bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biotechnological production of cyclic dinucleotides—Challenges and opportunities
Authors: Bartsch Tabea , Becker Martin , Rolf Jascha , Rosenthal Katrin , Lütz Stephan 
Published: December 2021

AbstractCyclic dinucleotides (CDNs) are widely used secondary signaling molecules in prokaryotic and eukaryotic cells. As strong agonists of the stimulator of interferon genes, they are of great interest for pharmaceutical applications. In particular, cyclic‐GMP‐AMP and related synthetic CDNs are promising candidates in preclinical work and even some in clinical phase 1 and 2 studies. The comparison of chemical and biocatalytic synthesis routes elucidated that biological CDN synthesis offers some advantages, such as shorter synthesis time, avoiding complex protective group chemistry, and the access to a new spectrum of CDNs. However, the synthesis of CDNs in preparative quantities is still a challenge, since the chemical synthesis of CDNs suffers from low yields and complex synthetic routes and the enzymatically catalyzed synthesis is limited by low product titers and process stability. We aim to review the latest discoveries and recent trends in chemical and biocatalytic synthesis of CDNs with a focus on the synthesis of a huge variety of CDN derivatives. We furthermore consider the most promising biotechnological processes for CDN production by evaluating key figures of the currently known processes.
Immunotherapies for hepatocellular carcinoma
Authors: Liu Justin K. H. , Irvine Andrew F. , Jones Rebecca L. , Samson Adel 
Published: December 2021

AbstractCases of hepatocellular carcinoma (HCC) are rapidly rising. This is particularly the case in the Western world, as a result of increasing rates of chronic liver disease, secondary to lifestyle‐associated risk factors and the lack of an established screening programme for the general population. Traditionally, radical/curative treatment options for HCC, including liver transplantation and surgical resection are reserved for the minority of patients, presenting with an early stage cancer. For patients with advanced disease, Sorafenib and Lenvatinib were, until recently, the only licensed systemic treatments, and provided only limited survival benefits at the cost of a multitude of potential side effects. Recent scientific advances in the field of cancer immunotherapy have renewed significant interest in advanced HCC, in order to fulfil this apparent area of unmet clinical need. This has led to the success and recent regulatory approval of an Atezolizumab/Bevacizumab combination for the first‐line treatment of advanced HCC following results from the IMbrave150 clinical trial in 2019, with further immune checkpoint inhibitors currently undergoing testing in advanced clinical trials. Furthermore, other cancer immunotherapies, including chimeric antigen receptor T‐cells, dendritic cell vaccines and oncolytic viruses are also in early stage clinical trials, for the treatment of advanced HCC. This review will summarise the major approaches that have been and are currently in development for the systemic treatment of advanced HCC, their advantages, drawbacks, and predictions of where this revolutionary treatment field will continue to travel for the foreseeable future.
Multimodal MR imaging signatures to identify brain diffuse midline gliomas with H3 K27M mutation
Authors: Su Xiaorui , Liu Yanhui , Wang Haoyu , Chen Ni , Sun Huaiqiang , Yang Xibiao , Wang Weina , Zhang Simin , Wan Xinyue , Tan Qiaoyue , Yue Qiang , Gong Qiyong 
Published: December 2021

AbstractBackgroundConventional MR imaging has limited value in identifying H3 K27M mutations. We aimed to investigate the capacity of quantitative MR imaging variables in identifying the H3 K27M mutation status of diffuse midline glioma.Materials and MethodsTwenty‐three patients with H3 K27M mutation and thirty‐two wild‐type patients were recruited in this retrospective study, all of whom underwent multimodal MR imaging. Clinical data and quantitative MR imaging variables were explored by subgroup analysis stratified by age (juveniles and adults). Then, a logistic model for all patients was constructed to identify potential variables for predicting K27M mutation status. Besides, a retrospective validation set including 13 patients was recruited. The C‐index and F1 score were used to evaluate the performance of the prediction model.ResultsIt turned out that patients with H3 K27M mutation were younger in the adult subgroup. In the mutation group, some relative apparent diffusion coefficient (rADC) histogram parameters and myo‐inositol/creatine plus phosphocreatine (Ins/tCr) ratio were lower than in the wild‐type group of both juveniles and adults (p < 0.05). After nested cross‐validation and LASSO algorithm, the age, Ins/tCr, and rADC_15th were selected as potential predictors for H3 K27M mutation in the model. The nomogram model showed good diagnostic power with a validated C‐index of 0.884. In addition, the area under the curve (AUC) was 0.898 (0.976 in validation set) and the F1 score was 0.732.ConclusionsIn conclusion, age, rADC_15th, and Ins/tCr values were helpful in identifying H3 K27M mutations in midline gliomas.
In Situ Polymerized and Imidized Si@Polyimide Microcapsules with Flexible Solid‐Electrolyte Interphase and Enhanced Electrochemical Activity for Li‐Storage
Authors: Li Yuchen , Lv Linze , Huang Weibo , Zhu Yunhao , Long Fu , Zheng Wei , Qu Qunting , Zheng Honghe 
Published: December 2021

AbstractA novel in situ polymerization and imidization method is adopted to synthesize Si‐based microcapsule materials with polyimide shell. As a mechanically stable polymer, polyimide microcapsule shell can effectively alleviate the volume effect of silicon nanoparticles during alloying/de‐alloying reactions, stabilize the electrode construction, suppress the serious side reactions of electrolyte components on silicon anode surface, and help to form a flexible, homogeneous and low‐resistance solid electrolyte interphase (SEI). In addition, the conjugated carbonyl groups of polyimide make it Li+‐conductive and electrochemically active, thus increasing the electrochemical activity of silicon anode. The as‐prepared Si@polyimide microcapsules manifest high initial coulombic efficiency of 91.1 %, high initial discharge capacity of 2798.7 mA h g−1 at 210 mA g−1 (0.05 C), good rate behavior with a capacity of 1954 mA h g−1 at 10 C current rate, and considerably improved cycling performance preserving a capacity of 1239.9 mA h g−1 at 4.2 A g−1 (1 C) after 300 cycles.
Nanosized Carbon Macrocycles Based on a Planar Chiral Pseudo Meta‐[2.2]Paracyclophane
Authors: He Jing , Yu Mohan , Pang Maofu , Fan Yanqing , Lian Zhe , Wang Ying , Wang Wenguang , Liu Yajun , Jiang Hua 
Published: December 2021

AbstractStructural designs combining cycloparaphenylenes (CPPs) backbone with planar chiral [2.2]paracyclophane ([2.2]PCP) lead to optical‐active chiral macrocycles with intriguing properties. X‐ray crystal analysis revealed aesthetic necklace‐shaped structures and size‐dependent packages with long‐range channels. The macrocycles exhibit unique photophysical properties with high fluorescence quantum yield of up to 82 %, and the fluorescent color varies with ring size. In addition, size‐dependent chiroptical properties with moderately large CPL dissymmetry factor of 10−3 and CPL brightness in the range of 30–40 M−1 cm−1 were observed.
Hydrazone Photoswitches for Structural Modulation of Short Peptides
Authors: Jeong Myeongsu , Park Jiyoon , Seo Yejin , Lee Kwonjung , Pramanik Susnata , Ahn Sangdoo , Kwon Sunbum 
Published: December 2021

AbstractMolecules that undergo light‐driven structural transformations constitute the core components in photoswitchable molecular systems and materials. Among various families of photoswitches, photochromic hydrazones have recently emerged as a novel class of photoswitches with superb properties, such as high photochemical conversion, spectral tunability, thermal stability, and fatigue resistance. Hydrazone photoswitches have been adopted in various adaptive materials at different length scales, however, their utilization for modulating biomolecules still has not been explored. Herein, we present new hydrazone switches that can photomodulate the structures of short peptides. Systematic investigation on a set of hydrazone derivatives revealed that installation of the amide group does not significantly alter the photoswitching behaviors. Importantly, a hydrazone switch comprising an upper phenyl ring and a lower quinolinyl ring was effective for structural control of peptides. We anticipate that this work, as a new milestone in the research of hydrazone switches, will open a new avenue for structural and functional control of biomolecules.
Computational Insights into the Allosteric Effect and Dynamic Structural Features of the SARS‐COV‐2 Spike Protein
Authors: Xue Qiao , Liu Xian , Pan Wenxiao , Zhang Aiqian , Fu Jianjie , Jiang Guibin 
Published: December 2021

AbstractCOVID‐19 caused by SARS‐COV‐2 is continuing to surge globally. The spike (S) protein is the key protein of SARS‐COV‐2 that recognizes and binds to the host target ACE2. In this study, molecular dynamics simulation was used to elucidate the allosteric effect of the S protein. Binding of ACE2 caused a centripetal movement of the receptor‐binding domain of the S protein. The dihedral changes in Phe329 and Phe515 played a key role in this process. Two potential cleavage sites S1/S2 and S2′ were exposed on the surface after the binding of ACE2. The binding affinity of SARS‐COV‐2 S protein and ACE2 was higher than that of SARS‐COV. This was mainly due to the mutation of Asp480 in SARS‐COV to Ser494 in SARS‐COV‐2, which greatly weakened the electrostatic repulsion. The result provides a theoretical basis for the SARS‐COV‐2 infection and aids the development of biosensors and detection reagents.
Berliner Blau im 21. Jahrhundert
Authors: Kraft Alexander 
Published: December 2021

ZusammenfassungNeben der in seiner Bedeutung immer mehr zurückgehenden Anwendung des Berliner Blaus als Pigment sind in den letzten Jahrzehnten immer neue Anwendungsfelder hinzugekommen. Die Bandbreite dafür reicht von der Medizin über die Sensorik und den Umweltschutz bis hin zu modernen Energiespeichertechnologien. Eine Vorrausetzung für die Erschließung neuer Anwendungsfelder waren neue Synthesewege, um Berliner Blau ohne Fehlstellen im Kristallgitter und ohne eingebaute Wassermoleküle herstellen zu können.
Use of oral anticoagulants and its associated factors among nonvalvular atrial fibrillation patients with new‐onset acute ischemic stroke: A report from the China Atrial Fibrillation Registry study
Authors: Wang Jing‐Rong , Du Xin , Dong Jian‐Zeng , Chang San‐Shuai , Jiang Chao , Sang Cai‐Hua , Long De‐Yong , Tang Ri‐Bo , Zhang Hai‐Bin , Guo Jin‐Cheng , Wen Yu‐Mei , He Liu , Ma Chang‐Sheng 
Published: December 2021

AbstractBackgroundThe adherence of oral anticoagulant (OAC) therapy among nonvalvular atrial fibrillation (NVAF) patients with acute ischemic stroke (AIS) in China during recent years was unclear, and the possible factors that influenced the initiation and persistent use of OAC were needed to be explored.MethodsA total of 1085 NVAF patients, who experienced new‐onset and nonfatal AIS from August 2011 to December 2020 during follow‐ups in the China Atrial Fibrillation Registry (China‐AF), were enrolled. Information including patients' demographic characteristics, medical history, medication usage, which were collected before and after the index stroke, were used in the analysis.ResultsOAC was initiated in 40% (434/1085) NVAF patients within 3 months after new‐onset AIS. High‐reimbursement‐rate insurance coverage (odds ratio [OR]: 1.51, 95% confidence interval [CI]: 1.03–2.22, p = .036), 3‐month‐peri‐stroke AF episodes (OR: 2.63, 95% CI: 1.88–3.69, p < .001), and pre‐stroke OAC usage (OR: 8.92, 95% CI: 6.01–13.23, p < .001), were positively associated with initiation of OAC within 3 months after new‐onset AIS, while age (OR: 0.98, 95% CI: 0.96–1.00, p = .024), female (OR: 0.63, 95% CI: 0.44–0.90, p = .012) and higher modified HASBLED score (OR: 0.45, 95% CI: 0.37–0.55, p < .001) were negatively associated with it. Among 3‐month‐post‐stroke OAC users, history of radiofrequency ablation (hazard ratio: 1.65, 95% CI: 1.16–2.35; p = .006) was positively associated with non‐persistence of OAC usage.ConclusionsIn China, the proportion of NVAF patients who initiated OAC therapy since new‐onset AIS was still low. More efforts are needed on improving patients' adherence to anticoagulant therapy.
The lateral posterior clock neurons of Drosophila melanogaster express three neuropeptides and have multiple connections within the circadian clock network and beyond
Authors: Reinhard Nils , Bertolini Enrico , Saito Aika , Sekiguchi Manabu , Yoshii Taishi , Rieger Dirk , Helfrich‐Förster Charlotte 
Published: December 2021

AbstractDrosophila’s lateral posterior neurons (LPNs) belong to a small group of circadian clock neurons that is so far not characterized in detail. Thanks to a new highly specific split‐Gal4 line, here we describe LPNs’ morphology in fine detail, their synaptic connections, daily bimodal expression of neuropeptides, and propose a putative role of this cluster in controlling daily activity and sleep patterns. We found that the three LPNs are heterogeneous. Two of the neurons with similar morphology arborize in the superior medial and lateral protocerebrum and most likely promote sleep. One unique, possibly wakefulness‐promoting, neuron with wider arborizations extends from the superior lateral protocerebrum toward the anterior optic tubercle. Both LPN types exhibit manifold connections with the other circadian clock neurons, especially with those that control the flies’ morning and evening activity (M‐ and E‐neurons, respectively). In addition, they form synaptic connections with neurons of the mushroom bodies, the fan‐shaped body, and with many additional still unidentified neurons. We found that both LPN types rhythmically express three neuropeptides, Allostatin A, Allostatin C, and Diuretic Hormone 31 with maxima in the morning and the evening. The three LPN neuropeptides may, furthermore, signal to the insect hormonal center in the pars intercerebralis and contribute to rhythmic modulation of metabolism, feeding, and reproduction. We discuss our findings in the light of anatomical details gained by the recently published hemibrain of a single female fly on the electron microscopic level and of previous functional studies concerning the LPN.
Inkjet Printing: A Cheap and Easy‐to‐Use Alternative to Wire Bonding for Academics
Authors: Liu Yingwen , Zhu Kaichen , Hui Fei , Yuan Bin , Zhang Chenhui , Ma Yinchang , Zhang Xixiang , Lanza Mario 
Published: December 2021

AbstractMany groups in academia are having problems patterning interconnections to small electrodes using wire bonding, including metal melting and detachment of previously bonded wires. It is a fact that the industry makes reliable wire bonding using automatic setups and expert personnel, and also that many groups in academia can do wire bonding reliably. However, it is also true that wire bonding is much more problematic than other techniques often employed to pattern interconnections, such as lithography or inkjet printing. In this article, the contact resistance and maximum currents driven by metallic interconnections patterned via wire bonding, lithography, and inkjet printing are compared. It is concluded that interconnections patterned via inkjet printing meet the requirements of many types of experiments, and that inkjet printing is a very cheap and easy‐to‐use alternative to wire bonding, especially attractive for academics.
Phenotypic analysis of the pediatric immune response to SARS‐CoV‐2 by flow cytometry
Authors: Sibbertsen Freya , Glau Laura , Paul Kevin , Mir Thomas S. , Gersting Søren W. , Tolosa Eva , Dunay Gabor A. 
Published: December 2021

AbstractPediatric SARS‐CoV‐2 infection is often mild or asymptomatic and the immune responses of children are understudied compared to adults. Here, we present and evaluate the performance of a two‐panel (16‐ and 17 parameter) flow cytometry‐based approach for immune phenotypic analysis of cryopreserved PBMC samples from children after SARS‐CoV‐2 infection. The panels were optimized based on previous SARS‐CoV‐2 related studies for the pediatric immune system. PBMC samples from seven SARS‐CoV‐2 seropositive children from early 2020 and five age‐matched healthy controls were stained for analysis of T‐cells (panel T), B and innate immune cells (panel B). Performance of the panels was evaluated in two parallel approaches, namely classical manual gating of known subpopulations and unbiased clustering using the R‐based algorithm PhenoGraph. Using manual gating we clearly identified 14 predefined subpopulations of interest for panel T and 19 populations in panel B in low‐volume pediatric samples. PhenoGraph found 18 clusters within the T‐cell panel and 21 clusters within the innate and B‐cell panel that could be unmistakably annotated. Combining the data of the two panels and analysis approaches, we found expected differentially abundant clusters in SARS‐CoV‐2 seropositive children compared to healthy controls, underscoring the value of these two panels for the analysis of immune response to SARS‐CoV‐2. We established a two‐panel flow cytometry approach that can be used with limited amounts of cryopreserved pediatric samples. Our workflow allowed for a rapid, comprehensive, and robust pediatric immune phenotyping with comparable performance in manual gating and unbiased clustering. These panels may be adapted for large multi‐center cohort studies to investigate the pediatric immune response to emerging virus variants in the ongoing and future pandemics.
Novel active fixation lead guided by electrical delay can improve response to cardiac resynchronization therapy in heart failure
Authors: Casale Matteo , Mezzetti Maurizio , Gigliotti De Fazio Marianna , Caccamo Loredana , Busacca Paolo , Dattilo Giuseppe 
Published: December 2021

AbstractAimsCardiac resynchronization therapy (CRT) for heart failure (HF) recently has shown optimal results by targeting electrically delayed sites in coronary sinus (CS) branches. However this purpose often cannot be reached because of unstable left ventricular (LV) lead position. In current study were assessed the long‐term effects of the novel active fixation LV lead in CS, guided by electrical delay (QLV), in patients with HF due to coronary artery disease.MethodsOne hundred eighty‐five consecutive patients underwent CRT with intraoperative evaluation of QLV in the target position of the LV lead. When the novel active fixation LV lead was available, 98 consecutive patients received it, composing the Fix group. They were compared with 87 patients with a conventional passive fixation lead (No Fix group). The final LV lead position was assessed by fluoroscopy. Clinical response to CRT was assessed within a period of about 3 years: patients experiencing HF rehospitalization and death due to HF were defined as non‐responders.ResultsThere were no significant differences between groups in the final position of LV lead in left anterior oblique view (Pearson χ2 = 0.12; P = 0.73). In right anterior oblique view, a basal position was reached more in the Fix group (38%) than in the No Fix group (6.5%) (Pearson χ2 = 23.095; P < 0.001). QLV was significantly greater in the Fix group (122.6 ± 33.2 ms; SE = 3.6) than in the No Fix group (97.5 ± 37.8 ms; SE = 4.9) (t = 4.17; P < 0.001). Rehospitalizations for HF were 37 in the No Fix group and 14 in the Fix group. Deaths due to HF were 49 in the No Fix group and 18 in the Fix group. Survival analysis, assessed by Cox regression, showed that the Fix group had a better outcome both for HF rehospitalizations [hazard ratio (HR) = 0.48; 95% confidence interval (CI) = 0.25–0.9; P = 0.023] and death due to HF (HR = 0.55; 95% CI = 0.31–0.97; P = 0.04) in comparison with the No Fix group. Adjustment for baseline characteristics by multivariate analysis showed that an active fixation lead in CS, as a covariate, was still significant both for HF rehospitalizations (HR 0.46; 95% CI = 0.24–0.88; P = 0.019) and for death due to HF (HR 0.5; 95% CI = 0.28–0.9; P = 0.021).ConclusionsThe novel active fixation LV lead allowed to target sites with greater QLV. Often maximum QLV was documented in basal segments, were stability of conventional passive fixation leads is not enough. Patients receiving it experienced less HF rehospitalizations and less death due to HF. Active fixation lead in CS guided by QLV can improve long‐term prognosis in patients with HF due to coronary artery disease undergoing to CRT.
Heart transplantation strategies in arrhythmogenic right ventricular cardiomyopathy: a tertiary ARVC centre experience
Authors: Scheel Paul J. , Giuliano Katherine , Tichnell Crystal , James Cynthia , Murray Brittney , Tandri Harikrishna , Carter Debra , Fehr Tracey , Umapathi Priya , Vaishnav Joban , Lewsey Sabra C. , Hsu Steven , Calkins Hugh , Sharma Kavita , Choi Chun Woo , Gilotra Nisha A. , Kilic Ahmet 
Published: December 2021

AbstractAimsEnd‐stage heart failure necessitating evaluation for heart transplantation is increasingly recognized in arrhythmogenic right ventricular cardiomyopathy (ARVC). These patients present unique challenges in pre‐transplant and peri‐transplant management given their predominantly right ventricular (RV) failure and propensity for ventricular arrhythmias. We sought to utilize a tertiary ARVC referral and heart transplant centre experience to describe management of a series of patients with ARVC undergoing heart transplantation at our centre.Methods and resultsWe queried the Johns Hopkins ARVC Registry for all patients who underwent heart transplantation and further studied the subset undergoing transplantation at the Johns Hopkins Hospital. Patient demographics, clinical characteristics, and pre‐transplant clinical course were obtained from the registry and electronic medical records. Of the 532 patients in the ARVC Registry, 63 (12%) underwent heart transplantation. Nine (six male) of these patients both had known ARVC prior to transplant and were transplanted at Johns Hopkins Hospital between 2006 and 2020 at a mean age of 42 ± 14 years old. Pathogenic ARVC genetic variants were identified in six (67%) patients, all of whom had variants in the plakophilin‐2 (PKP2) gene. RV failure was universal with median right atrial to pulmonary capillary wedge pressure (RA/PCWP) ratio of 1.4 [interquartile range (IQR) 1.2–1.5] and median right ventricular stroke work index (RVSWI) of 0 g·m/m2/beat (IQR 0–0.3). Six had a history of catheter ablation for ventricular arrhythmia with five of the six having at least three ablations. Transplant evaluation was initiated an average of 344 ± 407 days after first developing heart failure symptoms. The most common bridge to transplant support included inotropes (n = 3) and extracorporeal membrane oxygenation (ECMO) (n = 2). Contraindication to inotropes or mechanical support was common due to ventricular arrhythmia and RV predominant cardiomyopathy.ConclusionsHeart transplantation is a curative treatment for ARVC, but due to frequent ventricular arrhythmias and RV predominant pathology, patients require unique considerations in regard to timing of evaluation, haemodynamic support options, and wait listing qualification.