bluuebunny/crossref_metadata_2025 huggingface dataset:
Clathrate XI K58Zn122Sb207: A New Branch on the Clathrate Family Tree
Authors: Cox Tori , Gvozdetskyi Volodymyr , Bertolami Mark , Lee Shannon , Shipley Kristian , Lebedev Oleg I. , Zaikina Julia V.
Published: September 2020

The compositional screening of K‐Zn‐Sb ternary system aided by machine learning, rapid exploratory synthesis using KH salt‐like precursor and in situ powder X‐ray diffraction yielded a novel clathrate type XI K58Zn122Sb207. This clathrate consists of a 3D Zn‐Sb framework hosting K+ ions inside polyhedral cages, some of which are reminiscent of known clathrate types while others are unique to this structure type. The complex non‐centrosymmetric structure in the tetragonal space group
was solved by means of single crystal X‐ray diffraction as a 6‐component twin due to pseudocubic symmetry and further confirmed by high‐resolution synchrotron powder X‐ray diffraction and state‐of‐the‐art scanning transmission electron microscopy. The electron‐precise composition of this clathrate yields narrow‐gap p‐type semiconductor with extraordinarily low thermal conductivity due to displacement or “rattling” of K cations inside oversized cages and as well as to twinning, stacking faults and antiphase boundary defects.
Isolierbare Silicium‐basierte Polykationen mit Lewis‐Superacidität
Authors: Hermannsdorfer André , Driess Matthias
Published: September 2020

Molekulare Silicium‐Polykationen des Typs R2Si2+ und RSi3+ (R=H, organische Gruppe) sind Lewis‐Supersäuren und bisher in kondensierter Phase unbekannt. Wir berichten über die Synthese einer Reihe isolierbarer Terpyridinkomplexe von R2Si2+ und RSi3+, [R2Si(terpy)]2+ (R=Ph 12+; R2=C12H8 22+, (CH2)3 32+) und [RSi(terpy)]3+ (R=Ph 43+, C6H11 53+, m‐Xylyl 63+) in Form ihrer Triflat‐Salze. Die Stabilisierung dieser Spezies wird durch höhere Koordination erreicht, was aber niedrigere Fluoridionenaffinitäten (FIA) zur Folge hat. Trotzdem bleibt ein signifikantes Maß an Lewis‐Superacidität erhalten, wie durch Berechnungen und Experimente bestätigt wird. Die Komplexe aktivieren C(sp3)‐F‐Bindungen, was anhand der Fluoridabstraktion von 1‐Fluoradamantan (AdF) und der katalytischen Hydrodefluorierung von AdF demonstriert wird. Weiterhin veranschaulicht die Bildung der kristallinen Addukte [2(F)]+ und [5(H)]2+ die hohe Reaktivität gegenüber Fluorid‐ und Hydriddonoren.
Super‐Resolution Spatial Proximity Detection with Proximity‐PAINT
Authors: Schueder Florian , Lara‐Gutiérrez Juanita , Haas Daniel , Beckwith Kai Sandvold , Yin Peng , Ellenberg Jan , Jungmann Ralf
Published: September 2020

Visualizing the functional interactions of biomolecules such as proteins and nucleic acids is key to understanding cellular life on the molecular scale. Spatial proximity is often used as a proxy for the direct interaction of biomolecules. However, current techniques to visualize spatial proximity are either limited by spatial resolution, dynamic range, or lack of single‐molecule sensitivity. Here, we introduce Proximity‐PAINT (pPAINT), a variation of the super‐resolution microscopy technique DNA‐PAINT. pPAINT uses a split‐docking‐site configuration to detect spatial proximity with high sensitivity, low false‐positive rates, and tunable detection distances. We benchmark and optimize pPAINT using designer DNA nanostructures and demonstrate its cellular applicability by visualizing the spatial proximity of alpha‐ and beta‐tubulin in microtubules using super‐resolution detection.
Liquid‐Free All‐Solid‐State Zinc Batteries and Encapsulation‐Free Flexible Batteries Enabled by In Situ Constructed Polymer Electrolyte
Authors: Ma Longtao , Chen Shengmei , Li Xinliang , Chen Ao , Dong Binbin , Zhi Chunyi
Published: September 2020

Zn batteries are usually considered as safe aqueous systems that are promising for flexible batteries. On the other hand, any liquids, including water, being encapsulated in a deformable battery may result in problems. Developing completely liquid‐free all‐solid‐state Zn batteries needs high‐quality solid‐state electrolytes (SSEs). Herein, we demonstrate in situ polymerized amorphous solid poly(1,3‐dioxolane) electrolytes, which show high Zn ion conductivity of 19.6 mS cm−1 at room temperature, low interfacial impedance, highly reversible Zn plating/stripping over 1800 h cycles, uniform and dendrite‐free Zn deposition, and non‐dry properties. The in‐plane interdigital‐structure device with the electrolyte completely exposed to the open atmosphere can be operated stably for over 30 days almost without weight loss or electrochemical performance decay. Furthermore, the sandwich‐structure device can normally operate over 40 min under exposure to fire. Meanwhile, the interfacial impedance and the capacity using in situ‐formed solid polymer electrolytes (SPEs) remain almost unchanged after various bending tests, a key criterion for flexible/wearable devices. Our study demonstrates an approach for SSEs that fulfill the requirement of no liquid and mechanical robustness for practical solid‐state Zn batteries.
Genetic diversity, population structure, and historical demography of a highly vagile and human‐impacted seabird in the Pacific Ocean: The red‐tailed tropicbird, Phaethon rubricauda
Authors: Varela Andrea I. , Brokordt Katherina , Ismar‐Rebitz Stefanie M.H. , Gaskin Chris P. , Carlile Nicholas , O'Dwyer Terence , Adams Josh , VanderWerf Eric A. , Luna‐Jorquera Guillermo
Published: September 2020

Many seabird breeding colonies have recovered from heavy anthropogenic disturbance after conservation actions. The widely distributed red‐tailed tropicbird, Phaethon rubricauda, was used as a model species to assess potential anthropogenic impacts on the genetic diversity of breeding colonies in the Pacific Ocean.

Cytochrome c oxidase subunit I and control region sequences analyses were conducted across the range of the species in the Pacific Ocean. The study sites were at islands without human‐related disturbance (non‐impacted islands) and with human‐related disturbance (impacted islands). We hypothesized that (i) breeding colonies of the red‐tailed tropicbird on impacted islands have lower genetic diversity compared with colonies on non‐impacted islands, and (ii) breeding colonies of the red‐tailed tropicbird show significant fine and broad‐scale genetic structure across the Pacific Ocean. Bayesian skyline analyses were conducted to infer past changes in population sizes.

Genetic diversity was similar between impacted and non‐impacted islands. There was significant broad‐scale genetic structure among colonies separated by over 6,000 km, but a lack of significant fine‐scale genetic structure within Australasia and Hawai'i, although a significant level of differentiation was found within Chile with ΦST analyses. Skyline analyses showed that effective population sizes remained relatively constant through time, but experienced either a slight decrease or the end of an expansion event through the last 1,000 years. These changes may be related to the arrival of humans on Pacific islands.

Impacted islands may have received immigrants from other relatively close islands, buffering the loss of genetic diversity. However, it is also possible that colonies have retained ancestral variation or that a large effective population size coupled with a long generation time (13 years) has prevented the loss of genetic diversity in human‐impacted islands. Future research using higher‐resolution markers is needed to resolve the population genetic structure of the red‐tailed tropicbird in an ecological time‐scale.
Experimentelle Untersuchungen zur Verstärkung von Brückenfahrbahnplatten mit Textilbeton
Authors: Adam Viviane , Bielak Jan , Will Norbert , Hegger Josef
Published: September 2020

Etwa die Hälfte der Straßenbrücken in Deutschland wurde vor 1985 gebaut. Als Folge des gestiegenen Verkehrsaufkommens und strengerer normativer Anforderungen kann der Tragfähigkeitsnachweis durch eine Brückennachrechnung häufig nicht erbracht werden. Durch eine gezielte Tragwerksverstärkung lässt sich die Restnutzungsdauer verlängern, was eine erweiterte Planungsphase und Entzerrung der Baumaßnahmen von Ersatzneubauten ermöglicht. Am Institut für Massivbau (IMB) der RWTH Aachen wurden Versuche zur Ermittlung des Biege‐ und Querkraftverstärkungspotenzials einer Querschnittsergänzung der Brückenfahrbahnplatte mit Carbonbeton durchgeführt. Im vorliegenden Beitrag werden 17 Bauteilversuche an Fahrbahnplattenstreifen vorgestellt (verstärkte Versuchskörper und unverstärkte Referenzen). Dabei erfolgte ein Großteil der Versuche mit statischer Belastung, zwei Tastversuche wurden zyklisch beansprucht.
Copulation Song inDrosophila: Do Females Sing to Change Male Ejaculate Allocation and Incite Postcopulatory Mate Choice?
Authors: Kerwin Peter , von Philipsborn Anne C.
Published: September 2020

Drosophilamales sing a courtship song to achieve copulations with females. Females were recently found to sing a distinct song during copulation, which depends on male seminal fluid transfer and delays female remating. Here, it is hypothesized that female copulation song is a signal directed at the copulating male and changes ejaculate allocation. This may alter female remating and sperm usage, and thereby affect postcopulatory mate choice. Mechanisms of how female copulation song is elicited, how males respond to copulation song, and how remating is modulated, are considered. The potential adaptive value of female signaling during copulation is discussed with reference to vertebrate copulation calls and their proposed function in eliciting mate guarding. Female copulation song may be widespread within theDrosophilagenus. This newly discovered behavior opens many interesting avenues for future research, including investigation of how sexually dimorphic neuronal circuits mediate communication between nervous system and reproductive organs.
Dynamics of microbial competition, commensalism, and cooperation and its implications for coculture and microbiome engineering
Authors: Xu Peng
Published: September 2020

Microbial consortium is a complex adaptive system with higher‐order dynamic characteristics that are not present by individual members. To accurately predict the social interactions, we formulate a set of unstructured kinetic models to quantitatively capture the dynamic interactions of multiple microbial species. By introducing an interaction coefficient, we analytically derived the steady‐state solutions for the interacting species and the substrate‐depleting profile in the chemostat. We analyzed the stability of the possible coexisting states defined by competition, parasitism, amensalism, commensalism, and cooperation. Our model predicts that only parasitism, commensalism, and cooperation could lead to stable coexisting states. We also determined the optimal social interaction criteria of microbial coculture when sequential metabolic reactions are compartmentalized into two distinct species. Coupled with Luedeking–Piret and Michaelis–Menten equations, accumulation of metabolic intermediates in one species and formation of end‐product in another species could be derived and assessed. We discovered that parasitism consortia disfavor the bioconversion of intermediate to final product; and commensalism consortia could efficiently convert metabolic intermediates to final product and maintain metabolic homeostasis with a broad range of operational conditions (i.e., dilution rates); whereas cooperative consortia leads to highly nonlinear pattern of precursor accumulation and end‐product formation. The underlying dynamics and emergent properties of microbial consortia may provide critical knowledge for us to understand ecological coexisting states, engineer efficient bioconversion process, deliver effective gut therapeutics as well as elucidate probiotic‐pathogen or tumor‐host interactions in general.
Can symptoms of anosmia and dysgeusia be diagnostic for COVID‐19?
Authors: Zahra Syeda Anum , Iddawela Sashini , Pillai Kiran , Choudhury Rozina Yasmin , Harky Amer
Published: September 2020

Objective

Olfactory and taste dysfunction (OTD) is a potential neurological manifestation of coronavirus‐2019 (COVID‐19). We aimed to investigate the diagnostic value of symptoms of anosmia and dysgeusia for COVID‐19.

Methods

A comprehensive electronic search was conducted using PubMed, MEDLINE, Scopus, Cochrane database, and Google Scholar from 1 June 2020 to 12 June 2020. All studies reporting symptoms of anosmia and dysgeusia in COVID‐19‐positive patients were included. A total of 23 studies were included in the systematic review.

Results

Symptoms of anosmia and dysgeusia were frequently reported by COVID‐19‐positive patients. Symptoms were more common in females and in younger patients. There was no direct association between the severity of COVID‐19 and the presence of symptoms. However, some evidence was found for a longer duration of these symptoms and increased severity of COVID‐19 infection in young patients.

Conclusion

OTD is commonly reported by COVID‐19 patients. Due to limited literature on the association between OTD and COVID‐19, it is currently not possible to conclude that these symptoms alone can be used to diagnose COVID‐19. However, the presence of OTD can potentially be used as a screening tool for COVID‐19 especially in young and female patients. Further research is required to establish the true diagnostic value of these symptoms and efficacy as screening tools for COVID‐19 patients.
Development and external validation of a nomogram to predict the risk of Upper gastrointestinal precancerous lesions in a non‐high‐incidence area
Authors: Xiao Hai‐Fan , Yan Shi‐Peng , Li Ji‐Gang , Shi Zhao‐Hui , Zou Yan‐Hua , Xu Ke‐Kui , Liao Xian‐Zhen
Published: September 2020

Background

Upper gastrointestinal precancerous lesions (UGPL) is the major preventable disease in non‐high‐incidence area. A prognostic nomogram was constructed to predict and identity susceptible population of UGPL before endoscope screening.

Methods

We recruited 300 ,016 eligible participants for upper gastrointestinal cancer (UGC) screening aged 40‐74 years from two cities in Hunan province from 2012 to 2019. Individuals at high risk of UGC on basis of questionnaire estimation underwent endoscopic screening. Participants in two cities accepting endoscopy were used as training and external validation cohorts, respectively. A nomogram was developed based on independent prognostic factors of UGPL determined in multivariable logistic regression analysis.

Results

Of 35, 621 with high risk for UGC, 10, 364 subjects undertook endoscopy (participation rate of 29.1%). The detection rate for UGPL was 4.55%. The nomogram showed that age, gender, mental trama, picked food, and atrophic gastritis history in a descending order were significant contributors to UGPL risk. The C‐index value of internal and external validation of the model is 0.612 and 0.670, respectively. The calibration data for UGPL showed optimal agreement between the nomogram prediction and actual observation. Furthermore, high‐risk and low‐risk group divided based on score from the nomogram predicted a significantly distinct detection rate.

Conclusion

The nomogram provides screening workers a simple and accurate tool for identifying individuals at a higher risk of UGPL as primary screening before endoscopy among Chinese population in non‐high‐risk areas, thus reducing the incidence of UGC by improving the UGPL detection.
Nanofactories for Controlled Synthesis and Delivery of Nucleoside Analogue Therapeutics
Authors: Ebrahimi Kourosh H.
Published: September 2020

The ultimate nanomedicine will be a cell‐like machinery capable of reaching a specific target in the body and performing a desired therapeutic action in a controlled fashion. To make such machinery a reality, we need to combine fundamental knowledge and technological developments in different areas including polymer chemistry, biology, enzymology, and biochemical engineering. In this viewpoint, I put forward my vision of creating a nanofactory as a step towards developing cell‐like nanomedicines. To make the proposed nanofactory a reality there are many challenges ahead. I propose plausible solutions to address some of the main challenges.
Chemoproteomics: Towards Global Drug Target Profiling
Authors: Lu Kuan‐Yi
Published: September 2020

Illuminating drugs’ mechanisms of action and their effects on the biomolecules of pathogens and humans is a much‐needed next step to facilitate pharmaceutical development. Although studies have linked some drugs to their therapeutic targets by using transcriptomics and genomics, these approaches have intrinsic limitations and cannot directly assess drugs’ effects on their protein targets. In this regard, chemoproteomic methods can detect protein–ligand interactions and quantitate the chemical or thermal stability changes of the entire detectible proteomes induced by drugs of interest. These widely applicable techniques have recently been adapted to deconvolute the mechanisms of action of antiparasitic drugs and successfully identified an essential target that was previously not known to be druggable. A continued effort to Integrate chemoproteomics into the drug‐development pipeline could greatly improve our understanding of drugs’ mechanisms, toxicity and pharmacodynamic properties.
Epigenetic Modification 6‐Methyladenosine Can Impact the Potency and Specificity of siRNA
Authors: Rydzik Anna M. , Gottschling Dirk , Simon Eric , Skronska‐Wasek Wioletta , Rippmann Jörg F. , Riether Doris
Published: September 2020

The introduction of N6‐methyladenosine (m6 A) into siRNA targeting Factor VII impacts its potency in cells and has a significant influence on the selectivity of siRNA, including reduced off‐targeting. These effects are dependent on the position of m6 A in the siRNA duplex, with some of the sequences identified as more potent and/or selective than their non‐methylated counterpart. These findings broaden the repertoire of available chemical modifications for siRNA therapeutics and imply potential regulatory role of N6‐methyladenosine in the RNAi pathways.
Facile Stereoselective Reduction of Prochiral Ketones by using an F420‐dependent Alcohol Dehydrogenase
Authors: Martin Caterina , Tjallinks Gwen , Trajkovic Milos , Fraaije Marco W.
Published: September 2020

Effective procedures for the synthesis of optically pure alcohols are highly valuable. A commonly employed method involves the biocatalytic reduction of prochiral ketones. This is typically achieved by using nicotinamide cofactor‐dependent reductases. In this work, we demonstrate that a rather unexplored class of enzymes can also be used for this. We used an F420‐dependent alcohol dehydrogenase (ADF) from Methanoculleus thermophilicus that was found to reduce various ketones to enantiopure alcohols. The respective (S) alcohols were obtained in excellent enantiopurity (>99 % ee). Furthermore, we discovered that the deazaflavoenzyme can be used as a self‐sufficient system by merely using a sacrificial cosubstrate (isopropanol) and a catalytic amount of cofactor F420 or the unnatural cofactor FOP to achieve full conversion. This study reveals that deazaflavoenzymes complement the biocatalytic toolbox for enantioselective ketone reductions.
Chebulinic acid inhibits MDA‐MB‐231 breast cancer metastasis and promotes cell death through down regulation of SOD1 and induction of autophagy
Authors: Sharma Akshay , Mishra Tripti , Thacker Gatha , Mishra Mukul , Narender Tadigoppula , Trivedi Arun Kumar
Published: September 2020

Triple‐negative breast cancers (TNBC) are highly aggressive and drug resistant accounting for majority of cases with poor outcome. Purified natural compounds display substantial anticancer activity with reduced cytotoxicity providing a new avenue to combat TNBC. Chebulinic acid (CA), a polyphenol derived from the fruits of various medicinal plants has potent anticancer activity. Here, we demonstrate that CA shows significant cytotoxicity against triple negative MDA‐MB‐231 cells. CA exhibited cytotoxicity to MDA‐MB‐231 cells in 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Further, CA mitigated MDA‐MB‐231 cells viability and proliferation as shown by reduced live cell count, crystal violet staining, colony formation assay, soft agar assay and cell cycle analysis. Wound healing assay and trans‐well migration assay demonstrated that CA significantly inhibited migration of MDA‐MB‐231 cells. Also reduced MMP9 expression was observed in CA‐treated cells by gelatin zymography. CA negatively regulated mesenchymal characteristics of MDA‐MB‐231 cells demonstrated by F‐actin staining and reduced expression of N‐cadherin by confocal microscopy and western blot analysis. Annexin V/propidium iodide (PI) and active caspase‐3 staining showed that CA was able to induce apoptosis in MDA‐MB‐231 cells but did not activate caspase‐3. Two‐dimensional gel electrophoresis based proteomic analysis demonstrated that CA regulated proteins belonging to the oxidative stress pathway, apoptotic pathway and proteins with antiproliferative activity. Western blot analysis analysis revealed that CA negatively regulated superoxide dismutase 1 (SOD1) and enhanced oxidative stress in MDA‐MB‐231 cells. SOD1 in‐gel activity assay also showed reduced SOD1 activity upon CA treatment. Overexpression studies with GFP‐LC3 and tandem tagged RFP‐GFP‐LC‐3 also demonstrated enhanced autophagy upon CA treatment.
Collaterals in STEMI patients: An uncommon but critical lifeline
Authors: Kern Morton J. , Seto Arnold H.
Published: September 2020

Key Points

Angiographically visible collaterals are seen in a minority of STEMI patients, predominantly to the RCA and in patients with delays to reperfusion.

Patients with visible collaterals were less likely to have cardiogenic shock and tended to have a longer survival.

Further studies will determine the mechanisms of collateral formation and their protective associations.
One‐year clinical outcomes in patients with chronic kidney disease treated with COMBO stents: From the COMBO collaboration
Authors: Chandrasekhar Jaya , Kalkman Deborah N. , Sartori Samantha , Baber Usman , Blum Moritz , Aquino Melissa B. , Woudstra Pier , Beijk Marcel A. , Tijssen Jan G. , Koch Karel T. , Dangas George D. , Colombo Antonio , de Winter Robbert J. , Mehran Roxana ,   MASCOT and REMEDEE investigators
Published: September 2020

Background

Chronic kidney disease (CKD) patients undergoing percutaneous coronary intervention (PCI) experience greater ischemic events including clinically driven target lesion revascularization (CD‐TLR). Whether the COMBO biodegradable‐polymer sirolimus‐eluting stent promotes better outcomes in these patients by virtue of endothelial progenitor cell capture technology is unknown.

Objective

We examined one‐year outcomes by CKD status from the COMBO collaboration.

Methods

The COMBO collaboration was a patient‐level pooled dataset from the REMEDEE and MASCOT registries (3,614 patients) of all‐comers undergoing attempted COMBO stent PCI. The primary endpoint was one‐year target lesion failure (TLF), composite of cardiac death, target‐vessel myocardial infarction (TV‐MI) or CD‐TLR. Secondary endpoints included stent thrombosis (ST).

Results

The study included 6.4% (n = 231) CKD and 93.6% (n = 3,361) non‐CKD patients. CKD patients were older and included more women with greater prevalence of several comorbidities but similar rate of acute coronary syndrome (50.6% vs. 54.5%, p = .26). CKD patients underwent radial PCI less often (56.1% vs. 70.3%, p < .001) and received clopidogrel (78.6% vs. 68.3%) more often (p = .004). One‐year TLF occurred in 7.9% CKD vs. 3.7% non‐CKD patients, p = .001. CKD patients also demonstrated greater incidence of cardiac death (6.2% vs. 1.2%, p < .0001), TV‐MI (2.7% vs. 1.1%, p = .04) but similar CD‐TLR (2.7% vs 2.2%, p = .61) and definite/probable ST (1.4% vs. 0.8%, p = .42), compared to non‐CKD patients.

Conclusions

CKD patients treated with COMBO stents had significantly greater incidence of one‐year TLF compared to non‐CKD patients driven by cardiac death and to a lesser extent TV‐MI but not CD‐TLR. They had similar rates of definite/probable ST.
A rare case of nitrofurantoin‐induced acute lung injury
Authors: Karmali Rehan , Stawitzky Kyle , Srisethnil Isrin , Simpson Kaitlyn
Published: September 2020

Nitrofurantoin is a common treatment for urinary tract infections. Acute lung injury resulting from nitrofurantoin is a rare, life‐threatening complication with women being at greater risk. Symptoms include respiratory distress with fevers, rash, eosinophilia, and new‐onset atrial fibrillation. Treatment includes discontinuing the drug and possibly glucocorticoids for persistent oxygen demand.
Multiple brain abscesses and ventriculitis secondary to chronic periodontitis
Authors: Pedersen Torbjørn Østvik , Kråkenes Jostein , Løes Sigbjørn
Published: September 2020

Chronic marginal periodontitis is a common oral disease, but can in rare cases cause severe intracranial infection. This case illustrates that poor dental status can be life threatening, in particular for immunocompromised patients.
Comment on “Persistent Room‐Temperature Radicals from Anionic Naphthalimides: Spin Pairing and Supramolecular Chemistry” and on “Persistent Radical Pairs between N‐Substituted Naphthalimide and Carbanion Exhibit pKa‐Dependent UV/Vis Absorption”
Authors: Korth Hans‐Gert
Published: September 2020

EPR spectroscopic evidence for intramolecular electron transfer in anionic N‐substituted naphthalimides to yield persistent diradical anions and intermolecular electron transfer from a variety of carbanions to 6‐bromo‐N‐phenyl‐naphthalimide to yield persistent radical–radical anion pairs was recently claimed in two papers by Zhang et al. In this comment, it is shown that the EPR spectra published in both papers do not agree with the proposed triplet‐state species. Rather, the spectra are due to various doublet‐state radicals, deriving from minor side reactions. The misinterpretations invalidate the general conclusions of the papers.
Rearrangements of Aromatic Nitrile Oxides and Nitrile Ylides: Potential Ring Expansion to Cycloheptatetraene Derivatives Mimicking Arylcarbenes
Authors: Marchais Jérémy , Bégué Didier , Dargelos Alain , Wentrup Curt
Published: September 2020

Nitrile imines, nitrile oxides and nitrile ylides are widely used in 1,3‐dipolar cycloaddition reactions. They also undergo thermal and photochemical rearrangements to carbodiimides, isocyanates, and ketenimines, respectively. Calculations at DFT and CASPT2 levels of theory reveal novel, potential rearrangements, in which the aromatic 1,3‐dipoles mimic phenylcarbene and undergo ring expansion to cycloheptatetraene derivatives. These rearrangements can potentially take place in both the singlet ground states and the triplet excited states, and they are accelerated by m,m’‐bis(dimethylamino) substitution on the phenyl moieties. The new rearrangement becomes the energetically preferred path for m,m’‐bis(dimethylamino)benzonitrile oxide in the triplet state. In the m,m’‐bis(dimethylamino)benzo nitrile ylide, the cyclization to the 2‐phenyl‐1‐azirine is favored over the ring expansion to a cycloheptatetraene by ca. 5 kcal mol−1 in the singlet state. In the bent triplet states, 1,3‐hydrogen shifts interconverting nitrile ylides are potentially possible.
Asymmetric Acceptor–Donor–Acceptor Polymers with Fast Charge Carrier Transfer for Solar Hydrogen Production
Authors: Li Guosheng , Xie Zhipeng , Wang Qi , Chen Xiong , Zhang Yongfan , Wang Xinchen
Published: September 2020

Construction of local donor–acceptor architecture is one of the valid means for facilitating the intramolecular charge transfer in organic semiconductors. To further accelerate the interface charge transfer, a ternary acceptor–donor–acceptor (A1‐D‐A2) molecular junction is established via gradient nitrogen substituting into the polymer skeleton. Accordingly, the exciton splitting and interface charge transfer could be promptly liberated because of the strong attracting ability of the two different electron acceptors. Both DFT calculations and photoluminescence spectra elucidate the swift charge transfer at the donor‐acceptor interface. Consequently, the optimum polymer, N3‐CP, undergoes a remarkable photocatalytic property in terms of hydrogen production with AQY405 nm=26.6 % by the rational design of asymmetric molecular junctions on organic semiconductors.
Group 6 Hexacarbonyls as Ligands for the Silver Cation: Syntheses, Characterization, and Analysis of the Bonding Compared with the Isoelectronic Group 5 Hexacarbonylates
Authors: Bohnenberger Jan , Kratzert Daniel , Gorantla Sai Manoj N. V. T. , Pan Sudip , Frenking Gernot , Krossing Ingo
Published: September 2020

The syntheses of the two novel complexes [Ag{Mo/W(CO)6}2]+[F‐{Al(ORF)3}2]− (RF=C(CF3)3) are reported along with their structural and spectroscopic characterization. The X‐ray structure shows that three carbonyl ligands from each M(CO)6 fragment bend towards the silver atom within binding Ag−C distance range. DFT calculations of the free cations [Ag{M(CO)6}2]+ (M=Cr, Mo, W) in the electronic singlet state give equilibrium structures with C2 symmetry with two bridging carbonyl groups from each hexacarbonyl ligand. Similar structures with C2 symmetry (M=Nb) and D2 symmetry (M=V, Ta) are calculated for the isoelectronic group 5 anions [Ag{M(CO)6}2]− (M=V, Nb, Ta). The electronic structure of the cations is analyzed with the QTAIM and EDA‐NOCV methods, which provide detailed information about the nature of the chemical bonds between Ag+ and the {M(CO)6}2q (q = −2, M = V, Nb, Ta; q = 0, M = Cr, Mo, W) ligands.
The energy carriers hydrogen, natural gas and liquefied gas in comparism – part II
Authors: Grofe Theodor , Rubner Isabel
Published: September 2020

In diesem Artikel werden die Energieträger Wasserstoff, Erdgas und Autogas anhand von einfachen Schulexperimenten hinsichtlich ihrer Verbrennungsenthalpie untersucht. Anknüpfend an den Teil I der vergleichenden Betrachtung der Energieträger Wasserstoff, Erdgas und Autogas sollen in dieser Veröffentlichung die Messwerte und Ergebnisse aus dem ersten Teil optimiert werden. Die Optimierung der Werte gelingt mit aufwändigerem Experimentiermaterial, sodass deshalb zunehmend Demonstrationsexperimente an die Stelle von Schülerexperimenten rücken. Bei Einsatz des Verbrennungskalorimeters gelingt tatsächlich eine Annäherung an die Literaturwerte (Heizwert, Brennwert).
The Quest for the Best Dual Orexin Receptor Antagonist (Daridorexant) for the Treatment of Insomnia Disorders
Authors: Boss Christoph , Gatfield John , Brotschi Christine , Heidmann Bibia , Sifferlen Thierry , von Raumer Markus , Schmidt Gunther , Williams Jodi T. , Treiber Alexander , Roch Catherine
Published: September 2020

Since its discovery in 1998, the orexin system has been of interest to the research community as a potential therapeutic target for the treatment of sleep/wake disorders, stress and anxiety disorders, addiction or eating disorders. It consists of two G protein‐coupled receptors, the orexin 1 and orexin 2 receptors, and two neuropeptides with agonistic effects, the orexin A and orexin B peptides. Herein we describe our efforts leading to the identification of a promising set of dual orexin receptor antagonists (DORAs) which subsequently went through physiology‐based pharmacokinetic and pharmacodynamic modelling>[1] and finally led to the selection of daridorexant, currently in phase 3 clinical trials for the treatment of insomnia disorders.
Binding Mode Multiplicity and Multiscale Chirality in the Supramolecular Assembly of DNA and a π‐Conjugated Polymer
Authors: Fossépré Mathieu , Tuvi‐Arad Inbal , Beljonne David , Richeter Sébastien , Clément Sébastien , Surin Mathieu
Published: September 2020

Water‐soluble π‐conjugated polymers are increasingly considered for DNA biosensing. However, the conformational rearrangement, supramolecular organization and dynamics upon interaction with DNA have been overlooked, which prevents the rational design of such detection tools. To elucidate the binding of a cationic polythiophene (CPT) to DNA with atomistic resolution, we performed molecular simulations of their supramolecular assembly. Comparison of replicated simulations show a multiplicity of CPT binding geometries that contribute to the wrapping of CPT around DNA. The different binding geometries are stabilized by both electrostatic interactions between CPT lateral cations and DNA phosphodiesters and van der Waals interactions between the CPT backbone and the DNA grooves. Simulated circular dichroism (CD) spectra show that the induced CD signal stems from a conserved geometrical feature across the replicated simulations, i. e. the presence of segments of syn configurations between thiophene units along the CPT chain. At the macromolecular scale, we inspected the different shapes related to the CPT binding modes around the DNA through symmetry metrics. Altogether, molecular dynamics (MD) simulations, model Hamiltonian calculations of the CD spectra, and symmetry indices provide insights into the origin of induced chirality from the atomic to the macromolecular scale. Our multidisciplinary approach points out the hierarchical aspect of CPT chiral organization induced by DNA.
Can statistical learning models make early selection among sugarcane families easier and still efficient?
Authors: Moreira Édimo Fernando Alves , Barbosa Marcio Henrique Pereira , Peternelli Luiz Alexandre
Published: September 2020

The selection of genotypes at the early stages is one of the main challenges facing sugarcane (Saccharum officinarum L.) breeding programs. The present work aimed to compare classification techniques, namely, logistic regression (LR), k‐nearest neighbor (KNN), random forests (RF), and support vector machine (SVM) against the selection among families of sugarcane via artificial neural networks (ANN) and via a procrefers to the families incorrectly selected byedure based on the weighing of the plots. The data used in this work were obtained from 110 families. In the families, the number of stalks (NS), stalk diameter (SD), and stalk height (SH) were collected, in addition to the actual yield, expressed in tons of cane per hectare (TCH). We considered the NS, SD, and SH as explanatory variables for the training of the classifiers. The response used was the indicator Y = 0 if the family is not selected via TCH or Y = 1 otherwise. To increase the efficiency in training, we produced synthetic data based on the simulation of NS, SD, SH, and TCH values. Two models were also considered: a full model with all the predictors and a reduced model without the SH. We used the apparent error rate (AER) and the true positive rate (TPR) for the evaluation of the classifiers. All classifiers present low values for the AER and high values for the TPR in both models. The best performance was observed in the SVM. The reduced model should be preferred, since its performance is very close to that of the full model and its operation is more straightforward.
Corporate social responsibility and financial performance of companies: The puzzle of concepts, definitions and assessment methods
Authors: Barauskaite Gerda , Streimikiene Dalia
Published: September 2020

The definition of corporate social responsibility (CSR) states that companies must not only pursue their main goal—to maximize profits, but also contribute to the well‐being of society through voluntary efforts. The importance of CSR in today's global world is growing. It is becoming mandatory for companies to engage in socially responsible activities to support the growth of their business. It is argued that companies pursuing CSR initiatives can gain a competitive advantage over other competitors due to creation of a good public image or reputation and generate higher profits and a return on investment however some authors disagree with this. The aim of this article is to analyse the benefits and drawbacks of CSR based on systematic literature review and to develop the conceptual framework for linking CSR with the financial performance of companies. The conducted analysis revealed that in most studies the positive or neutral relationship between CSR and financial results were claimed. Though the negative and alternative connections between these issues are less frequently identified in scientific articles, they cannot be excluded from the analysis and require certain attention and further consideration.
Response of patients with chest tightness variant asthma with routine asthma treatment regimen: A 1‐year multicenter, prospective, real‐world study
Authors: Yan Fugui , Li Wen , Guan Wei‐jie , Chen Min , Qiu Chen , Tang Wei , Liu Xiansheng , Xiang Xudong , Li Jing , Jin Meiling , Dai Yuanrong , Chen Ping , Wu Xiaohong , Qiu Zhongmin , Dong Liang , Zhao Limin , Lin Xiaoping , Wu Changgui , Wu Bin , Yuan Yalian , Shi Fei , Zhang Ting , Zhou Jun , Xie Min , Fang Xiaoyu , Zhang Hongliang , Xiao Bing , Xian Mo , Wang Jian , Qiu Zhangwei , Lin Jie , Ji Bingbing , Zhou Yong , Li Yu , Liu Chunhong , Chen Yiping , Zeng Yiming , Liu Lingli , Hua Wen , Huang Huaqiong , Zhou Jiesen , Hu Yue , Che Luanqing , Ying Songmin , Chen Zhihua , Zhong Nanshan , Shen Huahao
Published: September 2020

Background

Asthmatic patients with chest tightness as their only presenting symptom (chest tightness variant asthma [CTVA]) have clinical characteristics of eosinophilic airway inflammation similar to those of classic asthma (CA); however, whether CTVA has similar response to antiasthma treatment as compared with CA remains unclear.

Objective

The response of 76 CTVA patients to standard asthma treatments with inhaled corticosteroids with long‐acting beta‐agonists was explored in a 52‐week multicenter, prospective, real‐world study.

Results

After 52 weeks of treatment with therapy regimens used for CA, the mean 5‐point Asthma Control Questionnaire (ACQ‐5) score decreased markedly from 1.38(first administration) to 0.71 (52 weeks, mean decrease: 0.674, 95%CI: 0.447‐0.900, P<.001).The mean asthma quality‐of‐life questionnaire (AQLQ) score increased from 5.77 (first administration) to 6.20 (52 weeks, mean increase: 0.441, 95% CI 0.258‐0.625, P<.001). Furthermore, at week 52, FVC, FEV1%, the diurnal variation in PEFand the PD20‐FEV1 were significantly improved. Subgroup analysis revealed that the patients at first administration in the responsive group had higher ACQ‐5 scores than those in the nonresponsive group (P < .05).

Conclusion

In conclusion, patients with CTVA had a good therapeutic response to the guideline‐recommended routine treatment (containing inhaled corticosteroids). The association between the treatment response and the severity of CTVA suggested that CTVA patients with higher ACQ‐5 scores had better therapeutic effects.
An institutional experience: A retrospective analysis of the effect of transitioning from follicular lesion of undetermined significance to atypia of undetermined significance with subclassified atypia on interobserver concordance, rates of neoplasia, and rates of malignancy
Authors: Kroll‐Wheeler Lauren , Cantley Richard , Pang Judy C. , Soles Brian S. , Smola Brian , Jing Xin , Lew Madelyn
Published: September 2020

Introduction

The rate of malignancy (ROM) in thyroid fine needle aspirations (FNA) classified under “atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS), including Hürthle cell type (HLUS)” category of The Bethesda system for reporting thyroid cytopathology (TBSRTC) in literature is highly variable. The 2018 TBSRTC was updated to note a preferred categorization of AUS cases into subcategories. This study evaluates the impact of AUS subclassification on rates of neoplasia (RON), rates of malignancy (ROM), and cytopathologist (CP) concordance.

Methods

93 thyroid FNAs previously diagnosed as FLUS or HLUS from January 1, 2013 to December 31, 2014 with subsequent surgical resection were identified. Four CPs reclassified these cases using TBSRTC AUS subcategories of follicular cells with architectural and/or cytologic atypia, predominantly Hürthle cells, and atypical lymphocytes. RON and ROM were calculated for each diagnostic subcategory for each CP.

Results

The original RON and ROM for FLUS cases were 31.4% and 15.1% and were 77.8% and 22.2% for HLUS cases. 10.8% of cases showed diagnostic concordance amongst the four CPs. The most frequently utilized subcategory was architectural atypia. RON ranges for architectural atypia, cytologic atypia, architectural and cytologic atypia, and predominantly Hürthle cells were 28.1% to 35.7%, 0% to 33.3%, 35.3% to 66.7%, and 57.1% to 87.5%. The range of ROM was 13.9% to 16.7%, 0% to 33%, 0% to 42.9%, and 0% to 25%, respectively.

Conclusion

RON for AUS predominantly Hürthle cells subcategory was higher than previously reported, which may indicate use for tailored patient management pathways. AUS subclassification can result in significant interobserver variability. Therefore, institutions may consider consensus/quality control sessions to optimize diagnostic concordance.
Phosphosite T674A mutation in kinesin family member 3A fails to reproduce tissue and ciliary defects characteristic of CILK1 loss of function
Authors: Gailey Casey D. , Wang Eric J. , Jin Li , Ahmadi Sean , Brautigan David L. , Li Xudong , Xu Wenhao , Scott Michael M. , Fu Zheng
Published: September 2020

Background

Kinesin family member 3A (KIF3A) is a molecular motor protein in the heterotrimeric kinesin‐2 complex that drives anterograde intraflagellar transport. This process plays a pivotal role in both biogenesis and maintenance of the primary cilium that supports tissue development. Ciliogenesis associated kinase 1 (CILK1) phosphorylates human KIF3A at Thr672. CILK1 loss of function causes ciliopathies that manifest profound and multiplex developmental defects, including hydrocephalus, polydactyly, shortened and hypoplastic bones and alveoli airspace deficiency, leading to perinatal lethality. Prior studies have raised the hypothesis that CILK1 phosphorylation of KIF3A is critical for its regulation of organ development.

Results

We produced a mouse model with phosphorylation site Thr674 in mouse Kif3a mutated to Ala. Kif3a T674A homozygotes are viable and exhibit no skeletal and brain abnormalities, and only mildly reduced airspace in alveoli. Mouse embryonic fibroblasts carrying Kif3a T674A mutation show a normal rate of ciliation and a moderate increase in cilia length.

Conclusion

These results indicate that eliminating Kif3a Thr674 phosphorylation by Cilk1 is insufficient to reproduce the severe developmental defects in ciliopathies caused by Cilk1 loss of function. This suggests KIF3A‐Thr672 phosphorylation by CILK1 is not essential for tissue development and other substrates are involved in CILK1 ciliopathies.
Big Data, Biomedical Research, and Ethics Review: New Challenges for IRBs
Authors: Ferretti Agata , Ienca Marcello , Hurst Samia , Vayena Effy
Published: September 2020

The increased use of big data in the medical field has shifted the way in which biomedical research is designed and carried out. The novelty of techniques and methods brought by big data research brings new challenges to institutional review boards (IRBs). Yet it is unclear if IRBs should be the responsible oversight bodies for big data research and, if so, which criteria they should use. A large but heterogenous set of ethics guidelines and normative responses have emerged to address these issues. In this study, we conducted a scoping review of soft‐law documents and guidelines with the aim of assessing ongoing normative efforts that are proliferating in this domain. We also synthesize a set of recurrent guidelines that could work as a baseline to create a harmonized process for big data research ethics.
Cardiovascular and renal effectiveness of empagliflozin in routine care in East Asia: Results from the EMPRISE East Asia study
Authors: Seino Yutaka , Kim Dae Jung , Yabe Daisuke , Tan Elise Chia‐Hui , Chung Wook‐Jin , Ha Kyoung Hwa , Nangaku Masaomi , Node Koichi , Klement Riho , Yasui Atsutaka , Lei Wei‐Yu , Lee Sunwoo , Kyaw Moe H. , Deruaz‐Luyet Anouk , Brodovicz Kimberly G. , H.‐H. Sheu Wayne ,   the EMPRISE East Asia study group
Published: September 2020

Aim

To evaluate the effectiveness of empagliflozin in clinical practice in East Asia in the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) East Asia study.

Materials and methods

Data were obtained from the Medical Data Vision database (Japan), National Health Insurance Service database (South Korea) and National Health Insurance database (Taiwan). Patients aged ≥ 18 years with type 2 diabetes initiating empagliflozin or a dipeptidyl peptidase‐4 (DPP‐4) inhibitor were 1:1 propensity score (PS) matched into sequentially built cohorts of new users naïve to both drug classes. This design reduces confounding due to switching treatments, time lag and immortal time biases. Outcomes included hospitalization for heart failure (HHF), end‐stage renal disease (ESRD) and all‐cause mortality. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional models, controlling for > 130 baseline characteristics in each data source and pooled by random‐effects meta‐analysis.

Results

Overall, 28 712 pairs of PS‐matched patients were identified with mean follow‐up of 5.7‐6.8 months. Compared with DPP‐4 inhibitors, the risk of HHF was reduced by 18% and all‐cause mortality was reduced by 36% with empagliflozin (HR 0.82; 95% CI 0.71‐0.94, and HR 0.64; 95% CI 0.50‐0.81, respectively). Reductions were consistent across countries, and in patients with and without baseline cardiovascular disease. ESRD was also significantly reduced with empagliflozin versus DPP‐4 inhibitors (HR 0.37; 95% CI 0.24‐0.58).

Conclusions

Empagliflozin treatment was associated with reduced risk for HHF, all‐cause mortality and ESRD compared with DPP‐4 inhibitors in routine clinical practice in Japan, South Korea and Taiwan.
A Facile Synthesis of 3‐(Arylthio)imidazo[1,2‐a]pyridin‐2(3H)‐ones from 2‐Aminopyridinium Bromides and Sodium Arenesulfinates
Authors: Saroj  , Rangan Krishnan , Kumar Anil
Published: September 2020

A simple and convenient method has been developed for the synthesis of 3‐(arylthio)imidazo[1,2‐a]pyridin‐2(3H)‐ones through a catalyst‐free reaction of 2‐aminopyridinium bromides with sodium arenesulfinates. A variety of 3‐(arylthio)imidazo[1,2‐a]pyridin‐2(3H)‐ones were obtained in moderate to excellent (33–85 %) yields. The developed protocol is operationally simple, exhibits a broad substrate scope with a wide range of functional groups, and is amenable for gram‐scale synthesis.
Increased Stability of Palladium‐Iridium‐Gold Electrocatalyst for the Hydrogen Oxidation Reaction in Polymer Electrolyte Membrane Fuel Cells
Authors: Allerston Laura K. , Hodgson David , Gibbs Christopher , Brett Dan J. L. , Rees Neil V.
Published: September 2020

The development of non‐Pt hydrogen oxidation reaction catalysts for hydrogen‐fuelled polymer electrolyte fuel cells allows for an overall reduction in electrode Pt content and therefore helps reduce the cost of devices, one of the biggest commercial challenges. Herein, a novel ternary alloy catalyst supported on carbon, PdIrAu/C, has been synthesised, characterised and compared to the binary PdIr/C to show how the addition of Au improves the stability of the catalyst. Transmission electron microscopy was utilised to analyse electrode structure as a function of the synthesis method, showing the optimum annealing temperature, of those tested, to be 400 °C, while inductively‐coupled plasma mass spectrometry provided analysis of the degradation of the two catalysts, confirming the PdIrAu/C catalyst is more stable at potentials similar to those at a fuel cell anode than PdIr/C.