bluuebunny/crossref_metadata_2025 huggingface dataset:
S3.5a Contamination in sand and water of sea, lakes, and river beaches: Risk factor for fungal human disease
Authors: Segal Esther
Published: September 2022

S3.5 Environmental exposure - risk for human fungal disease, September 21, 2022, 4:45 PM - 6:15 PM

Marine and freshwater bodies, such as rivers and lakes are known as possible niches harboring microbes that may affect human health.

 

These ecosystems have been extensively researched, and even regulated, for the presence of bacterial contamination.

 

Fungal contamination has been less researched and lacks regulation, notwithstanding the recent finding that the antifungal resistant yeast species Candida auris has been isolated from a marine ecosystem.

 

The present lecture will focus on a recent collaborative study, involving 13 countries, spanning from the Atlantic to the Eastern Mediterranean coasts, and including the Italian lakes and the Adriatic, Baltic, and Black Seas. The study explored fungal contamination of sand and water of the sea, lakes, and river beaches in 91 bathing sites, and water of 67 of these.

 

This study considered several fungal parameters: all fungi, several species of the genus Aspergillus and Candida, plus other yeasts, allergenic fungi, Dematiaceous fungi, and dermatophytes. The study took in account four variables that might influence the results of the analytical parameters, such as: (1) coast or inland location, (2) urban and non-urban sites, (3) period of the year, and (4) geographical proximity and type of sediment.

 

A site-blind median was found to be 89 Colony-Forming Units (CFU) of fungi per gram of sand in coastal and inland freshwaters, with variability between 0 and 6400 CFU/g. For freshwater sites, that number was 201.7 CFU/g [0, 6400 CFU/g (P = .01) and for coastal sites was 76.7 CFU/g (0, 3497.5 CFU/g)]. For coastal waters and all waters, the median was 0 CFU/ml (0, 1592 CFU/ml), and for freshwaters 6.7 (0, 310.0) CFU/ml (P <.001). The fungal load in water has to be further corroborated in additional ongoing studies.

Some of these will be presented herewith.

 

The lecture will also include, as an example, the data collected at the Israeli Mediterranean coast. This study included a screen of sand and water of six urban beaches, from north to south of the Israeli Mediterranean Coast. Sand samples were extracted by water, and the water wash was cultured and quantitated. Water samples were quantitated as well. The fungi were identified phenotypically, by MALDI-TOF MS system and ITS sequencing. The screen revealed that about 80% of the isolates were molds and about 20% yeasts. The mold species included opportunistic pathogens and potential allergens: Aspergillus fumigatus, Fusarium, Penicillium, and Mucorales species. Yeast isolates included Candida, Cryptococcus and Rhodotorula species. The collaborative study and the example study confirmed the relevance of all variables for some of the fungal parameters. The results suggest that beaches should be monitored for fungi for safer use and better management, and for the benefit of public health.
S5.3b Fungal spores: Initiators of colonization and infection
Authors: Baltussen Tim , Brule Tom van den , Dijksterhuis Jan
Published: September 2022

S5.3 Cellular pleomorphism and fungal virulence, September 22, 2022, 3:00 PM - 4:30 PM

Fungi produce asexual and sexual spores for reproduction and distribution, which can be both in space and time. Distribution in space occurs, by air movement, but also, by water or other vectors such as living organisms. Filamentous fungi from the division Ascomycota that belong to the order Eurotiales produce asexual spores called conidia. Conidia are moderately stress-tolerant cells and are able to survive unfavorable conditions such as thermal stress, dehydration, osmotic pressure, oxidative stress, variations in pH, and UV. For example, conidia of the fungus Penicillium chrysogenum are isolated worldwide and must be regarded as cosmopolitan. In many cases, conidia might ‘land’ closely to the location of production, but still many spores making into the higher air layers. There is indirect evidence that spores may be able to travel large distances through the air. For example, Aspergillus sydowii conidia have been suggested to travel over thousands of kilometers from the Sahara Desert to the Caribbean reefs.

 

Distribution in time is occurring as stress-resistant cells remain dormant at one location for an extended period, awaiting conditions that are more favorable for growth. Some ascospores (sexual spores) are extremely stress-resistant and dormant for very long periods. Other species show extended dormancy in a dried state. As microbial species are inherently variable, stress resistance varies between strains from the same species. For example, conidial heat resistance (D60) of various strains of the fungus Paecilomyces variotii ranged between 3.5 to 27.6 min. This intraspecific variation could have profound consequences on diagnostics, virulence, and antifungal treatment in clinical settings.

 

For conidial germination in most filamentous fungi, the presence of nutrients such as inorganic salts, sugars, and amino acids is required. The swelling phase of conidia is also called isotropic growth. Swollen conidia direct the growth to one side of the cell to grow in a polarized fashion, which leads to the formation of a germ tube (polarized growth). There is a notable drop in stress resistance during isotropic and polarized growth and genes expressed during these stages might represent novel targets for fungal infection.
S5.3d How mitochondrial complex I proteins in Candida albicans moderate phagocytosis and the production of pro-inflammatory cytokines in murine macrophages and dendritic cells
Authors: She Xiaodong , Zhang Pengyi , Calderone Richard , Liu Weida , Li Dongmei
Published: September 2022

S5.3 Cellular pleomorphism and fungal virulence, September 22, 2022, 3:00 PM - 4:30 PM

 

Objectives

Inhibition of respiration in Candida albicans impairs its colonization in the host tissues and causes avirulence in a murine vascular candidiasis model. Accordingly, blockage of the mitochondrial electron transport chain (ETC) of C. albicans by respiratory inhibitors promotes phagocytosis by increasing exposure of glucan which could be due to the mannan reduction. In our model, we have reported that 85% mannan reduction in goa1Δ, a deletion mutant of an ETC Complex I (CI) regulator, oppositely decreased phagocytosis. To understand such a difference, we broaden our investigation with three CI respiratory subunit mutants, which are either fungal-specific (nuo1Δ and nuo2Δ) or broadly conserved subunits (ndh51Δ) for cell wall analysis and innate immune responses.

Methods

We characterized mutant cell wall defects in these mutants, then analyzed their respective survival in macrophages. Fungal internalization into macrophages was visualized under fluorescent microscopy and live-cell imaging and analyzed through flow cytometry analysis. Cytokine production in dendritic cells (DCs) infected by fungal cells was measured by xMAP technology and the transcriptional profiles of murine macrophages-infected by different mutants were compared.

Results

We find that phosphopeptidomannan (PPM) reduction in goa1Δ and nuo1Δ and phospholipomannan (PLM) reduction in nuo2Δ correlate with massive inhibition of cytokine. PPM loss in nuo1Δ or goa1Δ fails to promote phagocytosis but promotes opsonized neutrophil killing. The cause of PPM insufficiency results from reduced phosphorylation of the Cek1 MAPK in goa1Δ and nuo1Δ. In contrast other three mutants, phagocytosis and cytokine production of ndh51Δ more resemble WT cells, which have shown an ∼ 30% glucan reduction due to a defective Mek1 MAPK response. The divergent immune responses to these CI mutants are shown at the transcriptional level in infected macrophages. We noted that those well-characterized host receptors such as dectins and TLR2/4 for PPM, PLM, and glucan ligands are not significantly affected at 1 h post-infection. However, the scavenger receptor CD36, integrin ICAM, and growth factor receptors are downregulated along with a generally downregulated endocytosis and antigen processing/presentation. In addition, the host metabolic processes, oxidative stress-induced senescence, apoptosis, and signaling pathways such as Ras1/Erk5, the cAMP/CREB, and TLR9 pathway, are each individually affected in the host cells.

Conclusion

We speculate that mitochondrial signals of fungal origin may also be sensed by the host immune cells to coordinate the immune responses together with cell replication and metabolism during the early stage of infection.
S5.4a Cutaneous manifestations of deep fungal infections: Aretrospective study from one tertiary hospital
Authors: Chen Peiran , Zhou Xin , Liu Wentao , Wu Angela , Feng Peiying
Published: September 2022

S5.4 Free oral paper session, September 22, 2022, 3:00 PM - 4:30 PM

 

Objectives

Analysis of the cutaneous manifestations in patients with deep fungal infections to provide a basis for clinical differentiation and diagnosis.

Method

Patients who presented to our hospital from 2016 to 2021, were definitively diagnosed with deep fungal infections by histopathology and mycological detection. Isolates of focal infections were cultured in vitro on SDA or MEA media for 14 days and the species were identified by morphological or molecular analysis. Relevant clinical data on epidemiologic, skin manifestations, underlying disease, causative fungal agent, treatment, and outcomes are collected and analyzed.

Results

A total of 15 patients were diagnosed with deep fungal infections. The respiratory system (7/15) was the most easily involved primary focus of deep fungal infection, digestive system (3/15), and nervous system (2/15) were less common. The mean age of the patients was 50.30 years. Of these, 8 were males. More than half of the cases (7/15) were presented in immunosuppressed patients, including long-term glucocorticoid use, organ transplantation, tuberculosis infection, and malignancy. Skin manifestations were varied, with plaques (5/15) being the most common type of lesion, and then papules (4/15), nodules (2/15), patches (2/15), and ulcers (2/15). Candida spp. (9/15) was the most common pathogens, followed by Talaromyces marneffei (2/15) (Fig. 1a), Cryptococcus spp. (2/15) (Fig. 1b), and Aspergillus spp. (2/15). One case had co-infection with C. albicans and Aspergillus spp.

Conclusions

Patients with deep fungal infections are often accompanied by skin manifestations, which vary between patients with deep fungal infections caused by different pathogenic fungi.
S5.4d Agrochemicals potentiate multidrug resistance and alter virulence in Cryptococcus neoformans via hitch-hiking effect of aneuploidy
Authors: Sun Liuliu , Cao Yong-bing , Yan Tian-hua , Jiang Yuan-ying , Yang Feng
Published: September 2022

S5.4 Free oral paper session, September 22, 2022, 3:00 PM - 4:30 PM

 

Objectives

Cryptococcus neoformans is an environmental fungal pathogen causing fatal pulmonary and disseminated infections in humans, especially in AIDS patients. However, only three antifungal drugs are available for the treatment of cryptococcosis: fluconazole, amphotericin B, and flucytosine. C. neoformans is worldwide distributed in nature, but environmental factors influencing antifungal drug susceptibility are largely unknown.

Methods

We tested the antifungal effect of agrochemicals against C. neoformans lab strain H99. We obtained drug-resistant adaptors. We sequenced the adaptors and got a list of adaptors bearing unique aneuploidy. We asked if aneuploidy caused multidrug resistance to antifungal drugs and if aneuploidy altered virulence in vitro and in vivo. We also investigated the molecular mechanism of aneuploidy-mediated multidrug resistance.

Results

Here we found tebuconazole and benomyl, belonging to two distinct classes of agrochemicals, could inhibit the growth of H99. However, H99 could gain resistance to both drugs mainly via aneuploidy. Importantly, particular aneuploidy also caused multidrug resistance to fluconazole, amphotericin B, and flucytosine. Furthermore, aneuploidy also altered virulence in vitro and in vivo. We found copy number variation of genes on the aneuploid chromosome caused a proportional increase in transcript and protein levels.

Conclusion

Therefore, we posit agrochemicals could enhance multidrug resistance and alter the virulence of C. neoformans via the hitch-hiking effect of aneuploidy.
S6.1d First case report of pediatric blood stream infection by Candida magnoliae in a known case of B cell ALL post -induction chemotherapy in Central India
Authors: Bhadra Subhasish , Tadepalli Karuna , Chaudhary Narendra Kumar , Bhadade Arati
Published: September 2022

S6.1 Antifungal Prophylaxis in Children with Cancer and HSCT, September 22, 2022, 4:45 PM - 6:15 PM

 

Objectives

Documentation and dissemination of findings of a rare fungal isolate in an immunosuppressed child.

Methods

A case study with rare fungal isolate in correlation to age, clinical condition, sample, and comorbidity was done. A 6-year-old male child was admitted for routine management of B cell acute lymphoid leukemia. The patient completed induction chemotherapy in July 2021. The patient was planned for consolidation in the last week of July and to rule out any infection blood and urine samples were sent. Paired blood samples were received in pediatric automated BacT/Alert blood culture bottles. After 8 days both the blood culture bottles flashed positive. On gram stain, budding yeast cells oval to globose were seen. No pseudohyphae were seen. Nigrosin staining result was negative. It was processed further on HiCrome™ agar showing cream-colored colonies at 370 C, cornmeal agar with 1% tween 80 for Dalmau technique showed only oval to globose yeast cells with blastoconidia, enlarged cells appearing as chlamydoconidia without pseudohyphae or true hyphae were seen. Glucose and sucrose were fermented and trehalose was weakly fermented. Urease was negative. Isolate was identified as Candida glabrata/Candida auris. Antifungal susceptibility showed elevated MIC for fluconazole but susceptible to amphotericin B, voriconazole, and caspofungin. As part of routine collaboration with reference center PGIMER, bloodstream Candida isolates were sent for confirmation, and quality control.

Results

The isolate phenotypically suspected as C. glabrata causing fungemia was confirmed by the reference center as C. magnoliae. Currently, patient is on routine follow-up and doing well. On reviewing of available literature on C. magnoliae; bloodstream infections in two low birth weight neonates from Brazil, one immunocompetent child with tenosynovitis from the USA, and a terminal oncology patient from Italy were noted.

In a Chinese study of 2007, phylogenetic analysis showed a close relationship of C. magnoliae to Candida krusei.

Conclusion

Immunosuppression with longstanding or repeated hospital admissions is a risk for nosocomial fungal infections, especially, bloodstream infections. Already confusing phenotypic identification among C. glabrata, C. auris, C. haemoulonii, and now the current isolate C. magnoliae further complicates and challenges diagnostic workflow impacting timely management of cases. Further studies and more documentation of such findings in literature are necessary for newer insights.
S6.3d Candida albicans commensalism in the oral mucosa is favored by limited virulence and metabolic adaptation
Authors: Gut-Landmann Salomé Leibund
Published: September 2022

S6.3 Fungal adaptation and evolution, September 22, 2022, 4:45 PM - 6:15 PM

 

Objectives

As part of the human microbiota, the fungus Candida albicans colonizes the oral cavity and other mucosal surfaces. Commensalism is tightly controlled by complex fungus-host interactions that preclude fungal elimination but also fungal overgrowth and invasion that would result in disease. As such, defects in antifungal T cell immunity render individuals susceptible to oral thrush due to interrupted immunosurveillance. The factors that promote commensalism and ensure persistence of C. albicans in a fully immunocompetent host remain less clear. In this study, we aimed at identifying determinants of C. albicans commensalism in the oral cavity.

Methods

We used an experimental model of C. albicans oral colonization in mice, profiled the transcriptome of the fungus in the mucosal tissue, and conducted functional studies with the prototypical commensal isolate 101 in host-free and host-involving conditions.

Results

C. albicans commensalism is associated with a characteristic metabolic profile tailored to the nutrient-poor conditions in the stratum corneum of the epithelium where the fungus resides. Metabolic adaptation of the commensal isolate 101 was also reflected in enhanced nutrient acquisition when grown on oral mucosa substrates. Persistent colonization of the oral mucosa by C. albicans also correlated inversely with the capacity of the fungus to induce epithelial cell damage and to elicit an inflammatory response. These immune evasive properties of isolate 101 are explained by a strong attenuation of numerous virulence genes, including those linked to filamentation. De-repression of the hyphal program by deletion or conditional repression of the transcriptional repressor NRG1 abolished the commensal behavior of isolate 101.

Conclusions

This study establishes a central role of NRG1 in the commensal lifestyle of C. albicans in the oral niche of the host.
S8.1b Is a search and destroy strategy still feasible for Candida auris in South Africa?
Authors: Govender Nelesh
Published: September 2022

S8.1 Tackling Candida auris in resource-limited settings, September 23, 2022, 3:00 PM - 4:30 PM

 

 

Candida auris was prospectively detected as a healthcare-associated pathogen in South Africa in 2014. However, a retrospective review of a culture collection from national laboratory-based surveillance for Candidaemia in 2009-10 showed that earlier cases had been missed owing to species misidentification. National surveillance, which was repeated during 2016-17, revealed that C. auris caused >10% of cases of Candidaemia in South Africa, with most (86%) cases detected in the Gauteng Province. We recommended all hospitals to passively monitor cases of C. auris disease and colonization by each maintaining a line list of culture-confirmed cases. Facilities were thus classified into three tiers. Tier 1 (‘green status’) included facilities with no prior known cases. Such facilities were requested to report their first cases for urgent intervention. This included active colonization surveys, isolation and/or cohorts of infected or colonized patients as well as intensified infection prevention and control and antifungal stewardship activities. Tier 2 (‘orange status’) included facilities with sporadic cases defined arbitrarily as fewer than 12 cases in the past 6 months and/or fewer than three units affected. Such facilities were requested to report any increase in the number of cases compared with a baseline, clinical units affected for the first time, or apparent case clustering within the facility for investigation. Tier 3 (‘red status’) included facilities with a relative endemicity defined as >12 cases and/or >3 units with cases in the last 6 months. Tier 3 facilities were only requested to report increases over a baseline or apparent clustering within the facility. Owing to limited resources, colonization screening of newly-admitted patients was not recommended in acute-care facilities in South Africa. During 2019-21, the proportion attributable to C. auris increased even further to 25% (of 12 959 national cases of Candidaemia), with a concomitant reduction in cases caused by C. parapsilosis. This suggested a concerning replacement of multidrug-resistant C. auris in an ecological healthcare niche previously occupied by azole-resistant C. parapsilosis. An epidemiological shift was also observed with an expanding number of acute healthcare facilities outside Gauteng Province reporting C. auris and large persistent healthcare-associated infection outbreaks in neonatal units, particularly in the under-resourced public health sector.
S8.4b Population biology of hedgehog fungus Trichophyton e r inacei
Authors: Hubka Vit
Published: September 2022

S8.4 Cases of animal mycoses, September 23, 2022, 3:00 PM - 4:30 PM

 

 

Trichophyton erinacei is a main cause of dermatophytosis in hedgehogs and is increasingly reported from human infections worldwide. It is found in wild European hedgehogs (Erinaceus europaeus) but also in the African four-toed hedgehog (Atelerix albiventris), a popular pet animal worldwide. Little is known about the taxonomy and population genetics of this pathogen despite its increasing importance in clinical practice. Notably, whether there are different populations or even cryptic species associated with different hosts or geographic regions is not known. To answer these questions, we collected 161 isolates, performed phylogenetic and population-genetic analyses, determined mating type, and characterized morphology and physiology. Multigene phylogeny and microsatellite analysis supported T. erinacei as a monophyletic species, in contrast to highly incongruent single-gene phylogenies. Two main subpopulations, one specific mainly to Atelerix and the second to Erinaceus hosts, were identified inside T. erinacei, and slight differences in the size of microconidia and antifungal susceptibilities were observed among them. Although the process of speciation into two lineages is ongoing in T. erinacei, there is still gene flow between these populations. Thus, we present T. erinacei as a single species, with notable intraspecies variability in genotype and phenotype. The data from wild hedgehogs indicated that sexual reproduction in T. erinacei and de novo infection of hedgehogs from soil are probably rare events and that clonal horizontal spread strongly dominates. The molecular typing approach used in this study represents a suitable tool for further epidemiological surveillance of this emerging pathogen in both animals and humans. The results of this study also highlighted the need to use a multigene phylogeny ideally in combination with other independent molecular markers to understand the species boundaries of dermatophytes.
S9.3d Antivirulence drug discovery to disarm Candida albicans with metabolites from myxobacteria.
Authors: Vij Raghav , Tröger Sophie , Walt Christine , Haeckl F.P. Jake , Müller Rolf , Kniemeyer Olaf , Brakhage Axel , Hube Bernhard , Brunke Sascha
Published: September 2022

S9.3 Drug resistance in emerging pathogenic fungi, September 23, 2022, 4:45 PM - 6:15 PM

Candida albicans is an opportunistic fungal pathogen. While nearly 40%-60% of humans are colonized harmlessly by C. albicans, prolonged use of antibiotics or an immune-compromised status can lead to mucosal or deadly systemic candidiasis (Kumamoto et al., 2020). There are only three classes of antifungals available to physicians to treat and prevent severe Candidiasis. These drugs, which include polyenes, echinocandins, and azoles, protect the host by killing or inhibiting growth of C. albicans, thereby exerting a strong selective pressure toward drug resistance.

 

Antivirulence drugs, by contrast, target virulence traits of pathogens without affecting their growth, making drug resistance less likely to evolve. We seek to discover novel antivirulence compounds against C. albicans that keep it at, or return it to, its baseline commensal state even under conditions that support pathogenicity.

 

Bacteria have evolved a large repository of metabolites that can inhibit and modulate the behavior of other organisms in their environment. Clades like the predatory myxobacteria are untapped for potential antifungal and antivirulence drug discovery (Vij et al., 2021). We here screened ≈ 2800 crude extracts from myxobacteria in an in situ C. albicans-mammalian epithelial cell infection model. Typically, when oral epithelial cells (TR146) are infected by C. albicans, the fungus proliferates, forms hyphae, and invades and damages the monolayer. In our assay, we estimate the damage to epithelial cells by released lactate dehydrogenase. We also note changes to the growth and morphology of the fungus. Based on these readouts we assign antivirulence and antifungal ranks to each extract, and confirm top-ranked hits with an independent propidium iodide-based assay for host cell damage, and a colorimetric assay of fungal metabolic activity. We found that several of the top-ranked antifungal extracts also showed effects on a multi-drug resistant strain of C. auris.

 

Using an established pipeline, we identified several of the antifungal and antivirulent bioactive components in these extracts. After scaling the production of promising lead compounds, we will test their drugability on clinical Candida spp. strains, and identify their mode of action using large-scale Candida spp. knock-out libraries and multi-omics approaches.

 

Our tested extracts are likely to contain new classes of non-toxic antifungals that can potentially treat infections by multi-drug resistant fungi. We identified and confirmed several myxobacteria extracts that protected mammalian epithelial cells without severely affecting the fungus’ growth, which are, therefore, considered antivirulent.

Sources
S9.4e Molecular epidemiology of Microsporum canis infection in Japan
Authors: Mochizuki Takashi , Futatsuya Taketoshi , Anzawa Kazushi , Yamada Shigeo , Shimizu Akira
Published: September 2022

S9.4 Free oral presentations (late breaking), September 23, 2022, 4:45 PM - 6:15 PM

 

Objectives

From a series of epidemiological surveys by the Japanese Society for Medical Mycology, it is estimated that the number of Microsporum canis (M. canis) infections in Japan has increased in recent years. The purpose of this study was to observe this trend by multilocus microsatellite (MLMT) analysis, a sensitive molecular marker.

Methods

DNA was extracted from 103 strains of M. canis isolated between 2017 and 2022 from Japanese patients and pet animals. Using the DNA, PCR targeting six individual microsatellites was performed. The size of each of these amplicons was measured by capillary electrophoresis, and their genotypes were determined from the combinations of their sizes.

Results

A total of 27 genotypes were detected among the 103 strains. Among the 27, 15 had been reported in studies of strains isolated before 2017, whereas 12 were newly determined in the present study. The genotype most frequently detected in the present study was genotype A, being present in 28 of the 103 strains. By geographical region, genotype A was found in strains distributed over a wide area of Japan. Genotype A strains have been isolated from cats purchased at pet shops and/or owners of these pet animals. The highest incidence of genotype in a study of strains isolated in 2010-2014 was also genotype A. Therefore, a large number of M. canis infections originating from pet shops and animal breeders are likely prevalent in Japan today. Furthermore, a relatively large number of strains were identified as genotypes rare or absent in 2010-2014.

Conclusions

The increase in the number of M. canis infections in recent years may be the increase in infections of different genotypes, in addition to the base of constant infections by genotype A, by the present MLMT analysis.
S9.5c Malassezia-host interactions and the Il-23/17 axis
Authors: LeibundGut-Landmann Salomé
Published: September 2022

S9.5 Malassezia: pathogenesis and disease, September 23, 2022, 4:45 PM - 6:15 PM

 

 

The mycobiome of the skin is dominated by a single fungal genus, Malassezia. While Malassezia normally exists as a commensal without inflicting disease, the fungus has also been associated with numerous skin disorders ranging from mild conditions such as dandruff or pityriasis versicolor to severe chronic pathologies such as seborrheic or atopic dermatitis. Maintaining stable colonization and preventing pathogenicity of Malassezia is key for skin homeostasis. Our understanding of the fungal factors and host mechanisms that, through mutual interactions, promote Malassezia commensalism in healthy skin remains incomplete. From studies in humans and mice, we learned that homeostatic immunity against Malassezia is characterized by IL-17-producing T cells, including Th17 and γδT17 cells. Recent endeavors start to unravel the cellular and molecular pathways responsible for driving the protective antifungal response in the skin. While Malassezia-responsive T cells are non-inflammatory and host-beneficial, they can bear pathogenic potential and thereby be involved in the pathogenesis of inflammatory and allergic skin conditions, as preclinical studies suggest. During my lecture, I will report on recent findings from my lab regarding the role and regulation of the IL-23/IL-17 axis in response to Malassezia under normal and diseased skin conditions.
Incidental diffuse low-grade gliomas: A systematic review and meta-analysis of treatment results with correction of lead-time and length-time biases
Authors: Nakasu Satoshi , Nakasu Yoko , Tsuji Atsushi , Fukami Tadateru , Nitta Naoki , Kawano Hiroto , Notsu Akifumi , Nozaki Kazuhiko
Published: September 2022

Background

Better overall survival (OS) reported in patients with incidental diffuse low-grade glioma (iLGG) in comparison to symptomatic LGG (sLGG) may be overestimated by lead-time and length-time.

Methods

We performed a systematic review and meta-analysis of studies on adult hemispheric iLGGs according to the PRISMA statement to adjust for biases in their outcomes. Survival data were extracted from Kaplan–Meier curves. Lead-time was estimated by 2 methods: Pooled data of time to become symptomatic (LTs) and time calculated from the tumor growth model (LTg).

Results

We selected articles from PubMed, Ovid Medline, and Scopus since 2000. Five compared OS between patients with iLGG (n = 287) and sLGG (n = 3117). The pooled hazard ratio (pHR) for OS of iLGG to sLGG was 0.40 (95% confidence interval [CI] {0.27–0.61}). The estimated mean LTs and LTg were 3.76 years (n = 50) and 4.16–6.12 years, respectively. The corrected pHRs were 0.64 (95% CI [0.51–0.81]) by LTs and 0.70 (95% CI [0.56–0.88]) by LTg. In patients with total removal, the advantage of OS in iLGG was lost after the correction of lead-time. Patients with iLGG were more likely to be female pooled odds ratio (pOR) 1.60 (95% CI [1.25–2.04]) and have oligodendrogliomas (pOR 1.59 [95% CI {1.05–2.39}]). Correction of the length-time bias, which increased the pHR by 0.01 to 0.03, preserved the statistically significant difference in OS.

Conclusions

The reported outcome in iLGG was biased by lead-time and length-time. Although iLGG had a longer OS after correction of biases, the difference was less than previously reported.
A trio of giant planets orbiting evolved star HD 184010
Authors: Teng Huan-Yu , Sato Bun’ei , Takarada Takuya , Omiya Masashi , Harakawa Hiroki , Nagasawa Makiko , Hasegawa Ryo , Izumiura Hideyuki , Kambe Eiji , Yoshida Michitoshi , Itoh Yoichi , Ando Hiroyasu , Kokubo Eiichiro , Ida Shigeru
Published: September 2022

We report the discovery of a triple-giant-planet system around an evolved star HD 184010 (HR 7421, HIP 96016). This discovery is based on observations from Okayama Planet Search Program, a precise radial velocity survey, undertaken at Okayama Astrophysical Observatory between 2004 April and 2021 June. The star is K0 type and located at the beginning of the red giant branch. It has a mass of $1.35_{-0.21}^{+0.19}\, M_{\odot }$, a radius of $4.86_{-0.49}^{+0.55} R_{\odot }$, and a surface gravity log g of $3.18_{-0.07}^{+0.08}$. The planetary system is composed of three giant planets in a compact configuration: the planets have minimum masses of $M_{\rm {b}}\sin i = 0.31_{-0.04}^{+0.03}\, M_{\rm {J}}$, $M_{\rm {c}}\sin i = 0.30_{-0.05}^{+0.04}\, M_{\rm {J}}$, and $M_{\rm {d}}\sin i = 0.45_{-0.06}^{+0.04}\, M_{\rm {J}}$, and orbital periods of $P_{\rm {b}}=286.6_{-0.7}^{+2.4}\:$d, $P_{\rm {c}}=484.3_{-3.5}^{+5.5}\:$d, and $P_{\rm {d}}=836.4_{-8.4}^{+8.4}\:$d, respectively, which are derived from a triple Keplerian orbital fit to three sets of radial velocity data. The ratio of orbital periods are close to Pd : Pc : Pb ∼ 21 : 12 : 7, which means the period ratios between neighboring planets are both lower than 2 : 1. The dynamical stability analysis reveals that the planets should have near-circular orbits. The system could remain stable over 1 Gyr, initialized from co-planar orbits, low eccentricities (e = 0.05), and planet masses equal to the minimum mass derived from the best-fitting circular orbit fitting. Besides, the planets are not likely in mean motion resonance. The HD 184010 system is unique: it is the first system discovered to have a highly evolved star (log g < 3.5 cgs) and more than two giant planets all with intermediate orbital periods (102 < P < 103 d).
A Mixed-Methods Evaluation of a Social Paediatrics Block Rotation for Paediatric Residents
Authors: Hunter A , Kay S , Parker K , Delahunty-Pike A , Wahi G
Published: September 2022

BACKGROUND: Poverty and social injustice have a direct link to health outcomes and health care utilization, especially for children. Understanding the complexity of impact of social determinants on health is essential in providing effective, compassionate care to vulnerable populations. Currently, there is a paucity of literature on the impact of various models of advocacy curricula on pediatric residents and future involvement in advocacy. Social Pediatrics is an approach to child health that focuses on the child, in illness, and in health, within the context of their society, environment, school, and family.

OBJECTIVES: 1) To determine if a social pediatrics rotation greater enables residents to become involved in advocacy projects during their residency and interest for career. 2) To identify resident knowledge translation of the social determinants of health and their impact on the pediatric population. 3) To characterize the barriers and enablers, if any, for residents to engage in advocacy.

DESIGN/METHODS: The Social Pediatrics rotation was embedded in the second year of a postgraduate pediatric curriculum. Knowledge and attitudes of resident participants before and after the rotation was assessed with written tests and surveys. A qualitative descriptive study of community partners and resident perspectives was semi-structured interviews, thematic coding and analysis via an inductive-iterative approach.

RESULTS: 21 residents completed pre-and post- written knowledge tests, and 12 residents completed optional attitudinal surveys. Knowledge increased from 68% prior to rotation, to 80% (p < 0.001) following the rotation. All residents completing written surveys indicated increased likelihood of participating in social pediatrics and advocacy in practice following this rotation. Results from 6 resident and 5 community partner interviews included: enhanced knowledge of social determinants of health, residency curricula development with further mental health placements, future practice models involving vulnerable populations, multi-disciplinary learning opportunities, and advocacy projects both at the patient and community level. Community partners shared experiences of residents demonstrating enthusiasm and engagement in placements, some logistical challenges but value in experiences outside hospital environment, particularly in learning from multidisciplinary team.

CONCLUSION: Pediatric residents demonstrate increase in knowledge of social determinants of health and an increased interest in community advocacy initiatives and vulnerable populations following a block rotation in Social Pediatrics. Community partners valued engagement with pediat-ric residents, identifying key learning opportunities in these unique environments and report few barriers to continued involvement. Future directions include impact on advocacy work or career decisions, and multi-centre collaboration.
Realizing Ubuntu in Global Health: An African Approach to Global Health Justice
Authors: Jecker Nancy S , Atuire Caesar A , Kenworthy Nora
Published: September 2022

The COVID-19 pandemic has highlighted the question, ‘What do we owe each other as members of a global community during a global health crisis?’ In tandem, it has raised underlying concerns about how we should prepare for the next infectious disease outbreak and what we owe to people in other countries during normal times. While the prevailing bioethics literature addresses these questions drawing on values and concepts prominent in the global north, this paper articulates responses prominent in sub-Saharan Africa. The paper first introduces a figurative ‘global health village’ to orient readers to African traditional thought. Next, it considers ethical requirements for governing a global health village, drawing on the ethic of ubuntu to formulate African renderings of solidarity, relational justice and sufficiency. The final section of the paper uses these values to critique current approaches, including COVAX, the vaccines pillar of the Access to COVID-19 Tools (ACT) accelerator, and a proposed international Pandemic Treaty. It proposes a path forward that better realizes ubuntu in global health.
Sustained degradation of hyaluronic acid using an in situ forming implant
Authors: Hopkins Kelsey , Buno Kevin , Romick Natalie , Freitas dos Santos Antonio Carlos , Tinsley Samantha , Wakelin Elizabeth , Kennedy Jacqueline , Ladisch Michael , Allen-Petersen Brittany L , Solorio Luis
Published: September 2022

In pancreatic cancer, excessive hyaluronic acid (HA) in the tumor microenvironment creates a viscous stroma, which reduces systemic drug transport into the tumor and correlates with poor patient prognosis. HA can be degraded through both enzymatic and nonenzymatic methods to improve mass transport properties. Here, we use an in situ forming implant to provide sustained degradation of HA directly at a local, targeted site. We formulated and characterized an implant capable of sustained release of hyaluronidase (HAase) using 15 kDa poly(lactic-co-glycolic) acid and bovine testicular HAase. The implant releases bioactive HAase to degrade the HA through enzymatic hydrolysis at early timepoints. In the first 24 h, 17.9% of the HAase is released, which can reduce the viscosity of a 10 mg/mL HA solution by 94.1% and deplete the HA content within primary human pancreatic tumor samples and ex vivo murine tumors. At later timepoints, as lower quantities of HAase are released (51.4% released in total over 21 d), the degradation of HA is supplemented by the acidic by-products that accumulate as a result of implant degradation. Acidic conditions degrade HA through nonenzymatic methods. This formulation has potential as an intratumoral injection to allow sustained degradation of HA at the pancreatic tumor site.
A forgotten element of the blue economy: marine biomimetics and inspiration from the deep sea
Authors: Blasiak Robert , Jouffray Jean-Baptiste , Amon Diva J , Moberg Fredrik , Claudet Joachim , Søgaard Jørgensen Peter , Pranindita Agnes , Wabnitz Colette C C , Österblom Henrik
Published: September 2022

The morphology, physiology, and behavior of marine organisms have been a valuable source of inspiration for solving conceptual and design problems. Here, we introduce this rich and rapidly expanding field of marine biomimetics, and identify it as a poorly articulated and often overlooked element of the ocean economy associated with substantial monetary benefits. We showcase innovations across seven broad categories of marine biomimetic design (adhesion, antifouling, armor, buoyancy, movement, sensory, stealth), and use this framing as context for a closer consideration of the increasingly frequent focus on deep-sea life as an inspiration for biomimetic design. We contend that marine biomimetics is not only a “forgotten” sector of the ocean economy, but has the potential to drive appreciation of nonmonetary values, conservation, and stewardship, making it well-aligned with notions of a sustainable blue economy. We note, however, that the highest ambitions for a blue economy are that it not only drives sustainability, but also greater equity and inclusivity, and conclude by articulating challenges and considerations for bringing marine biomimetics onto this trajectory.
Energy Transitions and Household Finance: Evidence from U.S. Coal Mining
Authors: Du Ding , Karolyi Stephen A
Published: September 2022

Between 2010 and 2020, the U.S. coal industry experienced a 50% drop in production, employment, and active mines, driven by regulatory factors and technological innovation in alternative energy sources. We study the impact of this energy transition on household employment, wages, migration, and home ownership in affected communities. Compared to non-coal-producing, resource-rich counties, coal-producing counties experience 6% and 4% drops in employment and wages, respectively, during this period. Economic mobility and access to banking services significantly moderate these real effects, suggesting a potential role for finance to shape the industrial and economic changes associated with climate transitions. (JEL G20, G50, J61, Q55, Q58)

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Amygdala and hippocampus dialogue with neocortex during human sleep and wakefulness
Authors: Muñoz-Torres Zeidy , Corsi-Cabrera María , Velasco Francisco , Velasco Ana Luisa
Published: September 2022

Previous studies have described synchronic electroencephalographic (EEG) patterns of the background activity that is characteristic of several vigilance states.

Study Objectives

To explore whether the background synchronous activity of the amygdala–hippocampal–neocortical circuit is modified during sleep in the delta, theta, alpha, sigma, beta, and gamma bands characteristic of each sleep state.

Methods

By simultaneously recording intracranial and noninvasive scalp EEG (10–20 system) in epileptic patients who were candidates for neurosurgery, we explored synchronous activity among the amygdala, hippocampus, and neocortex during wakefulness (W), Non-Rapid Eye Movement (NREM), and Rapid-Eye Movement (REM) sleep.

Results

Our findings reveal that hippocampal–cortical synchrony in the sleep spindle frequencies was spread across the cortex and was higher during NREM versus W and REM, whereas the amygdala showed punctual higher synchronization with the temporal lobe. Contrary to expectations, delta synchrony between the amygdala and frontal lobe and between the hippocampus and temporal lobe was higher during REM than NREM. Gamma and alpha showed higher synchrony between limbic structures and the neocortex during wakefulness versus sleep, while synchrony among deep structures showed a mixed pattern. On the one hand, amygdala–hippocampal synchrony resembled cortical activity (i.e. higher gamma and alpha synchrony in W); on the other, it showed its own pattern in slow frequency oscillations.

Conclusions

This is the first study to depict diverse patterns of synchronic interaction among the frequency bands during distinct vigilance states in a broad human brain circuit with direct anatomical and functional connections that play a crucial role in emotional processes and memory.
Individual and neighborhood socioeconomic status and long-term individual trajectories of sleep duration among Black and White adults: the Southern Community Cohort Study
Authors: Nyarko Samuel H , Luo Liying , Schlundt David G , Xiao Qian
Published: September 2022

Study Objectives

Sleep duration can change over the life course; however, previous studies rarely investigated the association between socioeconomic status (SES) and individual sleep trajectories over time. We examined the association between baseline socioeconomic characteristics and long-term sleep trajectories among Black and White adults.

Methods

This study used data from the Southern Community Cohort Study (N = 45 035). Diverse trajectories of sleep duration were constructed using self-reported sleep duration at baseline and after ~10 years of follow-up. The associations between baseline socioeconomic characteristics and sleep trajectories were examined using multinomial logistic regression.

Results

Both Black and White participants experienced similar long-term individual sleep trajectories for baseline educational attainment and employment status albeit the associations appeared stronger among White participants. Lower education and unemployment were associated with higher odds of various suboptimal sleep trajectories suggesting worsening long-term sleep patterns among both racial groups. However, there were some racial differences in the experience of long-term sleep trajectories for household income and neighborhood SES. Household income was notably more important among White than Black individuals; lower household income was associated with higher odds of more suboptimal long-term sleep trajectories for White than Black individuals. Also, neighborhood SES was slightly more important among White than Black individuals; lower neighborhood SES was associated with higher odds of a few suboptimal long-term sleep trajectories for both racial groups.

Conclusions

Lower socioeconomic characteristics were associated with various suboptimal long-term sleep trajectories among Black and White participants. Substantial improvements in socio-economic characteristics may contribute to improved sleep patterns.
Protective effect of quercetin against phthalates induced hepatotoxicity in rats
Authors: Xia Ling-Zi , Jiang Ming-Zhe , Liu Li-Lan , Wu Yi , Zhang Yi-Lin , Yang Li-Xia , Shen Xin-Yue , Zhang Qiu-Yu , Lin Min , Gao Hai-Tao
Published: September 2022

Humans are increasingly exposed to ubiquitous phthalates (PEs), e.g. butyl benzyl phthalate (BBP), dibutyl phthalate (DBP), and di(2-ethylhexyl) phthalate (DEHP), which are widely used plasticizers in polymer products. This study was aimed to investigate the effect of phytochemical quercetin (Que) on hepatotoxicity caused by the mixture of the 3 commonly used PEs (MPEs), and further to explore the underlying mechanism. Forty male Sprague–Dawley rats were randomly divided into control group, MPEs group, and MPEs combined Que at Low-, Median-, and High-dose groups; rats in MPEs group were orally administered with 900 mg/kg/d MPEs, whereas rats in MPEs combined Que groups were simultaneously treated with 900 mg/kg/d MPEs and respectively 10, 30, and 90 mg/kg/d Que. The intervention last 30 days. Compared with control group, serum ALT, AST, LDH and AKP, and hepatic MDA, SOD, CAT and GPx were significantly increased, whereas, serum albumin and total protein were significantly decreased in MPEs group (P < 0.05); hepatic histopathological observation showed numerous inflammatory cells infiltration, hepatocyte ballooning degeneration, and numerous residual erythrocytes in the central vein in MPEs group. Western-blot analysis showed that hepatic Keap1 was downregulated, whereas Nrf2 and HO-1 were upregulated in MPEs group (P < 0.05). However, the alterations of these parameters were alleviated in MPEs combined Que at Median- and High-dose groups. The results indicated that MPEs-induced hepatic oxidative stress, and caused hepatic injuries; whereas, Que inhibited MPEs’ hepatotoxicity, which might relate to Que’s ability of quenching free radicals directly, and restored the regulation of Nrf2 signaling pathway.