bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanoscale infrared spectroscopy identifies parallel to antiparallel beta sheet transformation of Aβ fibrils
Authors: Banerjee Siddhartha , Baghel Divya , Hasan-ul-Iqbal Md. , Ghosh Ayanjeet
Published: September 2022

Spontaneous aggregation of amyloid beta (Aβ) proteins leading to the formation of oligomers and eventually into fibrils has been identified as a key pathological signature of Alzheimer’s disease. Structure of late stage aggregates have been studied in depth by conventional structural biology techniques including Nuclear Magnetic Resonance, X-ray crystallography and Infrared Spectroscopy; however the structure of early-stage aggregates is less known due to their transient nature. As a result, the structural evolution of amyloid aggregates from its early oligomers to mature fibril is still not fully understood. Here we have applied AFM-IR nanospectroscopy to investigate the aggregation of Aβ 16-22, which spans the amyloidogenic core of the amyloid beta peptide. Our results demonstrate that Aβ 16-22 involves a structural transition from oligomers with parallel beta sheets to antiparallel fibrils through disordered and possibly helical intermediate fibril structures, contrary to the known aggregation pathway of full-length Aβ.
The TaxUMAP atlas: efficient display of large clinical microbiome data reveals ecological competition involved in protection against bacteremia
Authors: Schluter Jonas , Djukovic Ana , Taylor Bradford P. , Yan Jinyuan , Duan Caichen , Hussey Grant A. , Liao Chen , Sharma Sneh , Fontana Emily , Amoretti Luigi A. , Wright Roberta J. , Dai Anqi , Peled Jonathan U. , Taur Ying , Perales Miguel-Angel , Siranosian Benjamin A. , Bhatt Ami S. , van den Brink Marcel R.M. , Pamer Eric G. , Xavier Joao B.
Published: September 2022

The microbiome is associated with health and disease, but causal effects are hard to quantify— especially in humans where controlled experiments are nearly impossible. Akin to natural experiments, closely monitored patients offer an alternative to characterize microbiome effects. We present TaxUMAP, a taxonomically-informed visualization method to effectively display diverse microbiome states. TaxUMAP charts a microbiome atlas from 1,870 cancer patients as they progress through therapy-induced perturbations, and quantifies the microbiome contribution to patients’ risk for life-threatening bacteremia. We find that the lowest diversity states (gut dominations) that follow antibiotic treatments are stable, and that diverse communities harbor more diverse antimicrobial resistance genes than dominations. We reveal that certain Klebsiella species are associated with reduced risk for bacteremia, an effect driven by bacterial competition that we validate experimentally in vitro and in vivo. TaxUMAP effectively maps longitudinal microbiome data that can facilitate research into causal microbiome effects on human health.

HIGHLIGHTS

TaxUMAP charts an atlas of patients’ microbiome states and their clinical context to reveal new causal effects.

Antibiotics deplete the biodiversity and reduce the number of different antimicrobial resistance genes in the gut microbiome.

Certain Klebsiella species are associated with lower risk of bacteremia by other gut-borne pathogens.

These Klebsiella outcompete other gram-negative pathogens in vivo.
Rising novelty and homogenization of breeding bird communities in the U.S.
Authors: Latimer C. E. , Graves R. A. , Pidgeon A. M. , Gorzo J. M. , Henschell M. , Schilke P. R. , Hobi M. L. , Olah A. , Kennedy C.M. , Zuckerberg B. , Radeloff V. C.
Published: September 2022

Aim

Human modification has profound effects on the diversity of ecological communities. Yet, surprisingly little is known about how abiotic novelty due to human modification relates to biological novelty as measured by shifts in species composition from historical baselines. Using space-for-time substitution, we ask a) whether high human modification results in biotic homogenization or heterogenization across different spatial scales; b) if high modification results in the formation of novel, “no-analog” communities; and c) whether changes in bird community composition varies in response to proxies of historical land-use and duration-of-exposure to anthropogenic disturbances.

Location

Conterminous United States.

Time Period

2012 – 2016.

Major taxa studied

Passeriformes.

Methods

We analyzed continent-wide avian biodiversity data from an online checklist program, eBird, to examine how shifts in breeding bird species composition have been impacted by human modification at regional and continental scales and tested four hypotheses related to how abiotic novelty resulting from human modification generates biological novelty.

Results

At regional scales, bird communities in highly human-modified areas exhibited similar levels of β-diversity as those in the least modified areas. However, at the continental scale, spatial turnover in community composition was lower in human-modified areas, suggesting that anthropogenic disturbance has a strong homogenizing effect on bird communities at that scale. Lastly, human modification contributed more to community composition in regions where natural disturbance was infrequent and Euro-American settlement occurred later, consistent with the hypothesis that exposure to historical disturbances can shape how contemporary bird communities respond to human modification.

Main conclusions

The observed patterns of increased biotic novelty and homogenization in regions with less frequent disturbances and a longer history of human modification suggests that future extensive human modification could result in further homogenization of bird communities, particularly in the western U.S. We argue that current human-modified environments hold great potential for biodiversity conservation.
Commensal-specific CD4 T cells promote inflammation in the central nervous system via molecular mimicry
Authors: White Zachary , Cabrera Ivan , Ochoa-Raya Andrea , Kapustka Isabel , Koster Kevin P. , Matsuo Takashi , Jayawardena Dulari , Kageyama Takahiro , Dudeja Pradeep K , Lutz Sarah E. , Yoshii Akira , Sano Teruyuki
Published: September 2022

Commensal bacteria are critical regulators of both tissue homeostasis and the development and exacerbation of autoimmunity. However, it remains unclear how the intestinal microbiota contributes to inflammation in tissues such as the central nervous system (CNS) where these microbes are typically absent and whether T cell receptor (TCR) specificity for commensal-derived antigens is important to the development of tissue inflammation-related outcomes. Here, we found that ileum- and cecum-colonizing segmented filamentous bacteria (SFB)-specific T cells (clone TCR7B8) can infiltrate the CNS wherein they can be reactivated and produce high levels of inflammatory cytokines including IFNγ, IL-17A, TNFα, and GM-CSF in the absence of regulatory T cells. In contrast, other SFB-specific T cells (clone TCR1A2) recognizing an epitope in which 8/9 amino acids overlap with those recognized by TCR7B8 failed to induce such neuroinflammation. Despite their similar SFB-derived peptide antigen targets, TCR7B8 was found to recognize peptides derived from host proteins including receptor tyrosine-protein kinase ErbB2, trophinin 1, and anaphase-promoting complex subunit 2 in vitro, whereas TCR1A2 did not, indicating that TCR7B8 induces CNS inflammation via molecular mimicry. Immune checkpoint blockade accelerated TCR7B8-mediated CNS inflammation, suggesting a potential cause of immune-related adverse events induced in cancer patients undergoing such treatment. Together, our findings reveal a potential mechanism whereby gut commensal-specific T cells are dysregulated and contribute to extraintestinal inflammation.
In vivoproximity ligation reveals endogenous candidate interactors of Neurexin’s intracellular domain
Authors: Profes Marcos Schaan , Tiroumalechetty Araven , Patel Neel , Lauar Stephanie S. , Sidoli Simone , Kurshan Peri T.
Published: September 2022

Neurexins are highly-spliced transmembrane cell adhesion molecules that bind an array of partners via their extracellular domains. However, much less is known about the signaling pathways downstream of neurexin’s largely-invariant intracellular domain. C. elegans contains a single neurexin gene that we have previously shown is required for presynaptic assembly and stabilization. To gain insight into the signaling pathways mediating neurexin’s presynaptic functions, we employed a proximity ligation method, endogenously tagging neurexin’s intracellular domain with the promiscuous biotin ligase TurboID, allowing us to isolate adjacent biotinylated proteins by streptavidin pull-down and mass spectrometry. We compared our experimental strain to a control strain in which neurexin, endogenously tagged with TurboID, was dispersed from presynaptic active zones by the deletion of its C-terminal PDZ-binding motif. Using this approach we identified both known and novel intracellular interactors of neurexin, including active zone scaffolds, actin-binding proteins (including almost every member of the Arp2/3 complex), signaling molecules, and mediators of RNA trafficking, protein synthesis and degradation, among others. Characterization of mutants for candidate neurexin interactors revealed that they recapitulate aspects of thenrx-1mutant phenotype, suggesting they may be involved in neurexin signaling. Finally, to investigate a possible role for neurexin in local actin assembly, we endogenously tagged its intracellular domain with actin depolymerizing and sequestering peptides (DeActs), and found that this led to defects in active zone assembly.
Targeting the Hedgehog Signaling Pathway to Improve Tendon-to-Bone Integration
Authors: Kamalitdinov Timur B. , Fujino Keitaro , Lang Sinaia Keith , Jiang Xi , Madi Rashad , Evans Mary Kate , Zgonis Miltiadis H. , Kuntz Andrew F. , Dyment Nathaniel A.
Published: September 2022

Objective

While the role of Hedgehog (Hh) signaling in promoting zonal fibrocartilage production during development is well-established, whether this pathway can be leveraged to improve tendon-to-bone repair in adults is unknown. Our objective was to genetically and pharmacologically stimulate the Hh pathway in cells that give rise to zonal fibrocartilaginous attachments to promote tendon-to-bone integration.

Design

Hh signaling was stimulated genetically, via constitutive Smo (SmoM2 construct) activation of activated bone marrow stromal cells, or pharmacologically, via systemic agonist delivery, to mice following anterior cruciate ligament reconstruction (ACLR). To assess tunnel integration, we measured mineralized fibrocartilage (MFC) formation in these mice 28 days post-surgery and performed tunnel pullout testing.

Results

Hh pathway-related genes increased in cells forming the zonal attachments in WT mice. Both genetic and pharmacologic stimulation of the Hh pathway increased MFC formation and integration strength 28 days post-surgery. We next conducted studies to define the role of Hh in specific stages of the tunnel integration process. We found Hh agonist treatment increased proliferation of the progenitor pool in the first week post-surgery. Additionally, genetic stimulation led to continued MFC production in later stages of the integration process. These results indicate that Hh signaling plays an important biphasic role in cell proliferation and differentiation towards fibrochondrocytes following ACLR.

Conclusion

This study reveals a biphasic role for Hh signaling during the tendon-to-bone integration process after ACLR. In addition, the Hh pathway is a promising therapeutic target to improve tendon-to-bone repair outcomes.
Driver mutations in GNAQ and GNA11 genes as potential targets for precision immunotherapy in uveal melanoma patients
Authors: García-Mulero Sandra , Fornelino Roberto , Punta Marco , Lise Stefano , Varela Mar , Moreno Rafael , Costa-Garcia Marcel , Gros Alena , Alemany Ramón , María Piulats Josep , Sanz-Pamplona Rebeca
Published: September 2022

Uveal melanoma (UM) is the most common ocular malignancy in adults. Nearly 95% of UM patients carry the mutually exclusive mutations in the homologous genes GNAQ (aminoacid change Q209L/Q209P) and GNA11 (aminoacid change Q209L). UM is located in an immunosuppressed organ and do not suffer immunoediting. Therefore, we hypothesize that driver mutations in GNAQ/11 genes could be recognized by the immune system. Genomic and transcriptomic data for primary uveal tumors was collected from TCGA-UM dataset (n=80). The immunogenic potential for GNAQ/GNA11 Q209L/Q209P mutations was assessed using a variety of tools and HLA types information. The immune microenvironment was characterized using gene expression data. All prediction tools showed stronger GNAQ/11 Q209L binding to HLA. The immunogenicity analysis revealed that Q209L is likely to be presented by more than 73% of individuals in 1000G database whereas Q209P is only predicted to be presented in 24% of individuals. GNAQ/11 Q209L showed higher likelihood to be presented by HLA-I molecules than almost all driver mutations analyzed. Samples carrying Q209L had a higher immune-reactive phenotype: (i) expression of antigen presenting genes HLA-A (p=0.009) and B2M (p=0.043); (ii) immunophenoscore (p=0.008); (iii) infiltration of immune system cells NK (p=0.002) and CD8+ T lymphocytes (p=0.02). Results suggest a high potential immunogenicity of the GNAQ/11 Q209L variant that could allow the generation of novel therapeutic tools to treat UM like neoantigen vaccinations.
Long-ranged formation of the Bicoid gradient requires multiple dynamic modes that spatially vary across the embryo
Authors: Athilingam Thamarailingam , Nelanuthala Ashwin V.S. , Breen Catriona , Wohland Thorsten , Saunders Timothy E.
Published: September 2022

Morphogen gradients provide essential positional information to gene networks through their spatially heterogeneous distribution. Yet, how morphogen gradients form is still hotly contested, with multiple models proposed for different systems. Here, we focus on the transcription factor Bicoid (Bcd), a morphogen that forms an exponential gradient across the anterior-posterior (AP) axis of the earlyDrosophilaembryo. We utilise fluorescence correlation spectroscopy (FCS) and perturbations to Bcd, to dissect Bcd dynamics at multiple spatial and temporal locations. In both the cytoplasm and nucleus, we find two dynamic modes for Bicoid diffusion dynamics, consisting of fast and slow populations of Bcd. Surprisingly, there are spatial differences in Bcd diffusivity along the AP-axis, with Bcd diffusing more rapidly in the posterior. We establish that such spatially varying differences in the Bcd dynamics are sufficient to explain how Bcd can have a steep exponential gradient in the anterior half of the embryo and yet still have an observable fraction of Bcd near the posterior pole. We subsequently investigated which binding elements of Bcd are playing a role in its dynamics. In the nucleus, we demonstrate that the slower mode of Bcd transport is due to Bcd DNA binding. Addition of the Bcd homeodomain to eGFP::NLS can qualitatively replicate the observed Bcd concentration profile, suggesting this domain is the primary region regulating Bcd dynamics. This study provides a detailed analysis of morphogen dynamics at different spatial and temporal locations, revealing multiple modes of transport. These results explain how a long-ranged gradient can form while retaining a steep profile through much of its range.
Solid–solid phase transformation of aspirin at high pressures and room temperatures
Authors: Ali Imran , Han Yanqiang , Ji Qingfang , Zhang Yongli , Wei Zhiyun , Li Jinjin
Published: September 2022

Drug molecules undergo changes to their intermolecular binding patterns under extreme conditions, leading to structural phase transitions which produce different polymorphs. Polymorphism of aspirin (acetylsalicylic acid), one of the most widely consumed medications, has attracted many scientists, chemists and pharmacologists to identify its stable polymorphs and phase transformations at ambient temperatures and pressures. Here, density functional theory at the ωB97XD/6-31G* functional level is utilized to calculate the lattice constants, volumes, Gibbs free energies, vibrational spectra, stabilities and phase transitions of aspirin forms I and II at different pressures and temperatures. These computations confirm that phase transformation occurs between these two forms of aspirin at higher pressures (from 3 to 5 GPa) and near room temperatures. Taking aspirin as a case study, this work can help design, produce and store drugs, guiding scientists, chemists and pharmacologists to perform further experiments.
Has the fever left a burn?A study of the impact of COVID-19 remote working arrangements on public accountants’ burnout
Authors: Bakarich Kathleen M. , Marcy Amanda S. , O’Brien Patrick E.
Published: September 2022

Purpose

This study aims to investigate the effects of COVID-19 working arrangements on role stress, burnout and turnover intentions in public accounting professionals. Additionally, while all professionals have had to adapt to this rapid change in working environment, this paper explores whether the impact of this transition differs depending on demographic factors, namely, rank, gender, firm size and service line.

Design/methodology/approach

The authors survey 159 public accountants working in audit and tax on their perceptions of role stress, burnout and turnover intentions before COVID-19 and since. The survey used validated instruments from prior literature to capture these measures.

Findings

Results show that role stress, burnout and turnover intentions increased significantly since remote work began. Specifically, the rank of accountants significantly affects this association, with staff experiencing the most significant increases in role stress and burnout and seniors reporting significantly higher intentions to leave their current firms. Females experience a significant increase in feelings of emotional exhaustion and turnover intention, while males experience a significant increase in feelings of depersonalization and role overload. Finally, there is a positive association between firm size and burnout, with employees from national/midsize firms experiencing the largest increase in feelings of emotional exhaustion, reduced personal accomplishment and depersonalization.

Originality/value

Given that all prior research on role stressors, burnout tendencies and turnover intentions in the context of public accounting was conducted in the pre-COVID-19 work environment, this paper examines a timely and significant event that is likely to have a long-lasting impact on the way in which people work. As accounting firms seek to develop new working models and promote well-being among their employees, they should take note of the findings of this study that gender, rank and firm size result in differential impacts on role stress, burnout and turnover intentions.
Platform-centric vs. multi-party service failure: an examination of consumers’ negative word of mouth about sharing economy platforms
Authors: Wu Laurie , Liu Stephanie Q. , Ma Shihan (David) , Hanks Lydia
Published: September 2022

Purpose

This paper aims to identify platform-centric versus multiparty service failure on sharing economy platforms via topic modeling analysis of consumers’ negative online reviews. The authors also sought to understand consumers’ reactions to these experiences by detecting negative discrete emotions. The authors then contrasted consumers’ responses to platform-centric and multiparty service failure through the theoretical lens of failure controllability.

Design/methodology/approach

The authors used a large-scale data set containing more than 81,000 negative app reviews on eight representative hospitality and tourism sharing economy platforms. Topic modeling coupled with emotion detection algorithms revealed 11 themes reflecting diverse forms of platform-centric versus multiparty service failure and their associations with negative discrete emotions based on regression analysis.

Findings

The 11 themes reflecting diverse forms of platform-centric versus multiparty service failure were as follows: app glitch, customer service, locating and pooling, account issues, transaction, offer redemption, interface challenges, intermediary inaction, service lateness and cancellation, incorrect order and fee structure. The analysis suggests that platform-centric service failure is more likely than multiparty service failure to elicit negative discrete emotions.

Originality/value

The research enriches the understanding of platform-related service failure beyond dyadic service interaction. In particular, the authors bring to light two forms of platform-related service failure that warrant scholarly attention: platform-centric versus multiparty service failure. By uncovering the distinct negative emotional associations of platform-centric versus multiparty service failure, the research adds novel empirical evidence to the service failure literature and the relevant attribution theory. Findings offer long-term implications for the sustainable development of sharing economies and platform businesses in contemporary hospitality.
Growth implications of creation and discovery behavior among family firms: the moderating role of venture age
Authors: Donbesuur Francis , Hultman Magnus , Boso Nathaniel , Oghazi Pejvak
Published: September 2022

Purpose

The aim of the study is to examine the effects of opportunity creation and discovery on the performance of family firms. Specifically, from the tenets of dynamic capabilities and organizational contingency perspectives, this study proposes and tests a framework of how family firms' creation and discovery behavior impact venture growth and the conditions under which such impact can vary.

Design/methodology/approach

The study uses moderated-hierarchical regression to analyze survey data from 156 family-owned small and medium-sized enterprises (SMEs) operating within a sub-Saharan African economy.

Findings

The findings indicate that creation behavior has a curvilinear U-shaped relationship with venture growth, while discovery behavior has a direct positive relationship with venture growth. Further analysis reveals that the curvilinearity of the U-shaped relationship between creation and venture growth will be stronger for older family firms than for younger ones.

Research limitations/implications

The study findings may be limited by the cross-sectional nature of the data and the specific focus on family firms only.

Practical implications

The results highlight the significance of pursuing both opportunities among family firms. In fact, both creation and discovery opportunities are significant drivers of family firm growth, albeit in different capacities. Relatedly, managers of older family firms (compared to younger firms) can invest more in exploiting creative opportunities.

Social implications

From these findings, governments and other stakeholders should create enabling environment and institutional frameworks conducive to exploiting opportunities by entrepreneurial firms.

Originality/value

The study is novel – as it provides unique findings on the performance implications of creation and discovery behavior of entrepreneurial family firms within developing economies.
Patient engagement behaviors in hospitals: the role of word of mouth and patient helping behaviors
Authors: Fattahi Majid , Farzin Milad , Sadeghi Marzie , Makvandi Rosha
Published: September 2022

Purpose

The purpose of this study is to investigate patient perceived value as a stimulus of patient engagement behaviors both from the conceptual and empirical perspectives.

Design/methodology/approach

Based on the stimulus–organism–response framework, the authors developed a model to determine the impact of patient perceived value on patient engagement behavior in health care. The data were collected from a sample of 391 patients hospitalized in private hospitals. Structural equation modeling technique was used to test the research hypotheses.

Findings

The findings confirmed relevance of the service quality dimensions reliability, tangibility, responsiveness and empathy as significant antecedents of patient perceived value. Perceived value plays a significant role in shaping word of mouth and patient helping behaviors.

Research limitations/implications

The findings of this study are relevant and applicable to patients in private hospitals.

Practical implications

This study contributes to the literature by providing new evidence on patient perceived value and engagement behaviors as a response to care quality. With adequate focus on perceived value and service quality, service providers can strengthen the relationship with patients and build a sustainable competitive advantage, by stimulating engagement behaviors in patients.

Originality/value

This study is of unique value to the health-care literature, both from the theoretical and managerial point of views. This study proposes a conceptual model of patient perceived value which can be used in the private health sector. Moreover, this study contributes to the health-care literature by introducing patient-helping behavior.
Social exchange in buyer-supplier relationships and innovation speed: the mediating and moderating role of information sharing and knowledge channels
Authors: Ojha Divesh , Dayan Mumin , Struckell Beth , Dhir Amandeep , Pohlen Terrence
Published: September 2022

Purpose

This study recognizes service as the majority contributor to global and US gross domestic product and the importance of innovation speed to service innovation. Generating innovative products and services at a faster rate generates advantages for business-to-business (B2B) service organizations in keeping up with and moving ahead of rivals. This study aims to introduce the concept of capacity for social exchange (CSE) in buyer–supplier relationships, which reflects the degree to which individuals possess competencies that enable the exchange of information, and this study also explores how CSE affects knowledge sharing and innovation speed within a supply chain organization.

Design/methodology/approach

The sampling frame of this research consisted of service businesses in the USA. The data were collected through Zoomerang, an online survey research firm where the B2B panel of Zoomerang formed the sampling frame. The data was collected from 264 B2B service sector executives.

Findings

The key findings are as follows: CSE facilitates knowledge sharing; knowledge sharing is positively related to innovation speed; and the relationship between CSE and innovation speed is fully mediated by knowledge sharing. Additional analysis reveals that knowledge channels which are designed as boundary-spanning strategies used to transfer and create knowledge between business units, directly increase – and positively moderate – the relationship between CSE and innovation speed.

Originality/value

This study addresses the gap in literature focused on micro-level influencers on innovation. This study sets out by presenting the concept of CSE, and this study addresses limitations in prior work by examining the research questions.
URBAN NOSTALGIA, REGENERATION, AND CULTURAL MONOPOLY RENT: ‘Nanjing 1912’ and Its Branding Bubbles
Authors: Lan Cassidy I‐Chih , Chen Jianglong
Published: September 2022

Nostalgia has become an important aspect of culture‐led urban regeneration in advanced cities. Chinese cities have also experienced this tendency because many local states have used nostalgia as an instrument to brand their cities and promote business opportunities. However, culture‐led regeneration has resulted in the dilemma of cultural commodification and branding bubbles, as this approach is subordinate to capital circulation and property revitalization. We translate the Marxist idea of monopoly rent proposed by David Harvey into culture‐led regeneration by focusing on the influence of urban nostalgia on the production of the built environment and place distinctiveness for capital accumulation. Against the background of national capital in the Republic of China and its current fervor for culture‐led regeneration in what is known as the ‘Republican style’, in this article we explore the case of Nanjing 1912 to examine how urban cultural monopoly rent is produced through the project, and scrutinize its dilemma of over‐replication. Although nostalgia is associated with culture, creativity and history, Nanjing 1912's regeneration is underpinned by economic revenue and by investors experiencing branding bubbles as they tried to upscale the 1912 brand to Nanjing and its neighboring cities.
Effect of race on the measurement of angiogenic factors for prediction and diagnosis of pre‐eclampsia
Authors: Wright Alan , von Dadelszen Peter , Magee Laura A. , Syngelaki Argyro , Akolekar Ranjit , Wright Dave , Nicolaides Kypros H.
Published: September 2022

Objective

To examine the effect of self‐declared race on serum placental growth factor (PlGF) and sFlt‐1/PlGF ratio and the impact on pre‐eclampsia (PE) prediction.

Design

Prospective observational study.

Setting

Two UK maternity hospitals.

Population

29 035 women with singleton pregnancies attending a routine 35+0 to 36+6 weeks' gestation hospital visit, including 654 (2.3%) who subsequently developed PE.

Methods

The predictive performance of PlGF and sFlt‐1/PlGF for PE in minority racial groups (versus white) was examined.

Main outcome measure

Delivery with PE.

Results

Compared with white women, mean PlGF was higher and sFlt‐1/PlGF ratio lower in black, South Asian, East Asian and mixed race women. In white women at a PlGF concentration cut‐off corresponding to a screen‐positive rate (SPR) of 10%, detection rates (DRs) were 49.1% for PE at any time and 72.3% for PE within 2 weeks after screening. In black women, at the same PlGF concentration cut‐off for white women, the SPR was 5.5%, and DRs 33.6% and 55.0%, respectively; the number of PE cases was too small to evaluate screening performance in other racial groups. Using a fixed cut‐off in sFlt‐1/PlGF ratio to identify women at risk of developing PE, similarly diagnostically disadvantaged black women. Bias was overcome by adjusting metabolite concentrations for maternal characteristics and use of the competing risks model to estimate patient‐specific risks.

Conclusion

Screening for PE with fixed cut‐offs in PlGF or sFlt‐1/PlGF diagnostically disadvantages black women. It is essential that measured levels of PlGF be adjusted for race as well as other maternal characteristics.
Current progress on engineering microbial strains and consortia for production of cellulosic butanol through consolidated bioprocessing
Authors: Re Angela , Mazzoli Roberto
Published: September 2022

In the last decades, fermentative production of n‐butanol has regained substantial interest mainly owing to its use as drop‐in‐fuel. The use of lignocellulose as an alternative to traditional acetone–butanol–ethanol fermentation feedstocks (starchy biomass and molasses) can significantly increase the economic competitiveness of biobutanol over production from non‐renewable sources (petroleum). However, the low cost of lignocellulose is offset by its high recalcitrance to biodegradation which generally requires chemical‐physical pre‐treatment and multiple bioreactor‐based processes. The development of consolidated processing (i.e., single‐pot fermentation) can dramatically reduce lignocellulose fermentation costs and promote its industrial application. Here, strategies for developing microbial strains and consortia that feature both efficient (hemi)cellulose depolymerization and butanol production will be depicted, that is, rational metabolic engineering of native (hemi)cellulolytic or native butanol‐producing or other suitable microorganisms; protoplast fusion of (hemi)cellulolytic and butanol‐producing strains; and co‐culture of (hemi)cellulolytic and butanol‐producing microbes. Irrespective of the fermentation feedstock, biobutanol production is inherently limited by the severe toxicity of this solvent that challenges process economic viability. Hence, an overview of strategies for developing butanol hypertolerant strains will be provided.
An ethical assessment of the use of old and new methods to study sociality in wild animals
Authors: Gruber Thibaud
Published: September 2022

The use of novel tools and technologies is transforming our approaches to study wild animal behaviour. Yet, from disturbance of natural habitats through field experiments to tagging, there is much ground for researchers to provide clear ethical assessment of their research practices and how they can affect wild animals.

In this perspective, I review the current trends in field animal behaviour research, with a focus on studies on sociality, and investigate the forms under which such practices can impact animals. I focus particularly on the notions of disturbance and invasiveness.

I build a parallel with the legal classifications in terms of degrees of severity found in the Swiss law and aimed at protecting animal well‐being, inspired by the principles of the 3R (Replace, Refine, Reduce) used in invasive animal research.

I highlight how the impact of research can be assessed and monitored, particularly through behavioural and physiological means, identifying areas where such monitoring is critical, but also acknowledging the theoretical and practical limitations to such tools.

I hope to trigger discussions on an ethical use of new tools and technologies, which can both inspire new research while limiting the disturbance to wild animals.
Time to stop the hand‐wringing. ‘Net zero’ hysterectomy is not an appropriate goal
Authors: Nicklin James
Published: September 2022

Hysterectomy is an essential part of the treatment armamentarium for patients with malignant disease, severe prolapse, massive fibroids, with genetic mutations that predispose to endometrial cancer, and in selected patients with severe symptomatic endometriosis and adenomyosis. For patients with abnormal uterine bleeding unresponsive to non‐surgical measures, there is high‐level evidence that hysterectomy, particularly minimally invasive hysterectomy, is associated with higher rates of satisfaction and quality of life, comparable rates of serious adverse events and a lower incidence of further surgery, than endometrial resection or ablation. A ‘net zero’ hysterectomy is not an appropriate goal in contemporary gynaecological practice.
Researchers succeed in growing mouse embryos ex utero solely from stem cells
Authors: Han Jason J.
Published: September 2022

Synthetic mouse embryos grew ex utero to 8.5 days and showed early stages of organogenesis.
Rates and predictors of mortality of very low birthweight infants in three Nigerian tertiary hospitals
Authors: Fajolu Iretiola B. , Mairami Amsa B. , Okonkwo Ikechukwo , Ezenwa Beatrice , Otuneye Adekunle T. , Amuabunos Emmanuel A. , Mukhtar‐Yola Mariya , Audu Lamidi I. , Ezeaka Veronica C. , Ekhaguere Osayame A.
Published: September 2022

Aim

We aimed to describe in‐hospital mortality, and its predictors, in very low birthweight (VLBW) infants managed in tertiary centres in a low‐ to middle‐income country.

Methods

This was a retrospective cohort study of VLBW infants (birthweight 500 to 1500 grams) admitted within 72 h of life to the neonatal intensive care units (NICUs) of three tertiary centres in Nigeria from July 2017 to March 2021. We describe in‐hospital mortality rates, causes and when they died. The independent predictors of in‐hospital mortality were determined using multivariate logistic analysis.

Results

Of the 6187 NICU admissions, 1161 met the inclusion criteria: 545 (47%) VLBW infants died, including 309 (57%) from respiratory distress syndrome, and 55% occurred within 72 h of life. The adjusted odds (aOR) for mortality increased with each extra Downes respiratory distress score (aOR 1.27) with a 95% confidence interval (CI) of 1.14–1.41. Study site 3 had a higher aOR for mortality than site 1 (aOR 2.78, 95% CI 1.72–4.48) and site 2 (aOR 2.29, 95% CI 1.45–3.61).

Conclusion

Nearly half (47%) of all VLBW infants admitted to three tertiary referral hospitals in Nigeria died during hospitalisation. Mortality varied significantly by site and both the centre and respiratory distress independently predicted mortality.
Preventive interventions for children of parents with depression, anxiety, or bipolar disorder: A quasi‐experimental clinical trial
Authors: Wirehag Nordh Emme‐Lina , Grip Karin , Thorvaldsson Valgeir , Priebe Gisela , Afzelius Maria , Axberg Ulf
Published: September 2022

Aim

To investigate the effectiveness of preventive interventions for 8–17‐year‐old children of patients diagnosed with depression, anxiety, or bipolar disorder.

Methods

Sixty‐two families including 89 children received either the more extensive Family Talk Intervention (FTI; n = 35), the brief Let's Talk about Children (LTC; n = 16), or Interventions as Usual (IAU; n = 38) in routine care in adult psychiatry. Parent‐rated questionnaire data were collected at baseline, after 6 and 12 months. We used growth curve models to investigate the effect of intervention on child mental health problems (SDQ‐P Total Difficulties) and perceived parental control of child behaviour (PLOC‐PPC).

Results

Parents in the FTI and LTC groups, versus the IAU group, reported more favourable development in terms of preventing increase in child mental health problems with standardised intervention effects of d = −0.86 and −0.88 respectively, by study end, and reported improved perceived parental control, d = 1.08 and 0.71, respectively, by study end. No significant differences in effect were found when FTI and LTC were compared.

Conclusions

The results support continued use of FTI and LTC in adult psychiatry, and since LTC is a brief intervention, it might be useful as a minimum‐level preventive intervention.
Letter: the probability of predicting HBV‐specific CD8+ cell response derived from HLA‐A2+ may not closely predict functional cure in Asian patients who stop nucleoside analogues
Authors: Liu Yen‐Chun , Jeng Wen‐Juei
Published: September 2022

LINKED CONTENT

This article is linked to Pena‐Asensio et al papers. To view these articles, visit https://doi.org/10.1111/apt.16850 and https://doi.org/10.1111/apt.17212
Letter: should we have to include baclofen in the GORD therapy armamentarium? authors' reply
Authors: Raymenants Karlien , Van den Bergh Jolinde , Tack Jan
Published: September 2022

LINKED CONTENT

This article is linked to Pauwels et al papers. To view these articles, visit https://doi.org/10.1111/apt.17068 and https://doi.org/10.1111/apt.17183
Non‐recovery of vancomycin‐associated nephrotoxicity is related to worsening survival outcomes: Combined retrospective analyses of two real‐world databases
Authors: Chuma Masayuki , Hamano Hirofumi , Bando Takashi , Kondo Masateru , Okada Naoto , Izumi Yuki , Ishida Shunsuke , Yoshioka Toshihiko , Asada Mizuho , Niimura Takahiro , Zamami Yoshito , Takechi Kenshi , Goda Mitsuhiro , Miyata Koji , Yagi Kenta , Kasamo Sachiko , Izawa‐Ishizawa Yuki , Azuma Momoyo , Yanagawa Hiroaki , Tasaki Yoshikazu , Ishizawa Keisuke
Published: September 2022

There has been growing concern in worsening survival and renal outcomes following vancomycin‐associated nephrotoxicity (VAN) onset, but the factors associated with these phenomena remain unclear. To examine these factors, we performed a retrospective study combining the analysis of two real‐world databases. Initially, the FDA Adverse Event Reporting System (FAERS) was used to evaluate the relationship between VAN and mortality using odds ratios (ORs) and 95% confidence intervals (CIs). Next, electronic medical records (EMRs) were examined in a more robust cohort for evaluation of the association between renal outcomes and worsening survival using Cox proportional hazards regression models. FAERS analysis revealed a significant correlation between VAN occurrence and increased mortality (OR: 1.30; 95% CI: 1.17–1.46). EMR analysis showed that non‐recovery of VAN was associated with increased hospital mortality (hazard ratio [HR]: 4.05; 95% CI: 2.42–6.77) and 1‐year mortality (HR: 3.03, 95% CI: 1.98–4.64). The HR for VAN recovery was lower for patients with acute kidney injury (AKI) stage ≥2 (HR: 0.09; 95% CI: 0.02–0.40). Thus, worsening survival outcomes were associated with non‐recovery of VAN, whereby AKI stage ≥2 was a significant risk factor. Progression to severe VAN should be prevented for better survival outcomes.
Hepatic stellate cell‐released CXCL1 aggravates HCC malignant behaviors through the MIR4435‐2HG/miR‐506‐3p/TGFB1 axis
Authors: Li Shaling , Hu Xingwang , Yu Songman , Yi Panpan , Chen Ruochan , Huang Zebing , Huang Yan , Huang Yun , Zhou Rongrong , Fan Xuegong
Published: September 2022

Hepatic stellate cell (HSC) activation is a critical event in the development of hepatic fibrosis and hepatocellular carcinoma (HCC). By the release of soluble cytokines, chemokines, and chemotaxis, HSCs affect HCC cell phenotypes through a complex tumor microenvironment. In this study, weighted gene co‐expression network analysis (WGCNA) was used to identify the TGF‐β signaling pathway as a key signaling pathway in Hep3B cells cultured in HSC conditioned medium. MIR4435‐2HG is a hub lncRNA associated with the TGF‐β signaling pathway and HSC activation. HSC‐condition medium (CM) culture induced HCC cell malignant behaviors, which were partially reversed by MIR4435‐2HG silencing. miR‐506‐3p directly bound to MIR4435‐2HG and the 3′UTR of TGFB1. Similarly, overexpression of miR‐506‐3p also attenuated HSC‐CM‐induced malignant behavior of HCC cells. In HSC‐CM cultured HCC cells, the effects of MIR4435‐2HG knockdown on TGFB1 expression and HCC cell phenotypes were partially reversed by miR‐506‐3p inhibition. HSCs affected HCC cell phenotypes by releasing CXCL1. In an orthotopic xenotransplanted tumor model of HCC cells plus HSCs in mice, CXCR2 knockdown in HCC cells significantly inhibited tumorigenesis, which was partially reversed by MIR4435‐2HG overexpression in HCC cells. In HCC tissue samples, the levels of CXCL1, TGF‐β1, and MIR4435‐2HG were upregulated, while miR‐506‐3p expression was downregulated. In conclusion, HSC‐released CXCL1 aggravated HCC cell malignant behaviors through the MIR4435‐2HG/miR‐506‐3p/TGFB1 axis. In addition to CXCL1, the MIR4435‐2HG/miR‐506‐3p/TGFB1 axis might also be the underlying target for HCC therapy.
Maternal factors and risk of early childhood caries: A prospective cohort study
Authors: Foxman Betsy , Davis Elyse , Neiswanger Katherine , McNeil Daniel , Shaffer John , Marazita Mary L.
Published: September 2022

Objective

To evaluate the associations between time‐varying factors (mother's oral health, oral hygiene, smoking habits, diet, food insecurity and stress) socioeconomic factors (mother's employment, marital status, household income, insurance status, household size) and medical history on children's risk of developing a carious lesion in the first 3 years of life.

Methods

Longitudinal data from the Center for Oral Health Research in Appalachia Cohort Two (COHRA2) were analysed. Pregnant women ≥18 years in the USA were recruited during pregnancy; all consenting women delivering at term and their babies had regular dental assessments and complete in‐person surveys and telephone interviews regarding sociodemographic factors, medical and dental history, and oral health behaviours.

Results

In a logistic regression model adjusting for covariates, children whose mother had two or more prior pregnancies, smoked cigarettes post‐partum, or had a recent unfilled carious lesion were at least twice as likely to experience a dental lesion by the three‐year visit. The magnitude of these associations varied by maternal education and state of residence.

Conclusions

Untreated maternal decay but not maternal oral hygiene or diet were associated with cumulative risk of childhood caries by age three but were modified by maternal education and state of residence. Addressing structural and behavioural issues that reduce use of restorative dental care are needed to prevent the adverse impacts associated with early childhood caries.
Detail‐Aware Deep Clothing Animations Infused with Multi‐Source Attributes
Authors: Li T. , Shi R. , Kanai T.
Published: September 2022

This paper presents a novel learning‐based clothing deformation method to generate rich and reasonable detailed deformations for garments worn by bodies of various shapes in various animations. In contrast to existing learning‐based methods, which require numerous trained models for different garment topologies or poses and are unable to easily realize rich details, we use a unified framework to produce high fidelity deformations efficiently and easily. Specifically, we first found that the fit between the garment and the body has an important impact on the degree of folds. We then designed an attribute parser to generate detail‐aware encodings and infused them into the graph neural network, therefore enhancing the discrimination of details under diverse attributes. Furthermore, to achieve better convergence and avoid overly smooth deformations, we proposed to reconstruct output to mitigate the complexity of the learning task. Experimental results show that our proposed deformation method achieves better performance over existing methods in terms of generalization ability and quality of details.
Literacy skills seem to fuel literacy enjoyment, rather than vice versa
Authors: van Bergen Elsje , Hart Sara A. , Latvala Antti , Vuoksimaa Eero , Tolvanen Asko , Torppa Minna
Published: September 2022

Children who like to read and write tend to be better at it. This association is typically interpreted as enjoyment impacting engagement in literacy activities, which boosts literacy skills. We fitted direction‐of‐causation models to partial data of 3690 Finnish twins aged 12. Literacy skills were rated by the twins’ teachers and literacy enjoyment by the twins themselves. A bivariate twin model showed substantial genetic influences on literacy skills (70%) and literacy enjoyment (35%). In both skills and enjoyment, shared‐environmental influences explained about 20% in each. The best‐fitting direction‐of‐causation model showed that skills impacted enjoyment, while the influence in the other direction was zero. The genetic influences on skills influenced enjoyment, likely via the skills→enjoyment path. This indicates an active gene‐environment correlation: children with an aptitude for good literacy skills are more likely to enjoy reading and seek out literacy activities. To a lesser extent, it was also the shared‐environmental influences on children's skills that propagated to influence children's literacy enjoyment. Environmental influences that foster children's literacy skills (e.g., families and schools), also foster children's love for reading and writing. These findings underline the importance of nurturing children's literacy skills.

Highlights

It's known that how much children enjoy reading and writing and how good they are at it correlates ∼0.30, but causality remains unknown.

We tested the direction of causation in 3690 twins aged 12.

Literacy skills impacted literacy enjoyment, but not the other way around.

Genetics influence children's literacy skills and how much they like and choose to read and write, indicating genetic niche picking.