bluuebunny/crossref_metadata_2025 huggingface dataset:
The first genome‐wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease
Authors: Dalmasso Maria Carolina , de Rojas Itziar , Olivar Natividad , Muchnik Carolina , Angel Bárbara , Gloger Sergio , Sanchez Abalos Mariana Soledad , Chacón María Victoria , Aránguiz Rafael , Orellana Paulina , Cuesta Carolina , Galeano Pablo , Campanelli Lorenzo , Novack Gisela Vanina , Martinez Luis Eduardo , Medel Nancy , Lisso Julieta , Sevillano Zulma , Irureta Nicolás , Castaño Eduardo Miguel , Montrreal Laura , Thoenes Michaela , Hanses Claudia , Heilmann‐Heimbach Stefanie , Kairiyama Claudia , Mintz Inés , Villella Ivana , Rueda Fabiana , Romero Amanda , Wukitsevits Nancy , Quiroga Ivana , Gona Cristian , Lambert Jean‐Charles , Solis Patricia , Politis Daniel Gustavo , Mangone Carlos Alberto , Gonzalez‐Billault Christian , Boada Mercè , Tàrraga Lluís , Slachevsky Andrea , Albala Cecilia , Fuentes Patricio , Kochen Silvia , Brusco Luis Ignacio , Ruiz Agustín , Morelli Laura , Ramírez Alfredo
Published: November 2023

INTRODUCTION

Genome‐wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities.

METHODS

We performed GWAS on sporadic Alzheimer's disease (AD) including 539 patients and 854 controls from Argentina and Chile. We combined our results with those from the European Alzheimer and Dementia Biobank (EADB) in a meta‐analysis and tested their genetic risk score (GRS) performance in this admixed population.

RESULTS

We detected apolipoprotein E ε4 as the single genome‐wide significant signal (odds ratio  = 2.93 [2.37–3.63], P = 2.6 × 10−23). The meta‐analysis with EADB summary statistics revealed four new loci reaching GWAS significance. Functional annotations of these loci implicated endosome/lysosomal function. Finally, the AD‐GRS presented a similar performance in these populations, despite the score diminished when the Native American ancestry rose.

DISCUSSION

We report the first GWAS on AD in a population from South America. It shows shared genetics modulating AD risk between the European and these admixed populations.

Highlights

This is the first genome‐wide association study on Alzheimer's disease (AD) in a population sample from Argentina and Chile.

Trans‐ethnic meta‐analysis reveals four new loci involving lysosomal function in AD.

This is the first independent replication for TREM2L, IGH‐gene‐cluster, and ADAM17 loci.

A genetic risk score (GRS) developed in Europeans performed well in this population.

The higher the Native American ancestry the lower the GRS values.
Nature of Nonlocality in Triangle Network based on Elegant Joint Measurement
Authors: Kundu Amit , Sarkar Debasis
Published: November 2023

Defining nonlocality in a no‐input closed quantum network scenario is a new area of interest nowadays. Gisin, in [Entropy 21, 325 (2019)], proposed a possible condition for non‐tri‐locality of the trivial no‐input closed network scenario, triangle network, by introducing a new kind of joint measurement bases and a probability bound. In [npj Quantum Information (2020) 6:70] they found a shred of numerical evidence in support of Gisin's probability bound. Now based on that probability bound, it finds the nature of the correlation in a triangle network scenario. This study observes how far the probability lies from that Gisin's bound with every possible combination of entangled and local pure states distributed from three independent quantum sources. Here, it uses the generalized Elegant Joint Measurements bases for each party and find that there is a dependency of non‐locality on the entanglement of these joint measurement bases. It also checks the probability bound for the polygon structure.
Connecting Biological and Synthetic Approaches for Electrocatalytic CO2 Reduction
Authors: Cobb Samuel J. , Rodríguez‐Jiménez Santiago , Reisner Erwin
Published: November 2023

Electrocatalytic CO2 reduction has developed into a broad field, spanning fundamental studies of enzymatic ‘model’ catalysts to synthetic molecular catalysts and heterogeneous gas diffusion electrodes producing commercially relevant quantities of product. This diversification has resulted in apparent differences and a disconnect between seemingly related approaches when using different types of catalysts. Enzymes possess discrete and well understood active sites that can perform reactions with high selectivity and activities at their thermodynamic limit. Synthetic small molecule catalysts can be designed with desired active site composition but do not yet display enzyme‐like performance. These properties of the biological and small molecule catalysts contrast with heterogeneous materials, which can contain multiple, often poorly understood active sites with distinct reactivity and therefore introducing significant complexity in understanding their activities. As these systems are being better understood and the continuously improving performance of their heterogeneous active sites closes the gap with enzymatic activity, this performance difference between heterogeneous and enzymatic systems begins to close. This convergence removes the barriers between using different types of catalysts and future challenges can be addressed without multiple efforts as a unified picture for the biological‐synthetic catalyst spectrum emerges.
DNA‐Barcoded Plasmonic Nanostructures for Activity‐Based Protease Sensing
Authors: Pandit Subrata , Duchow Mark , Chao Wilson , Capasso Anna , Samanta Devleena
Published: November 2023

We report the development of a new class of protease activity sensors called DNA‐barcoded plasmonic nanostructures. These probes are comprised of gold nanoparticles functionalized with peptide‐DNA conjugates (GPDs), where the peptide is a substrate of the protease of interest. The DNA acts as a barcode identifying the peptide and facilitates signal amplification. Protease‐mediated peptide cleavage frees the DNA from the nanoparticle surface, which is subsequently measured via a CRISPR/Cas12a‐based assay as a proxy for protease activity. As proof‐of‐concept, we show activity‐based, multiplexed detection of the SARS‐CoV‐2‐associated protease, 3CL, and the apoptosis marker, caspase 3, with high sensitivity and selectivity. GPDs yield >25‐fold turn‐on signals, 100‐fold improved response compared to commercial probes, and detection limits as low as 58 pM at room temperature. Moreover, nanomolar concentrations of proteases can be detected visually by leveraging the aggregation‐dependent color change of the gold nanoparticles. We showcase the clinical potential of GPDs by detecting a colorectal cancer‐associated protease, cathepsin B, in three different patient‐derived cell lines. Taken together, GPDs detect physiologically relevant concentrations of active proteases in challenging biological samples, require minimal sample processing, and offer unmatched multiplexing capabilities (mediated by DNA), making them powerful chemical tools for biosensing and disease diagnostics.
Iron‐Catalyzed Asymmetric α‐Alkylation of 2‐Acylimidazoles via Dehydrogenative Radical Cross‐Coupling with Alkanes
Authors: Xu Nian , Pu Maoping , Yu Han , Yang Gaofei , Liu Xiaohua , Feng Xiaoming
Published: November 2023

The direct α‐alkylation of acyclic carbonyls with nonactivated hydrocarbons through C(sp3)−H functionalization is both extremely promising and notably challenging, especially when attempting to achieve enantioselectivity using iron‐based catalysts. We have identified a robust chiral iron complex for the oxidative cross‐coupling of 2‐acylimidazoles with benzylic and allylic hydrocarbons, as well as nonactivated alkanes. The readily available and tunable N,N′‐dioxide catalysts of iron in connection with oxidants exhibit precise asymmetric induction (up to 99 % ee) with good compatibility in moderate to good yields (up to 88 % yield). This protocol provides an elegant and straightforward access to optically active acyclic carbonyl derivatives starting from simple alkanes without prefunctionalization. Density functional theory (DFT) calculations and control experiments were made to gain insight into the nature of C−C bond formation and the origin of enantioselectivity. We propose a radical‐radical cross‐coupling process enabled by the immediate interconversion between chiral ferric species and ferrous species.
α‐Functionalisation of Cyclic Sulfides Enabled by Lithiation Trapping
Authors: Seling Nico , Atobe Masakazu , Kasten Kevin , Firth James D. , Karadakov Peter B. , Goldberg Frederick W. , O'Brien Peter
Published: November 2023

A general and straightforward procedure for the lithiation trapping of cyclic sulfides such as tetrahydrothiophene, tetrahydrothiopyran and a thiomorpholine is described. Trapping with a wide range of electrophiles is demonstrated, leading to more than 50 diverse α‐substituted saturated sulfur heterocycles. The methodology provides access to a range of α‐substituted cyclic sulfides that are not easily synthesised by the currently available methods.
Covalent Organic Frameworks: Opportunities for Rational Materials Design in Cancer Therapy
Authors: Zhou Le‐Le , Guan Qun , Dong Yu‐Bin
Published: November 2023

Nanomedicines are extensively used in cancer therapy. Covalent organic frameworks (COFs) are crystalline organic porous materials with several benefits for cancer therapy, including porosity, design flexibility, functionalizability, and biocompatibility. This review examines the use of COFs in cancer therapy from the perspective of reticular chemistry and function‐oriented materials design. First, the modification sites and functionalization methods of COFs are discussed, followed by their potential as multifunctional nanoplatforms for tumor targeting, imaging, and therapy by integrating functional components. Finally, some challenges in the clinical translation of COFs are presented with the hope of promoting the development of COF‐based anticancer nanomedicines and bringing COFs closer to clinical trials.
Prediction of Early Atherosclerotic Plaques Using a Sequence‐Activated Fluorescence Probe for the Simultaneous Detection of γ‐Glutamyl Transpeptidase and Hypobromous Acid
Authors: Wang Hui , Zhang Xiaoting , Li Ping , Huang Fang , Xiu Tiancong , Wang HongTong , Zhang Wei , Zhang Wen , Tang Bo
Published: November 2023

Atherosclerosis is a lipoprotein‐driven disease, and there is no effective therapy to reverse atherosclerosis or existing plaques. Therefore, it is urgently necessary to create a noninvasive and reliable approach for early atherosclerosis detection to prevent initial plaque formation. Atherosclerosis is intimately associated with inflammation, which is accompanied by an excess of reactive oxygen species (ROS), leading to cells requiring more glutathione (GSH) to resist severe oxidative stress. Therefore, the GSH‐hydrolyzed protein γ‐glutamyl transpeptidase (GGT) and the ROS‐hypobromous acid (HBrO) are potential biomarkers for predicting atherogenesis. Hence, to avoid false‐positive diagnoses caused by a single biomarker, we constructed an ingenious sequence‐activated double‐locked TP fluorescent probe, C‐HBrO‐GGT, in which two sequential triggers of GGT and HBrO are meticulously designed to ensure that the probe fluoresces in response to HBrO only after GGT hydrolyzes the probe. By utilization of C‐HBrO‐GGT, the voltage‐gated chloride channel (CLC‐1)‐HBrO‐catalase (CAT)‐GGT signaling pathway was confirmed in cellular level. Notably, the forthcoming atherosclerotic plaques were successfully predicted before the plaques could be observed via the naked eye or classical immunofluorescent staining. Collectively, this research proposed a powerful tool to indicate the precise position of mature plaques and provide early warning of atherosclerotic plaques.
Reaktivität von [Cp*Fe(η5‐As5)] gegenüber Carbenen, Silylenen und Germylenen
Authors: Reichl Stephan , Riesinger Christoph , Yadav Ravi , Timoshkin Alexey Y. , Roesky Peter W. , Scheer Manfred
Published: November 2023

Das Reaktionsverhalten von [Cp*Fe(η5‐As5)] (I) (Cp*=C5Me5) gegenüber Carbenen und ihren schwereren Analoga wurde untersucht. Die Reaktion von I mit NHCs (NHCs=N‐heterocyclische Carbene) gibt die ersten Substitutionsprodukte von Polyarsen‐Ligandkomplexen mittels NHCs [Cp*Fe(η4‐As5NHC)] (1 a: NHC=IMe=1,3,4,5‐Tetramethylimidazolin‐2‐yliden, 1 b: NHC=IMes=1,3‐Bis(2,4,6‐trimethylphenyl)‐imidazolin‐2‐yliden). Im Gegensatz dazu führt die Reaktion von I mit EtCAAC (EtCAAC=2,6‐Diisopropylphenyl)‐4,4‐diethyl‐2,2‐dimethyl‐pyrrolidin‐5‐yliden) zu einer Fragmentierung und Bildung einer neuartigen As6‐sägebockartigen Verbindung [As2(AsEtCAAC)4] (2). Die Reaktion von (LE)2 (L=PhC(NtBu)2; E=Si, Ge) mit I resultiert in einer Umlagerung und einer Insertion von LE‐Fragmenten, was zur Bildung einzigartiger silizium‐ (4: [Cp*Fe(η4‐As4SiL)], 5 a: [Cp*Fe(η4‐As6SiL)) und germanium‐haltiger (5 b: [Cp*Fe(η4‐As6GeL)) cyclischer Polyarsen‐Ligandkomplexe führt.
Effect of Feature Shape and Dimension of a Confinement Geometry on Selectivity of Electrocatalytic CO2 Reduction
Authors: Kim Yesol , Yun Geun‐Tae , Kim Minki , Jamal Aqil , Gereige Issam , Ager Joel W. , Jung Woo‐Bin , Jung Hee‐Tae
Published: November 2023

The local confinement effect, which can generate a high concentration of hydroxide ions and reaction intermediates near the catalyst surface, is an important strategy for converting CO2 into multi‐carbon products in electrocatalytic CO2 reduction. Therefore, understanding how the shape and dimension of the confinement geometry affect the product selectivity is crucial. In this study, we report for the first time the effect of the shape (degree of confinement) and dimension of the confined space on the product selectivity without changing the intrinsic property of Cu. We demonstrate that geometry influences the outcomes of products, such as CH4, C2H4, and EtOH, in different ways: the selectivity of CH4 and EtOH is affected by shape, while the selectivity of C2H4 is influenced by dimension of geometry predominantly. These phenomena are demonstrated, both experimentally and through simulation, to be induced by the local confinement effect within the confined structure. Our geometry model could serve as basis for designing the confined structures tailored for the production of specific products.
High Gas Permeability in Aged Superglassy Membranes with Nanosized UiO‐66−NH2/cPIM‐1 Network Fillers
Authors: Qiu Boya , Yu Ming , Luque‐Alled Jose Miguel , Ding Shengzhe , Foster Andrew B. , Budd Peter M. , Fan Xiaolei , Gorgojo Patricia
Published: November 2023

Superglassy membranes synthesised by polymers of intrinsic microporosity (PIMs) suffer from physical aging and show poor gas permeance over time, especially thin membranes, due to the fast rearrangement of nonequilibrium polymer chains. Herein, we constructed a novel PIM‐1 thin film nanocomposite membrane (TFN) using nanosized UiO‐66−NH2 (≈10 nm)/carboxylated PIM‐1 (cPIM‐1) as the composite filler. Unlike conventional fillers, which interact with the polymer only via the surface, the UiO‐66−NH2/cPIM‐1 forms a stable three‐dimensional (3D) network intertwining with the polymer chains, being very effective to impede chain relaxation, and thus physical aging. Nanosizing of UiO‐66−NH2 was achieved by regulating the nucleation kinetics using carbon quantum dots (CQD) during the synthesis. This led to increased surface area, and hence more functional groups to bond with cPIM‐1 (via hydrogen bonding between −NH2 and −COOH groups), which also improved interfacial compatibility between the 3D network and polymer chains avoiding defect formation. As a result, the novel TFN showed significantly improved performance in gas separation along with reduced aging (i.e. ≈6 % loss in CO2 permeability over 63 days); the aged membranes had a CO2 permeance of 2504 GPU and ideal selectivity values of 37.2 and 23.8 for CO2/N2 and CO2/CH4, respectively.
The missing father: why can't infant mental health services keep dads in mind?
Authors: Lim Izaak , McMillan Hannah , Robertson Paul , Fletcher Richard
Published: November 2023

Despite the weight of scientific evidence demonstrating the importance of fathers in the social and emotional development and well‐being of infants, infant mental health services struggle to engage fathers. Commonly, fathers are assumed to be unavailable, uninterested, unnecessary, or even unsafe in relation to infant mental health work. These outdated perspectives perpetuate the myth that this work pertains exclusively to the infant–mother dyad. This paper aims to explore some of the reasons for and barriers to involving fathers in infant mental health services. We present an imagined conversation between three mental health professionals working in a child and adolescent mental health service. Presented as a script, the various arguments, counterarguments, and reflections made by the three characters aim to bring the subject matter to life and capture something akin to an actual discussion between colleagues working in a child mental health service. A junior clinician notices that an infant case presented at the multidisciplinary team meeting did not mention the child's father. A senior clinician explains that the team's work usually focuses on the infant–mother relationship, as this is considered of primary importance clinically. A psychiatrist, who has only recently joined the team, explores some of the aspects of team culture that might exclude fathers from participating in the service. Several plausible objections to involving fathers are explored as the discussion unfolds between the three professionals. Infant mental health services should consider how their culture and processes influence whether fathers and/or other adult caregivers engage in these services. For clinicians, thinking about the infant's immediate interpersonal context from their unique development perspective can reveal opportunities and resources within the family that may lead to effective systemic treatment approaches.
Thinking three, revisited: infants, coparents, gender roles, and cultural contexts
Authors: McHale James P. , Jenkins Kacey L.
Published: November 2023

Tracing its beginnings to the mid‐1990s, coparenting theory and research, guided greatly by Minuchin's structural family theory, have deepened socialisation perspectives in the field of developmental psychology. Coparenting theory has perhaps had its largest impact in the field of infant‐family mental health, where empirical investigations of coparenting and family‐level dynamics have dovetailed with studies of family alliances and triangles and inspired creative interventions to support families of infants and toddlers. In this article, the authors retrace some of the early accounts of coparenting and triangular interactions during infancy, highlighting symmetries with analogue conceptualisations discovered in the field of family therapy. Emphasising key concepts and lessons divined from the infant‐family mental health literature holding value for the practice of family therapy, the article also recognises the dominant Euro‐Western bias that has shaped much of the extant literature to date. A closing section addresses two important areas calling for more concerted attention by infant‐family mental health experts and family therapists alike – under‐appreciated and misunderstood elements of men's psychology connected to their core self‐definition, and cultural distinctions in normal family processes. In both cases, if misread or misunderstood by the helping professional, the recipients of therapeutic services may experience failures of empathy.
Preparation of rigidity toughness balance and stable poly(glycolic acid) based on chain extension reaction
Authors: Chen Shiyuan , Meng Xin , Xin Zhong , Gong Weiguang , Li Chenyang , Wen Wei
Published: November 2023

As a completely degradable material, poly(glycolic acid) (PGA) has excellent rigidity, barrier properties, degradability and biocompatibility. However, the inherent brittleness and easily hydrolysable characteristics limit its widespread application. Herein, we introduced chain extension ADR to modify PGA to ameliorate these defects. The results showed that ADR could react with PGA to form “comb‐like” and “cross‐linked” chain extension structures resulting in the improvement of complex viscosity and formation of gel. Because of the chain entanglement of chain extension structures, the toughness of modified PGA was improved (which was verified by the impact strength value of 4.3 kJ/m2 that was about 126% of virgin PGA) without sacrificing its rigidity. Furthermore, the hydrolysis results indicated that the representative PGA/1.0ADR had better hydrolysis stability, it had more complete morphology and slower degradation rate than virgin PGA in the 17‐day hydrolysis experiment. Apart from better toughness and hydrolysis stability, there was also improvements in crystallization performance, the sample PGA/1.0ADR endowed with higher crystallization peak temperature (2.3°C higher than virgin PGA) and lower crystallization activation energy. In short, this work prepared a kind of modified PGA with rigidity toughness balance and better hydrolysis stability, which could expand the application range of PGA‐based materials.
Experimental study on the availability of polyurethane foam used as compressible layers in subsea tunnels
Authors: Zhang Zheyuan , Tian Hongming , Chen Weizhong , Qiu Xin
Published: November 2023

The yielding support comprising a compressive layer is considered as a solution to the time‐dependent damage of the lining in squeezing tunnels. The feasibility of the use of polyurethane foam (PUF) as the compressible layers in subsea tunnels was investigated in this study. Confined compression tests were conducted to investigate the compression performance degradation of PUF immersed in artificial seawater for 400 days. The yield strength and elastic modulus of PUF decreased within 180 days but then increased to over 80% of their initial values within the subsequent following 220 days, the degradation rate and strengthening rate of these parameters are of the same order of magnitude. The degradation rate of the yield strength and elastic modulus can be significantly inhibited by ions in artificial seawater, thus causing samples immersed in low‐salt‐concentration solutions to exhibit worse compression performance than those of samples immersed in a high‐salt‐concentration solution. The stress at the end of the yielding plateau and yielding plateau strain range were slightly affected by hydrolysis aging. The shape of the yielding plateau stage of the aged samples changed from a horizontal line to an inclined line owing to the variation in the yield strength. Even after immersion for 400 days, all the aged samples still exhibited compression failure and neither crumbled into pieces nor fractured into parts. The strengthening effect, unchanged failure mode, and almost constant yielding plateau strain range guarantee the safe utilization of PUF in marine environments.
Creation of NV Centers in Diamond under 155 MeV Electron Irradiation
Authors: Losero Elena , Goblot Valentin , Zhu Yuchun , Babashah Hossein , Boureau Victor , Burkart Florian , Galland Christophe
Published: November 2023

Single‐crystal diamond substrates presenting a high concentration of negatively charged nitrogen‐vacancy centers (NV−) are on high demand for the development of optically pumped solid‐state sensors such as magnetometers, thermometers, or electrometers. While nitrogen impurities can be easily incorporated during crystal growth, the creation of vacancies requires further treatment. Electron irradiation and annealing is often chosen in this context, offering advantages with respect to irradiation by heavier particles that negatively affect the crystal lattice structure and consequently the NV− optical and spin properties. A thorough investigation of electron irradiation possibilities is needed to optimize the process and improve the sensitivity of NV‐based sensors. In this work, the effect of electron irradiation is examined in a previously unexplored regime: extremely high energy electrons, at 155 MeV. A simulation model is developed to estimate the concentration of created vacancies and an increase of NV− concentration by more than three orders of magnitude following irradiation of a nitrogen‐rich HPHT diamond over a very large sample volume is experimentally demonstrated, which translates into an important gain in sensitivity. Moreover, the impact of electron irradiation in this peculiar regime on other figures of merits relevant for NV sensing is discussed, including charge state conversion efficiency and spin relaxation time. Finally, the effect of extremely high energy irradiation is compared with the more conventional low energy irradiation process, employing 200 keV electrons from a transmission electron microscope, for different substrates and irradiation fluences, evidencing 60‐fold higher yield of vacancy creation per electron at 155 MeV.
The decrease in uncited articles and its effect on the concentration of citations
Authors: Kozlowski Diego , Andersen Jens Peter , Larivière Vincent
Published: November 2023

Empirical evidence demonstrates that citations received by scholarly publications follow a pattern of preferential attachment, resulting in a power‐law distribution. Such asymmetry has sparked significant debate regarding the use of citations for research evaluation. However, a consensus has yet to be established concerning the historical trends in citation concentration. Are citations becoming more concentrated in a small number of articles? Or have recent geopolitical and technical changes in science led to more decentralized distributions? This ongoing debate stems from a lack of technical clarity in measuring inequality. Given the variations in citation practices across disciplines and over time, it is crucial to account for multiple factors that can influence the findings. This article explores how reference‐based and citation‐based approaches, uncited articles, citation inflation, the expansion of bibliometric databases, disciplinary differences, and self‐citations affect the evolution of citation concentration. Our results indicate a decreasing trend in citation concentration, primarily driven by a decline in uncited articles, which, in turn, can be attributed to the growing significance of Asia and Europe. On the whole, our findings clarify current debates on citation concentration and show that, contrary to a widely‐held belief, citations are increasingly scattered.
Molecular Reconstruction with Stereochemical Relay: An Investigation into the Rearrangement of Spiro[4.5]decadienone to Benzoxepane
Authors: Sittihan Satapanawat , Harada Shingo , Isono Tomohiro , Nemoto Tetsuhiro , Ruchirawat Somsak
Published: November 2023

Herein, we report the unusual skeletal rearrangement of spiro[4.5]decadienone to benzoxepane. In particular, Lewis acid‐promoted epoxide‐opening ipso‐cyclization of aryl epoxides afforded spiro[4.5]decadienone intermediates. Subsequent thermal activation assembled a benzoxepane core via rearomative molecular reorganization. The sequence was high‐yielding and highly diastereoselective but sensitive to the aromatic substitution pattern and the epoxide side chain. Mechanistic studies suggested that the rearrangement proceeded via an uncommon intramolecular enolate attack onto the electrophilic O of p‐quinone oxonium zwitterion. DFT calculations helped rationalize the product distribution and the origin of diastereoselectivity. Initial investigation into the application of this chemical transformation is also presented.
The miR‐17‐92 cluster in cardiac health and disease
Authors: Cao Yuhan , Zheng Mingjie , Sewani Maham A. , Wang Jun
Published: November 2023

MicroRNAs (miRs) are small noncoding RNAs that play important roles in both physiological and pathological processes through post‐transcriptional regulation. The miR‐17‐92 cluster includes six individual members: miR‐17, miR‐18a, miR‐19a, miR‐19b‐1, miR‐20a, and miR‐92a‐1. The miR‐17‐92 cluster has been extensively studied and reported to broadly function in cancer biology, immunology, neurology, pulmonology, and cardiology. This review focuses on its roles in heart development and cardiac diseases. We briefly introduce the nature of the miR‐17‐92 cluster and its crucial roles in both normal development and the pathogenesis of various diseases. We summarize the recent progress in understanding the versatile roles of miR‐17‐92 during cardiac development, regeneration, and aging. Additionally, we highlight the indispensable roles of the miR‐17‐92 cluster in pathogenesis and therapeutic potential in cardiac birth defects and adult cardiac diseases.
Pushing the boundaries of phosphorylase cascade reaction for cellobiose production I: Kinetic model development
Authors: Sigg Alexander , Klimacek Mario , Nidetzky Bernd
Published: November 2023

One‐pot cascade reactions of coupled disaccharide phosphorylases enable an efficient transglycosylation via intermediary α‐d‐glucose 1‐phosphate (G1P). Such transformations have promising applications in the production of carbohydrate commodities, including the disaccharide cellobiose for food and feed use. Several studies have shown sucrose and cellobiose phosphorylase for cellobiose synthesis from sucrose, but the boundaries on transformation efficiency that result from kinetic and thermodynamic characteristics of the individual enzyme reactions are not known. Here, we assessed in a step‐by‐step systematic fashion the practical requirements of a kinetic model to describe cellobiose production at industrially relevant substrate concentrations of up to 600 mM sucrose and glucose each. Mechanistic initial‐rate models of the two‐substrate reactions of sucrose phosphorylase (sucrose + phosphate → G1P + fructose) and cellobiose phosphorylase (G1P + glucose → cellobiose + phosphate) were needed and additionally required expansion by terms of glucose inhibition, in particular a distinctive two‐site glucose substrate inhibition of the cellobiose phosphorylase (from Cellulumonas uda). Combined with mass action terms accounting for the approach to equilibrium, the kinetic model gave an excellent fit and a robust prediction of the full reaction time courses for a wide range of enzyme activities as well as substrate concentrations, including the variable substoichiometric concentration of phosphate. The model thus provides the essential engineering tool to disentangle the highly interrelated factors of conversion efficiency in the coupled enzyme reaction; and it establishes the necessary basis of window of operation calculations for targeted optimizations toward different process tasks.
Genetic variation of the 5‐HT1A rs6295, 5‐HT2A rs6311, and CNR1 rs1049353 and an altered endocannabinoid system in depressed patients
Authors: Obermanns Jasmin , Meiser Hanna , Hoberg Saskia , Vesterager Cynthia Segura , Schulz Frank , Juckel Georg , Emons Barbara
Published: November 2023

Background

The reasons for developing depression are not fully understood. However, it is known that the serotonergic system plays a role in the etiology, but the endocannabinoid system receives attention.

Method

In this study, 161 patients with a depressive disorder and 161 healthy participants were examined for the distribution of the CNR1 rs4940353, 5‐HT2A rs6311, and 5‐HT1A rs6295 by high‐resolution melting genotyping. The concentration of arachidonoyl ethanolamide (AEA) and 2‐arachidonoylglycerol (2‐AG) in the blood was measured by liquid chromatography–tandem mass spectrometry. Additionally, depression and anxiety symptoms were evaluated based on self‐questionnaires. Fifty‐nine patients participated in a second appointment to measure the concentration of AEA, 2‐AG, and symptoms of depression and anxiety.

Results

We observed higher AEA and decreased 2‐AG concentrations in patients with depression compared to healthy participants. During the treatment, the concentrations of AEA and 2‐AG did not change significantly. In patients higher symptoms of anxiety correlated with lower concentrations of 2‐AG. Gender differences were found concerning increased 2‐AG concentration in male patients and increased anxiety symptoms in female patients. Genotypic variations of 5‐HT1A rs6295 and 5‐HT2A rs6311 are associated with altered serotonergic activity and serotonin content in patients.

Conclusion

In conclusion, it seems that the endocannabinoid system, especially the endocannabinoids 2‐AG and AEA, and genetic variations of the 5‐HT1A and 5‐HT2A could play a role in patients with depression and may be involved in a depressive disorder.
Depth filtration for clarification of intensified lentiviral vector suspension cell culture
Authors: Mayani Mukesh , Nellimarla Srinivas , Mangalathillam Ratish , Rao Hema , Patarroyo‐White Susannah , Ma Junfen , Figueroa Bruno
Published: November 2023

Depth filtration significantly impacts efficiency of lentiviral (LV) vector purification process. However, it is often deprioritized in the overall scope of viral vector manufacturing process optimization. The demand for LV vectors has increased with the rise in disease indications, making it crucial to improve current manufacturing processes. Upstream bioreactor process intensification has enabled cell densities of over 107 viable cells/mL, creating challenges for harvest unit operations. The larger size of LV vectors and their physiochemical similarity to host cell‐DNA (HC‐DNA) and poor clarification performance causes significant challenges for the subsequent chromatography‐based purifications. As a result, a robust and scalable harvest of LV process is needed, especially for LV in vivo therapeutic quality needs. In this study, we systematically evaluated the overlooked yet important issue of depth filtration systems to improve enveloped LV functional vector recovery. We found that an established depth filtration system in process A that provided 94% (n = 6) LV functional recovery could not be translated to intensified Process B cell culture. Hence, the depth filtration process became a bottleneck for the purification performance in an intensified process. We demonstrated an improvement in LV functional vector recovery from 34% to 82% via filter train optimization for an intensified suspension cell culture system (>107 cells/mL with higher titer), while still maintaining a loading throughput of ≥82 L/m2 and turbidity ≤20 NTU. It was demonstrated that the two or three‐stage depth filtration scheme is scalable and more suitable for high cell density culture for large scale for LV manufacturing process.
CDIO‐CT collaborative strategy for solving complex STEM problems in system modeling and simulation: An illustration of solving the period of mathematical pendulum
Authors: Zhang Hong‐Yan , Zhou Yu , Li Yu‐Tao , Li Fu‐Yun , Jiang Yong‐Hui
Published: November 2023

The problem‐project‐oriented STEM education plays a significant role in training students' ability of innovation. Although the conceive‐design‐implement‐operate (CDIO) approach and computational thinking (CT) are hot topics in recent decades, there are still two deficiencies: the CDIO approach and CT are discussed separately and a general framework of coping with complex STEM problems in system modeling and simulation is missing. In this paper, a collaborative strategy based on the CDIO and CT is proposed for solving complex STEM problems in system modeling and simulation with a general framework, in which the CDIO is about “how to do,” CT is about “how to think,” and the project means “what to do.” As an illustration, the problem of solving the period of mathematical pendulum is discussed in detail. The most challenging task involved in the problem is to compute the complete elliptic integral of the first kind (CEI‐1). In the philosophy of STEM education, all problems have more than one solution. For computing the CEI‐1, four methods are discussed with a top‐down strategy, which includes the infinite series method, arithmetic‐geometric mean method, Gauss–Chebyshev method, and Gauss‐Legendre method. The algorithms involved can be utilized for R & D projects of interest and be reused according to the requirements encountered. The general framework for solving complex STEM problems in system modeling and simulation is worth recommending to college students and instructors.
Perigraftitis and implant therapy: A case report
Authors: Do Jonathan H. , Cobb Charles M.
Published: November 2023

Background

A previous case study reported periimplantitis and concomitant perigraftitis of a second implant placed at a site that had alveolar ridge preservation three decades earlier. Infection at the site persisted 4 months after implant removal by flapless implant reversal. A flap was subsequently reflected, the grafted bone was removed, and a second alveolar ridge preservation was performed with a freeze‐dried bone allograft. The publication reported infection resolved, and the site healed uneventfully. However, it is unknown if placement of another implant at the site would be successful. The purpose of this paper is to report on the findings at surgical reentry and outcome of the third implant.

Methods

Eleven months after the second alveolar ridge preservation, the site was reentered. The bone graft was found to be partially soft tissue encapsulated. All encapsulated graft materials and soft tissue were removed. An implant was placed, and the alveolar defect was grafted with a demineralized bone allograft. Seventeen months after implant placement, a buccal free gingival graft was performed during which the crestal bone adjacent to the implant was found to be hard and corticated. The implant was deemed to be osseointegrated and restored after soft tissue healing.

Results

Twenty‐five months after implant placement, the third implant remained functional and asymptomatic with the peri‐implant bone exhibiting normal trabeculation.

Conclusions

Implant therapy can be successful following treatment and resolution of perigraftitis.

Key points

Perigraftitis may play a contributing role in the biologic complications of implants that have been placed into grafted bone.

Perigraftitis may be successfully resolved by completely removing all grafted bone.

Once perigraftitis has been eliminated, an implant may be successfully placed.
Translational approach to tooth autotransplantation: A 27‐year case study
Authors: Pini Prato GiovanPaolo , Franceschi Debora , Pace Riccardo , Di Gianfilippo Riccardo
Published: November 2023

Background

The aim of this case report was to present a translational approach to tooth autotransplantation using jiggling forces to enlarge the periodontal ligament (PDL) space before autotransplantation, with the goal of improving treatment success and long‐term survival.

Methods

A 23‐year‐old patient, undergoing orthodontic therapy and with an unrestorable maxillary first molar, was proposed to have a healthy and fully‐erupted maxillary third molar transplanted in the socket of the first molar. Jiggling forces were applied to the third molar to enlarge the PDL space and facilitate the preservation of PDL fibers on the root surfaces during the extraction.

Results

Jiggling forces induced hypermobility and widened PDL space of the third molar. The autotransplantation was successful and the patient was followed regularly over a 27‐year period. At the 27‐year visit, the patient showed optimal chewing function, oral plaque control, and absence of gingivitis. The transplanted molar exhibited periodontal health and absence of mobility. Probing depth of 5 mm and radiographic external root resorption was noted on a localized area of the transplanted tooth which had experienced traumatic and unintentional removal of PDL fibers during the extraction.

Conclusions

A translational approach was proposed by integrating knowledge from the fields of orthodontics, trauma from occlusion, and replantation. It validated the crucial importance of maintaining healthy PDL fibers on the root surface and demonstrated clinically the successful autotransplantation of a fully formed third molar into the socket of a first molar with a retention of 27 years.

Key points

Why is this case new information?

This case provided evidence of successful autotransplantation of a molar with complete root formation. It reported the longest‐term follow‐up (27 years) present in the literature. Most importantly, it used a translational medicine approach to apply concepts from the fields of orthodontics and traumatic occlusion to improve the success of the autotransplantation procedure.

What are the keys to the successful management of this case?

Jiggling forces induced tooth hypermobility and increased the PDL space of the tooth planned for autotransplantation. In turn, they facilitated the atraumatic extraction and preservation of the PDL fibers on the transplanted tooth, improving the success of the reattachment of periodontal fibers.

What are the primary limitations to success in this case?

Traumatic extraction resulting in the unintended removal of PDL fibers from the tooth planned for autotransplantation, or intentional removal of PDL fibers with root planing are expected to decrease the success rate of the autotransplantation procedure. This is due to the lack of viable PDL cells necessary for reattachment.
The social value and financial benefits of providing preventive and timely counselling to people with sight loss in Wales, UK
Authors: Anthony Bethany F. , Hartfiel Ned , Edwards Rhiannon T.
Published: November 2023

Background

Almost 2 million people in the UK live with sight loss, and this number is predicted to double by 2050. There is increasing recognition of the need to provide counselling services to people living with sight loss.

Aim

The aim of this research was to assess whether there is an unmet need for counselling services for people living with sight loss in North Wales and to estimate the social value and budget impact of the potential roll‐out of counselling services to this population.

Method

Between December 2020 and May 2021, a telephone survey was completed by 192 people living with sight loss in North Wales, UK. The survey instrument was a 19‐item questionnaire, which included the Short Warwick–Edinburgh Mental Well‐being Scale (SWEMWBS). Using data from the SWEMWBS and published statistics, a social return on investment (SROI) and budget impact analysis were conducted.

Results

Most respondents (84%, n = 161) had never been offered counselling in relation to sight loss. Thirty‐nine per cent (n = 74) stated that they would use a new counselling service if it were available. Fifty‐one per cent (n = 97) indicated that counselling could be especially beneficial for people who have recently been registered or diagnosed with sight loss (the timely window). Of those who completed the SWEMWBS, approximately 25% reported low mental well‐being or probable depression. Social return on investment analysis estimated that providing counselling services for people with sight loss in North Wales could generate a social value of £3.42 for every £1 invested.

Conclusion

Timely counselling may improve an individual's ability to cope with sight loss and improve their quality of life over time.
γ‐Glutamylation of Isopropylamine by Fermentation
Authors: Benninghaus Leonie , Zagami Laura , Tassini Giulio , Meyer Florian , Wendisch Volker F.
Published: November 2023

Glutamylation yields N‐functionalized amino acids in several natural pathways. γ‐Glutamylated amino acids may exhibit improved properties for their industrial application, e. g., as taste enhancers or in peptide drugs. γ‐Glutamyl−isopropylamide (GIPA) can be synthesized from isopropylamine (IPA) and l‐glutamate. In Pseudomonas sp. strain KIE171, GIPA is an intermediate in the biosynthesis of l‐alaninol (2‐amino‐1‐propanol), a precursor of the fluorochinolone antibiotic levofloxacin and of the chloroacetanilide herbicide metolachlor. In this study, fermentative production of GIPA with metabolically engineered Pseudomonas putida KT2440 using γ‐glutamylmethylamide synthetase (GMAS) from Methylorubrum extorquens was established. Upon addition of IPA during growth with glycerol as carbon source in shake flasks, the recombinant strain produced up to 21.8 mM GIPA. In fed‐batch bioreactor cultivations, GIPA accumulated to a titer of 11 g L−1 with a product yield of 0.11 g g−1 glycerol and a volumetric productivity of 0.24 g L−1 h−1. To the best of our knowledge, this is the first fermentative production of GIPA.
Infection of tendon sheaths, joints, bursae, soft tissue, and tendon rapture by brucella: A case report
Authors: Zangeneh Mehrangiz , Rezvanfar Kiana , Khosravani‐Nejad Yasamin , Faghani Yazdanali , Dezfulinejad Manije , Saadat Fakhr Masoud , Ghorbani Parastoo
Published: November 2023

Key Clinical Message

Arthritis is one of the main presentations of chronic brucellosis, but bursitis and tendon rupture are also caused by brucellosis. Therefore, brucellosis should be considered in the differential diagnosis of arthritis, bursitis, and tendon rupture by physicians. In addition, early diagnosis and treatment are very important in the prevention of disability.

Brucellosis is a zoonotic disease common in the Middle East. Manifestations of acute disease are fever, sweating, myalgia, and arthralgia. However, bone joint involvement occurs in 10%–85% of patients, and sacroiliac involvement occurs in up to 80% and vertebral joint involvement in up to 54%. A 57‐year‐old woman was admitted to the hospital of Islamic Azad University on February 26, 2021, with a history of one‐month pain and limited movement of the right shoulder joint with fever for surgery of the shoulder ligament. The standard agglutination titer (Wright) for brucellosis at first was 1/640 and then increased. MRI of the shoulder showed a supraspinatus tendon and anterosuperior labral of the glenoid labrum tear. Although the patient was a candidate for shoulder joint ligament surgery, with a diagnosis of brucellosis, the treatment of brucellosis was prescribed, symptoms disappeared with anti‐brucellosis antibiotic therapy without surgery, and the patient recovered. Supraspinatus tendon and antero superior labral of glenoid labrum tear of the shoulder joint in brucellosis is generally very rare. Failure or delay in the treatment of brucellosis can cause ligament rupture or joint disability. Sometimes, there are no symptoms except osteoarticular manifestations in brucellosis; therefore, brucellosis should be one of the differential diagnoses in osteoarticular diseases.
Accelerated Synthesis of Nanolayered MWW Zeolite by Interzeolite Transformation
Authors: Pornsetmetakul Peerapol , Coumans Ferdy J. A. G. , Heinrichs Jason M. J. J. , Zhang Hao , Wattanakit Chularat , Hensen Emiel J. M.
Published: November 2023

Hierarchical zeolites can offer substantial benefits over bulk zeolites in catalysis. A drawback towards practical implementation is their lengthy synthesis, often requiring complex organic templates. This work describes an accelerated synthesis of nanolayered MWW zeolite based on the combination of interzeolite transformation (IZT) with a dual‐templating strategy. FAU zeolite, hexamethyleneimine (HMI), and cetyltrimethylammonium bromide (CTAB) were respectively employed as Al source and primary zeolite, structure directing agent, and exfoliating agent. This approach allowed to reduce the synthesis of nanolayered MWW to 48 h, which is a considerable advance over the state of the art. Tracking structural, textural, morphological, and chemical properties during crystallization showed that 4‐membered‐ring (4MR) units derived from the FAU precursor are involved in the faster formation of MWW in comparison to a synthesis procedure from amorphous precursor. CTAB restricts the growth of the zeolite in the c‐direction, resulting in nanolayered MWW. Moreover, we show that this approach can speed up the synthesis of nanolayered FER. The merits of nanolayered MWW zeolites are demonstrated in terms of improved catalytic performance in the Diels‐Alder cycloaddition of 2,5‐dimethylfuran and ethylene to p‐xylene compared to bulk reference MWW sample.