bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative transcriptomic and metabolic analyses of the mammalian hibernating brain identifies a key role for succinate dehydrogenase in ischemic tolerance
Authors: Bernstock Joshua D. , Willis Cory M. , Garcia-Segura Monica Emili , Gaude Edoardo , Anni Daniela , Lee Yan-ja , Thomas Luke W. , Casey Alva , Vicario Nunzio , Leonardi Tommaso , Nicaise Alexandra M. , Gessler Florian A. , Izzy Saef , Buffelli Mario R. , Seidlitz Jakob , Srinivasan Shriya , Murphy Michael P. , Ashcroft Margaret , Cambiaghi Marco , Hallenbeck John M. , Peruzzotti-Jametti Luca
Published: March 2023

Ischemic stroke results in a loss of tissue homeostasis and integrity, the underlying pathobiology of which stems primarily from the depletion of cellular energy stores and perturbation of available metabolites1. Hibernation in thirteen-lined ground squirrels (TLGS),Ictidomys tridecemlineatus, provides a natural model of ischemic tolerance as these mammals undergo prolonged periods of critically low cerebral blood flow without evidence of central nervous system (CNS) damage2. Studying the complex interplay of genes and metabolites that unfolds during hibernation may provide novel insights into key regulators of cellular homeostasis during brain ischemia. Herein, we interrogated the molecular profiles of TLGS brains at different time points within the hibernation cycle via RNA sequencing coupled with untargeted metabolomics. We demonstrate that hibernation in TLGS leads to major changes in the expression of genes involved in oxidative phosphorylation and this is correlated with an accumulation of the tricarboxylic acid (TCA) cycle intermediates citrate, cis-aconitate, and α-ketoglutarate-αKG. Integration of the gene expression and metabolomics datasets led to the identification of succinate dehydrogenase (SDH) as the critical enzyme during hibernation, uncovering a break in the TCA cycle at that level. Accordingly, the SDH inhibitor dimethyl malonate (DMM) was able to rescue the effects of hypoxia on human neuronal cellsin vitroand in mice subjected to permanent ischemic strokein vivo. Our findings indicate that studying the regulation of the controlled metabolic depression that occurs in hibernating mammals may lead to novel therapeutic approaches capable of increasing ischemic tolerance in the CNS.
Impact of magnetite nanowires orientation on morphology and activity ofin vitrohippocampal neural networks
Authors: Cortés-Llanos Belén , Rauti Rossana , Ayuso-Sacido Ángel , Pérez Lucas , Ballerini Laura
Published: March 2023

Nanomaterials design, synthesis and characterization are ever-expanding approaches towards developing biodevices or neural interfaces to treat neurological diseases. The ability of nanomaterials features, to tune neuronal networks morphology or functionality is still under study. In this work, we unveil how, when interfacing mammalian brain cultured neurons, iron oxide nanowires (NWs) orientation affects neuronal and glial densities, and network activity. Iron oxide NWs were synthesized by electrodeposition, fixing the diameter to 100 nm and the length to 1 μm. Scanning electron microscopy, Raman and contact angle measurements were performed to characterize the NWs morphology, chemical composition and hydrophilicity. Hippocampal cultures were seeded on NWs devices and after 14 days the cell morphology was studied by immunocytochemistry and confocal microscopy. Live calcium imaging was performed to study neuronal activity. Using random (R-NWs) a higher neuronal and glial cell densities were obtained compared with the control and vertical (V-NWs), while using V-NWs more stellate glial cells were found. R-NWs produced a reduction in neuronal activity while V-NWs increased the neuronal network activity, possibly due to higher neuronal maturity and a lower number of GABAergic neurons, respectively. These results highlight the potential of NWs manipulations to design ad hoc regenerative interfaces.
Leptospiratranscriptome sequencing using long-read technology reveals unannotated transcripts and potential polyadenylation of mRNA molecules
Authors: Xu Ruijie , Prakoso Dhani , Salvador Liliana C. M. , Rajeev Sreekumari
Published: March 2023

Leptospirosis caused by the spirochete bacteriaLeptospirais an emerging zoonosis that causes life-threatening disease in humans and animals. However, a detailed understanding ofLeptospira’sRNA profiles is limited. In this study, we sequenced and analyzed the transcriptome of multipleLeptospiraserovars using Oxford Nanopore Technologies’ direct cDNA and direct RNA sequencing methods. We identified several operon transcriptional units, novel RNA coding regions, and evidence of potential posttranscriptional polyadenylation in theLeptospiratranscriptome. Some coding regions of multiple RNA molecules that have not been previously annotated could be potential sRNA or ncRNA molecules that support gene expression regulation purposes inLeptospira. Many of the relative positions of these unannotated RNA coding regions were consistent in their neighboring coding regions across the reference genomes of two pathogenicLeptospiraanalyzed in this study. Besides, the majority of the unannotated coding regions and operon transcriptional units were not detected in the nonpathogenicLeptospira, suggesting potential virulence-related functions for these RNA molecules coding regions. Overall, our study confirms the utility of ONT’s sequencing in studying prokaryotic transcriptome profiles and offers a tool to improve our understanding of the structural composition of RNA molecules and prokaryotic polyadenylation. However, the findings from our study also warrant that the presence of homopolymers of adenine bases in the transcripts may interfere with the interpretation of bacterial transcriptome profiles. Carefully designed experiments are needed to unravel the role of the features described in this study inLeptospiravirulence and pathogenesis.

Author Summary

Leptospirosis caused by the spirochete bacteria,Leptospira,is recognized as one of the most widespread zoonotic diseases. Leptospirosis is a neglected disease and has been estimated to cause over one million annual human clinical cases and over 60,000 deaths.Leptospiraare maintained in the renal tubules of asymptomatic animal reservoirs, and in contaminated environments, such as soil and water. Studying gene expression profiles is an important component of bacterial pathogenesis studies, and a number of methods are available to do it. Our study compared various transcriptome sequencing methods using one of the latest next generation sequencing tools (Oxford Nanopore Technologies) and evaluated the compositions of RNA in differentLeptospira’stranscriptomes. We identified many previously undescribed and potentially significant features within theLeptospiratranscriptome that may contribute to the virulence and pathogenesis ofLeptospira sp. Our findings lead to new opportunities for researchers to sequence prokaryotic RNA molecules and to unravel many regulatory mechanisms.
Retroelement decay by the exonuclease XRN1 is a viral mimicry dependency in cancer
Authors: Hosseini Amir , Lindholm Håvard T. , Chen Raymond , Mehdipour Parinaz , Marhon Sajid A. , Ishak Charles A. , De Carvalho Daniel D.
Published: March 2023

Viral mimicry describes the immune response induced by endogenous stimuli such as dsRNA formed by endogenous retroelements. Activation of viral mimicry has the potential to kill cancer cells or augment anti-tumor immune response. Paradoxically, cancer cells frequently present a dysregulated epigenome, leading to increased expression of retroelements. We previously found that ADAR1 p150 upregulation is an adaptation mechanism to tolerate high retroelement-derived dsRNA levels, leading to a druggable dependency. Here, we systematically identified novel mechanisms of viral mimicry adaptation associated with cancer cell dependencies. We correlated the gene knockout sensitivity from the DepMap dataset and interferon stimulated gene (ISG) expression in the Cancer Cell Line Encyclopedia (CCLE) dataset of 1005 human cell lines and identified pathways such as RNA modification and nucleic acid metabolism. Among the top hits was the RNA decay protein XRN1 as an essential gene for the survival of a subset of cancer cell lines. XRN1-sensitive cancer cell lines have a high level of cytosolic dsRNA and high ISG expression. Furthermore, sensitivity to XRN1 knockout was mediated by MAVS and PKR activation, indicating that the cells die due to XRN1-dependent induction of viral mimicry. XRN1-resistant cell lines had low basal dsRNA levels, but became synthetically dependent on XRN1 upon treatment with viral mimicry inducing drugs such as 5-AZA-CdR or palbociclib. Finally, XRN1-dependency is partly independent of ADAR1 activity. These results confirm the potential for our ISG correlation analysis to discover novel regulators of viral mimicry and show that XRN1 activation is an adaptive mechanism to control high dsRNA stress induced by dysregulated retroelements in cancer cells and creates a dependency that can be explored for novel cancer therapies.
Seasonal dynamics of a glycan-degrading flavobacterial genus in a tidally-mixed coastal temperate habitat
Authors: Brunet Maéva , Duff Nolwen Le , Rigaut-Jalabert Fabienne , Romac Sarah , Barbeyron Tristan , Thomas François
Published: March 2023

Coastal marine habitats constitute hotspots of primary productivity. In temperate regions, this is due both to massive phytoplankton blooms and dense colonization by macroalgae that mostly store carbon as glycans, contributing substantially to local and global carbon sequestration. Because they control carbon and energy fluxes, algae-degrading microorganisms are crucial for coastal ecosystem functions. Environmental surveys revealed consistent seasonal dynamics of alga-associated bacterial assemblages, yet resolving what factors regulate thein situabundance, growth rate and ecological functions of individual taxa remains a challenge. Here, we specifically investigated the seasonal dynamics of abundance and activity for a well-known alga-degrading marine flavobacterial genus in a tidally-mixed coastal habitat of the Western English Channel. We show that members of the genusZobelliaare a stable, low-abundance component of healthy macroalgal microbiota and can also colonize particles in the water column. This genus undergoes recurring seasonal variations with higher abundances in winter, significantly associated to biotic and abiotic variables.Zobelliacan become a dominant part of bacterial communities on decaying macroalgae, showing a strong activity and high estimatedin situgrowth rates. These results provide insights into the seasonal dynamics and environmental constraints driving natural populations of alga-degrading bacteria that influence coastal carbon cycling.

Originality-significance statement

Glycan-degrading bacteria play a crucial role in marine habitats to remineralize organic carbon sequestered in algal biomass. Yet, resolving what factors regulate thein situabundance, growth rate and ecological functions of individual taxa remains a challenge. Here, we investigate the seasonal dynamics of abundance and activity of an environmentally relevant glycan-degrading bacterial genus in two constrasted compartments of the same coastal habitat, i.e. the surface of diverse macroalgae and the water column. These results provide insights into the recurring temporal patterns and environmental constraints driving natural populations of alga-degrading bacteria that influence ocean carbon cycling.
Bacterial defences interact synergistically by disrupting phage cooperation
Authors: Maestri Alice , Pursey Elizabeth , Chong Charlotte , Pons Benoit J. , Gandon Sylvain , Custodio Rafael , Chisnall Matthew , Grasso Anita , Paterson Steve , Baker Kate , Houte Stineke van , Chevallereau Anne , Westra Edze R.
Published: March 2023

The constant arms race between bacteria and their phages has resulted in a large diversity of bacterial defence systems1,2, with many bacteria carrying several systems3,4. In response, phages often carry counter-defence genes5–9. If and how bacterial defence mechanisms interact to protect against phages with counter-defence genes remains unclear. Here, we report the existence of a novel defence system, coined MADS (Methylation Associated Defence System), which is located in a strongly conserved genomic defence hotspot inPseudomonas aeruginosaand distributed across Gram-positive and Gram-negative bacteria. We find that the natural co-existence of MADS and a Type IE CRISPR-Cas adaptive immune system in the genome ofP. aeruginosaSMC4386 provides synergistic levels of protection against phage DMS3, which carries an anti-CRISPR (acr) gene. Previous work has demonstrated that Acr-phages need to cooperate to overcome CRISPR immunity, with a first sacrificial phage causing host immunosuppression to enable successful secondary phage infections10,11. Modelling and experiments show that the co-existence of MADS and CRISPR-Cas provides strong and durable protection against Acr-phages by disrupting their cooperation and limiting the spread of mutants that overcome MADS. These data reveal that combining bacterial defences can robustly neutralise phage with counter-defence genes, even if each defence on its own can be readily by-passed, which is key to understanding how selection acts on defence combinations and their coevolutionary consequences.
Natural constraints explain working memory capacity limitations in sensory-cognitive models
Authors: Xie Yudi , Duan Yu , Cheng Aohua , Jiang Pengcen , Cueva Christopher J. , Yang Guangyu Robert
Published: March 2023

The limited capacity of the brain to retain information in working memory has been well-known and studied for decades, yet the root of this limitation remains unclear. Here we built sensory-cognitive neural network models of working memory that perform tasks using raw visual stimuli. Contrary to intuitions that working memory capacity limitation stems from memory or cognitive constraints, we found that pre-training the sensory region of our models with natural images imposes sufficient constraints on models to exhibit a wide range of human-like behaviors in visual working memory tasks designed to probe capacity. Examining the neural mechanisms in our model reveals that capacity limitation mainly arises in a bottom-up manner. Our models offer a principled and functionally grounded explanation for the working memory capacity limitation without parameter fitting to behavioral data or much hyperparameter tuning. This work highlights the importance of developing models with realistic sensory processing even when investigating memory and other high-level cognitive phenomena.
Crystal structure of bis[octakis(dimethyl sulfoxide-κO)ytterbium(III)] pentabromidoplumbate(II) tribromide dimethyl sulfoxide monosolvate: a ytterbium-doped lead halide perovskite precursor
Authors: Kinoshita Takumi , Fukumoto Kanna , Segawa Hiroshi
Published: March 2023

A mixture of PbBr2 and YbBr3·nH2O in a dimethyl sulfoxide (DMSO) solution yielded single crystals of a lead halide perovskite precursor with ytterbium, bis[octakis(dimethyl sulfoxide)ytterbium(III)]pentabromidoplumbate(II) tribromide with dimethyl sulfoxide as co-crystallite, [Yb(C2H6OS)8][PbBr5]0.5Br1.5·0.5C2H6OS. The complex ions PbBr5
3− and Yb(DMSO)8
3+ are present in the crystal together with three Br− ions and DMSO molecules. X-ray crystallography revealed that the Br− ions in YbBr3 are replaced by the solvent and bound to a PbII atom or remain free. The presence of PbBr5
3− units, which are molecular ions with a square-pyramidal structure, is also observed. These single crystals react with a caesium chloride solution, exhibiting near-infrared (NIR) luminescence by visible photoexcitation, suggesting the formation of Yb3+-doped lead halide perovskites (CsPbBr3-x
Cl
x
·Yb3+).
Exploring the effects of director network on open innovation: the moderating role of CEO short-sightedness
Authors: Xu Chaohui , Xu Yingjie
Published: March 2023

Purpose

This paper aims to explore the effects of director network on open innovation. As an informal institutional arrangement, the director network is an important source for the enterprise to obtain external information, which provide resource basis for open innovation. Chief Executive Officer (CEO) as the top of management team could make short-sighted decisions for personal interests; this paper also investigates the moderating role of CEO short-sightedness between director network and open innovation.

Design/methodology/approach

This paper takes 4,102 Chinese listed companies from 2007 to 2020 as the research sample. By introducing network centrality and structural hole to measure director network and using data mining to extract key words related to CEO short-sightedness from annual reports, this paper constructs several multiple linear regression models to analyze the impact of director network on open innovation and the moderating role of CEO short-sightedness.

Findings

The analysis finds that director network can facilitate corporate open innovation. Enterprises can acquire more external resources in high centrality and structural hole of director network and promote ability for corporate open innovation. The relationship between director network and open innovation is negatively moderated by CEO short-sightedness. When the level of corporate governance and analyst attention is high, the negative effect of CEO short-sightedness on the innovation effect of directors’ networks is suppressed.

Originality/value

This is the first empirical paper to investigate the promotion effect of director network on open innovation as well as the negative moderating role of CEO short-sightedness. The findings bring new perspectives to the open innovation and enlightenments for practical activities from social relationship aspect.
Impact of circular economy network building: resilience strategy to climate action
Authors: Lin Chun-Chien , Chang Yu-Chen
Published: March 2023

Purpose

This study aims to examine how external and internal conditions drive the impact of circular economy mechanism by decomposing into three policy networks in terms of reduce, reuse and recycle, to better understand the contingency model of climate change and effect of firm size on subsequent performance.

Design/methodology/approach

Drawing on circular economy network and resource-based view (RBV)-network-resilience strategy framework, a pooled longitudinal cross-sectional data model is developed using a sample of 4,050 Taiwanese manufacturing multinational corporations (MNCs) making foreign direct investment between 2013 and 2018. Structural equation modeling analysis is used to comprehensively examine and investigate each circular economy policy network in the context of climate change and firm size. Post hoc multigroup analysis (MGA) is also conducted.

Findings

MGA shows that the reduce policy network is positively and negatively related to manufacturing know-how and production size, respectively. The impact of reuse policy network can enhance the competence of large firms. The recycle policy network is more prominent in terms of competence enhancement of climate change.

Practical implications

MNCs are seeking to build circular economy policy networks to a greater extent, given climate change pressure and guidelines.

Originality/value

This study adds to the circular economy and RBV-network-related literature on climate change and interactions to enhance performance, echoing the recent call on the sustainability of the circular economy of MNCs.
Evaluation and adoption of artificial intelligence in the retail industry
Authors: Fu Hsin-Pin , Chang Tien-Hsiang , Lin Sheng-Wei , Teng Ying-Hua , Huang Ying-Zi
Published: March 2023

Purpose

The introduction of artificial intelligence (AI) technology has had a substantial influence on the retail industry. However, AI adoption entails considerable responsibilities and risks for senior managers. In this study, the authors developed an evaluation and selection mechanism for successful AI technology adoption in the retail industry. The multifaceted measurement and identification of critical factors (CFs) can enable retailers to adopt AI technology effectively and maintain a sustainable competitive advantage.

Design/methodology/approach

The evaluation and adoption of organisational AI technology involve multifaceted decision-making for management. Therefore, the authors used the analytic network process to develop an AI evaluation framework for calculating the weight and importance of each consideration. An expert questionnaire survey was distributed to senior retail managers and 17 valid responses were obtained. Finally, the Vlse Kriterijumska Optimizacija Kompromisno Resenje (VIKOR) method was used to identify CFs for AI adoption.

Findings

The results revealed five CFs for AI adoption in the retail industry. The findings indicated that after AI adoption, top retail management is most concerned with factors pertaining to business performance and minor concerned about the internal system's functional efficiency. Retailers pay more attention to technology and organisation context, which are matters under the retailers' control, than to external uncontrollable environmental factors.

Originality/value

The authors developed an evaluation framework and identified CFs for AI technology adoption in the retail industry. In terms of practical application, the results of this study can help AI service providers understand the CFs of retailers when adopting AI. Moreover, retailers can use the proposed multifaceted evaluation framework to guide their adoption of AI technology.
Asymmetric effects of climate variability on food security in Morocco: evidence from the nonlinear ARDL model
Authors: Soumbara Sid'Ahmed , El Ghini Ahmed
Published: March 2023

Purpose

This study aims to examine the asymmetric effects of average temperature (TP) and rainfall (RF) on the Moroccan food security, measured by the food production index (FPI), using annual data from 1961 to 2020.

Design/methodology/approach

The study uses the Climate Change and Food Security Framework (CCFS) developed by the Food and Agriculture Organization (FAO) and employs the nonlinear auto-regressive distributed lag (NARDL) model and various econometric techniques to show the effects of climate variability in the short and long-term. It also examines if the impacts on Moroccan food security are asymmetric by analyzing the positive and negative partial sums of mean temperature and rainfall.

Findings

The study shows that RF has a long-term relationship with FPI, with increased RF leading to increased FPI and decreased RF leading to decreased FPI. FPI responds more strongly and persistently to a positive shock in RF than to an adverse shock. The study also identifies an asymmetric relationship between FPI and RF, with increased TP enhancing food output in the long run and a decrease reducing food production in the long run.

Research limitations/implications

The current study could have some limitations. For instance, there are several other non-climate factors that might potentially impact food security. In particular, CO2 emissions which from the literature is a key variable that represent climate change impact on food security, was not included. The present research has not included those factors mainly because adding more variables to the model reduces the degree of freedom available to estimate the parameters, resulting in inaccurate results.

Originality/value

This paper contributes to the food security literature by utilizing the latest asymmetry methodology to decompose climate changes into their positive and negative trends and examining the contrasting impacts food production.
Does cognitive biased knowledge influence investor decisions? An empirical investigation using machine learning and artificial neural network
Authors: Bihari Anshita , Dash Manoranjan , Muduli Kamalakanta , Kumar Anil , Mulat-Weldemeskel Eyob , Luthra Sunil
Published: March 2023

Purpose

Current research in the field of behavioural finance has attempted to discover behavioural biases and their characteristics in individual investors’ irrational decision-making. This study aims to find out how biases in information based on knowledge affect decisions about investments.

Design/methodology/approach

In step one, through existing research and consultation with specialists, 13 relevant items covering major aspects of bias were determined. In the second step, multiple linear regression and artificial neural network were used to analyse the data of 337 retail investors.

Findings

The investment choice was heavily impacted by regret aversion, followed by loss aversion, overconfidence and the Barnum effect. It was observed that the Barnum effect has a statistically significant negative link with investing choices. The research also found that investors’ fear of making mistakes and their tendency to be too sure of themselves were the most significant factors in their decisions about where to put their money.

Practical implications

This research contributes to the expansion of the knowledge base in behavioural finance theory by highlighting the significance of cognitive psychological traits in how leading investors end up making irrational decisions. Portfolio managers, financial institutions and investors in developing markets may all significantly benefit from the information offered.

Originality/value

This research is a one-of-a-kind study, as it analyses the emotional biases along with the cognitive biases of investor decision-making. Investor decisions generally consider the shadowy side of knowledge management.
Does competitive asymmetry confer polyploid advantage under changing environments?
Authors: Guo Wen , Wei Na , Hao Guang‐You , Yang Shi‐Jian , Zhu Zhi‐Yong , Yang Yong‐Ping , Duan Yuan‐Wen
Published: March 2023

Competitive interactions drive critical ecological processes in plant communities. Yet, how competitive interactions are influenced by polyploidy that has a widespread incidence in plants remains largely unknown.

To evaluate the hypothesis of competitive asymmetry between polyploids and diploids, we competed tetraploid and diploid plants of perennial herbaceous Chrysanthemum indicum L. (Asteraceae) at different relative frequencies under contrasting soil water contents. We quantified the interaction intensity between competing plants of the same (intraploidy) and different ploidy levels (interploidy), and measured functional traits related to gas exchange and plant water use to understand the underlying mechanisms.

The stronger competitive effect of tetraploids on diploids than that of diploids on tetraploids provided evidence for the competitive asymmetry. As a stronger competitor, tetraploids were limited more by individuals of their own than by diploids. Such competitive asymmetry was not only maintained under reduced soil water content, but also translated into higher above‐ground biomass of tetraploids. Tetraploids showed more resource‐acquisitive traits than diploids under high soil water content and more resource‐conservative traits under reduced soil water content. As such, the higher trait plasticity in tetraploids than diploids likely explained the competitive asymmetry.

Synthesis. These results elucidate the nature and magnitude of species interactions between polyploid and diploid plants under changing environments and the underlying mechanisms, and provide important insights into the prevalence and persistence of polyploid plants under a changing climate.
Collective Trauma, Implicit Memories, the Body, and Active Imagination in Jungian Analysis1
Authors: Fleischer Karin
Published: March 2023

This presentation attempts to show the healing potential underlying the inclusion of the patient's body in the analytic process, while honouring and revisiting the understanding of the psyche‐body connection described by Jung in his early work. In addition, the author offers reflections on the impact of collective trauma whose aftermath, among others, has been the disappearance of thousands of people, consequently breaking the family genealogy, leaving hundreds of children stripped of their roots and true identity. Referencing clinical material, the author describes how the process of translation and integration—from the sensory‐perceptual to the conceptual‐symbolic—can be halted on account of collective trauma occurring at an early stage in development. Moreover, it is shown how the potential of the archetype or image schema, linked to the somatic‐affective early experiences encoded as implicit memories, can be recovered, when Embodied Active Imagination is included in the analytic work. The patient's bodily gestures and somatic experience may bridge the gap between the preverbal‐implicit knowledge and the emergence of emotions and images that allow for the creation of a new symbolic narrative.
Effects of 5‐year experimental warming in the Alpine belt on soil Archaea: Multi‐omics approaches and prospects
Authors: D'Alò Federica , Zucconi Laura , Onofri Silvano , Canini Fabiana , Cannone Nicoletta , Malfasi Francesco , Morais Daniel Kumazawa , Starke Robert
Published: March 2023

We currently lack a predictive understanding of how soil archaeal communities may respond to climate change, particularly in Alpine areas where warming is far exceeding the global average. Here, we characterized the abundance, structure, and function of total (by metagenomics) and active soil archaea (by metatranscriptomics) after 5‐year experimental field warming (+1°C) in Italian Alpine grasslands and snowbeds. Our multi‐omics approach unveiled an increasing abundance of Archaea during warming in snowbeds, which was negatively correlated with the abundance of fungi (by qPCR) and micronutrients (Ca and Mg), but positively correlated with soil water content. In the snowbeds transcripts, warming resulted in the enrichment of abundances of transcription and nucleotide biosynthesis. Our study provides novel insights into possible changes in soil Archaea composition and function in the climate change scenario.
Age‐dependent loss of hepatic SIRT1 enhances NLRP3 inflammasome signaling and impairs capacity for liver fibrosis resolution
Authors: Adjei‐Mosi Jennifer , Sun Qing , Smithson Steven Blake , Shealy Gavyn Lee , Amerineni Krupa Dhruvitha , Liang Zerong , Chen Hanqing , Wang Mei , Ping Qinggong , Han Jingyan , Morita Masahiro , Kamat Amrita , Musi Nicolas , Zang Mengwei
Published: March 2023

Our studies indicate that the longevity factor SIRT1 is implicated in metabolic disease; however, whether and how hepatocyte‐specific SIRT1 signaling is involved in liver fibrosis remains undefined. We characterized a functional link of age‐mediated defects in SIRT1 to the NLRP3 inflammasome during age‐related liver fibrosis. In multiple experimental murine models of liver fibrosis, we compared the development of liver fibrosis in young and old mice, as well as in liver‐specific SIRT1 knockout (SIRT1 LKO) mice and wild‐type (WT) mice. Liver injury, fibrosis, and inflammation were assessed histologically and quantified by real‐time PCR analysis. In a model of hepatotoxin‐induced liver fibrosis, old mice displayed more severe and persistent liver fibrosis than young mice during liver injury and after injury cessation, as characterized by inhibition of SIRT1, induction of NLRP3, infiltration of macrophages and neutrophils, activation of hepatic stellate cells (HSCs), and excessive deposition and remodeling of the extracellular matrix. Mechanistically, deletion of SIRT1 in hepatocytes resulted in NLRP3 and IL‐1β induction, pro‐inflammatory response, and severe liver fibrosis in young mice, mimicking the ability of aging to impair the resolution of established fibrosis. In an aging mouse model, chronic‐plus‐binge alcohol feeding‐induced liver fibrosis was attenuated by treatment with MCC950, a selective NLRP3 inhibitor. NLRP3 inhibition ameliorated alcoholic liver fibrosis in old mice by repressing inflammation and reducing hepatocyte‐derived danger signaling—ASK1 and HMGB1. In conclusion, age‐dependent SIRT1 defects lead to NLRP3 activation and inflammation, which in turn impairs the capacity to resolve fibrosis during aging.
Variant plantaris muscle with degenerated accessory head: Gross and histological analysis
Authors: Futa Brianne A. , Olewnik Łukasz , Konschake Marko , Cardona Juan J. , Iwanaga Joe , Aragones Paloma , Sanudo Jose , Tubbs R. Shane
Published: March 2023

The variant plantaris muscle has itself been reported to have variable presentations. Here, we report an unusual finding of the plantaris muscle and report its gross and histological findings. A duplicated head of the plantaris muscle was identified in the right leg of an adult cadaver age and sex. The more anterior head of the muscle was in the typical location and originated from the superolateral condyle of the femur. However, the more posteriorly located head arose from the iliotibial band at the level of the distal thigh. The two heads united and continued as the typical distal tendon of the plantaris muscle to insert into the calcaneus tendon (Achilles). The normally positioned head of the plantaris muscle was found to be composed of typical skeletal muscle fibres. However, the accessory head of the plantaris muscle was found to be severely degenerated and infiltrated with adipose tissue. We report a duplicated head of the plantaris muscle. Histologically, the accessory head was degenerated and infiltrated with adipose tissue. To our knowledge, this is the first report of such a case. Further cases are now necessary to further elucidate this finding.
The impact of multidisciplinary cancer meetings in guiding treatment intent in patients with upper tract urothelial carcinoma
Authors: Kealey Joshua , Ip Christopher , Davis Ian D. , Sengupta Shomik
Published: March 2023

Introduction

Patient presentation at multidisciplinary cancer meetings (MDMs) is a key quality indicator in cancer care and may have particular utility in rare malignancies, such as upper tract urothelial carcinoma (UTUC). This study aims to investigate what proportion of patients diagnosed with UTUC had treatment intent changed at MDM, the nature of these changes, and what patient factors may correlate with a suggested change.

Methods

This study analyzed patients diagnosed with UTUC between 2015 and 2020 at an Australian tertiary referral center. MDM discussion rate and suggested treatment intent changes were analyzed. Patient factors that may prompt change, including age, estimated glomerular filtration rate (eGFR), Charlson Comorbidity Index (CCI), and Eastern Cooperation Oncology Group performance status (ECOG PS), were assessed.

Results

Seventy‐five patients were diagnosed with UTUC of whom 71 (94.6%) were discussed at an MDM upon diagnosis. Change to palliative intent was suggested in 8/71 (11%) patients. Patients for whom change to palliative treatment was suggested had a higher age (median 85 vs. 78 years, p<.01), CCI (median 7 vs. 4, p<.005), ECOG PS (median 2 vs. 0, p<.002), and lower eGFR (mean 31 vs. 66 mL/min/1.73 m2, p< .0001), compared to those who underwent radical treatment. No patient had an MDM recommendation to change from palliative to curative treatment.

Conclusion

MDM discussion resulted in clinically important changes of treatment intent in a substantial proportion of patients with UTUC, potentially sparing futile treatments. Several patient factors were associated with suggested changes, highlighting the requirement for accurate, in‐depth patient information at MDM discussion.
Regulatory Alchemy: How the Water Cycle Becomes Capital in the California Desert
Authors: Sizek Julia
Published: March 2023

A proposed project will take water from an aquifer in the California desert to the coast. Lacking final approvals more than 30 years after it started, the project remains a plan despite sizeable opposition. What is its secret? In this paper, I examine the imaginaries of the underground aquifer underneath the lands of Cadiz Inc, the project proponent. While local theories insist the company is at the centre of a Chinatown conspiracy, I argue that the company stays alive through regulatory alchemy, a term that reveals the magic at the heart of scientific and regulatory approval processes. I examine narratives of the aquifer in environmental compliance and financial reporting in order to reveal how regulatory processes become the conditions of profit‐making, building on debates in critical legal geography and political ecology.
Spartan dependence on Laurion lead
Authors: Lloyd James Thomas
Published: March 2023

This article presents contextual evidence for the interpretation of lead isotope analysis (LIA) of artefacts from the Archaic Greek Mediterranean. In particular, I make a response to Wood’s suggestion in Archaeometry (2022, first view, ‘Other ways to examine the finances behind the birth of Classical Greece’) that the end of the production of lead votive figurines in Sparta might have been caused by Athenian restrictions to Laurion lead exports, drawing on new LIA of the Spartan lead votives and wider considerations concerning the trade, cost and volume of lead in the 7th to 5th century bce Mediterranean.
Off‐label and unlicensed medicine prescribing in university hospital paediatric wards in Finland: A prospective study
Authors: Kaisto Hanna , Sepponen Kati , Lindell‐Osuagwu Leena , Sankilampi Ulla
Published: March 2023

Aims

The aim of this research is to study the prevalence of prescribing medicines for off‐label (OL) use and unlicensed (UL) medicines for children during hospitalization in 2021 and to assess changes compared with 2011.

Methods

The study included all patients aged <18 years who were treated in the neonatal intensive care unit (NICU) or general paediatric ward of Kuopio University Hospital (KUH), Finland, during 4 weeks in April and May 2021. Their background data and daily information on medicine prescriptions were collected from patient records. The prescriptions were classified as OL, UL or on‐label/approved. The type of OL category was defined.

Results

Altogether, 165 children aged 0–17 years (median 3.2 years) were treated in the paediatric wards (46 in the NICU and 119 in the general ward). In total, 1402 prescriptions were made for 153 children (93%). The proportion of OL and UL prescriptions decreased significantly from 55% in 2011 to 45% (age‐adjusted proportion) in 2021 (P < .001). The proportion of patients receiving at least 1 UL medicine prescription decreased from 53% in 2011 to 30% (age‐adjusted proportion) in 2021 (P < .001). About 76% of hospitalized children were still prescribed either OL prescription or UL medicine in 2021.

Conclusion

The prescriptions for OL use and UL medicines were less prevalent in 2021 than 2011, but still a majority of hospitalized children were prescribed either medicine for OL use or UL medicine in 2021. This indicates a persisting need for approved medicines in children suggesting that revision of EU Paediatric Regulation 2007 is necessary.
Dermatopathology – Current status and development in German‐speaking dermatology
Authors: Mitteldorf Christina , Tronnier Michael
Published: March 2023

Dermatopathology has been an integral part of dermatology for more than 100 years and is essential for high quality patient care. In German‐speaking countries, dermatologists can acquire an additional qualification in dermatopathology after appropriate further training. For many years, dermatopathological diagnostics has advanced far beyond morphology. Immunohistochemistry and molecular pathology are nowadays an essential part and a prerequisite for the preservation of our discipline. Due to the increasing implementation of digitalization and artificial intelligence, dermatopathology is forward‐looking and offers an attractive working environment for young colleagues. Dermatopathology is also indispensable for research, and this fact should also be taken into account by creating academic positions and professorships in the future.
Dermatosurgery – from surgical option to integral part of dermatologic therapy
Authors: Hafner Jürg , Löser Christoph R. , Roka Florian
Published: March 2023

Dermatosurgery was long considered an isolated, and not always important, discipline within dermatology. As a therapeutic option, it was considered either the gold standard of first‐line therapy, for example in basal cell carcinoma surgery and treatment of early‐stage melanoma, or the last option, for instance in the treatment of warts. The fact that a profound change has taken place and that dermatosurgery is now an integral, equal, sometimes leading and always significant component of dermatology will be demonstrated in this review using three examples from geriatric dermatology, the treatment of hidradenitis suppurativa (acne inversa), and melanoma therapy. This review is supplemented by a section on the most important technique in dermatosurgery: microscopic (micrographic) surgery or Mohs Surgery.
Melanom
Authors: Ugurel Selma , Gutzmer Ralf
Published: March 2023

Melanoma is a highly aggressive skin tumor nicknamed “black cancer of the skin” because it originates from the pigment‐forming cells (melanocytes). The tumors are prone to invasive growth and early lymphogenic and hematogenic metastasis. Known risk factors are UV radiation, light skin type, the presence of multiple atypical nevi, and a positive family history. Decisive for the course of the disease are a guideline‐based diagnosis and therapy. In addition to complete excision of the primary tumor with an adequate safety margin, various systemic therapies are available. These are in particular BRAF‐targeted therapy and PD‐1‐based immune checkpoint therapy. This mini‐review does not claim to be exhaustive, but is intended to focus primarily on those aspects of the disease that are currently in clinical and scientific focus, and on which there are new developments to report. In particular, there are new therapeutic regimens for unresectable melanoma and studies of adjuvant treatments, as well as developments in diagnostics.
Right arcuate fasciculus as outcome predictor after low‐frequency repetitive transcranial magnetic stimulation in nonfluent aphasic stroke
Authors: Lin Bing‐Fong , Hon Fei , Lin Mu‐Yun , Tsai Po‐Yi , Lu Chia‐Feng
Published: March 2023

Background and purpose

A reliable neuroimaging biomarker to predict language improvement after neuromodulation in post‐stroke aphasia is lacking. It is hypothesized that aphasic patients with stroke injuries in the left primary language circuits but with sufficient right arcuate fasciculus (AF) integrity might respond to low‐frequency repetitive transcranial magnetic stimulation (LF‐rTMS), leading to language improvement. This study aimed to assess the microstructural indices of the right AF before LF‐rTMS treatment and further correlate with language improvement after the treatment.

Methods

Thirty‐three patients with at least 3 months after stroke in the left hemisphere and nonfluent aphasia were recruited in this randomized double‐blind study. All patients received real 1‐Hz LF‐rTMS (n = 16) or sham stimulation (n = 17) at the right pars triangularis for 10 consecutive weekdays. Fractional anisotropy, axial diffusivity, radial diffusivity and apparent diffusion coefficient of the right AF were extracted using diffusion tensor imaging before the rTMS treatment and correlated with the measured functional improvement by the Concise Chinese Aphasia Test.

Results

The Concise Chinese Aphasia Test change scores revealed a stronger language improvement in auditory/reading comprehension and expression in the rTMS group than in the sham group. Regression analysis showed that the pre‐treatment fractional anisotropy, axial diffusivity and apparent diffusion coefficient of the right AF significantly correlated with the expression abilities (R2 > 0.700, p < 0.044) and comprehension abilities (R2 > 0.702, p < 0.039) in the rTMS group.

Conclusions

It was concluded that the right AF could be a predictor in language recovery induced by LF‐rTMS after the injuries of primary language circuits.
Lipids and amyotrophic lateral sclerosis: A two‐sample Mendelian randomization study
Authors: Xia Kailin , Klose Veronika , Högel Josef , Huang Tao , Zhang Linjing , Dorst Johannes , Fan Dongsheng , Ludolph Albert C.
Published: March 2023

Objective

Previous observational studies revealed a potential but partially controversial relation between lipid metabolism and the risk of amyotrophic lateral sclerosis (ALS), potentially prone to bias. Therefore, we aimed to study whether lipid metabolism involves genetically determined risk factors for ALS through Mendelian randomization (MR) analysis.

Methods

Using genome‐wide association study summary‐level data for total cholesterol (TC) (n = 188,578), high‐density lipoprotein cholesterol (HDL‐C) (n = 403,943), low‐density lipoprotein cholesterol (LDL‐C) (n = 440,546), apolipoprotein A1 (ApoA1) (n = 391,193), apolipoprotein B (ApoB) (n = 439,214), and ALS (12,577 cases and 23,475 controls), we implemented a bidirectional MR study to evaluate a genetic relation between lipids and ALS risk. We performed a mediation analysis to assess whether LDL‐C is a potential mediator on the pathway from traits of LDL‐C‐related polyunsaturated fatty acids (PUFAs) to ALS risk.

Results

We identified genetically predicted increased lipid levels to be associated with the risk of ALS, whereby elevated LDL‐C had the most potent effect (OR 1.028, 95% CI 1.008–1.049, p = 0.006). The effect of increased levels of apolipoproteins on ALS was similar to their corresponding lipoproteins. ALS did not cause any changes in lipid levels. We found no relation between LDL‐C‐modifying lifestyles and ALS. The mediation analysis revealed that LDL‐C could act as an active mediator for linoleic acid, with the mediation effect estimated to be 0.009.

Conclusions

We provided high‐level genetic evidence verifying the positive link between preclinically elevated lipid and ALS risk that had been described in previous genetic and observational studies. We also demonstrated the mediating role of LDL‐C in the pathway from PUFAs to ALS.
Diversity in the clinical presentation of generalized pustular psoriasis (GPP): A series of case vignettes from around the world
Authors: Choon Siew Eng , Elewski Boni E. , Fujita Hideki , Geng Songmei , van de Kerkhof Peter , Mburu Sicily , Puig Lluís , Romiti Ricardo , Venturini Marina
Published: March 2023

A key principle of clinical studies and case reports is that they should reflect the demographics and epidemiology of the patient population concerned. Here, we have compiled a diverse group of clinical cases of generalized pustular psoriasis (GPP) to showcase the differences in GPP presentation in patients worldwide. We attempt to capture the broad spectrum of clinical presentations of GPP and showcase the diversity of the patient population. The patients included in this series are diverse in age, genetic background, skin phototype and medical history. Moreover, they present with a variety of clinical courses of GPP and different degrees of systemic involvement, and experience flares triggered by different inciting factors. The key learnings from this case series may support physicians in identifying and managing patients with this rare and multifaceted disease that can affect patients both physically and psychologically.