bluuebunny/crossref_metadata_2025 huggingface dataset:
A new species ofLethrinops(Cichliformes: Cichlidae) from a Lake Malawi satellite lake, believed to be extinct in the wild
Authors: Turner George F. , Crampton Denise A. , Genner Martin J.
Published: March 2023

A new species of cichlid fish,Lethrinops chilingaliis described from specimens collected from Lake Chilingali, near Nkhotakota, Malawi. It is assigned to the genusLethrinopsbased on the form of the lower jaw dental arcade and by the absence of traits diagnostic of the phenotypically similarCtenopharynx, TaeniolethrinopsandTramitichromis. It also lacks the enlarged cephalic lateral line canal pores found in species ofAlticorpusandAulonocara. The presence of a broken horizontal stripe on the flanks of females and immature/non-territorial males ofLethrinops chilingalidistinguishes them from all congeners, includingLethrinops lethrinus, in which the stripe is typically continuous.Lethrinops chilingalialso has a relatively shorter snout, shorter lachrymal bone and less ventrally positioned mouth thanLethrinops lethrinus. It appears likely thatLethrinops chilingaliis now extinct in the wild, as this narrow endemic species has not been positively recorded in the natural environment since 2009. Breeding populations remain in captivity.
Relationship Between Obesity and Balance in Parachinar, District Kurram, Kpk-An Analytical Cross-Sectional Study
Authors: Hussain Sayed Sajid
Published: March 2023

OBJECTIVE

To find out the effects of BMI on BBS and to determines the risk of falls due to impaired balance in Parachinar, District Kurram

METHODS

An analytical cross-section study was carried out to determine the effects of BMI on BBS; the study included 269 individuals who are classified based on their body mass index. There were 157 males and 112 female. The clinical evaluation instruments Berg balance scale and Time Up and Go test (TUG) were used to collect the data and investigate the relationship between body mass index-based obesity and balance. Data was collected in Parachinar District Kurram from individuals have BMI 22.5kg/m2 or greater and age 20-50 years.

RESULTS

The BBS and TUG scores revealed that obese people had poor balance due to their body weight, as well as a decline in body balance and stability performance. There were 71.4% individuals who had BMI of 27.5-32.5kg/m2(class 1 obesity) and 10% individuals had severed obesity (class 3). 66.9% individuals had low risk of fall, 20% had medium risk of fall, and 12.3% had high risk of fall.

CONCLUSION

This study concluded that obesity has effects on balance and obese individuals have poor balance performance. According to this study individuals with greater BMI have poor balance performance and have high risk of falls. The results of this study illustrates that there is an association of BMI and BBS because the P-value is <0.05 and concluded that obesity cause impaired balance and which leads to increase a risk of falls.
Relationship between neural activity and neuronal cell fate in regeneratingHydrarevealed by cell-type specific imaging
Authors: Escobar Alondra , Kim Soonyoung , Primack Abby S. , Duret Guillaume , Juliano Celina E. , Robinson Jacob T.
Published: March 2023

Understanding how neural circuits are regenerated following injury is a fundamental question in neuroscience.Hydrais a powerful model for studying this process because it has significant and reproducible regenerative abilities, a simple and transparent body that allows for whole nervous system imaging, and established methods for creating transgenics with cell-type-specific expression. In addition, cnidarians such asHydrasplit from bilaterians (the group that encompasses most model organisms used in neuroscience) over 500 million years ago, so similarities with other models likely indicates deeply conserved biological processes.Hydrais a long-standing regeneration model and is an emerging model for neuroscience; however, relatively little is known regarding the restoration of neural activity and behavior following significant injury. In this study, we ask if regenerating neurons reach a terminal cell fate and then reform functional neural circuits, or if neural circuits regenerate first and then guide the constituent cells toward their terminal fate. To address this question, we developed a dual-expression transgenicHydraline that expresses a cell-type-specific red fluorescent protein (tdTomato) in ec5 peduncle neurons, and a calcium indicator (GCaMP7s) in all neurons. This transgenic line allowed us to monitor neural activity while we simultaneously track the reappearance of terminally differentiated ec5 neurons as determined by the expression of tdTomato. Using SCAPE (Swept Confocally Aligned Planar Excitation) microscopy, we tracked both calcium activity and expression of tdTomato-positive neurons in 3D with single-cell resolution during regeneration ofHydra’saboral end. We observed tdTomato expression in ec5 neurons approximately four hours before the neural activity begins to display synchronized patterns associated with a regenerated neural circuit. These data suggest that regenerating neurons undergo terminal differentiation prior to re-establishing their functional role in the nervous system. The combination of dynamic imaging of neural activity and gene expression during regeneration makeHydraa powerful model system for understanding the key molecular and functional processes involved in neuro-regeneration following injury.
Quantification of elongation stalls and impact on gene expression in yeast
Authors: Hou Wanfu , Harjono Vince , Harvey Alex T. , Subramaniam Arvind Rasi , Zid Brian M.
Published: March 2023

Ribosomal pauses are a critical part of co-translational events including protein folding and localization. However, extended ribosome pauses can lead to ribosome collisions, resulting in the activation of ribosome rescue pathways and turnover of protein and mRNA. While this relationship has been known, the specific threshold between permissible pausing versus activation of rescue pathways has not been quantified. We have taken a method used to measure elongation time and adapted it for use inS. cerevisiaeto quantify the impact of elongation stalls. We find, in transcripts containing Arg CGA codon repeat-induced stalls, a Hel2-mediated dose-dependent decrease in protein expression and mRNA level and an elongation delay on the order of minutes. In transcripts that contain synonymous substitutions to non-optimal Leu codons, there is a decrease in protein and mRNA levels, as well as similar elongation delay, but this occurs through a non-Hel2-mediated mechanism. Finally, we find that Dhh1 selectively increases protein expression, mRNA level, and elongation rate. This indicates that distinct poorly translated codons in an mRNA will activate different rescue pathways despite similar elongation stall durations. Taken together, these results provide new quantitative mechanistic insight into the surveillance of translation and the roles of Hel2 and Dhh1 in mediating ribosome pausing events.
Flexible and site-specific manipulation of histones in live animals
Authors: Finkin-Groner Efrat , Al-Kachak Amni , Agustinus Albert , Bastle Ryan , Lepack Ashley , Lyu Yang , Maze Ian , David Yael
Published: March 2023

Recent advances in protein engineering have provided a wealth of methods that allow for the site-specific manipulation of proteinsin vitroand in cells. However, the efforts to expand these toolkits for use in live animals has been limited. Here, we report a new method for the semi-synthesis of site-specifically modified and chemically defined proteins in live animals. Importantly, we illustrate the usefulness of this methodology in the context of a challenging, chromatin bound N-terminal histone tail within rodent postmitotic neurons located in ventral striatum (Nucleus Accumbens/NAc). This approach provides the field with a precise and broadly applicable methodology for manipulating histonesin vivo, thereby serving as a unique template towards examining chromatin phenomena that may mediate transcriptomic and physiological plasticity within mammals.
Time-resolved cryo-EM of G protein activation by a GPCR
Authors: Papasergi-Scott Makaía M. , Pérez-Hernández Guillermo , Batebi Hossein , Gao Yang , Eskici Gözde , Seven Alpay B. , Panova Ouliana , Hilger Daniel , Casiraghi Marina , He Feng , Maul Luis , Gmeiner Peter , Kobilka Brian K. , Hildebrand Peter W. , Skiniotis Georgios
Published: March 2023

G protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by stimulating the exchange of guanine nucleotide in the Gα subunit. To visualize this mechanism, we developed a time-resolved cryo-EM approach that examines the progression of ensembles of pre-steady-state intermediates of a GPCR-G protein complex. Using variability analysis to monitor the transitions of the stimulatory Gs protein in complex with the β2-adrenergic receptor (β2AR) at short sequential time points after GTP addition, we identified the conformational trajectory underlying G protein activation and functional dissociation from the receptor. Twenty transition structures generated from sequential overlapping particle subsets along this trajectory, compared to control structures, provide a high-resolution description of the order of events driving G protein activation upon GTP binding. Structural changes propagate from the nucleotide-binding pocket and extend through the GTPase domain, enacting alterations to Gα Switch regions and the α5 helix that weaken the G protein-receptor interface. Molecular dynamics (MD) simulations with late structures in the cryo-EM trajectory support that enhanced ordering of GTP upon closure of the alpha-helical domain (AHD) against the nucleotide-bound Ras-homology domain (RHD) correlates with irreversible α5 helix destabilization and eventual dissociation of the G protein from the GPCR. These findings also highlight the potential of time-resolved cryo-EM as a tool for mechanistic dissection of GPCR signaling events.
Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease
Authors: Wang Zixi , Zhu Shijia , Jia Yuemeng , Wang Yunguan , Kubota Naoto , Fujiwara Naoto , Gordillo Ruth , Lewis Cheryl , Zhu Min , Sharma Tripti , Li Lin , Zeng Qiyu , Lin Yu-Hsuan , Hsieh Meng-Hsiung , Gopal Purva , Wang Tao , Hoare Matt , Campbell Peter , Hoshida Yujin , Zhu Hao
Published: March 2023

Somatic mutations in non-malignant tissues accumulate with age and insult, but whether these mutations are adaptive on the cellular or organismal levels is unclear. To interrogate mutations found in human metabolic disease, we performed lineage tracing in mice harboring somatic mosaicism subjected to non-alcoholic steatohepatitis (NASH). Proof-of-concept studies with mosaic loss ofMboat7, a membrane lipid acyltransferase, showed that increased steatosis accelerated clonal disappearance. Next, we induced pooled mosaicism in 63 known NASH genes, allowing us to trace mutant clones side-by-side. Thisin vivotracing platform, which we coined MOSAICS, selected for mutations that ameliorate lipotoxicity, including mutant genes identified in human NASH. To prioritize new genes, additional screening of 472 candidates identified 23 somatic perturbations that promoted clonal expansion. In validation studies, liver-wide deletion ofBcl6, Tbx3,orSmyd2resulted in protection against NASH. Selection for clonal fitness in mouse and human livers identifies pathways that regulate metabolic disease.

Highlights:

MosaicMboat7mutations that increase lipotoxicity lead to clonal disappearance in NASH.

In vivo screening can identify genes that alter hepatocyte fitness in NASH.

MosaicGpammutations are positively selected due to reduced lipogenesis.

In vivo screening of transcription factors and epifactors identified new therapeutic targets in NASH.
2,2′:4,4′′:4′,4′′′-Quaterpyridine: synthesis, crystal-structure description, and Hirshfeld surface analysis
Authors: Aderinto Stephen O. , Thomas Jim A. , Robertson Craig C.
Published: March 2023

The title compound, 2,2′:4,4′′:4′,4′′′-quaterpyridine (Qtpy), C20H14N4, crystallizes in the triclinic P\overline{1} space group and has half of the molecule in the asymmetric unit, corresponding to 4,4′-bipyridine (4,4′-bpy) that serves as the building block for the molecule. C4,4′-bpy—N—C4,4′-bpy and/or N—C4,4′-bpy—C4,4′-bpy bond-angle parameters show that the 4,4′-bpy ligands are highly rigid, displaying values lower than the linear bond angle of 180°. In the crystal, the 4,4′-bpy units are seen to be facing each other in relatively close proximity. The most important interactions on the Hirshfeld Surface of the compound are C—H...N/H...N—C interactions (constituting 10.6% and 7.6% of the total surface).
Crystal structure and Hirshfeld surface analysis of mono/bis(aqua-κO)[N-(2-oxidobenzylidene)valinato-κ3
O,N,O′]copper(II): dimeric Schiff base copper(II) complexes having different numbers of coordinated water molecules
Authors: Akiyama Yukihito , Suzuki Soma , Suda Shintaro , Takiguchi Yuji , Nakane Daisuke , Akitsu Takashiro
Published: March 2023

The molecular structure of the title compound, [Cu(C12H13N2O3)(H2O)2]·[Cu(C12H13N2O3)(H2O)], consists of two different molecules in the asymmetric unit. Both of the structures consist of a tridentate ligand synthesized from L-valine and salicylaldehyde, and one water molecule or two water molecules coordinating to CuII. They have a square-planar (molecule 1) or a square-pyramidal (molecule 2) coordination geometry. In the crystal, the molecules form intra- and intermolecular O—H...O hydrogen bonds involving the coordinated water molecules and other sites. A Hirshfeld surface analysis indicated that the most important contributions to the packing are from H...H [52.9% (molecule 1) and 51.1% (molecule 2)] and H...O/ O...H [21.2% (molecule 1) and 25.8% (molecule 2)] contacts. In addition, an electrostatic potential map was also obtained from DFT calculations to support the discussion of the intermolecular interactions.
Automation in architecture, engineering and construction: a scientometric analysis and implications for management
Authors: Klarin Anton , Xiao Qijie
Published: March 2023

Purpose

Many economic, political and socio-cultural events in the 2020s have been strong headwinds for architecture, engineering and construction (AEC). Nevertheless, technological advancements (e.g. artificial intelligence (AI), big data and robotics) provide promising avenues for the development of AEC. This study aims to map the state of the literature on automation in AEC and thereby be of value not only to those researching automation and its composition of a variety of distinct technological and system classes within AEC, but also to practitioners and policymakers in shaping the future of AEC.

Design/methodology/approach

This review adopts scientometric methods, which have been effective in the research of large intra and interdisciplinary domains in the past decades. The full dataset consists of 1,871 articles on automation in AEC.

Findings

This overarching scientometric review offers three interdisciplinary streams of research: technological frontiers, project monitoring and applied research in AEC. To support the scientometric analysis, the authors offer a critical integrative review of the literature to proffer a multilevel, multistage framework of automation in AEC, which demonstrates an abundance of technological paradigm discussions and the inherent need for a holistic managerial approach to automation in AEC.

Originality/value

The authors underline employee well-being, business sustainability and social growth outcomes of automation and provide several managerial implications, such as the strategic management approach, ethical management view and human resource management perspective. In doing so, the authors seek to respond to the Sustainable Development Goals proposed by the United Nations as this becomes more prevalent for the industry and all levels of society in general.
Are financially illiterate individuals all the same? A study on incorrect and “do not know” answers to financial knowledge questions
Authors: Cucinelli Doriana , Soana Maria Gaia
Published: March 2023

Purpose

Are financially illiterate individuals all the same? This study aims to answer this question. Specifically, the authors investigate whether people answering incorrectly and “do not know” to the big five questions about financial knowledge (FK), all identified by previous literature as financially illiterate, are two sides of the same coin, or rather individuals with different socio-economic and demographic characteristics, and whether this leads to different levels of risk of falling victim to financial fraud.

Design/methodology/approach

Using a large and representative sample of Italian adults, the authors run both ordered probit and probit regressions to test the determinants of financially illiterate individuals, distinguishing between those answering FK questions incorrectly and those answering “do not know”. The authors also measure the probability of falling victim to financial fraud for the two groups. To check the robustness of our results, the authors run a multinomial regression, a structural equation model and an instrumental variable regression model.

Findings

The authors demonstrate that the socio-demographic and socio-economic characteristics of individuals selecting incorrect responses to FK questions are different from those of individuals selecting the “do not know” option. Moreover, the results show that the former are more likely to be victims of financial frauds.

Practical implications

The “one-size-fits-all” approach is not suitable for financial education. It is important to consider socio-demographic and socio-economic characteristics of individuals in order to identify specific targets of education programmes aiming to reduce insecurity and excessive self-confidence as well as to increase objective FK. The study’s findings also identify vulnerable groups to which financial fraud prevention schemes should be targeted.

Originality/value

To date, financial illiteracy has been measured as the sum of incorrect and “do not know” responses given to FK questions. This approach does not allow to observe the socio-demographic and socio-economic differences between people choosing the “do not know” option and those answering incorrectly. The paper aims to overcome this limit by investigating the socio-demographic and socio-economic characteristics of individuals selecting “do not know” and incorrect responses, respectively. The authors also investigate whether the two groups have different probabilities of being victims of financial fraud.
An overview of research trends on sustainability in higher education – an exploratory study
Authors: Leal Filho Walter , Frankenberger Silva Fernanda , Salvia Amanda , Shiel Chris , Paço Arminda , Price Elizabeth , Brandli Luciana Londero , Rampasso Izabela Simon , Anholon Rosley , Quelhas Osvaldo Luiz Gonçalves , Pretorius Rudi Wessel
Published: March 2023

Purpose

This study aims to investigate the main areas in which researchers are focusing their efforts in terms of sustainability in higher education (curriculum, campus greening, research, governance or outreach), the format in which this research is performed (in terms of individual or combined efforts) and the primary research focus (in terms of local or global issues).

Design/methodology/approach

Trends on sustainability research were investigated by means of an online survey – the World Survey on Sustainability Publishing and Research in Higher Education, which was disseminated among members of the European School of Sustainability Science and Research and the Inter-University Sustainable Development Research Programme.

Findings

The survey collected responses from 103 researchers across over 40 countries. Three trends emerged: in spite of the intrinsic value of sustainability research in higher education, this area is not as mature as one could expect; the range of themes covered is wide and addresses a variety of areas; and individuals working alone is the most common means of doing research, whereas research at the university, department and faculty level appears to be less common.

Originality/value

The paper outlines some measures via which higher education institutions may be able to take more advantage of the many opportunities sustainability research offers to them.
Reproductive phenology of critical native plant species for mineland restoration in the eastern Amazon
Authors: da Costa Ana Carolina Galindo , Vasconcelos Liziane Vilela , de Lima Carla Teixeira , Caldeira Cecílio Frois , Zappi Daniela Cristina , Giulietti Ana Maria , Watanabe Maurício Takashi Coutinho
Published: March 2023

Amazon ironstone outcrops vegetation, or canga, is a remarkable environment in which the plants are adapted to peculiar circumstances. Knowledge regarding different aspects of this ecosystem remains modest, including necessary insights for its conservation and recovery, such as the reproductive phenology of priority species that form the plant community. This study aimed to monitor the reproductive phenology of critical native species that are categorized as rare, endemic, and/or threatened in the canga of the Amazon Rainforest, in Pará, Brazil. During February 2016 and May 2017, eleven species were evaluated regarding the presence or absence of flowering and fruiting phenophases, and these were associated with environmental variables. Phenological data were evaluated through circular statistical analysis. All studied species flowered and produced fruit during the monitoring period. The evaluated species have an annual reproductive cycle marked by seasonality and flowering peaks between March and April, during the wet season, and fruiting peaks during May, at the beginning of the dry season. The best period for collecting ripe seeds, a primary tool for the restoration of degraded areas, is June. Water availability may be essential for the establishment of annual plants and to induce flowering in both annual and perennial species. The reproductive phenophases of the studied species are concentrated within a short period and are synchronized, which may increase the possibility of cross‐pollination and minimize flower and seed predation. We discuss the challenges in including annual plants and the importance of having them and perennial species in conservation and restoration of degraded areas projects.
Transformative systemic changes to embed environmental sustainability in foodservices: A grounded theory exploration
Authors: Smeltzer Madison E. , Davidson Alexandra R. , Reidlinger D. P. , MacKenzie‐Shalders Kristen L.
Published: March 2023

Aims

Foodservices are a strong contributor to global environmental impact. Systemic change is required to lead the transformation towards environmentally sustainable foodservices. However, guidance to support foodservices to be more environmentally sustainable is lacking. The aim was to explore food‐related environmentally sustainable strategies and their transferability to foodservices in a range of settings, to inform a framework for future application and research.

Methods

A constructivist grounded theory study design was used. Semi‐structured interviews with foodservice sustainability consultants, who support foodservice organisations to improve environmental sustainability, were conducted. Interviews were recorded, transcribed, and coded line‐by‐line. Ten consultants were purposively sampled for diversity in location, organisation type, funding model, and services provided. Codes were collapsed into categories, to inform the development of themes and a framework for the implementation of strategies.

Results

Four sub‐themes were created under an overarching theme of ‘Transforming the Foodservice System’: embedding leadership, shifting perspective, constructing collaborative networks, and fostering momentum. A range of implementation strategies were captured within the sub‐themes.

Conclusion

These themes informed the development of a practical application framework for implementing sustainable strategies in foodservices that is useful for practice and future research in the area.
Delineation of a lactococcal conjugation system reveals a restriction‐modification evasion system
Authors: Ortiz Charneco Guillermo , Kelleher Philip , Buivydas Andrius , Dashko Sofia , de Waal Paul P. , van Peij Noël N. M. E. , Roberts Richard J. , Mahony Jennifer , van Sinderen Douwe
Published: March 2023

Plasmid pUC11B is a 49.3‐kb plasmid harboured by the fermented meat isolate Lactococcus lactis subsp. lactis UC11. Among other features, pUC11B encodes a pMRC01‐like conjugation system and tetracycline‐resistance. In this study, we demonstrate that this plasmid can be conjugated at high frequencies to recipient strains. Mutational analysis of the 22 genes encompassing the presumed pUC11B conjugation cluster revealed the presence of several genes with essential conjugation functions, as well as a gene, trsR, encoding a putative transcriptional repressor of this conjugation cluster. Furthermore, plasmid pUC11B encodes an anti‐restriction protein, TrsAR, which facilitates higher conjugation frequencies when pUC11B is transferred into recipient strains containing Type II or Type III RM systems. These findings demonstrate how RM mechanisms can be circumvented when they act as a biological barrier for conjugation events.
β‐Cell glucokinase expression was increased in type 2 diabetes subjects with better glycemic control
Authors: Liu Jingwen , Fu Hui , Kang Fuyun , Ning Guang , Ni Qicheng , Wang Weiqing , Wang Qidi
Published: March 2023

Background

Type 2 diabetes (T2D) is characterized by a progressive deterioration of β‐cell function with a continuous decline in insulin secretion. Glucokinase (GCK) facilitates the rate‐limiting step of glycolysis in pancreatic β‐cells, to acquire the proper glucose‐stimulated insulin secretion. Multiple glucokinase activators (GKAs) have been developed and clinically tested. However, the dynamic change of human pancreatic GCK expression during T2D progression has not been investigated.

Methods

We evaluated GCK expression by measuring the average immunoreactivity of GCK in insulin+ or glucagon+ cells from pancreatic sections of 11 nondiabetic subjects (ND), 10 subjects with impaired fasting glucose (IFG), 9 with well‐controlled T2D (wT2D), and 5 individuals with poorly controlled T2D (uT2D). We also assessed the relationship between GCK expression and adaptive unfolded protein response (UPR) in human diabetic β‐cells.

Results

We did not detect changes of GCK expression in IFG islets. However, we found β‐cell GCK levels were significantly increased in T2D with adequate glucose control (wT2D) but not in T2D with poor glucose control (uT2D). Furthermore, there was a strong positive correlation between GCK expression and adaptive UPR (spliced X‐box binding protein 1 [XBP1s] and activating transcription factor 4 [ATF4]), as well as functional maturity marker (urocortin‐3 [UCN3]) in human diabetic β‐cells.

Conclusions

Our study demonstrates that inductions of GCK enhanced adaptive UPR and UCN3 in human β‐cells, which might be an adaptive mechanism during T2D progression. This finding provides a rationale for exploring novel molecules that activate β‐cell GCK and thereby improve pharmacological treatment of T2D.
First‐degree relatives of patients with systemic lupus erythematosus: Autoreactivity but not autoimmunity?
Authors: Penev Bogdan , Vasilev Georgi , Todorova Ekaterina Ivanova , Tumangelova‐Yuzeir Kalina , Kurteva Ekaterina , Monov Simeon , Kyurkchiev Dobroslav
Published: March 2023

Background

Systemic lupus erythematosus (SLE) is a disorder with a complex immunopathogenesis. It is well known that the disease begins with immunological alterations and autoantibody appearance in the serum years before clinical onset. As SLE has a strong tendency to familial aggregation, first‐degree relatives (FDRs) constitute a group at elevated risk. The current understanding is that external risk factors trigger underlying immune dysregulations, leading to overt disease in those with elevated genetic risk.

Objective

This cross‐sectional study investigates the degree to which clinical features, external risk factors, and immunological profiles differ in SLE FDRs from healthy individuals and SLE patientts.

Methods

Three groups were studied: Lupus patient FDRs (n = 56), healthy controls (n = 20), and SLE patients (n = 20). FDRs and healthy participants completed a detailed clinical questionnaire that included questions regarding smoking and estrogen drug history. All participants were tested for the presence of the following antinuclear autoantibodies (ANAs) against: nRNP/Sm, Sm, Ro60, Ro‐52, La, Scl‐70, PM‐Scl, PM‐ Scl, Jo‐1, CENP B, PCNA, dsDNA, nucleosomes, histones, RibP, AMA M2, DFS70, and eight soluble cytokines, including transforming growth factor‐β (TGF‐β), vitamin D levels, and antibodies against Epstein‐Barr virus (EBV).

Results

Compared with the healthy controls, FDRs had higher titers of ANA, more specific staining immunofluorescent patterns, and more autoantibody specificities. Furthermore, FDRs differed significantly in their TGF‐β levels from the other two groups. In FDRs, some clinical features (hair loss, skin, and oral ulcer‐like lesions) were associated with higher ANA titers and some (oral ulcer‐like lesions) with the anti‐Ro60‐specific antibody. Interestingly, there was an association between ANA titers and levels of antibodies against EBV only in the FDR group.

Conclusion

First‐degree relatives display unique clinical and immunological profiles, placing them between healthy individuals and SLE patients, with a balance between compensated immune dysregulation and disease‐developing potential. A possible association between ANA titer and the number of clinical complaints is observed, which needs to be confirmed in more extensive studies.
Public health clauses in international investment agreements: Sword or shield?
Authors: Thow Anne Marie , Alschner Wolfgang , Aljunied Faisal
Published: March 2023

The interaction of international investment agreements and public health is marked by ambivalence. Investment treaties can help attract investment into the health sector but also enable international legal claims by foreign investors against public health measures. This paper seeks to better understand their relationship by systematically mapping the purpose of health inclusions in bilateral investment treaties (BITs) between 1959 and 2021. We find that health‐related clauses, present in 18% of all BITs, are used both as a shield and a sword. Most health mentions protect host countries from claims against public health measures, yet an increasing number of recent BITs, primarily from developing countries, also pursue an offensive public health agenda by advancing health safety at work and health‐related corporate social responsibility of investors.
Longitudinal Incremental Propensity Score Interventions for Limited Resource Settings
Authors: Sarvet Aaron L. , Wanis Kerollos N. , Young Jessica G. , Hernandez-Alejandro Roberto , Stensrud Mats J.
Published: March 2023

Many real-life treatments are of limited supply and cannot be provided to all individuals in the population. For example, patients on the liver transplant waiting list usually cannot be assigned a liver transplant immediately at the time they reach highest priority because a suitable organ is not immediately available. In settings with limited supply, investigators are often interested in the effects of treatment strategies in which a limited proportion of patients receive an organ at a given time, that is, treatment regimes satisfying resource constraints. Here, we describe an estimand that allows us to define causal effects of treatment strategies that satisfy resource constraints: incremental propensity score interventions (IPSIs) for limited resources. IPSIs flexibly constrain time-varying resource utilization through proportional scaling of patients' natural propensities for treatment, thereby preserving existing propensity rank ordering compared to the status quo. We derive a simple class of inverse-probability-weighted estimators, and we apply one such estimator to evaluate the effect of restricting or expanding utilization of “increased risk” liver organs to treat patients with end-stage liver disease.
Potent antitumor effects of the conditioned medium of bone marrow‐derived mesenchymal stem cells via IGFBP‐4
Authors: Furusaka Yuma , Inoue Shinya , Mizoguchi Izuru , Hasegawa Hideaki , Katahira Yasuhiro , Watanabe Aruma , Sakamoto Eri , Sekine Ami , Miyakawa Satomi , Umezu Tomohiro , Owaki Toshiyuki , Yoneto Toshihiko , Yoshimoto Takayuki
Published: March 2023

Cell transfer therapy using mesenchymal stem cells (MSCs) has pronounced therapeutic potential, but concerns remain about immune rejection, emboli formation, and promotion of tumor progression. Because the mode of action of MSCs highly relies on their paracrine effects through secretion of bioactive molecules, cell‐free therapy using the conditioned medium (CM) of MSCs is an attractive option. However, the effects of MSC‐CM on tumor progression have not been fully elucidated. Herein, we addressed this issue and investigated the possible underlying molecular mechanisms. The CM of MSCs derived from human bone marrow greatly inhibited the in vitro growth of several human tumor cell lines and the in vivo growth of the SCCVII murine squamous cell carcinoma cell line with reduced neovascularization. Exosomes in the MSC‐CM were only partially involved in the inhibitory effects. The CM contained a variety of cytokines including insulin‐like growth factor binding proteins (IGFBPs). Among them, IGFBP‐4 greatly inhibited the in vitro growth of these tumors and angiogenesis, and immunodepletion of IGFBP‐4 from the CM significantly reversed these effects. Of note, the CM greatly reduced the phosphorylation of AKT, ERK, IGF‐1 receptor beta, and p38 MAPK in a partly IGFBP4‐dependent manner, possibly through its binding to IGF‐1/2 and blocking the signaling. The CM depleted of IGFBP‐4 also reversed the inhibitory effects on in vivo tumor growth and neovascularization. Thus, MSC‐CM has potent inhibitory effects on tumor growth and neovascularization in an IGFBP4‐dependent manner, suggesting that cell‐free therapy using MSC‐CM could be a safer promising alternative for even cancer patients.
Dihydroorotate dehydrogenase regulates ferroptosis in neurons after spinal cord injury via the P53‐ALOX15 signaling pathway
Authors: Li Dachuan , Lu Xiao , Xu Guangyu , Liu Siyang , Gong Zhaoyang , Lu Feizhou , Xia Xinlei , Jiang Jianyuan , Wang Hongli , Zou Fei , Ma Xiaosheng
Published: March 2023

Background

Spinal cord injury (SCI) is a highly disabling condition in spinal surgery that leads to neuronal damage and secondary inflammation. Ferroptosis is a non‐apoptotic type of cell death that has only recently been identified, which is marked primarily by iron‐dependent and lipid‐derived reactive oxygen species accumulation, and accompanied by morphological modifications such as mitochondrial atrophy and increase in membrane density. Dihydroorotate dehydrogenase (DHODH) is a powerful inhibitor of ferroptosis and has been demonstrated to inhibit cellular ferroptosis in tumor cells, but whether it can inhibit neuronal injury following spinal cord injury remains ambiguous.

Methods

In this study, the effect of DHODH on neuronal ferroptosis was observed in vivo and in vitro using a rat spinal cord injury model and erastin‐induced PC12 cells, respectively. A combination of molecular and histological approaches was performed to assess ferroptosis and explore the possible mechanisms in vivo and in vitro.

Results

First, we confirmed the existence of neuronal ferroptosis after spinal cord injury and that DHODH attenuates neuronal damage after spinal cord injury. Second, we showed molecular evidence that DHODH inhibits the activation of ferroptosis‐related molecules and reduces lipid peroxide production and mitochondrial damage, thereby reducing neuronal ferroptosis. Further analysis suggests that P53/ALOX15 may be one of the mechanisms regulated by DHODH. Importantly, we determined that DHODH inhibits ALOX15 expression by inhibiting P53.

Conclusions

Our findings reveal a novel function for DHODH in neuronal ferroptosis after spinal cord injury, suggesting a unique therapeutic target to alleviate the disease process of spinal cord injury.
A Manifesto for project management research
Authors: Locatelli Giorgio , Ika Lavagnon , Drouin Nathalie , Müller Ralf , Huemann Martina , Söderlund Jonas , Geraldi Joana , Clegg Stewart
Published: March 2023

Project management research has evolved over the past five decades and is now a mature disciplinary field investigating phenomena of interest to academics, practitioners and policymakers. Studies of projects and project management practices are theoretically rich and scientifically rigorous. They are practically relevant and impactful when addressing the pursuit of operational, tactical and strategic advancements in the world of organisations. We want to broaden the conversation between project management scholars and other scholars from cognate disciplines, particularly business and management, in a true scholarship of integration and cross‐fertilisation. This Manifesto invites the latter scholars to join efforts providing a foundation for further creative, theoretical and empirical contributions, including but not limited to tackling grand challenges such as climate change, pandemics, and global poverty. To this end, we identify five theses:

Projects are often ‘agents of change’ and hence fundamental to driving the innovation and change required to tackle grand challenges.

Much project management research leverages and challenges theories across disciplines, including business, organisation and management studies, contributing to developing new theories, including those specific to projects and temporary organisations.

‘Projects’ are useful units of analysis, project management research is ideal for scientific cross‐fertilisation and project management scholars welcome academics from other communities to engage in fruitful conversations.

As in many other fields of knowledge, the project management research community embraces diversity, welcoming researchers of different genders and various scientific and social backgrounds.

Historically rooted in ‘problem‐solving’ and normative studies, project management research has become open to interpretative and emancipatory research, providing opportunities for other business, management and organisational scholars to advance their knowledge communities.
Novel partial deletions, frameshift and missense mutations of CSF1R in patents with CSF1R‐related leukoencephalopathy
Authors: Ishiguro Takanobu , Konno Takuya , Hara Norikazu , Zhu Bin , Okada Satoshi , Shibata Mamoru , Saika Reiko , Kitano Takaya , Toko Megumi , Nezu Tomohisa , Hama Yuka , Kawazoe Tomoya , Takahashi‐Iwata Ikuko , Yabe Ichiro , Sato Kota , Takeda Hayato , Toda Shintaro , Nishimiya Jin , Teduka Toshiyuki , Nozaki Hiroaki , Kasuga Kensaku , Miyashita Akinori , Onodera Osamu , Ikeuchi Takeshi
Published: March 2023

Background and purpose

Colony‐stimulating factor 1 receptor (CSF1R)‐related leukoencephalopathy is an adult‐onset leukoencephalopathy caused by mutations in CSF1R. The present study aimed to explore the broader genetic spectrum of CSF1R‐related leukoencephalopathy in association with clinical and imaging features.

Methods

Mutational analysis of CSF1R was performed for 100 consecutive patients with adult‐onset leukoencephalopathy. Sequence and copy number variation (CNV) analyses of CSF1R were performed. The genomic ranges of the deletions were determined by long‐read sequencing. Ligand‐dependent autophosphorylation of CSF1R was examined in cells expressing the CSF1R mutants identified in this study.

Results

CSF1R mutations were identified in 15 patients, accounting for 15% of the adult‐onset leukoencephalopathy cases. Seven novel and five previously reported CSF1R mutations were identified. The novel mutations, including three missense and one in‐frame 3 bp deletion, were located in the tyrosine kinase domain (TKD) of CSF1R. Functional assays revealed that none of the novel mutations in the TKD showed autophosphorylation of CSF1R. Two partial deletions of CSF1R were identified that resulted in lack of the C‐terminal region, including the distal TKD, in two patients. Various clinical features including cognitive impairment, psychiatric symptoms and gait disturbance were observed. Various degrees of the white matter lesions and corpus callosum abnormalities on magnetic resonance imaging and characteristic calcifications on computed tomography were observed as imaging features.

Conclusions

Our results highlight the importance of examining the CNV of CSF1R even when Sanger or exome sequencing reveals no CSF1R mutations. Genetic examination of sequences and CNV analyses of CSF1R are recommended for an accurate diagnosis of CSF1R‐related leukoencephalopathy.
Do different platforms of coronavirus vaccines have different impacts on psoriasis flares?
Authors: Chularojanamontri Leena , Likittanasombat Surachanee , Chaiyabutr Chayada , Silpa‐archa Narumol , Wongpraparut Chanisada
Published: March 2023

This study evaluated the impacts on psoriasis flares of 3 vaccine platforms: inactivated, viral vector and mRNA. Respectively, 198 and 96 psoriasis patients with and without COVID‐19 vaccination during the study period. Group comparison revealed no increased risk of psoriasis flaring after COVID‐19 vaccination. The vaccinated group received 425 doses of vaccine (140 inactivated, 230 viral vector and 55 mRNA). Patients' self‐reported symptoms included all three platforms causing psoriasis flare, but the highest was among patients administered with mRNA vaccines. Most flares were mild to moderate, and most patients (89.8%) managed their flare‐up lesions without rescue therapy. In conclusion, our study showed that the rate of psoriasis flare was not significantly different between vaccinated and unvaccinated groups. Factors that might explain psoriasis flare include vaccine‐related psychological stress and side effects from vaccination. Different platforms of corona vaccines seemed to have different impact of psoriasis flares. Based on our results and the recommendations of several consensus guidelines, the benefits of COVID vaccinations outweigh the risks to patients with psoriasis. Patients with psoriasis should receive a COVID vaccine as soon as one is available.
Nanoindentation characterization on competing propagation between the transgranular and intergranular cracking of 316H steel under creep‐fatigue loading
Authors: Song Yuxuan , Pan Zhouxin , Yu Ting , Zhou Shuiqing , Li Yuebing , Jin Weiya , Gao Zengliang , Ma Yi
Published: March 2023

316H austenitic stainless is regarded as an excellent candidate in the most advanced generation of nuclear reactor at elevated temperature. The effects of dwell times and strain amplitudes on the creep‐fatigue (CF) fracture mechanism of 316H steel were studied by using nanoindentation. The cyclic lives are observed to decrease with increasing strain amplitudes, while they are insensitive to the variation in dwell times. In comparison to the as‐received specimen, the nano‐hardness was evidently enhanced in both the fracture and interior regions for the CF‐tested one, whereas elastic modulus was little changed. As related to the creep resistance, creep flow could be suppressed with increasing strain amplitudes and dwell times, especially for the fracture edge. And the correlation between strain rate sensitivity (m) during creep flow and CF testing conditions was obtained. Based on the morphologies of fracture surface and variation in H, E, and m, a normalized damage indicator ln(H/E)/m is proposed to characterize the competing propagation of the transgranular (fatigue damage) and intergranular (creep damage) cracking in the CF fracture.
Fatigue properties of resistance spot‐welded maraging steel produced by selective laser melting
Authors: Shi Yandong , Luo Cheng , Li Wenkai , Shi Liting , Zhang Yansong , Su Xuming
Published: March 2023

This research study investigates the fatigue properties of resistance spot welds (RSWs) made from selective laser‐melted (SLMed) maraging steel (MS1) and compares them with dual‐phase (DP) steel RSWs. The findings reveal that MS1 spot welds exhibit superior fatigue properties compared with DP steel RSWs, regardless of the printing orientation of the MS1 substrate. Furthermore, fatigue fracture occurs at the MS1 substrate, with a transition of fracture location observed from MS1 to itself and MS1‐to‐DP600 dissimilar welds. The results of structural stress analysis indicate that the weld nugget diameter is not the only factor affecting the fatigue life. The study also highlights the importance of considering materials inhomogeneity and fracture modes in fatigue life assessment. Based on the findings, the study recommends the development of a new fatigue life prediction curve for spot welds of additive manufacturing (AM) materials. Such a curve would be beneficial in promoting the further application of AM technology for functional parts of design verification vehicles (DCV) and production cars. Overall, the research contributes to the understanding of the fatigue properties of RSWs made from SLMed MS1 and DP steel, which has implications for the design and manufacturing of parts in the automotive industry.
Motivating and demotivating factors for Chinese as a foreign language learners in a British CLIL program
Authors: Zheng Ying , Lu Yanbin , Li Jia
Published: March 2023

This study investigates Mandarin Chinese learners’ motivation in a Content and Language Integrated Learning (CLIL) program in a British secondary school from the perspective of learning environment, learner engagement, and learner identities. Fifteen pupils who are learning Chinese as a foreign language (CFL) have been interviewed individually or in a focus group. The results indicate that the context of L2 learning and pupils’ learning experience contribute to their sustained motivation. More specifically, the nature of the CLIL subjects, teachers and their teaching methods, peers, tasks, and examinations all play an important role in motivating or demotivating students. Pedagogical implications have been discussed with suggestions for maintaining students’ motivation in CLIL programs. This article fills the gap in the field of motivational study by bridging the learning of CFL and the CLIL context.