bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of RbF and NaF Postdeposition Treatments on Charge Carrier Transport and Recombination in Ga‐Graded Cu(In,Ga)Se2 Solar Cells
Authors: Chang Yu‐Han , Carron Romain , Ochoa Mario , Tiwari Ayodhya N. , Durrant James R. , Steier Ludmilla
Published: July 2021

Two key strategies for enhancing the efficiency of Cu(In,Ga)Se2 solar cells are the bandgap gradient across the absorber and the incorporation of alkali atoms. The combined incorporation of Na and Rb into the absorber has brought large efficiency gains compared to Na‐containing or alkali‐free layers. Here, transient absorption spectroscopy is employed to study the effect of NaF or combined NaF+RbF postdeposition treatments (PDT) on minority carrier dynamics in different excitation volumes of typical composition‐graded Cu(In,Ga)Se2 solar cells. Electron lifetimes are found to be highly dependent on the film composition and morphology, varying from tens of nanoseconds in the energy notch to only ≈100 ps in the Ga‐rich region near the Mo‐back contact. NaF PDT improves recombination lifetimes by a factor of 2–2.5 in all regions of the absorber, whereas the effectiveness of the RbF PDT is found to decrease for higher Ga‐concentrations. Electron mobility measured in the absorber region with large grains is promoted by both alkali PDTs. The data suggest that NaF PDT passivates shallow defect states (Urbach tail) throughout the Cu(In,Ga)Se2 film (including the interior of large grains), whereas the additional RbF PDT is effective at grain boundary surfaces (predominantly in regions with medium to low Ga‐concentrations).
Hundreds of nuclear and plastid loci yield novel insights into orchid relationships
Authors: Pérez‐Escobar Oscar Alejandro , Dodsworth Steven , Bogarín Diego , Bellot Sidonie , Balbuena Juan A. , Schley Rowan J. , Kikuchi Izai A. , Morris Sarah K. , Epitawalage Niroshini , Cowan Robyn , Maurin Olivier , Zuntini Alexandre , Arias Tatiana , Serna‐Sánchez Alejandra , Gravendeel Barbara , Torres Jimenez Maria Fernanda , Nargar Katharina , Chomicki Guillaume , Chase Mark W. , Leitch Ilia J. , Forest Félix , Baker William J.
Published: July 2021

PREMISE

The inference of evolutionary relationships in the species‐rich family Orchidaceae has hitherto relied heavily on plastid DNA sequences and limited taxon sampling. Previous studies have provided a robust plastid phylogenetic framework, which was used to classify orchids and investigate the drivers of orchid diversification. However, the extent to which phylogenetic inference based on the plastid genome is congruent with the nuclear genome has been only poorly assessed.

METHODS

We inferred higher‐level phylogenetic relationships of orchids based on likelihood and ASTRAL analyses of 294 low‐copy nuclear genes sequenced using the Angiosperms353 universal probe set for 75 species (representing 69 genera, 16 tribes, 24 subtribes) and a concatenated analysis of 78 plastid genes for 264 species (117 genera, 18 tribes, 28 subtribes). We compared phylogenetic informativeness and support for the nuclear and plastid phylogenetic hypotheses.

RESULTS

Phylogenetic inference using nuclear data sets provides well‐supported orchid relationships that are highly congruent between analyses. Comparisons of nuclear gene trees and a plastid supermatrix tree showed that the trees are mostly congruent, but revealed instances of strongly supported phylogenetic incongruence in both shallow and deep time. The phylogenetic informativeness of individual Angiosperms353 genes is in general better than that of most plastid genes.

CONCLUSIONS

Our study provides the first robust nuclear phylogenomic framework for Orchidaceae and an assessment of intragenomic nuclear discordance, plastid‐nuclear tree incongruence, and phylogenetic informativeness across the family. Our results also demonstrate what has long been known but rarely thoroughly documented: nuclear and plastid phylogenetic trees can contain strongly supported discordances, and this incongruence must be reconciled prior to interpretation in evolutionary studies, such as taxonomy, biogeography, and character evolution.
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

Aim

The 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.

Methods

This 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.

Results

Differences (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).

Conclusion

These 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

We 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

Development 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

Cells 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

Since 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

Das 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

The 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

The 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.
Microporosity Enhancement in a One‐Dimensional Imidazolium Caged Metal‐Organic Framework by Highly Selective Postsynthetic Removal of Inner Yttrium Clusters
Authors: Ko Nakeun , Lee Hyun‐Jung , Seo Younggyu , Jung Daesung , Hwang Chan‐Cuk , Kim Jaheon , Lee Eunsung
Published: July 2021

A one‐dimensional (1D) metal‐organic caged framework (YMOF‐Y) was obtained via self‐assembly of yttrium cations with a U‐shape imidazolium based ligand and the structure was elucidated by single‐crystal X‐ray diffraction analysis. The YMOF‐Y has a unique 1D chain structure composed of octa‐imidazolium based cages. Inside the cage, an inner Y4 cluster connected to yttrium cations of the cage through formate anions is present. The microporosity and flexibility of YMOF‐Y can be improved by an unprecedented postsynthetic removal of the Y4 clusters from the cage by washing with alkali metal solutions. The removal of the Y4 cluster is reflected in a significant change in the properties of the metal‐organic framework (MOF), as confirmed by carbon dioxide sorption measurements and variable temperature powder X‐ray diffraction analysis.
Counsellors’ experiences of providing counselling to students in university‐level institutions in Ireland: An evolving phenomenon
Authors: Harrison Grace , Gordon Evelyn
Published: July 2021

Background

The 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.

Aim

To explore counsellors’ experiences of providing counselling to students in university‐level institutions in Ireland.

Method

This 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.

Findings

Two 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.

Conclusion

The 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

The 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

The 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

With 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

Alkylammonium 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

Polyoxometalates (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

The 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

The 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

Many 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.
Rosmarinic acid relieves cisplatin‐induced ovary toxicity in female mice via suppression of oxidative stress and inflammation
Authors: Gui Hua , Jin Yue , Lin Aini , Wang Peihong , Wang Yan , Zhu Haibin
Published: July 2021

Rosmarinic acid having potential anti‐inflammatory and free radical scavenging activity. We examined the chemotherapeutic effect of rosmarinic against cisplatin (CIS)‐induced ovarian toxicity via modulation of oxidative stress and inflammation. Swiss BALB mice used in experimental protocol and mice were divided into different groups. Intraperitoneal injection of CIS (7 mg/kg) was used for ovarian cancer induction. The rats were received rosmarinic acid (2.5, 5, and 10 mg/kg, body weight) treatment for 22 weeks. Body weight, ovary weight food, and water intake were estimated at regular time intervals. Hormonal and antioxidant parameters were estimated in the ovary tissue and serum at the end of the study. Cytokines, inflammatory, and apoptosis parameters were determined at the end of the study. Finally, the ovary tissue histopathology was performed at end of the experimental study. Rosmarinic acid significantly (p < 0.001) improved the body weight and reduced the ovary weight. Rosmarinic acid considerably reduced the hormonal assay parameters, such as antimullerian hormone, estradiol, luteinizing hormone, and follicle‐stimulating hormone compared to model control mice. Rosmarinic treatment significantly (p < 0.001) reduced the level of nitric oxide, myeloperoxidase, and boosted the level of antioxidant parameters, such as glutathione, superoxide dismutase, catalase, and glutathione peroxidase in serum and ovary tissue. Rosmarinic acid downregulated the cytokines like interleukin‐6, tumor necrosis factor‐α, interleukin‐1β; inflammatory parameter includes prostaglandin E2, cyclooxygenase‐2, and inducible nitric oxide synthase at a dose‐dependently. Ovary tissue histopathology showed improvement after rosmarinic acid treatment. The result suggests that rosmarinic acid is a protective effect in ameliorating CIS‐induced ovary toxicity via alteration of inflammatory and apoptosis parameters.
Clinical experience with maintenance therapeutic plasma exchange in refractory generalized myasthenia gravis
Authors: Sheckley Hunter , Malhotra Kunal , Katyal Nakul , Narula Naureen , Govindarajan Raghav
Published: July 2021

Background

Despite the availability of several immunomodulatory therapies, about 20% of myasthenia gravis (MG) patients remain refractory to conventional treatments. There is limited evidence to support the use of maintenance therapeutic plasma exchange (TPE) therapy for refractory generalized MG.

Methods

Retrospective chart review of 14 patients with refractory generalized MG treated for 12 months with maintenance TPE therapy. Outcome measures were myasthenia gravis composite (MGC) score, myasthenia gravis activities of daily living (MG‐ADL), number of acute exacerbations, medication changes, and adverse events. Data were collected at 3 monthly intervals for 12 months before and after initiation of TPE therapy.

Results

Clinically meaningful reductions in mean MG‐ADL (>2 points) (mean MG‐ADL score: 9.9 ± 0.5; 12‐month pre‐TPE to 5.2 ± 0.9; 12‐month post‐TPE) and MGC (>3 points) (mean MGC score: 25.2 ± 1.6; 12‐month pre‐TPE to 11.7 ± 1.4; 12‐month post‐TPE) were observed at 3 months following initiation of TPE and were maintained up to 12 months in all patients. After 12 months of TPE therapy, all patients had a significant reduction in daily prednisone and pyridostigmine use. Patients previously on IVIG or rituximab therapy were successfully weaned off both treatments. There was a significant reduction in acute MG exacerbations; 7.8 ± 1.1 mean exacerbations/patient (12‐month pre‐TPE) to 2 ± 1.1 mean exacerbations/patient (12‐month post‐TPE).

Conclusion

Over a period of 12 months, maintenance TPE therapy improved MG‐ADL, and MGC with decreased immunosuppressant requirement, while being well‐tolerated.
Investigation of the relationship between continuing bonds and adjustment after the death of a first‐degree family member by using the Multidimensional Continuing Bonds Scale
Authors: Keser Emrah , Işıklı Sedat
Published: July 2021

Objectives

The study aims to develop a continuing bonds scale, investigate the relationship between continuing bonds and adjustment after loss, and test the moderating role of meaning reconstruction in this relationship.

Methods

Data were collected from two different samples of 306 (Study 1) and 271 (Study 2) bereaved adults.

Results

The four factors structure of the Multidimensional Continuing Bonds Scale (MCBS) was explored and confirmed. Hierarchical regression analysis revealed that continuing bonds showed a significant relationship with prolonged grief symptoms after controlling the risk factors such as gender, age of the deceased, time since loss, and cause of death. Meaning reconstruction moderated the relationship between continuing bonds and prolonged grief symptoms.

Conclusion

The results revealed that the MCBS can be used as a valid and reliable scale to assess the continuing bonds construct. The relationship between continuing bonds and prolonged grief symptoms varies according to the levels of meaning reconstruction.
Psychometric properties of the spanish version of the Valuing Questionnaire in Colombian clinical and nonclinical samples
Authors: Ruiz Francisco J. , Suárez‐Falcón Juan C. , Segura‐Vargas Miguel A. , Gil‐Luciano Bárbara
Published: July 2021

Objective

To examine the psychometric properties of the Spanish version of the Valuing Questionnaire (VQ) in Colombian clinical and nonclinical samples.

Method

The VQ was administered to a total sample of 1820 participants, which included undergraduates (N = 762), general population (N = 724), and a clinical sample (N = 334). The questionnaire packages included measures of experiential avoidance, cognitive fusion, mindfulness, life satisfaction, and psychological difficulties.

Results

Across the different samples, internal consistency was good (global Cronbach's alpha of 0.83 for Progress and 0.82 for obstruction). Measurement invariance was found across samples and gender, and the two‐factor model obtained a good fit to the data. The latent means of progress and obstruction of the clinical sample were lower and higher, respectively, than the latent means of the nonclinical samples. Correlations with other variables were in the expected direction.

Conclusion

The Spanish version of the VQ showed good psychometric properties.
Death and taxes: Examining the racial inequality in premature death across neighborhoods
Authors: Zuberi Anita , Teixeira Samantha
Published: July 2021

Legacies of residential segregation have led to deep inequities felt in communities of color across the nation and have been established as a fundamental cause of health disparities. Historical practices such as the redlining of majority Black neighborhoods in cities have led to long term consequences on these communities, including concentrated poverty and disadvantage. Research shows a strong connection between living in a poor neighborhood and poorer health outcomes, including early death, but questions remain about what characteristics of poor neighborhoods drive these disparities. We combined data from the American Community Survey with administrative data from Pittsburgh, Pennsylvania to examine the difference in premature death in Black and white neighborhoods (N = 87) using measures of socioeconomic disadvantage and less commonly studied neighborhood features including vacancy, tax delinquency, and property sales and conditions. Results suggest that features of abandonment, particularly the percent of tax delinquent properties in a neighborhood, may capture an important structural difference between majority Black and majority white neighborhoods with impacts beyond socioeconomic disadvantage on community health. We discuss implications of these findings for research and practice.
#COVID#BACKTOSCHOOL: Qualitative study based on the voice of Portuguese adolescents
Authors: Branquinho Cátia , Santos Anabela Caetano , Ramiro Lúcia , Gaspar de Matos Margarida
Published: July 2021

Due to the COVID‐19 pandemic and the exponential increase in cases, educational institutions worldwide were forced to close, making way for digital learning. After a period of confinement and an online teaching methodology, a new school year has begun. However, this new school year included the application of a wide range of measures that transformed the educative setting. The present study aimed to understand the health consequences for adolescents and young adults (AYA) during the back to school period after the COVID‐19 lockdown. This mixed‐method study included 304 participants between 16 and 24 years old (M = 18.4, SD = 2.12), female (71.1%), Portuguese (90.8%) and students (85.2%). In general, it was with a pessimistic perspective that young people in general, particularly girls and university students, understood the new school reality postconfinement, the effects on friendship relations, leisure activities and physical activity. By demonstrating AYA's ability and competence to identify and expose their problems, this study intends to raise awareness of the need for their involvement in the issues that affect them.
Gill morphology of Bagrus bayad (Forskal, 1775) using scanning electron microscopy
Authors: Bassuoni Naglaa F.
Published: July 2021

The work under investigation is carried out to describe the gross morphology and ultrastructure of the gills of the species Bagrus bayad grossly and with the help of scanning electron microscopy. The current work carried on ten fresh adult Bagrus bayad. Bagrus bayad is a genus of the Bagridae family. Our results revealed that the operculum opened caudoventrally. The wide interbranchial septum consisted of four transverse raised areas on each side that connected by transverse lines caudal to the base of the tongue. The gill arch is divided into long ceratobranchial and the short epibranchial clearly and formed an angle between them in the first three gill arches but in the fourth‐gill arch is not clear. The first two gill arches have only lateral rackers. The first arch carried well‐developed long rackers while rackers on the following rows were short. The majority of gill rackers were short as an adaptation of the carnivorous feeding habit of the Bagrus bayad. The gill arch and rackers were covered by pavement cells with chloride and mucus cells. The pavement cell surface has numerous microridges giving them the fingerprint's appearance. The gill filament's length is nearly fixed along the entire gill arch. Along the gill arch, and the gill filament carried leaf‐like gill lamellae. At higher magnification, the gill filament appeared covered by irregular polygonal cells that have concentric microridges.
Easing the burden of multi‐state genetic counseling licensure in the United States: Process, pitfalls, and possible solutions
Authors: Tschirgi Matthew L. , Owens Kailey M. , Mackall Mia S. , Allen Jamie , Allen Rachel
Published: July 2021

State‐based genetic counseling licensure creates standardization, ensures high‐quality care, and supports the credentialing of genetic counselors (GCs) in the United States. However, it also has the unintended consequence of requiring substantial time and resources from genetic counselors who need to obtain licensure in multiple states. There is a wide range of variability among state licensure applications, required supporting documentation, verification processes, and cost—all of which are barriers for genetic counselors. New licensure laws are being passed on a regular basis, further complicating this process. Resources may be available to some genetic counselors such as employer reimbursement and administrative support; however, access to this support is not universal. This paper reviews the current condition of genetic counseling multi‐state licensure, including barriers, unique challenges, and possible solutions for increased efficiencies, based on the authors’ experiences and examples found in other healthcare fields.
Genomic characterization of SARS‐CoV‐2 isolates from patients in Turkey reveals the presence of novel mutations in spike and nsp12 proteins
Authors: Sahin Erdem , Bozdayi Gulendam , Yigit Selin , Muftah Hager , Dizbay Murat , Tunccan Ozlem G. , Fidan Isil , Caglar Kayhan
Published: July 2021

Novel mutations have been emerging in the genome of severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2); consequently, the evolving of more virulent and treatment resistance strains have the potential to increase transmissibility and mortality rates. The characterization of full‐length SARS‐CoV‐2 genomes is critical for understanding the origin and transmission pathways of the virus, as well as identifying mutations that affect the transmissibility and pathogenicity of the virus. We present an analysis of the mutation pattern and clade distribution of full‐length SARS‐CoV‐2 genome sequences obtained from specimens tested at Gazi University Medical Virology Laboratory. Viral RNA was extracted from nasopharyngeal specimens. Next‐generation sequencing libraries were prepared and sequenced on Illumina iSeq 100 platform. Raw sequencing data were processed to obtain full‐length genome sequences and variant calling was performed to analyze amino acid changes. Clade distribution was determined to understand the phylogenetic background in relation to global data. A total of 293 distinct mutations were identified, of which 152 missense, 124 synonymous, 12 noncoding, and 5 deletions. The most frequent mutations were P323L (nsp12), D614G (ORF2/S), and 2421C>T (5′‐untranslated region) found simultaneously in all sequences. Novel mutations were found in nsp12 (V111A, H133R, Y453C, M626K) and ORF2/S (R995G, V1068L). Nine different Pangolin lineages were detected. The most frequently assigned lineage was B.1.1 (17 sequences), followed by B.1 (7 sequences) and B.1.1.36 (3 sequences). Sequence information is essential for revealing genomic diversity. Mutations might have significant functional implications and analysis of these mutations provides valuable information for therapeutic and vaccine development studies. Our findings point to the introduction of the virus into Turkey through various sources and the subsequent spread of several key variants.
Evaluation of the relationship between macrophage migration inhibitory factor level and clinical course in patients with COVID‐19 pneumonia
Authors: Aksakal Alperen , Kerget Buğra , Kerget Ferhan , Aşkın Seda
Published: July 2021

The COVID‐19 pandemic, which has ravaged our world for more than a year, still shapes our agenda with a scale of intensity that fluctuates over time. In our study, we aimed to determine the correlation between serum migration inhibitory factor (MIF) level and disease severity in COVID‐19 with different prognoses. Between 15 October 2020 and 20 January 2021, 110 patients over the age of 18 who were diagnosed with COVID‐19 and 40 volunteer healthcare personnel were included in our study. MIF levels were measured by enzyme‐linked immunosorbent assay. In the comparison of serum MIF values in the patient and control group, it was observed that the MIF level was significantly higher in patients with both moderate and severe COVID‐19 levels compared to the control group (p = 0.001, 0.001). In the comparison of serum MIF values of moderate to severe COVID‐19 patients, it was observed that MIF level was higher in severe patients (p = 0.001). In the receiver operating characteristic curve analysis performed to differentiate between severe and moderate COVID‐19 patients with MIF levels, the area under the curve was observed as 0.78. When the cutoff value of the MIF level was taken as 4.455 ng/ml, the sensitivity was 83% and the specificity was 62%. Failure to adequately balance the pro‐inflammatory cytokines synthesized in COVID‐19 with anti‐inflammatory effect is the most important reason for the aggravation of the disease course. Playing a role in pro‐inflammatory cytokine synthesis, MIF can provide important information about the disease prognosis in the early period.
Genomic monitoring unveil the early detection of the SARS‐CoV‐2 B.1.351 (beta) variant (20H/501Y.V2) in Brazil
Authors: Slavov Svetoslav N. , Patané José S. L. , Bezerra Rafael dos Santos , Giovanetti Marta , Fonseca Vagner , Martins Antonio J. , Viala Vincent L. , Rodrigues Evandra S. , Santos Elaine V. , Barros Claudia R. S. , Marqueze Elaine C. , Santos Bibiana , Aburjaile Flavia , Neto Raul M. , Moretti Debora B. , Haddad Ricardo , Calado Rodrigo T. , Kitajima João P. , Freitas Erika , Schlesinger David , Junior de Alcantara Luiz C. , Elias Maria C. , Sampaio Sandra C. , Kashima Simone , Covas Dimas T.
Published: July 2021

Sao Paulo State, currently experiences a second COVID‐19 wave overwhelming the healthcare system. Due to the paucity of SARS‐CoV‐2 complete genome sequencing, we established a Network for Pandemic Alert of Emerging SARS‐CoV‐2 Variants to rapidly understand and monitor the spread of SARS‐CoV‐2 variants into the state. Through analysis of 210 SARS‐CoV‐2 complete genomes obtained from the largest regional health departments we identified cocirculation of multiple SARS‐CoV‐2 lineages such as B.1.1 (0.5%), B.1.1.28 (23.2%), B.1.1.7 (alpha variant, 6.2%), B.1.566 (1.4%), B.1.544 (0.5%), C.37 (0.5%) P.1 (gamma variant, 66.2%), and P.2 (zeta variant, 1.0%). Our analysis allowed also the detection, for the first time in Brazil, the South African B.1.351 (beta) variant of concern, B.1.351 (501Y.V2) (0.5%), characterized by the following mutations: ORF1ab: T265I, R724K, S1612L, K1655N, K3353R, SGF 3675_F3677del, P4715L, E5585D; spike: D80A, D215G, L242_L244del, A262D, K417N, E484K, N501Y, D614G, A701V, C1247F; ORF3a: Q57H, S171L, E: P71L; ORF7b: Y10F, N: T205I; ORF14: L52F. The most recent common ancestor of the identified strain was inferred to be mid‐October to late December 2020. Our analysis demonstrated the P.1 lineage predominance and allowed the early detection of the South African strain for the first time in Brazil. We highlight the importance of SARS‐CoV‐2 active monitoring to ensure the rapid detection of potential variants for pandemic control and vaccination strategies.

Highlights Identification of B.1.351 (beta) variant of concern in the Sao Paulo State. Dissemination of SARS‐CoV‐2 variants of concern and interest in the Sao Paulo State. Mutational Profile of the circulating variants of concern and interest.
Pricing optimization and competition under the linear nested stochastic choice model
Authors: Li Lixiang , Ke Ginger Y. , Li Min , Zhang Lianmin
Published: July 2021

In this article, we investigate the pricing optimization of firms selling multiple alternatives to the market where consumer purchase behavior follows the linear nested stochastic choice (LNSC) model. As a special case of the nested stochastic choice (NSC) model, LNSC similarly features a two‐step Luce procedure. Considering differentiated price sensitivities in a non‐exact preference function form, the present research specifically shows that, for any product in each nest, the adjusted markup is constant under certain conditions; and the adjusted nest‐level markup is constant among nests under another sufficient condition. The “loss‐leader” effect is observed, which indicates that it may be optimal to price a product with a negative adjusted markup or even a negative margin to attract more attention to the corresponding nest. Based on these results, the pricing optimization can be simplified to a single‐variable problem where the objective function is unimodal. Then, a special case with an exponential preference function is discussed along with its concavity of the total expected profit. The above results are also used to construct the oligopoly multiproduct price competition and characterize the Nash equilibrium. Finally, a series of sensitivity analyses are conducted to reveal the impacts of key parameters on the optimal solutions.