bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with COVID‐19 vaccine uptake and hesitancy among multinational refugees and migrants in Jordan
Authors: Ali Manal , Salam Mahmoud
Published: June 2024

This article explores the factors associated with COVID‐19 vaccine uptake and hesitancy among multinational refugees and migrants residing in various regions of Jordan. Drawing on an analysis of data collected from 636 participants in December 2021, only 58.2 per cent of the refugee community in Jordan received COVID‐19 vaccines, knowing that vaccine hesitancy compromises vaccination campaign efforts to control the spread of the disease. In fact, the International Organization for Migration (IOM) and local Jordanian authorities are well aware that, unless sufficiently vaccinated, the clustered populations of refugees and migrants might witness future infectious outbreaks similar to COVID‐19. This study reveals that COVID‐19 vaccine hesitancy is evident among the refugee and migrant populations, who are mainly sceptical of its efficiency and safety. Migrants and refugees also have a preference for certain types of COVID‐19 vaccines. In light of the findings, future interventions are needed to mitigate their concerns and boost vaccine confidence. A more holistic policy approach should prioritize migrants and refugees who are female, unemployed, less educated, and/or have poor knowledge about COVID‐19 and its vaccines. Unfortunately, imposing the COVID‐19 vaccination as a compulsory measure has been poorly received by some migrants and refugees, making them more hesitant.
Aggregate uncertainty, information acquisition, and analyst stock recommendations
Authors: Singh Amanjot , Singh Harminder , Welagedara Venura
Published: June 2024

We examine the informativeness of analyst stock recommendations in the presence of aggregate uncertainty. Our results suggest that a one standard deviation increase in aggregate uncertainty decreases the likelihood of influential recommendation revisions by 5.26%. Increased aggregate uncertainty leads to a small stock price impact for upgrade and downgrade recommendations. Our findings reveal consistent search for information by investors, which, support a post‐recommendation price drift amidst high aggregate uncertainty. We further find that investors of firms with fewer distracted shareholders, less readable financial statements, and more informed trading seek more information when aggregate uncertainty is high. Our study highlights that investors become more cautious while responding to analysts' stock recommendations during high aggregate uncertainty.
Integrative bioinformatics approach yields a novel gene expression risk model for prognosis and progression prediction in prostate cancer
Authors: Zhang Yunyan , Liu Zhuolin , Yu Liu , Fan Aoyu , Li Yunpeng , Li Xiaobo , Chen Wei
Published: June 2024

Prostate cancer (PCa), a prevalent malignancy among elderly males, exhibits a notable rate of advancement, even when subjected to conventional androgen deprivation therapy or chemotherapy. An effective progression prediction model would prove invaluable in identifying patients with a higher progression risk. Using bioinformatics strategies, we integrated diverse data sets of PCa to construct a novel risk model predicated on gene expression and progression‐free survival (PFS). The accuracy of the model was assessed through validation using an independent data set. Eight genes were discerned as independent prognostic factors and included in the prediction model. Patients assigned to the high‐risk cohort demonstrated a diminished PFS, and the areas under the curve of our model in the validation set for 1‐year, 3‐year, and 5‐year PFS were 0.9325, 0.9041 and 0.9070, respectively. Additionally, through the application of single‐cell RNA sequencing to two castration‐related prostate cancer (CRPC) samples and two hormone‐related prostate cancer (HSPC) samples, we discovered that luminal cells within CRPC exhibited an elevated risk score. Subsequent molecular biology experiments corroborated our findings, illustrating heightened SYK expression levels within tumour tissues and its contribution to cancer cell migration. We found that the knockdown of SYK could inhibit migration in PCa cells. Our progression‐related risk model demonstrated the potential prognostic value of SYK and indicated its potential as a target for future diagnosis and treatment strategies in PCa management.
Amentoflavone reverses epithelial‐mesenchymal transition in hepatocellular carcinoma cells by targeting p53 signalling pathway axis
Authors: Jian Hui‐Ying , Zhang Jing‐Ting , Liu Zhuo , Zhang Zhen , Zeng Pu‐Hua
Published: June 2024

Epithelial‐mesenchymal transition (EMT) and its reversal process are important potential mechanisms in the development of HCC. Selaginella doederleinii Hieron is widely used in Traditional Chinese Medicine for the treatment of various tumours and Amentoflavone is its main active ingredient. This study investigates the mechanism of action of Amentoflavone on EMT in hepatocellular carcinoma from the perspective of bioinformatics and network pharmacology. Bioinformatics was used to screen Amentoflavone‐regulated EMT genes that are closely related to the prognosis of HCC, and a molecular prediction model was established to assess the prognosis of HCC. The network pharmacology was used to predict the pathway axis regulated by Amentoflavone. Molecular docking of Amentoflavone with corresponding targets was performed. Detection and evaluation of the effects of Amentoflavone on cell proliferation, migration, invasion and apoptosis by CCK‐8 kit, wound healing assay, Transwell assay and annexin V‐FITC/propidium iodide staining. Eventually three core genes were screened, inculding NR1I2, CDK1 and CHEK1. A total of 590 GO enrichment entries were obtained, and five enrichment results were obtained by KEGG pathway analysis. Genes were mainly enriched in the p53 signalling pathway. The outcomes derived from both the wound healing assay and Transwell assay demonstrated significant inhibition of migration and invasion in HCC cells upon exposure to different concentrations of Amentoflavone. The results of Annexin V‐FITC/PI staining assay showed that different concentrations of Amentoflavone induces apoptosis in HCC cells. This study revealed that the mechanism of Amentoflavone reverses EMT in hepatocellular carcinoma, possibly by inhibiting the expression of core genes and blocking the p53 signalling pathway axis to inhibit the migration and invasion of HCC cells.
MST1 knockdown inhibits osteoarthritis progression through Parkin‐mediated mitophagy and Nrf2/NF‐κB signalling pathway
Authors: Ye Hantao , Cai Tingwen , Shen Yang , Zhao Lin , Zhang Haojie , Yang Jianxin , Li Feida , Chen Jiaoxiang , Shui Xiaolong
Published: June 2024

Osteoarthritis (OA) is a complicated disease that involves apoptosis and mitophagy. MST1 is a pro‐apoptotic factor. Hence, decreasing its expression plays an anti‐apoptotic effect. This study aims to investigate the protective effect of MST1 inhibition on OA and the underlying processes. Immunofluorescence (IF) was used to detect MST1 expression in cartilage tissue. Western Blot, ELISA and IF were used to analyse the expression of inflammation, extracellular matrix (ECM) degradation, apoptosis and mitophagy‐associated proteins. MST1 expression in chondrocytes was inhibited using siRNA and shRNA in vitro and in vivo. Haematoxylin–Eosin, Safranin O‐Fast Green and alcian blue staining were used to evaluate the therapeutic effect of inhibiting MST1. This study discovered that the expression of MST1 was higher in OA patients. Inhibition of MST1 reduced inflammation, ECM degradation and apoptosis and enhanced mitophagy in vitro. MST1 inhibition slows OA progression in vivo. Inhibiting MST1 suppressed apoptosis, inflammation and ECM degradation via promoting Parkin‐mediated mitophagy and the Nrf2‐NF‐κB axis. The results suggest that MST1 is a possible therapeutic target for the treatment of osteoarthritis as its inhibition delays the progression of OA through the Nrf2‐NF‐κB axis and mitophagy.
Assessment in community settings: Is there any role for individual competency‐based assessment?
Authors: Kleve Sue , Palermo Claire , Davidson Zoe E.
Published: June 2024

Background

Oral forms of assessment remain a common part of competency‐based assessment systems, yet their feasibility is being challenged. The focus on individual competence is problematic given the need to prepare health professionals for teamwork. The present study aimed to investigate how the assessment of collective competence compares to individual assessment, and to explore whether there is a need for individual assessment at all in community or population‐based practice.

Methods

A behavioural‐based interview assessment was developed and trialled and correlated to performance as a team on placement. Correlation between student performance on individual behavioural‐based interview and teamwork artefacts was assessed using Spearman rho. Differences between performance on individual oral assessment and team performance on artefacts at the cohort level was determined using the Mann–Whitney U‐test. Bland–Altman analysis was completed to analyse agreement between performance on the individual oral assessment and team performance at the student level.

Results

Students were final year nutrition and dietetics students from 2020, 2021 and 2022 years (total sample = 216) from one Australian university. There was a difference in performance between assessment types in each year and as a total cohort (p < 0.001) with students performing better in teamwork. There was no correlation between individual oral interview and team performance across all years. The results of the Bland–Altman analysis showed little agreement between the two assessment tasks.

Conclusions

Assessment of teamwork performance as part of a program of assessment is essential. More valid and reliable tools are needed to assess collective competence.
Comparison of dietary inflammatory index and total antioxidant capacities of familial Mediterranean fever and healthy adolescents
Authors: Ozkan Nilufer , Sahin Habibe , Kısaarslan Aysenur Pac , Saracoglu Hatice
Published: June 2024

Background

Although it is known that consumed nutrition affects inflammatory load, and total antioxidant capacity (TAC) is affected by inflammatory diseases and consumed nutrients, these conditions have not been adequately investigated in adolescents with familial Mediterranean fever (FMF). Therefore, this study aimed to compare the dietary inflammatory index (DII), TAC and total oxidant capacity (TOC) of adolescents with FMF and healthy adolescents.

Methods

This case‐controlled study consisted of 180 adolescents (aged 10–19) divided into FMF (n = 135) and control (n = 45 healthy) groups. Study data were collected face‐to‐face using a survey on demographic characteristics, anthropometric measurements, biochemical biomarkers and 3‐day dietary recall to calculate DII scores.

Results

FMF group had lower DII score than controls (2.12 ± 0.78 vs. 2.33 ± 1.06, p < 0.05). In addition, they had higher C‐reactive protein (CRP), TOC (p < 0.05) and oxidative stress index (OSI) (p = 0.51) than the control group. On the contrary, the control group had significantly higher tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) values (p < 0.05). There was a positive correlation between DII scores and TNF‐α in the FMF group (p < 0.05). The control group had significantly higher energy, protein, medium‐chain fatty acids (MCT) and saturated fatty acids (SFA) intake than FMF (p < 0.05). On the contrary, the FMF group had significantly higher vitamin A and D, niacin and zinc intake (p < 0.05).

Conclusion

The results showed that adolescents with FMF had lower DII and higher OSI than healthy adolescents. It may be beneficial for adolescents with FMF to consume a diet containing anti‐inflammatory nutrients to maintain normal growth and development and to prevent symptoms and complications of the disease.
Re‐partnering and single mothers' mental health and life satisfaction trajectories
Authors: Dierker Philipp , Kühn Mine , Myrskylä Mikko
Published: June 2024

Objective

This study examines single mothers' mental health and life satisfaction trajectories around re‐partnering transitions, and the driving factors of these associations.

Background

Single mothers are a particularly disadvantaged group in terms of their mental health and life satisfaction. According to the resource model, re‐partnering has a positive effect on these outcomes because it provides additional social, emotional, and financial resources. In contrast, the crisis model suggests that when a mother re‐partners, her mental health and life satisfaction further decline because re‐partnering can trigger conflicts in the family.

Method

Using long‐term annual panel data from Germany and the United Kingdom, fixed‐effects regressions reveal effects among 1101 single mothers from Germany and 549 from the UK.

Results

Life satisfaction was positively affected by re‐partnering in Germany, mainly driven by income‐related factors. The positive association in the UK was less strong. Patterns of mental health trajectories indicate clearer differences between the two countries: based on point estimates, we observed an increasing trajectory in Germany and a declining trajectory in the UK after the re‐partnering transition. There were no significant mental health patterns observed in either country.

Conclusion

The findings suggest varying associations between well‐being and re‐partnering. Positive trends for life satisfaction in Germany and partially in the UK highlight the importance of financial resources. However, less clear patterns were observed for mental health, revealing differences between countries and underscoring the role of family policies.
Multiple hybridization events and repeated evolution of homoeologue expression bias in parthenogenetic, polyploid New Zealand stick insects
Authors: Choi Seung‐Sub , Mc Cartney Ann , Park Duckchul , Roberts Hester , Brav‐Cubitt Talia , Mitchell Caroline , Buckley Thomas R.
Published: June 2024

During hybrid speciation, homoeologues combine in a single genome. Homoeologue expression bias (HEB) occurs when one homoeologue has higher gene expression than another. HEB has been well characterized in plants but rarely investigated in animals, especially invertebrates. Consequently, we have little idea as to the role that HEB plays in allopolyploid invertebrate genomes. If HEB is constrained by features of the parental genomes, then we predict repeated evolution of similar HEB patterns among hybrid genomes formed from the same parental lineages. To address this, we reconstructed the history of hybridization between the New Zealand stick insect genera Acanthoxyla and Clitarchus using a high‐quality genome assembly from Clitarchus hookeri to call variants and phase alleles. These analyses revealed the formation of three independent diploid and triploid hybrid lineages between these genera. RNA sequencing revealed a similar magnitude and direction of HEB among these hybrid lineages, and we observed that many enriched functions and pathways were also shared among lineages, consistent with repeated evolution due to parental genome constraints. In most hybrid lineages, a slight majority of the genes involved in mitochondrial function showed HEB towards the maternal homoeologues, consistent with only weak effects of mitonuclear incompatibility. We also observed a proteasome functional enrichment in most lineages and hypothesize this may result from the need to maintain proteostasis in hybrid genomes. Reference bias was a pervasive problem, and we caution against relying on HEB estimates from a single parental reference genome.
Information apocalypse or overblown fears—whatAImis‐ and disinformation is all about? Shifting away from technology toward human reactions
Authors: Łabuz Mateusz , Nehring Christopher
Published: June 2024

The rise of generative artificial intelligence (AI) has ignited a debate about its effects on the mis‐ and disinformation landscape. The doomsday scenarios of epistemic and information apocalypse presented for many years are recently being questioned, and the previous fears are called “overblown.” These phenomena are analyzed mostly through the factors of quantity and quality of AI‐powered content and the potential for personalization possessed by AI. We argue that using quantitative arguments carries a high risk of underestimating the threat, especially in the context of the so‐called detection challenge. We point out that this discourse is affected by the narrow conceptualization of how we understand quantity, quality, and personalization with regard to AI. In our opinion, apocalyptic visions are speculative in nature, difficult to quantify, and carry signs of a self‐fulfilling prophecy, but disregarding risks hinders appropriate countermeasures against AI‐powered dis‐ and misinformation, which adversely affects policy‐making activities. We propose a paradigm shift to focus more on social reactions to technology rather than technological attributes. By expanding the understanding of the analyzed phenomena, we indicate that the potential of AI is both overestimated and underestimated and above all—still misunderstood.

Related Articles

Norman, Emma R., and Rafael Delfin. 2012. “Wizards under Uncertainty: Cognitive Biases, Threat Assessment, and Misjudgments in Policy Making.”Politics & Policy40(3): 369–402.https://doi.org/10.1111/j.1747‐1346.2012.00356.x.

Robles, Pedro, and Daniel J. Mallinson. 2023. “Catching Up with AI: Pushing Toward a Cohesive Governance Framework.”Politics & Policy51(3): 355–72.https://doi.org/10.1111/polp.12529.

Veloso Meireles, Adriana. 2024. “Digital Rights in Perspective: The Evolution of the Debate in the Internet Governance Forum.”Politics & Policy52(1): 12–32.https://doi.org/10.1111/polp.12571.
IT as a driver of R&D processes and strategic renewal
Authors: Tuncdogan Aybars , Wang Fatima , Volberda Henk , Enkel Ellen
Published: June 2024

Recent advancements in information technology are profoundly impacting a variety of business functions across different industries. R&D and strategic renewal, as critical drivers of organisational innovation, are particularly influenced by these tectonic shifts in the technological landscape. In response, there has been a growing interest among business academics and practitioners in understanding how these technologies can be leveraged to maximise benefits and foster the creation of new value in organisations. This editorial paper proposes a moderated mediation model that provides a comprehensive view of the connections between IT‐related antecedents and outcomes in R&D, strategic renewal, and innovation performance. Through this model, we elucidate the pathways through which IT impacts organisational processes and identify key areas for future research. Additionally, we introduce six papers published in this special issue that explore these themes across various contexts, contributing to the discourse on the strategic implications of IT in digital transformation and business sustainability.
Demographic change threat, preference for nondemocratic governance, and support for political violence
Authors: Piazza James A.
Published: June 2024

Objective

This study examines whether white Americans who fear projected demographic trends leading to increasing racial and ethnic diversity in the United States, an attitude labeled demographic change threat, also exhibit greater support for the use of political violence. The study also examines whether preference for nondemocratic governance among whites mediates the relationship between demographic change threat and support for political violence.

Methods

The study uses two original public opinion surveys of U.S. whites fielded at separate times and employs two different operationalizations of support for political violence: support for political violence in the abstract and support for specific incidents of political violence. The study also uses mediation analysis to determine the mediation effects of preference for nondemocratic governance.

Results

The findings reveal that U.S. whites exhibiting demographic change threat are substantially more likely to express support for all forms of political violence. Preference for nondemocratic governance is also found to be a significant and substantial mediator between demographic change threat and support for political violence.

Conclusion

The study concludes that demographic change threat is an important factor for support for political violence among U.S. whites by driving anti‐democratic attitudes.
Shaking the tin cup: Celebrity candidate fundraising in American elections
Authors: Longoria Richard T.
Published: June 2024

Background

The literature on celebrity politics often asserts that celebrity politicians are good at fundraising. They are wealthy people in wealthy social networks, and this should give them a fundraising advantage compared to their noncelebrity opponents. Yet, this hypothesis has never been tested.

Method

Fundraising data from 1964 to 2022 was collected from multiple sources.

Results

This study finds that celebrity candidates are typically not able to out‐fundraise their opponents. Yet they perform remarkably well despite this disadvantage.

Conclusions

Celebrities tend to win elections when they raise more money than their opponents, run in open‐seat contests or local elections. They tend to lose elections when they lose the fundraising battle, challenge incumbents, or seek federal offices.
Post‐transplant de novo anti‐HLA donor specific antibodies may contribute to poor graft function after haploidentical haematopoietic stem cell transplantation
Authors: Ji Xinyu , Yang Luxin , Lai Xiaoyu , Ye Yishan , Wu Yibo , Xiang Shipei , Luo Yi , Liu Lizhen
Published: June 2024

De novo anti‐HLA donor‐specific antibodies (DSAs) were rarely reported in stem cell transplantation patients. We present a case of 39‐year‐old acute myelogenous leukaemia patient who developed de novo DSAs only 16 days after transplantation with the highest mean fluorescence intensity (MFI) of 7406.23, which were associated with poor graft function (PGF). We used plasma exchange (PE) and intravenous immunoglobulin (IVIg) to reduce DSA level. A series of treatment including mesenchymal stem cells and donor cell transfusion were used to help recover graft function. On day 130, the patient achieved a successful engraftment.
Rigidity of inverse problems for nonlinear elliptic equations on manifolds
Authors: Feizmohammadi Ali , Kian Yavar , Oksanen Lauri
Published: June 2024

We consider the inverse problem of determining coefficients appearing in semilinear elliptic equations stated on Riemannian manifolds with boundary given the knowledge of the associated Dirichlet‐to‐Neumann map. We begin with a negative answer to this problem. Owing to this obstruction, we consider a new formulation of our inverse problem in terms of a rigidity problem. Precisely, we consider cases where the Dirichlet‐to‐Neumann map of a semilinear equation coincides with the one of a linear equation and ask whether this implies that the equation must indeed be linear. We give a positive answer to this rigidity problem under some assumptions imposed on the Riemannian manifold and the semilinear term under consideration.
Tof-SIMS spectra of historical inorganic pigments: Calcium white pigments in both polarities
Authors: Bouvier Caroline , Van Nuffel Sebastiaan , Brunelle Alain
Published: June 2024

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is increasingly used to analyze cultural heritage materials because it can simultaneously detect organic and inorganic materials while mapping them on a surface. The precise identification of a pigment in a specific layer of a painting or of remaining color on a statue can inform about the technique used or the time of manufacture as well as expose possible forgeries when anachronistic ingredients are identified. Reference spectra are required to confidently identify a given pigment using ToF-SIMS. This database focuses on six white pigments made from calcium-rich natural or synthetized materials, prepared following traditional processes. Such pigments are frequently found in the preparation layers, namely, “ground,” separating the support from the observable paint layers, and providing a smooth surface to hold the paint on while preventing its absorption by the substrate. Differentiating between these pigments is helpful to better describe the painting practice. Here, ToF-SIMS reference spectra using a Bi3+ primary ion species are presented for both polarities.
Determining the ERK-regulated phosphoproteome driving KRAS-mutant cancer
Authors: Klomp Jennifer E. , Diehl J. Nathaniel , Klomp Jeffrey A. , Edwards A. Cole , Yang Runying , Morales Alexis J. , Taylor Khalilah E. , Drizyte-Miller Kristina , Bryant Kirsten L. , Schaefer Antje , Johnson Jared L. , Huntsman Emily M. , Yaron Tomer M. , Pierobon Mariaelena , Baldelli Elisa , Prevatte Alex W. , Barker Natalie K. , Herring Laura E. , Petricoin Emanuel F. , Graves Lee M. , Cantley Lewis C. , Cox Adrienne D. , Der Channing J. , Stalnecker Clint A.
Published: June 2024

To delineate the mechanisms by which the ERK1 and ERK2 mitogen-activated protein kinases support mutant KRAS–driven cancer growth, we determined the ERK-dependent phosphoproteome in KRAS-mutant pancreatic cancer. We determined that ERK1 and ERK2 share near-identical signaling and transforming outputs and that the KRAS-regulated phosphoproteome is driven nearly completely by ERK. We identified 4666 ERK-dependent phosphosites on 2123 proteins, of which 79 and 66%, respectively, were not previously associated with ERK, substantially expanding the depth and breadth of ERK-dependent phosphorylation events and revealing a considerably more complex function for ERK in cancer. We established that ERK controls a highly dynamic and complex phosphoproteome that converges on cyclin-dependent kinase regulation and RAS homolog guanosine triphosphatase function (RHO GTPase). Our findings establish the most comprehensive molecular portrait and mechanisms by which ERK drives KRAS-dependent pancreatic cancer growth.
A master regulator of opioid reward in the ventral prefrontal cortex
Authors: Smith Alexander C. W. , Ghoshal Soham , Centanni Samuel W. , Heyer Mary P. , Corona Alberto , Wills Lauren , Andraka Emma , Lei Ye , O’Connor Richard M. , Caligiuri Stephanie P. B. , Khan Sohail , Beaumont Kristin , Sebra Robert P. , Kieffer Brigitte L. , Winder Danny G. , Ishikawa Masago , Kenny Paul J.
Published: June 2024

In addition to their intrinsic rewarding properties, opioids can also evoke aversive reactions that protect against misuse. Cellular mechanisms that govern the interplay between opioid reward and aversion are poorly understood. We used whole-brain activity mapping in mice to show that neurons in the dorsal peduncular nucleus (DPn) are highly responsive to the opioid oxycodone. Connectomic profiling revealed that DPn neurons innervate the parabrachial nucleus (PBn). Spatial and single-nuclei transcriptomics resolved a population of PBn-projecting pyramidal neurons in the DPn that express μ-opioid receptors (μORs). Disrupting μOR signaling in the DPn switched oxycodone from rewarding to aversive and exacerbated the severity of opioid withdrawal. These findings identify the DPn as a key substrate for the abuse liability of opioids.
Spontaneous chiral symmetry breaking in polar fluid–heliconical ferroelectric nematic phase
Authors: Karcz Jakub , Herman Jakub , Rychłowicz Natan , Kula Przemysław , Górecka Ewa , Szydlowska Jadwiga , Majewski Pawel W. , Pociecha Damian
Published: June 2024

Spontaneous mirror symmetry breaking by formation of chiral structures from achiral building blocks and emergent polar order are phenomena rarely observed in fluids. Separately, they have both been found in certain nematic liquid crystalline phases; however, they have never been observed simultaneously. Here, we report a heliconical arrangement of achiral molecules in the ferroelectric nematic phase. The phase is thus spontaneously both polar and chiral. Notably, the pitch of the heliconical structure is comparable to the wavelength of visible light, giving selective reflection controllable by temperature or application of a weak electric field. Despite bearing resemblance to the heliconical twist-bend nematic phase, this chiral ferroelectric nematic phase arises from electrical interactions that induce a noncollinear orientation of electric dipoles.
WS
2
ribbon arrays with defined chirality and coherent polarity
Authors: Xue Guodong , Zhou Ziqi , Guo Quanlin , Zuo Yonggang , Wei Wenya , Yang Jiashu , Yin Peng , Zhang Shuai , Zhong Ding , You Yilong , Sui Xin , Liu Chang , Wu Muhong , Hong Hao , Wang Zhu-Jun , Gao Peng , Li Qunyang , Zhang Libo , Yu Dapeng , Ding Feng , Wei Zhongming , Liu Can , Liu Kaihui
Published: June 2024

One-dimensional transition metal dichalcogenides exhibiting an enhanced bulk photovoltaic effect have the potential to exceed the Shockley–Queisser limit efficiency in solar energy harvest within
p
-
n
junction architectures. However, the collective output of these prototype devices remains a challenge. We report on the synthesis of single-crystalline WS
2
ribbon arrays with defined chirality and coherent polarity through an atomic manufacturing strategy. The chirality of WS
2
ribbon was defined by substrate couplings into tunable armchair, zigzag, and chiral species, and the polarity direction was determined by the ribbon-precursor interfacial energy along a coherent direction. A single armchair ribbon showed strong bulk photovoltaic effect and the further integration of ~1000 aligned ribbons with coherent polarity enabled upscaling of the photocurrent.
Developing fatigue-resistant ferroelectrics using interlayer sliding switching
Authors: Bian Renji , He Ri , Pan Er , Li Zefen , Cao Guiming , Meng Peng , Chen Jiangang , Liu Qing , Zhong Zhicheng , Li Wenwu , Liu Fucai
Published: June 2024

Ferroelectric materials have switchable electrical polarization that is appealing for high-density nonvolatile memories. However, inevitable fatigue hinders practical applications of these materials. Fatigue-free ferroelectric switching could dramatically improve the endurance of such devices. We report a fatigue-free ferroelectric system based on the sliding ferroelectricity of bilayer 3R molybdenum disulfide (3R-MoS
2
). The memory performance of this ferroelectric device does not show the wake-up effect at low cycles or a substantial fatigue effect after 10
6
switching cycles under different pulse widths. The total stress time of the device under an electric field is up to 10
5
s, which is long relative to other devices. Our theoretical calculations reveal that the fatigue-free feature of sliding ferroelectricity is due to the immobile charge defects in sliding ferroelectricity.
Ultrafast high-endurance memory based on sliding ferroelectrics
Authors: Yasuda Kenji , Zalys-Geller Evan , Wang Xirui , Bennett Daniel , Cheema Suraj S. , Watanabe Kenji , Taniguchi Takashi , Kaxiras Efthimios , Jarillo-Herrero Pablo , Ashoori Raymond
Published: June 2024

The persistence of voltage-switchable collective electronic phenomena down to the atomic scale has extensive implications for area- and energy-efficient electronics, especially in emerging nonvolatile memory technology. We investigate the performance of a ferroelectric field-effect transistor (FeFET) based on sliding ferroelectricity in bilayer boron nitride at room temperature. Sliding ferroelectricity represents a different form of atomically thin two-dimensional (2D) ferroelectrics, characterized by the switching of out-of-plane polarization through interlayer sliding motion. We examined the FeFET device employing monolayer graphene as the channel layer, which demonstrated ultrafast switching speeds on the nanosecond scale and high endurance exceeding 10
11
switching cycles, comparable to state-of-the-art FeFET devices. These characteristics highlight the potential of 2D sliding ferroelectrics for inspiring next-generation nonvolatile memory technology.
A new twist in ferroelectric liquids
Authors: Lucchetti Liana
Published: June 2024

Spontaneous chirality emerges in a highly polar liquid of achiral molecules
Unpacking climate policy
Authors: Dubash Navroz K.
Published: June 2024

As temperatures and evidence of climate impacts mount, so too do pressures to enhance climate policy ambition and implementation. In a previous piece, I have
argued
that to respond to these pressures requires rebalancing focus from target setting to implementation through policy formulation and enactment. But following through on policy and its implementation brings its own challenges. One size seldom fits all, and effective climate action requires bespoke policy-making to
tailor policy to national context
. This includes, critically, framing policy to win support in diverse national political contexts.
Authors move to retract discredited Alzheimer’s study
Authors: Piller Charles
Published: June 2024

The high-profile paper contains manipulated images, senior author acknowledges
Determining tissue distribution of the oral antileishmanial agent miltefosine: a physiologically-based pharmacokinetic modeling approach
Authors: Ramisetty Bhargavi Srija , Yang Sihyung , Dorlo Thomas P. C. , Wang Michael Zhuo
Published: June 2024

Miltefosine (MTS) is the only approved oral drug for treating leishmaniasis caused by intracellular
Leishmania
parasites that localize in macrophages of the liver, spleen, skin, bone marrow, and lymph nodes. MTS is extensively distributed in tissues and has prolonged elimination half-lives due to its high plasma protein binding, slow metabolic clearance, and minimal urinary excretion. Thus, understanding and predicting the tissue distribution of MTS help assess therapeutic and toxicologic outcomes of MTS, especially in special populations, e.g., pediatrics. In this study, a whole-body physiologically-based pharmacokinetic (PBPK) model of MTS was built on mice and extrapolated to rats and humans. MTS plasma and tissue concentration data obtained by intravenous and oral administration to mice were fitted simultaneously to estimate model parameters. The resulting high tissue-to-plasma partition coefficient values corroborate extensive distribution in all major organs except the bone marrow. Sensitivity analysis suggests that plasma exposure is most susceptible to changes in fraction unbound in plasma. The murine oral-PBPK model was further validated by assessing overlay of simulations with plasma and tissue profiles obtained from an independent study. Subsequently, the murine PBPK model was extrapolated to rats and humans based on species-specific physiological and drug-related parameters, as well as allometrically scaled parameters. Fold errors for pharmacokinetic parameters were within acceptable range in both extrapolated models, except for a slight underprediction in the human plasma exposure. These animal and human PBPK models are expected to provide reliable estimates of MTS tissue distribution and assist dose regimen optimization in special populations.
Catching some air: a method to spatially quantify aerial triazole resistance in
Aspergillus fumigatus
Authors: Kortenbosch Hylke H. , van Leuven Fabienne , van den Heuvel Cathy , Schoustra Sijmen E. , Zwaan Bas J. , Snelders Eveline
Published: June 2024

Airborne triazole-resistant spores of the human fungal pathogen
Aspergillus fumigatus
are a significant human health problem as the agricultural use of triazoles has been selecting for cross-resistance to life-saving clinical triazoles. However, how to quantify exposure to airborne triazole-resistant spores remains unclear. Here, we describe a method for cost-effective wide-scale outdoor air sampling to measure both spore abundance as well as antifungal resistance fractions. We show that prolonged outdoor exposure of sticky seals placed in delta traps, when combined with a two-layered cultivation approach, can regionally yield sufficient colony-forming units (CFUs) for the quantitative assessment of aerial resistance levels at a spatial scale that was up to now unfeasible. When testing our method in a European pilot sampling 12 regions, we demonstrate that there are significant regional differences in airborne CFU numbers, and the triazole-resistant fraction of airborne spores is widespread and varies between 0 and 0.1 for itraconazole (∼4 mg/L) and voriconazole (∼2 mg/L). Our efficient and accessible air sampling protocol opens up extensive options for fine-scale spatial sampling and surveillance studies of airborne
A. fumigatus.

IMPORTANCE

Aspergillus fumigatus
is an opportunistic fungal pathogen that humans and other animals are primarily exposed to through inhalation. Due to the limited availability of antifungals, resistance to the first choice class of antifungals, the triazoles, in
A. fumigatus
can make infections by this fungus untreatable and uncurable. Here, we describe and validate a method that allows for the quantification of airborne resistance fractions and quick genotyping of
A. fumigatus
TR-types. Our pilot study provides proof of concept of the suitability of the method for use by citizen-scientists for large-scale spatial air sampling. Spatial air sampling can open up extensive options for surveillance, health-risk assessment, and the study of landscape-level ecology of
A. fumigatus
, as well as investigating the environmental drivers of triazole resistance.
“Tear down that wall”—a critical evaluation of bioinformatic resources available for lysin researchers
Authors: Bałdysz Sophia , Nawrot Robert , Barylski Jakub
Published: June 2024

Lytic enzymes, or lysins for short, break down peptidoglycan and interrupt the continuity of the cell wall, which, in turn, causes osmotic lysis of the bacterium. Their ability to destroy bacteria from within makes them promising antimicrobial agents that can be used as alternatives or supplements to antibiotics. In this paper, we briefly summarize basic terms and concepts used to describe lysin sequences and delineate major lysin groups. More importantly, we describe the domain repertoire found in lysins and critically review bioinformatic tools or databases which are used in studies of these enzymes (with particular emphasis on the repositories of Hidden Markov models). Finally, we present a novel comprehensive, meticulously curated set of lysin-related family and domain models, sort them into clusters that reflect major families, and demonstrate that the selected models can be used to efficiently search for new lysins.
An expanded genetic toolkit for inducible expression and targeted gene silencing in
Rickettsia parkeri
Authors: McGinn Jon , Wen Annie , Edwards Desmond L. , Brinkley David M. , Lamason Rebecca L.
Published: June 2024

Pathogenic species within the
Rickettsia
genus are transmitted to humans through arthropod vectors and cause a spectrum of diseases ranging from mild to life-threatening. Despite rickettsiae posing an emerging global health risk, the genetic requirements of their infectious life cycles remain poorly understood. A major hurdle toward building this understanding has been the lack of efficient tools for genetic manipulation, owing to the technical difficulties associated with their obligate intracellular nature. To this end, we implemented the Tet-On system to enable conditional gene expression in
Rickettsia parkeri
. Using Tet-On, we show inducible expression of antibiotic resistance and a fluorescent reporter. We further used this inducible promoter to screen the ability of
R. parkeri
to express four variants of the catalytically dead Cas9 (dCas9). We demonstrate that all four dCas9 variants can be expressed in
R. parkeri
and used for CRISPR interference (CRISPRi)-mediated targeted gene knockdown. We show targeted knockdown of an antibiotic resistance gene as well as the endogenous virulence factor
sca2
. Altogether, we have developed systems for inducible gene expression and CRISPRi-mediated gene knockdown for the first time in rickettsiae, laying the groundwork for more scalable, targeted mechanistic investigations into their infectious life cycles.

IMPORTANCE

The spotted fever group of
Rickettsia
contains vector-borne pathogenic bacteria that are neglected and emerging threats to public health. Due to the obligate intracellular nature of rickettsiae, the development of tools for genetic manipulation has been stunted, and the molecular and genetic underpinnings of their infectious lifecycle remain poorly understood. Here, we expand the genetic toolkit by introducing systems for conditional gene expression and CRISPR interference (CRISPRi)-mediated gene knockdown. These systems allow for relatively easy manipulation of rickettsial gene expression. We demonstrate the effectiveness of these tools by disrupting the intracellular life cycle using CRISPRi to deplete the
sca2
virulence factor. These tools will be crucial for building a more comprehensive and detailed understanding of rickettsial biology and pathogenesis.
Changes in the chikungunya virus E1 glycoprotein domain II and hinge influence E2 conformation, infectivity, and virus-receptor interactions
Authors: Thannickal Sara A. , Battini Leandro , Spector Sophie N. , Noval Maria G. , Álvarez Diego E. , Stapleford Kenneth A.
Published: June 2024

In a previous study to understand how the chikungunya virus (CHIKV) E1 glycoprotein β-strand c functions, we identified several attenuating variants at E1 residue V80 and the emergence of second-site mutations in the fusion loop (E1-M88L) and hinge region (E1-N20Y) with the V80 variants
in vivo
. The emergence of these mutations led us to question how changes in E1 may contribute to CHIKV infection at the molecular level. Here, we use molecular dynamics to understand how changes in the E1 glycoprotein may influence the CHIKV glycoprotein E1-E2 complex. We found that E1 domain II variants lead to E2 conformational changes, allowing us to hypothesize that emerging variants E1-M88L and E1-N20Y could also change E2 conformation and function. We characterized CHIKV E1-M88L and E1-N20Y
in vitro
and
in vivo
to understand how these regions of the E1 glycoprotein contribute to host-specific infection. We found that CHIKV E1-N20Y enhanced infectivity in mosquito cells, while the CHIKV E1-M88L variant enhanced infectivity in both BHK-21 and C6/36 cells and led to changes in viral cholesterol-dependence. Moreover, we found that E1-M88L and E1-N20Y changed E2 conformation, heparin binding, and interactions with the receptor Mxra8. Interestingly, the CHIKV E1-M88L variant increased replication in Mxra8-deficient mice compared to WT CHIKV, yet was attenuated in mouse fibroblasts, suggesting that residue E1-M88 may function in a cell-type-dependent entry. Taken together, these studies show that key residues in the CHIKV E1 domain II and hinge region function through changes in E1-E2 dynamics to facilitate cell- and host-dependent entry.

IMPORTANCE

Arboviruses are significant global public health threats, and their continued emergence around the world highlights the need to understand how these viruses replicate at the molecular level. The alphavirus glycoproteins are critical for virus entry in mosquitoes and mammals, yet how these proteins function is not completely understood. Therefore, it is critical to dissect how distinct glycoprotein domains function
in vitro
and
in vivo
to address these gaps in our knowledge. Here, we show that changes in the CHIKV E1 domain II and hinge alter E2 conformations leading to changes in virus-receptor and -glycosaminoglycan interactions and cell-specific infection. These results highlight that adaptive changes in E1 can have a major effect on virus attachment and entry, furthering our knowledge of how alphaviruses infect mammals and insects.
Supplemental Material: The distribution and generation of carbonatites
Authors: Gibson Sally , al. et
Published: June 2024

 Description of methods (File S1) and the numerical code for the thermal model. The data sets are available in Files S2 and S3, and the Fortran code is available in Files S4 and S5.  
Pseudoaneurysm of the superolateral genicular artery following ACL outside-in reconstruction
Authors: Castroviejo Carmen , Siegrist Olivier , Gousopoulos Lampros
Published: June 2024

A female underwent arthroscopic anterior cruciate ligament reconstruction (ACLR) via an outside-in drilling technique. At 4 weeks after surgery, she presented with a pulsatile painful mass on the lateral femoral condyle. Imaging confirmed a superolateral genicular artery pseudoaneurysm. Thrombin injections were administered twice, resulting in reduced size and minimal pain. This case emphasises the rare occurrence of pseudoaneurysms post-ACLR and highlights the importance of early detection and intervention for vascular complications. Although debated, we suggest tourniquet deflation before closure to facilitate identification and management of vascular issues. This report contributes valuable insights into managing pseudoaneurysms following ACLR.
Early predictive value of lipocalin-type prostaglandin D synthase for 28-day mortality in cardiac arrest patients: study protocol for a prospective study
Authors: Fu Huimin , Wang Shangyuan , Xu peixian , Feng Zhihui , Pan Shuming , Ge Xiaoli
Published: June 2024

Introduction

Public training in cardiopulmonary resuscitation and treatment in emergency and intensive care unit have made tremendous progress. However, cardiac arrest remains a major health burden worldwide, with brain damage being a significant contributor to disability and mortality. Lipocalin-type prostaglandin D synthase (L-PGDS), which is mainly localised in the central nervous system, has been previously shown to inhibit postischemia neuronal apoptosis. Therefore, we aim to observe whether serum L-PGDS can serve as a potential biomarker and explore its role in determining the severity and prognosis of patients who have achieved restoration of spontaneous circulation (ROSC).

Methods and analysis

This is a prospective observational study. The participants (n = 60) who achieve ROSC will be distributed into two groups (non-survivor and survivor) based on 28-day survival. Healthy volunteers (n = 30) will be enrolled as controls. Each individual’s relevant information will be extracted from Electronic Medical Record System in Xinhua Hospital, including demographic characteristics, clinical data, laboratory findings and so on. On days 1, 3 and 7 after ROSC, blood samples will be drawn and batch tested on the level of serum neuron-specific enolase, soluble protein 100β, L-PGDS, procalcitonin, tumour necrosis factor-alpha and interleukin-6. The cerebral performance category score was assessed on the 28th day after ROSC.

Ethics and dissemination

This study was performed with the approval of the Clinical Ethical Committee of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Approval No. XHEC-C-2023-130-1). The results will be published in a peer-reviewed journal.

Trial registration number

Chinese Clinical Trial Registry (ChiCTR2300078564).