bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using real‐world data to predict health outcomes—The prediction design: Application and sample size planning
Authors: Erdmann Stella , Edelmann Dominic , Kieser Meinhard 
Published: July 2023

AbstractThe gold standard for investigating the efficacy of a new therapy is a (pragmatic) randomized controlled trial (RCT). This approach is costly, time‐consuming, and not always practicable. At the same time, huge quantities of available patient‐level control condition data in analyzable format of (former) RCTs or real‐world data (RWD) are neglected. Therefore, alternative study designs are desirable. The design presented here consists of setting up a prediction model for determining treatment effects under the control condition for future patients. When a new treatment is intended to be tested against a control treatment, a single‐arm trial for the new therapy is conducted. The treatment effect is then evaluated by comparing the outcomes of the single‐arm trial against the predicted outcomes under the control condition. While there are obvious advantages of this design compared to classical RCTs (increased efficiency, lower cost, alleviating participants’ fear of being on control treatment), there are several sources of bias. Our aim is to investigate whether and how such a design—the prediction design—may be used to provide information on treatment effects by leveraging external data sources. For this purpose, we investigated under what assumptions linear prediction models could be used to predict the counterfactual of patients precisely enough to construct a test and an appropriate sample size formula for evaluating the average treatment effect in the population of a new study. A user‐friendly R Shiny application (available at: https://web.imbi.uni‐heidelberg.de/PredictionDesignR/) facilitates the application of the proposed methods, while a real‐world application example illustrates them.
Organic fluorescent compounds based on phenanthroimidazole: A review of highlight studies
Authors: Zurnacı Merve , Şener İzzet , Gür Mahmut , Şener Nesrin 
Published: July 2023

AbstractOrganic compounds containing phenanthroimidazole, and its optical, thermal, chemical, and high fluorescence, have drawn the interest of numerous researchers. Phenanthroimidazole derivatives are appealing for various applications due to these characteristics. This research provides a summary of the general information contained in studies on the synthesis, characterization, photophysical characteristics, and possible applications of phenanthroimidazole derivative compounds. The focus of this study revolves around the topic of utilization in technological fields such as sensors, solar cells, optical brighteners, and organic light‐emitting diodes, and covers significant studies on mentioned topics. We anticipate that this study will provide an outline for researchers aiming to further examine fluorescent organic compounds for technological innovations. Furthermore, we anticipate that this research will be crucial in developing long‐term high‐organic compounds for optoelectronic devices.
Symptom aggravation after withdrawal of metal chelating agent therapy in patients with Wilson's disease
Authors: Zhou Xiangxue , Liao Jian , Liu Yinjie , Qin Haolin , Xiao Xia 
Published: July 2023

AbstractObjectiveTo study the aggravation of clinical symptoms after discontinuation of metal chelating agent therapy in Wilson's disease (WD) patients, analyze the causes of aggravation, and observe the prognosis.Methods40 WD patients (cerebral type 30 cases and hepatic type 10 cases) who stopped using metal chelating agent were selected, 40 WD patients with normal therapy, and 10 normal control cases were selected. All patients underwent neurological symptom evaluation using modified Young scale, Child‐Pugh liver function grading, metal metabolism, and disease typing. Magnetic sensitivity imaging (SWI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy imaging (MRS) were performed. According to the imaging results, WD patients were divided into metal deposition stage, fiber damage stage, and neuron necrosis stage. All patients were treated with metal chelating agent for 6 months.ResultsThe score of modified Young scale in drug withdrawal group was lower than that in normal treatment group before drug withdrawal (p = .032). The score of modified Young scale was higher after drug withdrawal than before (p = .011). The number of Child‐Pugh B‐grade patients after drug withdrawal was more than that before drug withdrawal and in normal treatment group. The proportion of patients in the stage of neuronal necrosis after drug withdrawal (25%) was higher than that before drug withdrawal (10%) (p = .025). After drug withdrawal, urine copper was significantly higher than that before drug withdrawal and in the normal treatment group (p = .032, .039). After the withdrawal group resumed metal chelating agent treatment, 34.2% of neurological symptoms worsened.ConclusionsWD patients showed neurological symptoms aggravation and increased liver injury after metal chelating agent withdrawal. Increased metal deposition and new nerve injury occurred in the brain. After re‐treatment, the aggravated neurological symptoms of WD patients are difficult to reverse.
Intraventricular SEEG and laser ablation for the treatment of infantile spasm: Technical note
Authors: Xu Xinghua , Wang Qun , Zhao Yining , Xu Xin , Gan Zhichao , Zhang Shiyu , Chen Xiaolei 
Published: July 2023

AbstractObjectivesInfantile spasm (IS) is an epileptic encephalopathy with ongoing neurological damage due to seizures and epileptiform abnormalities. Epilepsy surgery is considered for children refractory to drug therapy, especially when there is a focal brain lesion. In this study, we investigated the feasibility and efficacy of intraventricular stereotactic electroencephalography (SEEG) and laser ablation for the treatment of IS children with focal brain lesions.MethodsWe performed the first reported study using ventriculoscopic laser ablation to treat IS. Seven IS children with drug‐resistant epilepsy and definite encephalomalacia on brain magnetic resonance imaging scan were included in this study. Ablation was performed after confirmation of epileptiform discharges by SEEG under the surveillance of ventriculoscope.ResultsThe median follow‐up time for the cohort was 3.1 years and 86% (6/7) of the children had an Engel class ≤III epilepsy at the final follow‐up. Five (71%) children had a reduction in seizure medication usage, and the other two were on the same amount as preablation. None of the children experienced serious new neurological deficits. Laser ablation might result in seizure freedom by destroying the local brain network and blocking the spread of abnormal discharges.ConclusionsIntraventricular SEEG and laser ablation was feasible and effective for the treatment of IS. Further studies are warranted.
The prognosis of clinical stage IIIa non‐small cell lung cancer in Taiwan
Authors: Cheng Ya‐Fu , Huang Jing‐Yang , Lin Ching‐Hsiung , Wang Bing‐Yen 
Published: July 2023

AbstractLung cancer is the leading cause of cancer death. The treatment of stage IIIa remained the most controversial of all stages of non‐small cell lung cancer (NSCLC). We reported on the heterogenicity and current treatment strategies of stage IIIa NSCLC in Taiwan. This study is a retrospective analysis using data from the Taiwan Society of Cancer Registry between January 2010 and December 2018. 4232 patients with stage IIIa NSCLC were included. Based on cell type, the best 5‐year OS (40.40%) occurred among adenocarcinoma victims. The heterogenicity of T1N2 had the best 5‐year OS (47.62%), followed by T4N0 (39.82%), and the others. Patients who underwent operations had better 5‐year OS (over 50%) than those who did not (less than 30%). Segmentectomy (75.28%) and lobectomy (54.06%) showed better 5‐year OS than other surgical methods (less than 50%). In multivariable analysis, young age, female, lower Charlson Comorbidity Index score, adenocarcinoma cell type, well differentiated, T1N2/T4N0 heterogenicity, treatment with operation, and segmentectomy/lobectomy/bilobectomy were significant factors. In conclusions, the heterogenicity of T1N2 had the best outcomes followed by T4N0. Patients received surgical treatment revealed much better outcomes than those did not. As always, multimodal therapies with individualized treatment tend to provide better survival outcomes.
Preoperative alkaline phosphatase‐to‐platelet count ratio as a prognostic factor for hepatocellular carcinoma with microvascular invasion
Authors: Zhang Yongxin , Zhang Bin , Gong Lianggeng , Xiong Liangxia , Xiao Xuehong , Bu Chao , Liang Zhiying , Li Liangcai , Tang Binghang , Lu Yangbai 
Published: July 2023

AbstractObjectivesThe association between platelet status and hepatocellular carcinoma (HCC) prognoses remains controversial. Herein, we aimed to clarify the prognostic value of multiple platelet‐related biomarkers, including platelet count, platelet/lymphocyte ratio (PLR), aspartate aminotransferase to platelet ratio index (APRI), and alkaline phosphatase‐to‐platelet count ratio index (APPRI) in HCC with microvascular invasion (MVI) after curative resection or liver transplantation.Materials and MethodsA retrospective review of 169 patients with solitary HCC and MVI who underwent resection or liver transplantation between January 2015 and December 2018 was conducted. Preoperative clinical, laboratory, pathologic, and imaging data were collected and analyzed. Overall survival (OS) and disease‐free survival (DFS) were defined as the clinical endpoints. Univariate and multivariate Cox proportional hazards regression analyses were conducted to investigate potential predictors of DFS and OS.ResultsMultivariate Cox regression analyses revealed that maximum tumor diameter, poor cell differentiation, and APPRI were independent predictors of DFS; while poor cell differentiation, APRI, APPRI, prothrombin time, and alpha‐fetoprotein were independent prognostic factors for OS. The 1‐, 3‐, and 5‐year DFS rates were 66.90%, 48.40%, and 37.40% for patients with APPRI ≤0.74 and 40.40%, 24.20%,and 24.20% for patients with APPRI>0.74. The corresponding rates of OS over 1, 3, and 5 years were 92.40%, 88.10% and 77.70%, and 72.30%, 38.20%, and 19.10%, respectively. The DFS and OS rates of patients whose APPRI was more than 0.74 were substantially lower than those of patients whose APPRI was less than or equal to 0.74 (p = 0.002 and p < 0.001, respectively).ConclusionElevated preoperative APPRI is a noninvasive, simple, and easily assessable parameter linked to poor prognosis in individuals with single HCC and MVI after resection or liver transplantation.
Tn antigen promotes breast cancer metastasis via impairment of CASC4
Authors: Li Ruijun , Dong Xichen , Chen Shibin , Tan Jingyu , Chen Xiangyu , Liu Jian , Wen Tao , Ru Xiaoli 
Published: July 2023

AbstractBreast cancer is one of the most serious and deadly cancers in women worldwide, with distant metastases being the leading cause of death. Tn antigen, a tumor‐associated carbohydrate antigen, was frequently detected in breast cancer, but its exact role in breast cancer metastasis has not been well elucidated. Here we investigated the impact of Tn antigen expression on breast cancer metastasis and its underlying mechanisms. The expression of Tn antigen was induced in two breast cancer cell lines by deleting T‐synthase or Cosmc, both of which are required for normal O‐glycosylation. It showed that Tn‐expressing cancer cells promoted epithelial–mesenchymal transition (EMT) and metastatic features as compared to Tn(−) control cells both in vitro and in vivo. Mechanistically, we found that cancer susceptibility candidate 4 (CASC4), a heavily O‐glycosylated protein, was significantly downregulated in both Tn(+) cells. Overexpression of CASC4 suppressed Tn‐induced activation of EMT and cancer metastasis via inhibition of Cdc42 signaling. Furthermore, we confirmed that O‐glycosylation is essential for the functional role of CASC4 because defective O‐glycosylated CASC4 (mutant CASC4, which lacks nine O‐glycosylation sites) exerted marginal metastatic‐suppressing effects in comparison with WT CASC4. Collectively, these data suggest that Tn‐mediated aberrant O‐glycosylation contributes to breast cancer metastasis via impairment of CASC4 expression and function.
Zero‐Dimensional Sn‐Based Enantiomeric Phase‐Transition Materials with High‐Tc and Dielectric Switching
Authors: Huang Yan‐Le , Ying Ting‐Ting , Zhao Yi‐Ran , Tang Yun‐Zhi , Tan Yu‐Hui , Li Qiao‐Lin , Liu Wei‐Fei , Wan Ming‐Yang , Wang Fang‐Xin 
Published: July 2023

AbstractThe combination of chirality and phase‐transition materials has broad application prospects. Therefore, based on the quasi‐spherical theory and the thought strategy of introducing chirality, we have successfully synthesized a pair of chiral enantiomeric ligands (R/S)‐triethyl‐(2‐hydroxypropyl)ammonium iodide, which can be combined with a tin hexachloride anion to obtain a pair of new organic–inorganic hybrid enantiomeric high‐temperature plastic phase‐transition materials: (R/S)‐[CH3CH(OH)CH2N(CH2CH3)3]2SnCl6 (1‐R/1‐S), which have a high temperature phase transition of Tc=384 K, crystallize in the P21 chiral space group at room temperature, and have obvious CD signals. In addition, compounds 1‐R and 1‐S have a good low‐loss dielectric switch and broadband gap. This work is conducive to the research into chiral high‐temperature reversible plastic phase‐transition materials, and promotes the development of multi‐functional phase‐transition materials.
Geometry‐Independent Ultrafast Energy Transfer in Bioinspired Arrays Containing Electronically Coupled BODIPY Dimers as Energy Donors
Authors: Ansteatt Sara , Gelfand Rachel , Pelton Matthew , Ptaszek Marcin 
Published: July 2023

AbstractIn photosynthetic light‐harvesting complexes, strong interaction between chromophores enables efficient absorption of solar radiation and has been suggested to enable ultrafast energy funneling to the reaction center. To examine whether similar effects can be realized in synthetic systems, and to determine the mechanisms of energy transfer, we synthesized and characterized a series of bioinspired arrays containing strongly‐coupled BODIPY dimers as energy donors and chlorin derivatives as energy acceptors. The BODIPY dimers feature broad absorption in the range of 500–600 nm, complementing the chlorin absorption to provide absorption across the entire visible spectrum. Ultrafast (~10 ps) energy transfer was observed from photoexcited BODIPY dyads to chlorin subunits. Surprisingly, the energy‐transfer rate is nearly independent of the position where the BODIPY dimer is attached to the chlorin and of the type of connecting linker. In addition, the energy‐transfer rate from BODIPY dimers to chlorin is slower than the corresponding rate in arrays containing BODIPY monomers. The lower rate, corresponding to less efficient through‐bond transfer, is most likely due to weaker electronic coupling between the ground state of the chlorin acceptor and the delocalized electronic state of the BODIPY dimer, compared to the localized state of a BODIPY monomer.
Regime Switch in the Dual‐Catalyzed Coupling of Alkyl Silicates with Aryl Bromides
Authors: Jaouadi Khaoula , Abdellaoui Mehdi , Levernier Etienne , Payard Pierre‐Adrien , Derat Etienne , Le Saux Thomas , Ollivier Cyril , Torelli Stéphane , Jullien Ludovic , Plasson Raphaël , Fensterbank Louis , Grimaud Laurence 
Published: July 2023

AbstractMetallaphotoredox catalyzed cross‐coupling of an arylbromide (Ar−Br) with an alkyl bis(catecholato)silicate (R−Si⊖) has been analyzed in depth using a continuum of analytical techniques (EPR, fluorine NMR, electrochemistry, photophysics) and modeling (micro‐kinetics and DFT calculations). These studies converged on the impact of four control parameters consisting in the initial concentrations of the iridium photocatalyst ([Ir]0), nickel precatalyst ([Ni]0) and silicate ([R−Si⊖]0) as well as light intensity I0 for an efficient reaction between Ar−Br and R−Si⊖. More precisely, two regimes were found to be possibly at play. The first one relies on an equimolar consumption of Ar−Br with R−Si⊖ smoothly leading to Ar−R, with no side‐product from R−Si⊖ and a second one in which R−Si⊖ is simultaneously coupled to Ar−Br and degraded to R−H. This integrative approach could serve as a case study for the investigation of other metallaphotoredox catalysis manifolds of synthetic significance.
Characterization of clock‐related proteins and neuropeptides in Drosophila littoralis and their putative role in diapause
Authors: Manoli Giulia , Zandawala Meet , Yoshii Taishi , Helfrich‐Förster Charlotte 
Published: July 2023

AbstractInsects from high latitudes spend the winter in a state of overwintering diapause, which is characterized by arrested reproduction, reduced food intake and metabolism, and increased life span. The main trigger to enter diapause is the decreasing day length in summer–autumn. It is thus assumed that the circadian clock acts as an internal sensor for measuring photoperiod and orchestrates appropriate seasonal changes in physiology and metabolism through various neurohormones. However, little is known about the neuronal organization of the circadian clock network and the neurosecretory system that controls diapause in high‐latitude insects. We addressed this here by mapping the expression of clock proteins and neuropeptides/neurohormones in the high‐latitude fly Drosophila littoralis. We found that the principal organization of both systems is similar to that in Drosophila melanogaster, but with some striking differences in neuropeptide expression levels and patterns. The small ventrolateral clock neurons that express pigment‐dispersing factor (PDF) and short neuropeptide F (sNPF) and are most important for robust circadian rhythmicity in D. melanogaster virtually lack PDF and sNPF expression in D. littoralis. In contrast, dorsolateral clock neurons that express ion transport peptide in D. melanogaster additionally express allatostatin‐C and appear suited to transfer day‐length information to the neurosecretory system of D. littoralis. The lateral neurosecretory cells of D. littoralis contain more neuropeptides than D. melanogaster. Among them, the cells that coexpress corazonin, PDF, and diuretic hormone 44 appear most suited to control diapause. Our work sets the stage to investigate the roles of these diverse neuropeptides in regulating insect diapause.
Changes in the use of color in Japanese cities
Authors: Yamamoto Sari 
Published: July 2023

AbstractThis study examines how the use of color in the Japanese urban landscape has changed over time and what the future holds. The colors of contemporary Japanese cities are not beautiful, but it is said that they were harmonious and beautiful in the Edo period (1603–1868). In the 1850s, as the country opened up to the outside world, Western‐style architecture was introduced and emerged side by side with Japanese architecture. As economic growth took precedence in the 20th century, there was a lack of awareness of the city's public ownership and the appearance of buildings. The attempt to achieve industrial standards and rapid urbanization were also cited as reasons for the absence of harmony in the built environment. Additionally, many outdoor advertisements appeared. The lack of effective regulations on outdoor advertising is one factor that has heavily affected the contemporary Japanese cityscape. The “Landscape Act,” which went into effect in 2004, aims to regulate landscape color use in present‐day Japan. This law allows local governments to enact regulations for urban landscape color use primarily by setting the upper limit for color saturation in terms of Munsell Chroma. It is questionable whether this will really lead to the creation of more unique cityscapes. Training in color in architecture, urban objects, and infrastructure should be compulsory as part of civic education, and more time should be devoted to the subject of color in architects' educational programs to create beautiful cities in the future. Students of architecture need time to think about the idea that the exterior of a building is part of the urban landscape, to consider the importance of color, and to study color harmony.
Solvent Effects on the 1H‐NMR Chemical Shifts of Imidazolium‐Based Ionic Liquids
Authors: Du Ming‐Xuan , Han Lin‐Xue , Wang Shi‐Rong , Xu Kuang‐Jie , Zhu Wen‐Rui , Qiao Xin , Liu Chen‐Yang 
Published: July 2023

AbstractThe 1H nuclear magnetic resonance (1H‐NMR) spectrum is a useful tool for characterizing the hydrogen bonding (H‐bonding) interactions in ionic liquids (ILs). As the main hydrogen bond (H‐bond) donor of imidazolium‐based ILs, the chemical shift (δH2) of the proton in the 2‐position of the imidazolium ring (H2) exhibits significant and complex solvents, concentrations and anions dependence. In the present work, based on the dielectric constants (ϵ) and Kamlet‐Taft (KT) parameters of solvents, we identified that the δH2 are dominated by the solvents polarity and the competitive H‐bonding interactions between cations and anions or solvents. Besides, the solvents effects on δH2 are understood by the structure of ILs in solvents: 1) In diluted solutions of inoizable solvents, ILs exist as free ions and the cations will form H‐bond with solvents, resulting in δH2 being independent with anions but positively correlated with βS. 2) In diluted solutions of non‐ionzable solvents, ILs exist as contact ion‐pairs (CIPs) and H2 will form H‐bond with anions. Since non‐ionizable solvents hardly influence the H‐bonding interactions between H2 and anions, the δH2 are not related to βS but positively correlated with βIL.
Chemical Conversion of 5‐Fluoromethyl‐ and 5‐Difluoromethyl‐Uracil Bases in Oligonucleotides Using Postsynthetic Modification Strategy
Authors: Ito Yuta , Takemori Chisa , Hari Yoshiyuki 
Published: July 2023

AbstractThis article describes the postsynthetic modification of oligonucleotides (ONs) containing 2′‐deoxy‐5‐fluoromethyluridine (dUCH2F) and 2′‐deoxy‐5‐difluoromethyluridine (dUCHF2). Reactions of fully protected and controlled pore glass (CPG)‐attached ONs containing dUCH2F and dUCHF2 in basic solutions result in deprotection of all protecting groups except for the 4,4′‐dimethoxytrityl group, cleavage from CPG, and conversion of the fluoromethyl or difluoromethyl groups to afford the corresponding ONs containing 5‐substituted 2′‐deoxyuridines. Moreover, the difluoromethyl group can be converted to formyl, oxime, or hydrazone via the postsynthetic conversion of protection‐ and CPG‐free ON containing dUCHF2. © 2023 Wiley Periodicals LLC.Basic Protocol 1: Synthesis of fully protected and CPG‐attached oligonucleotides containing 2′‐deoxy‐5‐fluoromethyluridine and 2′‐deoxy‐5‐difluoromethyluridineBasic Protocol 2: Postsynthetic modification of fully protected and CPG‐attached oligonucleotides containing 2′‐deoxy‐5‐fluoromethyluridineBasic Protocol 3: Postsynthetic modification of fully protected and CPG‐attached oligonucleotide containing 2′‐deoxy‐5‐difluoromethyluridineBasic Protocol 4: Postsynthetic modification of protection‐ and CPG‐free oligonucleotide containing 2′‐deoxy‐5‐difluoromethyluridineSupport Protocol: Synthesis of 2′‐deoxy‐5‐fluoromethyluridine and 2′‐deoxy‐5‐difluoromethyluridine phosphoramidites