bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simple prognostic factors and change of inflammatory markers in patients with severe coronavirus disease 2019: a single‐center observational study
Authors: Domi Hisaya , Matsuura Hiroshi , Kuroda Maiko , Yoshida Motoharu , Yamamura Hitoshi 
Published: July 2021

AimThe aim of this study was to investigate the prognostic factors and evaluate the change in inflammatory markers of patients with coronavirus disease 2019 (COVID‐19) requiring mechanical ventilation.MethodsThis retrospective observational study conducted from April 1, 2020, to February 18, 2021, included 97 adult patients who required mechanical ventilation for severe COVID‐19 pneumonia and excluded nonintubated patients with a positive COVID‐19 polymerase chain reaction test and those who had any obvious bacterial infection on admission. All patients were followed up to discharge or death. We obtained clinical information and laboratory data including levels of presepsin, interleukin‐6, procalcitonin, and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) antibody every day. Poor outcome was defined as death or receiving a tracheostomy during hospitalization, and favorable outcome was defined as discharge after extubation.ResultsDifferences (median [interquartile range]) were detected in age (76 [70–82] versus 66 [55–74] years), day from the onset of first symptoms to admission for mechanical ventilation (5 [3–7] versus 10 [8–12] days), and P/F ratio (i.e., ratio of arterial oxygen concentration to the fraction of inspired oxygen) after intubation (186 [149–251] versus 236 [180–296]) in patients with poor outcome versus those with favorable outcome on admission. Serum SARS‐CoV‐2 antibody levels had already increased on admission in patients with favorable outcome. We determined the day from the onset of first symptoms to admission for mechanical ventilation to be one of the independent prognostic factors of patients with COVID‐19 (adjusted odds ratio 0.69, confidence interval 0.56–0.85).ConclusionThese results may contribute to understanding the mechanism of progression in severe COVID‐19 and may be helpful in devising an effective therapeutic strategy.
Indolizy Carbene Ligand. Evaluation of Electronic Properties and Applications in Asymmetric Gold(I) Catalysis
Authors: Martinez Thibaut , Vanitcha Avassaya , Troufflard Claire , Vanthuyne Nicolas , Forté Jérémy , Gontard Geoffrey , Lemière Gilles , Mouriès‐Mansuy Virginie , Fensterbank Louis 
Published: July 2021

AbstractWe report herein a new family of carbene ligands based on an indolizine‐ylidene (Indolizy) moiety. The corresponding gold(I) complexes are easily obtained from the gold(I)‐promoted cyclization of allenylpyridine precursors. Evaluation of the electronic properties by experimental methods and also by DFT calculations confirms strong σ‐donating and π‐accepting properties of these ligands. Cationization of the gold(I) complexes generates catalytic species that trigger diverse reactions of (poly)unsaturated precursors. When armed with a methylene phosphine oxide moiety on the stereogenic center adjacent to the nitrogen atom, the corresponding bifunctional carbene ligands give rise to highly enantioselective heterocyclizations. DFT calculations brought some rationalization and highlighted the critical roles played by the phosphine oxide group and the tosylate anion in the asymmetric cyclization of γ‐allenols.
Aptamer‐PROTAC Conjugates (APCs) for Tumor‐Specific Targeting in Breast Cancer
Authors: He Shipeng , Gao Fei , Ma Junhui , Ma Haoqian , Dong Guoqiang , Sheng Chunquan 
Published: July 2021

AbstractDevelopment of proteolysis targeting chimeras (PROTACs) is emerging as a promising strategy for targeted protein degradation. However, the drug development using the heterobifunctional PROTAC molecules is generally limited by poor membrane permeability, low in vivo efficacy and indiscriminate distribution. Herein an aptamer‐PROTAC conjugation approach was developed as a novel strategy to improve the tumor‐specific targeting ability and in vivo antitumor potency of conventional PROTACs. As proof of concept, the first aptamer‐PROTAC conjugate (APC) was designed by conjugating a BET‐targeting PROTAC to the nucleic acid aptamer AS1411 (AS) via a cleavable linker. Compared with the unmodified BET PROTAC, the designed molecule (APR) showed improved tumor targeting ability in a MCF‐7 xenograft model, leading to enhanced in vivo BET degradation and antitumor potency and decreased toxicity. Thus, the APC strategy may pave the way for the design of tumor‐specific targeting PROTACs and have broad applications in the development of PROTAC‐based drugs.
Mechanically Triggered Hybridization Chain Reaction
Authors: Duan Yuxin , Glazier Roxanne , Bazrafshan Alisina , Hu Yuesong , Rashid Sk Aysha , Petrich Brian G. , Ke Yonggang , Salaita Khalid 
Published: July 2021

AbstractCells transmit piconewton forces to receptors to mediate processes such as migration and immune recognition. A major challenge in quantifying such forces is the sparsity of cell mechanical events. Accordingly, molecular tension is typically quantified with high resolution fluorescence microscopy, which hinders widespread adoption and application. Here, we report a mechanically triggered hybridization chain reaction (mechano‐HCR) that allows chemical amplification of mechanical events. The amplification is triggered when a cell receptor mechanically denatures a duplex revealing a cryptic initiator to activate the HCR reaction in situ. Importantly, mechano‐HCR enables direct readout of pN forces using a plate reader. We leverage this capability and measured mechano‐IC50 for aspirin, Y‐27632, and eptifibatide. Given that cell mechanical phenotypes are of clinical importance, mechano‐HCR may offer a convenient route for drug discovery, personalized medicine, and disease diagnosis.
Fetal development and growth of the fissula ante fenestram in the human ear
Authors: Rodríguez‐Vázquez José Francisco , Iglesias‐Moreno María Cruz , Poch Adriana , Murakami Gen , Abe Hiroshi , Honkura Yohei 
Published: July 2021

AbstractSince the fissula ante fenestram (FAF) is considered as a focus of otosclerotic lesion and a route of perilymph leakage, there are few description of prenatal development of the cartilaginous canal passing though the cochlear wall. We examined the sagittal and frontal histological sections of the ear from 32 human fetuses at 8–37 weeks of gestational age. At 8–12 weeks, in the immediately anterior side of a connection between the cochlear and canalicular parts of the otic capsule cartilage, the FAF appeared as a tear of a cartilage between the basal and second turns of the cochlea. The tear became a slit opening to the scala vestibuli. At 13–15 weeks, the FAF, less than 1.2 mm in length, had the anterosuperior and postero‐inferior apertures: the former was near the geniculate ganglion and became closed after 15 weeks, while the latter approached the oval window. Third trimester fetuses, the FAF, 1.5–2.0 mm in length, consistently carried a single, postero‐inferior aperture extending along the anterior margin of the oval window and it contained no definite epithelium and vessel. Although it was endochondral ossification, there was no clear zonation in cartilage cells of the FAF. A mechanical stress during three‐dimensional coiling of the cochlear ducts seemed to provide the FAF. After the FAF was established, the stapes footplate might use a part of the inferior aperture for the syndesmosis. A specific ossification was seen in the FAF, but it might rarely cause the pathological syndesmosis.
Zur Ertüchtigung der Rheinbrücke Maxau mit hochfestem Beton
Authors: Shepherd David Alós , Scherer Mathias , Katzik Walter , Dehn Frank 
Published: July 2021

AbstractDas Bauwerk B 10 Rheinbrücke Maxau ist eine 1966 fertiggestellte Stahlbrücke mit orthotroper Fahrbahnplatte, welche über die Jahre sukzessive instand gesetzt wurde. Durch die stark gestiegene Verkehrsbelastung und damit einhergehender Ermüdungsschäden wurde die Brücke jedoch stark beschädigt, weshalb eine Ertüchtigung aktuell unerlässlich war. Hierbei wird die Fahrbahn erstmalig in Deutschland durch das Aufbringen einer bewehrten stahlfaserverstärkten Platte aus hochfestem Beton (HFB) verstärkt. Der HFB wurde hierbei in einer Schichtdicke von nur ca. 7 cm und einer Mindestbetondeckung von 2 cm ohne zusätzliche Abdichtung an der befahrenen Oberseite maschinell eingebracht. Im vorliegenden Beitrag wird auf das Einbau‐ und Qualitätssicherungskonzept des verwendeten HFB näher eingegangen und der Ablauf der Ertüchtigungsmaßnahme detailliert beschrieben. Hierbei werden insbesondere die durchgeführten Frisch‐ und Festbetonuntersuchungen erläutert und die an einer Probeplatte ermittelten Ergebnisse sowie die der beiden Betonierabschnitte eingehend diskutiert. Die gesammelten Erfahrungen zeigen, dass unter Einhaltung der entsprechenden Qualitätssicherungsmaßnahmen der hochfeste Beton erfolgreich und ohne nennenswerte Schwankungen hergestellt und eingebaut werden konnte. Zukünftig ist hierbei eine Regelbauweise denkbar, die unter funktionaler Ausschreibung der Betoneigenschaften eine zielsichere und wirtschaftliche Ertüchtigung orthotroper Fahrbahnplatten ermöglichen kann.
Asymptotic‐based bootstrap approach for matched pairs with missingness in a single arm
Authors: Amro Lubna , Pauly Markus , Ramosaj Burim 
Published: July 2021

AbstractThe issue of missing values is an arising difficulty when dealing with paired data. Several test procedures are developed in the literature to tackle this problem. Some of them are even robust under deviations and control type‐I error quite accurately. However, most of these methods are not applicable when missing values are present only in a single arm. For this case, we provide asymptotic correct resampling tests that are robust under heteroskedasticity and skewed distributions. The tests are based on a meaningful restructuring of all observed information in quadratic form–type test statistics. An extensive simulation study is conducted exemplifying the tests for finite sample sizes under different missingness mechanisms. In addition, illustrative data examples based on real life studies are analyzed.
Best practices on critical reagent characterization, qualification, and life cycle management for HCP immunoassays
Authors: Graf Tobias , Seisenberger Christina , Wiedmann Michael , Wohlrab Stefanie , Anderka Oliver 
Published: July 2021

AbstractThe performance of immunoassays for the detection and quantification of host‐cell proteins (HCPs) in biopharmaceuticals depends on the quality of the critical assay reagents. Not only their preparation, but also a stringent life‐cycle management, including reagent qualification, requalification, and replacement, plays a crucial role in ensuring consistent and reliable results. To provide a cross‐industry perspective on HCP reagent management, we conducted a survey on common practices among several pharmaceutical and biotech companies. Based on its outcome, as well as informed by a corresponding roundtable session (“Managing critical reagents over time”) at the BioPharmaceutical Emerging Best Practices Association HCP conference in 2019, this study presents specific recommendations and proven concepts to support immunoassay reagent management for monitoring HCPs.
Counsellors’ experiences of providing counselling to students in university‐level institutions in Ireland: An evolving phenomenon
Authors: Harrison Grace , Gordon Evelyn 
Published: July 2021

AbstractBackgroundThe mental health of university‐level students has become a global concern due to the increased level and complexity of mental health presentations among students and the rise in demand for university‐level counselling services, often the primary source of support for these students. However, to date, few studies have explored counsellors’ experiences of working in this context.AimTo explore counsellors’ experiences of providing counselling to students in university‐level institutions in Ireland.MethodThis interpretative phenomenological analysis (IPA) study used one‐to‐one semi‐structured interviews to capture the lived experience of qualified counsellors who were actively providing counselling in university‐level institutions (N = 8). Data were analysed following the six stages of the IPA analytic method.FindingsTwo superordinate themes were identified: ‘fighting for recognition’ captures participants’ struggle to gain and/or maintain a sense of value in their professional identity and to explain the complexity of their role to others; and ‘zigzagging’ describes how they need to respond flexibly and creatively to meet student needs in a context that is unpredictable and evolving.ConclusionThe study highlights the growing complexity of the university‐level student counsellor role and identifies the challenges and rewards associated with working in this context. It suggests the importance of role recognition and counsellor capacity to adjust to protect their well‐being and ultimately the quality of the service provided to students.
Targeted Chemical Modifications Identify Key Features of Carbohydrate Assemblies and Generate Tailored Carbohydrate Materials
Authors: Gim Soeun , Fittolani Giulio , Yu Yang , Zhu Yuntao , Seeberger Peter H. , Ogawa Yu , Delbianco Martina 
Published: July 2021

AbstractThe molecular level description of carbohydrate assemblies is hampered by their structural complexity and the lack of suitable analytical methods. Here, we employed systematic chemical modifications to identify key non‐covalent interactions that triggered the supramolecular assembly of a disaccharide model. While some modifications disrupted the supramolecular organization, others were tolerated, delivering important information on the aggregation process. The screening identified new geometries, including nanotubes, and twisted ribbons that were characterized with electron tomography and electron diffraction (ED) methods. This work demonstrates that the combination of synthetic chemistry and ED methods is a powerful tool to draw correlations between the molecular structure and the nanoscale architecture of carbohydrate assemblies.
Xenon Diffusion in Ionic Liquids with Blurred Nanodomain Separation
Authors: Saielli Giacomo , Castiglione Franca , Mauri Michele , Simonutti Roberto , Mele Andrea 
Published: July 2021

AbstractThe dynamics of xenon gas, loaded in a series of 1‐alkyl‐3‐methylimidazolium based ionic liquids, probes the formation of increasingly blurred polar/apolar nanodomains as a function of the anion type and the cation chain length. Exploiting 129Xe NMR spectroscopy techniques, like Pulse Gradient Spin Echo (PGSE) and inversion recovery (IR), the diffusion motion and relaxation times are determined for 1‐alkyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide [CnC1im][TFSI]. A correlation between the ILs nano‐structure and both xenon diffusivity and relaxation times, as well as chemical shifts, is outlined. Interestingly, comparison with previous results of the same properties in the homologous imidazolium chlorides and hexafluorophospate shows an opposite trend with the alkyl chain length. Classical molecular dynamics (MD) simulations are used to calculate the xenon and cation and anion diffusion coefficients in the same systems, including imidazolium cations with longer chains (n=4, 6, 8 … 20). An almost quantitative agreement with the experiments validates the MD simulations and, at the same time, provides the necessary structural and dynamic microscopic insights on the nano‐segregation and diffusion of xenon in bistriflimide, chloride and hexafluorphosphate salts allowing to observe and rationalize the shaping effect of the cation in the nanostructure.
Whole‐Cell‐Based Photosynthetic Biohybrid Systems for Energy and Environmental Applications
Authors: Li Luxuan , Xu Zhijun , Huang Xin 
Published: July 2021

AbstractWith the increasing awareness of sustainable development, energy and environment are becoming two of the most important issues of concern to the world today. Whole‐cell‐based photosynthetic biohybrid systems (PBSs), an emerging interdisciplinary field, are considered as attractive biosynthetic platforms with great prospects in energy and environment, combining the superiorities of semiconductor materials with high energy conversion efficiency and living cells with distinguished biosynthetic capacity. This review presents a systematic discussion on the synthesis strategies of whole‐cell‐based PBSs that demonstrate a promising potential for applications in sustainable solar‐to‐chemical conversion, including light‐facilitated carbon dioxide reduction and biohydrogen production. In the end, the explicit perspectives on the challenges and future directions in this burgeoning field are discussed.
Alkylammonium Cation Affinities of Nitrogenated Organobases: The Roles of Hydrogen Bonding and Proton Transfer
Authors: Sanchez‐Andrada Pilar , Vidal‐Vidal Angel , Prieto Tania , Elguero José , Alkorta Ibon , Marin‐Luna Marta 
Published: July 2021

AbstractAlkylammonium cation affinities of 64 nitrogen‐containing organobases, as well as the respective proton transfer processes from the alkylammonium cations to the base, have been computed in the gas phase by using DFT methods. The guanidine bases show the highest proton transfer values (191.9–233 kJ mol−1) whereas thecis‐2,2’‐biimidazole presents the largest affinity towards the alkylammonium cations (>200 kJ mol−1) values. The resulting data have been compared with the experimentally reported proton affinities of the studied nitrogen‐containing organobases revealing that the propensity of an organobase for the proton transfer process increases linearly with its proton affinity. This work can provide a tool for designing senors for bioactive compounds containing amino groups that are protonated at physiological pH.
Mitochondrial Targeting Cationic Purpurinimide–Polyoxometalate Supramolecular Complexes for Enhanced Photodynamic Therapy with Reduced Dark Toxicity
Authors: Lee Tae Heon , Liu Yang , Kim Hye Jeong , Lee Sang Hyeob , Song Hyeon Ho , Shim Young Key , Lee Woo Kyoung , Yoon Il 
Published: July 2021

AbstractPolyoxometalates (POMs), that are well‐defined metal‐oxygen cluster anions, are functional molecules extensively used in various research applications. The synthesis of neutral purpurinimides, followed by conversion to cationic purpurinimides (CPIs), formed CPI–POM supramolecular complexes via electrostatic interactions between each CPI and the polyanionic POM. The cellular uptake of purpurinimides, CPIs, and their CPI–POMs in A549 and HeLa cell lines was confirmed by confocal laser scanning microscopy. CPIs showed concentration‐dependent dark cytotoxicity; however, CPI–POMs exhibited reduced low dark cytotoxicity. After photoirradiation, CPIs and CPI–POMs revealed enhanced photodynamic therapy (PDT) compared to free purpurinimides against A549 and HeLa cells. The CPIs exhibit low cell viability by incorporating their PDT effect with intrinsic dark cytotoxicity; however, the CPI–POMs exhibited a POM delivery effect‐based enhanced PDT activity in the supramolecular complex system with low dark cytotoxicity. In particular, the clicked CPI–POM revealed two times higher PDT activity compared with the clicked free CPI, due to the good delivery effect of POM.
Synthesis of Natural Rubrolides B, I, K, L, M, O and Analogues
Authors: de Vries Jessica , Assmann Maik , Janneschütz Jasmin , Krauß Judith , Gudzuhn Mirja , Stanelle‐Bertram Stephanie , Gabriel Gülsah , Streit Wolfgang R. , Schützenmeister Nina 
Published: July 2021

AbstractThe chlorinated natural products, rubrolides B, I, K, L, M and O and analogues were synthesized in only five steps employing a robust and divergent synthetic strategy. The synthesis is performed without using protecting groups starting from a key intermediate, which can be synthesized from commercially available tetronic acid in only two steps. Selective halogenation and vinylogous aldol condensation enable the efficient synthesis of highly halogenated natural occurring rubrolides as well as synthetic analogues to build up a compound library for antiviral and antibiofilm testing. All synthesized compounds were then tested for their activity against the two influenza A virus strains pH1N1 and H3N2 as well as for their antibiofilm activity. Naturally occurring as well as synthetic analogues showed promising antiviral and antibiofilm activities.
Switchable Mono‐ and Dipropargylation of Amino Alcohols: A Unique Property of the Iodide Anion in Controlling Ring‐Opening Alkynylation
Authors: Feng Huangdi , Wang Fang , Cao Leilei , Van der Eycken Erik V. , Yin Xiaoying 
Published: July 2021

AbstractThe application of multicomponent reactions has been recognized as the most versatile strategy to achieve molecular diversity in organic synthesis. The reaction pathway and selectivity control of multicomponent reactions are associated with the effectiveness, the economy, and cleanliness of the process. Herein, a copper‐catalyzed switchable process for the selective synthesis of N‐propargyl oxazolidines and N,N‐dipropargyl vicinal amino alcohols, by propargylation of amino alcohols, is disclosed. Mechanistic studies support a sequential process involving a copper‐catalyzed annulation/A3‐coupling of amino alcohol, and copper‐catalyzed ring‐opening alkynylation of the oxazolidine intermediate. Notably, the iodide anion would not affect the generation of oxazolidines, but it could shut down the cascade procedure of the alkynylation of these oxazolidines.
A Simple Strategy to Obtain Synthetic Ca2+‐Dependent Lectin Mimics
Authors: Timmer Brian J. J. , Mooibroek Tiddo J. 
Published: July 2021

AbstractMany lectins require a Ca2+ ion as structure directing co‐factor to function as carbohydrate binders. Such lectins are implicated in various important biological processes such as inflammation and infection, yet a simple strategy to mimic their function is lacking. Herein, a very simple dipyridyl ligand (6) is reported that can organize around a Pd2+ ion to form the ring‐like complexes [PdCl26] and [Pd62]2+. In CD2Cl2 with 5 % dmso‐d6, ligand 6 does not associate with glycosides, while its Pd2+ complexes selectively bind to β‐n‐octyl‐glycosides over α‐n‐octyl‐glycosides. The highest affinity (Ka1:1≈116 M−1) was found between the dicationic [Pd62]2+ and n‐octyl‐β‐D‐galactoside. Molecular modelling suggests a common binding motif with an important role of C−H⋅⋅⋅π interactions and two charge assisted bifurcated [N−H/C−H]+⋅⋅⋅O hydrogen bonds. Ligand 6 and its metal complexes thus provide a proof‐of‐concept for a very simple strategy to mimicking Ca2+‐dependent lectins.