bluuebunny/crossref_metadata_2025 huggingface dataset:
The survey and analysis of brochs
Authors: Cavers Graeme , Barber John , Ritchie Matthew
Published: May 2023

Developments in surveying technology over the past decade have facilitated new approaches to the survey and presentation of complex upstanding archaeological sites. Recent surveys carried out on behalf of Forestry Commission Scotland, allied to ongoing research into the architecture and engineering of brochs – or complex Atlantic roundhouses – across Scotland, have prompted a reassessment of approaches to the recording and interpretation of brochs as structures and a reconsideration of the information required to record their character. This paper highlights the importance of archaeological measured survey and explores the influence of zeitgeistic preconceptions, not only on the survey itself but on its interpretation. Pre-survey analysis, selection of evidence to be surveyed and post-survey analyses are intimately interlinked. While modern survey techniques address some of these issues, improvements in recording must be matched by improved interpretational models to maximise their benefits to broch studies.
A medieval logboat from the River Conon
Authors: Mowat Robert J C , Cowie Trevor , Crone Anne , Cavers Graeme
Published: May 2023

Three timbers held in store at the National Museums of Scotland have been identified as the incomplete remains of a logboat that was found in the River Conon near Dingwall in 1874. Notwithstanding their poor condition, they were felt to justify dating (by both radiocarbon and dendrochronology), laser scanning (to create a ‘virtual’ reconstruction) and re-publication, subsequent to that by Mowat (1996: 22, 24, no 28 and 86, nos A21–22). Radiocarbon dating showed the vessel to be of medieval date, while tree-ring evidence indicated that it was probably fashioned in the late 13th or early 14th centuries from an oak tree of some 300 years growth. This is the first logboat in Scotland to be dated by dendrochronology, and the results significantly extend the coverage of Scottish medieval tree-ring dates north of Inverness. Specific features suggest that the remains may have formed one element within a vessel of paired (or possibly multiple) form, intended for the cross-river transport of heavy loads. These results invite wider consideration of the role of simple or ‘undeveloped’ types of watercraft in riverine transport in Highland Scotland and elsewhere.
Excavations at Achanduin Castle, Lismore, Argyll, 1970–5
Authors: Caldwell David H , Stell Geoffrey P , Turner Dennis J
Published: May 2023

Excavations were undertaken at Achanduin Castle, Lismore, Argyll (NGR: NM 8043 3927), over six seasons from 1970 to 1975 under the direction of the late Dennis John Turner (1932–2013), henceforward referred to as DJT. Publication of a full report as a SAIR, assembled from the papers of DJT, has now been achieved by the other two authors of this paper, neither of whom were directly involved in the excavations. They have undertaken this task because of their friendship with DJT and their realisation of the importance of his work at Achanduin, the results of which are distilled and discussed here. Achanduin is a small rectangular enclosure castle, built about the very end of the 13th century or early in the 14th century. Although it was occupied intermittently by bishops of Argyll, perhaps as late as the 1680s, DJT has made a case for it being constructed for either Alexander MacDougall, lord of Argyll, or his son John.
Seventh century or seventeenth century? Identifying glass beads from Scotland
Authors: Blackwell Alice , Kirk Susanna
Published: May 2023

This paper reconsiders glass beads that have hitherto been regarded as early medieval in date. Although several groups of these beads are known from important early Christian sites – St Ninian’s Isle, Shetland, and Morham, East Lothian – a case is made here for a manufacture date between the 17th and 19th centuries AD on the basis of typological parallels and surface analysis of the glass composition. Several of the groups of beads appear to have been found in graves and their significance in the context of early modern burial practice is explored. Here it is argued that, in the face of the sheer quantity of beads produced in post-medieval Europe, extreme care should be exercised when identifying glass beads, particularly when the objects in question have complex or uncertain archaeological contexts. Although surface analysis of glass composition has limitations, with careful interpretation it can nonetheless provide a quick, inexpensive and non-destructive means of narrowing the range of possible identifications. The type of glass can give a broad indication of date, and in some cases the detection of particular ingredients or quality of materials can indicate a more precise origin.
Prelims
Authors: - -
Published: May 2023

Front matter for Volume 145

Table of Contents

List of abbreviations commonly used in the Proceedings

Editorial board for the Proceedings Vol 145

Society of Antiquaries of Scotland Council from 1 December 2014

Patron and Honorary Fellows of the Society of Antiquaries of Scotland, 2015-6

Laws of the Society of Antiquaries of Scotland
Prelims
Authors: - -
Published: May 2023

Front matter for Volume 147

Table of Contents

List of abbreviations commonly used in the Proceedings

Editorial board for the Proceedings Vol 147

Society of Antiquaries of Scotland Council from 1 December 2016

Patron and Honorary Fellows of the Society of Antiquaries of Scotland, 2017-8

Laws of the Society of Antiquaries of Scotland
Analysis of Plasma Metabolic Profile on Ganglion Cell–Inner Plexiform Layer Thickness With Mortality and Common Diseases
Authors: Yang Shaopeng , Zhu Zhuoting , Yuan Yixiong , Chen Shida , Shang Xianwen , Bulloch Gabriella , He Mingguang , Wang Wei
Published: May 2023

Importance

The neural retina is considered a unique window to systemic health, but its biological link with systemic health remains unknown.

Objective

To investigate the independent associations of retinal ganglion cell–inner plexiform layer thickness (GCIPLT) metabolic profiles with rates of mortality and morbidity of common diseases.

Design, Setting, and Participants

This cohort study evaluated UK Biobank participants enrolled between 2006 and 2010, and prospectively followed them up for multidisease diagnosis and mortality. Additional participants from the Guangzhou Diabetes Eye Study (GDES) underwent optical coherence tomography scanning and metabolomic profiling and were included for validation.

Main Outcomes and Measures

Systematic analysis of circulating plasma metabolites to identify GCIPLT metabolic profiles; prospective associations of these profiles with mortality and morbidity of 6 common diseases with their incremental discriminative value and clinical utility.

Results

Among 93 838 community-based participants (51 182 [54.5%] women), the mean (SD) age was 56.7 (8.1) years and mean (SD) follow-up was 12.3 (0.8) years. Of 249 metabolic metrics, 37 were independently associated with GCIPLT, including 8 positive and 29 negative associations, and most were associated with the rates of future mortality and common diseases. These metabolic profiles significantly improved the models for discriminating type 2 diabetes over clinical indicators (C statistic: 0.862; 95% CI, 0.852-0.872 vs clinical indicators only, 0.803; 95% CI, 0.792-0.814; P < .001), myocardial infarction (0.792; 95% CI, 0.775-0.808 vs 0.768; 95% CI, 0.751-0.786; P < .001), heart failure (0.803; 95% CI, 0.786-0.820 vs 0.790; 95% CI, 0.773-0.807; P < .001), stroke (0.739; 95% CI, 0.714-0.764 vs 0.719; 95% CI, 0.693-0.745; P < .001), all-cause mortality (0.747; 95% CI, 0.734-0.760 vs 0.724; 95% CI, 0.711-0.738; P < .001), and cardiovascular disease mortality (0.790; 95% CI, 0.767-0.812 vs 0.763; 95% CI, 0.739-0.788; P < .001). Additionally, the potential of GCIPLT metabolic profiles for risk stratification of cardiovascular diseases were further confirmed in the GDES cohort using a different metabolomic approach.

Conclusions and Relevance

In this prospective study of multinational participants, GCIPLT-associated metabolites demonstrated the potential to inform mortality and morbidity risks. Incorporating information on these profiles may facilitate individualized risk stratification for these health outcomes.
Association of 5α-Reductase Inhibitor Prescription With Bladder Cancer Progression in Males in South Korea
Authors: An Min Ho , Kim Min Seo , Kim Chungsoo , Noh Tae Il , Joo Kwan Joong , Lee Dong Hun , Yi Kyu-Ho , Kwak Jeong Woo , Hwang Tae-Ho , Park Rae Woong , Kang Seok Ho
Published: May 2023

Importance

The antiandrogenic effect of the 5α-reductase inhibitor (5-ARI) has been investigated for its role in preventing male-predominant cancers. Although 5-ARI has been widely associated with prostate cancer, its association with urothelial bladder cancer (BC), another cancer experienced predominantly by males, has been less explored.

Objective

To assess the association between 5-ARI prescription prior to BC diagnosis and reduced risk of BC progression.

Design, Setting, and Participants

This cohort study analyzed patient claims data from the Korean National Health Insurance Service database. The nationwide cohort included all male patients with BC diagnosis in this database from January 1, 2008, to December 31, 2019. Propensity score matching was conducted to balance the covariates between 2 treatment groups: α-blocker only group and 5-ARI plus α-blocker group. Data were analyzed from April 2021 to March 2023.

Exposure

Newly dispensed prescriptions of 5-ARIs at least 12 months prior to cohort entry (BC diagnosis), with a minimum of 2 prescriptions filled.

Main Outcomes and Measures

The primary outcomes were the risks of bladder instillation and radical cystectomy, and the secondary outcome was all-cause mortality. To compare the risk of outcomes, the hazard ratio (HR) was estimated using a Cox proportional hazards regression model and difference in restricted mean survival time analysis.

Results

The study cohort initially included 22 845 males with BC. After propensity score matching, 5300 patients each were assigned to the α-blocker only group (mean [SD] age, 68.3 [8.8] years) and 5-ARI plus α-blocker group (mean [SD] age, 67.8 [8.6] years). Compared with the α-blocker only group, the 5-ARI plus α-blocker group had a lower risk of mortality (adjusted HR [AHR], 0.83; 95% CI, 0.75-0.91), bladder instillation (crude HR, 0.84; 95% CI, 0.77-0.92), and radical cystectomy (AHR, 0.74; 95% CI, 0.62-0.88). The differences in restricted mean survival time were 92.6 (95% CI, 25.7-159.4) days for all-cause mortality, 88.1 (95% CI, 25.2-150.9) days for bladder instillation, and 68.0 (95% CI, 31.6-104.3) days for radical cystectomy. The incidence rates per 1000 person-years were 85.59 (95% CI, 80.53-90.88) for bladder instillation and 19.57 (95% CI, 17.41-21.91) for radical cystectomy in the α-blocker only group and 66.43 (95% CI, 62.22-70.84) for bladder instillation and 13.56 (95% CI, 11.86-15.45) for radical cystectomy in the 5-ARI plus α-blocker group.

Conclusions and relevance

Results of this study suggest an association between prediagnostic prescription of 5-ARI and reduced risk of BC progression.
Allostatic load and risk of all‐cause, cancer‐specific, and cardiovascular mortality in older cancer survivors: An analysis of the National Health and Nutrition Examination Survey 1999–2010
Authors: Yang Danting , Wheeler Meghann , Karanth Shama D. , Aduse‐Poku Livingstone , Leeuwenburgh Christiaan , Anton Stephen , Guo Yi , Bian Jiang , Liang Muxuan , Yoon Hyung‐Suk , Akinyemiju Tomi , Braithwaite Dejana , Zhang Dongyu
Published: May 2023

Background

Allostatic load (AL) has been linked to an increased risk of death in various populations. However, to date, there is no research specifically investigating the effect of AL on mortality in older cancer survivors.

Aims

To investigate the association between AL and mortality in older cancer survivors.

Method

A total of 1291 adults aged 60 years or older who survived for ≥1 year since cancer diagnoses were identified from the 1999 to 2010 National Health and Nutrition Examination Survey. AL was the exposure of interest incorporating nine clinical measures/biomarkers; one point was added to AL if any of the measures/biomarkers exceeded the normal level. The sum of points was categorized as an ordinal variable to reflect low, moderate, and high ALs. Our outcomes of interest were all‐cause, cancer‐specific, and cardiovascular disease–specific mortality. Death was identified by linkage to the National Death Index. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (aHR) and 95% confidence intervals (CI) of mortality by AL category.

Results

Overall, 53.6% of participants were male and 78.4% were white. The mean age of study participants at interview was 72.8 years (standard deviation = 7.1). A total of 546 participants died during the follow‐up (median follow‐up time: 8.0 years). Among them, 158 died of cancer, and 106 died of cardiovascular events. Results from multivariable Cox proportional hazards models showed that higher ALS was positively associated with higher all‐cause mortality (ALS = 4–9 vs. ALS = 0–1: aHR = 1.52, 95% CI = 1.17–1.98, p‐trend < 0.01) and higher cancer‐specific mortality (ALS = 4–9 vs. ALS = 0–1: aHR = 1.80, 95% CI = 1.12–2.90, p‐trend = 0.01). The association between ALS and cardiovascular mortality was positive but nonsignificant (ALS = 4–9 vs. ALS = 0–1: aHR = 1.59, 95% CI = 0.86–2.94, p‐trend = 0.11).

Conclusions

Our study suggests that older cancer survivors can have a higher risk of death if they have a high burden of AL.
Controlling Degree of Inversion in MgFe2O4 Spinel Films Grown in External Magnetic Fields
Authors: Lee Hyeonkwon , Aytuna Ziyaad T. , Bhardwaj Aman , Wilhelm Michael , Lê Khan , May Benjamin , Mueller David N. , Mathur Sanjay
Published: May 2023

Single‐phase magnesium ferrite spinel films (MgFe2O4) were grown by magnetic field‐assisted chemical vapor deposition (mfCVD) of a mixed‐metal precursor compound, [MgFe2(OtBu)8]. The formation of monophasic MgFe2O4 deposits as a function of the applied magnetic field strength (B = 0.0, 0.5, and 1.0 T) was investigated and confirmed by X‐ray diffraction and photoelectron spectroscopy analyses. Thin film cross‐sectional electron microscopic analysis (FIB‐SEM) exhibited higher grain growth and densification in MgFe2O4 films obtained under the magnetic field influence when compared to spinel samples grown under zero‐field conditions. Application of an external magnetic field of varying strengths during the chemical vapor deposition process resulted in a change in the light absorption properties and crystal orientation in the MgFe2O4 films, evident in the decreased photoabsorbance analyzed by the UV‐Vis spectra and the decrease of intensity of the (400) peak in MgFe2O4 films grown under magnetic field. A comprehensive analysis of X‐ray diffraction and X‐ray magnetic circular dichroism (XMCD) results indicated a higher degree of inversion in MgFe2O4 deposits grown in an external magnetic field corroborated by a larger contribution of ligand field transitions of tetrahedrally coordinated Fe(III) centers affecting the visible light absorption of MgFe2O4 films.
A Simple Poly(Vinyl Sulfonate) Coating for All‐Purpose, Self‐Cleaning Applications: Molecular Packing Density–Defined Surface Superhydrophilicity
Authors: Wang Rong , Cheng Chongling , Wang Huiyun , Tao Qi , Wang Dayang
Published: May 2023

In this study, poly(vinyl sulfonate) (PVS)–capped surfaces are constructed on the polyelectrolyte multilayers (PEMs) of poly(diallyldimethylammonium chloride) and poly(styrene sulfonate) via electrostatic assembly. The water wetting behavior on the resulting PVS‐capped PEMs is meticulously correlated with the number of surface sulfonate groups with the aid of sum frequency generation spectroscopy and quartz crystal microbalance. It is found that when the molecular packing density of surface sulfonate groups is adjusted to be comparable to the maximal packing density of spheres in two dimensions (≈0.9), the PVS capping is able to effectively adsorb water molecules from the surrounding to form hydrogen‐bonded networks, which not only promote complete surface wetting by water in air but also diminish surface affinity to adhesion of ice, oil and wax deposited atop. As a result, the PVS‐capped PEMs are able to fulfil all the self‐cleaning functions proposed for superhydrophilic surfaces including anti‐fogging, anti‐icing, anti‐grease, anti‐smudge, anti‐graffiti, and anti‐wax. After being coated with the self‐cleaning PVS‐capped PEMs, conventional stainless steel meshes are able to perform oil‐water separation without prior water wetting.
Flexible Solution‐Processable Black‐Phosphorus‐Based Optoelectronic Memristive Synapses for Neuromorphic Computing and Artificial Visual Perception Applications
Authors: Kumar Dayanand , Li Hanrui , Das Uttam Kumar , Syed Abdul Momin , El‐Atab Nazek
Published: May 2023

Being renowned for operating with visible‐light pulses and electrical signals, optoelectronic memristive synaptic devices have excellent potential for neuromorphic computing systems and artificial visual information processing. Here, a flexible back‐end‐of‐line‐compatible optoelectronic memristor based on a solution‐processable black phosphorus/HfOx bilayer with excellent synaptic features, toward biomimetic retinas is presented. The device shows highly stable synaptic features such as long‐term potentiation (LTP) and long‐term depression (LTD) for repetitive 1000 epochs, having 400 conductance pulses, each. The device presents advanced synaptic features in terms of long‐term memory (LTM)/short term memory (STM), as well as learning–forgetting–relearning when visible light is induced on it. These advanced synaptic features can improve the information processing abilities for neuromorphic applications. Interestingly, the STM can be converted into LTM by adjusting the intensity of light and illumination time. Using the light‐induced characteristics of the device, a 6 × 6 synaptic array is developed to exhibit possible use in artificial visual perception. Moreover, the devices are flexed using a silicon back‐etching process. The resulting flexible devices demonstrate stable synaptic features when bent down to 1 cm radius. These multifunctional features in a single memristive cell make it highly suitable for optoelectronic memory storage, neuromorphic computing, and artificial visual perception applications.
Performance Study of Graphene Oxide as an Antierosion Coating for Ornamental and Heritage Dolostone
Authors: Martínez‐García Rebeca , González‐Campelo David , Fraile‐Fernández Fernando J. , Castañón Ana María , Caldevilla Pablo , Giganto Sara , Ortiz‐Marqués Almudena , Zelli Flavia , Calvo Víctor , González‐Domínguez José M. , Fernández‐Raga María
Published: May 2023

Concern for the perpetuation of stone monuments is deeply ingrained in humans; however, despite the attempts made in this field, there is still a great deal of effort needed to bring about advancements in the conservation of ornamental stone. Erosive agents, such as rain, extreme temperatures, and chemical and biological agents, threaten our stone heritage and gradually wear away buildings, sculptures, and other monuments found all around the world. Limestone and dolostone have been widely used throughout history, given their ease of extraction and workability. Nevertheless, these properties make them particularly vulnerable to the aforementioned erosive agents, for which the main solution at present is costly and time‐consuming restoration. Given the scarcity of effective and durable agents to prevent the deterioration of ornamental and heritage stones, and as graphene oxide (GO) has recently shown impressive effectiveness for this task, this work will further explore the viability of GO as a protective coating for monumental dolostone. For this purpose, GO is sprayed over dolostone surfaces by water dispersion with no adjuvants. The coating performance is assessed in terms of thermal stress, optical inspection (structured light 3D scanner), colorimetry, leachate analysis, and electron microscopy. The main results show that spray‐coated GO over stone surfaces creates a highly protective and durable barrier without altering their aesthetic qualities.
Gold Nanomaterial‐Based Optical Modulators for Wideband Pulse Laser Generation
Authors: Kang Zhe , Wang Cong , Liu Mingyi , Jia Zhixu , Liu Delong , Zhang Han , Qin Weiping , Qin Guanshi
Published: May 2023

Pulsed lasers have wide applications in several fields, such as basic research, telecommunications, and industrial materials processing. A saturable absorber (SA) is a key component for pulse laser generation. However, the current SAs exhibit certain limitations. Hence, developing new nonlinear optical materials as SAs for pulse lasers generation is significantly important in ultrafast photonics and related applications. Metallic nanomaterials have attracted considerable attention because of their higher nonlinearity coefficients and wideband nonlinear response, which are induced by the surface plasmon resonance (SPR) effect. The SPR effect depends on the size and morphology of materials. Thus, the nonlinear optical absorption effect of gold nanomaterials for pulse laser generation must be explored. In this review, the optical properties of gold nanomaterials are introduced, including SPR absorption, photoluminescence properties, and surface‐enhanced Raman scattering effect. Then, the synthesis and characterization of different gold nanomaterials are reviewed. Subsequently, the nonlinear optical characteristics and devices based on gold nanomaterials are also introduced. Furthermore, the generation of different types of lasers using gold nanomaterial‐based devices is also reviewed. A comparison between gold nanomaterials and other SA materials is presented. Finally, the conclusion and outlook on gold nanomaterial‐based nonlinear optical devices are presented.
Implantable Sensors for Post‐Surgical Monitoring of Vascular Complications
Authors: Zhao Binfan , Eid Loy , Zhang Yuguang , Sun Xiaoming , Cui Wenguo
Published: May 2023

For surgeries involving vessel anastomosis, it is critical to ensure fluent blood flow and to monitor the occurrence of vascular complications. However, the current clinical methods are ineffective in achieving direct, continuous, and accurate monitoring. At present, implantable sensors are widely used and explored in various biomedical applications, including cardiovascular disease, neurological disorders, cancer treatment, and health monitoring. They can be easily placed during surgical procedures and offer irreplaceable advantages including directness, continuity, and higher accuracy of monitoring. Based on this, the types of implantable sensors for vascular monitoring are reviewed, and some preclinical research advances which are expected to provide promising methods for post‐surgical vascular complications are discussed. In the end, the future perspectives of the research of implantable sensors for post‐surgical monitoring are put forward. It is believed that implantable sensors hold great promise in clinical translation, providing physicians with more accurate, continuous, and real‐time monitoring results, helping to improve surgical success and patient outcomes.
Dynamical Numerical Model of the Molluscan Radula in its Interaction with the Substrate and Food Particles
Authors: Filippov Alexander E. , Gorb Stanislav N. , Kovalev Alexander E. , Krings Wencke
Published: May 2023

The radula, a chitinous membrane with teeth, is the molluscan autapomorphy for food gathering and processing. Even though this structure is studied for decades, the interplay between the structure and the particular food or/and the substrate remains mostly enigmatic. Here, we provide a numerical model approach to understand the relationship between structure, feeding efficiency, and partial work performed by the system. This first simple dynamic numerical radular model interacts with the food particles and the uneven substrate. This protocol can be applied to any system in the future, as the parameters (interaction between structures, adhesion, size of food particles, attachment angle of teeth to membrane, etc.) can be easily altered. This will shed light on the biomechanical adaptations of this feeding structure (e.g., wear and failure prevention) to the specific environment.
Organic Memristor‐Based Flexible Neural Networks with Bio‐Realistic Synaptic Plasticity for Complex Combinatorial Optimization
Authors: Kim Hyeongwook , Kim Miseong , Lee Aejin , Park Hea‐Lim , Jang Jaewon , Bae Jin‐Hyuk , Kang In Man , Kim Eun‐Sol , Lee Sin‐Hyung
Published: May 2023

Hardware neural networks with mechanical flexibility are promising next‐generation computing systems for smart wearable electronics. Several studies have been conducted on flexible neural networks for practical applications; however, developing systems with complete synaptic plasticity for combinatorial optimization remains challenging. In this study, the metal‐ion injection density is explored as a diffusive parameter of the conductive filament in organic memristors. Additionally, a flexible artificial synapse with bio‐realistic synaptic plasticity is developed using organic memristors that have systematically engineered metal‐ion injections, for the first time. In the proposed artificial synapse, short‐term plasticity (STP), long‐term plasticity, and homeostatic plasticity are independently achieved and are analogous to their biological counterparts. The time windows of the STP and homeostatic plasticity are controlled by the ion‐injection density and electric‐signal conditions, respectively. Moreover, stable capabilities for complex combinatorial optimization in the developed synapse arrays are demonstrated under spike‐dependent operations. This effective concept for realizing flexible neuromorphic systems for complex combinatorial optimization is an essential building block for achieving a new paradigm of wearable smart electronics associated with artificial intelligent systems.
Preserved autophagy in cognitively intact non‐demented individuals with Alzheimer's neuropathology
Authors: Tumurbaatar Batbayar , Fracassi Anna , Scaduto Pietro , Guptarak Jutatip , Woltjer Randall , Jupiter Daniel , Taglialatela Giulio
Published: May 2023

INTRODUCTION

Growing evidence supports that dysfunctional autophagy, the major cell mechanism responsible for removing protein aggregates and a route of clearance for Tau in healthy neurons, is a major finding in demented Alzheimer's disease (AD) patients. However, the association of autophagy with maintenance of cognitive integrity in resilient individuals who have AD neuropathology but remain non‐demented (NDAN) has not been evaluated.

METHODS

Using post mortem brain samples from age‐matched healthy control, AD, and NDAN subjects, we evaluated autophagy in relation to Tau pathology using Western blot, immunofluorescence and RNA‐seq.

RESULTS

Compared to AD patients, NDAN subjects had preserved autophagy and reduced tauopathy. Furthermore, expression of autophagy genes and AD‐related proteins were significantly associated in NDAN compared to AD and control subjects.

DISCUSSION

Our results suggest preserved autophagy is a protective mechanism that maintains cognitive integrity in NDAN individuals. This novel observation supports the potential of autophagy‐inducing strategies in AD therapeutics.

Highlights

NDAN subjects have preserved autophagic protein levels comparable with control subjects.

Compared to control subjects, NDAN subjects have significantly reduced Tau oligomers and PHF Tau phosphorylation at synapses that negatively correlate with autophagy markers.

Transcription of autophagy genes strongly associates with AD‐related proteins in NDAN donors.
Cladribine Effects on T and B Cells and T Cell Reactivity in Multiple Sclerosis
Authors: Holm Hansen Rikke , von Essen Marina Rode , Mahler Mie Reith , Cobanovic Stefan , Binko Tomas Sorm , Sellebjerg Finn
Published: May 2023

Objective

Cladribine tablet therapy is an efficacious treatment for multiple sclerosis (MS), however, its mechanism of action on T and B cell subsets remains unclear. The purpose of this study was to investigate the treatment effects of cladribine on the peripheral pool of T and B cells subsets and reactivity toward central nervous system (CNS) antigens.

Methods

In this cross‐sectional exploratory study, frequencies and absolute counts of peripheral T and B cell subsets and B cell cytokine production from untreated patients with relapsing–remitting MS (RRMS) and patients treated with cladribine for 1 year were measured using flow cytometry. Autoreactivity was assessed using a FluoroSpot assay.

Results

We found that 1 year after initiation of cladribine treatment, a lower number of CD4+ T cells was persisting whereas CD19+ B cell counts were normalized compared to untreated patients with RRMS. Follicular helper T cells and their effecter subsets producing cytokines exerting distinct B cell helper activity were lower and, additionally, the peripheral B cell pool was skewed toward a naïve and anti‐inflammatory phenotype. Finally, reactivity to the recently identified CNS‐enriched autoantigen RAS guanyl‐releasing protein 2 (RASGRP2), but not to myelin basic protein and myelin oligodendrocyte glycoprotein, was lower in cladribine‐treated patients.

Interpretation

Together, these investigations on T and B cell subsets suggest that cladribine treatment impairs the B–T cell crosstalk and reduces their ability to mediate pathogenic effector functions. This may result in specific reduction of autoreactivity to RASGRP2 which is expressed in B cells and brain tissue. ANN NEUROL 2023;94:518–530
Charting the Chemical Reaction Space around a Multicomponent Combination: Controlled Access to a Diverse Set of Biologically Relevant Scaffolds
Authors: Nadal Rodríguez Pau , Ghashghaei Ouldouz , Schoepf Anna M. , Benson Sam , Vendrell Marc , Lavilla Rodolfo
Published: May 2023

Charting the chemical reaction space around the combination of carbonyls, amines, and isocyanoacetates allows the description of new multicomponent processes leading to a variety of unsaturated imidazolone scaffolds. The resulting compounds display the chromophore of the green fluorescent protein and the core of the natural product coelenterazine. Despite the competitive nature of the pathways involved, general protocols provide selective access to the desired chemotypes. Moreover, we describe unprecedented reactivity at the C‐2 position of the imidazolone core to directly afford C, S, and N‐derivatives featuring natural products (e.g. leucettamines), potent kinase inhibitors, and fluorescent probes with suitable optical and biological profiles.
Research on air‐cooled thermal management of energy storage lithium battery
Authors: Zhang Dongwang , Zhao Xin , Zhang Man , Yang Hairui , Li Shiyuan , Zhou Tuo
Published: May 2023

Battery energy storage system occupies most of the energy storage market due to its superior overall performance and engineering maturity, but its stability and efficiency are easily affected by heat generation problems, so it is important to design a suitable thermal management system. Due to the huge scale, complex composition, and high cost of stationary energy storage systems, it is difficult to optimize its parameters and structures by direct experimental research. In order to explore the cooling performance of air‐cooled thermal management of energy storage lithium batteries, a microscopic experimental bench was built based on the similarity criterion, and the charge and discharge experiments of single battery and battery pack were carried out under different current, and their temperature changes were analyzed. The numerical simulation study of the thermal management system of the battery pack is carried out by using ANSYS Fluent software, and the numerical simulation results are compared with the experimental results to verify its feasibility. And the influence of structural and parametric factors such as inlet and outlet position, battery spacing, and inlet air volume on the performance of the air‐cooled thermal management system is explored by means of numerical simulation. The results show that the heat generation of the battery in the discharge process is higher than that of the charging process, and the air from the top of the battery pack can achieve a better cooling effect, and there is an optimal battery spacing to achieve the best cooling effect, and the research conclusion provides some reference for the optimal design of the actual stationary energy storage system.
Rheumatoid Arthritis–Specific Autoimmunity in the Lung Before and at the Onset of Disease
Authors: Joshua Vijay , Loberg Haarhaus Malena , Hensvold Aase , Wähämaa Heidi , Gerstner Christina , Hansson Monika , Israelsson Lena , Stålesen Ragnhild , Sköld Magnus , Grunewald Johan , Klareskog Lars , Grönwall Caroline , Réthi Bence , Catrina Anca , Malmström Vivianne
Published: May 2023

Objective

The lung is implicated as a site for breach of tolerance prior to onset of seropositive rheumatoid arthritis (RA). To substantiate this, we investigated lung‐resident B cells in bronchoalveolar lavage (BAL) samples from untreated early RA patients and anti–citrullinated protein antibody (ACPA)–positive individuals at risk for developing RA.

Methods

Single B cells (n = 7,680) were phenotyped and isolated from BAL samples from individuals at risk of RA (n = 3) and at RA diagnosis (n = 9). The immunoglobulin variable region transcripts were sequenced and selected for expression as monoclonal antibodies (n = 141). Monoclonal ACPAs were tested for reactivity patterns and binding to neutrophils.

Results

Using our single‐cell approach, we found significantly increased proportions of B lymphocytes in ACPA+ compared to ACPA– individuals. Memory and double‐negative B cells were prominent in all subgroups. Upon antibody re‐expression, 7 highly mutated citrulline‐autoreactive clones originating from different memory B cell subsets were identified, both in individuals at risk of RA and early RA patients. Lung IgG variable gene transcripts from ACPA+ individuals carried frequent mutation‐induced N‐linked Fab glycosylation sites (P < 0.001), often in the framework 3 of the variable region. Two of the lung ACPAs bound to activated neutrophils, 1 from an individual at risk of RA and 1 from an early RA patient.

Conclusion

T cell–driven B cell differentiation resulting in local class switching and somatic hypermutation are evident in lungs before as well as in early stages of ACPA+ RA. Our findings add to the notion of lung mucosa being a site for initiation of citrulline autoimmunity preceding seropositive RA.

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Dynamische Zug‐Brücken‐Kompatibilität: Das Referenzverfahren als neue Nachweisform
Authors: Grunert Günther , Behnke Ronny , Liu Xiaohan
Published: May 2023

Neu entwickelte Schienenfahrzeuge sind vor ihrem Einsatz auf dem Schienennetz der DB Netz AG hinsichtlich dynamischer Brückenkompatibilität zu untersuchen. Hierbei wird die dynamische Einwirkung auf Brücken aus Zugüberfahrt (Zug‐Brücken‐Interaktion) anhand von dynamischen Berechnungsergebnissen im Grenzzustand der Tragfähigkeit (GZT) und im Grenzzustand der Gebrauchstauglichkeit (GZG) bewertet und mit rechnerischen (bisher statischen) Mindestkapazitäten der Infrastruktur (Widerstand) verglichen. In diesem Beitrag wird eine neue Nachweisform vorgestellt, welche ermöglicht, die vorhandenen statischen Kapazitäten der Brücken um vorhandene dynamische Kapazitäten zu erweitern. Diese erlauben i. d. R. höhere zulässige Fahrzeuggeschwindigkeiten im Netz. Hierfür wird auf rechnerische Ergebnisse und datenbankgestütztes Expertenwissen (Fusion) aus Kurz‐ und Langzeitüberwachungen von Bestandsfahrzeugen und deren Einwirkung auf die Infrastruktur zurückgegriffen, um den Brückenbestand für diese Bestandsfahrzeuge als betriebserprobt zu erklären. Auf dieser Basis ist eine ansetzbare dynamische Kapazität für Neufahrzeuge formulierbar. Das Vorgehen wird exemplarisch für den ICE 3 (Bestandsfahrzeug) und die Neuentwicklung der Baureihe (BR) 408 (ICE 3neo) gezeigt.
Digitalisierung im Verkehrswasserbau – von der Bestandspflege zur Neubauidee
Authors: Akkermann Jan , Müller Stephan
Published: May 2023

Neubau‐, Sanierungs‐, Erweiterungs‐ und Instandsetzungsplanungen von Verkehrswasserbauwerken setzen sich nahezu immer mit zum Teil sehr alter Bauwerkssubstanz auseinander. Im Kontext von Digitalisierung und infraBIM sind Bestandsmodelle ein wichtiger Startpunkt. Ein Bauwerksinformationsmodell, welches oftmals in ganzheitlicher Abschnittsbetrachtung von Wasserstraßen mit Teilmodellen zu sehen ist, dient als Basis der weiteren Instandhaltungs‐ und Neubauplanung. Die im Verkehrswasserbau im Vergleich zum Hoch‐ und Brückenbau noch relativ unerprobte BIM‐Planung steht vor der Herausforderung überwiegend unikaler Bauwerke. Darüber hinaus stellen die Schnittstellen zwischen Bauingenieurkonstruktionen und integriertem Maschinenbau wichtige Bereiche der integralen Planung dar. Der Beitrag gibt anhand von Praxisbeispielen einen Überblick über die verschiedenen Digitalisierungsansätze im Konstruktiven Verkehrswasserbau und legt hierbei den Fokus auf Besonderheiten und Best Practice.
Geotechnik beim Bau des neuen Schiffshebewerks Niederfinow
Authors: Puscher Christian , Heeling Anne , Bäumker Jan , Cudmani Roberto , Schwab Christian
Published: May 2023

Das neue Schiffshebewerk Niederfinow an der Havel‐Oder‐Wasserstraße überbrückt einen Geländesprung von 36 m und verbindet eine Hochebene mit überwiegend bindigen Böden mit dem Oderbruch, wo unterhalb von bindigen und organischen Schichten v. a. nichtbindige Sedimente anstehen. Der Baugrund besteht überwiegend aus eiszeitlichen Böden (Geschiebemergel, Schmelzwasser‐ und Beckensedimente). Untergeordnet treten in den tieferen Bereichen tertiäre Schichten (tertiäre Sande, Tone und Schluffe sowie kohlige Bildungen) und oberflächennah nacheiszeitliche Böden (holozäne Sande und Schluffe sowie Mudde und Torf) auf. Der Bau des Hebewerks erfolgt in einer 13 m, in Teilbereichen bis zu 16 m tiefen Baugrube mit nur einer Verankerungslage aus Verpressankern, einer kombinierten Wand sowie einer mit GEWI‐Pfählen rückverankerten Unterwasserbetonsohle im Bereich der gut tragfähigen nichtbindigen Sedimente. Da die Hebewerksmechanik gegenüber einer Schleuse nur ein vergleichsweise geringes Maß an Schrägstellung erfahren darf, wurde besonderes Augenmerk auf das Setzungsverhalten gerichtet. Hierzu wurden vor Baubeginn und baubegleitend vom Technischen Büro der Bilfinger Berger Ingenieurbau GmbH umfangreiche numerische Betrachtungen ausgeführt, um diese mit den während des Baus gemessenen Verformungen abzugleichen. Zusätzlich waren umfangreiche Erdarbeiten an hohen und steilen Dammböschungen mit entsprechenden Einbauanforderungen und Verdichtungsprüfungen auszuführen. Hier wurden auch entsprechende geohydraulische Untersuchungen ausgeführt.
Comprehensive mRNA‐sequencing‐based characterization of three HEK‐293 cell lines during an rAAV production process for gene therapy applications
Authors: Pistek Martina , Kahlig Carolin‐Isabel , Hackl Matthias , Unterthurner Sabine , Kraus Barbara , Grabherr Reingard , Grillari Johannes , Hernandez Bort Juan A.
Published: May 2023

Human embryonal kidney cells (HEK‐293) are the most common host cells used for transient recombinant adeno‐associated virus (rAAV) production in pharmaceutical industry. To better cover the expected gene therapy product demands in the future, different traditional strategies such as cell line sub‐cloning and/or addition of chemical substances to the fermentation media have been used to maximize titers and improve product quality. A more effective and advanced approach to boost yield can be envisaged by characterizing the transcriptome of different HEK‐293 cell line pedigrees with distinct rAAV productivity patterns to subsequently identify potential gene targets for cell engineering. In this work, the mRNA expression profile of three HEK‐293 cell lines, resulting in various yields during a fermentation batch process for rAAV production, was investigated to gain basic insight into cell variability and eventually to identify genes that correlate with productivity. Mock runs using only transfection reagents were performed in parallel as a control. It finds significant differences in gene regulatory behaviors between the three cell lines at different growth and production stages. The evaluation of these transcriptomics profiles combined with collected in‐process control parameters and titers shed some light on potential cell engineering targets to maximize transient production of rAAV in HEK‐293 cells.
Determination of binding affinities between nuclear localization signal peptides of irradiated EGFR and KPNA using single‐molecule pull‐down assay and development of assay system for inhibitor screening
Authors: Oh Jiwon , Park Namwuk , Ham Seung Wook
Published: May 2023

Epidermal growth factor receptor (EGFR) is transported into the nucleus during irradiation therapy and can cause the radiation resistance. It has been shown that irradiation activates EGFR transport to the nuclear by karyopherin alpha (KPNA) in the classical pathway, whereas ligand‐activated EGFR binds with karyopherin subunit beta 1 (KPNB1). Phosphorylation of T654 located within the nuclear localization signal (NLS) of EGFR is known to activate radiation‐induced nuclear EGFR transport. Therefore, we investigated the binding affinities between the NLS peptides of EGFR (645RRRHIVRKRXLRR657) and KPNA using a single‐molecule pull‐down assay in this study. We also showed the possible assay system for developing small molecules to modulate nuclear EGFR transport by high throughput screening, which potentially reduces the resistance during radiation therapy.
The value of vestibular graviceptive pathway evaluation in the diagnosis of unilateral peripheral vestibular dysfunction
Authors: Zhao Tong‐tong , Zhang Meng‐lu , Feng Yu‐fei , Wang Qian‐qian , Song Ning , Yang Xu , Ba Xiao‐hong
Published: May 2023

Background

Evaluation of vestibular graviceptive pathway (VGP) in patients with unilateral peripheral vestibular dysfunction (UPVD) has received increasing attention from researchers. The study aimed to investigate the value of VGP evaluation in the diagnosis of UPVD.

Methods

Ninety‐five UPVD patients were divided into attack and remission phase groups. VGP evaluation‐related indicators, including subjective visual vertical (SVV), subjective visual horizontal (SVH), head tilt, ocular torsion (OT), and skew deviation (SD), were measured, and their correlations with cochleovestibular function test results were analyzed. The possible etiologies of contralesional VGP (c‐VGP) were analyzed.

Results

Positive rates of SVV, SVH, OT, and SD were significantly higher, and the degrees of SVV, SVH, and OT were significantly greater in the attack phase group than the remission phase group. The sides with abnormal VGP evaluation results were correlated with the sides with hearing loss, abnormal caloric, and video head impulse test (vHIT) results. A total of 14 patients showed c‐VGP, and possible etiologies included contralateral benign paroxysmal positional vertigo (n = 4), bilateral hearing loss (n = 8), bilateral vHIT gain reduction (n = 1), autoimmune diseases (n = 6), vascular risk factors (n = 6), lacunar infarction (n = 3), and endolymphatic hydrops (n = 3).

Conclusions

Alterations in SVV, SVH, OT, and SD were noted in UPVD patients in different phases, which are presumed to be related to dynamic vestibular compensation; correlations between VGP evaluation results and cochleovestibular function test results indicate that VGP evaluation may be helpful for the diagnosis of the side affected in UPVD; the presence of c‐VGP may be related to bilateral labyrinth lesions or endolymphatic hydrops on the affected side; and the involvement of autoimmune mechanisms also deserves attention.
Altered brain activity in patients with end‐stage renal disease: A meta‐analysis of resting‐state functional imaging
Authors: Song Wenjuan , Zhao Liuyan , Li Xuekun , Wu Baolin
Published: May 2023

Introduction

: Previous studies have revealed abnormal resting‐state brain activity in patients with end‐stage renal disease (ESRD); however, the results are inconsistent. Thus, we conducted a coordinate‐based meta‐analysis of whole‐brain resting‐state functional neuroimaging studies in ESRD to identify the most consistent neural activity alterations in ESRD patients and explore their relation to serological indicators.

Methods

: A comprehensive literature search strategy was applied to select pertinent studies up to December 2022 in PubMed, Web of Science, and Embase databases. Voxel‐wise meta‐analysis was conducted via the latest meta‐analytic algorithm, seed‐based d mapping with permutation of subject images software. Meta‐regression analyses were also conducted to explore the potential effect of clinical variables on resting‐state neural activity.

Results

: Eleven studies comprising 304 patients with ESRD and 296 healthy controls (HCs) were included. Compared with HCs, ESRD patients showed decreased brain activity in the default mode network (DMN) regions, including the bilateral anterior cingulate cortex/medial prefrontal cortex, bilateral midcingulate cortex/posterior cingulate cortex, bilateral precuneus, and right angular gyrus. The neural activities in the bilateral midcingulate cortex, bilateral midcingulate cortex/posterior cingulate cortex, and right angular gyrus were significantly associated with serological indexes including hemoglobin, urea, and creatinine levels.

Conclusion

: The present study provides a quantitative overview of brain activity alterations in patients with ESRD, and the results confirm the essential role of the DMN in ESRD patients, which may be the potential neural basis of their cognitive deficits. Additionally, some serological indicators may be used as predictive markers for progressive impairment of brain function.
Youth involvement in alcohol and drug prevention: A systematic review
Authors: Aresi Giovanni , Ferrari Valentina , Marta Elena , Simões Francisco
Published: May 2023

To review and analyse how youth involvement was conceptualised and applied in published alcohol and drug preventive interventions. A systematic review of the scientific literature on alcohol and drug prevention where young people (18–29 years old) participated at any stage of the intervention was conducted. We searched relevant bibliographic databases and online repositories for peer‐reviewed studies published between 2001 and 2021. Twenty‐seven articles reporting on studies in different countries and settings and using a variety of intervention strategies were eligible for inclusion. The analysis of the stages of youth involvement and the dimension of power sharing in decision‐making showed that only a minority of studies could be considered genuinely youth‐led whereas many involved young people merely as implementers of highly controlled research‐led interventions. However, the few studies that promoted sustained youth involvement struggled with translating results into rigorously evaluated interventions, thus demonstrating a tension between adoption of effective interventions and support to genuinely participatory processes. Knowledge gaps and implications for practice and research are discussed from a participatory research perspective. Please refer to the Supplementary Material section to find this article's Community and Social Impact Statement.