bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo
efficacy of pitavastatin combined with itraconazole against
Aspergillus fumigatus
in silkworm models
Authors: Majima Hidetaka , Arai Teppei , Kamei Katsuhiko , Watanabe Akira 
Published: September 2023

ABSTRACT

Azole resistance in
Aspergillus fumigatus
is a worldwide concern and new antifungal drugs are required to overcome this problem. Statin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, has been reported to suppress the growth of
A. fumigatus
, but little is known about its
in vivo
antifungal effect against
A. fumigatus
. In this study, we evaluated the
in vivo
efficacy of pitavastatin (PIT) combined with itraconazole (ITC) against azole-susceptible and azole-resistant strains with silkworm models. Prolongation of survival was confirmed in the combination-therapy (PIT and ITC) group compared to the no-treatment group in both azole-susceptible and azole-resistant strain models. Furthermore, when the azole-susceptible strain was used, the combination-therapy resulted in a higher survival rate than with ITC alone. Histopathological analysis of the silkworms revealed a reduction of the hyphal amount in both azole-susceptible and azole-resistant strain models. Quantitative evaluation of fungal DNA by qPCR in azole-susceptible strain models clarified the reduction of fungal burden in the combination-therapy group compared with the no-treatment group and ITC-alone group. These results indicate that the efficacy of PIT was enhanced when combined with ITC
in vivo
. As opposed to most statins, PIT has little drug–drug interaction with azoles in humans and can be used safely with ITC. This combination therapy may be a promising option as an effective treatment in clinical settings in the future.

IMPORTANCE

Azole resistance among
A. fumigatus
isolates has recently been increasingly recognized as a cause of treatment failure, and alternative antifungal therapies are required to overcome this problem. Our study shows the
in vivo
efficacy of PIT combined with ITC against
A. fumigatus
using silkworm models by several methods including evaluation of survival rates, histopathological analysis, and assessment of fungal burden. Contrary to most statins, PIT can be safely administered with azoles because of less drug–drug interactions, so this study should help us to verify how to make use of the drug in clinical settings in the future.
The GGDEF protein Dgc2 suppresses both motility and biofilm formation in the filamentous cyanobacterium
Leptolyngbya boryana
Authors: Toida Kazuma , Kushida Wakana , Yamamoto Hiroki , Yamamoto Kyoka , Ishii Kaichi , Uesaka Kazuma , Kanaly Robert A. , Kutsuna Shinsuke , Ihara Kunio , Fujita Yuichi , Iwasaki Hideo 
Published: September 2023

ABSTRACT

Colony pattern formations of bacteria with motility manifest complicated morphological self-organization phenomena.
Leptolyngbya boryana
is a filamentous cyanobacterium, which has been used as a genetic model organism for studying metabolism including photosynthesis and nitrogen fixation. A widely used type strain [wild type (WT) in this article] of this species has not been reported to show any motile activity. However, we isolated a spontaneous mutant strain that shows active motility (gliding activity) to give rise to complicated colony patterns, including comet-like wandering clusters and disk-like rotating vortices on solid media. Whole-genome resequencing identified multiple mutations in the genome of the mutant strain. We confirmed that inactivation of the candidate gene
dgc2
(
LBDG_02920
) in the WT background was sufficient to give rise to motility and morphologically complex colony patterns. This gene encodes a protein containing the GGDEF motif which is conserved at the catalytic domain of diguanylate cyclase (DGC). Although DGC has been reported to be involved in biofilm formation, the
dgc2
mutant significantly facilitated biofilm formation, suggesting a role for the
dgc2
gene in suppressing both gliding motility and biofilm formation. Thus,
Leptolyngbya
is expected to be an excellent genetic model for studying dynamic colony pattern formation and to provide novel insights into the role of DGC family genes in biofilm formation.

IMPORTANCE

Self-propelled bacteria often exhibit complex collective behaviors, such as formation of dense-moving clusters, which are exemplified by wandering comet-like and rotating disk-like colonies; however, the molecular details of how these structures are formed are scant. We found that a strain of the filamentous cyanobacterium
Leptolyngbya
deficient in the GGDEF protein gene
dgc2
elicits motility and complex and dynamic colony pattern formation, including comet-like and disk-like clusters. Although c-di-GMP has been reported to activate biofilm formation in some bacterial species, disruption of
dgc2
unexpectedly enhanced it, suggesting a novel role for this GGDEF protein for inhibiting both colony pattern formation and biofilm formation.
Barriers to childhood asthma care in sub-Saharan Africa: a multicountry qualitative study with children and their caregivers
Authors: Naidoo Kimesh Loganathan , Dladla Sindisiwe , Mphahlele Reratilwe Ephenia , Mosler Gioia , Muyemayema Sophie , Ssemata Andrew Sentoogo , Mkutumula Elizabeth , Adeyeye Olayinka Olufunke , Moyo Melinda , Goodman Olayinka , Kuyinu Yetunde , Nantanda Rebecca , Ticklay Ismail , Mujuru Hilda Angela , Grigg Jonathan , Masekela Refiloe 
Published: September 2023

ObjectivesThis study identifies barriers and provides recommendations to improve asthma care in children across sub-Saharan Africa, where qualitative data is lacking despite high rates.DesignOne of the aims of our National Institute for Health Research global health research group ‘Achieving Control of Asthma in Children in Africa’ was to use qualitative thematic analysis of transcribed audio recordings from focus group discussions (FGDs) to describe barriers to achieving good asthma control.SettingSchools in Blantyre (Malawi), Lagos (Nigeria), Durban (South Africa), Kampala (Uganda) and Harare (Zimbabwe).ParticipantsChildren (n=136), 12–14 years with either asthma symptoms or a diagnosis and their caregivers participated in 39 FGDs. All were recruited using asthma control questions from the Global Asthma Network survey.ResultsThere were four key themes identified: (1) Poor understanding, (2) difficulties experienced with being diagnosed, (3) challenges with caring for children experiencing an acute asthma episode and (4) suboptimal uptake and use of prescribed medicines. An inadequate understanding of environmental triggers, a hesitancy in using metred dose inhalers and a preference for oral and alternate medications were identified as barriers. In addition, limited access to healthcare with delays in diagnosis and an inability to cope with expected lifestyle changes was reported. Based on these findings, we recommend tailored education to promote access to and acceptance of metred dose inhalers, including advocating for access to a single therapeutic, preventative and treatment option. Furthermore, healthcare systems should have simpler diagnostic pathways and easier emergency access for asthma.ConclusionsIn a continent with rapidly increasing levels of poorly controlled asthma, we identified multiple barriers to achieving good asthma control along the trajectory of care. Exploration of these barriers reveals several generalisable recommendations that should modify asthma care plans and potentially transform asthma care in Africa.Trial registration number269211.
Year-to-year trajectories of hospital utilisation rates among patients with COPD: a real-world, single-centre, retrospective cohort study
Authors: Yii Anthony , Xu Xiaomeng , Loh Chee Hong , Bahety Priti , Navarro Rojas Aldo Amador , Milea Dominique , Tee Augustine 
Published: September 2023

ObjectivesThe long-term clinical trajectory of chronic obstructive pulmonary disease (COPD) in terms of year-to-year hospital utilisation rates can be highly variable and is not well studied. We investigated year-to-year trends of hospitalisation or emergency department (ED) visits among patients with COPD over 3 years, identified distinct trajectories and examined associated predictive factors.DesignA retrospective cohort study.SettingData were extracted from the Changi General Hospital, Singapore COPD data warehouse.ParticipantsPatients with COPD aged ≥40 years with 3 years of follow-up data.Primary and secondary outcome measuresThe yearly rates of hospitalisations or ED visits, stratified by COPD-related or all-cause, were described. Group-based trajectory modelling was used to identify clinically distinct trajectories year-by-year. Baseline predictive factors associated with different trajectories were examined.ResultsIn total, 396 patients were analysed (median age 70 years; 87% male). Four trajectories were generated for year-to-year trends in COPD-related hospitalisations/ED visits (C1–C4: consistently frequent, consistently infrequent, improving and worsening); post-bronchodilator forced expiratory volume in 1 second (FEV1) was a significant predictor of trajectory, with worse lung function being the main factor associated with less favourable trajectories. For all-cause hospitalisations/ED visits, four trajectories were identified (A1–A4: infrequent and stable, frequent and stable, frequent and decreasing, frequent and increasing); significant differences in age (p=0.041), sex (p=0.016) and ethnicity (p=0.005) were found between trajectories. Higher overall comorbidity burden was a key determinant in less favourable trajectories of all-cause hospitalisations/ED visits.ConclusionsDistinct trajectories were demonstrated for hospitalisations/ED visits related to COPD or all causes, with predictive associations between FEV1and COPD trajectory and between comorbidities and all-cause trajectory. Trajectories carry nuanced prognostic information and may be useful for clinical risk stratification to identify high-risk individuals for preventative treatments.
Acute respiratory distress syndrome: potential of therapeutic interventions effective in treating progression from COVID-19 to treat progression from other illnesses—a systematic review
Authors: Ragel Emma J , Harris Lynda K , Campbell Richard A 
Published: September 2023

BackgroundAcute respiratory distress syndrome (ARDS) is the most severe form of lung injury, rendering gaseous exchange insufficient, leading to respiratory failure. Despite over 50 years of research on the treatment of ARDS when developed from illnesses such as sepsis and pneumonia, mortality remains high, and no robust pharmacological treatments exist. The progression of SARS-CoV-2 infections to ARDS during the recent global pandemic led to a surge in the number of clinical trials on the condition. Understandably, this explosion in new research focused on COVID-19 ARDS (CARDS) rather than ARDS when developed from other illnesses, yet differences in pathology between the two conditions mean that optimal treatment for them may be distinct.AimThe aim of the present work is to assess whether new therapeutic interventions that have been developed for the treatment of CARDS may also hold strong potential in the treatment of ARDS when developed from other illnesses. The study objectives are achieved through a systematic review of clinical trials.ResultsThe COVID-19 pandemic led to the identification of various therapeutic interventions for CARDS, some but not all of which are optimal for the management of ARDS. Interventions more suited to CARDS pathology include antithrombotics and biologic agents, such as cytokine inhibitors. Cell-based therapies, on the other hand, show promise in the treatment of both conditions, attributed to their broad mechanisms of action and the overlap in the clinical manifestations of the conditions. A shift towards personalised treatments for both CARDS and ARDS, as reflected through the increasing use of biologics, is also evident.ConclusionsAs ongoing CARDS clinical trials progress, their findings are likely to have important implications that alter the management of ARDS in patients that develop the condition from illnesses other than COVID-19 in the future.
Economic insecurity exposure and cognitive function in late life
Authors: Luo Yanan , Xu Ming , Liang Richard 
Published: September 2023

ObjectivesThis study took the State-owned Enterprises (SOE) reform from 1996 to 2002 in China as a natural experiment to explore the consequences of economic insecurity exposure during early-adulthood and mid-adulthood on cognitive function in later life.MethodsData were obtained from the China Health and Retirement Longitudinal Survey (CHARLS), 2014 and 2015. CHARLS is a nationally representative survey covering 28 provinces in China. A total of 4536 urban dwellers born earlier than 1971 (aged 25 years old and above at the start of the SOE reform in 1996) were included in our analyses. Using province-year-level economic loss from the layoffs, we examined the impact of economic insecurity exposure on the cognitive function score by using a difference-in-differences model with 1996–2002 as the cut-off.ResultsIndividuals exposed to economic insecurity have significantly decreased cognitive function, in which a 1% point increase in expected economic loss would decrease the cognitive function score by 0.09 (95% CI: −0.17 to –0.01). Given that the average intensity of expected economic loss was 11.59% and the mean score of cognitive function was 21.26, exposure to the SOE reforms led to an average decrease in the cognitive function score by at least 4.91%.ConclusionsProviding cognitive health surveillance and psychological counselling may be important for preventing cognitive decline among those experiencing economic insecurity.
Assessment of twin tunnelling induced settlement and load transfer mechanism of a single pile in dry sand
Authors: Lu Hu , Shi Jiangwei , Shi Chao , Pei Weiwei , Chen Shaoming 
Published: September 2023

This study conducted both three-dimensional physical model tests and numerical back-analyses to examine the performance of a single pile subjected to twin tunnelling beneath the pile toe in dry sand. Moreover, numerical parametric analyses were carried out to assess the impact of working load level and tunnel volume loss on pile behaviour. The findings revealed that the first tunnelling induced a 1.9% dp (pile diameter) settlement in the pile when the pile toe was 0.5 D (tunnel diameter) above the twin tunnels, which had a 1.0% volume loss. The settlement was accompanied by an upward load transfer mechanism. The second tunnelling had a reduced impact and induced only 76% of the settlement caused by the first tunnelling. The study also showed that tunnelling-induced shearing behaviours weakened beneath the pile toe with a decrease in working load, resulting in reduced pile head settlement. Moreover, the computed pile settlement increased by 178% when the tunnel volume loss increased from 0.5% to 2%. The findings of this study offer valuable data for the validation and calibration of numerical models. In addition, the outcome from this study provides useful insights into the prediction of the pile-soil-tunnel interaction when subjected to twin tunnelling.
Revisiting canonical quantization of radiation: the role of the vacuum field
Authors: Cetto A. M. , de la Peña L. , Pérez-Barragán J. F. 
Published: September 2023

AbstractCanonical quantization has conventionally been adopted as a necessary procedure for the description of the quantum radiation field by analogy between quantum-mechanical oscillators and field oscillators. In this paper we provide the physical basis for the formal quantization of the radiation field interacting with matter in the presence of the vacuum field, taken here as a solution of classical Maxwell equations. Just as the canonical particle operators $$\hat{x}$$

x
^

, $$\hat{p}$$

p
^

have been shown to be the response functions of the particle to this field, here we derive the creation and annihilation operators $$\hat{a}^{\dagger }$$

a
^

†

, $$\hat{a}$$

a
^

, with $$[\hat{a},\hat{a}^{\dagger }]=1$$

[

a
^

,

a
^

†

]
=
1

, as an expression of the field’s response to this interaction. The results obtained shed new light on the physical meaning of the description of light in terms of operators and suggest that neither matter nor radiation are quantized in isolation.
An overview of the eruption of La Soufrière Volcano, St Vincent 2020–21
Authors: Robertson Richard E. A. , Barclay Jenni , Joseph E. P. , Sparks R. S. J. 
Published: September 2023

Abstract
This paper provides an overview of the eruption of La Soufrière Volcano on the island of St Vincent which occurred between 27 December 2020 and 22 April 2022. It sets the stage for the 17 papers included in this Special Publication that showcase the initial scientific findings arising from analysis of the crisis. Here we present a chronology of the eruption and discuss the key findings from these papers while underscoring the areas for which further research is needed.
The detailed account of the eruption offers several lessons for volcanic crisis management and provides insights into the most effective communication process through this type of crisis. It highlights the need for and benefits of planning and preparedness activities prior to an eruption as well as of long-term engagement with disaster management officials and at-risk communities. The value of partnerships both within the island and with external collaborators was shown to be critical as was the use of a multiparametric dataset to assess the course of the eruption. We contend that the papers contained in this publication provide key insights into the mechanisms by which volcanic eruptions can impact populations at risk. The suite of analyses and data have generated a canonical dataset that can provide the framework for new advances in understanding the causes and consequences of varying eruptions worldwide.
Structural Basis of PML-RARA Oncoprotein Targeting by Arsenic Unravels a Cysteine Rheostat Controlling PML Body Assembly and Function
Authors: Bercier Pierre , Wang Qian Qian , Zang Ning , Zhang Jie , Yang Chang , Maimaitiyiming Yasen , Abou-Ghali Majdouline , Berthier Caroline , Wu Chengchen , Niwa-Kawakita Michiko , Dirami Thassadite , Geoffroy Marie-Claude , Ferhi Omar , Quentin Samuel , Benhenda Shirine , Ogra Yasumitsu , Gueroui Zoher , Zhou Chun , Naranmandura Hua , de Thé Hugues , Lallemand-Breitenbach Valérie 
Published: September 2023

Abstract

PML nuclear bodies (NB) are disrupted in PML-RARA–driven acute promyelocytic leukemia (APL). Arsenic trioxide (ATO) cures 70% of patients with APL, driving PML-RARA degradation and NB reformation. In non-APL cells, arsenic binding onto PML also amplifies NB formation. Yet, the actual molecular mechanism(s) involved remain(s) elusive. Here, we establish that PML NBs display some features of liquid–liquid phase separation and that ATO induces a gel-like transition. PML B-box-2 structure reveals an alpha helix driving B2 trimerization and positioning a cysteine trio to form an ideal arsenic-binding pocket. Altering either of the latter impedes ATO-driven NB assembly, PML sumoylation, and PML-RARA degradation, mechanistically explaining clinical ATO resistance. This B2 trimer and the C213 trio create an oxidation-sensitive rheostat that controls PML NB assembly dynamics and downstream signaling in both basal state and during stress response. These findings identify the structural basis for arsenic targeting of PML that could pave the way to novel cancer drugs.

Significance:
Arsenic curative effects in APL rely on PML targeting. We report a PML B-box-2 structure that drives trimer assembly, positioning a cysteine trio to form an arsenic-binding pocket, which is disrupted in resistant patients. Identification of this ROS-sensitive triad controlling PML dynamics and functions could yield novel drugs.
See related commentary by Salomoni, p. 2505.
This article is featured in Selected Articles from This Issue, p. 2489
Meta-Analysis: Triggering Factors of Atopic Dermatitis in Children
Authors: Eka Sari Luthfiana , Haq Arini , Rakhmawati Yustian 
Published: September 2023

Background: Atopic dermatitis is a non-communicable skin disorder characterized by intense itching. It is relapsing, recurring, and can have a negative impact on the quality of life of patients and their family members. Atopic dermatitis occurs most often in early infancy and childhood. Atopic dermatitis can occur if there is dysregulation of IgE resulting in a breakdown of the epidermal barrier. There are several factors that trigger the occurrence of atopic rheumatism in children, which can come from environmental factors or medical history.
Aim: For this reason, this study aims to analyze the similarity of output regarding the magnitude of risk factors for atopic dermatitis in children.
Methods: This study was analyzed using a meta-analysis using PRISMA, where there were 7 of 8654 articles that met the criteria for analysis. Meanwhile, the data presentation was carried out using a forest plot with a random effect statistical model.
Results: The presence of pets, children living in environments that have pets (cats or dogs) are known to increase the risk of atopic dermatitis by 5 times compared to children living in environments that do not have animals. pet. The health history factor seen from exclusive breastfeeding, where babies who are exclusively breastfed are significantly less likely to experience atopic dermatitis by 12.5 times compared to babies who are not exclusively breastfed.
Conclusion: Not giving exclusive breastfeeding and pets affect atopic dermatitis in children (p<0,05).
The Correlation between Nutritional Status and Clinical Outcome of Liver Sirosis Patients at RSUD Dr. Saiful Anwar Malang
Authors: Supriono Supriono , Dianita Mayasari Ema 
Published: September 2023

Introduction: Nutritional status is often associated with mortality and disease morbidity, including liver cirrhosis. Assessment of Tricep Skin Fold (TSF) and mid-arm muscle circumference (MAMC) is an easy parameter of nutritional status.
Objective: This study aims to determine the relationship between nutritional status and clinical outcomes in patients with liver cirrhosis.
Methods: The study used a retrospective cohort observational design with a sample of 57 patients with liver cirrhosis with various etiologies. The data comes from the results of anthropometric measurements of patients in the poly or inpatient ward and interviews regarding the history of the disease and complications experienced during the last month. Data analysis used the Chi-square test with a 95% Confidence Interval (CI), p < 0.05, to analyze the relationship between nutritional status (TSF and MAMC) with clinical outcomes of liver cirrhosis (hematemesis melena, degree of esophageal varices grade Hepatic encephalopathy (HE) and degree of ascites).
Results: Based on the TSF and MAMC values, data on cirrhotic patients who experienced nutritional status with the “low” criteria were 33.3% and 57.89%, respectively. The 'low” TSF value significantly correlates with the HE incidence (p = 0.049) with the RR value of 0.461. The relationship between MAMC and the incidence of ascites was statistically significant (0.004), with an RR value of 0.462.
Conclusion: Nutritional status affects the incidence of HE and ascites in liver cirrhosis patients