bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the Cross-Study Replicability of Tuberculosis Gene Signatures Using 49 Curated Transcriptomic Datasets
Authors: Wang Xutao , Harper Katie , Sinha Pranay , Johnson W. Evan , Patil Prasad
Published: December 2023

Background

Tuberculosis (TB) is the leading cause of infectious disease mortality worldwide. Numerous blood-based gene expression signatures have been proposed in the literature as alternative tools for diagnosing TB infection. Ongoing efforts are actively focused on developing additional signatures in other TB-related contexts. However, the generalizability of these signatures to different patient contexts is not well-characterized. There is a pressing need for a well-curated database of TB gene expression studies for the systematic assessment of existing and newly developed TB gene signatures.

Results

We built the curatedTBData, a manually-curated database of 49 TB transcriptomic studies. This data resource is freely available through GitHub and as an R Bioconductor package that allows users to validate new and existing biomarkers without the challenges of harmonizing heterogeneous studies. We also demonstrate the use of this data resource with cross-study comparisons for 72 TB gene signatures. For the comparison of subjects with active TB from healthy controls, 19 gene signatures had weighted mean AUC of 0.90 or greater, with the highest result of 0.94. In active TB disease versus latent TB infection, 7 gene signatures had weighted mean AUC of 0.90 or greater, with a maximum of 0.93. We also explore ensembling methods for averaging predictions from multiple gene signatures to significantly improve diagnostic ability beyond any single signature.

Conclusions

The curatedTBData data package offers a comprehensive resource of curated gene expression and clinically annotated data. It could be used to identify robust new TB gene signatures, to perform comparative analysis of existing TB gene signatures, and to develop alternative gene set scoring or ensembling methods, among other things. This resource will also facilitate the development of new signatures that are generalizable across cohorts or more applicable to specific subsets of patients (e.g. with rare comorbid conditions, etc.). We demonstrated that these blood-based gene signatures could distinguish patients with distinct TB outcomes; moreover, the combination of multiple gene signatures could improve the overall predictive accuracy in differentiating these subtypes, which point out an important aspect for the translation of genomics to clinical implementation.
A mitochondrial quality control mechanism reverses the phagosome maturation arrest caused byMycobacterium tuberculosis
Authors: Verma Surbhi , Das Mrinmoy , Sharma Raman D. , Yadav Vikas , Thakur Shweta , Sharma Priya , Marzuki Mardiana , Foo Shihui , Piperno Giulia M. , Khan Mehak Z. , Mathew Babu , Bajpai Meenu , Maras Jaswinder Singh , Howland Shanshan , Sarkar Sovan , Benvenuti Federica , Singh Amit , Nandicoori Vinay , Singhal Amit , Kumar Dhiraj
Published: December 2023

Phagosome maturation arrest (PMA) imposed byMycobacterium tuberculosis(Mtb) is a classic tool that helpsMtbevade macrophage anti-bacterial responses. The exclusion of RAB7, a small GTPase, fromMtb-phagosomes underscores PMA. Here we report an unexpected mechanism that triggers crosstalk between the mitochondrial quality control (MQC) and the phagosome maturation pathways that reverses the PMA. CRISPR-mediated p62/SQSTM1 depletion (p62KD) blocks mitophagy flux without impacting mitochondrial quality. Inp62KDcells,Mtbgrowth and survival are diminished, mainly through witnessing an increasingly oxidative environment and increased lysosomal targeting. The lysosomal targeting ofMtbis facilitated by enhanced TOM20+mitochondria-derived vesicles (MDVs) biogenesis, a key MQC mechanism. Inp62KDcells, TOM20+-MDVs biogenesis is MIRO1/MIRO2-dependent and delivered to lysosomes for degradation in a RAB7-dependent manner. Upon infection inp62KDcells, TOM20+-MDVs get extensively targeted toMtb-phagosomes, inadvertently facilitating RAB7 recruitment, PMA reversal and lysosomal targeting ofMtb. Triggering MQC collapse inp62KDcells further diminishesMtbsurvival signifying cooperation between redox- and lysosome-mediated mechanisms. The MQC-anti-bacterial pathway crosstalk could be exploited for host-directed anti-tuberculosis therapies.
High-throughput Microfluidic 3D Outer Blood-Retinal Barrier Model in a 96-Well Format: Analysis of Cellular Interactions and Barrier Function in Retinal Health and Disease
Authors: Kim Jiho , Song Youngsook , Jolly Amber L. , Hwang Taeseon , Kim Suryong , Lee Byungjun , Jang Jinhwan , Jo Dong Hyun , Baek Kyusuk , Liu Tsung-Li , Yoo Sanghee , Jeon Noo Li
Published: December 2023

Numerous diseases, including AMD (age-related macular degeneration), arise from the blood-retinal barrier and blood vessel abnormalities in the eye; unfortunately, there is a lack of reliable in-vitro models for their systematic study. This study describes a high-throughput microphysiological system (MPS) designed to model the outer Blood-Retinal Barrier (oBRB). The MPS platform is engineered to integrate seamlessly with high-content screening technologies, utilizing a design with a single oBRB model incorporating RPE (retina pigment epithelial cells) and endothelial cell co-culture to fit within a single 96-well. Arranged in the standard 96-well plate format, the platform allows high-throughput assessment of barrier integrity through 3D confocal imaging (ZO-1 staining), Trans Epithelial Electrical Resistance (TEER), and permeability measurements.

The oBRB model enables the investigation of crosstalk among different cell types in co-culture. This includes assessing changes in the barrier integrity of the Retinal Pigment Epithelium (RPE) monolayer and investigating neovascularization events resulting from endothelial cell remodeling. The platform is positioned for utility in drug discovery and development efforts targeting diseases involving oBRB damage and choroidal neovascularization, such as age-related macular degeneration (AMD).
Biosensors Characterization: Formal methods from the Perspective of Proteome Fractions
Authors: Vaccari Nicolás A. , Zevallos-Aliaga Dahlin , Peeters Tom , Guerra Daniel G.
Published: December 2023

Many studies characterize transcription factors and other regulatory elements to control the expression of heterologous genes in recombinant systems. However, most lack a formal approach to analyse the parameters and context-specific variations of these regulatory components. This study addresses this gap by establishing formal and convenient methods for characterising regulatory circuits. We model the bacterial cell as a collection of a small number of proteome fractions. Then, we derive the proteome fraction over time and obtain a general theorem describing its change as a function of its expression fraction, which represents a specific portion of the total biosynthesis flux of the cell. Formal deduction reveals that when the proteome fraction reaches a maximum, it becomes equivalent to its expression fraction. This equation enables the reliable measurement of the expression fraction through direct protein quantification. In addition, experimental data demonstrate a linear correlation between protein production rate and specific growth rate over a significant time period. This suggests a constant expression fraction within this window. The expression fractions estimated from the slopes of these intervals and those obtained from maximum protein amount points can both be independently fitted to a Hill function. In the case of an IPTG biosensor, in five cellular contexts, expression fractions determined by the maximum method and the slope method produced similar dose-response parameters. Additionally, by analysing two more biosensors, for mercury and cumate detection, we demonstrate that the slope method can be effectively applied to various systems, generating reliable Hill function parameters.
Caveolin scaffolding domain (CSD) peptide LTI-2355 modulates the phagocytic and synthetic activity of lung derived myeloid cells in Idiopathic Pulmonary Fibrosis (IPF) and Post-acute sequelae of COVID-fibrosis (PASC-F)
Authors: Creyns Brecht , MacKenzie BreAnne , Sa Yago , Coelho Ana Lucia , Christensen Dale , Parimon Tanyalak , Windsor Brian , Hogaboam Cory M.
Published: December 2023

Rationale

The role of the innate immune system in Idiopathic Pulmonary Fibrosis (IPF) remains poorly understood. However, a functional myeloid compartment is required to remove dying cells and cellular debris, and to mediate innate immune responses against pathogens. Aberrant macrophage activity has been described in patients with Post-acute sequelae of COVID fibrosis (PASC-F). Therefore, we examined the functional and synthetic properties of myeloid cells isolated from normal donor lung and lung explant tissue from both IPF and PASC-F patients and explored the effect of LTI-2355, a Caveolin Scaffolding Domain (CSD) peptide, on these cells.

Methods & Results

CD45+myeloid cells isolated from lung explant tissue from IPF and PASC-F patients exhibited an impaired capacity to clear autologous dead cells and cellular debris. Uptake of pathogen-coated bioparticles was impaired in myeloid cells from both fibrotic patient groups independent of type of pathogen highlighting a cell intrinsic functional impairment. LTI-2355 improved the phagocytic activity of both IPF and PASC-F myeloid cells, and this improvement was paired with decreased pro-inflammatory and pro-fibrotic synthetic activity. LTI-2355 was also shown to primarily target CD206-expressing IPF and PASC-F myeloid cells.

Conclusions

Primary myeloid cells from IPF and PASC-F patients exhibit dysfunctional phagocytic and synthetic properties that are reversed by LTI-2355. Thus, these studies highlight an additional mechanism of action of a CSD peptide in the treatment of IPF and progressive fibrotic lung disease.
Spatial segregation and aging of metabolic processes underlie phenotypic heterogeneity in mycobacteria
Authors: Gwin Celena M. , Gupta Kuldeepkumar R. , Lu Yao , Shao Lin , Rego E. Hesper
Published: December 2023

Individual cells within clonal populations of mycobacteria vary in size, growth rate, and antibiotic susceptibility. Heterogeneity is, in part, determined by LamA, a protein found exclusively in mycobacteria. LamA localizes to sites of new cell wall synthesis where it recruits proteins important for polar growth and establishing asymmetry. Here, we report that in addition to this function, LamA interacts with complexes involved in oxidative phosphorylation (OXPHOS) at a subcellular location distinct from cell wall synthesis. Importantly, heterogeneity depends on a unique extension of the mycobacterial ATP synthase, and LamA mediates the coupling between ATP production and cell growth in single cells. Strikingly, as single cells age, concentrations of proteins important for oxidative phosphorylation become less abundant, and older cells rely less on oxidative phosphorylation for growth. Together, our data reveal that central metabolism is spatially organized within a single mycobacterium and varies within a genetically identical population of mycobacteria. Designing therapeutic regimens to account for this heterogeneity may help to treat mycobacterial infections faster and more completely.
Autoethnography in the modern workplace: a reflexive journey
Authors: Orel Marko
Published: December 2023

Purpose

This conceptual paper seeks to critically evaluate and illuminate the diverse autoethnographic methodologies that are pivotal for understanding the dynamics of contemporary workspaces. The objective is to contribute to the ongoing scholarly debate on the value of autoethnography in workplace research and explore how it can shed light on complex organizational phenomena.

Design/methodology/approach

The paper adopts a narrative literature review approach, focusing on four main forms of autoethnography: realist, impressionistic, expressionistic and conceptualistic autoethnographies. Each form is discussed and dissected, emphasizing their specific sub-forms and illustrating their application through representative examples. The paper engages in a critical debate on utilizing autoethnography in workplace research.

Findings

The findings illuminate how autoethnographic methods can be used to gain nuanced and complex understandings of personal experiences situated in workplace culture, as well as how broader social and cultural contexts shape these experiences. The study also highlights the potential of these methods to explore marginalized and silenced stories within workplaces and contribute to the knowledge on power dynamics, inequalities and injustices embedded in the organizational culture.

Practical implications

The following contribution discusses approaches for conducting autoethnographic explorations of selected work environments, offering researchers valuable insights into these methods' application. Through better comprehension and application of these methodologies, researchers can enhance their contribution toward cultivating more inclusive and equitable workplace environments.

Originality/value

The paper stands out in its extensive review and critical discussion of the autoethnographic methods as applied in workplace research. It expands upon individual autoethnographic studies by providing a comprehensive, multifaceted perspective, delving into the merits and limitations of these approaches in particular context of researching contemporary places of work.
Dynamic energy landscapes of predators and the implications for modifying prey risk
Authors: Papastamatiou Yannis P. , Binder Benjamin M. , Boswell Kevin M. , Malone Margaret A. , Heithaus Michael R. , Huveneers Charlie , Mourier Johann , Harborne Alastair R.
Published: December 2023

Landscapes of fear describe a spatial representation of an animal's perceived risk of predation and the associated foraging costs, while energy landscapes describe the spatial representation of their energetic cost of moving and foraging. Fear landscapes are often dynamic and change based on predator presence and behaviour, and variation in abiotic conditions that modify risk. Energy landscapes are also dynamic and can change across diel, seasonal, and climatic timescales based on variability in temperature, snowfall, wind/current speeds, etc.

Recently, it was suggested that fear and energy landscapes should be integrated. In this paradigm, the interaction between landscapes relates to prey being forced to use areas of the energy landscape they would avoid if risk were not a factor. However, dynamic energy landscapes experienced by predators must also be considered since they can affect their ability to forage, irrespective of variation in prey behaviour. We propose an additional component to the fear and dynamic energy landscape paradigm that integrates landscapes of both prey and predators, where predator foraging behaviour is modulated by changes in their energyscape.

Specifically, we integrate the predator's energy landscape into foraging theory that predicts prey patch‐leaving decisions under the threat of predation. We predict that as a predator's energetic cost of foraging increases in a habitat, then the prey's foraging cost of predation and patch quitting harvest rate, will decrease. Prey may also decrease their vigilance in response to increased energetic foraging costs for predators, which will lower giving‐up densities of prey.

We then provide examples in terrestrial, aerial, and marine ecosystems where we might expect to see these effects. These include birds and sharks which use updrafts that vary based on wind and current speeds, tidal state, or temperature, and terrestrial predators (e.g. wolves) whose landscapes vary seasonally with snow depth or ice cover which may influence their foraging success and even diet selection.

A predator perspective is critical to considering the combination of these landscapes and their ecological consequences. Dynamic predator energy landscapes could add an additional spatiotemporal component to risk effects, which may cascade through food webs.

Read the free Plain Language Summary for this article on the Journal blog.
Benchmarking the Mantel test and derived methods for testing association between distance matrices
Authors: Quilodrán Claudio S. , Currat Mathias , Montoya‐Burgos Juan I.
Published: December 2023

Testing the association between objects is central in ecology, evolution, and quantitative sciences in general. Two types of variables can describe the relationships between objects: point variables (measured on individual objects), and distance variables (measured between pairs of objects). The Mantel test and derived methods have been extensively used for distance variables. Yet, these methods have been criticized due to low statistical power and inflated type I error when spatial autocorrelation is present. Here, we assessed the statistical power between different types of tested variables and the type I error rate over a wider range of autocorrelation intensities than previously assessed, both on univariate and multivariate data. We also illustrated the performance of distance matrix statistics through computational simulations of genetic diversity. We show that the Mantel test and derived methods are not affected by inflated type I error when spatial autocorrelation affects only one variable when investigating correlations, or when either the response or the explanatory variable(s) is affected by spatial autocorrelation while investigating causal relationships. As previously noted, with autocorrelation affecting more variables, inflated type I error could be reduced by modifying the significance threshold. Additionally, the Mantel test has no problem of statistical power when the hypothesis is formulated in terms of distance variables. We highlight that transformation of variable types should be avoided because of the potential information loss and modification of the tested hypothesis. We propose a set of guidelines to help choose the appropriate method according to the type of variables and defined hypothesis.
Non‐invasive age estimation based on faecal DNA using methylation‐sensitive high‐resolution melting for Indo‐Pacific bottlenose dolphins
Authors: Yagi Genfu , Qi Huiyuan , Arai Kana , Kita Yuki F. , Kogi Kazunobu , Morisaka Tadamichi , Yoshioka Motoi , Inoue‐Murayama Miho
Published: December 2023

Age is necessary information for the study of life history of wild animals. A general method to estimate the age of odontocetes is counting dental growth layer groups (GLGs). However, this method is highly invasive as it requires the capture and handling of individuals to collect their teeth. Recently, the development of DNA‐based age estimation methods has been actively studied as an alternative to such invasive methods, of which many have relied on used biopsy samples. However, if DNA‐based age estimation can be developed from faecal samples, age estimation can be performed entirely non‐invasively. We developed an age estimation model using the methylation rate of two gene regions, GRIA2 and CDKN2A, measured through methylation‐sensitive high‐resolution melting (MS‐HRM) from faecal samples of wild Indo‐Pacific bottlenose dolphins (Tursiops aduncus). The age of individuals was known through conducting longitudinal individual identification surveys underwater. Methylation rates were quantified from 36 samples collected from 30 individuals. Both gene regions showed a significant correlation between age and methylation rate. The age estimation model was constructed based on the methylation rates of both genes which achieved sufficient accuracy (after LOOCV: MAE = 5.08, R2 = 0.33) for the ecological studies of the Indo‐Pacific bottlenose dolphins, with a lifespan of 40–50 years. This is the first study to report the use of non‐invasive faecal samples to estimate the age of marine mammals.
A new centrality index designed for multilayer networks
Authors: Lotfi Nastaran , Requejo Henrique S. , Rodrigues Francisco A. , Mello Marco A. R.
Published: December 2023

Since its inception, the keystone species concept has become a central theoretical framework in ecology. Among many approaches, keystones have been operationalized in natural and human environments using centrality metrics applied to monolayer networks. Despite the great success of this approach, as species make several types of interactions, recent studies on keystones moved from monolayer to multilayer networks.

To help fulfil the need for a centrality metric designed for multilayer networks, here we introduce Gnorm. We tested the performance of our new metric using in silico data in addition to an empirical data set of frugivory and nectarivory interactions between bats and plants in the Neotropics. A comparison between the results obtained with different random and scale‐free networks demonstrates the performance of our new metric.

First, a modularity analysis based on the multilayer version of the Louvain algorithm enables the modules to be composed of nodes from different layers. Second, by setting the coupling parameter () and the resolution parameter (), module identity changes gradually, from single‐ to multiple‐node modules and from mono‐ to multilayer composition. Third, we check the number of modules from different layers to which a node belongs (G) at different levels of and . Finally, by observing how average G decreases with and , it is possible to calculate Gnorm and detect which nodes are most resistant to change in these two parameters. Those resistant nodes are identified as central in the multilayer structure. After applying this new analysis to the bat–plant network, we observed that it identified a different set of potential keystone species compared to previous analyses performed separately for each layer or the aggregated network.

In conclusion, our new metric opens a new way of operationalizing the keystone species concept in multilayer networks. It may help identify keystone species involved in different interaction types.
Partial cellular reprogramming: A deep dive into an emerging rejuvenation technology
Authors: Paine Patrick T. , Nguyen Ada , Ocampo Alejandro
Published: December 2023

Aging and age‐associated disease are a major medical and societal burden in need of effective treatments. Cellular reprogramming is a biological process capable of modulating cell fate and cellular age. Harnessing the rejuvenating benefits without altering cell identity via partial cellular reprogramming has emerged as a novel translational strategy with therapeutic potential and strong commercial interests. Here, we explore the aging‐related benefits of partial cellular reprogramming while examining limitations and future directions for the field.
Mocking while working with problematic representations: The irony of ethnographic sensibility in Indonesia
Authors: Riyanto Geger
Published: December 2023

In this essay, I contemplate the value of ethnography by reflecting on my experience and that of other anthropology‐trained individuals who engage with public socio‐ecological issues in Indonesia. While these issues are portrayed as urgent and are packaged with established representations of people and communities, ethnographic engagement produces representations that are at odds with them. Nevertheless, anthropology‐trained individuals in Indonesia have no way to address these issues other than to work with institutions that produce the problematic representations, and in doing so, inadvertently contribute to their reproduction. Furthermore, the academic anthropology ecosystem does not support the exhaustive exploration of these issues. Eventually, the sensibility generated by the practice of ethnography becomes more of a latent sensibility, which is critical of the predominant representations. It evokes internal conflict and a sense of irony, which most of the time cannot be expressed or practically addressed.
Comparing return of bowel function after right versus extended right hemicolectomy: a retrospective analysis
Authors: Maas Zak , Carson Daniel A. , McIntyre Rachel A. , Rahiri Jamie‐Lee , Wells Cameron , Cribb Benjamin , Omundsen Mark , Holm Teresa M.
Published: December 2023

Background

Prolonged postoperative ileus (PPOI) is associated with higher morbidity and extended inpatient stay. Although evidence suggests that PPOI is more common following right‐sided resections, it is uncertain if return to bowel function is similar following extended right (ERH) versus right hemicolectomy (RH).

Methods

The recovery of patients undergoing ERH and RH in a regional hospital in New Zealand was retrospectively compared, from 2012 to 2021. Rates of PPOI, return of bowel function and postoperative complications were compared. Other factors potentially relating to PPOI were analysed.

Results

293 patients were included (42 who underwent ERH, and 251 RH). PPOI was more common following ERH than RH (43% vs. 25%, P = 0.02). When accounting for the operative approach, rate of PPOI was not significantly different (42% open ERH vs. 36% open RH; P = 0.56). Excluding PPOI, return of bowel function did not differ between groups. Patient undergoing ERH versus RH had significantly higher length of stay (1 day) and Hb drop (2.5 g/L) postoperatively.

Conclusion

Higher rates of PPOI have been demonstrated in ERH versus RH however when controlling for approach, there was not a significant difference. Further interrogation into rates of PPOI (particularly after laparoscopic surgery) are warranted to tailor locoregional ERAS protocols.
Structure–function correlation of retinal photoreceptors in PRPH2‐associated central areolar choroidal dystrophy patients assessed by high‐resolution scanning laser imaging and microperimetry
Authors: Mulders Timo , van der Zanden Ludo , Klevering B. Jeroen , Hoyng Carel , Theelen Thomas
Published: December 2023

Purpose

High Magnification Module (HMM™, Heidelberg Engineering, Heidelberg, Germany) imaging is a novel technique, designed to visualize the retina at a cellular level. To assess the potential of HMM™‐based metrics as endpoints for future trials, we evaluated correlations between structural HMM™ cone metrics, spectral‐domain OCT (SD‐OCT, Heidelberg Engineering, Heidelberg, Germany) and retinal sensitivity on microperimetry (MP, MAIA, CenterVue, Padova, Italy) in healthy subjects and p.(Arg142Trp) PRPH2‐associated Central Areolar Choroidal Dystrophy (CACD) patients.

Methods

We projected a default 10° MP grid on composite HMM™ images and performed automated cone density (CD), intercell distance (ICD) and nearest neighbour distance (NND) analysis at stimuli located at 3° and 5° retinal eccentricity. We manually measured intrasubject outer retinal thickness on SD‐OCT in absolute and relative scotomas, located outside of focal atrophy.

Results

We included 15 CACD patients and five healthy subjects. We found moderate‐to‐strong correlations of HMM™ metrics and MP sensitivity at 3° eccentricity from the fovea. We found the outer retina at the locations of absolute scotomas to be statistically significant thinner (p = 0.000003, one‐sample t‐test), as the outer retinal thickness at locations of relative scotomas. Interestingly, HMM™ metrics of these areas did not differ significantly.

Conclusions

We found significant correlations between structural photoreceptors metrics on HMM™ imaging and retinal sensitivity on MP in healthy subjects and CACD patients. A multimodal approach, combining SD‐OCT, MP and HMM™ imaging, allows for detailed mapping of retinal photoreceptor integrity and restitution potential, important data that could serve as biomarkers in future clinical trials.
Navigating the Australian child protection system: The importance of formal and informal support for carers to effectively provide care to children in out‐of‐home care
Authors: Venables Jemma , Povey Jenny , Boman Madonna , Healy Karen , Baxter Janeen , Austerberry Sophie , Thompson Kate
Published: December 2023

Children in out‐of‐home care (OOHC) are a vulnerable group who often experience poorer outcomes than their peers who are not in OOHC. In 2020–2021, there were approximately 46 200 children in OOHC in Australia, with 91% in a family setting with foster or kinship carers. Data from other countries show similar patterns indicating that foster and kinship carers provide care for most children in OOHC. To effectively provide children in OOHC with the care they require, including safety, stability, and connection, the carers need a social support system that equips them to meet the needs of these vulnerable children and to prevent the breakdown of placements. The study presented in this paper draws on social constructivist and critical perspectives to examine the formal and informal social support available to carers using data from a qualitative study investigating OOHC in Queensland, Australia. Our sample is 113 carers, caring for 194 children aged 1–12 years old. We find lack of integration across formal support systems and failure to recognize the invisible workload undertaken by carers are two key challenges faced by carers. Upskilling and stabilizing the child protection work force, as well as better training for carers, is also required. Addressing these issues will enhance the social support systems of carers and improve the safety, stability, and connection of children in OOHC.
Organizational and service support for boys' pathways out of commercial sexual exploitation in Nepal: Key learning for an under‐recognized population
Authors: Zhou Xiaochen , Jordan Lucy P. , O'Leary Patrick
Published: December 2023

Boys are a group who experience commercial sexual exploitation (CSE) but are often less visible than girls with the same experience. There is limited evidence regarding the experiences of organizational support from the perspectives of boys with CSE experience. This study, conducted in Kathmandu, Nepal, adopted a mixed‐method approach, combining data from actor mapping, survey, and in‐depth case studies. It explores (1) what services are available for boys with CSE experience; (2) how services help boys to exit the commercial sex sector; and (3) what the future service needs are for boys with CSE experience. In our sample, most of the boys who had been involved in the CSE industry as minors, identified themselves as sexual minorities. The findings suggest that despite the inadequacy of the services available for boys with CSE experience, around half of the boys who successfully exited the industry reported that support from non‐governmental organization (NGOs) was crucial to their pathways out. The findings indicate the continuity of follow‐up services is needed. This study underscores the importance of organizational and service support. It highlights ongoing needs regarding economic determinants. This study sheds light on future NGO service programme development and policy initiatives on protecting boys with CSE experience.
Space, people, activity and time: A theoretical model for understanding children's outdoor play with specific reference to the historical protected central areas of Beijing, China
Authors: Tang Pai , Woolley Helen
Published: December 2023

Aiming to document children's daily outdoor play experiences in a rapidly developing urban environment, this research is based on a case study involving children living in the central Shichahai area in Beijing to provide an understanding from the scarce Chinese perspective. Based on the development of the SPIT model, this study proposes the SPAT model and investigates its subject from dimensions of space, people, activities and time. This study employs a qualitative triangulation approach to investigating childhood experience, using data collection methods including interviews, observations and diaries. This data record the children's outdoor play experience and its analysis addresses the lack of knowledge and understanding of childhood play experience in Chinese cities. The factors which have a profound influence on children's play experience in a developing urban contexts are discussed and interpreted in terms of a range of factors which have influenced the transformation of the urban environment, including economic development, policy implications and cultural traditions. Based on the insights from this evidence, this study offers recommendations that the SPAT model provides a mechanism for exploring children and their experiences of outdoor environments in different contexts which has a strong adaptation to various contexts.
Re‐assessing prolonged cold ischemia time in kidney transplantation through machine learning consensus clustering
Authors: Jadlowiec Caroline C. , Thongprayoon Charat , Tangpanithandee Supawit , Punukollu Rachana , Leeaphorn Napat , Cooper Matthew , Cheungpasitporn Wisit
Published: December 2023

Background

We aimed to cluster deceased donor kidney transplant recipients with prolonged cold ischemia time (CIT) using an unsupervised machine learning approach.

Methods

We performed consensus cluster analysis on 11 615 deceased donor kidney transplant patients with CIT exceeding 24 h using OPTN/UNOS data from 2015 to 2019. Cluster characteristics of clinical significance were identified, and post‐transplant outcomes were compared.

Results

Consensus cluster analysis identified two clinically distinct clusters. Cluster 1 was characterized by young, non‐diabetic patients who received kidney transplants from young, non‐hypertensive, non‐ECD deceased donors with lower KDPI scores. In contrast, the patients in cluster 2 were older and more likely to have diabetes. Cluster 2 recipients were more likely to receive transplants from older donors with a higher KDPI. There was lower use of machine perfusion in Cluster 1 and incrementally longer CIT in Cluster 2. Cluster 2 had a higher incidence of delayed graft function (42% vs. 29%), and lower 1‐year patient (95% vs. 98%) and death‐censored (95% vs. 97%) graft survival compared to Cluster 1.

Conclusions

Unsupervised machine learning characterized deceased donor kidney transplant recipients with prolonged CIT into two clusters with differing outcomes. Although Cluster 1 had more favorable recipient and donor characteristics and better survival, the outcomes observed in Cluster 2 were also satisfactory. Overall, both clusters demonstrated good survival suggesting opportunities for transplant centers to incrementally increase CIT.
Detrimental impact of early biopsy‐proven rejection in liver transplantation
Authors: Aufhauser David D. , Stalter Lily , Marka Nicholas , Leverson Glen , Al‐Adra David P. , Foley David P.
Published: December 2023

Existing literature offers conflicting conclusions about whether early acute cellular rejection influences long‐term outcomes in liver transplantation. We retrospectively collected donor and recipient data on all adult, first‐time liver transplants performed at a single center between 2008 and 2020. We divided this population into two cohorts based on the presence of early biopsy‐proven acute cellular rejection (EBPR) within the first 90 days post‐transplant and compared outcomes between the groups. There were 896 liver transplants that met inclusion criteria with 112 cases (12.5%) of EBPR. Recipients who developed EBPR had higher biochemical Model for End‐Stage Liver Disease scores (28 vs. 24, p < .01), but other donor and recipient characteristics were similar. Recipients with EBPR had similar overall survival compared to patients without EBPR (p = .09) but had decreased graft survival (p < .05). EBPR was also associated with decreased time to first episode of late (> 90 days post‐transplant) rejection (p < .0001) and increased vulnerability to bacterial and viral infection (p < .05). In subgroup analysis of recipients with autoimmune indications for liver transplantation, EBPR had a more pronounced association with patient death (hazard ratio [HR] 3.9, p < .05) and graft loss (HR 4.0, p < .01). EBPR after liver transplant is associated with inferior graft survival, increased susceptibility to late rejections, and increased vulnerability to infection.
Simultaneous split liver/kidney transplantation: A national and single center experience report
Authors: Rastogi Radhika , Vargas Paola A. , Oberholzer Jose , Pelletier Shawn , Goldaracena Nicolas
Published: December 2023

Background

End‐stage liver disease (ESLD) and end‐stage renal disease (ESRD) are prevalent diseases for which the definitive treatment is transplantation. With limited organ supply, strategies to maximize organ availability has led to increasing rates of split liver transplantations for ESLD patients. Therefore, simultaneous split liver and kidney transplantations (SSLK) for patients with ESLD and ESRD could represent a treatment option for comorbid patients. However, current practice and outcomes after SSLK are unknown.

Methods

We aim to report national trends and our experience with patients undergoing SSLK. We performed a retrospective review of the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research file from January 2011–April 2022. Descriptive analysis of preoperative characteristics, postoperative outcomes and actuarial graft and patient survivals are reported.

Results

National review of the UNOS transplant registry from 2011–2021 of adult patients undergoing initial transplantation via SSLK demonstrates that this procedure remains uncommon, with only 76 such cases captured in that time. Nevertheless, survival rates at 1, 3, and 5 years remains robust, at 94%, 92%, and 90% for patients overall, 90%, 88%, 88%, for the liver graft, and 93%, 91%, 88% for the kidney graft, respectively. Review of a single center experience with three such patients from 2019–2021 has shown a safe, enduring transplant option with no graft complications seen.

Conclusions

SSLK is both safe and a feasible option to optimize organ supply while allowing recipients to receive quality liver and kidney grafts and should be considered more often by transplant centers going forward.
Impact of pancreas transplantation alone on kidney function: A multicenter clinical cohort study
Authors: Kaur Ravinder Jeet , Mujtahedi Syed Saad , Fridell Jonathan A. , Benavides Xiomara , Smith Byron , Larson Timothy S. , Rizvi Shafaq R. , Kukla Aleksandra , Dean Patrick , Kudva Yogish C. , Odorico Jon , Stegall Mark
Published: December 2023

Pancreas transplantation alone (PTA) is a β cell replacement option for selected patients with type 1 diabetes mellitus; concerns have been raised regarding deterioration in kidney function (KF) after PTA. This retrospective multicenter study assessed actual impact of transplantation and immunosuppression on KF in PTA recipients at three Transplant Centers. The primary composite endpoint 10 years after PTA was >50% eGFR decline, eGFR < 30 mL/min/1.73 m2, and/or receiving a kidney transplant (KT). Overall, 822 PTA recipients met eligibility. Median baseline and 10‐year eGFR (mL/min/1.73 m2) were 76.3 (58.1–100.8) and 51.3 (35.3–65.9), respectively. Primary composite endpoint occurred in 98 patients (53.5%) with 45 experiencing a >50% decrease in eGFR by 10 years post‐transplant, 38 eGFR < 30 mL/min/1.73 m2 and 49 requiring KT. KF declined most significantly within 6 months post‐PTA, more often in females and patients with better preserved GFR up to 5 years with 11.6% kidney failure at 10 years. Patient survival and death‐censored graft survival were both 68% at 10 years with overall graft thrombosis rate 8%. KF declined initially after PTA but stabilized with further slow progression. In conclusion, prospective intervention studies are needed to test renal sparing interventions while gathering more granular data.
Cytological features of cranial and paraspinal nerve Tumours
Authors: Mittenzwei Rhonda , Yoda Rebecca A.
Published: December 2023

The 2021 World Health Organization Classification of Central Nervous System Tumours introduced significant revisions to the categorization of paraspinal and nerve sheath tumours. This updated system encompasses seven tumour types: schwannoma, neurofibroma, perineurioma, hybrid nerve sheath tumours, malignant melanotic nerve sheath tumour, malignant peripheral nerve sheath tumour and cauda equina neuroendocrine tumour. This review provides an image‐rich cytologic reference of these tumours, with particular emphasis on intraoperative smear preparations. Knowledge of the key cytological features of these tumours and their differential diagnoses will help guide classification of these challenging entities.
Use of cytology fluid samples for predictive biomarker testing in lung cancer patients
Authors: Hawkins Paul , Stevenson Tracey , Powari Manish
Published: December 2023

Objective

To provide a method of directly using cytology fluid samples for predictive biomarker testing in lung cancer patients and to determine the efficacy of a variety of fluid sample types.

Method

A review of our in‐house data from a range of cytology samples including endobronchial ultrasound (EBUS) fine‐needle aspirate (FNA) needle washings (NW) and serous effusions tested on the Biocartis Idylla platform. All fluid samples were originally tested using Sanger sequencing.

Results

Using our method for fluid samples all of our cytology samples tested for epithelial growth factor receptor (EGFR) yielded valid results on this platform and all variant cases identified. The data showed serous fluids provided the best quality DNA, and variant genotype reports were obtained within 150 minutes.

Conclusion

Cytology fluid samples can be used for predictive biomarker testing for lung cancer patients to provide in‐house results with all fluids providing good‐quality DNA.
Forecasting the spread of an invasive forest‐defoliating insect
Authors: Walter Jonathan A. , Grage Kathryn , Nunez‐Mir Gabriela C. , Grayson Kristine L.
Published: December 2023

Aim

Biological invasions are an escalating environmental challenge due to their substantial ecological and socio‐economic consequences. Accurate near‐term forecasts of future areas occupied by an invasive species could enhance the efficiency and efficacy of invasion monitoring and management but spread forecasting models have been developed and tested for few invasive species thus far.

Location

Northeastern USA.

Methods

We developed a quantitative model to forecast 1‐year‐ahead occupancy of Lymantria dispar dispar, an expanding invasive forest insect introduced into the eastern United States in 1869 that causes large‐scale defoliation of forests. We validated and tested the model using historical distribution and density data from a large‐scale network of pheromone‐baited traps. We first assessed how forecast accuracy depended on trap catch density thresholds for determining occupancy and on the spatial scale of local connectivity measures. Next, we tested how increasing the computational complexity and biological detail encoded in the models affected prediction accuracy.

Results

Models using lower occupancy thresholds and measuring connectivity over shorter distances tended to perform best. A simple model using only coarse and generic representations of habitat suitability and local diffusive spread potential performed at least as well as more complex models. Our best models achieved total accuracy and true‐positive rates exceeding 95%.

Conclusions

Our baseline model illustrates the utility of a mechanistic model to forecast year‐to‐year occupancy dynamics of L. dispar. Near‐term spread forecasting can be a valuable tool for invasion management, even for species without detailed a priori ecological knowledge.
Pathological neurons generate ripples at the UP‐DOWN transition disrupting information transfer
Authors: Weiss Shennan A. , Fried Itzhak , Engel Jerome , Bragin Anatol , Wang Shuang , Sperling Michael R. , Wong Robert K. S. , Nir Yuval , Staba Richard J.
Published: December 2023

Objective

To confirm and investigate why pathological high‐frequency oscillations (pHFOs), including ripples (80–200 Hz) and fast ripples (200–600 Hz), are generated during the UP‐DOWN transition of the slow wave and if information transmission mediated by ripple temporal coupling is disrupted in the seizure‐onset zone (SOZ).

Methods

We isolated 217 total units from 175.95 intracranial electroencephalography (iEEG) contact‐hours of synchronized macro‐ and microelectrode recordings from 6 patients. Sleep slow oscillation (.1–2 Hz) epochs were identified in the iEEG recording. iEEG HFOs that occurred superimposed on the slow wave were transformed to phasors and adjusted by the phase of maximum firing in nearby units (i.e., maximum UP). We tested whether, in the SOZ, HFOs and associated action potentials (APs) occur more often at the UP‐DOWN transition. We also examined ripple temporal correlations using cross‐correlograms.

Results

At the group level in the SOZ, HFO and HFO‐associated AP probability was highest during the UP‐DOWN transition of slow wave excitability (p < < .001). In the non‐SOZ, HFO and HFO‐associated AP was highest during the DOWN‐UP transition (p < < .001). At the unit level in the SOZ, 15.6% and 20% of units exhibited more robust firing during ripples (Cohen's d = .11–.83) and fast ripples (d = .36–.90) at the UP‐DOWN transition (p < .05 f.d.r. corrected), respectively. By comparison, also in the SOZ, 6.6% (d = .14–.30) and 8.5% (d = .33–.41) of units had significantly less firing during ripples and fast ripples at the UP‐DOWN transition, respectively. Additional data shows that ripple and fast ripple temporal correlations, involving global slow waves, between the hippocampus, entorhinal cortex, and parahippocampal gyrus were reduced by >50% in the SOZ compared to the non‐SOZ (N = 3).

Significance

The UP‐DOWN transition of slow wave excitability facilitates the activation of pathological neurons to generate pHFOs. Ripple temporal correlations across brain regions may be important in memory consolidation and are disrupted in the SOZ, perhaps by pHFO generation.
Permutation entropy‐derived parameters to estimate the epileptogenic zone network
Authors: Bratu Ionuț‐Flavius , Makhalova Julia , Garnier Elodie , Villalon Samuel Medina , Jegou Aude , Bonini Francesca , Lagarde Stanislas , Pizzo Francesca , Trébuchon Agnès , Scavarda Didier , Carron Romain , Bénar Christian , Bartolomei Fabrice
Published: December 2023

Objective

Quantification of the epileptogenic zone network (EZN) most frequently implies analysis of seizure onset. However, important information can also be obtained from the postictal period, characterized by prominent changes in the EZN. We used permutation entropy (PE), a measure of signal complexity, to analyze the peri‐ictal stereoelectroencephalography (SEEG) signal changes with emphasis on the postictal state. We sought to determine the best PE‐derived parameter (PEDP) for identifying the EZN.

Methods

Several PEDPs were computed retrospectively on SEEG‐recorded seizures of 86 patients operated on for drug‐resistant epilepsy: mean baseline preictal entropy, minimum ictal entropy, maximum postictal entropy, the ratio between the maximum postictal and the minimum ictal entropy, and the ratio between the maximum postictal and the baseline preictal entropy. The performance of each biomarker was assessed by comparing the identified epileptogenic contacts or brain regions against the EZN defined by clinical analysis incorporating the Epileptogenicity Index and the connectivity epileptogenicity index methods (EZNc), using the receiver‐operating characteristic and precision‐recall.

Results

The ratio between the maximum postictal and the minimum ictal entropy (defined as the Permutation Entropy Index [PEI]) proved to be the best‐performing PEDP to identify the EZNC. It demonstrated the highest area under the curve (AUC) and F1 score at the contact level (AUC 0.72; F1 0.39) and at the region level (AUC 0.78; F1 0.47). PEI values gradually decreased between the EZN, the propagation network, and the non‐involved regions. PEI showed higher performance in patients with slow seizure‐onset patterns than in those with fast seizure‐onset patterns. The percentage of resected epileptogenic regions defined by PEI was significantly correlated with surgical outcome.

Significance

PEI is a promising tool to improve the delineation of the EZN. PEI combines ease and robustness in a routine clinical setting with high sensitivity for seizures without fast activity at seizure onset.