bluuebunny/crossref_metadata_2025 huggingface dataset:
In situ encapsulated subnanometric CoO clusters within silicalite‐1 zeolite for efficient propane dehydrogenation
Authors: Song Shaojia , Li Jun , Wu Zhijie , Zhang Peng , Sun Yuanqing , Song Weiyu , Li Zhenxing , Liu Jian
Published: September 2021

Cobalt‐based catalysts are promising alternatives to replace Pt‐ and Cr‐based catalysts for propane dehydrogenation (PDH). However, the sintering and reduction of unstable Co sites cause fast deactivation. Herein, the ultrasmall cobalt oxide clusters encapsulated within silicalite‐1 zeolites (CoO@S‐1) has been obtained via a ligand assistance in situ crystallization method. This CoO@S‐1 catalyst exhibits an attractive propylene formation rate of 13.66 mmolC3H6·gcat−1·h−1 with selectivity of >92% and is durable during 120‐h PDH reaction with five successive regeneration cycles. The high PDH activity of CoO@S‐1 is assigned to the encapsulated CoO clusters are favorable for propane adsorption and can better stabilize the detached H* species from propane, leading to the lower dehydrogenation barriers than framework Co2+ cations and Co3O4 nanoparticles. Additionally, the π‐binding propylene on CoO clusters can prevent the over‐dehydrogenation reaction compared with the di‐σ binding propylene on metallic Co, leading to the superior propylene selectivity and catalytic stability.
Scalable3D‐printed lattices for pressure control in fluid applications
Authors: Woodward Ian R. , Attia Lucas , Patel Premal , Fromen Catherine A.
Published: September 2021

Additive manufacturing affords precise control over geometries with high degrees of complexity and predefined structure. Lattices are one class of additive‐only structures which have great potential in directing transport phenomena because they are highly ordered, scalable, and modular. However, a comprehensive description of how these structures scale and interact in heterogeneous systems is still undetermined. To advance this aim, we designed cubic and Kelvin lattices at two sub‐5‐mm length scales and compared published correlations to the experimental pressure gradient in pipes ranging from 12 to 52 mm diameter. We further investigated all combinations of the four lattices to evaluate segmented combinatorial behavior. The results suggest that a single correlation can describe pressure behavior for different lattice geometries and scales. Furthermore, combining lattice systems in series has a complex effect that is sensitive to part geometry. Together, these developments support the promise for tailored, modular lattice systems at laboratory scales and beyond.
Machine‐learning‐based construction of barrier functions and models for safe model predictive control
Authors: Chen Scarlett , Wu Zhe , Christofides Panagiotis D.
Published: September 2021

In this paper, we propose a control Lyapunov‐barrier function‐based model predictive control method utilizing a feed‐forward neural network specified control barrier function (CBF) and a recurrent neural network (RNN) predictive model to stabilize nonlinear processes with input constraints, and to guarantee that safety requirements are met for all times. The nonlinear system is first modeled using RNN techniques, and a CBF is characterized by constructing a feed‐forward neural network (FNN) model with unique structures and properties. The FNN model for the CBF is trained based on data samples collected from safe and unsafe operating regions, and the resulting FNN model is verified to demonstrate that the safety properties of the CBF are satisfied. Given sufficiently small bounded modeling errors for both the FNN and the RNN models, the proposed control system is able to guarantee closed‐loop stability while preventing the closed‐loop states from entering unsafe regions in state‐space under sample‐and‐hold control action implementation. We provide the theoretical analysis for bounded unsafe sets in state‐space, and demonstrate the effectiveness of the proposed control strategy using a nonlinear chemical process example with a bounded unsafe region.
Predictors of mortality and outcomes of liver transplant in spur cell hemolytic anemia
Authors: Virk Zain M. , Patel Arpan A. , Leaf Rebecca K. , Al‐Samkari Hanny
Published: September 2021

Spur cell hemolytic anemia (SCHA) is a rare, acquired, nonimmune hemolytic anemia of decompensated cirrhosis. Data describing prognostic impact, outcomes of liver transplant, and clinical hematologic characteristics of SCHA are absent or limited. We performed a multicenter, 24‐year observational cohort study of patients with SCHA, retrospectively analyzing hepatic and hematologic parameters, independent predictors of mortality, and long‐term outcomes of liver transplant. Sixty‐nine patients with SCHA met eligibility for inclusion. The median (interquartile range) age was 53 (42–59) years; 46.4% were female, and 11 (15.9%) received liver transplant. Thirty‐nine patients (56.5%) were red blood celltransfusion‐dependent. All 11 patients undergoing transplant had rapid and complete resolution of SCHA, with improvement in median hematocrit from 22.1% to 34.6% post‐transplant (p = .001) and excellent post‐transplant outcomes. In multivariable logistic models adjusting for age, sex, etiology of cirrhosis, active/recent variceal bleeding, and Child–Turcotte–Pugh score, transfusion dependence had an odds ratio (OR) for 90‐day mortality of 9.14 (95% CI, 2.46–34.00) and reduced pre‐transfusion hematocrit had an OR of 4.73 (95% CI, 1.42–15.82) per 6% decrease; increased red cell transfusion requirement, reduced hemoglobin, increased lactate dehydrogenase, and increased indirect bilirubin were also independently predictive of higher 90‐day mortality. Model for end‐stage liver disease (MELD)‐Na and Child–Turcotte–Pugh scores consistently significantly underestimated 90‐day mortality, with standardized mortality ratios (SMRs) >1 across all scores/classes [MELD‐Na 20–29, SMR 2.42 (1.18–4.44); Child—Turcotte–Pugh class B, SMR 4.46 (1.64–9.90)]. In conclusion, SCHA is associated with substantial excess mortality than predicted by MELD‐Na or Child–Turcotte–Pugh scores and uniformly resolves with liver transplant, without recurrence. Multiple parameters of hemolytic anemia severity independently predict higher 90‐day mortality.
Triazolyl Dibenzo[a,c]phenazines Stabilize Telomeric G‐quadruplex and Inhibit Telomerase
Authors: Pal Sarmistha , Fatma Khushnood , Ravichandiran Velayutham , Dash Jyotirmayee
Published: September 2021

We herein report the synthesis and biophysical evaluation of triazolyl dibenzo[a,c]phenazine derivatives as a novel class of G‐quadruplex ligands. The aromatic core facilitates π‐π interaction and the flexible, protonable side chains interact with the phosphate backbone of DNA via electrostatic interactions. Förster resonance energy transfer (FRET) melting assay and isothermal titration calorimetry (ITC) studies suggest that these ligands show binding preference for the hTELO G‐quadruplex over G‐quadruplexes found in the promoter region of various oncogenes and duplex DNA. The in vitro telomeric repeat amplification protocol (Q‐TRAP) assay reveals that these ligands reduce telomerase activity in cancer cells.
A Platform for Site‐Specific DNA‐Antibody Bioconjugation by Using Benzoylacrylic‐Labelled Oligonucleotides
Authors: Konč Juraj , Brown Libby , Whiten Daniel R. , Zuo Yukun , Ravn Peter , Klenerman David , Bernardes Gonçalo J. L.
Published: September 2021

Many bioconjugation strategies for DNA oligonucleotides and antibodies suffer limitations, such as site‐specificity, stoichiometry and hydrolytic instability of the conjugates, which makes them unsuitable for biological applications. Here, we report a new platform for the preparation of DNA‐antibody bioconjugates with a simple benzoylacrylic acid pentafluorophenyl ester reagent. Benzoylacrylic‐labelled oligonucleotides prepared with this reagent can be site‐specifically conjugated to a range of proteins and antibodies through accessible cysteine residues. The homogeneity of the prepared DNA‐antibody bioconjugates was confirmed by a new LC‐MS protocol and the bioconjugate probes were used in fluorescence or super‐resolution microscopy cell imaging experiments. This work demonstrates the versatility and robustness of our bioconjugation protocol that gives site‐specific, well‐defined and plasma‐stable DNA‐antibody bioconjugates for biological applications.
trans Single‐Stranded DNA Cleavage via CRISPR/Cas14a1 Activated by Target RNA without Destruction
Authors: Wei Yangdao , Yang Zhiqing , Zong Chengli , Wang Buhua , Ge Xiaolin , Tan Xiao , Liu Xin , Tao Zhenzhen , Wang Peng , Ma Chunxin , Wan Yi , Li Jinghong
Published: September 2021

As a CRISPR‐Cas system (clustered regularly interspaced short palindromic repeats and CRISPR associated proteins), Cas14a1 can cis/trans cleave single‐stranded DNA (ssDNA). Here, we describe an unreported capacity of Cas14a1: RNA can trigger the trans ssDNA cleavage. This Cas14a1‐based RNA‐activated detection platform (Amplification, Transcription, Cas14a1‐based RNA‐activated trans ssDNA cleavage, ATCas‐RNA) has an outstanding specificity for the detection of target RNAs with point mutation resolution, which is better than that of the Cas14a1‐based ssDNA‐activation. Using ATCas‐RNA via a fluorophore quencher‐labeled ssDNA reporter (FQ), we were able to detect 1 aM pathogenic nucleic acid within 1 h, and achieve 100 % accuracy with 25 milk samples. This platform can serve as a new tool for high‐efficiency nucleic acid diagnostics. Importantly, this work can expand our understanding of Cas14a1 and inspire further mechanisms and applications of Class‐2 Cas systems.
Smart Nanozyme Platform with Activity‐Correlated Ratiometric Molecular Imaging for Predicting Therapeutic Effects
Authors: Teng Lili , Han Xiaoyu , Liu Yongchao , Lu Chang , Yin Baoli , Huan Shuangyan , Yin Xia , Zhang Xiao‐Bing , Song Guosheng
Published: September 2021

Nanozymes with intrinsic enzyme‐like characteristics have attracted enormous research interest in biological application. However, there is a lack of facile approach for evaluating the catalytic activity of nanozymes in living system. Herein, we develop a novel manganese‐semiconducting polymer‐based nanozyme (MSPN) with oxidase‐like activity for reporting the catalytic activity of itself in acid‐induced cancer therapy via ratiometric near‐infrared fluorescence (NIRF)‐photoacoustic (PA) molecular imaging. Notably, MSPN possess oxidase‐like activity in tumor microenvironment, owing to the mixed‐valent MnOx nanoparticles, which can effectively kill cancer cells. Because the semiconducting polymer (PFODBT) is conjugated with oxidase‐responsive molecule (ORM), the catalytic activity of nanozyme can be correlated with the ratiometric signals of NIRF (FL695/FL825) and PA (PA680/PA780), which may provide new ideas for predicting anticancer efficacy of nanozymes in living system.
Nitrosobenzene‐Enabled Chiral Phosphoric Acid Catalyzed Enantioselective Construction of Atropisomeric N‐Arylbenzimidazoles
Authors: An Qian‐Jin , Xia Wang , Ding Wei‐Yi , Liu Huan‐Huan , Xiang Shao‐Hua , Wang Yong‐Bin , Zhong Guofu , Tan Bin
Published: September 2021

Described herein is an imidazole ring formation strategy for the synthesis of axially chiral N‐arylbenzimidazoles by means of chiral phosphoric acid catalysis. Two sets of conditions were developed to transform two classes of 2‐naphthylamine derivatives into structurally diverse N‐arylbenzimidazole atropisomers with excellent chemo‐ and regioselectivity as well as high levels of enantiocontrol. It is worth reflecting on the unique roles played by the nitroso group in this domino reaction. It functions as a linchpin by first offering an electrophilic site (N) for the initial C−N bond formation while the resulting amine performs the nucleophilic addition to form the second C−N bond. Additionally, it could facilitate the final oxidative aromatization as an oxidant. The atropisomeric products could be conveniently elaborated to a series of axially chiral derivatives, enabling the exploitation of N‐arylbenzimidazoles for their potential utilities in asymmetric catalysis.
gem‐Difluoroallylation of Aryl Halides and Pseudo Halides with Difluoroallylboron Reagents in High Regioselectivity
Authors: Sakamoto Shu , Butcher Trevor W. , Yang Jonathan L. , Hartwig John F.
Published: September 2021

We report the palladium‐catalyzed gem‐difluoroallylation of aryl halides and pseudo halides with 3,3‐difluoroallyl boronates in high yield with high regioselectivity, and we report the preparation of the 3,3‐difluoroallyl boronate reactants by a copper‐catalyzed defluorinative borylation of inexpensive gaseous 3,3,3‐trifluoropropene with bis(pinacolato)diboron. The gem‐difluoroallylation of aryl and heteroaryl bromides proceeds with low catalyst loading (0.1 mol % [Pd]) and tolerates a wide range of functional groups, including primary alcohols, secondary amines, ethers, ketones, esters, amides, aldehydes, nitriles, halides, and nitro groups. This protocol extends to aryl iodides, chlorides, and triflates, as well as substituted difluoroallyl boronates, providing a versatile synthesis of gem‐difluoroallyl arenes that we show to be valuable intermediates to a series of fluorinated building blocks.
Deciphering and Suppressing Over‐Oxidized Nitrogen in Nickel‐Catalyzed Urea Electrolysis
Authors: Li Jianan , Li Jili , Liu Tao , Chen Lin , Li Yefei , Wang Hualin , Chen Xiurong , Gong Ming , Liu Zhi‐Pan , Yang Xuejing
Published: September 2021

Urea electrolysis is a prospective technology for simultaneous H2 production and nitrogen suppression in the process of water being used for energy production. Its sustainability is currently founded on innocuous N2 products; however, we discovered that prevalent nickel‐based catalysts could generally over‐oxidize urea into NO2− products with ≈80 % Faradaic efficiencies, posing potential secondary hazards to the environment. Trace amounts of over‐oxidized NO3− and N2O were also detected. Using 15N isotopes and urea analogues, we derived a nitrogen‐fate network involving a NO2−‐formation pathway via OH−‐assisted C−N cleavage and two N2‐formation pathways via intra‐ and intermolecular coupling. DFT calculations confirmed that C−N cleavage is energetically more favorable. Inspired by the mechanism, a polyaniline‐coating strategy was developed to locally enrich urea for increasing N2 production by a factor of two. These findings provide complementary insights into the nitrogen fate in water–energy nexus systems.
Biosynthesis of phenylpyruvic acid from l‐phenylalanine using chromosomally engineered Escherichia coli
Authors: Xiong Tianzhen , Bai Yajun , Fan Tai‐Ping , Zheng Xiaohui , Cai Yujie
Published: September 2021

The efficiency of whole‐cell biotransformation is often affected by the genetic instability of plasmid‐based expression systems, which require selective pressure to maintain the stability of the plasmids. To circumvent this shortcoming, we constructed a chromosome engineering strain for the synthesis of phenylpyruvic acid (PPA) from l‐phenylalanine. First, l‐amino acid deaminase (pmLAAD) from Proteus myxofaciens was incorporated into Escherichia coli BL21 (DE3) chromosome and the copy numbers of pmLAAD were increased by chemically induced chromosomal evolution (CIChE). Fifty‐nine copies of pmLAAD were obtained in E. coli BL8. The PPA titer of E. coli BL8 reached 2.22 g/L at 6 h. Furthermore, the deletion of lacI improved PPA production. In the absence of isopropyl‐β‐d‐thiogalactopyranoside, the resulting strain, E. coli BL8△recA△lacI, produced 2.65 g/L PPA at 6 h and yielded a 19.37% increase in PPA production compared to E. coli BL8△recA. Finally, the engineered E. coli BL8△recA△lacI strain achieved 19.14 g/L PPA at 24 h in a 5‐L bioreactor.
Maternotoxicity and fetotoxicity in Rattus norvegicus albinus exposed to tramadol during the late phase of pregnancy
Authors: Akhtar Muhammad Furqan , Younas Sobia , Saleem Ammara , Baig Mirza Muhammad Faran Ashraf , Sharif Ali , Abdel‐Daim Mohamed M. , Rasul Azhar , Saleem Mohammad
Published: September 2021

Objectives

Tramadol, an atypical opioid, is clinically efficacious in treating moderate to severe pain. The aim of current study was to find out the toxicological effects of tramadol exposure to pregnant rats and fetuses during the late phase of pregnancy.

Methods

Wistar pregnant rats were exposed to 1.25, 2.5, or 5 mg/kg/day tramadol from 14th to 20th day of pregnancy. The same therapy was given to nonpregnant rats for 7 days. The body weight, oral glucose and lipid tolerance tests, and effect on complete blood parameters in both pregnant and nonpregnant rats were determined. On 20th day, maternal placentas were excised and weighed while fetuses were observed for any deformity and growth retardation. Oxidative stress biomarkers were estimated in the liver and kidney tissue homogenates of the pregnant and nonpregnant rats while the whole fetus homogenate was processed for the same. Moreover, histopathology of the liver and kidney of pregnant and nonpregnant rats were carried out.

Results

Tramadol administration did not significantly alter the area under curve of the blood glucose and triglyceride levels in both the pregnant and nonpregnant rats. It reduced the live fetuses, placental weights, fetal length, and fetal weights. Tramadol treated pregnant rats showed significantly (p < .05) reduced red blood cells, hematocrit, hemoglobin, and platelets with reference to control group. Similarly, structural abnormalities and malfunctioning of the liver and kidney of pregnant rats were instituted; however, it did not affect the structural integrity of nonpregnant rats. A substantial (p < .001–.0001) altered glutathione and malondialdehyde levels in the fetuses, pregnant, and nonpregnant animals (tissue homogenates) at all dosage levels were indicative of tramadol induced oxidative stress. Furthermore, tramadol exposure resulted in more significant (p < .01–.001) alteration of lipid profile in the pregnant than the nonpregnant animals.

Conclusion

Acquired results suggested the maternotoxic and fetotoxic effects of tramadol exposure during the late gestation period.
Structural Basis of Cyclic 1,3‐Diene Forming Acyl‐Coenzyme A Dehydrogenases
Authors: Kung Johannes W. , Meier Anne‐Katrin , Willistein Max , Weidenweber Sina , Demmer Ulrike , Ermler Ulrich , Boll Matthias
Published: September 2021

The biologically important, FAD‐containing acyl‐coenzyme A (CoA) dehydrogenases (ACAD) usually catalyze the anti‐1,2‐elimination of a proton and a hydride of aliphatic CoA thioesters. Here, we report on the structure and function of an ACAD from anaerobic bacteria catalyzing the unprecedented 1,4‐elimination at C3 and C6 of cyclohex‐1‐ene‐1‐carboxyl‐CoA (Ch1CoA) to cyclohex‐1,5‐diene‐1‐carboxyl‐CoA (Ch1,5CoA) and at C3 and C4 of the latter to benzoyl‐CoA. Based on high‐resolution Ch1CoA dehydrogenase crystal structures, the unorthodox reactivity is explained by the presence of a catalytic aspartate base (D91) at C3, and by eliminating the catalytic glutamate base at C1. Moreover, C6 of Ch1CoA and C4 of Ch1,5CoA are positioned towards FAD‐N5 to favor the biologically relevant C3,C6‐ over the C3,C4‐dehydrogenation activity. The C1,C2‐dehydrogenation activity was regained by structure‐inspired amino acid exchanges. The results provide the structural rationale for the extended catalytic repertoire of ACADs and offer previously unknown biocatalytic options for the synthesis of cyclic 1,3‐diene building blocks.
LncRNA TUG1 acts as a competing endogenous RNA to mediate CTGF expression by sponging miR‐133b in myocardial fibrosis after myocardial infarction
Authors: Zhang Songlin , Wang Ningbo , Ma Qingyan , Fan Fenling , Ma Xiancang
Published: September 2021

Myocardial fibrosis (MF) is one of the basic causes of many cardiovascular diseases. Noncoding RNAs (ncRNAs), including microRNA (miRNA) and long noncoding RNA (lncRNA), have been reported to play an indispensable role in MF. The current work is focused on investigating the biological role of lncRNA taurine upregulation gene 1 (TUG1) in activating cardiac myofibroblasts as well as the underlying mechanism. The outcome revealed that after myocardial infarction TUG1 expression increased and miR‐133b expression decreased in the rat model of MF. The expression level of TUG1 increased following AngII treatment in cardiac myofibroblast. TUG1 knockdown inhibited the Ang‐II induced cardiac myofibroblast activation and TUG1 overexpression increased proliferation and collagen generation of cardiac myofibroblasts. Bioinformatic prediction programs predicted that TUG1 had MRE directly combined with miR‐133b seed sequence, luciferase activity, and RIP experiments indicated that TUG1, acted as a sponger and interacted with miR‐133b in cardiac myofibroblasts. Furthermore, a target of miR‐133b was CTGF and CTGF knockdown counteracted the promotion of MF by miR‐133b knockdown. Collectively, our study suggested that TUG1 mediates CTGF expression by sponging miR‐133b in the activation of cardiac myofibroblasts. The current work reveals a unique role of the TUG1/miR‐133b/CTGF axis in MF, thus suggesting its immense therapeutic potential in the treatment of cardiac diseases.
Determination of Relative Stabilities of Metal‐Peptide Bonds in the Gas Phase
Authors: Cziferszky Monika , Truong Dianna , Hartinger Christian G. , Gust Ronald
Published: September 2021

Understanding binding site preferences in biological systems as well as affinities to binding partners is a crucial aspect in metallodrug development. We here present a mass spectrometry‐based method to compare relative stabilities of metal‐peptide adducts in the gas phase. Angiotensin 1 and substance P were used as model peptides. Incubation with isostructural N‐heterocyclic carbene (NHC) complexes of RuII, OsII, RhIII, and IrIII led to the formation of various adducts, which were subsequently studied by energy‐resolved fragmentation experiments. The gas‐phase stability of the metal‐peptide bonds depended on the metal and the binding partner. Of the four complexes used, the OsII derivative bound strongest to Met, while RuII formed the most stable coordination bond with His. RhIII was identified as the weakest peptide binder and IrIII formed peptide adducts with intermediate stability. Probing these intrinsic gas‐phase properties can help in the interpretation of biological activities and the design of site‐specific protein binding metal complexes.
Domino Dehydrative π‐Extension: A Facile Path to Extended Perylenes and Terrylenes
Authors: Feofanov Mikhail , Akhmetov Vladimir , Amsharov Konstantin
Published: September 2021

Herein, we report a new method for synthesis of extended perylenes and terrylenes. The technique is based on the cascade dehydrative π‐extensions (DPEX) of aryl aldehydes, in which stepwise annulations activate previously “dormant” substituents. Two‐ and fourfold cyclizations of 3‐aryl‐biphenyl‐2,2′‐dicarbaldehydes offer a rapid path to unsymmetrical perylenes and elusive terrylene derivatives, respectively. DPEX of 3,3′′‐(phenanthrene‐1,8‐diyl)bis (([1,1′‐biphenyl]‐2,2′‐dicarbaldehyde)) leads to the biradical structure, which proceeds in situ into oxidative electrocyclization at room temperature. The described domino process complements and expands DPEX approach to a large family of fused acenes and related PAHs.
Perfluorinated Trialkoxysilanol with Dramatically Increased Brønsted Acidity
Authors: Feige Felix , Malaspina Lorraine A. , Rychagova Elena , Ketkov Sergey , Grabowsky Simon , Hupf Emanuel , Beckmann Jens
Published: September 2021

The Brønsted acidity of the perfluorinated trialkoxysilanol {(F3C)3CO}3SiOH is more than 13 orders of magnitude higher than that of orthosilicic acid, Si(OH)4, and even more for most previously known silanols. It is easily deprotonated by simple amines and pyridines to give the conjugate silanolates [OSi{OC(CF3)3}3]−, which possess extremely short Si−O bonds, comparable to those of silanones.
Genetic features of B‐cell lymphoblastic lymphoma with TCF3‐PBX1
Authors: Shirai Ryota , Osumi Tomoo , Sato‐Otsubo Aiko , Nakabayashi Kazuhiko , Mori Takeshi , Yoshida Masanori , Yoshida Kaoru , Kohri Mika , Ishihara Takashi , Yasue Shiho , Imamura Toshihiko , Endo Mikiya , Miyamoto Satoshi , Ohki Kentaro , Sanada Masashi , Kiyokawa Nobutaka , Ogawa Seishi , Yoshioka Takako , Hata Kenichiro , Takagi Masatoshi , Kato Motohiro
Published: September 2021

Background

Lymphoblastic lymphoma (LBL) and acute lymphoblastic leukemia (ALL) are categorized as the same entity under precursor lymphoid neoplasms in the World Health Organization classification. However, compared to B‐cell ALL, the molecular genetic makeup of B‐cell LBL remains to be understood, mainly due to its rarity. We performed whole exome sequencing (WES) on seven patients with TCF3‐PBX1‐positive B‐cell LBL.

Methods

WES was performed using DNA extracted from tumor specimens and paired blood samples at remission for six patients, and tumor‐only analysis was performed for one patient whose remission sample was not available. For one patient, a relapsed sample was also analyzed.

Results

KMT2D variants and 6q LOH were found as recurrent alterations. Somatic variants of KMT2D were identified in three of the seven patients. Of note, the two patients with heterozygous nonsense variant of KMT2D were at stage III, without bone marrow infiltration. 6q LOH was also identified in two others, out of the seven patients. The common 6q deleted region of the two patients ranged from 6q12 to 6q16.3. Both patients had bone marrow infiltration. Analysis of recurrent case also revealed that the relapsed clone might be derived from a minor clone of the bone marrow at diagnosis.

Conclusion

In this study, through WES for seven patients with TCF3‐PBX1‐positive B‐LBL, we identified KMT2D mutations and 6q LOH as recurrent alterations. In order to elucidate the relationship between these recurrent alterations and disease specificity or outcomes, further studies comparing with TCF3‐PBX1‐positive B‐ALL are required.
An improved efficient class of estimators for the population variance
Authors: Niaz Iqra , Sanaullah Aamir , Saleem Iram , Shabbir Javid
Published: September 2021

In this article, we propose an improved class of estimators for a finite population variance in presence of the auxiliary information. The expressions of the bias and mean squared error of the proposed class of estimators are obtained up to the first order of approximation. The conditions under which the proposed class of estimators is more efficient than the other estimators have also been derived. It is observed from the simulation results that the proposed class of estimators is more efficient than the usual linear regression estimator.
Expressed emotion and long‐term outcome among adolescents with anorexia nervosa
Authors: Rienecke Renee D. , Gorrell Sasha , Blalock Dan V. , Smith Kathryn , Lock James , Le Grange Daniel
Published: September 2021

Objective

The purpose of the current study is to examine expressed emotion (EE) and long‐term treatment outcome among adolescents participating in a randomized controlled trial (RCT) for treatment of anorexia nervosa (AN). It was hypothesized that patients with high EE parents at baseline would show more severe symptoms at end‐of‐treatment, 12‐month follow‐up, and 4‐year follow‐up than patients from low EE families.

Method

Secondary data analysis was conducted of original RCT data from a two‐site eating disorder treatment trial conducted in the United States. Participants were 121 adolescents with AN who completed measures of EE, eating disorder psychopathology, depression, and self‐esteem.

Results

Generalized estimating equations showed that participants who were in the Low EE group achieved a more accelerated drop in depression scores in the context of treatment (first 12 months) than participants in the High EE group. No other significant Group × Time interactions were found.

Discussion

Findings suggest that high parental EE at baseline does not indicate that adolescent patients with AN will fare poorly 4 years later.
Depth diversity gradients of macrophytes: Shape, drivers, and recent shifts
Authors: Lewerentz Anne , Hoffmann Markus , Sarmento Cabral Juliano
Published: September 2021

Investigating diversity gradients helps to understand biodiversity drivers and threats. However, one diversity gradient is rarely assessed, namely how plant species distribute along the depth gradient of lakes. Here, we provide the first comprehensive characterization of depth diversity gradient (DDG) of alpha, beta, and gamma species richness of submerged macrophytes across multiple lakes. We characterize the DDG for additive richness components (alpha, beta, gamma), assess environmental drivers, and address temporal change over recent years. We take advantage of yet the largest dataset of macrophyte occurrence along lake depth (274 depth transects across 28 deep lakes) as well as of physiochemical measurements (12 deep lakes from 2006 to 2017 across Bavaria), provided publicly online by the Bavarian State Office for the Environment. We found a high variability in DDG shapes across the study lakes. The DDGs for alpha and gamma richness are predominantly hump‐shaped, while beta richness shows a decreasing DDG. Generalized additive mixed‐effect models indicate that the depth of the maximum richness (Dmax) is influenced by light quality, light quantity, and layering depth, whereas the respective maximum alpha richness within the depth gradient (Rmax) is significantly influenced by lake area only. Most observed DDGs seem generally stable over recent years. However, for single lakes we found significant linear trends for Rmax and Dmax going into different directions. The observed hump‐shaped DDGs agree with three competing hypotheses: the mid‐domain effect, the mean–disturbance hypothesis, and the mean–productivity hypothesis. The DDG amplitude seems driven by lake area (thus following known species–area relationships), whereas skewness depends on physiochemical factors, mainly water transparency and layering depth. Our results provide insights for conservation strategies and for mechanistic frameworks to disentangle competing explanatory hypotheses for the DDG.
No escape: The influence of substrate sodium on plant growth and tissue sodium responses
Authors: Santiago‐Rosario Luis Y. , Harms Kyle E. , Elderd Bret D. , Hart Pamela B. , Dassanayake Maheshi
Published: September 2021

As an essential micronutrient for many organisms, sodium plays an important role in ecological and evolutionary dynamics. Although plants mediate trophic fluxes of sodium, from substrates to higher trophic levels, relatively little comparative research has been published about plant growth and sodium accumulation in response to variation in substrate sodium. Accordingly, we carried out a systematic review of plants' responses to variation in substrate sodium concentrations.

We compared biomass and tissue‐sodium accumulation among 107 cultivars or populations (67 species in 20 plant families), broadly expanding beyond the agricultural and model taxa for which several generalizations previously had been made. We hypothesized a priori response models for each population's growth and sodium accumulation as a function of increasing substrate NaCl and used Bayesian Information Criterion to choose the best model. Additionally, using a phylogenetic signal analysis, we tested for phylogenetic patterning of responses across taxa.

The influence of substrate sodium on growth differed across taxa, with most populations experiencing detrimental effects at high concentrations. Irrespective of growth responses, tissue sodium concentrations for most taxa increased as sodium concentration in the substrate increased. We found no strong associations between the type of growth response and the type of sodium accumulation response across taxa. Although experiments often fail to test plants across a sufficiently broad range of substrate salinities, non‐crop species tended toward higher sodium tolerance than domesticated species. Moreover, some phylogenetic conservatism was apparent, in that evolutionary history helped predict the distribution of total‐plant growth responses across the phylogeny, but not sodium accumulation responses.

Our study reveals that saltier plants in saltier soils proves to be a broadly general pattern for sodium across plant taxa. Regardless of growth responses, sodium accumulation mostly followed an increasing trend as substrate sodium levels increased.
Renoprotection by long‐term low‐dose tolvaptan in patients with heart failure and hyponatremia
Authors: Oka Tatsufumi , Hamano Takayuki , Ohtani Tomohito , Doi Yohei , Shimada Karin , Matsumoto Ayumi , Yamaguchi Satoshi , Hashimoto Nobuhiro , Senda Masamitsu , Sakaguchi Yusuke , Matsui Isao , Nakamoto Kei , Sera Fusako , Hikoso Shungo , Sakata Yasushi , Isaka Yoshitaka
Published: September 2021

Aims

In previous randomized controlled trials, the use of tolvaptan (TLV) at a fixed dose of 30 mg/day for 1 year did not provide renal benefits in patients with heart failure (HF). This retrospective, cohort study examined the renoprotective effects of long‐term, flexible‐dose, and lower‐dose TLV use.

Methods and results

Tolvaptan users were defined as patients receiving TLV for at least 180 consecutive days or those who continued it until death, any cardiac events, or renal replacement therapy even if it was taken for <180 days. Of a total of 584 HF patients, 78 TLV users were identified. The median age, baseline B‐type natriuretic peptide, and estimated glomerular filtration rate (eGFR) were 71 years, 243 pg/mL, and 54 mL/min/1.73 m2, respectively. During follow‐up (median, 461 days), TLV use (median average dose, 7.5 mg/day) was associated with frequent dose reductions of loop diuretics (incidence rate ratio [IRR], 1.5; 95% confidence interval [CI], 1.1–2.2), particularly in patients with serum sodium ≤135 mEq/L (IRR, 2.9; 95% CI, 1.5–5.7) (Pinteraction = 0.04). In a mixed effects model, propensity score (PS)‐matched TLV users had higher eGFRs over time than PS‐matched never‐users (P < 0.01). The entire cohort analyses (N = 584) yielded similar results. The renal benefit of TLV in terms of annualized eGFR slope was more pronounced in patients with lower sodium levels (Pinteraction = 0.03). This effect modification was extinguished when patients who underwent a loop diuretic dose reduction during the follow‐up period were excluded from the analysis.

Conclusions

Long‐term, flexible‐dose, and low‐dose TLV use was associated with better renal function, particularly in hyponatremic HF, possibly due to its loop diuretic dose‐sparing effect in the long term.
Variability in estimated glomerular filtration rate and patients' outcomes in a real‐world heart failure population
Authors: Oka Tatsufumi , Hamano Takayuki , Ohtani Tomohito , Tanaka Akihiro , Doi Yohei , Yamaguchi Satoshi , Senda Masamitsu , Sakaguchi Yusuke , Matsui Isao , Nakamoto Kei , Sera Fusako , Hikoso Shungo , Nishino Masami , Sakata Yasushi , Isaka Yoshitaka
Published: September 2021

Aims

The prognostic significance of renal function variability has not been fully elucidated in heart failure (HF). This multicentre, prospective cohort study aimed to evaluate the usefulness of visit‐to‐visit variability in estimated glomerular filtration rate (eGFR) for predicting patients' outcomes in a real‐world HF population.

Methods

A total of 564 patients who had survived HF hospitalization were randomly assigned with a 2:1 ratio to derivation and validation cohorts, and they were then followed after discharge. Using the data for 6 months after discharge, each patient's visit‐to‐visit eGFR variability (EGV) was estimated. In the derivation cohort, Cox regression analyses were performed to assess the association of EGV with a subsequent composite event (death and HF hospitalization). In the validation cohort, the predictive performance was compared among Cox regression models with EGV, those with B‐type natriuretic peptide (BNP) and those with eGFR.

Results

In the derivation cohort (376 patients), median age, left ventricular ejection fraction (LVEF), BNP and eGFR at discharge were 72 years, 53.3%, 134.8 pg/mL and 58.7 mL/min/1.73 m2, respectively. During a median follow‐up of 2.2 years, higher EGV was associated with an increased risk of the composite event (adjusted hazard ratio [per standard deviation increase in log‐transformed EGV], 1.5; 95% confidence interval, 1.1–2.0). A similar finding was observed in a stratified analysis by LVEF. In the validation cohort (188 patients), better model fit, discrimination, reclassification and calibration were observed for EGV than for 6‐month averaged BNP or eGFR for predicting the composite event when added to HF risk prediction models. Adding EGV to models with BNP or eGFR improved model discrimination and reclassification.

Conclusions

EGV predicts HF outcomes regardless of LVEF. Risk prediction models with EGV have good performance in real‐world HF patients. The study findings highlight the clinical importance of observing visit‐to‐visit fluctuations in renal function in this population.
Solvent‐Dependent Spin‐Crossover Behavior in Semiconducting Co–Crystals of [Fe(1‐bpp)2]2+ Cations and TCNQδ− Anions (0<δ<1)
Authors: Üngör Ökten , Choi Eun Sang , Shatruk Michael
Published: September 2021

Co‐crystallization of the spin‐crossover (SCO) cationic complex, [Fe(1‐bpp)2]2+ (1‐bpp=2,6‐bis(pyrazol‐1‐yl)pyridine) with fractionally charged organic anion TCNQδ− (0<δ<1) afforded hybrid materials [Fe(1‐bpp)2](TCNQ)3.5 ⋅ 3.5MeCN (1) and [Fe(1‐bpp)2](TCNQ)4 ⋅ 4DCE (2), where TCNQ=7,7,8,8‐tetracyanoquinodimethane, MeCN=acetonitrile, and DCE=1,2‐dichloroethane. Both materials exhibit semiconducting behavior, with the room‐temperature conductivity values of 1.1×10−4 S/cm and 1.7×10−3 S/cm, respectively. The magnetic behavior of both complexes exhibits strong dependence on the content of the interstitial solvent. Complex 1 undergoes a gradual temperature‐driven SCO, with the midpoint temperature of T1/2=234 K. The partial solvent loss by 1 leads to the increase in the T1/2 value while complete desolvation renders the material high‐spin (HS) in the entire studied temperature range. In the case of 2, the solvated complex shows a gradual SCO with T1/2=166 K only when covered with a mother liquid, while the facile loss of interstitial solvent, even at room temperature, leads to the HS‐only behavior.
The role of efflux transporters and metabolizing enzymes in brain and peripheral organs to explain drug‐resistant epilepsy
Authors: Vázquez Marta , Fagiolino Pietro
Published: September 2021

Drug‐resistant epilepsy has been explained by different mechanisms. The most accepted one involves overexpression of multidrug transporters proteins at the blood brain barrier and brain metabolizing enzymes. This hypothesis is one of the main pharmacokinetic reasons that lead to the lack of response of some antiseizure drug substrates of these transporters and enzymes due to their limited entrance into the brain and limited stay at the sites of actions. Although uncontrolled seizures can be the cause of the overexpression, some antiseizure medications themselves can cause such overexpression leading to treatment failure and thus refractoriness. However, it has to be taken into account that the inductive effect of some drugs such as carbamazepine or phenytoin not only impacts on the brain but also on the rest of the body with different intensity, influencing the amount of drug available for the central nervous system. Such induction is not only local drug concentration but also time dependent. In the case of valproic acid, the deficient disposition of ammonia due to a malfunction of the urea cycle, which would have its origin in an intrinsic deficiency of L‐carnitine levels in the patient or by its depletion caused by the action of this antiseizure drug, could lead to drug‐resistant epilepsy. Many efforts have been made to change this situation. In order to name some, the administration of once‐daily dosing of phenytoin or the coadministration of carnitine with valproic acid would be preferable to avoid iatrogenic refractoriness. Another could be the use of an adjuvant drug that down‐regulates the expression of transporters. In this case, the use of cannabidiol with antiseizure properties itself and able to diminish the overexpression of these transporters in the brain could be a novel therapy in order to allow penetration of other antiseizure medications into the brain.
A probabilistic strong floor motion duration model for seismic performance assessment of non‐structural building elements
Authors: Rodriguez Derek , Perrone Daniele , Filiatrault Andre , Brunesi Emanuele
Published: September 2021

Non‐structural elements (NSEs) are not designed to be part of the structural load‐bearing system of a building but are subjected to the same dynamic environment as the supporting structure during an earthquake. Non‐structural damage and ensuing losses have exceeded structural damage and losses in many buildings during recent earthquakes that have occurred in urban regions around the world. Damage to NSEs is strongly influenced by the amplitude, the frequency content and the duration of floor motions. Although the effects of amplitude and frequency content of floor motions are well captured by floor response spectra, little attention has been given on the characterisation of floor motion duration and how it can impact damage to NSEs, particularly for those responding in the inelastic range. To contribute to a better understanding of these issues, this paper develops a probabilistic strong floor motion duration model through multiple stripes non‐linear time‐history analyses of a population of 100 code‐compliant reinforced concrete frame building models designed for a medium‐to‐high seismicity site in Italy. The resulting probabilistic model can be used when selecting historical or generating synthetic floor motions for the seismic response assessment of NSEs or when generating shake‐table test records for the seismic qualification of NSEs.
Concepts with consequences in geomorphology: A fluvial perspective
Authors: Lewin John
Published: September 2021

Imagined concepts – made real by down‐to‐earth field verification, validated modelling, and using available technologies and empirical methods – are fundamental to research outcomes in geomorphology. This article reviews the functions that consequential concepts have served: as overall driving and embracing stimuli, or playing permissive roles at lower levels within projects; when they have come to the fore and declined in usage; how knowledge of them gets spread and tested; and where needs seem to be driving for the future. Within fluvial geomorphology there is demonstrably a multiplicity of conceptual approaches. Modern times also now involve greater external appraisal including financial and management control and research and teaching quality assessments. These are taking place in parallel with novel environmental changes that themselves pose new needs for hazard understandings and safeguarding. Challenges to address for practical reasons include forecasting the likely future geomorphic effects of climate change, tracking system impacts from the spread of human hardware across landscapes, and monitoring pollutant incursions into fluvial systems. Nevertheless, conceptual progress in understanding is also fundamentally dependent on advancing ‘blue skies’ research objectives. In a changing world, geomorphology has to pursue holistic goals and the multi‐temporal and multi‐scale spatial appreciation of landform development, and how this relates to other changing global systems, but also to grow what it conceives of doing for the public good.
Updating the dual‐mechanism model for cross‐sensory attentional spreading: The influence of space‐based visual selective attention
Authors: Zhao Song , Li Yang , Wang Chongzhi , Feng Chengzhi , Feng Wenfeng
Published: September 2021

Selective attention to visual stimuli can spread cross‐modally to task‐irrelevant auditory stimuli through either the stimulus‐driven binding mechanism or the representation‐driven priming mechanism. The stimulus‐driven attentional spreading occurs whenever a task‐irrelevant sound is delivered simultaneously with a spatially attended visual stimulus, whereas the representation‐driven attentional spreading occurs only when the object representation of the sound is congruent with that of the to‐be‐attended visual object. The current study recorded event‐related potentials in a space‐selective visual object‐recognition task to examine the exact roles of space‐based visual selective attention in both the stimulus‐driven and representation‐driven cross‐modal attentional spreading, which remain controversial in the literature. Our results yielded that the representation‐driven auditory Nd component (200–400 ms after sound onset) did not differ according to whether the peripheral visual representations of audiovisual target objects were spatially attended or not, but was decreased when the auditory representations of target objects were presented alone. In contrast, the stimulus‐driven auditory Nd component (200–300 ms) was decreased but still prominent when the peripheral visual constituents of audiovisual nontarget objects were spatially unattended. These findings demonstrate not only that the representation‐driven attentional spreading is independent of space‐based visual selective attention and benefits in an all‐or‐nothing manner from object‐based visual selection for actually presented visual representations of target objects, but also that although the stimulus‐driven attentional spreading is modulated by space‐based visual selective attention, attending to visual modality per se is more likely to be the endogenous determinant of the stimulus‐driven attentional spreading.
Efficiency of district hospitals in Zimbabwe: Assessment, drivers and policy implications
Authors: Guillon Marlène , Audibert Martine , Mathonnat Jacky
Published: September 2021

The Government of Zimbabwe is committed to making progress towards universal health coverage. Unmet health needs are huge and the health system suffers from serious dysfunctions and weaknesses. The situation is further complicated by a weak governance. To address these challenging issues, many of which would require an increase in public health expenditures, the government faces severe macroeconomic constraints. In this context, improving the efficiency of public health expenditures is of paramount importance. This study focuses on the efficiency of district hospitals, whose role is crucial for the strengthening of the health care system and achieving significant results in implementing the universal health coverage. Based on a sample of 31 district hospitals observed from 2015 to 2017 we use the double bootstrap procedure developed by Simar and Wilson to (a) estimate bias‐adjusted DEA efficiency scores and to (b) investigate the factors associated with the previously calculated scores using truncated regression. The average efficiency of district hospitals is low and stagnant over 2015–2017. The findings suggest the existence of a significant room for maneuver to get more results with the resources spent. The analysis of the efficiency drivers shows the importance of both supply and demand‐side factors, leading to several policy‐oriented considerations. The study also highlights important shortcomings in the routine collection of basic data that need to be addressed by the Ministry of Health and Child Care.