bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of multi epitope subunit vaccines against emerging carp viruses Cyprinid herpesvirus 1 and 3 using immunoinformatics approach
Authors: Rani Nurul Amin , Robin Tanjin Barketullah , Prome Anindita Ash , Ahmed Nadim , Moin Abu Tayab , Patil Rajesh B. , Sikder Mohammad Nurul Azim , Bappy Md Nazmul Islam , Afrin Dilruba , Hossain Ferdaus Mohd Altaf , Islam Tofazzal , Zinnah Kazi Md. Ali
Published: May 2024

Cyprinid herpesvirus is a causative agent of a destructive disease in common and koi carp (Cyprinus carpio), which leads to substantial global financial losses in aquaculture industries. Among the strains of C. herpesvirus, C. herpesvirus 1 (CyHV-1) and C. herpesvirus 3 (CyHV-3) are known as highly pathogenic to carp fishes in Europe, Asia, and Africa. To date, no effective vaccine has been developed to combat these viruses. This study aimed to develop unique multi-epitope subunit vaccines targeting the CyHV-1 and CyHV-3 using a reverse vaccinology approach. The study began with a comprehensive literature review to identify the most critical proteins, which were then subjected to in silico analyses to predict highly antigenic epitopes. These analyses involved assessing antigenicity, transmembrane topology screening, allergenecity, toxicity, and molecular docking approaches. We constructed two multi-epitope-based vaccines incorporating a suitable adjuvant and appropriate linkers. It revealed that both the vaccines are non-toxic and immunogenic. The tertiary structures of the vaccine proteins were generated, refined, and validated to ensure their suitability. The binding affinity between the vaccine constructs and TLR3 and TLR5 receptors were assessed by molecular docking studies. Molecular dynamics simulations indicated that vaccine construct V1 exhibited greater stability with both TLR3 and TLR5 based on RMSD analysis. Hydrogen bond analysis revealed a stronger binding affinity between the vaccine constructs and TLR5 compared to TLR3. Furthermore, MM-PBSA analysis suggested that both vaccine constructs exhibited a better affinity for TLR5. Considering all aspects, the results suggest that in silico development of CyHV vaccines incorporating multiple epitopes holds promise for management of diseases caused by CyHV-1 and CyHV-3. However, further in vivo trials are highly recommended to validate the efficacies of these vaccines.
Trends in chlamydia prevalence in the United States, 2005–2016
Authors: Cheng Yu , Zheng Guanghao , Song Zhen , Zhang Gan , Rao Xuepeng , Zeng Tao
Published: May 2024

In the United States (US), chlamydia is the most frequently reported sexually transmitted infection that is nationally notifiable. We examined trends in chlamydia prevalence in the US in 2011–2016 compared with 2005–2010. Cross-sectional, nationally representative surveys, National Health and Nutrition Examination Surveys (NHANES), were used to compare national chlamydia prevalence estimates from 2011 to 2016 with those from 2005 to 2010, and changes in prevalence since 1999–2004 were also reviewed. Persons aged 18–39 years were included in these analyses. Prevalence of chlamydia was based on results from urine specimens. Results were weighted to represent the U.S. civilian, noninstitutionalized population. The baseline characteristics of the study population were similar in gender, age and race/ethnicity between the two groups (P > 0.05). The overall chlamydia prevalence was 1.88% (95% confidence interval [CI] 1.55–2.22%) in 2011–2016 and 1.57% (95% CI 1.27–1.87%) in 2005–2010, a relative increase of 19.7% (95% CI 0.2–39.2%; P < 0.05) between the two surveys. Increases in chlamydia prevalence was especially concentrated in persons who were male, aged 18 to 29 years, had > high school educational level, never married, age at first sex < 18 years, had 2–5 sexual partners in lifetime and had no past sexually transmitted diagnosis between 2005 and 2016 (P < 0.05). Multivariable logistic regression analysis demonstrated that chlamydia was more prevalent in those aged 18–29 years, being non-Hispanic Blacks, had high school educational level, being widowed/divorced/separated and had > 5 sexual partners. The chlamydia prevalence had an increasing trend from 2005–2010 to 2011–2016. Those with high chlamydia prevalence such as sexually active young adults and Non-Hispanic Black should be screened annually so that infected persons can be diagnosed and they and their sex partners can be treated promptly.
Biomechanical assessment of mandibular fracture fixation using finite element analysis validated by polymeric mandible mechanical testing
Authors: Daqiq Omid , Roossien Charlotte Christina , Wubs Frederik Wilhelm , van Minnen Baucke
Published: May 2024

The clinical finite element analysis (FEA) application in maxillofacial surgery for mandibular fracture is limited due to the lack of a validated FEA model. Therefore, this study aims to develop a validated FEA model for mandibular fracture treatment, by assessing non-comminuted mandibular fracture fixation. FEA models were created for mandibles with single simple symphysis, parasymphysis, and angle fractures; fixated with 2.0 mm 4-hole titanium miniplates located at three different configurations with clinically known differences in stability, namely: superior border, inferior border, and two plate combinations. The FEA models were validated with series of Synbone polymeric mandible mechanical testing (PMMT) using a mechanical test bench with an identical test set-up. The first outcome was that the current understanding of stable simple mandibular fracture fixation was reproducible in both the FEA and PMMT. Optimal fracture stability was achieved with the two plate combination, followed by superior border, and then inferior border plating. Second, the FEA and the PMMT findings were consistent and comparable (a total displacement difference of 1.13 mm). In conclusion, the FEA and the PMMT outcomes were similar, and hence suitable for simple mandibular fracture treatment analyses. The FEA model can possibly be applied for non-routine complex mandibular fracture management.
Automatic segmentation and classification of frontal sinuses for sex determination from CBCT scans using a two-stage anatomy-guided attention network
Authors: da Silva Renan Lucio Berbel , Yang Su , Kim DaEl , Kim Jun Ho , Lim Sang-Heon , Han Jiyong , Kim Jun-Min , Kim Jo-Eun , Huh Kyung-Hoe , Lee Sam-Sun , Heo Min-Suk , Yi Won-Jin
Published: May 2024

Sex determination is essential for identifying unidentified individuals, particularly in forensic contexts. Traditional methods for sex determination involve manual measurements of skeletal features on CBCT scans. However, these manual measurements are labor-intensive, time-consuming, and error-prone. The purpose of this study was to automatically and accurately determine sex on a CBCT scan using a two-stage anatomy-guided attention network (SDetNet). SDetNet consisted of a 2D frontal sinus segmentation network (FSNet) and a 3D anatomy-guided attention network (SDNet). FSNet segmented frontal sinus regions in the CBCT images and extracted regions of interest (ROIs) near them. Then, the ROIs were fed into SDNet to predict sex accurately. To improve sex determination performance, we proposed multi-channel inputs (MSIs) and an anatomy-guided attention module (AGAM), which encouraged SDetNet to learn differences in the anatomical context of the frontal sinus between males and females. SDetNet showed superior sex determination performance in the area under the receiver operating characteristic curve, accuracy, Brier score, and specificity compared with the other 3D CNNs. Moreover, the results of ablation studies showed a notable improvement in sex determination with the embedding of both MSI and AGAM. Consequently, SDetNet demonstrated automatic and accurate sex determination by learning the anatomical context information of the frontal sinus on CBCT scans.
The impact of psychopathic traits on anxiety-related behaviors in a mixed reality environment
Authors: Voulgaris Alexander , Biedermann Sarah V. , Biedermann Daniel , Bründl Susanne , Roth Lateefah , Wiessner Christian , Briken Peer , Fuss Johannes
Published: May 2024

There is an ongoing debate about anxiety deficits in psychopathy and their possible impact on individual behavior. Data on actual anxiety- and threat-related behavior associated with psychopathy is still limited. We performed a mixed reality study using the elevated plus-maze (EPM) in a non-clinical sample (N = 160) to test anxiety-related behavior in relation to psychopathic personality traits measured through the Brief Questionnaire of Psychopathic Personality Traits (FPP). The psychopathy sum score correlated significantly with all measures of anxiety-related behavior on the EPM. Sensation seeking, but not general levels of acrophobia was moreover associated with psychopathic traits. Multivariate analyses revealed that the subscales Fearlessness and Lack of Empathy of the FPP predicted anxious behavior. Our findings are the first to demonstrate the relationship between psychopathic traits and actual behavior in an anxiety-inducing environment. This supports the low-anxiety hypothesis in psychopathy research. Implications for potentially harmful or risky behavior are discussed.
Classification and identification of tea diseases based on improved YOLOv7 model of MobileNeXt
Authors: Xia Yuxin , Yuan Wenxia , Zhang Shihao , Wang Qiaomei , Liu Xiaohui , Wang Houqiao , Wu Yamin , Yang Chunhua , Xu Jiayi , Li Lei , He Junjie , Cao Zhiyong , Wang Zejun , Zhao Zihua , Wang Baijuan
Published: May 2024

To address the issues of low accuracy and slow response speed in tea disease classification and identification, an improved YOLOv7 lightweight model was proposed in this study. The lightweight MobileNeXt was used as the backbone network to reduce computational load and enhance efficiency. Additionally, a dual-layer routing attention mechanism was introduced to enhance the model’s ability to capture crucial details and textures in disease images, thereby improving accuracy. The SIoU loss function was employed to mitigate missed and erroneous judgments, resulting in improved recognition amidst complex image backgrounds.The revised model achieved precision, recall, and average precision of 93.5%, 89.9%, and 92.1%, respectively, representing increases of 4.5%, 1.9%, and 2.6% over the original model. Furthermore, the model’s volum was reduced by 24.69M, the total param was reduced by 12.88M, while detection speed was increased by 24.41 frames per second. This enhanced model efficiently and accurately identifies tea disease types, offering the benefits of lower parameter count and faster detection, thereby establishing a robust foundation for tea disease monitoring and prevention efforts.
Climate change impact on groundwater resources in sandbar aquifers in southern Baltic coast
Authors: Gumuła-Kawęcka Anna , Jaworska-Szulc Beata , Jefimow Maciej
Published: May 2024

Shallow coastal aquifers are vulnerable hydrosystems controlled by many factors, related to climate, seawater-freshwater interactions and human activity. Given on-going climate change, sea level rise and increasing human impact, it is especially true for groundwater resources situated in sandbars. We developed numerical models of unsaturated zone water flow for two sandbars in northern Poland: the Vistula Spit and the Hel Spit using HYDRUS-1D. The simulations were performed for three types of land use: pine forest, grass cover and bare soil, for 2024–2100 based on weather data and sea level rise forecasts for two emissions scenarios (RCP 4.5 and RCP 8.5). The results present prognosis of groundwater recharge, water table level and water content changeability in near-term (2023–2040), mid-term (2041–2060), and long-term period (2081–2100). Expected sea level rise and decreasing hydraulic gradient of the sandbar aquifers will probably cause in-land movement of the freshwater–saltwater interface, leading to significant decrease or complete salinization of groundwater resources. The study shows that holistic monitoring including groundwater level and salinization, sea level rise, and metheorological data (precipitation amount and variability, temperature) is crucial for sustainable management of vulnerable aquifers located in sandbars.
Integrated analysis identified the role of three family members of ARHGAP in pancreatic adenocarcinoma
Authors: Fei Haoran , Shi Xiao , Sun Dan , Yang Haishen , Wang Dali , Li Kai , Si Xinxin , Hu Wei
Published: May 2024

The Rho GTPase activating protein family (ARHGAPs) is expressed in pancreatic adenocarcinoma (PAAD) but its function is unclear. The aim of this study was to explore the role and potential clinical value of ARHGAPs in PAAD. Using TCGA and GEO databases to analyze expression of ARHGAPs in PAAD and normal tissues. Survival curve was drawn by Kaplan–Meier. ARHGAPs were integrated analyzed by GEPIA2, TIMER, UCLCAN, cBioPortal and R language. Protein level and prognostic value were evaluated via IHC staining or survival analysis. We totally identify 18 differentially expressed (DE) ARHGAPs in PAAD. Among the 18 DE genes, 8 were positively correlated with tumor grade; abnorrmal expression of 5 was positively correlated with copy number variation; expression of 4 was positively correlated with promoter hypomethylation. Multivariate Cox regression identified ARHGAP5, ARHGAP11A, and ARHGAP12 as independent prognostic factors of PAAD. The function of ARHGAPs was mainly related to GTPase activity and signaling, axon guidance, proteoglycans in cancer and focal adhesion. Expression of 7 ARHGAPs was strongly correlated with immune infiltration. Immunohistochemistry showed increased protein levels of ARHGAP5, ARHGAP11A, and ARHGAP12 in PAAD tissues. Survival analysis confirmed a negative correlation between ARHGAP5, ARHGAP11A, and ARHGAP12 expression and patient prognosis. Multivariate Cox regression proved ARHGAP5, ARHGAP11A, and ARHGAP12 could serve as independent prognostic indicators for PAAD. Finally, this study verified ARHGAP5, ARHGAP11A, and ARHGAP12 as independent prognostic factors in PAAD, suggesting their significance for the diagnosis and treatment of PAAD.
Comparative chloroplast genomics, phylogenetic relationships and molecular markers development of Aglaonema commutatum and seven green cultivars of Aglaonema
Authors: Li Dong-Mei , Pan Yan-Gu , Wu Xiao-Ye , Zou Shui-Ping , Wang Lan , Zhu Gen-Fa
Published: May 2024

Aglaonema commutatum is a famous species in the Aglaonema genus, which has important ornamental and economic value. However, its chloroplast genome information and phylogenetic relationships among popular green cultivars of Aglaonema in southern China have not been reported. Herein, chloroplast genomes of one variety of A. commutatum and seven green cultivars of Aglaonema, namely, A. commutatum ‘San Remo’, ‘Kai Sa’, ‘Pattaya Beauty’, ‘Sapphire’, ‘Silver Queen’, ‘Snow White’, ‘White Gem’, and ‘White Horse Prince’, were sequenced and assembled for comparative analysis and phylogeny. These eight genomes possessed a typical quadripartite structure that consisted of a LSC region (90,799–91,486 bp), an SSC region (20,508–21,137 bp) and a pair of IR regions (26,661–26,750 bp). Each genome contained 112 different genes, comprising 79 protein-coding genes, 29 tRNA genes and 4 rRNA genes. The gene orders, GC contents, codon usage frequency, and IR/SC boundaries were highly conserved among these eight genomes. Long repeats, SSRs, SNPs and indels were analyzed among these eight genomes. Comparative analysis of 15 Aglaonema chloroplast genomes identified 7 highly variable regions, including trnH-GUG-exon1-psbA, trnS-GCU-trnG-UCC-exon1, trnY-GUA-trnE-UUC, psbC-trnS-UGA, trnF-GAA-ndhJ, ccsA-ndhD, and rps15-ycf1-D2. Reconstruction of the phylogenetic trees based on chloroplast genomes, strongly supported that Aglaonema was a sister to Anchomanes, and that the Aglaonema genus was classified into two sister clades including clade I and clade II, which corresponded to two sections, Aglaonema and Chamaecaulon, respectively. One variety and five cultivars, including A. commutatum ‘San Remo’, ‘Kai Sa’, ‘Pattaya Beauty’, ‘Silver Queen’, ‘Snow White’, and ‘White Horse Prince’, were classified into clade I; and the rest of the two cultivars, including ‘Sapphire’ and ‘White Gem’, were classified into clade II. Positive selection was observed in 34 protein-coding genes at the level of the amino acid sites among 77 chloroplast genomes of the Araceae family. Based on the highly variable regions and SSRs, 4 DNA markers were developed to differentiate the clade I and clade II in Aglaonema. In conclusion, this study provided chloroplast genomic resources for Aglaonema, which were useful for its classification and phylogeny.
Multiple factor assessment for determining resting metabolic rate in young adults
Authors: Zhou Wanqing , Su Hong , Tong Jiali , Du Wenwen , Wang Bo , Chen Pei , Wan Hua , Zhou Ming
Published: May 2024

Existing formulas cannot fully explain the variation of resting metabolic rate (RMR). This study aims to examine potential influencing factors beyond anthropometric measurements and develop more accurate equations using accessible parameters. 324 healthy adults (230 females; 18–32 years old) participated in the study. Height, fat-free mass (FFM), fat mass (FM) and RMR were measured. Menstrual cycle, stress levels, living habits, and frequency of consuming caffeinated foods were collected. Measured RMR were compared with predictive values of the new equations and previous 11 equations. Mean RMR for men and women was 1825.2 ± 248.8 and 1345.1 ± 178.7 kcal/day, respectively. RMR adjusted for FFM0.66FM0.066 was positively correlated with BMI. The multiple regression model showed that RMR can be predicted in this population with model 1 (with FFM, FM, age, sex and daily sun exposure duration) or model 2 (with weight and height replacing FFM and FM). The accuracy was 75.31% in the population for predictive model 1 and 70.68% for predictive model 2. The new equations had overall improved performance when compared with existing equations. The predictive formula that consider daily sun exposure duration improve RMR prediction in young adults. Additional investigation is required among individuals in the middle-aged and elderly demographic.
Development-induced dispossession: Adivasi existence in the milieu of contemporary Indian texts in translation
Authors: Varughese Roshan , Mukherjee Soumen
Published: May 2024

The paradigms of development around the globe involves mechanisms associated with its social purpose, which is more often than not dubious in nature! Natural resources form the fundamental aspect of any developmental activity. But in the process of accumulating these resources, the beneficiaries often rely on malignant mechanisms. The capitalist discourse has always been successful in manifesting their agendas of development as constructive and profitable for the entire humanity. Periodically, when the utility of development is foregrounded by dominant cultural forms, often the ramifications of progress remain uncritiqued. The developmental projects earmarked for the rural population remain unnoticed, for it serves the interest of the elite and the urban middle class. Many a time, the indigenous population, who inhabit the resource rich area are swayed away by the false propaganda for development, ultimately aggravating their existing deprivation. In the case of India, too, amidst all the development activities, the marginalized populace or the so-called Adivasis are the worst sufferers, because they have been encountering displacement for ages. The current study attempts to unveil the displacement of the tribal population (Adivasi) of India due to development projects, thereby offering a critical analysis of the social policies. The study employs select translated literary narratives to examine the development-induced dispossession of tribal population in the colonial, postcolonial and neo-liberal phase of Indian history, adopting the theoretical framework of new historicism.
New memory circuit can handle the heat
Authors: Wilson R. Mark
Published: May 2024

A ferroelectric device can store data at temperatures up to 600 °C for dozens of hours at a time.
Organic amendments improved soil properties and native plants’ performance in an Australian degraded land
Authors: Larsen Jonas , Rezaei Rashti Mehran , Esfandbod Maryam , Chen Chengrong
Published: May 2024

Context Land degradation poses a substantial threat to both the sustainable environment and human health. Efforts towards rehabilitation and remediation often require addition of soil amendments and careful selection of plant species. Aims We assessed the effect of recycled organic amendments on improvement of soil physicochemical properties and performance of native plant species in an Australian degraded soil. Methods A glasshouse pot experiment investigated the effects of compost (CO), biochar (BC), and compost-biochar (COBC) mixture on performance of three native Australian plant species (Eucalyptus tereticornis (EU), Acacia leiocalyx (AC), and Banksia integrifolia (BA)) in a degraded soil. Key results Application of CO, BC, and COBC organic amendments increased soil dissolved organic carbon and microbial biomass carbon contents compared to the control treatment. COBC amendment increased nutrient retention and reduced CO2 emissions compared to CO amendment. BC amendment also resulted in low CO2 emissions similar to the control treatment, where no significant differences were observed. AC outperformed the EU and BA species in biomass production due to its leguminous nature, with amendment application had an insignificant effect on AC performance. Within the EU treatments, the COBC:EU demonstrated the highest biomass production, followed by CO:EU, BC:EU, and CK:EU, respectively. Conclusion All amendments exhibited overall improvements in soil and plant parameters, with more significant outcomes observed with COBC application. However, the observed improvements from biochar application were minimal in this short-term experiment, which may not have allowed for the manifestation of long-term benefits. Implications Further research is warranted to investigate the effects of compost and biochar amendments on diverse soil types and native plant species.
The decision of male medaka to mate or fight depends on two complementary androgen signaling pathways
Authors: Nishiike Yuji , Okubo Kataaki
Published: May 2024

Adult male animals typically court and attempt to mate with females, while attacking other males. Emerging evidence from mice indicates that neurons expressing the estrogen receptor ESR1 in behaviorally relevant brain regions play a central role in mediating these mutually exclusive behavioral responses to conspecifics. However, the findings in mice are unlikely to apply to vertebrates in general because, in many species other than rodents and some birds, androgens—rather than estrogens—have been implicated in male behaviors. Here, we report that male medaka (
Oryzias latipes
) lacking one of the two androgen receptor subtypes (Ara) are less aggressive toward other males and instead actively court them, while those lacking the other subtype (Arb) are less motivated to mate with females and conversely attack them. These findings indicate that, in male medaka, the Ara- and Arb-mediated androgen signaling pathways facilitate appropriate behavioral responses, while simultaneously suppressing inappropriate responses, to males and females, respectively. Notably, males lacking either receptor retain the ability to discriminate the sex of conspecifics, suggesting a defect in the subsequent decision-making process to mate or fight. We further show that Ara and Arb are expressed in intermingled but largely distinct populations of neurons, and stimulate the expression of different behaviorally relevant genes including galanin and vasotocin, respectively. Collectively, our results demonstrate that male teleosts make adaptive decisions to mate or fight as a result of the activation of one of two complementary androgen signaling pathways, depending on the sex of the conspecific that they encounter.
Foraging mechanisms in excavate flagellates shed light on the functional ecology of early eukaryotes
Authors: Suzuki-Tellier Sei , Miano Federica , Asadzadeh Seyed Saeed , Simpson Alastair G. B. , Kiørboe Thomas
Published: May 2024

The phagotrophic flagellates described as “typical excavates” have been hypothesized to be morphologically similar to the Last Eukaryotic Common Ancestor and understanding the functional ecology of excavates may therefore help shed light on the ecology of these early eukaryotes. Typical excavates are characterized by a posterior flagellum equipped with a vane that beats in a ventral groove. Here, we combined flow visualization and observations of prey capture in representatives of the three clades of excavates with computational fluid dynamic modeling, to understand the functional significance of this cell architecture. We record substantial differences amongst species in the orientation of the vane and the beat plane of the posterior flagellum. Clearance rate magnitudes estimated from flow visualization and modeling are both like that of other similarly sized flagellates. The interaction between a vaned flagellum beating in a confinement is modeled to produce a very efficient feeding current at low energy costs, irrespective of the beat plane and vane orientation and of all other morphological variations. Given this predicted uniformity of function, we suggest that the foraging systems of typical excavates studied here may be good proxies to understand those potentially used by our distant ancestors more than 1 billion years ago.
Astrocyte-to-microglia communication via Sema4B-Plexin-B2 modulates injury-induced reactivity of microglia
Authors: Casden Natania , Belzer Vitali , El Khayari Abdellatif , El Fatimy Rachid , Behar Oded
Published: May 2024

After central nervous system injury, a rapid cellular and molecular response is induced. This response can be both beneficial and detrimental to neuronal survival in the first few days and increases the risk for neurodegeneration if persistent. Semaphorin4B (Sema4B), a transmembrane protein primarily expressed by cortical astrocytes, has been shown to play a role in neuronal cell death following injury. Our study shows that after cortical stab wound injury, cytokine expression is attenuated in
Sema4B
−/−
mice, and microglia/macrophage reactivity is altered. In vitro, Sema4B enhances the reactivity of microglia following injury, suggesting astrocytic Sema4B functions as a ligand. Moreover, injury-induced microglia reactivity is attenuated in the presence of
Sema4B
−/−
astrocytes compared to
Sema4B
+/-
astrocytes. In vitro experiments indicate that Plexin-B2 is the Sema4B receptor on microglia. Consistent with this, in microglia/macrophage-specific
Plexin-B2
−/−
mice, similar to
Sema4B
−/−
mice, microglial/macrophage reactivity and neuronal cell death are attenuated after cortical injury. Finally, in
Sema4B
/
Plexin-B2
double heterozygous mice, microglial/macrophage reactivity is also reduced after injury, supporting the idea that both Sema4B and Plexin-B2 are part of the same signaling pathway. Taken together, we propose a model in which following injury, astrocytic Sema4B enhances the response of microglia/macrophages via Plexin-B2, leading to increased reactivity.
Equal Opportunities in Rural Tourism Entrepreneurship: Challenges in Malaysia
Authors: Gan Joo-Ee
Published: May 2024

Malaysia’s rural demography is multi-racial, with a blend of indigenous sub-groups. To advance the socio-economic status of rural communities, the government introduced various incentives and protectionist policies, including targeted measures in tourism development. As rural Malaysia is predominantly home to the Malays, the indigenous Orang Asli and the natives of Sabah and Sarawak, these policies are consistent with the government’s constitutional responsibility to safeguard these groups’ welfare. Notwithstanding the equal opportunity premise of the tourism policies, the government’s initiatives to advance rural tourism entrepreneurship arguably benefit some groups more than others. In West Malaysia, this is due to the indigenous Orang Asli’s lack of entrepreneurial readiness, which means that they are less able to capitalize on these opportunities. Consequently, the Malay entrepreneurs reap the benefits of protectionist policies and government aid, while the Orang Asli lag behind in tourism participation. This is arguably the outcome of a broad-brush approach in capacity building, with limited differentiation between the rural communities.

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© The Author 2024
Evidence Use in Policymaking: The Case of a Hotel Policy in Western Australia
Authors: Garcia Carolina I. , Pforr Christof , Volgger Michael
Published: May 2024

This case study explores the development of a policy launched in 2011 to incentivise hotel investments in Western Australia, especially in its capital city, Perth. To understand the policy process, we studied relevant documents, including policy plans, promotional material, annual reports, industry reports and records of Parliament debates. This approach allowed us to assess the use of evidence throughout three policy phases: (i) the process of building a case for the development of hotel incentives (the
why
); (ii) the design of hotel incentives as part of a broader tourism strategy (the
what
); and (iii) the implementation of this policy and the outcomes it achieved (the
how
).

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© The Authors 2024
Community Tourism and Indigenous Territory Defense: The Case of San Miguel del Bala in the Bolivian Amazon
Authors: Machaca Natalia M. , Leigue Gabriela R.
Published: May 2024

In Bolivia, the Madidi National Park is home to the Tacana Indigenous Community “San Miguel del Bala,” which, within the framework of the plurinational process, obtained its title as a Community Territory of Origin in 2021. Concurrently, during the 1990s, the government began establishing the first protected areas, adopting regulations with a primary focus on biodiversity conservation. In some cases, this led to restrictions and limitations on economic and subsistence activities rooted in ancestral practices. Community-based tourism, implemented by San Miguel del Bala, emerged as one of the few possibilities to alleviate and address these restrictions. Simultaneously, it became a means of revaluing the culture. The overlapping of San Miguel del Bala as a Community Territory of Origin and a protected area involves constitutional rights for shared management, a process that currently has several limitations. Adding to this complex situation is the entrance of extractive projects that contradict conservation regulations and the rights of prior consultation with indigenous populations regarding resource exploitation. As a result, they pose threats to the lives, cultures, and territories of the Tacana. In this context, the development of indigenous community tourism is transforming into a strategy for the defense of ancestral Indigenous territory.

Information

© The Authors 2024
British Architecture
Authors: Arnold Dana
Published: May 2024

British Architecture: A Very Short Introduction presents an original and engaging introduction to the architecture of the British Isles from medieval times to the present. Avoiding the traditional approach of a chronological survey of architects and architectural style, the chapters present thematic explorations of key aspects of British architecture that still have relevance today. The illustrated chapters demonstrate the cultural significance of British architecture, how it reflects social trends, and the ways in which it can project identity. Written in an accessible jargon-free style, this VSI is a refreshing and sophisticated consideration of British architecture that is essential reading for students, professionals, and those wishing to know more about this fascinating topic.
There’s no place like home
Authors: Arnold Dana
Published: May 2024

This chapter looks into how different concepts of a home shaped British architecture. In British society, home refers to a place that embodies an impact on society while also being a place upon which society impacts. The chapter shows how the country house served as an indicator of the owners’ social status and wealth, and in turn how the growing interest in landscape design and developments in farming practices led to significant changes to other forms of housing, including new forms of urban dwellings. The chapter then notes that standardization and basic quantity surveying were the hallmarks of the production of the Georgian terraced house. Housing types in the 19th century and the development of New Towns in the 20th century are also considered.
Gradient boosted regression as a tool to reveal key drivers of temporal dynamics in a synthetic yeast community
Authors: Conacher Cleo Gertrud , Watson Bruce William , Bauer Florian Franz
Published: May 2024

Microbial communities are vital to our lives, yet their ecological functioning and dynamics remain poorly understood. This understanding is crucial for assessing threats to these systems and leveraging their biotechnological applications. Given that temporal dynamics are linked to community functioning, this study investigated the drivers of community succession in the wine yeast community. We experimentally generated population dynamics data and used it to create an interpretable model with a gradient boosted regression tree approach. The model was trained on temporal data of viable species populations in various combinations, including pairs, triplets, and quadruplets, and was evaluated for predictive accuracy and input feature importance. Key findings revealed that the inoculation dosage of non-Saccharomyces species significantly influences their performance in mixed cultures, while Saccharomyces cerevisiae consistently dominates regardless of initial abundance. Additionally, we observed multispecies interactions where the dynamics of Wickerhamomyces anomalus were influenced by Torulaspora delbrueckii in pairwise cultures, but this interaction was altered by the inclusion of S. cerevisiae. This study provides insights into yeast community succession and offers valuable machine learning-based analysis techniques applicable to other microbial communities, opening new avenues for harnessing microbial communities.
#956 Exome sequencing in adults with secondary thrombotic microangiopathy with kidney involvement
Authors: Lombardi Yannis , Rafat Cédric , Doreille Alice , Mousseaux Cyril , Luque Yosu , Dancer Marine , Coppo Paul , Mesnard Laurent
Published: May 2024

Background and Aims

Currently, genetic testing is recommended in patients with thrombotic microangiopathy (TMA) and renal involvement when a complement-dependent TMA is clinically suspected. Due to a possibly poor phenotype-genotype correlation, this strategy may be suboptimal. We aimed to assess the impact of a strategy using Exome Sequencing (ES) regardless of initial suspicion.

Method

We conducted a prospective observational study. Data was collected in all consecutive adult patients who received a primary diagnostic ES test as part of routine care for unexplained chronic kidney disease between October 10, 2017, and December 31, 2022, at the Nephrology Department of Assistance Publique-Hôpitaux de Paris/Sorbonne University, Paris, France (Tenon and Pitié-Salpêtrière hospitals). Patients with thrombotic thrombocytopenic purpura or typical hemolytic and uremic syndrome were not included. The association between patients’ phenotypes and genotypes was explored using a validated method relying on Term Frequency-Inverse Document Frequency (TF-IDF).

Results

1 413 patients underwent ES, of whom 153 (11%) had biological and/or histological indicators of TMA. ES identified a variant consistent with the renal phenotype in 20/153 (13%) cases. In 13/20 cases (65%), a genetic disorder which was not complement TMA was diagnosed: five patients had nephronophthisis (TTC21B, n = 4, NPHP3, n = 1); two had Alport's disease (COL4A4 and COL4A3, n = 1); one had Cobalamin-C deficiency (MMACHC); five had other distinct conditions (variants in SOX18, IFT140, WT1, TREX1 and UMOD). Direct clinical implications of performing ES were observed in 35/153 (23%) cases. An interactive web-app was developed to enable in-depth exploration of phenotype-genotype association, and no association between patients’ phenotypes and genotypes were observed.

Conclusion

First-tier ES in patients with TMA and renal involvement, irrespective of clinical suspicion, revealed diagnoses that would not have been initially obtained according to the currently recommended strategy. In patients with TMA and renal involvement, we did not find an association between patients’ phenotypes and genotypes.
#2045 Epigenetic data can predict initial treatment response in nephrotic syndrome
Authors: Hayward Samantha , Suderman Matthew , Welsh Gavin , Saleem Moin
Published: May 2024

Background and Aims

The majority of children with idiopathic nephrotic syndrome (INS) and adults with Focal Segmental Glomerulosclerosis (FSGS) and Minimal Change Disease (MCD) receive glucocorticoid treatment at diagnosis. Only those with a high likelihood of having monogenic disease or a contraindication to steroids might avoid this treatment. About 10% overall will not respond to steroids and we have no reliable way of prospectively identifying these patients. Therefore, some patients will receive a futile treatment which is accompanied by significant side effects.

DNA methylation (DNAm) is an epigenetic mechanism meaning that it can induce stable but reversible changes in gene expression without any change in underlying DNA sequence. DNAm has shown great potential as a treatment stratification tool, for example, DNAm data is used in oncology to identify which patients are likely to benefit from alkylating chemotherapy.

We investigated whether DNAm can predict initial response to steroids in children and young adults with nephrotic syndrome.

Method

Three hundred and seventeen patients with INS were selected from the NephroS and NURTuRE cohorts. All patients were diagnosed with INS ≤ 30 years of age and those who underwent a renal biopsy had a histological diagnosis of either FSGS or MCD. Peripheral blood DNAm measurements were generated using the Illumina MethylationEPIC Beadchip (>850, 000 CpG sites). Clinical data was used to label patients by their initial response to steroids (sensitive, n = 156, or resistant, n = 161).

Machine learning models were created to predict steroid response from the DNAm data. Models were generated using elastic net following feature filtering, and model hyperparameters were tuned and performance measured within the context of cross validation.

To exclude whether cumulative steroid exposure prior to sample collection had impacted our results, the CpG sites in the final model were compared to those identified in a published study examining steroid exposure and DNAm (4).

Results

The 317 INS patients had a median age at diagnosis of 5 years (IQR 2-10) and a median time between diagnosis and DNAm sample collection of 4 years (IQR 1-10). The steroid resistant group were made up of patients with known monogenic disease (n = 75, 24%) and those without pathogenic variants (n = 86, 27%).

Initial response to steroid treatment could be predicted with 65% accuracy and an area under the curve (AUC) of 0.75, (sensitivity 0.65, specificity of 0.66, see Fig. 1) using DNAm levels at 14 CpG sites. There was no overlap between the 14 CpG sites in our prediction model and those that are known to alter with steroid treatment.

Conclusion

We have demonstrated that peripheral blood cell DNAm profiles are a promising predictor of steroid response in INS. Further work to incorporate genetic data into the prediction models is underway and external validation of the results in a separate cohort of patients is required.
#162 Single-nucleus RNA-seq of biopsy-confirmed IgA nephropathy reveals cell-specific transcriptomic alteration
Authors: Kim Dong Ki , Park Sehoon , Joo Jeongho , Cho Jeong Min , Joo Kwon Wook
Published: May 2024

Background and Aims

Single-nucleus RNA-seq (SnRNA-seq) is a valuable method for identifying cell-specific transcriptomic alterations in kidney cells. Our objective was to investigate SnRNA-seq data from biopsy-confirmed IgA nephropathy (IgAN) cases and identify cell-specific alterations in the transcriptome.

Method

We collected snap-frozen kidney biopsy tissues from 6 cases of IgA nephropathy (IgAN) and 7 nephrectomy control cases. The disease control group included 3 cases of diabetic kidney disease, 6 cases of minimal change disease, and 6 PLA2R-Ab positive membranous nephropathy cases. SnRNA-seq was performed on the kidney tissues, and kidney cells were identified in the dataset through UMAP clustering. We investigated differences in the proportion of kidney cell types and identified differentially expressed genes (DEGs). Additionally, we searched for representative gene loci previously reported in a multiethnic genome-wide association study (GWAS).

Results

We successfully collected transcriptomic profiles of >50 000 cells from IgAN, with a considerable enrichment of intraglomerular cells. The DEG analysis revealed a high number of DEGs in mesangial cells, fibroblasts, and vascular smooth muscle cells in the IgAN transcriptome compared to the nephrectomy and disease control cases. In the gene set enrichment analysis, the epithelial-mesenchymal transition pathway was enriched in the glomerular cells of IgAN. Furthermore, among various GWAS loci, ETS1 was the gene significantly highly expressed in the mesangial cells of IgAN, consistent across the compared control groups.

Conclusion

This investigation represents the largest SnRNA-Seq profiling of IgAN kidney cells to date. We identified notable enriched cell-specific pathways in IgAN. ETS1 may be a kidney-indwelling causal factor for IgAN pathophysiology, considering its notable significance in both previous GWAS results and the current SnRNA-Seq data.
#369 Anti-nephrin antibodies identify patients with steroid-resistant nephrotic syndrome responsive to immunosuppressants
Authors: Raglianti Valentina , Angelotti Maria Lucia , Cirillo Luigi , Landini Samuela , Palazzo Viviana , Ghiggeri Gian Marco , Angeletti Andrea , Mazzinghi Benedetta , Francesca Becherucci , Romagnani Paola
Published: May 2024

Background and Aims

The presence of circulating anti-nephrin antibodies has been recently reported in some patients with nephrotic syndrome (NS) and minimal change lesions, implying an autoimmune podocytopathy subset. We hypothesized that the presence of anti-nephrin antibodies would identify a subset of patients with steroid resistant NS (SRNS) and explain their response to second-line immunosuppressant therapy before and after kidney transplantation.

Method

We evaluated 31 patients with available kidney biopsy samples of our previously described prospective cohort of SRNS patients, genetically tested with whole exome sequencing at Meyer University Hospital IRCCS. By using high-resolution confocal microscopy, we assessed the co-localization between IgG and nephrin staining on kidney biopsy. To unequivocally establish anti-nephrin specificity of the deposited IgG, we performed super-resolution STimulated Emission Depletion (STED) microscopy.

Results

We observed anti-nephrin antibodies in 35.5% of patients with SRNS irrespective of podocytopathy lesion pattern. Antibody-positive (Antibody+) patients had a more severe NS at onset and better response to immunosuppression therapy compared to antibody-negative (Antibody-) patients. Only 1/11 Antibody+ patient developed chronic kidney disease compared to 9/20 Antibody- patients over a 10-year period. The single multidrug-resistant Antibody+ patient reached kidney failure had a pathogenic variant in the autosomal dominant-transmitted LMX1B. The patient experienced recurrence of NS after kidney transplantation with a positive response to plasmapheresis and rituximab. The allograft biopsy confirmed the presence of anti-nephrin antibodies.

Conclusion

The observed variability in patients with SRNS, influenced by a combination of genetic factors and nephrin autoimmunity, likely contributes to the diverse long-term outcomes and variations in responses to second-line immunosuppressant therapy.
#2510 Urokinase plasminogen activator receptor upregulation in lupus nephritis associates with distinct interferon hub genes in stressed podocytes
Authors: Zeisberg Michael , Tampe Björn
Published: May 2024

Background and Aims

Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease characterized by immune system dysfunction, leading to inflammation and damage in various organs and tissues. Renal involvement known as lupus nephritis is one of the most severe complications occurring in 60% of patients with SLE, significantly impacting patient morbidity and mortality. Understanding the intricate relationship between SLE and renal manifestations is crucial for effective management and improved patient outcomes. Recently, the cell surface urokinase plasminogen activator receptor (uPAR) has emerged as a significant player in the pathogenesis of lupus nephritis. However, the molecular mechanisms through which uPAR influences lupus nephritis remain an active area of investigation. Therefore, we here pursued a transcriptome array-based approach to identify molecular patterns in association with uPAR in lupus nephritis.

Method

PLAUR mRNA expression levels (encoding uPAR, reporter ID: 210845_s_at, platform: Affymetrix Human Genome U133 Plus 2.0 Array, altCDF v10) were extracted from microdissected control kidneys (glomerular compartment: n = 14) and lupus nephritis (glomerular: n = 32, tubulointerstitial: n = 32). Pathway analysis was performed for gene enrichment associated with PLAUR mRNA expression with a correlation threshold of ≥0.5 by using reactome (https://reactome.org), pathways with a predefined entities value of P ≤ .001 were included. Data was validated in cultured podocytes stressed with Adriamycin, protein expression profiling was performed by mass spectrometry in combination with stable isotope labelling by amino acids in cell culture (SILAC).

Results

We here identified a predominant glomerular expression of uPAR in lupus nephritis that was increased as compared to healthy controls. While glomerular uPAR expression was predominantly associated with interferon signaling, none of type I or type II interferons were induced. Interestingly, we identified distinct interferon hub genes that were associated with uPAR in lupus nephritis and enriched in stressed podocytes (GBP2: P < .0001, IFI30: P = .0006, IFIT1: P < .0001, IFITM3: P = .0308). Finally, uPAR and associated interferon hub genes correlated with proteinuria in lupus nephritis.

Conclusion

The therapeutic implications of targeting uPAR in lupus nephritis are promising, and ongoing research endeavors are aimed at unraveling the complexities of uPAR as a potential diagnostic marker and therapeutic target for this challenging renal pathology. We here expand our current knowledge and link uPAR upregulation in lupus nephritis to distinct interferon hub genes in stressed podocytes.