bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolomics and incident dementia in older Chinese adults: The Shanghai Aging Study
Authors: Cui Mei , Jiang Yanfeng , Zhao Qianhua , Zhu Zhen , Liang Xiaoniu , Zhang Kexun , Wu Wanqing , Dong Qiang , An Yanpeng , Tang Huiru , Ding Ding , Chen Xingdong
Published: April 2020

Introduction

Metabolomics provide a promising tool to understand the pathogenesis and to identify novel biomarkers of dementia. This study aimed to determine circulating metabolites associated with incident dementia in a Chinese cohort, and whether a selected metabolite panel could predict dementia.

Methods

Thirty‐eight metabolites in baseline serum were profiled by nuclear magnetic resonance in 1440 dementia‐free participants followed 5 years in the Shanghai Aging Study.

Results

Higher serum levels of glutamine and O‐acetyl‐glycoproteins were associated with increased risk of dementia, whereas glutamate, tyrosine, acetate, glycine, and phenylalanine were negatively related to incident dementia. A panel of five metabolites selected by least absolute shrinkage and selection operator within cross‐validation regression analysis could predict incident dementia with an area under the receiver‐operating characteristic curve of 0.72.

Discussion

We identified seven candidate serum metabolic biomarkers for dementia. These findings and the underlying biological mechanisms need to be further replicated and elucidated in future studies.
Organic Printed Core–Shell Heterostructure Arrays: A Universal Approach to All‐Color Laser Display Panels
Authors: Zhou Zhonghao , Zhao Jinyang , Du Yuxiang , Wang Kang , Liang Jie , Yan Yongli , Zhao Yong Sheng
Published: April 2020

A universal approach is demonstrated for realizing dual‐wavelength lasing in organic core–shell structured microlaser arrays, which show great promise in serving as all‐color laser display panels. By alternately printing hydrophilic and hydrophobic laser dye solutions on preprocessed substrates, precisely patterned core–shell heterostructure arrays were obtained. The spatially separated core and shell independently function as optical resonators to support dual‐wavelength tunable lasing in each heterostructure. Such a general method enables to flexibly control the lasing wavelength of the core–shell microlasers across a wide spectral range by systematically designing the gain media. Using as‐prepared microlaser arrays as display panels, full‐color laser displays were achieved with a color gamut much larger than that of standard RGB space. These results provide insights for design concepts and device construction for novel optoelectronic applications.
Diboran(4)azide als stabile Quelle für kurzlebige Iminoborane
Authors: Thiess Torsten , Bélanger‐Chabot Guillaume , Fantuzzi Felipe , Michel Maximilian , Ernst Moritz , Engels Bernd , Braunschweig Holger
Published: April 2020

Wir berichten über die ersten isolierbaren, elektronen‐präzisen Diborane(4) mit Azidresten: das acyclische 1,2‐Diazido‐1,2‐bis(dimethylamino)diboran(4) und eine Reihe cyclischer 1,4‐Diaryl‐2,3‐diazido‐1,4‐diaza‐2,3‐diborine (Aryl=Mesityl, 2,6‐Xylyl, 4‐Tolyl). Im Gegensatz zu den kürzlich von uns beschriebenen kurzlebigen Diboran(4)aziden, welche sich bereits bei Raumtemperatur spontan zersetzen, erweisen sich die hier dargestellten Moleküle als thermisch äußerst robust. So können diese kontrollierte Pyrolysereaktionen bei Temperaturen weit über 100 °C eingehen, ohne dass es zu deren explosionsartiger Zersetzung kommt. Überraschenderweise konnten in zwei Fällen nach der Pyrolyse komplexe Diazadiboretidine isoliert werden, welche formal die Dimerisierungsprodukte von endo‐cyclischen Boryliminoboranen darstellen.
Chemie der Chitosan‐Aerogele: Lenkung der dreidimensionalen Poren für maßgeschneiderte Anwendungen
Authors: Takeshita Satoru , Zhao Shanyu , Malfait Wim J. , Koebel Matthias M.
Published: April 2020

In diesem Aufsatz diskutieren wir die schnell wachsende Zahl an Literaturbeiträgen zu Chitosan‐basierten porösen Materialien, mit Schwerpunkt auf Gelierungsmechanismen, dreidimensionaler multiskaliger Strukturkontrolle sowie der mannigfaltigen chemischen Funktionalität, die mit anderen Biopolymeren nicht erreichbar ist. Die Eigenschaften unterscheiden sich von letzteren teils stark: von überkritisch getrockneten, mesoporösen Chitosan‐Aerogelen bis hin zu äußerst leichten, gefriergetrockneten makroporösen Gerüsten. Im Labormaßstab erreicht poröses Chitosan beeindruckende Eigenschaften, der hoch (meso)poröse Charakter verstärkt jedoch nicht nur die vorteilhafte Funktionalität des Chitosans, sondern auch seine Nachteile, was eine mögliche Industrialisierung ernsthaft einschränkt. Zur Förderung des Technologietransfers diskutieren wir in kritischer Weise die praktische Umsetzbarkeit möglicher Anwendungen von Chitosan‐Aerogelen im Vergleich zu konventionellen und anderen biopolymerbasierten porösen oder nichtporösen Materialien.
Total Synthesis of (±)‐Phyllantidine: Development and Mechanistic Evaluation of a Ring Expansion for Installation of Embedded Nitrogen‐Oxygen Bonds
Authors: Lambert Kyle M. , Cox Joshua B. , Liu Lin , Jackson Amy C. , Yruegas Sam , Wiberg Kenneth B. , Wood John L.
Published: April 2020

The development of a concise total synthesis of (±)‐phyllantidine (1), a member of the securinega family of alkaloids containing an unusual oxazabicyclo[3.3.1]nonane core, is described. The synthesis employs a unique synthetic strategy featuring the ring expansion of a substituted cyclopentanone to a cyclic hydroxamic acid as a key step that allows facile installation of the embedded nitrogen‐oxygen (N−O) bond. The optimization of this sequence to effect the desired regiochemical outcome and its mechanistic underpinnings were assessed both computationally and experimentally. This synthetic approach also features an early‐stage diastereoselective aldol reaction to assemble the substituted cyclopentanone, a mild reduction of an amide intermediate without N−O bond cleavage, and the rapid assembly of the butenolide found in (1) via use of the Bestmann ylide.
Diborane(4) Azides: Surprisingly Stable Sources of Transient Iminoboranes
Authors: Thiess Torsten , Bélanger‐Chabot Guillaume , Fantuzzi Felipe , Michel Maximilian , Ernst Moritz , Engels Bernd , Braunschweig Holger
Published: April 2020

Herein we describe the first examples of isolable electron‐precise diboranes(4) that bear azide moieties: the acyclic 1,2‐diazido‐1,2‐bis(dimethylamino)diborane(4) and the cyclic 1,4‐diaryl‐2,3‐diazido‐1,4‐diaza‐2,3‐diborinines (aryl=mesityl, 2,6‐xylyl, 4‐tolyl). The reported examples are not only stable enough to be observed and isolated (putative transient diborane(4) azides previously reported by our group spontaneously decompose even below room temperature), but some of them are even robust enough to undergo controlled pyrolysis without explosive decomposition at temperatures well above 100 °C. In two cases, the controlled pyrolysis allows the isolation of complex diazaboretidines, which are the apparent dimerization products of endocyclic boryl‐iminoboranes.
Application and Structural Analysis of Triazole‐Bridged Disulfide Mimetics in Cyclic Peptides
Authors: White Andrew M. , de Veer Simon J. , Wu Guojie , Harvey Peta J. , Yap Kuok , King Gordon J. , Swedberg Joakim E. , Wang Conan K. , Law Ruby H. P. , Durek Thomas , Craik David J.
Published: April 2020

Ruthenium‐catalysed azide–alkyne cycloaddition (RuAAC) provides access to 1,5‐disubstituted 1,2,3‐triazole motifs in peptide engineering applications. However, investigation of this motif as a disulfide mimetic in cyclic peptides has been limited, and the structural consequences remain to be studied. We report synthetic strategies to install various triazole linkages into cyclic peptides through backbone cyclisation and RuAAC cross‐linking reactions. These linkages were evaluated in four serine protease inhibitors based on sunflower trypsin inhibitor‐1. NMR and X‐ray crystallography revealed exceptional consensus of bridging distance and backbone conformations (RMSD<0.5 Å) of the triazole linkages compared to the parent disulfide molecules. The triazole‐bridged peptides also displayed superior half‐lives in liver S9 stability assays compared to disulfide‐bridged peptides. This work establishes a foundation for the application of 1,5‐disubstituted 1,2,3‐triazoles as disulfide mimetics.
An Arylazopyrazole‐Based N‐Heterocyclic Carbene as a Photoswitch on Gold Surfaces: Light‐Switchable Wettability, Work Function, and Conductance
Authors: Nguyen D. Thao , Freitag Matthias , Gutheil Christian , Sotthewes Kai , Tyler Bonnie J. , Böckmann Marcus , Das Mowpriya , Schlüter Friederike , Doltsinis Nikos L. , Arlinghaus Heinrich F. , Ravoo Bart Jan , Glorius Frank
Published: April 2020

A novel photoresponsive and fully conjugated N‐heterocyclic carbene (NHC) has been synthesized that combines the excellent photophysical properties of arylazopyrazoles (AAPs) with an NHC that acts as a robust surface anchor (AAP‐BIMe). The formation of self‐assembled monolayers (SAMs) on gold was proven by ToF‐SIMS and XPS, and the organic film displayed a very high stability at elevated temperatures. This stability was also reflected in a high desorption energy, which was determined by temperature‐programmed SIMS measurements. E‐/Z‐AAP‐BIMe@Au photoisomerization resulted in reversible alterations of the surface energy (i.e. wettability), the surface potential (i.e. work function), and the conductance (i.e. resistance). The effects could be explained by the difference in the dipole moment of the isomers. Furthermore, sequential application of a dummy ligand by microcontact printing and subsequent backfilling with AAP‐BIMe allowed its patterning on gold. To the best of our knowledge, this is the first example of a photoswitchable NHC on a gold surface. These properties of AAP‐BIMe@Au illustrate its suitability as a molecular switch for electronic devices.
Developing New Cancer Nanomedicines by Repurposing Old Drugs
Authors: Yang Bowen , Shi Jianlin
Published: April 2020

The high morbidity and mortality of cancer requires innovative therapeutics. Very recently, several old drugs approved by the U.S. Food and Drug Administration (FDA) or currently undergoing clinical trials, such as 2‐deoxy‐d‐glucose, disulfiram, artemisinin, chloroquine, metformin, and aspirin, which have been extensively applied clinically for the treatment of other diseases with reliable evidence of biosafety, have been engineered into nanosystems for enhancing cancer therapy. These old drugs can cooperate with other components of nanosystems or the ambient biological environment, to favor tumor‐specific therapeutics by nontoxicity‐to‐toxicity transition. This Minireview provides a concentrated summary of the most recent progress made in this emerging field, highlighting the “old drugs, new uses” strategy for the construction of next‐generation nanomedicines. It is expected that the clinical translation of nanomedicines can be accelerated by repurposing old drugs to elevate cancer therapeutic efficacy and specificity.
Isolation and characterization of a novel nanobody for detection of GRP78 expressing cancer cells
Authors: Aghamollaei Hossein , Ghanei Mostafa , Rasaee Mohammad Javad , Latifi Ali Mohammad , Bakherad Hamid , Fasihi‐Ramandi Mahdi , Taheri Ramezan Ali , Gargari Seyed Latif Mousavi
Published: April 2020

Glucose‐regulated protein 78 (GRP78) is an endoplasmic reticulum (ER) chaperone that has been shown that is overexpressed in cancer cells. Overexpression of GRP78 on cancer cells makes this molecule a suitable candidate for cancer detection and targeted therapy. VHH is the binding fragment of camelid heavy‐chain antibodies also known as “nanobody.” The aim of this study is to isolate and produce a new recombinant nanobody using phage display technique to detect cancer cells. Using the c‐terminal domain of GRP78 (CGRP) as an antigen, four rounds of biopanning were performed, and high‐affinity binders were selected by ELISA. Their affinity and functionality were characterized by surface plasmon resonance (SPR) cell ELISA and immunocytochemistry. A unique nanobody named V80 was purified. ELISA and SPR showed that this antibody had high specificity and affinity to the GRP78. Immunofluorescence analysis showed that V80 could specifically bind to the HepG2 and A549 cancer cell lines. This novel recombinant nanobody could bind to the cell surface of different cancer cells. After further evaluation, this nanobody can be used as a new tool for cancer detection and tumor therapy.
Applications of Functional Metal‐Organic Frameworks in Biosensors
Authors: Du Liping , Chen Wei , Zhu Ping , Tian Yulan , Chen Yating , Wu Chunsheng
Published: April 2020

In recent decades, fast advancements in the fields of metal‐organic frameworks (MOFs) are providing unprecedented opportunities for the development of novel functional MOFs for various biosensing applications. Exciting progress is achieved due to the combination of MOFs with various functional components, which introduces novel structures and new features to the MOFs‐based biosensing applications, such as higher stability, higher sensitivity, higher flexibility, and higher specificity. This review aims to be a comprehensive summary of the most recent advances in the development of functional MOFs for various biosensing applications, placing special attention on important contributions in recent 3 years. In this review, the most recent developments in design and synthesis of functional MOFs for biosensing applications are summarized. MOFs‐based biosensing applications are outlined according to the central roles of MOFs in biosensors, which include carriers of sensitive elements, enzyme‐mimic elements, electrochemical signaling, optical signaling, and gas sensing. Finally, the current challenges and future development trends of functional MOFs for biosensing applications are proposed and discussed.
Commentary: Challenges for PhD students during COVID‐19 pandemic: Turning crisis into an opportunity
Authors: Aydemir Duygu , Ulusu Nuriye N.
Published: April 2020

COVID‐19 results in the suspension of life all over the world. Universities suspended their academic activities except for online courses for undergrad and grad students. However, PhD students in both biochemistry and molecular biology fields must hold their experiments at the laboratories. Even under these extreme circumstances, the academic journey of a master's or PhD student should not be stopped; on contrary, they need to use these times to improve their knowledge related to their fields. Therefore, they can turn this COVID‐19 crisis into an opportunity for themselves.
Do anxiety, depression, and intolerance of uncertainty contribute to social problem solving in adult women with anorexia nervosa?
Authors: Sternheim Lot , Danner Unna , van Elburg Annemarie , Harrison Amy
Published: April 2020

Introduction

Inefficient problem solving in the social domain may be one of the difficulties underlying the interpersonal challenges thought to maintain anorexia nervosa (AN). However, past studies have neglected to control for depression, anxiety, and intolerance of uncertainty (IU), which are known to contribute to social problem solving.

Methods

This study aimed to investigate whether adults with AN would show differences in social problem solving on an experimental task (Means‐End Problem Solving; MEPS) and report differences in their attitudes (positive, negative) toward social problem solving and their use of social problem‐solving styles (rational, impulsive–careless, avoidant) on the Social Problem‐Solving Inventory Revised (SPSRI) compared to a non‐AN control group.

Results

Seventy‐four adult women took part (30 with AN and 44 non‐AN controls), and data show that those with AN generated significantly less effective solutions on the MEPS (d = 1.96) reported overall poorer social problem solving on the SPSRI (d = 0.58), reporting more negative and less positive attitudes toward social problem solving, and less impulsive and more avoidant social problem‐solving styles. However, those with AN did not differ from controls in being able to rationalize social problems. Once depression (Beck Depression Inventory: BDI), state anxiety (State‐Trait Anxiety Inventory: STAI), and IU (Intolerance of Uncertainty Scale‐12; IUS‐12) were included as covariates, these differences were no longer significant, suggesting that comorbid depression, anxiety, and IU symptoms may contribute to social problem solving in AN.

Conclusions

There was no specific effect of depression. Treating anxiety and IU might help to improve social problem solving and enable people with AN to be able to better access social support to aid their recovery.
Immunosenescent characteristics of T cells in young patients following haploidentical haematopoietic stem cell transplantation from parental donors
Authors: Lee Ga Hye , Hong Kyung Taek , Choi Jung Yoon , Shin Hee Young , Lee Won‐Woo , Kang Hyoung Jin
Published: April 2020

Objectives

Paediatric and adolescent patients in need of allogeneic haematopoietic stem cell transplantation (HSCT) generally receive stem cells from older, unrelated or parental donors when a sibling donor is not available. Despite encouraging clinical outcomes, it has been suggested that immune reconstitution accompanied by increased replicative stress and a large difference between donor and recipient age may worsen immunosenescence in paediatric recipients.

Methods

In this study, paired samples were collected at the same time from donors and recipients of haploidentical haematopoietic stem cell transplantation (HaploSCT). We then conducted flow cytometry‐based phenotypic and functional analyses and telomere length (TL) measurements of 21 paired T‐cell sets from parental donors and children who received T‐cell‐replete HaploSCT with post‐transplant cyclophosphamide (PTCy).

Results

Senescent T cells, CD28− or CD57+ cells, were significantly expanded in patients. Further, not only CD4+CD28− T cells, but also CD4+CD28+ T cells showed reduced cytokine production capacity and impaired polyfunctionality compared with parental donors, whereas their TCR‐mediated proliferation capacity was comparable. Of note, the TL in patient T cells was preserved, or even slightly longer, in senescent T cells compared with donor cells. Regression analysis showed that senescent features of CD4+ and CD8+ T cells in patients were influenced by donor age and the frequency of CD28− cells, respectively.

Conclusion

Our data suggest that in paediatric HaploSCT, premature immunosenescent changes occur in T cells from parental donors, and therefore, long‐term immune monitoring should be conducted.
Religious and/or Spiritual Social Justice Advocacy: Guidance From the Multicultural and Social Justice Counseling Competencies
Authors: Mintert Jeffrey , Tran Alisia G. T. T. , Kurpius Sharon
Published: April 2020

The Multicultural and Social Justice Counseling Competencies (MSJCC; Ratts, Singh, Nassar‐McMillan, Butler, & McCullough, 2015) provide recommendations for social justice advocacy through a socioecological lens. The authors conceptualize and apply the MSJCC to inform counselor engagement in social justice advocacy for an often‐neglected area of diversity: religion and/or spirituality. Practice and ethical examples, considerations, and recommendations related to religion and/or spirituality in MSJCC‐compatible social justice advocacy are provided.
Assessing the Intersectionality of Religious and Sexual Identities During the Coming‐Out Process
Authors: Shurts W. Matthew , Kooyman Leslie , Rogers Robert C. , Burlew Larry
Published: April 2020

Lesbian, gay, and bisexual (LGB) individuals often experience internalized and/or externalized religious rejection due to their sexual orientation. Initial steps in the coming‐out process can be especially difficult and can result in existential crises, including questioning one's place within the religious/spiritual realm. The authors propose a developmental framework for conceptualizing the role of religion and spirituality in the coming‐out process. Cass's (1979, 1984) stage model of coming out and Genia's (1995) model of religious development, along with additional literature addressing LGB spirituality, serve as foundations for this framework. Counseling and research implications of the framework are also discussed.
“Coming Out” to Parents in a Christian Context: A Consensual Qualitative Analysis of LGB Student Experiences
Authors: Reed Jeffrey L. , Stratton Stephen P. , Koprowski Gregory , Dillon Christina , Dean Janet B. , Yarhouse Mark A. , Lastoria Michael , Bucher Emma K.
Published: April 2020

Disclosures of same‐sex attraction are some of the most difficult experiences for lesbian, gay, and bisexual (LGB) individuals. For LGB individuals of faith, disclosure to parents is often complicated by the intersection of religion/spirituality and sexuality. This study presents a grounded theory about a particular subgroup to address gaps in the literature concerning how LGB students on Christian college campuses describe and experience their parental disclosures. Consensual qualitative research analysis (Hill, Knox, Thompson, Williams, & Hess, 2005; Hill, Thompson, & Williams, 1997) revealed themes related to predisclosure influencing factors, the disclosure event experience, and longer term impacts of the disclosure. Implications for parents, counselors, and college faculty/staff are provided.
The Role of Decision‐Making Models and Reflection in Navigating Ethical Dilemmas
Authors: Burkholder Jessica , Burkholder David , Gavin Martin
Published: April 2020

The ACA Code of Ethics (American Counseling Association [ACA], 2014) mandates counselor competency in using ethical decision‐making models (EDMs) and mandates that counselors use an EDM when confronted with making ethical decisions. Additionally, researchers have highlighted the importance of counselors continually evaluating and reflecting when faced with ethical dilemmas and working through a decision‐making model. Using a phenomenological research design, the authors examined how counselors address ethical dilemmas, including how reflection and EDMs are incorporated into the decision‐making process. Emergent themes from data analysis include (a) incomplete following of EDMs, (b) varied dilemmas, (c) power, and (d) ethics training.
Gamna‐Gandy bodies in fine‐needle aspiration from abdominal splenosis: A clue to underlying portal hypertension
Authors: Angelova Evgeniya A. , Bagherpour Arya , Schnadig Vicki J , He Jing
Published: April 2020

A 40‐year‐old woman presented with abdominal pain and jaundice. Past medical history was significant only for splenectomy following a motor vehicle accident. Owing to presence of multiple peritoneal nodules on computerized tomography (CT) and elevated serum CA‐125, ovarian peritoneal carcinomatosis was suspected. Ultrasound‐guided fine‐needle aspiration (FNA) revealed presence of abundant hemosiderin, leukocytes, endothelial cells, and fungal hypha‐like structures. No evidence of neoplasia was found. Findings were consistent with Gamna‐Gandy bodies (GGBS) within splenic tissue. Based on history of splenectomy and FNA findings, a diagnosis of abdominal splenosis with presence of GGBS was made. Workup for hepatic cirrhosis and portal hypertension was recommended. Liver biopsy confirmed presence of cirrhosis. To our knowledge, this is the first report of GGBS identified within abdominal splenosis. It is important for pathologists to be able to recognize GGBS and to be aware of their relationship to portal hypertension and other conditions associated with severe vascular congestion or hemorrhage. History and pathogenesis of GGBS, their diagnostic morphologic features and a review of cases of GGBS diagnosed via cytology are given.
Justice sensitivity and rejection sensitivity as predictors and outcomes of eating disorder pathology: A 5‐year longitudinal study
Authors: Bondü Rebecca , Bilgin Ayten , Warschburger Petra
Published: April 2020

Objective

Rejection sensitivity and justice sensitivity are personality traits that are characterized by frequent perceptions and intense adverse responses to negative social cues. Whereas there is good evidence for associations between rejection sensitivity, justice sensitivity, and internalizing problems, no longitudinal studies have investigated their association with eating disorder (ED) pathology so far. Thus, the present study examined longitudinal relations between rejection sensitivity, justice sensitivity, and ED pathology.

Method

Participants (N = 769) reported on their rejection sensitivity, justice sensitivity, and ED pathology at 9–19 (T1), 11–21 (T2), and 14–22 years of age (T3).

Results

Latent cross‐lagged models showed longitudinal associations between ED pathology and anxious rejection sensitivity, observer and victim justice sensitivity. T1 and T2 ED pathology predicted higher T2 and T3 anxious rejection sensitivity, respectively. In turn, T2 anxious rejection sensitivity predicted more T3 ED pathology. T1 observer justice sensitivity predicted more T2 ED pathology, which predicted higher T3 observer justice sensitivity. Furthermore, T1 ED pathology predicted higher T2 victim justice sensitivity.

Discussion

Rejection sensitivity—particularly anxious rejection sensitivity—and justice sensitivity may be involved in the maintenance or worsening of ED pathology and should be considered by future research and in prevention and treatment of ED pathology. Also, mental health problems may increase rejection sensitivity and justice sensitivity traits in the long term.
Harnessing knowledge of animal behavior to improve habitat restoration outcomes
Authors: Hale Robin , Blumstein Daniel T. , Mac Nally Ralph , Swearer Stephen E.
Published: April 2020

Restoring degraded habitat to increase biodiversity is a global challenge. While habitat restoration for animals should lead to self‐sustaining breeding populations of target species, often this does not occur. Understanding the factors constraining progress toward this goal and how these constraints can be overcome is vital. We use a review to highlight how insights from animal behavior can help plan restoration projects, and identify and ameliorate some of the reasons why restoration may fail to meet biodiversity goals. We present a decision tree to highlight how behavioral knowledge can identify and address two ways in which restoration can fail when: (1) target animals do not colonize restored sites and (2) they colonize restored sites but experience conditions that do not match their habitat requirements. Investing in the collection of behavioral information may be difficult for management agencies when funding is limited. We highlight when behavioral information is likely to be most important, and some of the practical considerations for its application in restoration projects. We conclude by identifying key knowledge gaps and future directions that can improve restoration outcomes for biodiversity by incorporating behavioral knowledge. Restoration is needed to ameliorate the effects of habitat loss, degradation, and fragmentation on fauna. Unfortunately, restoration does not always lead to the intended optimal outcomes for target animals. A greater consideration of animal behavior and its consequences can help during both the planning and evaluation of restoration projects. We hope to stimulate dialogue between restoration and behavioral ecologists to improve restoration outcomes for animals.
Relating N–H Bond Strengths to the Overpotential for Catalytic Nitrogen Fixation
Authors: Chalkley Matthew J. , Peters Jonas C.
Published: April 2020

Nitrogen (N2) fixation to produce bio‐available ammonia (NH3) is essential to all life but is a challenging transformation to catalyze owing to the chemical inertness of N2. Transition metals can, however, bind N2 and activate it for functionalization. Significant opportunities remain in developing robust and efficient transition metal catalysts for the N2 reduction reaction (N2RR). One opportunity to target in catalyst design concerns the stabilization of transition metal diazenido species (M‐NNH) that result from the first N2 functionalization step. Well‐characterized M‐NNH species remain very rare, likely a consequence of their low N–H bond dissociation free energies (BDFEs). In this essay, we discuss the relationship between the BDFEN–H of a given M‐NNH species to the observed overpotential and selectivity for N2RR catalysis with that catalyst system. We note that developing strategies to either increase the N–H BDFEs of M‐NNH species, or to avoid M‐NNH intermediates altogether, are potential routes to improved N2RR efficiency.
Enhancement of Selective Fixation of Dinitrogen to Ammonia under Modal Strong Coupling Conditions
Authors: Oshikiri Tomoya , Shi Xu , Misawa Hiroaki
Published: April 2020

Invited for the cover of this issue is the group of Hiroaki Misawa from Hokkaido University, Sapporo, Japan. The cover image shows a two‐electrode system for ammonia photosynthesis composed of a strong coupling photoanode and a Zr mesh cathode.
Unsettling ourselves: Notes on reflective listening beyond discomfort
Authors: Petillo April
Published: April 2020

Reflecting on Melissa Harris‐Perry's 2016 American Anthropological Association (AAA) keynote address and conversations that followed, this semi‐autoethnographic exploration considers disciplinary tensions and complicities concerning our (un)willingness to hear content when discomforted by academic affect. The article considers why feminist anthropologists might “listen through discomfort,” a process Petillo describes as “embodied listening where self‐reflection is deeply entangled,” and advocates including this in intersectional feminist, queer activist ethnographic praxis. Attuned to the benefits of feminist activist ethnographic self‐corrective action (Morgensen 2013) and aware that research is always somewhat performative (Oikarinen‐Jabai 2003), Petillo focuses on the enhanced potential of embodied listening—a listening reliant on kinesthetic literacy (Gill 2012, 33) turned inward or the ability to read our own “vocabulary of actions.” Through notes and intimately personal observations, Petillo highlights where self‐reflective embodied listening through the “discomforts” of engaging lived realities without “academic affect” affords the feminist, queer ethnographic activist a path for transdisciplinary listening across identities and intimacies.
Needlework
Authors: Chin Elizabeth
Published: April 2020

Exploring needlework as a mode of feminist ethnographic knowledge‐making, this reflexive and reflective piece focuses on the ways in which making Vodou flags serves to expand my own practice. In particular, how does needlework compel ways of thinking and feeling that exist beyond language? How do durational investments of time and work allow an expansion of ethnographic knowing?
Human Leukocyte Antigen B*14:01 and B*35:01 Are Associated With Trimethoprim‐Sulfamethoxazole Induced Liver Injury
Authors: Li Yi‐Ju , Phillips Elizabeth J. , Dellinger Andrew , Nicoletti Paola , Schutte Ryan , Li Danmeng , Ostrov David A. , Fontana Robert J. , Watkins Paul B. , Stolz Andrew , Daly Ann K , Aithal Guruprasad P , Barnhart Huiman , Chalasani Naga ,   the Drug‐induced Liver Injury Network
Published: April 2020

Background and Aims

Trimethoprim (TMP)–sulfamethoxazole (SMX) is an important cause of idiosyncratic drug‐induced liver injury (DILI), but its genetic risk factors are not well understood. This study investigated the relationship between variants in the human leukocyte antigen (HLA) class 1 and 2 genes and well‐characterized cases of TMP‐SMX DILI.

Approach and Results

European American and African American persons with TMP‐SMX DILI were compared with respective population controls. HLA sequencing was performed by Illumina MiSeq (Illumina, San Diego, CA) for cases. The HLA genotype imputation with attribute bagging program was used to impute HLA alleles for controls. The allele frequency difference between case patients and controls was tested by Fisher’s exact tests for each ethnic group. For European Americans, multivariable logistic regression with Firth penalization was used to test the HLA allelic effect after adjusting for age and the top two principal components. Molecular docking was performed to assess HLA binding with TMP and SMX. The European American subset had 51 case patients and 12,156 controls, whereas the African American subset had 10 case patients and 5,439 controls. Four HLA alleles were significantly associated in the European American subset, with HLA‐B*14:01 ranking at the top (odds ratio, 9.20; 95% confidence interval, 3.16, 22.35; P = 0.0003) after covariate adjustment. All carriers of HLA‐B*14:01 with TMP‐SMX DILI possessed HLA‐C*08:02, another significant allele (P = 0.0026). This pattern was supported by HLA‐B*14:01–HLA‐C*08:02 haplotype association (P = 1.33 × 10−5). For the African American patients, HLA‐B*35:01 had 2.8‐fold higher frequency in case patients than in controls, with 5 of 10 patients carrying this allele. Molecular docking showed cysteine at position 67 in HLA‐B*14:01 and phenylalanine at position 67 in HLA‐B*35:01 to be the predictive binding sites for SMX metabolites.

Conclusions

HLA‐B*14:01 is associated with TMP‐SMX DILI in European Americans, and HLA‐B*35:01 may be a potential genetic risk factor for African Americans.
B‐cell maturation antigen‐specific chimeric antigen receptor T cells for multiple myeloma: Clinical experience and future perspectives
Authors: Sellner Leopold , Fan Fuli , Giesen Nicola , Schubert Maria‐Luisa , Goldschmidt Hartmut , Müller‐Tidow Carsten , Dreger Peter , Raab Marc S. , Schmitt Michael
Published: April 2020

Despite major advances in the treatment of multiple myeloma (MM), it remains a largely incurable disease with long‐term control often dependent on continuous therapy. More effective, better tolerated treatments are therefore required to achieve durable remissions and to improve the quality of life of MM patients. Adoptive immunotherapy employing T cells expressing chimeric antigen receptors (CAR) is currently among the most promising treatment approaches in cancer. Within the target portfolio for MM immunotherapy, B‐cell maturation antigen (BCMA) is among the most widely studied target antigens. BCMA is consistently expressed on MM cells and, importantly, is not expressed in critical healthy tissue. For this reason, it is an ideal target for MM immunotherapy. Several clinical trials evaluating different BCMA‐targeting CAR constructs have been initiated and early results are very promising. However, in this rapidly developing clinical landscape, the ultimate role of BCMA‐specific CAR‐T cell therapy remains unclear. In this review, we will summarize currently available clinical data on BCMA‐directed CAR‐T cells and discuss potential future perspective for this promising treatment approach in MM.
C─H⋯O hydrogen bonds in kinase‐inhibitor interfaces
Authors: Derewenda Zygmunt S. , Hawro Izabela , Derewenda Urszula
Published: April 2020

C─H⋯O hydrogen bonds constitute a unique class of cohesive interactions. Their properties are similar to those of canonical H‐bonds, although their energy is significantly lower, typically in the 0.5–2.5 kcal/mol range. Polarised C─H groups, such as those adjacent to electronegative groups, or within aromatic moieties, are particularly strong donors. C─H⋯O bonds are ubiquitous in nucleic acids and in proteins, notably stabilizing the β‐sheet secondary structure. They have also been observed in numerous protein‐ligand interactions. Here, we analysed crystal structures, deposited in the Protein Data Bank, of complexes of FDA‐approved protein kinase inhibitors with cognate kinases, to assess the possible role of C─Hinhibitor⋯Oprotein hydrogen bonds. The conserved hinge motif of protein kinases with two solvent‐exposed carbonyl groups and one exposed backbone amide, is well known to be involved in canonical H‐bonding with inhibitors. We now find that in virtually all complexes where the inhibitor interacts with the hinge backbone, at least one of the hinge carbonyl groups accepts an H‐bond from a C─H inhibitor group, which is either aromatic or adjacent to an electronegative group. These observations are important for design of hinge‐binding scaffolds of novel kinase inhibitors for therapeutic use.
The promise of regenerative medicine in the treatment of urogenital disorders
Authors: Keshel Saeed Heidari , Rahimi Azam , Hancox Zoe , Ebrahimi Maryam , Khojasteh Arash , Sefat Farshid
Published: April 2020

Polymers and scaffolds are the most significant tools in regenerative medicine. Urogenital disorders are an important group of diseases that greatly affect the patient's life expectancy and quality. Reconstruction of urogenital defects is one of the current challenges in regenerative medicine. Regenerative medicine, as well as tissue engineering, may offer suitable approaches, while the tools needed are appropriate materials and cells. Autologous urothelial cells obtained from biopsy, bone marrow‐derived stem cells, adipose stem cells and urine‐derived stem cells that expressed mesenchymal cell markers are the cells that mainly used. In addition, two main types of biomaterials mainly exist; synthetic polymers and composite scaffolds that are biodegradable polymers with controllable properties and naturally derived biomaterials such as extracellular matrix components and acellular tissue matrices. In this review, we present and evaluate the most appropriate and suitable scaffolds (naturally derived and synthetic polymers) and cells applied in urogenital reconstruction.
Diagnostic Value of Magnetic Resonance Imaging in Fibrodysplasia Ossificans Progressiva
Authors: Botman Esmée , Teunissen Bernd P , Raijmakers Pieter , de Graaf Pim , Yaqub Maqsood , Treurniet Sanne , Schoenmaker Ton , Bravenboer Nathalie , Micha Dimitra , Pals Gerard , Bökenkamp Arend , Netelenbos J Coen , Lammertsma Adriaan A , Eekhoff Elisabeth MW
Published: April 2020

Using [18F] Sodium Fuoride (NaF) Positron Emission Tomography (PET) it is not only possible to identify the ossifying potency of a flare‐up, but also to identify an asymptomatic chronic stage of fibrodysplasia ossificans progressiva (FOP). The purpose of this study was to investigate the diagnostic role of a more widely available imaging modality, Magnetic Resonance Imaging (MRI), which is of special interest for studies in pediatric FOP patients. MRI and [18F]NaF PET/CT images at time of inclusion and subsequent follow‐up CT scans of 4 patients were analyzed retrospectively. Presence, location, and intensity of edema identified by MRI were compared with activity on [18F]NaF PET. Occurrence or progression of heterotopic ossification (HO) was examined on the follow‐up CT images. Thirteen different lesions in various muscle groups were identified: five lesions with only edema, five lesions with both edema and increased [18F]NaF uptake, one lesion with only increased [18F]NaF uptake, and two lesions with neither edema nor uptake of [18F]NaF. Mild edema, found in three lesions, was present at asymptomatic sites, which did not show increased [18F] NaF uptake or progression of HO on consecutive CT images. Moderate edema was found in three symptomatic lesions, with increased [18F]NaF on PET and progression of HO on CT. Severe edema was identified in four lesions. Interestingly, two of these lesions did not develop HO during follow‐up; one of these two even gave obvious symptoms of a flare‐up. MRI can identify whether symptoms are the result of an acute flare‐up by the presence of moderate to severe edema. The occurrence of severe edema on MRI was not always related to an ossifying lesion. The additional diagnostic value of MRI requires further investigation, but MRI does not seem to fully replace the diagnostic characteristics of [18F]NaF PET/CT in FOP. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
College students’ attitudes, stigma, and intentions toward seeking online and face‐to‐face counseling
Authors: Bird Matthew D. , Chow Graig M. , Yang Yanyun
Published: April 2020

Objective(s)

To investigate differences in public stigma, self‐stigma, attitudes (value and discomfort), and intentions to seek help between online and face‐to‐face counseling. To identify a difference in the relationship between these variables and both counseling modalities.

Method

An online survey completed by 538 college students from one university in the Southeastern United States. The sample included 412 females and 126 males with a mean age of 20.21 years (standard deviation [SD] = 1.26).

Results

Significantly higher levels of self‐stigma and discomfort toward online counseling were reported. Significantly higher value and intentions were reported toward face‐to‐face counseling. Self‐stigma was positively related to public stigma, value was negatively related to self‐stigma, and intentions toward seeking help was positively related to value.

Conclusions

Results suggest face‐to‐face counseling is seen as a more favorable method of service delivery compared to online counseling. Value toward online counseling is an important predictor for seeking this type of help.
Pevonedistat, a NEDD8‐activating enzyme inhibitor, induces apoptosis and augments efficacy of chemotherapy and small molecule inhibitors in pre‐clinical models of diffuse large B‐cell lymphoma
Authors: Torka Pallawi , Mavis Cory , Kothari Shalin , Belliotti Sarah , Gu Juan , Sundaram Suchitra , Barth Matthew , Hernandez‐Ilizaliturri Francisco J.
Published: April 2020

We studied the biological activity of pevonedistat, a first‐in‐class NEDD8‐activating enzyme (NAE) inhibitor, in combination with various cytotoxic chemotherapy agents and small molecule inhibitors in lymphoma preclinical models. Pevonedistat induced cell death in activated B‐cell (ABC) diffuse large B‐cell lymphoma (DLBCL) cell lines and to a lesser degree in germinal center B‐cell (GCB) DLBCL cell lines. In pevonedistat sensitive cells, we observed inhibition of NF‐κB activity by p65 co‐localization studies, decreased expression of BCL‐2/Bcl‐XL, and upregulation of BAK levels. Pevonedistat enhanced the activity of cytarabine, cisplatin, doxorubicin, and etoposide in ABC‐, but not in the GCB‐DLBCL cell lines. It also exhibited synergy with ibrutinib, selinexor, venetoclax, and A‐1331852 (a novel BCL‐XL inhibitor). In vivo, the combination of pevonedistat and ibrutinib or pevonedistat and cytarabine prolonged survival in SCID mice xenograft models when compared with monotherapy controls. Our data suggest that targeting the neddylation pathway in DLBCL is a viable therapeutic strategy and support further clinical studies of pevonedistat as a single agent or in combination with chemotherapy or novel targeted agents.
Synthesis, anticancer, and computational studies of 1, 3, 4‐oxadiazole‐purine derivatives
Authors: Shahzadi Irum , Zahoor Ameer F. , Rasul Azhar , Rasool Nasir , Raza Zohaib , Faisal Shahla , Parveen Bushra , Kamal Shagufta , Zia‐ur‐Rehman Muhammad , Zahid Faisal M.
Published: April 2020

Theophylline‐7‐acetic acid (acefylline) (3) and its derivatives are pharmacologically active compounds and generally recognized as bronchodilators for the treatment of respiratory diseases like acute asthma for over 70 years. In this article, synthesis of 2‐((5‐((1,3‐dimethyl‐2,6‐dioxo‐2,3‐dihydro‐1H‐purin‐7(6H)‐yl)methyl)‐1,3,4‐oxadiazol‐2‐yl)thio)‐N‐arylacetamides (10a‐j) has been reported. All the synthesized derivatives (10a‐j) were structurally verified by FT‐IR, 1H NMR, 13C NMR and evaluated for their anti‐cancer (using MTT assay), hemolytic and thrombolytic potential. N‐(4‐Chlorophenyl)‐2‐(5‐((1,3‐dimethyl‐2,6‐dioxo‐2,3‐dihydro‐1H‐purin‐7(6H)‐yl)methyl)‐1,3,4‐oxadiazol‐2‐ylthio)acetamide (10g) was found to be the most active against human liver cancer cell lines (Huh7) having cell viability 53.58 ± 1.28 using 100 μg/mL concentration of compound which was further in‐silico modelled to describe the possible mechanistic insights for its anti‐proliferative activity. The results of hemolytic and thrombolytic activities indicated that these derivatives were less toxic and hold considerable potential as a drug candidate. 2‐(5‐((1,3‐Dimethyl‐2,6‐dioxo‐2,3‐dihydro‐1H‐purin‐7(6H)‐yl)methyl)‐1,3,4‐oxadiazol‐2‐ylthio)‐N‐(2‐fluorophenyl)acetamide (10c) of the series was found to be least toxic with 0.1% hemolysis relative to ABTS (95.5%) as positive control. 2‐(5‐((1,3‐Dimethyl‐2,6‐dioxo‐2,3‐dihydro‐1H‐purin‐7(6H)‐yl)methyl)‐1,3,4‐oxadiazol‐2‐ylthio)‐N‐(tetrahydro‐2H‐pyran‐4‐yl)acetamide (10j) exhibited potent clot lysis activity (90%) as compared to negative control DMSO (0.57%).
Berberine suppresses influenza virus-triggered NLRP3 inflammasome activation in macrophages by inducing mitophagy and decreasing mitochondrial ROS
Authors: Liu Hui , You Leiming , Wu Jun , Zhao Mengfan , Guo Rui , Zhang Haili , Su Rina , Mao Qin , Deng Di , Hao Yu
Published: April 2020

Berberine (BBR) is an isoquinoline alkaloid extracted from several commonly used Chinese herbs. Our previous studies demonstrated BBR-mediated alleviation of lung injury due to inflammation and decrease in the mortality of mice with influenza viral pneumonia. The recent argument of autophagy against inflammatory responses has aroused wide concerns. This study focuses on the reactive oxygen species-Nod-like receptor protein 3 (ROS-NLRP3) pathway to investigate whether BBR inhibits NLRP3 inflammasome activation by inducing mitophagy. Our results demonstrate that BBR and mitochondrion-targeted superoxide dismutase mimetic (Mito-TEMPO; a specific mitochondrial ROS scavenger) significantly restricted NLRP3 inflammasome activation, increased mitochondrial membrane potential (MMP), and decreased mitochondrial ROS (mtROS) generation in J774A.1 macrophages infected with PR8 influenza virus. These observations suggest that the inhibitory effects of BBR on NLRP3 inflammasome activation were associated with the amelioration of mtROS generation. BBR treatment induced regular mitophagy, as evident from the increase in microtubule-associated protein 1 light chain 3 II, decrease in p62, colocalization of LC3 and mitochondria, and formation of autophagosomes. However, 3-methyladenine, an autophagy inhibitor, reversed the inhibitory effects of BBR on mitochondrial damage and NLRP3 inflammasome activation in influenza virus-infected macrophages, indicating the involvement of mitophagy in mediating the inhibitory effects of BBR on NLRP3 inflammasome activation. Furthermore, the knockdown of Bcl-2/adenovirus E18-19-kDa interacting protein 3 (BNIP3) expression attenuated the effects of BBR on mitophagy induction to some extent, suggesting that the BBR-induced mitophagy may be, at least in part, mediated in a BNIP3-dependent manner. Similar results were obtained in vivo using a mouse model of influenza viral pneumonia that was administered with BBR. Taken together, these findings suggest that restricting NLRP3 inflammasome activation by decreasing ROS generation through mitophagy induction may be crucial for the BBR-mediated alleviation of influenza virus-induced inflammatory lesions.