bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of dental bleaching on the pulp tissue: A systematic review of in vivo studies
Authors: Donato Mariana Viana , dos Reis‐Prado Alexandre Henrique , Abreu Lucas Guimarães , de Arantes Lara Cancella , Goto Juliana , Chaves Hebertt Gonzaga dos Santos , Cintra Luciano Tavares Angelo , Briso André Luiz Fraga , Peixoto Isabella Faria da Cunha , Benetti Francine
Published: March 2024

Background

Although several studies indicate the harmful effects of bleaching on pulp tissue, the demand for this procedure using high concentrations of hydrogen peroxide (HP) is high.

Objectives

To investigate the influence of bleaching on the pulp tissue.

Methods

Electronic searches were conducted (PubMed/MEDLINE, Scopus, Cochrane Library and grey literature) until February 2021. Only in vivo studies that evaluated the effects of HP and/or carbamide peroxide (CP) bleaching gels on the inflammatory response in the pulp tissue compared with a non‐bleached group were included. Risk of bias was performed according to a modified Methodological Index for Non‐Randomized Studies scale for human studies and the Systematic Review Centre for Laboratory Animal Experimentation's RoB tool for animal studies. Meta‐analysis was unfeasible.

Results

Of the 1311 studies, 30 were eligible. Of these, 18 studies evaluated the inflammatory response in animal models. All these studies reported a moderate‐to‐strong inflammatory response in the superficial regions of pulp, characterized by cell disorganization and necrotic areas, particularly during the initial periods following exposure to 35%–38% HP, for 30–40 min. In the evaluation of human teeth across 11 studies, seven investigated inflammatory responses, with five observing significant inflammation in the pulp of bleached teeth. In terms of tertiary dentine deposition, 11 out of 12 studies noted its occurrence after bleaching with 35%–38% HP in long‐term assessments. Additionally, three studies reported significant levels of osteocalcin/osteopontin at 2 or 10 days post‐treatment. Other studies indicated an increase in pro‐inflammatory cytokines ranging from immediately up to 10 days after bleaching. Studies using humans' teeth had a low risk of bias, whereas animal studies had a high risk of bias.

Discussion

Despite the heterogeneity in bleaching protocols among studies, High‐concentrations of HP shows the potential to induce significant pulp damage.

Conclusions

High‐concentrations of bleaching gel increases inflammatory response and necrosis in the pulp tissue at short periods after bleaching, mainly in rat molars and in human incisors, in addition to greater hard tissue deposition over time. However, further well‐described histological studies with long‐term follow‐up are encouraged due to the methodological limitations of these studies.

Registration

PROSPERO (CRD42021230937).
University students’ metaphors for Canadian multiculturalism: Diverse perceptions
Authors: Shakoury Kayvan , Boers Frank
Published: March 2024

This study investigated the beliefs of university students at a university in Canada regarding multiculturalism and multicultural society, through examining the metaphors they use to talk about these concepts. We interviewed 50 students about their perceptions and experiences of multiculturalism in Canada and then asked them to explain their choice of metaphors. Many of the metaphors could be grouped under more general metaphor themes, such as a multicultural society is a varied multicomponent piece of art/craft (comprising, e.g., mosaic and tapestry metaphors) and multicultural society is a container to mix things (comprising, e.g., melting pot and salad bowl metaphors). According to the literature, the former theme is compatible with the view that multiculturalism involves integration while preserving diversity, whereas the latter is associated with the notion of assimilation. Canadian students appeared to be more inclined than international students to use the (positive) varied multicomponent piece of art/craft theme relative to the other metaphors in the total data set. The interview data also revealed marked differences among participants as regards their awareness of metaphor but prompting them to reflect on their choice of metaphors often had an awareness‐raising effect.
Organizational change towards the circular economy: A systematic review of the literature
Authors: Graessler Sophie , Guenter Hannes , de Jong Simon B. , Henning Klaus
Published: March 2024

Scholars have long studied how organizations can transition towards greater sustainability, but it is only recently that they have begun to investigate a fundamentally new stream in sustainability thinking: the circular economy paradigm. Instead of the ‘make‐use‐dispose’ approach of a linear economy, a circular economy aims at eliminating waste and avoiding damage to the environment by closing resource loops. Given the recent surge of scholarly interest in the ways in which organizations can change towards working in a more circular way, it is important and timely to verify what scholars have learnt, what remains contested, and what should be done next. To this end, we are reviewing literature on the emerging field of ‘Organizational Change towards a Circular Economy’ (OCCE). We identify and analyse research that sits at the interface of organizational change theory and the circular economy paradigm and provide a systematic literature review. Our review reveals consensus, ambiguities, and differences in the OCCE literature along three main dimensions of organizational change (i.e., content, process, and context). Furthermore, we develop a novel and encompassing conceptualization of OCCE as well as outline future research opportunities. Overall, our study brings together the growing but fragmented body of OCCE research and outlines scientific and practical avenues for making progress in a more unified and systematic way.
Effectiveness of the knowledge, attitude, practice intervention model in the management of hypertension in the elderly
Authors: Xu Li‐Shuang , Gao Zhi‐Guang , He Mei , Yang Ming‐Da
Published: March 2024

This study illustrated the effectiveness of the knowledge, attitude, practice (KAP) intervention model for community hypertension in the elderly by the community physician‐led, describing the study design and baseline data. The aim of the study was to compare the changes in the elderly hypertensive population before and after the KAP intervention model by managing the elderly hypertensive patients for a period of 1 year. Basic information and risk factors affecting blood pressure control based on baseline data of recruited elderly hypertensive patients. The management approach consists of two parts: (1) the unified management of the community physician to whom the patient belongs; and (2) the management of the contracted patient by the community physician. The aim was to demonstrate the anti‐hypertensive effectiveness (control rate, blood pressure reduction, and pulse pressure), the distribution of blood pressure types, and the change of the KAP in elderly hypertensive patients before and after the intervention. The KAP intervention model was administered to 2660 elderly hypertensive patients in a 1‐year period. The blood pressure control rate improved by 54.03%. Mean values of overall systolic and diastolic blood pressure decreased by 16.00 and 5.31 mmHg, respectively. The proportion of isolated systolic hypertension (ISH) and systolic‐diastolic hypertension (SDH) decreased by 29.14% and 24.81%, respectively. The KAP compliance improved significantly. These results suggest that the community physician‐led KAP intervention model is effective in the management of hypertension in the elderly.
Mechanisms and durations of metamorphic garnet crystallization in the lower nappes of the Caledonian Kalak Nappe Complex, Arctic Norway
Authors: Yogi Maria Thereza A. G. , Gaidies Fred , Heldwein Olivier K. A. , Rice A. Hugh N.
Published: March 2024

The 3D microstructure and compositional zoning of garnet populations in micaschists from the Kolvik and Bekkarfjord nappes indicate the quasi‐equilibration of their major components across the rock matrices during interface‐controlled, size‐independent garnet growth. There is microstructural evidence for foliation‐parallel, small‐scale resorption of garnet rims in the Kolvik Nappe, influencing the metamorphic peak conditions obtained from thermodynamic modelling. The local chemical compositions of rims less affected by resorption indicate a peak temperature of ~630°C, which is ~40°C higher than the temperature obtained from resorbed rims of the largest garnet crystal. Using a diffusion geospeedometry approach that considers the geometry of the compositional zoning of the garnet population, as well as the higher, more realistic peak temperature, a duration of 1 to 4.9 Myr is obtained for garnet growth in the Kolvik Nappe. This is approximately 1 order of magnitude faster than duration estimates obtained when using the apparent, lower temperature estimated from the resorbed garnet rims. Concomitantly to garnet growth in the Kolvik Nappe, garnet overgrowths formed in the Bekkarfjord Nappe for circa 2.5 Myr at metamorphic peak temperatures of ~560°C. The garnet growth durations obtained here are comparable with the uncertainty on the Lu–Hf garnet–whole rock isochron ages of 419.9 ± 2.4 Ma and 423.0 ± 1.9 Ma, previously obtained for these rocks. These results provide new insight into the timescales of repeated Barrovian‐type metamorphic events experienced by the lower nappes of the Kalak Nappe Complex during the Caledonian Orogeny in Arctic Norway. This study emphasizes the importance of microstructural and chemical characterization of garnet populations in assessing metamorphic crystallization mechanisms and the extent of equilibration of garnet‐forming components during prograde metamorphism. Moreover, our results provide means for reducing the uncertainty on metamorphic durations obtained via diffusion geospeedometry and, so, contributing to our understanding of geological timescales and processes.
Organizational Engagement: One State's Experience With Invigorating Affiliate Membership and Building a Sustainable Fundraising Model
Authors: Narbey Lauren , Ingalls Rebecca , Cline Alice , McGahey Emily C. , Shafton Amanda , Amsley‐Camp Kim
Published: March 2024

Over the last 6 years, the Pennsylvania Affiliate of the American College of Nurse‐Midwives has worked to meet the needs of its diverse membership and increase the capacity of the affiliate board by taking a series of strategic steps. This article details the key components of this journey, which has culminated in a successful annual conference with over $118,000 in net revenue to help meet affiliate goals, including pursuing midwifery modernization legislation for Pennsylvania and an increase in our affiliate membership by almost 100 individuals. The annual conference, Midwifery Forward, which completed its fifth year in 2023, has also given our community of midwives a yearly reason to gather and reconnect, celebrate accomplishments, welcome new graduates, and make plans for the year ahead. The goal of this article is to share the specifics of our strategic planning, so that other affiliates and organizations may benefit as they develop strategic plans in the larger effort to increase membership and engagement and generate sustainable income for their midwifery organizations.
The mediating role of psychological flexibility in the relationship between psychotic symptom severity and depression in individuals diagnosed with schizophrenia
Authors: Yıldız Erman , Yıldırım Özlem
Published: March 2024

Accessible Summary

What is known about the subject?

Psychotic symptoms and depression are common problems in people diagnosed with schizophrenia.

Psychological flexibility is a skill that facilitates coping with difficulties.

There is limited research on the role of psychological flexibility in the relationship between psychotic symptoms and depression in people diagnosed with schizophrenia.

What does the article add to existing knowledge?

This article investigates the role of psychological flexibility in the link between psychotic symptom severity and depression in people diagnosed with schizophrenia.

The article shows that psychological flexibility partially mediates the relationship between psychotic symptom severity and depression.

The article suggests that interventions aimed at improving psychological flexibility may be beneficial in reducing depressive symptoms in people diagnosed with schizophrenia.

What are the implications for practice?

Mental health nurses should consider psychotic symptom severity and psychological flexibility when assessing and intervening for depressive symptoms in people diagnosed with schizophrenia.

Mental health nurses should receive training to improve psychological flexibility and pass this skill on to their patients.

Mental health nurses should continue to research the effectiveness and outcomes of interventions aimed at improving psychological flexibility.

Introduction

Psychological flexibility may help people diagnosed with schizophrenia (PWS) cope with their psychotic symptoms and reduce their depressive symptoms, but the mechanism of this effect is unclear.

Aim

To investigate whether psychological flexibility mediates the relationship between psychotic symptom severity and depression in PWS.

Method

A cross‐sectional study was conducted, in which a total of 111 PWS were assessed with DSM‐5 Clinician‐Rated Dimensions of Psychosis Symptom Severity, Calgary Depression Scale for Schizophrenia and Acceptance and Action Questionnaire. Data analysis was performed using SPSS 25 and PROCESS macro.

Results

Significant correlations were found between psychotic symptoms, depression and psychological flexibility. Psychological flexibility partially mediated the relationship between psychotic symptom severity and depression.

Discussion

Psychological flexibility could weaken the impact of psychotic symptom severity on depression in PWS. Higher psychotic symptoms were associated with lower psychological flexibility and higher depression.

Implications for Practice

Interventions to improve psychological flexibility may prevent depressive symptoms in PWS. Psychiatric nurses can use psychological flexibility as a goal for evaluation and intervention.
Prior knowledge‐infused neural network for efficient performance assessment of structures through few‐shot incremental learning
Authors: Chen Shi‐Zhi , Feng De‐Cheng , Taciroglu Ertugrul
Published: March 2024

Structural seismic safety assessment is a critical task in maintaining the resilience of existing civil and infrastructures. This task commonly requires accurate predictions of structural responses under stochastic intensive ground accelerations via time‐costly numerical simulations. While numerous studies have attempted to use machine learning (ML) techniques as surrogate models to alleviate this computing burden, a large number of numerical simulations are still required for training ML models. Therefore, this study proposes a prior knowledge‐infused neural network (PKNN) for achieving efficient structural seismic response predictions and seismic safety assessment at a low computation cost. In this approach, first, the prior knowledge inherently within a theoretical dynamic model of a structure is infused into a neural network. Then, by utilizing the few‐shot incremental learning technique, this network would be further fine‐tuned by only a few numerical simulations. The resulting PKNN would be able to accurately predict the seismic response of a structure and facilitate seismic safety assessment. In this study, the PKNN's accuracy and computational efficiency are validated on a typical frame structure. The results revealed that the proposed PKNN could be used for accurately predicting the structural seismic responses and assessing the structural safety under a low computational cost.
Learning to govern: A typology of ministerial learning styles
Authors: Boswell John , Smith Jessica C. , Devine Daniel , Corbett Jack
Published: March 2024

A quirk of the Westminster system is that Ministers invariably have to “learn on the job”. Yet “learning” has been surprisingly understudied in work on executive government in Britain especially. In this paper, we offer a systematic account of Ministerial learning based on a comprehensive analysis of the Ministers Reflect archive—the largest dataset of research interviews with former Westminster ministers ever assembled. We identify six distinct learning styles—incremental, risk‐averse, managerial, creative, instrumental and instinctive—and assess the implications for how Ministers adjust to the challenges of high political office. We conclude by showing what an appreciation for this variety of Ministerial learning styles can offer the study and practice of executive government in Britain and beyond.
Deflation by Expenditure Components: A Harmless Adjustment?
Authors: Amendola Nicola , Mancini Giulia , Redaelli Silvia , Vecchi Giovanni
Published: March 2024

We investigate the effect that seemingly minor features of the implementation of cost‐of‐living adjustments have on the distribution of household expenditures, by developing an analytical framework that is consistent with standard consumer theory, and mindful of data limitations faced by practitioners. The main result is at odds with common sense: even when multiple price indices are available (e.g., a food Consumer Price Index and a non‐food one), it turns out that using a single price index (e.g., the total Consumer Price Index), to adjust the consumption aggregate is recommended. The practice of adjusting subcomponents of consumption separately (food with a food index and nonfood with a nonfood index) can lead to a systematic bias in the welfare measure, and consequently in poverty and inequality measures. Using Iran's 2019 Household Expenditures and Income Survey, we find that the bias manifests as a systematic underestimation of urban poverty and overestimation of rural poverty.
The hidden biotic face of microbialite morphogenesis – a case study from Laguna de Los Cisnes, southernmost Patagonia (Chile)
Authors: Pollier Clément G. L. , Guerrero Alejandro N. , Rabassa Jorge , Ariztegui Daniel
Published: March 2024

Microbialites provide geological evidence into Earth's early ecosystems, recording long‐standing interactions between co‐evolving life and the environment. Yet, after more than 100 years of research, the complex interplay between environmental and biological forces involved in microbialite growth is still debated. Laguna de Los Cisnes, located in Chilean Tierra del Fuego, Patagonia, provides a unique opportunity to study these interactions. This lake, which became ice‐free around 10 000 years ago, features carbonate microbialites developed by algal–microbial communities. Macroscopically, the organo‐sedimentary deposits exhibit a consistent primary crater‐like architecture, showcasing macrostructural variations such as dish‐shaped, hemispherical, columnar and lenticular morphologies. This study explores the environmental and biological factors shaping microbialite macrostructure by analysing the distribution of dominant morphotypes across the basin. Concurrently, it examines the internal mesostructure and microstructure of microbialites in association with prevailing algal–microbial communities. The incremental development of these communities contributes to the distinct crater‐like morphology observed in microbialites from Laguna de Los Cisnes. The mineral encrustation of the green alga Percursaria percursa emerges as a primary driver of lithification, evidenced by the preservation of microfossils within the microstructure of the microbialites. Simultaneously, physical environmental factors, including waves, Langmuir cells and accommodation space influence the location of the algal–microbial carbonate factory, determining the spatial distribution and temporal succession of different crater architecture variants. Laguna de Los Cisnes, hosting well‐preserved subfossil outcrops and living microbialites, serves as a remarkable living laboratory for understanding microbialite morphogenesis. This study contributes to a novel model that captures the fundamental role of algal–microbial communities in determining the primary macrostructural architecture of microbialites before environmental factors come into play, merely reshaping this architecture into different morphotypes.
Inhibiting IL11RA to mitigate hepatic metastasis in skin cutaneous melanoma: Comprehensive insights from in vitro and in vivo investigations
Authors: Zhang Zhen‐Guo , Zhu Hong‐Mei , Hua Huai‐Kang
Published: March 2024

Objective

This study aimed to investigate the role of Interleukin‐11 receptor alpha (IL11RA) in skin cutaneous melanoma (SKCM) metastasis to the liver.

Methods

Human SKCM cell lines (A375, A375‐MA2, SK‐MEL‐28, RPMI‐7951) and primary dermal fibroblasts (HDFa) were utilized to assess IL11RA expression. IL11RA siRNA was transfected into RPMI‐7951 and A375‐MA2 cells for Wound healing and Transwell invasion assays. Il11ra knockout (KO) mice and wild‐type (WT) mice were injected with B16‐F10 cells into the spleen to evaluate hepatic melanoma metastasis. Correlation between IL11RA and MMP family genes was explored using online databases, including LinkedOmics, TIMER (Tumor Immune Estimation Resource), and GEPIA (Gene Expression Profiling Interactive Analysis). RT‐qPCR and Western blotting were performed for expression analysis of Mmp2 and Mmp9 in liver tissues of mice. The impact of IL11RA on the STAT3 pathway was investigated in vitro and in vivo.

Results

Elevated expression of IL11RA was observed in SKCM cell lines compared to normal cells. IL11RA downregulation significantly inhibited migratory and invasive capabilities of A375‐MA2 and RPMI‐7951 in vitro. Il11ra gene knockout in mice demonstrated a substantial reduction in hepatic melanoma metastasis. Correlation analyses revealed associations between IL11RA and MMP2/MMP8. Il11ra gene knockout significantly decreased Mmp2 expression while increasing Mmp8 in liver tissues. IL11RA correlated positively with STAT3, and its inhibition led to a suppressed STAT3 pathway in SKCM cells and mouse liver tissue.

Conclusion

IL11RA plays a crucial role in SKCM metastasis, affecting migratory and invasive abilities. Targeting IL11RA may offer a promising avenue for therapeutic interventions in cutaneous melanoma progression.
Close contacts of xenograft recipients: Ethical considerations due to risk of xenozoonosis
Authors: Hurst Daniel J. , Padilla Luz , Rodger Daniel , Schiff Tamar , Cooper David K. C.
Published: March 2024

With decades of pre‐clinical studies culminating in the recent clinical application of xenotransplantation, it would appear timely to provide recommendations for operationalizing oversight of xenotransplantation clinical trials. Ethical issues with clinical xenotransplantation have been described for decades, largely centering on animal welfare, the risks posed to the recipient, and public health risks posed by potential spread of xenozoonosis. Much less attention has been given to considerations relating to potentially elevated risks faced by those who may care for or otherwise have close contact with xenograft recipients. This paper examines the ethical and logistical issues raised by the potential exposure to xenozoonotic disease faced by close contacts of xenotransplant recipients—defined herein as including but not limited to caregivers, household contacts, and sexual partners—which warrants special attention given their increased risk of exposure to infection compared to the general public. We discuss implications of assent or consent by these close contacts to potentially undergo, along with the recipient, procedures for infection screening and possible quarantine. We then propose several options and recommendations for operationalizing oversight of xenotransplantation clinical trials that could account for and address close contacts’ education on and agency regarding the risk of xenozoonosis.
Development of a genetic system for
Haloferax gibbonsii
LR2-5, model host for haloarchaeal viruses
Authors: Tittes Colin , Nijland Jeroen , Schoentag Anna M. C. , Hackl Thomas , Di Cianni Nadia , Marchfelder Anita , Quax Tessa E. F.
Published: March 2024

Archaeal viruses are among the most enigmatic members of the virosphere, and their diverse morphologies raise many questions about their infection mechanisms. The study of molecular mechanisms underlying virus-host interactions hinges upon robust model organisms with a system for gene expression and deletion. Currently, there are only a limited number of archaea that have associated viruses and have a well-developed genetic system. Here, we report the development of a genetic system for the euryarchaeon
Haloferax gibbonsii
LR2-5. This strain can be infected by multiple viruses and is a model for the study of virus-host interactions. We created a
Hfx. gibbonsii
LR2-5 ∆
pyrE
strain, resulting in uracil auxotrophy, which could be used as a selection marker. An expression plasmid carrying a
pyrE
gene from the well-established
Haloferax volcanii
system was tested for functionality. Expression of a GFP-MinD fusion under a tryptophan inducible promoter was fully functional and showed similar cellular localization as in
Hfx. volcanii
. Thus, the plasmids of the
Hfx. volcanii
system can be used directly for the
Hfx. gibbonsii
LR2-5 genetic system, facilitating the transfer of tools between the two. Finally, we tested for the functionality of gene deletions by knocking out two genes of the archaeal motility structure, the archaellum. These deletion mutants were as expected non-motile and the phenotype of one deletion could be rescued by the expression of the deleted archaellum gene from a plasmid. Thus, we developed a functional genetic toolbox for the euryarchaeal virus host
Hfx. gibbonsii
LR2-5, which will propel future studies on archaeal viruses.

IMPORTANCE

Species from all domains of life are infected by viruses. In some environments, viruses outnumber their microbial hosts by a factor of 10, and viruses are the most important predators of microorganisms. While much has been discovered about the infection mechanisms of bacterial and eukaryotic viruses, archaeal viruses remain understudied. Good model systems are needed to study their virus-host interactions in detail. The salt-loving archaeon
Haloferax gibbonsii
LR2-5 has been shown to be infected by a variety of different viruses and, thus, is an excellent model to study archaeal viruses. By establishing a genetic system, we have significantly expanded the toolbox for this model organism, which will fuel our understanding of infection strategies of the underexplored archaeal viruses.
Plasmodium falciparum
selectively degrades α-spectrin of infected erythrocytes after invasion
Authors: Zheng Kexin , Li Qilong , Jiang Ning , Zhang Yanxin , Zheng Yuxin , Zhang Yiwei , Feng Ying , Chen Ran , Sang Xiaoyu , Chen Qijun
Published: March 2024

Remodeling the erythrocyte membrane and skeleton by the malarial parasite
Plasmodium falciparum
is closely associated with intraerythrocytic development. However, the mechanisms underlying this association remain unclear. In this study, we present evidence that erythrocytic α-spectrin, but not β-spectrin, was dynamically ubiquitinated and progressively degraded during the intraerythrocytic development of
P. falciparum,
from the ring to the schizont stage. We further observed an upregulated expression of
P. falciparum
phosphatidylinositol 3-kinase (PfPI3K) in the infected red blood cells during the intraerythrocytic development of the parasite. The data indicated that PfPI3K phosphorylated and activated erythrocytic ubiquitin-protein ligase, leading to increased α-spectrin ubiquitination and degradation during
P. falciparum
development. We further revealed that inhibition of the activity of PfPI3K impaired
P. falciparum
development
in vitro
and
Plasmodium berghei
infectivity in mice. These findings collectively unveil an important mechanism of PfPI3K-ubiquitin-mediated degradation of α-spectrin during the intraerythrocytic development of
Plasmodium
species. Proteins in the PfPI3K regulatory pathway are novel targets for effective treatment of severe malaria.

IMPORTANCE

Plasmodium falciparum
is the causative agent of severe malaria that causes millions of deaths globally. The parasite invades human red blood cells and induces a cascade of alterations in erythrocytes for development and proliferation. Remodeling the host erythrocytic cytoskeleton is a necessary process during parasitization, but its regulatory mechanisms remain to be elucidated. In this study, we observed that erythrocytic α-spectrin is selectively degraded after
P. falciparum
invasion, while β-spectrin remained intact. We found that the α-spectrin chain was profoundly ubiquitinated by E3 ubiquitin ligase and degraded by the 26S proteasome. E3 ubiquitin ligase activity was regulated by
P. falciparum
phosphatidylinositol 3-kinase (PfPI3K) signaling. Additionally, blocking the PfPI3K-ubiquitin-proteasome pathway in
P. falciparum
-infected red blood cells reduced parasite proliferation and infectivity. This study deepens our understanding of the regulatory mechanisms of host and malarial parasite interactions and paves the way for the exploration of novel antimalarial drugs.
Advanced genetic techniques in fungal pathogen research
Authors: Ross Robbi L. , Santiago-Tirado Felipe H.
Published: March 2024

Although fungi have been important model organisms for solving genetic, molecular, and ecological problems, recently, they are also becoming an important source of infectious disease. Despite their high medical burden, fungal pathogens are understudied, and relative to other pathogenic microbes, less is known about how their gene functions contribute to disease. This is due, in part, to a lack of powerful genetic tools to study these organisms. In turn, this has resulted in inappropriate treatments and diagnostics and poor disease management. There are a variety of reasons genetic studies were challenging in pathogenic fungi, but in recent years, most of them have been overcome or advances have been made to circumvent these barriers. In this minireview, we highlight how recent advances in genetic studies in fungal pathogens have resulted in the discovery of important biology and potential new antifungals and have created the tools to comprehensively study these important pathogens.
Formation of a constructed microbial community in a nutrient-rich environment indicates bacterial interspecific competition
Authors: Wang Jia , Appidi Manasa R. , Burdick Leah H. , Abraham Paul E. , Hettich Robert L. , Pelletier Dale A. , Doktycz Mitchel J.
Published: March 2024

Understanding the organizational principles of microbial communities is essential for interpreting ecosystem stability. Previous studies have investigated the formation of bacterial communities under nutrient-poor conditions or obligate relationships to observe cooperative interactions among different species. How microorganisms form stabilized communities in nutrient-rich environments, without obligate metabolic interdependency for growth, is still not fully disclosed. In this study, three bacterial strains isolated from the
Populus deltoides
rhizosphere were co-cultured in complex medium, and their growth behavior was tracked. These strains co-exist in mixed culture over serial transfer for multiple growth-dilution cycles. Competition is proposed as an emergent interaction relationship among the three bacteria based on their significantly decreased growth levels. The effects of different initial inoculum ratios, up to three orders of magnitude, on community structure were investigated, and the final compositions of the mixed communities with various starting composition indicate that community structure is not dependent on the initial inoculum ratio. Furthermore, the competitive relationships within the community were not altered by different initial inoculum ratios. The community structure was simulated by generalized Lotka-Volterra and dynamic flux balance analysis to provide mechanistic predictions into emergence of community structure under a nutrient-rich environment. Metaproteomic analyses provide support for the metabolite exchanges predicted by computational modeling and for highly altered physiologies when microbes are grown in co-culture. These findings broaden our understanding of bacterial community dynamics and metabolic diversity in higher-order interactions and could be significant in the management of rhizospheric bacterial communities.

IMPORTANCE

Bacteria naturally co-exist in multispecies consortia, and the ability to engineer such systems can be useful in biotechnology. Despite this, few studies have been performed to understand how bacteria form a stable community and interact with each other under nutrient-rich conditions. In this study, we investigated the effects of initial inoculum ratios on bacterial community structure using a complex medium and found that the initial inoculum ratio has no significant impact on resultant community structure or on interaction patterns between community members. The microbial population profiles were simulated using computational tools in order to understand intermicrobial relationships and to identify potential metabolic exchanges that occur during stabilization of the bacterial community. Studying microbial community assembly processes is essential for understanding fundamental ecological principles in microbial ecosystems and can be critical in predicting microbial community structure and function.
A method to correct for local alterations in DNA copy number that bias functional genomics assays applied to antibiotic-treated bacteria
Authors: Sullivan Geraldine J. , Barquist Lars , Cain Amy K.
Published: March 2024

Functional genomics techniques, such as transposon insertion sequencing and RNA-sequencing, are key to studying relative differences in bacterial mutant fitness or gene expression under selective conditions. However, certain stress conditions, mutations, or antibiotics can directly interfere with DNA synthesis, resulting in systematic changes in local DNA copy numbers along the chromosome. This can lead to artifacts in sequencing-based functional genomics data when comparing antibiotic treatment to an unstressed control. Further, relative differences in gene-wise read counts may result from alterations in chromosomal replication dynamics, rather than selection or direct gene regulation. We term this artifact “chromosomal location bias” and implement a principled statistical approach to correct it by calculating local normalization factors along the chromosome. These normalization factors are then directly incorporated into statistical analyses using standard RNA-sequencing analysis methods without modifying the read counts themselves, preserving important information about the mean-variance relationship in the data. We illustrate the utility of this approach by generating and analyzing a ciprofloxacin-treated transposon insertion sequencing data set in
Escherichia coli
as a case study. We show that ciprofloxacin treatment generates chromosomal location bias in the resulting data, and we further demonstrate that failing to correct for this bias leads to false predictions of mutant drug sensitivity as measured by minimum inhibitory concentrations. We have developed an R package and user-friendly graphical Shiny application, ChromoCorrect, that detects and corrects for chromosomal bias in read count data, enabling the application of functional genomics technologies to the study of antibiotic stress.

IMPORTANCE

Altered gene dosage due to changes in DNA replication has been observed under a variety of stresses with a variety of experimental techniques. However, the implications of changes in gene dosage for sequencing-based functional genomics assays are rarely considered. We present a statistically principled approach to correcting for the effect of changes in gene dosage, enabling testing for differences in the fitness effects or regulation of individual genes in the presence of confounding differences in DNA copy number. We show that failing to correct for these effects can lead to incorrect predictions of resistance phenotype when applying functional genomics assays to investigate antibiotic stress, and we provide a user-friendly application to detect and correct for changes in DNA copy number.
Recurrent inferior oblique myositis and its outcomes
Authors: Caltabiano Carmelo , Tong Jessica Y , Huang Sonia , Selva Dinesh
Published: March 2024

This report presents a unique case of recurrent idiopathic inferior oblique myositis (IOM) with a focus on clinico-radiological characteristics and histological features. A woman in her early 40s presented with a third episode of IOM following a 12-year period of quiescence. The first two episodes were characterised by unilateral IOM with rapid resolution following oral prednisone treatment. MRI revealed anterior focal enlargement of the left inferior oblique muscle with ipsilateral lacrimal gland enlargement. An inferior oblique muscle and lacrimal gland biopsy demonstrated significant inflammatory infiltrate. An intraorbital injection of triamcinolone acetonide was administered with complete resolution of symptoms within 1 week.
Change in pelvic incidence due to sacral stress fracture following multilevel instrumented fusion
Authors: Pozzi Pierrenzo , Morselli Carlotta , Cirullo Agostino , Bassani Roberto
Published: March 2024

Multilevel-instrumented fusion is a common surgical technique used to treat adult spinal deformity (ASD), but it can occasionally lead to rare complications such as sacral insufficiency fractures. The impact of sacral fractures on spinopelvic parameters, particularly pelvic incidence (PI), has not been thoroughly investigated even though they have been documented in the literature. Here, we present a case of a patient who underwent aTh11-sacrum instrumented fusionfor ASD. She underwent a revision surgery 18 months after the first procedure to treatproximal junctional painbrought on by a localised kyphosis of the rods. An asymptomatic sacral fracture was discovered during the radiological evaluation: the PI had increased from 71° to 103° between the 2 surgical procedures.
Pseudoparalysis in an infant with otitis media: an evolving presentation of scapular osteomyelitis
Authors: Butler Dominic , Moylett Edina
Published: March 2024

A female infant presented to an Irish hospital with a 4-day history of fever, irritability and reduced oral intake. Initial inflammatory markers were significantly elevated, an erythematous tympanic membrane was noted on examination and an initial diagnosis of acute otitis media was made. By the third hospital day, the infant was noted to be irritable when being lifted up; pseudoparalysis of the right upper limb was observed. A radiograph of the right shoulder was normal; MRI identified acute scapular osteomyelitis with subperiosteal abscess formation. The child underwent 3 washout procedures and received 6 weeks of antibiotic therapy, with full clinical recovery at 3 months. This case highlights the importance of remaining flexible in the context of an evolving presentation and recognising hallmarks of musculoskeletal infection, fever, localised pain and pseudoparalysis. Additionally, we review the literature to highlight clues in diagnosis, treatment and outcome for paediatric acute scapular osteomyelitis.
Spontaneous and asymptomatic rupture of an RCC with resolution of symptoms
Authors: Chaudhry Maaria , Botterbush Kathleen , Zhang Justin K , Coppens Jeroen
Published: March 2024

There is no standard of care for management of Rathke cleft cysts (RCCs), and protocol for spontaneous rupture or residual capsule fragments is not well documented.

Our case involves a Caucasian man in his 80s who presented with muscle weakness, fatigue, bitemporal hemianopia and pain. Further examination demonstrated decreased thyroid and cortisol levels. MRI revealed a 1.6×1.5×1.3 cm sellar homogenous mass with extension into the suprasellar cistern. While the size of the cyst was rather large, a decision was made to follow conservatively with serial MRI. At 3 years, the mass had spontaneously regressed. The patient was asymptomatic without imaging evidence of RCC recurrence at 4-year follow-up.

Classic indications for surgical intervention in suprasellar cysts were subtle in our patient and his advanced age made us take a conservative approach. Current data are lacking regarding management of RCCs presenting with endocrine dysfunction. Our case suggests that RCCs presenting with endocrine dysfunction may be managed conservatively with serial imaging-based monitoring.
Dry eye symptoms and health-related quality of life among Chinese individuals: a national-based study
Authors: Kai Jia-Yan , Wu Yi-Bo , Shi Bing , Li Dan-Lin , Dong Xing-Xuan , Wang Pei , Pan Chen-Wei
Published: March 2024

Aims

To assess the impact of dry eye symptoms (DESs) on health-related quality of life (HRQOL) among Chinese residents.

Methods

A total of 21 916 participants were involved in this nationwide cross-sectional study. All of them completed the Ocular Surface Disease Index-6 and the five-level European Quality of Life 5-Dimensional (EQ-5D) Questionnaire to assess the severity of DES and HRQOL, respectively. Multiple linear regression models were used to explore the associations of DES with EQ-5D health utility score (HUS) and visual analogue scale (VAS) score. We used logistic regression models to assess the relationships between DES and self-reported problems in the EQ-5D dimensions.

Results

Overall, 43.6% of participants reported DESs. Of them, 2511 (11.5%) were with mild symptoms, 2762 (12.6%) were with moderate symptoms and 4288 (19.6%) were with severe symptoms. Both EQ-5D HUS and VAS score were significantly negatively associated with the severity of DES. The difference in HUS between patients with no symptoms and severe symptoms (0.085) was larger than the minimally clinical important difference for EQ-5D. The loss in HRQOL was greater for patients with severe DES than those just with other comorbidities. Participants with DES had a significantly higher risk of reporting problems in all five EQ-5D dimensions, especially in pain/discomfort and anxiety/depression for patients with mild or moderate symptoms and in mobility, self-care and usual activities for severe patients.

Conclusion

Patients with more severe DES tend to have lower HRQOL. Effective interventions targeted at different HRQOL dimensions should be taken according to the severity of DES.
Landscape of pharmacogenetic variants associated with non-insulin antidiabetic drugs in the Indian population
Authors: Sivadas Ambily , Sahana S , Jolly Bani , Bhoyar Rahul C , Jain Abhinav , Sharma Disha , Imran Mohamed , Senthivel Vigneshwar , Divakar Mohit Kumar , Mishra Anushree , Mukhopadhyay Arpita , Gibson Greg , Narayan KM Venkat , Sivasubbu Sridhar , Scaria Vinod , Kurpad Anura V
Published: March 2024

Introduction

Genetic variants contribute to differential responses to non-insulin antidiabetic drugs (NIADs), and consequently to variable plasma glucose control. Optimal control of plasma glucose is paramount to minimizing type 2 diabetes-related long-term complications. India’s distinct genetic architecture and its exploding burden of type 2 diabetes warrants a population-specific survey of NIAD-associated pharmacogenetic (PGx) variants. The recent availability of large-scale whole genomes from the Indian population provides a unique opportunity to generate a population-specific map of NIAD-associated PGx variants.

Research design and methods

We mined 1029 Indian whole genomes for PGx variants, drug–drug interaction (DDI) and drug–drug–gene interactions (DDGI) associated with 44 NIADs. Population-wise allele frequencies were estimated and compared using Fisher’s exact test.

Results

Overall, we found 76 known and 52 predicted deleterious common PGx variants associated with response to type 2 diabetes therapy among Indians. We report remarkable interethnic differences in the relative cumulative counts of decreased and increased response-associated alleles across NIAD classes. Indians and South Asians showed a significant excess of decreased metformin response-associated alleles compared with other global populations. Network analysis of shared PGx genes predicts high DDI risk during coadministration of NIADs with other metabolic disease drugs. We also predict an increased CYP2C19-mediated DDGI risk for CYP3A4/3A5-metabolized NIADs, saxagliptin, linagliptin and glyburide when coadministered with proton-pump inhibitors (PPIs).

Conclusions

Indians and South Asians have a distinct PGx profile for antidiabetes drugs, marked by an excess of poor treatment response-associated alleles for various NIAD classes. This suggests the possibility of a population-specific reduced drug response in atleast some NIADs. In addition, our findings provide an actionable resource for accelerating future diabetes PGx studies in Indians and South Asians and reconsidering NIAD dosing guidelines to ensure maximum efficacy and safety in the population.
Role of perirenal adiposity in renal dysfunction among CKD individuals with or without diabetes: a Japanese cross-sectional study
Authors: Kono Teruyuki , Maimaituxun Gulinu , Tanabe Hayato , Higa Moritake , Saito Haruka , Tanaka Kenichi , Masuzaki Hiroaki , Sata Masataka , Kazama Junichiro J. , Shimabukuro Michio
Published: March 2024

Introduction

It remains unclear whether increased perirenal fat (PRF) accumulation is equally related to renal involvement in patients with and without diabetes mellitus (DM). We evaluated the association between PRF volume (PRFV) and low glomerular filtration rate (GFR) and proteinuria in people with or without type 2 diabetes mellitus (T2DM).

Research design and methods

We performed a cross-sectional analysis of 473 individuals without T2DM (non-DM, n=202) and with T2DM (DM, n=271). PRFV (cm3), obtained from non-contrast CT, was indexed as PRF index (PRFV/body surface area, cm3/m2). Multivariate-adjusted models were used to determine the ORs of PRFV and PRFV index for detecting estimated GFR (eGFR) decrease of <60 mL/min/1.73 m2proteinuria onset, or both.

Results

Although body mass index (BMI), visceral fat area, and waist circumference were comparable between the non-DM and DM groups, kidney volume, PRFV, and PRFV index were higher in individuals with T2DM than in those without T2DM. In the multivariate analysis, after adjusting for age, sex, BMI, hypertension, smoking history, and visceral fat area ≥100 cm2, the cut-off values of PRFV index were associated with an eGFR<60 in individuals with DM (OR 6.01, 95% CI 2.20 to 16.4, p<0.001) but not in those without DM.

Conclusions

PRFV is associated with low eGFR in patients with T2DM but not in those without T2DM. This suggests that PRF accumulation is more closely related to the onset and progression of diabetic kidney disease (DKD) than non-DKD. Clarifying the mechanisms through which PRF influences DKD development could pave the way for novel prevention and treatment strategies.
Quantifying the time-varying association between objectively measured physical activity and mortality in US older adults over a 12-year follow-up period: the NHANES 2003–2006 study
Authors: Agarwala Neha , Zipunnikov Vadim , Crainiceanu Ciprian , Leroux Andrew
Published: March 2024

Objectively measuring physical activity (PA) has consistently shown an association with reduced all-cause mortality risk in cross-sectional studies. However, the strength of this association may change over time. We quantify the time-varying, covariate-adjusted association between the total volume of PA and all-cause mortality over a 12-year follow-up period using Cox regression with a time varying effect of population-referenced quantile total activity count adjusted for traditional risk factors. Analyses focus on participants 50–84 years old with adequate accelerometer wear time and without missing covariates. The findings suggest that (1) the use of baseline PA in Cox models with long follow-up periods may be inappropriate without time-varying effects and (2) the use of accelerometry derived volume of PA in risk score calculations may be most appropriate for short-term to medium-term risk scores.