bluuebunny/crossref_metadata_2025 huggingface dataset:
EIF2AK2 Missense Variants Associated with Early Onset Generalized Dystonia
Authors: Kuipers Demy J. S. , Mandemakers Wim , Lu Chin‐Song , Olgiati Simone , Breedveld Guido J. , Fevga Christina , Tadic Vera , Carecchio Miryam , Osterman Bradley , Sagi‐Dain Lena , Wu‐Chou Yah‐Huei , Chen Chiung C. , Chang Hsiu‐Chen , Wu Shey‐Lin , Yeh Tu‐Hsueh , Weng Yi‐Hsin , Elia Antonio E. , Panteghini Celeste , Marotta Nicolas , Pauly Martje G. , Kühn Andrea A. , Volkmann Jens , Lace Baiba , Meijer Inge A. , Kandaswamy Krishna , Quadri Marialuisa , Garavaglia Barbara , Lohmann Katja , Bauer Peter , Mencacci Niccolò E. , Lubbe Steven J. , Klein Christine , Bertoli‐Avella Aida M. , Bonifati Vincenzo
Published: November 2020

Objective

The study was undertaken to identify a monogenic cause of early onset, generalized dystonia.

Methods

Methods consisted of genome‐wide linkage analysis, exome and Sanger sequencing, clinical neurological examination, brain magnetic resonance imaging, and protein expression studies in skin fibroblasts from patients.

Results

We identified a heterozygous variant, c.388G>A, p.Gly130Arg, in the eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2) gene, segregating with early onset isolated generalized dystonia in 5 patients of a Taiwanese family. EIF2AK2 sequencing in 191 unrelated patients with unexplained dystonia yielded 2 unrelated Caucasian patients with an identical heterozygous c.388G>A, p.Gly130Arg variant, occurring de novo in one case, another patient carrying a different heterozygous variant, c.413G>C, p.Gly138Ala, and one last patient, born from consanguineous parents, carrying a third, homozygous variant c.95A>C, p.Asn32Thr. These 3 missense variants are absent from gnomAD, and are located in functional domains of the encoded protein. In 3 patients, additional neurological manifestations were present, including intellectual disability and spasticity. EIF2AK2 encodes a kinase (protein kinase R [PKR]) that phosphorylates eukaryotic translation initiation factor 2 alpha (eIF2α), which orchestrates the cellular stress response. Our expression studies showed abnormally enhanced activation of the cellular stress response, monitored by PKR‐mediated phosphorylation of eIF2α, in fibroblasts from patients with EIF2AK2 variants. Intriguingly, PKR can also be regulated by PRKRA (protein interferon‐inducible double‐stranded RNA‐dependent protein kinase activator A), the product of another gene causing monogenic dystonia.

Interpretation

We identified EIF2AK2 variants implicated in early onset generalized dystonia, which can be dominantly or recessively inherited, or occur de novo. Our findings provide direct evidence for a key role of a dysfunctional eIF2α pathway in the pathogenesis of dystonia. ANN NEUROL 2021;89:485–497
“Überschuss”‐Elektronen in LuGe
Authors: Freccero Riccardo , Hübner Julia‐Maria , Prots Yurii , Schnelle Walter , Schmidt Markus , Wagner Frank R. , Schwarz Ulrich , Grin Yuri
Published: November 2020

Das Monogermanid LuGe wurde durch Hochdruck‐Hochtemperatursynthese (5–15 GPa, 1023–1423 K) erhalten. Die Kristallstruktur wurde aus Einkristall‐Röntgenbeugungsdaten gelöst und verfeinert (Strukturtyp FeB, RaumgruppePnma,a=7.660 (2) Å,b=3.875 (1) Å undc=5.715 (2) Å, RF=0.036 für 206 symmetrie‐unabhängige Reflexe). Die Analyse der chemischen Bindung wurde mit Hilfe quantenchemischer Techniken im Ortsraum durchgeführt. Neben den erwarteten 2c‐Ge‐Ge‐Bindungen im Germaniumpolyanion wurde eine eher unerwartete vieratomige Wechselwirkung zwischen Lutetium‐Atomen gefunden, was auf die Bildung eines Polykations durch die überschüssigen Elektronen im System Lu3+(2b)Ge2−×1 e−hinweist. Trotz der reduzierten Valenzelektronen‐Konzentration von 3.5 folgt Lutetium‐Monogermanid der erweiterten 8‐N‐Regel durch die Bildung von Lutetium‐Lutetium‐Bindungen unter Verwendung der Elektronen, die nach der Bindungssättigung in der anionischen Ge‐Ge‐Zickzackkette übrigbleiben.
Large branchial arch cyst excision using superficial and deep cervical plexus blocks in a patient with severe comorbidities
Authors: Nutcharoen A. A. , Kim D. D. , Volio A. E. , Skolaris A. T. , Bhatnagar N. , Ayad S. S.
Published: November 2020

Branchial arches are embryologic structures that develop between the fourth and seventh gestational week. Anomalies may form if these structures fail to develop. The majority of cases are diagnosed during childhood, with surgical excision recommended to prevent risk of infection, growth or malignancy. We report an unusual case of a 72‐year‐old man with severe cardiac comorbidities who presented with a large second branchial arch cyst extending into the oropharynx. General anaesthesia to facilitate surgical excision was deemed too risky. Therefore, we performed successful ultrasound‐guided superficial and deep cervical plexus blocks as a sole mode of anaesthesia. This case highlights how regional anaesthesia can be utilised to facilitate surgery in high‐risk patients, as well as presenting an alternative for general anaesthesia.
Awake proning of a 2‐year‐old extubated child with severe COVID‐19 pneumonitis
Authors: Alseoudy M. M. , Abo Elfetoh M. A. , Alrefaey A. K.
Published: November 2020

With the progress of the coronavirus disease 2019 (COVID‐19) pandemic, available data suggest lower complications and disease severity in children and young patients. Despite most paediatric cases being mild in severity, some children require intensive care and mechanical ventilation due to the development of paediatric severe acute respiratory distress. The use of adjuvant therapies in severely ill paediatric patients has not been reported widely in the literature. Prone positioning in spontaneously breathing children has, to our knowledge, not yet been described. In our report, the trachea of a 2‐year‐old child was intubated, and he was mechanically ventilated for severe bilateral pneumonia. The infant and his mother tested positive for severe acute respiratory syndrome coronavirus disease‐2 (SARS‐CoV‐2) infection with reverse transcription‐polymerase chain reaction testing from nasopharyngeal swabs. Immediately after tracheal extubation, the child developed severe respiratory distress and refractory hypoxia. Awake prone position was employed as a rescue therapy for the management of post‐extubation hypoxia, resulting in a dramatic improvement in oxygenation. Prone positioning in the paediatric patient may improve oxygenation and can be a useful adjuvant for respiratory therapy either before, during or after invasive mechanical ventilation. Awake prone position may be considered as an option for the management of COVID‐19 in paediatric patients, but it requires patient cooperation.
Antimicrobial, computational, and molecular docking studies of Zn (II) and Pd (II) complexes derived from piperidine dithiocarbamate
Authors: Al‐Janabi Ahmed S.M. , Kadhim Mustafa M. , Al‐Nassiry Amenah I.A. , Yousef Tarek A.
Published: November 2020

Mixed ligand complexes of Zn (II) and Pd (II) have been prepared from piperidine dithiocarbamate (PipDT) and amine ligand {2,2′‐bipyridine (Bipy), 1,10‐phenanthroline (Phen), and 3‐aminopyridine (3Apy)} to afford complexes of the type [M(κ1‐PipDT)(κ2‐Bipy)] {MIIZn, Pd} (1,4), [M(κ1‐PipDT)(κ2‐Phen)] (2,5), and [M(κ1‐PipDT)(κ1‐3Apy)2] (3,6). The reaction of equivalent molar of sodium benzisothiazolinate (Nabit) or sodium saccharinate (Nasac) with cis‐[PdCl2(PPh3)2], followed by addition, sodium piperidine dithiocarbamate (NaPipDT) afforded complexes of the type trans‐[Pd(κ1‐PipDT)(κ1‐N‐bit)(PPh3)2] (7) and trans‐[Pd(κ1‐PipDT)(κ1‐N‐sac)(PPh3)2] (8). The obtained complexes were characterized by elemental analysis and spectroscopic techniques. The PipDT− was bonded as monodentate fashion via sulfur atom, whereas the diamine ligands were coordinated as bidentate chelating, while the 3Apy ligand bonded as monodentate mode through the nitrogen of heterocyclic ring. In complexes (7) and (8), the bit− and sac− ligand coordinated as monodentate through the nitrogen atom of heterocyclic ring. The antimicrobial activity of the complexes was tested. All the complexes showed moderate to good activity compared with standard antimicrobial. Moreover, the calculations of the density functional theory (DFT) were performed to estimate the thermal parameters, dipole moment, polarizability, and molecular electrostatic potential of the present complexes; in addition, Mulliken atomic charges of the complexes, total electron density (TED), electrostatic surface potential (ESP), lethal concentration (LC50), and docking studies as well as the descriptors of chemical reactivity were studied.
Fabrication and characterization of a novel Nafion‐PTFE composite hollow fiber membrane
Authors: Yu Sha , Zhu Zhihao , Zhou Meiqing , Yu Haijun , Kang Guodong , Cao Yiming
Published: November 2020

Nafion has been widely used in electrochemistry, but there are only a few reports on its application in other fields, such as, gas separation, even though it exhibits good performance. The primary reason for that is the high cost of Nafion and making a composite membrane with a thin Nafion layer is a potential solution to solve this problem. In this study, a novel Nafion‐PTFE composite hollow fiber membrane, which had a thin (~5 μm) and detect‐free Nafion layer on PTFE surface, without Nafion filling substrate pores was developed, differing from the reported ones in which Nafion resin was required to impregnate into porous PTFE membrane as thorough as possible to ensure the ion conductivity and operation stability. The surface morphology, crystallite, solubility in ethanol/water mixture, and water uptake of membranes were systemically investigated. The gas permeance tests were also conducted. The permeances of different gasses of prepared composite membranes were significantly enhanced compared with the commercial membranes due to the decrease of Nafion thicknesses, while the selectivity remained the same, verifying the detect‐free structure of Nafion layer on PTFE substrate. This study provided a good reference for the preparation and application of low‐cost Nafion composite membranes.
Isolation and expression of five genes in the mevalonate pathway of the Chinese white pine beetle, Dendroctonus armandi (Curculionidae: Scolytinae)
Authors: Sun Yaya , Dai Lulu , Kang Xiaotong , Fu Danyang , Gao Haiming , Chen Hui
Published: November 2020

The Chinese white pine beetle Dendroctonus armandi (Tsai and Li) is a significant pest of the Qinling and Bashan Mountains pine forests of China. The Chinese white pine beetle can overcome the defences of Chinese white pine Pinus armandi (Franch) through pheromone‐assisted aggregation that results in a mass attack of host trees. We isolated five full‐length complementary DNAs encoding mevalonate pathway‐related enzyme genes from the Chinese white pine beetle (D. armandi), which are acetoacetyl‐CoA thiolase (AACT), geranylgeranyl diphosphate synthase (GGPPS), mevalonate kinase (MK), mevalonate diphosphate decarboxylase (MPDC), and phosphomevalonate kinase (PMK). Bioinformatic analyses were performed on the full‐length deduced amino acid sequences. Differential expression of these five genes was observed between sexes, and within these significant differences among topically applied juvenile hormone III (JH III), fed on phloem of P. armandi, tissue distribution, and development stage. Mevalonate pathway genes expression were induced by JH III and feeding.
Psychometric properties of the stress control mindset measure in university students from Australia and the UK
Authors: Keech Jacob J. , Orbell Sheina , Hagger Martin S. , O’Callaghan Frances V. , Hamilton Kyra
Published: November 2020

Introduction

Beliefs about the consequences of stress, stress mindsets, are associated with health and performance outcomes under stress. This article reports the development and examination of the psychometric properties of a measure of stress mindset: The Stress Control Mindset Measure (SCMM). The measure is consistent with theory on mindsets about self‐attributes and conceptualizes stress mindset as the extent to which individuals endorse beliefs that stress can be enhancing.

Methods

The study adopted a correlational cross‐sectional survey design in two student samples. Undergraduate students from an Australian university (Sample 1, N = 218) and a UK university (Sample 2, N = 214) completed the SCMM and measures of health and well‐being outcomes.

Results

Confirmatory factor analyses supported a four‐factor structure and strict measurement invariance across samples (ΔCFI < 0.01). Reliability, convergent validity, discriminant validity, and concurrent validity of the overall SCMM were supported in both samples. Incremental validity was supported for most outcomes, accounting for significantly more variance (between 2.2% and 5.9%) in health and well‐being outcomes than an existing measure.

Conclusions

Current data provide preliminary support for the SCMM as a reliable and valid measure with good psychometric properties and theoretically consistent relations with health outcomes under stress. Findings provide initial evidence supporting the potential utility of the SCMM in future research examining relations between stress mindsets and health and performance outcomes.
Investigation of drugs affecting hypertension in bevacizumab‐treated patients and examination of the impact on the therapeutic effect
Authors: Yagi Kenta , Mitstui Marin , Zamami Yoshito , Niimura Takahiro , Izawa‐Ishizawa Yuki , Goda Mitsuhiro , Chuma Masayuki , Fukunaga Kimiko , Shibata Takahiro , Ishida Shunsuke , Sakurada Takumi , Okada Naoto , Hamano Hirofumi , Horinouchi Yuya , Ikeda Yasumasa , Yanagawa Hiroaki , Ishizawa Keisuke
Published: November 2020

Background

In patients treated with bevacizumab, hypertension may be a biomarker of therapeutic efficacy. However, it is not clear whether drugs that control blood pressure influence bevacizumab's efficacy. In this study, we investigated drugs that may affect hypertension in bevacizumab‐treated patients and examined the impact on the therapeutic effect.

Patients and methods

We analyzed 3,724,555 reports from the third quarter of 2010 to the second quarter of 2015. All data were obtained from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) analysis. In this retrospective cohort study, we investigated a total of 58 patients diagnosed with colorectal cancer and treated for the first time with bevacizumab containing XELOX or mFOLFOX6 at The University of Tokushima Hospital between January 2010 and December 2015. The effect of the treatment was evaluated according to Response Evaluation Criteria in Solid Tumors version 1.0. Thereafter, the effect was confirmed using Gene Expression Omnibus (GEO) and cultured cells.

Results

There are few reports in FAERS of hypertension in patients treated with omeprazole on bevacizumab. Based on the chart review, patients who used proton pump inhibitors (PPI) had a lower response to treatment than those who did not (response rate: 25% vs 50%). Furthermore, experiments on GEO and cell lines suggested that induction of vascular endothelial growth factor (VEGF) gene expression by PPIs is the cause of the reduced therapeutic effect.

Conclusion

PPIs prevent hypertension in bevacizumab‐treated patients but may reduce bevacizumab's anti‐tumoral effects by inducing VEGF expression.
Design and in Vitro Characterization of Tricyclic Benzodiazepine Derivatives as Potent and Selective Antileukemic Agents
Authors: Mieczkowski Adam , Frączyk Tomasz , Psurski Mateusz , Wińska Patrycja , Siedlecki Paweł , Dziełak Monika , Trzybiński Damian , Wilczek Marcin , Bagiński Maciej , Bieszczad Bartosz , Woźniak Krzysztof
Published: November 2020

Currently available chemotherapeutic treatments for blood cancers (leukemia) usually have strong side effects. More selective, efficient, and less toxic anticancer agents are needed. We synthesized seven, new, optically pure (12aS)‐1,3,4,12a‐tetrahydropyrazino[2,1‐c][1,4],12(2H,11H)‐dione derivatives and examined their cytotoxicity towards eight cancer cell lines, including urinary bladder (TCC‐SUP, UM‐UC‐3, KU‐19‐9), colon (LoVo), and breast (MCF‐7, MDA‐MB‐231) cancer representatives, as well as two leukemic cell lines (MV‐4‐11, CCRF‐CEM) and normal murine fibroblasts (Balb/3T3) as reference cell line. Three of the seven newly‐obtained compounds ((12aS)‐8‐bromo‐2‐(3‐phenylbenzoyl)‐1,3,4,12a‐tetrahydropyrazino[2,1‐c][1,4],12(2H,11H)‐dione, (12aS)‐8,9‐dimethoxy‐2‐(4‐phenylbenzoyl)‐1,3,4,12a‐tetrahydropyrazino[2,1‐c][1,4],12(2H,11H)‐dione and (12aS)‐8‐nitro‐2‐(4‐phenylbenzoyl)‐1,3,4,12a‐tetrahydropyrazino[2,1‐c][1,4],12(2H,11H)‐dione, showed enhanced activity and selectivity toward the leukemic MV‐4‐11 cell lines when compared to our previously reported compounds, with IC50 values in the range of 2.9–5.6 μM. Additionally, (12aS)‐9‐nitro‐2‐(4‐phenylbenzoyl)‐1,3,4,12a‐tetrahydropyrazino[2,1‐c][1,4],12(2H,11H)‐dione exhibited a strong cytotoxic effect against the leukemic CCRF‐CEM (IC50=6.1 μM) and MV‐4‐11 (IC50=11.0 μM) cell lines, a moderate cytotoxic effect toward other tumor lines (IC50=31.8–55.0 μM) and very weak cytotoxic effect toward the Balb/3T3 reference cell lines. Selected compounds were further evaluated for their potential to induce apoptotic cell death in MV‐4‐11 cells by measuring caspase‐3 activity. We also established the crystal structure of three products and investigated the effect of 22 derivatives of 1,3,4,12a‐tetrahydropyrazino[2,1‐c][1,4],12(2H,11H)‐dione on the activity of the cancer‐associated enzyme autotaxin. All compounds proved to be weak inhibitors of autotaxin, although some (R) and (S) enantiomers had Ki values of 10–19 μM. The obtained results showed that the tested compounds exhibited a selective antileukemic effect, which appeared not to be related directly to autotaxin. Molecular targets responsible for this effect remain to be identified. The newly obtained compounds can be used in the search for new, selective anticancer therapies.
A systematic review and meta‐analysis of impact of baseline thrombocytopenia on cardiovascular outcomes and mortality in patients undergoing percutaneous coronary intervention
Authors: Ahsan Muhammad J. , Lateef Noman , Latif Azka , Malik Saad U. , Batool Syeda S. , Fazeel Hafiz M. , Ahsan Mohammad Z. , Faizi Zaheer , Thandra Abhishek , Mirza Mohsin , Kabach Amjad , Core Michael Del
Published: November 2020

Background

Thrombocytopenia (TP) is associated with higher incidence of bleeding in the setting of percutaneous coronary intervention (PCI) leading to increased morbidity and mortality. Herein, we report a meta‐analysis evaluating the effects of baseline thrombocytopenia (bTP) on cardiovascular outcomes in patients undergoing PCI.

Methods

Literature search was performed using PubMed, Embase, Cochrane library and clinicaltrials.gov from inception till October 2019. Patients were divided into two groups: Patients with (a) no Thrombocytopenia (nTP) (b) bTP before PCI. Primary endpoints were in‐hospital, and all‐cause mortality rates at the longest follow‐up. The main summary estimate was random effects risk ratio (RR) with 95% confidence intervals (CIs).

Results

A total of 6,51,543 patients from 10 retrospective studies were included. There was increased in‐hospital all‐cause mortality (RR 2.58 [1.7–3.8], p < .001) and bleeding (RR 2.37 [1.41–3.98], p < .005), in the bTP group compared to the nTP group. There was no difference for in‐hopsital major adverse cardiovascular outcomes (MACE) (RR 1.38 [0.94–2.0], p < .10), post‐PCI MI (RR 1.17 [0.9–1.5], p = .19) and TVR (RR 1.65 [0.8–3.6], p = .21), respectively. Outcomes at longest follow‐up showed increased incidence of all‐cause mortality (RR 1.86 [1.2–2.9], p < .006) and bleeding (RR 1.72 [1.1–2.9], p = .04) in bTP group, while there was no significant difference for post‐PCI MI (RR 1.07 [0.91–1.3], p = .42), MACE (RR 1.86 [0.69–1.8], p = .68) and TVR (RR 1.1 [0.9–1.2], p = .93) between both groups.

Conclusions

bTP in patients undergoing PCI is associated with increased mortality and predicts risk of bleeding.
Adsorption of Iodide and Bromide on Au(111) Electrodes from Aprotic Electrolytes: Role of the Solvent
Authors: Shatla Ahmed S. , Bawol Pawel P. , Baltruschat Helmut
Published: November 2020

The adsorption of iodide and bromide ions on Au(111) single‐crystal electrodes in three organic solvents [propylene carbonate (PC), diglyme (DG), and dimethyl sulfoxide (DMSO)] was studied by differential capacity measurements, cyclic voltammetry (CV), X‐ray photoelectron spectroscopy (XPS) and electrochemical impedance spectroscopy (EIS). The anion adsorption charge in DMSO is approximately half as large as in propylene carbonate and that in water. Quantification of the adsorbed iodide amount from XPS spectra confirms the coverage estimated from the adsorption charge in CVs. As expected, the rate of anion adsorption on Au(111) is higher for I− than for Br− due to better solvation of the latter. The extent of anion adsorption on Au(111) electrode decreases and the corresponding adsorption rate decreases in the solvent order H2O>PC>DG>DMSO. Since the donor number (DN) of the solvent increases in the same order (PC<DG<DMSO), we assume that it plays a decisive role since it determines the chemical interaction of the solvent with the metal surface. Moreover, the adsorption rate of iodide and the extent of its adsorption is increased with increasing water content in PC and DMSO. This effect, and the much higher adsorption rate in water is explained by the closer approach of the solvated halogen ion to the surface and the resulting stronger interaction of the transition state with the electrode.
A Domino Fusion of an Organic Ligand Depended on Metal‐Induced and Oxygen Insertion, Unraveled by Crystallography, Mass Spectrometry, and DFT Calculations
Authors: Chen Jin‐Ming , Peng Liang , Zhou Fu‐Fang , Liu Bin , Hou Cheng , Li Jia‐Wei , Huang Zhou , Kurmoo Mohamedally , Zeng Ming‐Hua
Published: November 2020

Herein, the reaction of (1‐methyl‐1 H‐benzo[d]imidazol‐2‐yl)methanamine (L1) with Co(H2O)6Cl2, in CH3CN at 120 °C, leading to the 2,3,5,6‐tetrakis(1‐methyl‐1 H‐benzo[d]imidazol‐2‐yl)pyrazine (3), isolated as a dimeric cluster {[CoII2(3)Cl4]⋅2 CH3CN} (2), is reported. When O2 and H2O are present, (1‐methyl‐1 H‐benzo[d]imidazole‐2‐carbonyl)amide (HL1′) is first formed and crystallized as [CoIII(L1)2(L1′)]Cl2⋅2 H2O (4) before fusion of HL1′ with L1, giving 1‐methyl‐N‐(1‐methyl‐1 H‐benzo[d]imidazol‐2‐carbonyl)‐1 H‐benzo[d]imidazol‐2‐carboxamide (HL2′′) forming a one‐dimensional (1D) chain of [CoII3(L2′′)2Cl4]n (5). The combination of crystallography and mass spectrometry (ESI‐MS) of isolated crystals and the solutions taken from the reaction as a function time reveal seven intermediate steps leading to 2, but six steps for 5, for which a different sequence takes place. Control and isotope labeling experiments confirm the two carbonyl oxygen atoms in 5 originate from both air and water. The dependence on the metals, compared with FeCl3⋅6 H2O leading to a stable triheteroarylmethyl radical, is quite astounding, which could be attributed to the different oxidation states of the metals and coordination modes confirmed by DFT calculations. This metal and valence dependent process is a very useful way for selectively obtaining these large molecules, which are unachievable by common organic synthesis.
Replacing the Rhamnose‐Xylose Moiety of QS‐21 with Simpler Terminal Disaccharide Units Attenuates Adjuvant Activity in Truncated Saponin Variants
Authors: Fuentes Roberto , Ruiz‐de‐Angulo Ane , Sacristán Nagore , Navo Claudio Daniel , Jiménez‐Osés Gonzalo , Anguita Juan , Fernández‐Tejada Alberto
Published: November 2020

Adjuvants are key immunostimulatory components in vaccine formulations, which improve the immune response to the co‐administered antigen. The saponin natural product QS‐21 is one of the most promising immunoadjuvants in the development of vaccines against cancer and infectious diseases but suffers from limitations that have hampered its widespread human use. Previous structure–activity relationship studies have identified simplified saponin variants with truncated carbohydrate chains, but have not focused on the influence of the linear oligosaccharide domain of QS‐21 in adjuvant activity. Herein, an expeditious 15‐step synthesis of new linear trisaccharide variants of simplified QS‐21‐derived adjuvants is reported, in which the complex terminal xylose‐rhamnose moiety has been replaced with commercially available, simpler lactose and cellobiose disaccharides in a β‐anomeric configuration. In vivo immunological evaluation of the synthetic saponins showed attenuated antibody responses, highlighting the negative impact of such carbohydrate modifications on adjuvant activity, which could be associated with higher saponin conformational flexibility.
Understanding the C−F Bond Activation Mediated by Frustrated Lewis Pairs: Crucial Role of Non‐covalent Interactions
Authors: Cabrera‐Trujillo Jorge Juan , Fernández Israel
Published: November 2020

The activation of a single C−F bond in di‐ and trifluoromethyl groups by frustrated Lewis pairs (FLPs) has been computationally explored by means of Density Functional Theory calculations. It is found that in this activation reaction the FLP partners exhibit a peculiar cooperative action, which is markedly different from related FLP‐mediated processes, and where non‐covalent interactions established between the Lewis base and the substrate play a decisive role. In addition, the process proceeds through the intermediacy of a hypervalent species featuring a pentacoordinate carbon atom, which is rare in the chemistry of FLPs. The physical factors controlling this process as well as the bonding situation of these hypervalent intermediates have been quantitatively analyzed in detail by using state‐of‐the‐art computational methods to not only rationalize the mechanism of the transformation but also to guide experimentalists towards the realization of these so far elusive hypervalent systems.
Interdisciplinary care of pediatric oncology patients in Central America and the Caribbean
Authors: Graetz Dylan E. , Chen Yichen , Devidas Meenakshi , Antillon‐Klussmann Federico , Fu Ligia , Quintero Karina , Fuentes‐Alabi Soad L. , Gassant Pascale Y. , Kaye Erica C. , Baker Justin N. , Rodriguez Galindo Carlos , Mack Jennifer W.
Published: November 2020

Background

Interdisciplinary teamwork supports high‐quality cancer care and effective utilization of limited resources. This study purposed to examine the value, structure, process, and effectiveness of interdisciplinary care (IDC) among pediatric oncology providers in low‐income and middle‐income countries in Central America and the Caribbean.

Methods

A cross‐sectional survey was disseminated to pediatric oncology providers at 5 centers participating in the Pediatric Hematology‐Oncology Association of Central America. The survey included previously validated items and novel questions assessing the value (importance), structure (multidisciplinary meeting attendance), process (team climate), and effectiveness (job satisfaction, quality of care and communication) of IDC.

Results

The survey was completed by 174 providers, including 22 oncologists, 9 pathologists, 9 radiologists, 5 radiation oncologists, 12 surgeons, 35 subspecialists, 60 nurses, 20 psychosocial providers, and 2 other staff. Participants agreed that IDC benefits team members (95%) and patients (96%). IDC structure and processes varied across the region. Multidisciplinary meeting attendance differed by center (P = .005) and discipline (P < .0001). Participants who frequently attended multidisciplinary meetings reported a more positive team climate (P = .0003). Team climate was positively associated with job satisfaction (P < .001). In multivariable analyses, team climate was predictive of an improved perception of communication between professionals (P < .0001), with families (P < .0001), and with patients (P = .0005), as well as with quality of the care environment (P = .006) and overall care quality (P < .0001).

Conclusions

Nearly all surveyed participants valued IDC, and the structure and processes supporting IDC varied by center. Associations between a collaborative professional climate, job satisfaction, and the perception of quality care encourage continued investigation and prioritization of IDC in these settings.
Gait speed, survival, and recommended treatment intensity in older adults with blood cancer requiring treatment
Authors: Hantel Andrew , DuMontier Clark , Odejide Oreofe O. , Luskin Marlise R. , Sperling Adam S. , Hshieh Tammy , Chen Richard , Soiffer Robert , Driver Jane A. , Abel Gregory A.
Published: November 2020

Background

Brief measures of physical function such as gait speed may be useful to optimize treatment intensity for older adults who have blood cancer; however, little is known about whether such assessments are already captured within oncologists' “gestalt” assessments.

Methods

Gait speed was assessed in 782 patients ≥75 years of age who had blood cancer, with results reported to providers after treatment decisions were made; 408 patients required treatment when different intensities were available per National Comprehensive Cancer Network (NCCN) guidelines. We performed structured abstractions of treatment intensity recommendations into standard intensity, reduced intensity, or supportive care, based on NCCN guidelines. We modeled gait speed and survival using Cox regression and performed ordinal logistic regression to assess predictors of NCCN‐based categorizations of oncologists' treatment intensity recommendations, including gait speed.

Results

The median survival by gait speed category was 10.8 months (<0.4 m/s), 18.6 months (0.4‐0.6 m/s), 34.0 months (0.6‐0.8 m/s), and unreached (>0.8 m/s). Univariable hazard ratios (HRs) for death increased for each lower category compared with ≥0.8 m/s (0.6‐0.8 m/s: HR, 1.76; 0.4‐0.6 m/s: HR, 2.30; <0.4 m/s: HR, 3.31). Gait speed predicted survival in multivariable Cox regression (all P < .05). In multivariable models including age, sex, and Eastern Cooperative Oncology Group performance status, gait speed did not predict oncologists' recommended treatment intensity (all P > .05) and did not add to a base model predicting recommended treatment intensity.

Conclusion

In older adults with blood cancer who presented for treatment, gait speed predicted survival but not treatment intensity recommendation. Incorporating gait speed into decision making may improve optimal treatment selection.
Enhancement of 1T‐MoS2 Superambient Temperature Stability and Hydrogen Evolution Performance by Intercalating a Phenanthroline Monolayer
Authors: Goloveshkin Alexander S. , Lenenko Natalia D. , Naumkin Alexander V. , Pereyaslavtsev Alexander Yu. , Grigorieva Anastasia V. , Shapovalov Aleksei V. , Talanova Valeria N. , Polezhaev Alexander V. , Zaikovskii Vladimir I. , Novikov Valentin V. , Korlyukov Alexander A. , Golub Alexandre S.
Published: November 2020

Metastable modification of MoS2 (1T) is widely recognized as a hopeful non‐precious electrocatalyst in hydrogen production. This paper describes an approach to impart a superambient temperature stability to 1T‐MoS2 by incorporating it in 2D hybrid architecture with cationic monomolecular phenanthrolinium (PhenH+) hydrate layers. The atomic structure and bonding interactions of the assembled architecture revealed by PXRD, TEM, XPS, Raman and UV‐Vis spectroscopy data coupled with DFT calculations and quantum theory of atoms in molecules (QTAIM) analysis suggest that the 1T‐MoS2 sheets are involved in strong bonding with the PhenH‐H2O layers. This results in a highly stable layered system, which is kept intact in 0.5 M sulfuric acid electrolyte and tolerates superambient temperature heating. As compared with pure 1T‐MoS2, the compound with a phenanthroline interlayer provides greater activity and better current‐voltage efficiency in electrocatalytic hydrogen evolution after heating treatment owing to stabilization of the 1T phase. The obtained results could be useful for the design of novel electrocatalytic devices exploiting 1T‐MoS2 modification.
A Guide to Fluorescence Lifetime Microscopy and Förster's Resonance Energy Transfer in Neuroscience
Authors: Liput Daniel J. , Nguyen Tuan A. , Augustin Shana M. , Lee Jeong Oen , Vogel Steven S.
Published: November 2020

Fluorescence lifetime microscopy (FLIM) and Förster's resonance energy transfer (FRET) are advanced optical tools that neuroscientists can employ to interrogate the structure and function of complex biological systems in vitro and in vivo using light. In neurobiology they are primarily used to study protein‐protein interactions, to study conformational changes in protein complexes, and to monitor genetically encoded FRET‐based biosensors. These methods are ideally suited to optically monitor changes in neurons that are triggered optogenetically. Utilization of this technique by neuroscientists has been limited, since a broad understanding of FLIM and FRET requires familiarity with the interactions of light and matter on a quantum mechanical level, and because the ultra‐fast instrumentation used to measure fluorescent lifetimes and resonance energy transfer are more at home in a physics lab than in a biology lab. In this overview, we aim to help neuroscientists overcome these obstacles and thus feel more comfortable with the FLIM‐FRET method. Our goal is to aid researchers in the neuroscience community to achieve a better understanding of the fundamentals of FLIM‐FRET and encourage them to fully leverage its powerful ability as a research tool. Published 2020. U.S. Government.
Pharmacogenetics at Scale: An Analysis of the UK Biobank
Authors: McInnes Gregory , Lavertu Adam , Sangkuhl Katrin , Klein Teri E. , Whirl‐Carrillo Michelle , Altman Russ B.
Published: November 2020

Pharmacogenetics (PGx) studies the influence of genetic variation on drug response. Clinically actionable associations inform guidelines created by the Clinical Pharmacogenetics Implementation Consortium (CPIC), but the broad impact of genetic variation on entire populations is not well understood. We analyzed PGx allele and phenotype frequencies for 487,409 participants in the UK Biobank, the largest PGx study to date. For 14 CPIC pharmacogenes known to influence human drug response, we find that 99.5% of individuals may have an atypical response to at least 1 drug; on average they may have an atypical response to 10.3 drugs. Nearly 24% of participants have been prescribed a drug for which they are predicted to have an atypical response. Non‐European populations carry a greater frequency of variants that are predicted to be functionally deleterious; many of these are not captured by current PGx allele definitions. Strategies for detecting and interpreting rare variation will be critical for enabling broad application of pharmacogenetics.
Grass Gazers: Using citizen science as a tool to facilitate practical and online science learning for secondary school students during the COVID‐19 lockdown
Authors: Van Haeften Shanice , Milic Andelija , Addison‐Smith Beth , Butcher Christopher , Davies Janet Mary
Published: November 2020

The coronavirus disease of 2019 (COVID‐19) pandemic has impacted educational systems worldwide during 2020, including primary and secondary schooling. To enable students of a local secondary school in Brisbane, Queensland, to continue with their practical agricultural science learning and facilitate online learning, a “Grass Gazers” citizen science scoping project was designed and rapidly implemented as a collaboration between the school and a multidisciplinary university research group focused on pollen allergy. Here, we reflect on the process of developing and implementing this project from the perspective of the school and the university. A learning package including modules on pollen identification, tracking grass species, measuring field greenness, using a citizen science data entry platform, forensic palynology, as well as video guides, risk assessment and feedback forms were generated. Junior agriculture science students participated in the learning via online lessons and independent data collection in their own local neighborhood and/or school grounds situated within urban environments. The university research group and school coordinator, operating in their own distributed work environments, had to develop, source, adopt, and/or adapt material rapidly to meet the unique requirements of the project. The experience allowed two‐way knowledge exchange between the secondary and tertiary education sectors. Participating students were introduced to real‐world research and were able to engage in outdoor learning during a time when online, indoor, desk‐based learning dominated their studies. The unique context of restrictions imposed by the social isolation policies, as well as government Public Health and Department of Education directives, allowed the team to respond by adapting teaching and research activity to develop and trial learning modules and citizen science tools. The project provided a focus to motivate and connect teachers, academic staff, and school students during a difficult circumstance. Extension of this citizen project for the purposes of research and secondary school learning has the potential to offer ongoing benefits for grassland ecology data acquisition and student exposure to real‐world science.
Evaluation of foliar fungus‐mediated interactions with below and aboveground enemies of the invasive plant Ageratina adenophora
Authors: Fang Kai , Chen Li‐Min , Zhang Han‐Bo
Published: November 2020

Plant–fungal associations are frequently key drivers of plant invasion success. Foliar fungi can benefit their invasive hosts by enhancing growth promotion, disease resistance and environmental stress tolerance. However, the roles of foliar fungi may vary when a given invasive plant faces different stresses. In this study, we designed three independent experiments to evaluate the effects of a foliar fungus, Colletotrichum sp., on the growth performance of the invasive plant Ageratina adenophora under different soil conditions, as well as the responses of A. adenophora to the foliar fungal pathogen Diaporthe helianthi and to herbivory. We found that the soil type was the most influential factor for the growth of A. adenophora. The role of the foliar fungus Colletotrichum sp. varied in the different soil types but generally adversely affected leaf development in A. adenophora. Colletotrichum sp. may be a weak latent foliar pathogen that can enhance the pathogenicity of D. helianthi on leaves of A. adenophora and marginally reduce signs of herbivory by natural insects in the wild on A. adenophora seedlings. In general, the benefits of the foliar fungus Colletotrichum to the fitness of A. adenophora are not significant in the context of this experimental design. However, our data highlight the need to consider both aboveground and belowground biota in different soil habitats when evaluating the effects of foliar fungi.
Endothelial dysfunction and C‐reactive protein predict the incidence of heart failure in hypertensive patients
Authors: Maio Raffaele , Perticone Maria , Suraci Edoardo , Sciacqua Angela , Sesti Giorgio , Perticone Francesco
Published: November 2020

Aims

Endothelial dysfunction and heart failure are associated, but no prospective studies demonstrated that impaired endothelium‐dependent vasodilation predicts incident heart failure. We designed this study to test whether endothelial dysfunction is associated with incident heart failure in a group of hypertensives.

Methods and results

We enrolled 735 White never‐treated hypertensive outpatients free from heart failure, diabetes, chronic kidney disease, and previous cardiovascular events. Endothelium‐dependent vasodilation was investigated by intra‐arterial infusion of acetylcholine, and laboratory determinations were obtained by standard procedures. During the follow‐up [median 114 months (range 26–206)], there were 208 new cases of heart failure (3.1 events/100 patient‐years). Dividing the study population in progressors and non‐progressors, we observed that progressors were older, showed a higher prevalence of being female, and had a higher baseline heart rate, glucose, insulin, Homeostatic Model Assessment (HOMA), creatinine, and high‐sensitivity C‐reactive protein (hs‐CRP) mean values, while estimated glomerular filtration rate and maximal acetylcholine‐stimulated forearm blood flow were lower. In the multiple Cox regression analysis, female gender [hazard ratio (HR) = 1.454, 95% CI = 1.067–1.981], fasting glucose (HR = 1.186, 95% CI = 1.038–1.357), hs‐CRP (HR = 1.162, 95% CI = 1.072–1.259), HOMA (HR = 1.124, 95% CI = 1.037–1.219), acetylcholine‐stimulated forearm blood flow (HR = 0.779, 95% CI = 0.695–0.874), and estimated glomerular filtration rate (HR = 0.767, 95% CI = 0.693–0.849) maintained an independent association with the outcome. Successively, testing the interaction between forearm blood flow and hs‐CRP, we observed that patients who have hs‐CRP values above the median and forearm blood flow under the median show a higher risk of developing heart failure (HR = 7.699, 95% CI = 4.407–13.451).

Conclusions

The present data demonstrate that an impaired endothelium‐dependent vasodilation and hs‐CRP predict development of incident heart failure in hypertensives.
Transgenerational effects in offspring of chronically irradiated populations of Drosophila melanogaster after the Chernobyl accident
Authors: Yushkova Elena , Bashlykova Ludmila
Published: November 2020

The zone of the Chernobyl nuclear disaster represents the largest area of chronic low‐intensity radioactive impact on the natural ecosystems. The effects of chronic low‐dose irradiation for natural populations of organisms and their offspring are unknown. The natural populations of Drosophila melanogaster sampled in 2007 in Chernobyl sites with different levels of radiation contamination were investigated. The offspring of specimens from these populations were studied under laboratory conditions to assess the effects of parental irradiation on the mutation process and survival of the offspring. Transgenerational effects of radioactive contamination were observed at the level of gross chromosomal rearrangements (dominant lethal mutations). The frequency of point/gene mutations (recessive sex‐linked lethal mutations) of the offspring of the irradiated parents corresponded to the actual level of spontaneous mutations. The survival rate of offspring decreased over 160 generations and significantly correlated with the dominant lethal mutation levels. Our results provide a compelling evidence that other factors (distance from the Chernobyl Nuclear Power Plant, time after the initial exposure, selection site and origin of population) can affect the changes in the levels of the studied parameters along with the parental radiation exposure. They can also make a significant contribution to the health of the offspring of animals exposed to radioactive contamination. These data should be useful for future radioecological studies which will clarify the true mechanisms of transgenerational inheritance and generation of mutations to the offspring of chronically irradiated animals and their reactions to the interaction of various environmental factors.
Towards a Greener and Scalable Synthesis of Na2Ti6O13 Nanorods and Their Application as Anodes in Batteries for Grid‐Level Energy Storage
Authors: De Carolis Dario M. , Vrankovic Dragoljub , Kiefer Samira A. , Bruder Enrico , Dürrschnabel Michael Thomas , Molina‐Luna Leopoldo , Graczyk‐Zajac Magdalena , Riedel Ralf
Published: November 2020

Grid applications require high power density (for frequency regulation, load leveling, and renewable energy integration), achievable by combining multiple batteries in a system without strict high capacity requirements. For these applications however, safety, cost efficiency, and the lifespan of electrode materials are crucial. Titanates, safe and longevous anode materials providing much lower energy density than graphite, are excellent candidates for this application. The innovative molten salt synthesis approach proposed in this work provides exceptionally pure Na2Ti6O13 nanorods generated at 900–1100 °C in a yield ≥80 wt%. It is fast, cost‐efficient, and suitable for industrial upscaling. Electrochemical tests reveal stable performance providing capacities of ≈100 mA h g−1 (Li) and 40 mA h g−1 (Na). Increasing the synthesis temperature to 1100 °C leads to a capacity decrease, most likely resulting from 1) the morphology/volume change with the synthesis temperature and 2) distortion of the Na2Ti6O13 tunnel structure indicated by electron energy‐loss and Raman spectroscopy. The suitability of pristine Na2Ti6O13 as the anode for grid‐level energy storage systems has been proven a priori, without any performance‐boosting treatment, indicating considerable application potential especially due to the high yield and low cost of the synthesis route.
A history of Hanford tank waste, implications for waste treatment, and disposal
Authors: Colburn Heather A. , Peterson Reid A.
Published: November 2020

More than 40 years of plutonium processing have left almost 56 million gallons of mixed radioactive waste sequestered in 177 underground tanks on the Hanford Site. Three different processing technologies were employed for plutonium purification in addition to uranium scavenging and fission product removal from the tank waste. All of these chemical processes have contributed to a complex waste stream that varies from tank to tank that presents downstream processing challenges to render the waste into a safe form for long‐term storage. The current disposition pathway for Hanford tank waste is vitrification. To maximize waste loading and minimize the number of high‐level waste canisters stored in a geologic repository, pretreatment of the waste is required. Both pretreatment and vitrification operations are impacted by the waste composition.
Selection of seismic intensity measures for prescribed limit states using alternative nonlinear dynamic analysis methods
Authors: Ebrahimian Hossein , Jalayer Fatemeh
Published: November 2020

In performance‐based earthquake engineering, the suitability of an intensity measure (IM) is expressed through its efficiency and sufficiency. An efficient IM leads to a small record‐to‐record variability in the estimation of demand given seismic intensity. A sufficient IM is one that renders the estimation of demand for all intensity levels independent of all other ground motion parameters. Given that establishing sufficiency is not a trivial task, the relative sufficiency measure (RSM) has been proposed previously based on information theory concepts. RSM can be employed for quantifying the relative sufficiency of an IM with respect to another IM by the amount of extra information that it relays on average about the ground motion for the estimation of a demand parameter of interest. RSM has been so far conditioned on a linear logarithmic regression probability model, better known as the Cloud Analysis (CA), which relies on unscaled ground‐motion records. This work lays out the methodology for estimating both the efficiency and RSM in terms of the damage measure directly (instead of demand parameter) and by employing alternative nonlinear dynamic analysis procedures (NDAPs), such as, a modified version of CA that considers the collapse‐cases explicitly and the incremental dynamic analysis. It is demonstrated that the RSM can be sensitive to the NDAP employed, while it does not demonstrate significant sensitivity to the limit state of interest. An alternative measure of efficiency (known in literature as proficiency), directly measured as the dispersion in the fragility curve, shows more sensitivity to the limit state.