived microcarriers. Overall, the findings demonstrate the versatility of the electrospraying methods and support the further development of the microcarriers as cell culture and delivery platforms.
Effect of COOH in organic linkers on the hydrochlorination performance of SnMOF‐based catalysts
Authors: Wu Yibo , Li Fuxiang , Song Guoqiang , Cao Yunli , Xv Fu , Pan Zihong , Feng Yangyang , Li Qingbin
Published: September 2021

A series of tin‐organic frameworks materials (SnMOF) were synthesized using different organic linkers, including phthalic acid, isophthalic acid, 1,4‐dicarboxybenzene, and 1,3,5‐benzenetricarboxylic acid. The structure and morphology of SnMOF were characterized by Fourier Transform infrared spectroscopy (FT‐IR), X‐ray diffraction, N2 adsorption/desorption isortherm (BET), scanning electron microscope‐Energy Dispersive System (EDS), and Thermogravimetry (TG). Taking together, these experimental results indicated that the different types and amounts of COOH in organic linkers have a significant effect on the physical properties of SnMOF. Among them, carbon‐supported SnMOF as catalysts for acetylene hydrochlorination features the considerable activity and vinyl chloride selectivity. Such excellent performance is attributed to the fact that 1,3,5‐benzenetricarboxylic acid can effectively strengthen the interaction effect between C2H2 and Sn‐O‐C, according to the results of C2H2‐TPD, HCl adsorption experiments, and X‐ray photoelectron spectroscopy (XPS).
GJB2 mutations in Iranian Azeri population with autosomal recessive nonsyndromic hearing loss (ARNSHL): First report of c.238 C>A mutation in Iran
Authors: Abbaspour Rodbaneh Ehsan , Panahi Mohammad , Rahimi Bahareh , Mokabber Haleh , Farajollahi Reza , Davarnia Behzad
Published: September 2021

Objective

Autosomal‐recessive nonsyndromic hearing loss (ARNSHL) is a heterogeneous genetic disorder. Mutations in the gap junction protein beta 2 (GJB2) gene, encoding connexin 26, are a significant cause of ARNSHL in different ethnic groups. This study aimed to identify the frequency and type of GJB2 mutations in the Iranian Azeri population.

Methods

Fifty unrelated families presenting ARNSHL in Ardabil Province, the northwest of Iran, were studied to determine the frequency and type of GJB2 mutations leading to ARNSHL. ARMS‐PCR screened all DNA samples to detect c.35delG; p. Gly12Val mutation. In addition, normal samples for c.35delG; p. Gly12Val were analyzed by direct sequencing for other GJB2 mutations.

Result

Of the fifty families, 13 (26%) showed a GJB2 gene mutation, with c.35delG; p. Gly12Val mutation was the most prevalent one that occurred in eight (61.5%) out of the 13 families. Of the families, two were homozygous for c.358‐360delGAC; p. Glu120del mutation, and one was homozygous for c.290dupA; p. Tyr97Ter and c.299–300delAT; p. His100Arg mutations. Also, we detected a novel mutation, c.238C>A; p. Gln80lys, in one of the families.

Conclusion

Our findings are comparable to previous studies, indicating c.35d3lG; p. Gly12Val mutation in the GJB2 gene is the most common cause of GJB2‐related hearing loss in the Iranian Azeri population. Furthermore, our study highlights the significance of ARNSHL screening programs of live births based on local population data in Iran.
Performance of SPINK1 and SPINK1‐based diagnostic model in detection of hepatocellular carcinoma
Authors: Wang Fang , Liu Hui , Bai Youxi , Li Hui , Wang Zhonglin , Xu Xin
Published: September 2021

Objectives

To identify the SPINK1 or SPINK1‐based model as a more reliable biomarker for the diagnosis of hepatocellular carcinoma (HCC).

Methods

Serum samples and related laboratory parameters were collected from 540 subjects (119 healthy donors, 113 patients with chronic hepatitis B, 122 patients with liver cirrhosis, and 186 patients with HCC). SPINK1 was determined by ELISA assay. Differences in each variable were compared by one‐way ANOVA or Kruskal‐Wallis test. ROC (receiver operating characteristic) curve analysis was conducted to compare the diagnostic efficiency of alpha‐fetoprotein (AFP), SPINK1, and a SPINK1‐based combine model constructed by binary Logistic regression.

Results

In detecting HCC using the other three groups as control, ROC curve analysis revealed that SPINK1 alone reached AUC of 0.899 (0.866–0.933), with the sensitivity of 0.812 of and specificity of 0.953. The combined model increased the AUC to 0.945 (0.926–0.964) with the sensitivity and specificity of 0.860 and 0.910, respectively. For AFP, significantly lower AUC (p < 0.0001) was shown, which was 0.695 (0.645–0.745) with the sensitivity and specificity of 0.634 and 0.718, respectively. In discriminating HCC from liver disease control, AUC of SPINK1 was 0.863(0.826–0.894), the sensitivity and specificity were 0.823 and 0.906, respectively. For combined model, the AUC, sensitivity, and specificity were 0.915 (0.884–0.940), 0.863, and 0.916, respectively. For detecting early‐stage HCC, SPINK1 and combined model achieved the sensitivity of 0.788 and 0.818, respectively, much higher than AFP of 0.485 (p < 0.05); however, the difference between SPINK1 and combined model was not statistically significant (p = 1).

Conclusion

We provided solid evidence for SPINK1 as a robust serological tool for HCC diagnosis.
Bioinspiration of the vein structure of dragonfly wings on its flight characteristics
Authors: Liu Chao , Du Ruijuan , Li Fadong , Sun Jiyu
Published: September 2021

Dragonflies have excellent flight characteristics, which are inextricably related to the characteristics of their wings. Their wings not only support a variety of loads during flight but also maintain high‐efficiency flight characteristics. In this study, the forewing of a dragonfly (Pantala flavescens (Fabricius)) was used as a research object to explore the microstructure of the surface, cross section, and the vein distribution. Three‐dimensional models of three different structures of the forewing vein, including an oval‐shaped hollow tube, a circular hollow tube, and a circular solid tube, were established. Fluid dynamics analysis of these three forewing models under different angles of attack during gliding was carried out by FLUENT software, and subsequently, the influence of the dragonfly forewing vein structure on its flight characteristics was analyzed. The numerical simulation results indicated that the vein structure has a considerable influence on the lift, drag, and lift–drag ratio of the P. flavescens forewing. It was indicated that among the tested models, the forewing model with oval‐shaped hollow tubular veins has better flight efficiency and aerodynamic characteristics. The results of this study may provide the basis for a novel bionic concept of flapping wing microaircraft design.
Unfinished business
Authors: Crews David
Published: September 2021

At the time of my retirement there were two topics that I considered unfinished business. The first is the Evolution of Sex Differences and the second, the she‐male controversy in the Canadian red‐sided snake (Thamnophis sirtalis parietalis). These questions are developed in this perspective.
Impact of conversion surgery on survival in locally advanced pancreatic cancer patients treated with FOLFIRINOX chemotherapy
Authors: Lee Mirang , Kang Jae Seung , Kim Hongbeom , Kwon Wooil , Lee Sang Hyub , Ryu Ji Kon , Kim Yong‐Tae , Oh Do‐Youn , Chie Eui Kyu , Jang Jin‐Young
Published: September 2021

Background

Locally advanced (unresectable) pancreatic cancer (LAPC) is surgically unresectable and often treated with chemotherapy. Most previous studies, that have evaluated conversion surgery after chemotherapy, included heterogeneous patients and chemotherapy regimens, making it challenging to determine the impact of FOLFIRINOX. The present study evaluated the survival benefit of conversion surgery in patients with LAPC who received FOLFIRINOX chemotherapy, and analyzed the prognostic factors.

Methods

Patients with LAPC who received FOLFIRINOX as first‐line therapy for at least four cycles were included. During chemotherapy, surgical eligibility was determined based on radiologic and metabolic response to the treatment. Clinicopathologic characteristics were compared between the curative‐intent surgery and non‐resection groups, and the prognostic factors were analyzed.

Results

A total of 279 patients were included. The rates of partial response (PR) and stable disease (SD) were 34.1% and 51.4%, respectively, and 16.8% patients underwent curative‐intent surgery. The median survival was significantly longer in the resection group than in the non‐resection group (56 vs 21 months, P < .001). In a multivariate analysis, curative‐intent surgery (HR 0.260; P < .001) was the most important factor.

Conclusions

Conversion surgery after FOLFIRINOX chemotherapy effectively rescues patients with LAPC. Patients without progression after FOLFIRINOX could be considered as potential candidates for conversion surgery.
Phenotype and pathology of the dilated cardiomyopathy with ataxia syndrome in children
Authors: Machiraju Pranav , Degtiarev Vlad , Patel Dhwani , Hazari Hassan , Lowry R. Brian , Bedard Tanya , Sinasac David , Brundler Marie‐Anne , Greenway Steven C. , Khan Aneal
Published: September 2021

The dilated cardiomyopathy with ataxia syndrome (DCMA) is an autosomal recessive mitochondrial disease caused by mutations in the DnaJ heat shock protein family (Hsp40) member C19 (DNAJC19) gene. DCMA or 3‐methylglutaconic aciduria type V is globally rare, but the largest number of patients in the world is found in the Hutterite population of southern Alberta in Canada. We provide an update on phenotypic findings, natural history, pathological findings, and our clinical experience. We analyzed all available records for 43 patients diagnosed with DCMA between 2005 and 2015 at the Alberta Children's Hospital. All patients studied were Hutterite and homozygous for the causative DNAJC19 variant (c.130‐1G>C, IVS3‐1G>C) and had elevated levels of 3‐methyglutaconic acid. We calculated a birth prevalence of 1.54 cases per 1000 total births in the Hutterite community. Children were small for gestational age at birth and frequently required supplemental nutrition (63%) or surgical placement of a gastrostomy tube (35%). Early mortality in this cohort was high (40%) at a median age of 13 months (range 4‐294 months). Congenital anomalies were common as was dilated cardiomyopathy (50%), QT interval prolongation (83%), and developmental delay (95%). Tissue pathology was analyzed in a limited number of patients and demonstrated subendocardial fibrosis in the heart, macrovesicular steatosis and fibrosis in the liver, and structural abnormalities in mitochondria. This report provides clinical details for a cohort of children with DCMA and the first presentation of tissue pathology for this disorder. Despite sharing common genetic etiology and environment, the disease is highly heterogeneous for reasons that are not understood. DCMA is a clinically heterogeneous systemic mitochondrial disease with significant morbidity and mortality that is common in the Hutterite population of southern Alberta.
Polyethylene oxide–polyacrylic acid–folic acid (PEO‐PAAc) nanogel as a99mTc targeting receptor for cancer diagnostic imaging
Authors: Soliman Moamen M. , Sakr Tamer M. , Rashed Hassan M. , Hamed Ashraf A. , Abd El‐Rehim Hassan A.
Published: September 2021

Nanoparticles are frequently used as targeting delivery systems for therapeutic and diagnostic radiopharmaceuticals. Polyethylene oxide–polyacrylic acid (PEO–PAAc) nanogel was prepared via γ‐radiation‐induced polymerization. Variable factors affecting nanoparticles size were investigated. The nanogel was radiolabeled with the imaging radioisotope99mTc and finally conjugated with folic acid to target folate receptor actively. PEO–PAAc–folic acid gel was characterized by dynamic light scattering (DLS) and atomic force microscopy (AFM). Biodistribution was studied in normal mice and solid tumor‐bearing mice via intravenous and intratumor injections of the radiolabeled PEO–PAAc–folic acid nanogel. Results of biodistribution showed high selective uptake of the prepared complex in tumor muscle compared with normal muscle for both intravenous and intratumor injections. The T/NT ratio was found to be 6.186 and 294.5 for intravenous and intratumor injections, respectively. Consequently,99mTc–PEO–PAAc–folic acid complex could be a promising agent for cancer diagnostic imaging.
Improved Assessment of Longitudinal Spinal Cord Atrophy in Multiple Sclerosis Using a Registration‐Based Approach: Relevance for Clinical Studies
Authors: Valsasina Paola , Horsfield Mark A. , Meani Alessandro , Gobbi Claudio , Gallo Antonio , Rocca Maria A. , Filippi Massimo
Published: September 2021

Background

Reliable measurements of cervical cord atrophy progression may be useful for monitoring neurodegeneration in multiple sclerosis (MS).

Purpose

To compare a new, registration‐based (Reg) method with two existing methods (active surface [AS] and propagation segmentation [PropSeg]) to measure cord atrophy changes over time in MS.

Study Type

Retrospective.

Subjects

Cohort I: Eight healthy controls (HC) and 28 MS patients enrolled at a single institution, and cohort II: 25 HC and 63 MS patients enrolled at three European sites.

Field Strength/Sequence

3D T1‐weighted gradient echo sequence, acquired at 1.5 T (cohort I) and 3.0 T (cohort II).

Assessment

Percentage cord area changes (PCACs) between baseline and follow‐up (cohort I: 2.34 years [interquartile range = 2.00–2.55 years], cohort II: 1.05 years [interquartile range = 1.01–1.18 years]) were evaluated for all subjects using Reg, AS, and PropSeg. Reg included an accurate registration of baseline and follow‐up straightened cord images, followed by AS‐based optimized cord segmentation. A subset of studies was analyzed twice by two observers.

Statistical Tests

Linear regression models were used to estimate annualized PCAC, and effect sizes expressed as the ratio between the estimated differences and HC error term (P < 0.05). Reproducibility was assessed by linear mixed‐effect models. Annualized PCACs were used for sample size calculations (significance: α = 0.05, power: 1 − β = 0.80).

Results

Annualized PCACs and related standard errors (SEs) were lower with Reg than with other methods: PCAC in MS patients at 1.5 T was −1.12% (SE = 0.22) with Reg, −1.32% (SE = 0.30) with AS, and −1.40% (SE = 0.33) with PropSeg, while at 3.0 T PCAC was −0.83% (SE = 0.25) with Reg, −0.92% (SE = 0.32) with AS, and −1.18 (SE = 0.53) with PropSeg. This was reflected in larger effect sizes and lower sample sizes. Intra‐ and inter‐observer agreement range was 0.72–0.91 with AS, and it was >0.96 with Reg.

Data Conclusion

The results support the use of the registration method to measure cervical cord atrophy progression in future MS clinical studies.

Level of Evidence

3

Technical Efficacy Stage

2