bluuebunny/crossref_metadata_2025 huggingface dataset:
Leadership and Governance, Financing, and Coordination and their Impact on the Operationalization of Health Interventions in the Humanitarian-Development Nexus in South Sudan
Authors: Qaddour Amany , Yan Lauren , Wendo Dan , Elisama Laura , Lindahl Christopher , Spiegel Paul
Published: October 2024

South Sudan ranks among the most fragile nations in the world. Protracted conflict and recurrent shocks have weakened its health system and contributed to high maternal and child mortality rates, despite large amounts of humanitarian and development assistance injected into the country since independence. Factors related to the leadership and governance, financing, and coordination of health services impact the feasibility of implementing the humanitarian-development nexus (HDN). Researchers employed a qualitative case study design drawing from document reviews and individual and group semi-structured interviews with humanitarian and development stakeholders in South Sudan (Juba capital and Bor town). Data was analyzed and findings were synthesized and organized into distinct themes. Forty-one interviews were conducted with 68 participants between November 2022 and January 2023, and 57 documents were analyzed. Findings showed that limited government investment in the health sector has perpetuated reliance on international assistance, and barriers to engagement with government counterparts have restricted coordination. Some nascent HDN coordination platforms exist with minimal political buy-in. Recent reductions in development health funding have complicated progress towards longer-term development objectives, including health systems strengthening. Structural barriers within multi-mandate agencies and differences in programming cycles, funding, and reporting contribute to silos. Continued fragility, a restricted operational environment, shrinking funds, and fragmented coordination have made it challenging to plan, finance, and implement HDN-health interventions. Informal efforts to bridge silos between humanitarian and development actors should become more formalized to use resources more efficiently. Despite certain restrictions in engagement with government, coordination and planning at the sub-national level may still be feasible. Such engagement should be enhanced to ensure sustainability of health services. Investment in health systems strengthening and resilience by humanitarian and development actors should enable communities to absorb recurrent shocks and prevent backsliding in health provision.
Extensive monolayer formation depends on a subpopulation of transplanted human iPSC-derived RPE cells
Authors: Tessmer Karen , Gasparini Sylvia J. , Schmidtke Klara , Adhikari Trishla , Michalke Lea , Hammer Juliane , Loureiro Liliana R. , Last Annika , Chelius Nadine , Kurtz Annett , Johannsen Hannah , Carido Madalena , Ferguson Susanne , Petzold Andreas , Friedrich Ulrike A. , Kurth Thomas , Dahl Andreas , Feldmann Anja , Almedawar Seba , Knöbel Sebastian , Ader Marius
Published: October 2024

Loss of retinal pigment epithelium (RPE) cells in the eye leads to photoreceptor death and vision loss. Cell replacement strategies using RPE derivedin vitrofrom pluripotent stem cells (PSCs) has emerged as a promising therapeutic strategy. Generation of polarized monolayers represents an essential prerequisite for proper RPE function, however, monolayer formation following transplantation of RPE cell suspensions has not been systematically assessed. Using the sodium iodate mouse model of RPE depletion, significant increase in monolayer formation capacity of passage (P) 1 vs. P2 human iPSC-derived RPE cells was observed three weeks after transplantation. Transplant-derived monolayers showed characteristic apicobasal polarity, RPE marker expression, phagocytosis function, and preservation of the host outer nuclear layer. The cell surface marker panel CD54+/PSA-NCAM-was identified to enrich for an RPE subpopulation with high potential for monolayer formation following transplantation. Results underline the importance of defining and isolating competent cell subpopulations for successful RPE transplantation.
A Cortical Microcircuit for Region-Specific Credit Assignment in Reinforcement Learning
Authors: Chevy Quentin , Szadai Zoltán , Hertäg Loreen , Moll Morgan , Gibson Elizabeth T , Costa Rui Ponte , Kepecs Adam
Published: October 2024

The distributed architecture of the cortex poses a fundamental challenge for reinforcement learning: how to assign credit specifically to regions that contribute to successful behavior? Cortical neurons can be driven by both global reinforcers, like rewards, and local sensory features, making it difficult to disentangle these influences. To address this, we investigated cortical reinforcement learning by manipulating the reward-predictive sensory modality during learning tasks, while monitoring key regulators of cortical activity-local inhibitory neurons, and cholinergic inputs. We found that VIP interneurons are broadly recruited by reward-predictive cues via a modality-independent cholinergic signal. However, when task demands aligned with local computation, SST interneurons suppressed VIP recruitment through an inhibitory feedback loop. A computational model demonstrates that this cholinergic-VIP-SST interneuron circuit motif enables targeted reinforcement learning and region-specific credit assignment in the cortex. These results offer a neurobiologically-grounded framework for how the cortex uses global reinforcement signals to direct plasticity to task-relevant regions, enabling those regions to adapt and fine-tune their responses.
Chromosome-scale assembly and annotation of the wild wheat relative Aegilops comosa
Authors: Li Hongna , Rehman Shams ur , Song Rui , Qiao Liang , Hao Xiaohua , Zhang Jing , Li Kairong , Hou Lifeng , Hu Wanyi , Wang Le , Chen Shisheng
Published: October 2024

Wild relatives of wheat are valuable sources for enhancing the genetic diversity of common wheat. Aegilops comosa, an annual diploid species with an MM genome constitution, possesses numerous agronomically valuable traits that can be exploited for wheat improvement. In this study, we report a chromosome-level genome assembly of Ae. comosa accession PI 551049, generated using PacBio high-fidelity (HiFi) reads and high-throughput chromosome conformation capture (Hi-C) data. The assembly spans 4.47 Gb, featuring a contig N50 of 23.59 Mb and a scaffold N50 of 619.05 Mb. A total of 39,063 gene models were annotated through a combination of homoeologous proteins, Iso-Seq, and RNA-Seq data. Comparative genome analysis revealed a terminal intrachromosomal translocation in chromosome 2M of Ae. comosa (and Ae. umbellulata) compared to its homoeologous chromosomes in other diploid wheat species. Phylogenetic analysis showed a close relationship between Ae. comosa and Ae. umbellulata. This newly constructed reference genome of Ae. comosa will serve as an important genomic resource for comparative genomic studies and the cloning of agriculturally important genes.
Genetic diversity, population structure and differentiation of farmed and wild African catfish (Clarias gariepinus) in Nigeria
Authors: Sanda Mark K. , Metcalfe Neil B. , Capstick Maria , Nichols Jenna , Mable Barbara K.
Published: October 2024

The African catfish (Clarias gariepinus) is a commercially important species, for both fisheries and aquaculture, and is now the most commonly farmed fish in sub-Saharan Africa. However, knowledge about the genetic diversity and population structure of wild and farmed populations, which is crucial for effective conservation and sustainable aquaculture management, is scarce. Using mitochondrial DNA (mtDNA) cytochrome c oxidase 1 gene (COI) sequencing and genomic analysis using triple restriction site-associated DNA sequencing (3RAD), we investigated the genetic diversity and population structure of farmed and wildC. gariepinuspopulations from Nigeria, including an albino form found in the wild. Eleven COI haplotypes were identified, of which seven were unique to wild samples. Wild sampling sites had a slightly broader range and higher maximum values for observed heterozygosity (Ho= 0.109 – 0.165), expected heterozygosity (He= 0.111 – 0.216), and nucleotide diversity (pi= 0.125 – 0.225) compared to the farmed populations (Ho= 0.118 – 0.147,He= 0.112-0.144,pi= 0.117 – 0.151). Conversely, genetic differentiation (Fst) was higher among farmed sampling sites compared to the wild ones and there was high genetic differentiation between the farmed and wildC. gariepinussampling sites (Fst= 0.31 – 0.47). Despite evidence for admixture for both farmed and wild fish, there was little evidence of admixture between the two groups. Nevertheless, both mtDNA and 3RAD data strongly suggested that the albino fish, collected from the wild, were in fact farm escapees. Despite overall differentiation farmed genotypes suggesting that overall genetic integrity of wild fish has been maintained, this evidence of escape provides a warning about potential risks of increasing aquaculture activities. Specifically, this indicates the need for greater regulation of fish farms to monitor and reduce the risk of escapes.
Distinct neuronal processes in the ventromedial prefrontal cortex mediate changes in attention load and nicotine pro-cognitive effects
Authors: Vouillac-Mendoza Caroline , Biendon Nathalie , Dovero Sandra , Guillem Karine
Published: October 2024

The prefrontal cortex (PFC) plays a key role in attention. In particular, neuronal activity in the ventromedial PFC (vmPFC) has been implicated in the preparatory attentional period that immediately precedes cue presentation. However, whether vmPFC neuronal activity during this preparatory period is also sensitive to changes in task demand and to the pro-cognitive effects of nicotine remained to be investigated. Here, we usedin vivoelectrophysiology to record vmPFC neuronal activity during two distinct manipulations: a task manipulation that increased task demand by reducing the cue stimulus duration (from 1s to 0.5s), and a pharmacological manipulation by administrating an acute nicotine injection (10 µg/inj, i.v.) before the session. We found that increasing task demand decreased attentional performances and vmPFC precue neuronal activity, but had no effect on gamma oscillations. In contrast, nicotine injection increased attention and gamma oscillations, but almost abolished vmPFC phasic precue responses. Together, these findings indicate the existence of two distinct neuronal mechanisms operating at different timescales and suggests that allocation of attention could be achieved through multiple complementary neuronal mechanisms within the vmPFC.
Stabilizing selection and adaptation shapecisandtransgene expression variation inC. elegans
Authors: Bell Avery Davis , Valencia Francisco , Paaby Annalise B.
Published: October 2024

An outstanding question in the evolution of gene expression is the relative influence of neutral processes versus natural selection, including adaptive change driven by directional selection as well as stabilizing selection, which may include compensatory dynamics. These forces shape patterns of gene expression variation within and between species, including the regulatory mechanisms governing expression incisandtrans. In this study, we interrogate intraspecific gene expression variation among seven wildC. elegansstrains, with varying degrees of genomic divergence from the reference strain N2, leveraging this system’s unique advantages to comprehensively evaluate gene expression evolution. By capturing allele-specific and between-strain changes in expression, we characterize the regulatory architecture and inheritance mode of gene expression variation withinC. elegansand assess their relationship to nucleotide diversity, genome evolutionary history, gene essentiality, and other biological factors. We conclude that stabilizing selection is a dominant influence in maintaining expression phenotypes within the species, and the discovery that genes with higher overall expression tend to exhibit fewer expression differences supports this conclusion, as do widespread instances ofcisdifferences compensated intrans. Moreover, analyses of human expression data replicate our finding that higher expression genes have less variable expression. We also observe evidence for directional selection driving expression divergence, and that expression divergence accelerates with increasing genomic divergence. To provide community access to the data from this first analysis of allele-specific expression inC. elegans, we introduce an interactive web application, where users can submit gene-specific queries to view expression, regulatory pattern, inheritance mode, and other information:https://wildworm.biosci.gatech.edu/ase/.
Reconstructing the sequence specificities of RNA-binding proteins across eukaryotes
Authors: Sasse Alexander , Ray Debashish , Laverty Kaitlin U , Tam Cyrus L , Albu Mihai , Zheng Hong , Lyudovyk Olga , Dalal Taykhoom , Nie Kate , Magis Cedrik , Notredame Cedric , Weirauch Matthew T , Hughes Timothy R , Morris Quaid
Published: October 2024

RNA-binding proteins (RBPs) are key regulators of gene expression. Here, we introduce EuPRI (Eukaryotic Protein-RNA Interactions) — a freely available resource of RNA motifs for 34,736 RBPs from 690 eukaryotes. EuPRI includesin vitrobinding data for 504 RBPs, including newly collected RNAcompete data for 174 RBPs, along with thousands of reconstructed motifs. We reconstruct these motifs with a new computational platform — Joint Protein-Ligand Embedding (JPLE) — which can detect distant homology relationships and map specificity-determining peptides. EuPRI quadruples the number of known RBP motifs, expanding the motif repertoire across all major eukaryotic clades, and assigning motifs to the majority of human RBPs. EuPRI drastically improves knowledge of RBP motifs in flowering plants. For example, it increases the number ofArabidopsis thalianaRBP motifs 7-fold, from 14 to 105. EuPRI also has broad utility for inferring post-transcriptional function and evolutionary relationships. We demonstrate this by predicting a role for 12Arabidopsis thalianaRBPs in RNA stability and identifying rapid and recent evolution of post-transcriptional regulatory networks in worms and plants. In contrast, the vertebrate RNA motif set has remained relatively stable after its drastic expansion between the metazoan and vertebrate ancestors. EuPRI represents a powerful resource for the study of gene regulation across eukaryotes.
Targeting long non-coding RNA RP11-502I4.3 delays the trend of angiogenesis in diabetic retinopathy
Authors: Zeng Lan , Wu Yuhao , Zhu Lijuan , He Junhao , Yuan Yuan , Wang Xiaocong , Tang Kai , Tan Wei
Published: October 2024

Based on our previous findings, we hypothesized that the long non-coding RNA RP11-502I4.3 may be involved in angiogenesis associated with Diabetic retinopathy (DR). We investigated the role of RP11-502I4.3 in DR by examining its regulation of vascular endothelial growth factor (VEGF). We assessed differences in RP11-502I4.3 expression between the normal control group and streptozotocin-induced diabetic rats or high glucose (HG)-stimulated human retinal microvascular endothelial cells (HRMECs). VEGF expression was measured with and without lentiviral vectors overexpressing RP11-502I4.3. We analyzed the structural and functional alterations related to DR. Our analysis revealed that RP11-502I4.3 expression was lower in the retinas of diabetic rats and in HG-stimulated HRMECs compared with normal glucose conditions. Overexpressing of RP11-502I4.3 resulted in decreased VEGF levels. Diabetic rats exhibited retinopathy characterized by thinning of the retinal layer thickness, structural changes in the inner and outer nuclear layers, a reduced count of retinal ganglion cells, and the presence of acellular capillaries. The proliferative activity, migration count, and tube formation ability of HG-treated HRMECs were significantly higher than those of the normal control group; however, these changes were delayed by RP11-502I4.3 overexpression. RP11-502I4.3 downregulation in DR appears to promote angiogenesis.
Epigenetic state and gene expression remain stable after CRISPR/Cas-mediated chromosomal inversions
Authors: Khosravi Solmaz , Hinrichs Rebecca , Rönspies Michelle , Haghi Reza , Puchta Holger , Houben Andreas
Published: October 2024

InArabidopsis thaliana,the chromosome arms are DNA-hypomethylated and enriched in the euchromatin-specific histone mark H3K4me3. In contrast, pericentromeric regions are DNA-hypermethylated and enriched in H3K9me2. In order to investigate how chromosomal location affects epigenetic stability and gene activity, we induced two differently-sized inversions by CRISPR/Cas and introduced heterochromatic, pericentric sequences into an euchromatic chromosomal arm. The epigenetic status of the lines was investigated by whole genome bisulfite sequencing and chromatin immunoprecipitation. Additionally, we studied the effect of the chromosomal inversions on gene expression. Our analysis revealed that both inversions affected neither the global distribution of eu- and heterochromatin-specific histone marks nor the global DNA methylation landscape. However, minor epigenetic changes were found across the entire genome. Importantly, the inverted chromosome regions and their border regions did not change their epigenetic profile. The transcription analysis of both inversion lines revealed that 0.5 - 1 % of genes were differentially expressed across the entire genome. However, the expression activity of those genes encoded by the inverted segments, and located around the cutting sites of CRISPR/Cas was less affected. Thus, gene expression levels and the epigenetic landscape remain preserved following engineered chromosomal restructuring, at least in the following generations.
Neuropeptide Dynamics Coordinate Layered Plasticity Mechanisms Adapting Drosophila Circadian Behavior to Changing Environment
Authors: Chatterjee Abhishek , De Joydeep , Martin Béatrice , Chélot Elisabeth , Rouyer François
Published: October 2024

The Drosophila brain contains distinct sets of circadian oscillators responsible for generating the morning and evening bouts of locomotor activity, giving rise to a bimodal rest-activity pattern in light-dark cycles. We lack a mechanistic understanding of how environmental changes reshape this daily profile of rest-activity pattern. Here, we uncover a seasonal switch mechanism that remodels the evening bout of activity. Under summer-like conditions, an environment favored by fruit flies in temperate climates, levels of the PDF neuropeptide diminish, triggering a cascade. Lowered PDFR signaling disinhibits GSK3/SGG to advance the evening output. Upon sensing PDF loss, the neural activity weakens in the DN1p-SIFacircuit, responsible for promoting afternoon rest; leading to an earlier appearance of the evening peak. At the same time, the functional connections from DN1p to LNd oscillators strengthen, consequently handing over the evening pacemaker role to the DN1ps. Taken together, our findings elucidate how environment-induced changes in PDFR signaling tip the balanced output of the clock network, aligning daily rhythms with seasonal time. Neuropeptide-driven parallel adjustment of clock circuitry and clock protein functioning likely represents a conserved strategy across animal species, enabling them to adapt their daily behavior to seasonal changes throughout the year.
Uniaxial force modifies the length of the mammary ductal network and the orientation of ducts during pubertal development: Findings from computational modeling and laboratory experiments
Authors: Ulloa Daisy , Temple Kelsey M. , Casey Theresa M. , George Uduak Z
Published: October 2024

Mammary gland forms an extensive tree-like network of epithelium ducts during puberty. The orientation of the ducts determine the overall shape of the epithelium ductal network which in turn impacts the delivery of milk through the ducts to breastfeeding infants. However, how the orientation of the ducts are specified is not well understood. This study examines if an applied force can regulate the orientation of the epithelium ducts during puberty, in vivo. Exogenous forces were applied continuously to pairs of abdominal number four mammary glands in mice, during pubertal formation of the epithelium ductal network at 5-7 weeks of age. In each mice (n=10), one of the abdominal number four mammary gland was exposed to a uniaxial force (TEN) and the other was exposed to a contralateral (CONTRA) force. Subsequently, microscopy images of the epithelium ductal network for the TEN and CONTRA glands were analyzed and compared to controls to determine differences in ductal orientation. Findings from image-based analysis indicate that uniaxial and contralateral forces increase the length of the ductal network. Though the ductal network were longer in the TEN and CONTRA glands, there were no significant differences in the total cross-sectional area of the ductal network compared to controls. However, the orientation of the epithelium ducts in TEN and CONTRA glands were different compared to controls. In-silico simulations of ductal network formation with a branching and annihilating random walk model predicts that the orientation of the epithelium ducts may significantly alter the length of the ductal network. These findings suggest that the increased length of the ductal network resulted from the changes in the orientation of the epithelium ducts. This study therefore determines that exogeneous mechanical forces may regulate ductal network architecture and orientation of ductal branches in vivo.
Lifespan of male and female APP/PS1 and APPNL-F/NL-Fmouse models of Alzheimer’s disease
Authors: Roberts Hannah , Fang Yimin , Quinn Kathleen , Hill Tiarra , Peck Mackenzie R. , Bartke Andrzej , Hascup Kevin N. , Hascup Erin R.
Published: October 2024

Alzheimer’s disease (AD) disproportionately affects women, yet most preclinical research studies are male-centric. We performed lifespan analyses of male and female AD mouse models (APP/PS1 and APPNL-F/NL-F) and their shared genetic background control (C57BL/6). Survival curves support significant sex differences between within genotypes. Minimal longevity revealed increased age in male APP/PS1, and decreased age in APPNL-F/NL-Fmice. Maximal longevity revealed an increased average age in males. Furthermore, median lifespan differed between sex and genotype. This study supports sexual dimorphic survival in two mouse models of AD, emphasizing the need to examine mechanisms and treatments in both sexes.
Training deep learning models on personalized genomic sequences improves variant effect prediction
Authors: He Adam Y , Palamuttam Nathan P , Danko Charles G
Published: October 2024

Sequence-to-function models have broad applications in interpreting the molecular impact of genetic variation, yet have been criticized for poor performance in this task. Here we show that training models on functional genomic data with matched personal genomes improves their performance at variant effect prediction. Variant effect representations are retained even when transfer learning models to unseen cellular contexts and experimental readouts. Our results have implications for interpreting trait-associated genetic variation.
Restriction of innate Tγδ17 cell plasticity by an AP-1 regulatory axis
Authors: Parker Morgan E. , Mehta Naren U. , Liao Tzu-Chieh , Tomaszewski William H. , Snyder Stephanie A. , Busch Julia , Ciofani Maria
Published: October 2024

IL-17-producing γδ T (Tγδ17) cells are innate-like mediators of intestinal barrier immunity. While Th17 cell and ILC3 plasticity have been extensively studied, the mechanisms governing Tγδ17 cell effector flexibility remain undefined. Here, we combined type 3 fate-mapping with single cell ATAC/RNA-seq multiome profiling to define the cellular features and regulatory networks underlying Tγδ17 cell plasticity. During homeostasis, Tγδ17 cell effector identity was stable across tissues, including for intestinal T-bet+Tγδ17 cells that restrained IFNγ production. However, S. typhimurium infection induced intestinal Vγ6+Tγδ17 cell conversion into type 1 effectors, with loss of IL-17A production and partial RORγt downregulation. Multiome analysis revealed a trajectory along Vγ6+Tγδ17 effector conversion, with TIM-3 marking ex-Tγδ17 cells with enhanced type 1 functionality. Lastly, we characterized and validated a critical AP-1 regulatory axis centered around JunB and Fosl2 that controls Vγ6+Tγδ17 cell plasticity by stabilizing type 3 identity and restricting type 1 effector conversion.
NicheFlow: Towards a foundation model for Species Distribution Modelling
Authors: Dinnage Russell
Published: October 2024

1. Species distribution models (SDMs) are crucial tools for understanding and predicting biodiversity patterns, yet they often struggle with limited data, biased sampling, and complex species-environment relationships. Here I present NicheFlow, a novel foundation model for SDMs that leverages generative AI to address these challenges and advance our ability to model and predict species distributions across taxa and environments.

2. NicheFlow employs a two-stage generative approach, combining species embeddings with two chained generative models, one to generate a distribution in environmental space, and a second to generate a distribution in geographic space. This architecture allows for the sharing of information across species and captures complex, non-linear relationships in environmental space. I trained NicheFlow on a comprehensive dataset of reptile distributions and evaluated its performance using both standard SDM metrics and zero-shot prediction tasks.

3. NicheFlow demonstrates good predictive performance, particularly for rare and data-deficient species. The model successfully generated plausible distributions for species not seen during training, showcasing its potential for zero-shot prediction. The learned species embeddings captured meaningful ecological information, revealing patterns in niche structure across taxa, latitude and range sizes.

4. As a proof-of-principle foundation model, NicheFlow represents a significant advance in species distribution modeling, offering a powerful tool for addressing pressing questions in ecology, evolution, and conservation biology. Its ability to model joint species distributions and generate hypothetical niches opens new avenues for exploring ecological and evolutionary questions, including ancestral niche reconstruction and community assembly processes. This approach has the potential to transform our understanding of biodiversity patterns and improve our capacity to predict and manage species distributions in the face of global change.
Gut bacteria-derived succinate induces enteric nervous system regeneration
Authors: Aydin Begüm , Mamede Izabela , Cardoso Joana , Deere Julia , Alvarez Yelina , Qiao Shanshan , Sharma Ved P. , Scavuzzo Marissa A. , Donaldson Gregory P. , Guo Chun-Jun , Mucida Daniel
Published: October 2024

Enteric neurons control gut physiology by regulating peristalsis, nutrient absorption, and secretion1. Disruptions in microbial communities caused by antibiotics or enteric infections result in the loss of enteric neurons and long-term motility disorders2–5. However, the signals and underlying mechanisms of this microbiota–neuron communication are unknown. We studied the effects of microbiota on the recovery of the enteric nervous system after microbial dysbiosis caused by antibiotics. We found that both enteric neurons and glia are lost after antibiotic exposure, but recover when the pre-treatment microbiota is restored. Using murine gnotobiotic models and fecal metabolomics, we identified neurogenic bacterial species and their derived metabolite succinate as sufficient to rescue enteric neurons and glia. Unbiased single-nuclei RNA-seq analysis uncovered a novel neural precursor-like population marked by the expression of the neuronal gene Nav2. Genetic fate-mapping showed that Plp1+ enteric glia differentiate into neurons following antibiotic exposure. In contrast, Nav2+ neurons expand upon succinate treatment and indicate an alternative mode of neuronal regeneration under recovery conditions. Our findings highlight specific microbial species, metabolites, and the underlying cellular mechanisms involved in neuronal regeneration, with potential therapeutic implications for peripheral neuropathies.
Fentanyl Overdose Deaths Decreased Following Scanner Use at Ports-of-Entry
Authors: Miron Oren
Published: October 2024

Overdose deaths in the United States surged from 2018 to 2022 due to the smuggling of fentanyl through ports-of-entry. To combat this epidemic, the U.S. used advanced scanners at southern ports-of-entry, which tripled inspections and improved screening, especially since March 2023. Following March 2023, fentanyl domestic seizures decreased by 29% and fentanyl overdose deaths decreased by 35%. Fentanyl overdose deaths decreased in 90% of states and increased only in states that receive fentanyl through ports-of-entry that lack these scanners. If this decrease in overdose deaths continues until November 2025, the death rate would be lower than at the start of the opioid epidemic. These results support urgent funding for advanced scanners at ports-of-entry that lack them.
Intensity of care and the health status of caregivers to elderly rural South Africans
Authors: Matina Sostina S , Manderson Lenore , Gómez-Olivé F. Xavier , Berkman Lisa , Harling Guy
Published: October 2024

Objectives

Informal caregivers play an indispensable role in and are often the sole source of care for older adults in low and middle-income settings worldwide. Intensive informal care predicts mortality and morbidity among caregivers in higher-income settings. However, there is limited evidence from poorer settings, including Africa countries, where caregiving is shared widely, including across generations. We therefore investigated caregivers’ health status in rural South Africa.

Methods

We conducted quantitative interviews with all household members and all non-household caregivers aged ≥12 (n=1012) of 106 older adults in rural Mpumalanga, South Africa. We used multivariable regression with care-recipient random intercepts to assess the relationships between four caregiving characteristics and both self-reported chronic conditions and self-reported health status, considering how caregiver age moderated each association.

Results

Over half of all caregivers reported at least one chronic health condition, despite half being aged under 40. Caregivers self-reporting the worst health status provided high hours of care. However, caregivers’ health status was not significantly associated with weekly care quantity or history of caring. Those aged ≥40 who reported being a main caregiver had 52% increased odds of reporting poorer health compared to other same-aged carers (95% confidence interval: 0.99, 2.35), while having more chronic conditions was associated with being expected to act as a sole caregiver more often among caregivers aged ≤39.

Discussion

Greater caring responsibilities for older adults were not consistently associated with caregivers’ health in a setting where poor health is common, and caregiving is spread widely. Longitudinal data is necessary to unpack possible explanations of these findings, and to determine whether intensive caregiving speeds downward health trajectories for carers.
Optimisation of a cervical cancer screening model based on self-sampling for human papillomavirus testing
Authors: Besó Delgado María , Ibáñez Cabanell Josefa , Castán Cameo Susana , Mira Solves José Joaquín , Guilabert Mora Mercedes , Vanaclocha Espí Mercedes , Pinto Carbó Marina , Salas Trejo Dolores , Llorens Oscar Zurriaga , Molina-Barceló Ana
Published: October 2024

The use of self-sampling devices in population-based cervical cancer screening programmes (CCSP) is both an opportunity and a challenge in terms of implementation.

Objective

To understand the expectations, preferences, and difficulties perceived by women as regards different screening models and self-sampling devices, with the aim of identifying strategies to achieve high CCSP participation rates.

Methods

This study is based on qualitative research techniques, consisting of an individual interview using a questionnaire with semi-structured questions, followed by a group interview. Sessions were held simultaneously with 4 groups (7-8 women aged between 35 and 65). Women assessed various aspects of the programme (information dissemination, invitation, receipt of results, etc.) and five self-sampling devices.

Results

If screening were carried out via self-sampling, 96.4% of women said they would take the test. Most women preferred to receive information on the CCSP or return their samples at their health centres (86.2% and 86.2%), and the most popular method for receiving both the programme invitation and results is by SMS (58.6%, 65.5%).

Simplicity and ease of use are the key features of the device accepted by the largest number of women, the FLOQSwab. Another highly rated feature is the attractive design of the Evalyn Brush, as this was the preferred device of the largest number of women.

The existence of other screening programmes that use self-sampling devices (the colorectal cancer prevention programme) is an opportunity as regards acceptance of this new programme. Some women are unsure of how to use the devices correctly.

A large number of women accept self-sampling and reveals significant differences in the degree of acceptance of different self-sampling devices. Selecting the most accepted device is key to achieving high CCSP participation rates, and these programmes should be accompanied by adapted information campaigns to reach the most vulnerable groups and ensure equity.
Cross-modality image translation of 3 Tesla Magnetic Resonance Imaging to 7 Tesla using Generative Adversarial Networks
Authors: Diniz Eduardo , Santini Tales , Helmet Karim , Aizenstein Howard J. , Ibrahim Tamer S.
Published: October 2024

The rapid advancements in magnetic resonance imaging (MRI) technology have precipitated a new paradigm wherein cross-modality data translation across diverse imaging platforms, field strengths, and different sites is increasingly challenging. This issue is particularly accentuated when transitioning from 3 Tesla (3T) to 7 Tesla (7T) MRI systems. This study proposes a novel solution to these challenges using generative adversarial networks (GANs)—specifically, the CycleGAN architecture— to create synthetic 7T images from 3T data. Employing a dataset of 1112 and 490 unpaired 3T and 7T MR images, respectively, we trained a 2-dimensional (2D) CycleGAN model, evaluating its performance on a paired dataset of 22 participants scanned at 3T and 7T. Independent testing on 22 distinct participants affirmed the model’s proficiency in accurately predicting various tissue types, encompassing cerebral spinal fluid, gray matter, and white matter. Our approach provides a reliable and efficient methodology for synthesizing 7T images, achieving a median Dice of 6.82%,7,63%, and 4.85% for Cerebral Spinal Fluid (CSF), Gray Matter (GM), and White Matter (WM), respectively, in the testing dataset, thereby significantly aiding in harmonizing heterogeneous datasets. Furthermore, it delineates the potential of GANs in amplifying the contrast-to-noise ratio (CNR) from 3T, potentially enhancing the diagnostic capability of the images. While acknowledging the risk of model overfitting, our research underscores a promising progression towards harnessing the benefits of 7T MR systems in research investigations while preserving compatibility with existent 3T MR data. This work was previously presented at the ISMRM 2021 conference (Diniz, Helmet, Santini, Aizenstein, & Ibrahim, 2021).
The Water, Sanitation, and Hygiene (WASH) for Everyone controlled before-and-after (CBA) trial: trial protocol and baseline results
Authors: Chidziwisano Kondwani , Panulo Mindy , MacLeod Clara , Vignieri Marcella , White Blessings , Ross Ian , Morse Tracy , Dreibelbis Robert
Published: October 2024

Community-based behaviour change interventions are a common approach to Water, Sanitation, and Hygiene (WASH). Yet, published evaluations of how these interventions work in district-wide approaches are rare. This study reports the baseline characteristics and study design for a trial assessing the effectiveness of a district-level Community-led Total Sanitation (CLTS) intervention compared to the additional integration of local Care Groups on sanitation coverage and use and hygiene behaviours in Chiradzulu District, Malawi.

This study is a controlled before-and-after trial with two treatment arms and a control group. Clusters are rural villages in three Traditional Authorities (TAs). One arm receives CLTS and the Care Group Model, one arm receives CLTS only, and one serves as the control group. The trial is part of the wider WASH for Everyone (W4E) project, led by World Vision Malawi which aims to expand access to WASH services across the entire district by 2025. Study participants were selected from the three TAs. Systematic sampling procedures were used to select 20 households per cluster with a total of 1,400 households at both baseline and endline. The primary outcome is sanitation coverage. Secondary outcome measures include sanitation use, safe disposal of child faeces, observed handwashing facility, and Sanitation-related Quality of Life index (SanQoL-5).

Baseline results show a no difference for primary and secondary outcomes between arms. We noted low coverage of handwashing facilities with soap and water in all the three arms (i.e., CLTS only = 7%; CLTS and Care Groups = 4%; and control = 10%). Further, there was a slight variation (p= 0.08) in handwashing practice and sanitation coverage among the study arms.

The baseline observations indicate a balanced distribution of potential demographic confounders in the trial arms. The trial intervention is under implementation. The evaluation report is expected to be published in 2025.
Effects of Health Education to Reduce Stroke Recurrence by Controlling Modifiable Factors: A Randomized Controlled Trial
Authors: Afrin Mahabuba , Khan Sharif Uddin , Das Subir Chandra , Ehsanul Huq K. A. T. M , Chowdhury Mohammad Shah Jahirul Hoque , Fukuoka Yasuko , Fukushima Yasuko , Moriyama Michiko
Published: October 2024

BACKGROUND

Health education could be an effective measure to prevent stroke recurrence; however, the evidence is still ambiguous. The aim of this study was to evaluate the effectiveness of a health education program among stroke patients and their family caregivers to reduce stroke recurrence.

METHODS

A parallel (1:1), open-label, prospective randomized controlled trial was conducted at the National Institute of Neuroscience & Hospital in Bangladesh between October 2022 and March 2024. We enrolled stroke patients who were discharged from the inpatient department or attended as an outpatient of the hospital. The primary endpoint was the recurrence rate of stroke within 12 months of intervention. The secondary endpoints were the rate of all adverse events related to stroke that occurred within 12 months of follow-up visits.

RESULTS

We analyzed data from 432 patients (216 in each group). We found recurrence was 14 (6.5%) in the IG and 8 (3.7%) in the CG after 28 days of first-stroke attack, and the difference was not significant (p=0.189). We observed stroke-related adverse events 116 (26.9%) (25.0% in IG and 28.7% in CG, p=0.294) including death 95 (22.0%) (18.1% in IG and 25.9% in CG, p=0.041) during 12-month period. Even though stroke patient’s medication adherence was significantly improved at 6-month and 12-month after intervention in IG (p<0.001 and p=0.002, respectively), all events and all causes of death were not significant after adjusted by the severity of stroke (mRS) (p=0.933, p=0.341, respectively).

CONCLUSIONS

The findings of this newly approached intervention can be used as the most reliable evidence for epidemiological figures for Bangladesh. Health education could reduce death and enhance medication adherence significantly among stroke patients. This study results suggest the importance of structuring the acute care system and health education programs to integrate into the health system for the management of stroke. However, an accurate diagnostic and follow-up system is crucial.

CLINICAL TRIAL REGISTRATION

https://clinicaltrials.gov/ct2/show/NCT05520034.
Exploratory Randomised Trial of Tranexamic Acid to Decrease Postoperative Delirium in Adults Undergoing Lumbar Fusion: A trial stopped early
Authors: Hindman Bradley J. , Olinger Catherine R. , Woodroffe Royce W. , Zanaty Mario , Streese Carolina Deifelt , Zacharias Zeb R. , Houtman Jon C. D. , Wendt Linder H. , Ten Eyck Patrick P. , O’Connell-Moore Debra J. , Ray Emanuel J. , Lee Sarah J. , Waldschmidt Daniel F. , Havertape Lauren G. , Nguyen Lanchi B. , Chen Pei-fu , Banks Matthew I. , Sanders Robert D. , Howard Matthew A.
Published: October 2024

Background

Postoperative delirium may be mediated by perioperative systemic- and neuro-inflammation. By inhibiting the pro-inflammatory actions of plasmin, tranexamic acid (TXA) may decrease postoperative delirium. To explore this hypothesis, we modified an ongoing randomised trial of TXA, adding measures of postoperative delirium, cognitive function, systemic cytokines, and astrocyte activation.

Methods

Adults undergoing elective posterior lumbar fusion randomly received intraoperative intravenous TXA (n=43: 10 mg kg-1loading dose, 2 mg kg-1h-1infusion) or Placebo (n=40). Blood was collected pre- and at 24 h post-operatively (n=32) for biomarkers of systemic inflammation (cytokines) and astrocyte activation (S100B). Participants had twice daily delirium assessments using the 3-minute diagnostic interview for Confusion Assessment Method (n=65). Participants underwent 4 measures of cognitive function preoperatively and during post-discharge follow-up.

Results

Delirium incidence in the TXA group (7/32=22%) was not significantly less than in the Placebo group (11/33=33%);P=0.408, absolute difference=11%, relative difference=33%, effect size = −0.258 (95% CI −0.744 to 0.229). In the Placebo group (n=16), delirium severity was associated with the number of instrumented vertebral levels (P=0.001) and with postoperative interleukin −8 and −10 concentrations (P=0.00008 andP=0.005, respectively) and these associations were not significantly modified by TXA. In the Placebo group, delirium severity was associated with S100B concentration (P=0.0009) and the strength of the association was decreased by TXA (P=0.002).

Conclusions

A potential 33% relative decrease in postoperative delirium incidence justifies an adequately powered clinical trial to determine if intraoperative TXA decreases delirium in adults undergoing lumbar fusion.
Modelling the potential spread of Clade Ib MPXV in Asian cities
Authors: Jin Shihui , Gan Gregory , Endo Akira , Prem Kiesha , Jin Tan Rayner Kay , Lim Jue Tao , Ejima Keisuke , Dickens Borame L
Published: October 2024

Background

The ongoing 2023–2024 mpox outbreak in several African countries, driven by the novel Clade Ib strain, has resulted in imported cases reported in Sweden, Thailand, and India. The potentially high transmissibility of this new strain and shifts in transmission modes may make territories in Asia, which were minimally affected by previous mpox waves, vulnerable to community-wide transmission following importation. While this highlights the importance of early preparedness, current knowledge of the virus’s transmission dynamics remains too limited to effectively inform policy-making and resource planning.

Methods

A compartmental model was constructed to characterise the potential mpox transmission dynamics. Importation- triggered outbreaks were simulated in 37 Asian cities under scenarios with one, three, and five initial local infections. The impacts of various non-pharmaceutical interventions (NPIs), including isolation and quarantine, were projected and compared.

Findings

Our simulations revealed substantial disparities in outbreak sizes among the 37 Asian cities, with large-scale outbreaks expected in territories with a high proportion of sexually active individuals at risk or low immunity from smallpox vaccination. Total case count in one year following initial local infections would increase linearly with initial infection size. In the scenario with three initial local infections, up to 340 cases per million residents were expected without interventions. Isolation for diagnosed cases was projected to lower the outbreak size by 43.8% (interquartile range [IQR]: 42.7%–44.5%), 67.8% (IQR: 66.5%–68.9%), 80.8% (IQR: 79.5%–82.0%), and 88.0% (IQR: 86.8%–89.1%) when it reduced interpersonal contacts by 25%, 50%, 75%, and 100%, respectively. Quarantining close contacts would contribute to a further decrease in cases of up to 22 percentage points over one year.

Interpretation

The potential mpox outbreak in an Asian setting could be alleviated through strong surveillance and timely response from stakeholders. NPIs are recommended for outbreak management due to their demonstrated effectiveness and practicability.
Genetic architecture of lumbar spinal stenosis
Authors: Salo Ville , Määttä Juhani , Takala Jasmin , Heikkilä Anni , FinnGen  , Reimann Ene , Mägi Reedik ,   Estonian Biobank Research Team, Reis Kadri , G.Elhanas Abdelrahman , Reigo Anu , Palta Priit , Esko Tõnu , Leinonen Ville , Karppinen Jaro , Sliz Eeva , Kettunen Johannes
Published: October 2024

Introductory paragraph

Over 100 million people worldwide suffer from lumbar spinal stenosis (LSS) with increasing incidence with ageing population, yet little is known about the LSS genetic background. Given the high cost of treating LSS, a deeper understanding of LSS pathogenesis may eventually result in the development of novel preventative and treatment methods, potentially leading to reductions in related societal costs. Our aim is to gain a better understanding of the genetic components underlying LSS. In the FinnGen, Estonian, and UK biobanks, we conduct a genome-wide association study (GWAS) of LSS and merge the results in the genome-wide meta-analysis. In addition to the seven known risk loci, our meta-analysis reveals 47 loci that have not been associated with LSS in previous studies. Many downstream analyses and multiple candidate genes discovered from the LSS-associated loci suggest that spinal degeneration plays a major role in the pathogenesis of LSS.