bluuebunny/crossref_metadata_2025 huggingface dataset:
An Inflammation‐Related lncRNA Signature for Prognostic Prediction in Colorectal Cancer
Authors: Zhang Zhenling , Luo Yingshu , Liu Yuan , Ren Jiangnan , Fang Zhaoxiong , Han Yanzhi
Published: December 2024

Background

Colorectal cancer (CRC) represents a commonly diagnosed malignancy affecting the digestive system. Mounting evidence shows long noncoding RNAs (lncRNAs) contribute to carcinogenesis. However, inflammation‐related lncRNAs (IRLs) regulating CRC are poorly defined.

Aims

The current study aimed to develop an IRL signature for predicting prognosis in CRC and to examine the involved molecular mechanism.

Methods and Results

RNA‐seq findings and patient data were retrieved from The Cancer Genome Atlas (TCGA), and inflammation‐associated genes were obtained from the GeneCards database. IRLs with differential expression were determined with “limma” in R. Using correlation and univariable Cox analyses, prognostic IRLs were identified. The least absolute shrinkage and selection operator (LASSO) algorithm was employed to construct a prognostic model including 13 IRLs. The model's prognostic value was examined by Kaplan–Meier (K‐M) survival curve and receiver operating characteristic (ROC) curve analyses. Furthermore, the association of the signature with the immune profile was assessed. Finally, RT‐qPCR was carried out for verifying the expression of inflammation‐related lncRNAs in nonmalignant and malignant tissue samples. A model containing 13 inflammation‐related lncRNAs was built and utilized to classify cases into two risk groups based on risk score. The signature‐derived risk score had a higher value in predicting survival compared with traditionally used clinicopathological properties in CRC cases. In addition, marked differences were detected in immune cells between the two groups, including CD4+ T cells and M2 macrophages. Furthermore, RT‐qPCR confirmed the expression patterns of these 13 lncRNAs were comparable to those of the TCGA‐CRC cohort.

Conclusion

The proposed 13‐IRL signature is a promising biomarker and may help the clinical decision‐making process and improve prognostic evaluation in CRC.
TMS and EEG Pharmacodynamic Effects of a Selective Sphingosine‐1‐Phosphate Subtype 1 Receptor Agonist on Cortical Excitability in Healthy Subjects
Authors: de Cuba Catherine M. K. E. , de Goede Annika A. , Klaassen Erica S. , Otto Marije E. , Doll Robert J. , Kim Jessica , Demitrack Mark A. , Chen Ruihua , Groeneveld Geert Jan , Heuberger Jules A. A. C.
Published: December 2024

Current anti‐epileptic drugs lack efficacy, cause many side effects and one third of all patients are treatment‐resistant. Drugs targeting the sphingosine‐1‐phosphate receptor show potential anti‐convulsant effects in animal models and decrease cortical excitability in patients with multiple sclerosis, but available compounds alter lymphocyte trafficking and cause immunosuppression, limiting their clinical anti‐epileptic potential. TRV045 is a selective sphingosine‐1‐phosphate subtype 1 receptor agonist without effects on lymphocyte trafficking, demonstrating efficacy in animal models of epilepsy, with the potential to target abnormal cortical excitability. This randomized, double‐blind, placebo‐controlled, two‐way cross‐over, multiple‐dose study evaluated the effects of TRV045 on cortical excitability in healthy male adults, measured by pharmaco‐electroencephalography and transcranial magnetic stimulation (TMS). Subjects received TRV045 250 mg or placebo, once daily for 4 days, in randomized order. Endpoints were analyzed with a mixed effects model analysis of covariance. Twenty‐five of the 27 subjects completed the study. There was a significant increase in alpha power with eyes open after treatment with TRV045 on Day 1, increasing after 4 days of dosing. Less pronounced significant effects in beta, gamma, and delta power were observed after 4 days. For TMS‐Electromyography there was a non‐significant decreased post‐dose single‐pulse peak‐to‐peak amplitude on Day 1 only, and there were no effects on paired‐pulse parameters. Several significant TMS‐Electroencephalography clusters were seen after 4 days of dosing. These findings show that TRV045 has central nervous system activity with evolving effects following repeated dosing. These data support further studies to elucidate the mechanism of action of TRV045 and its potential anti‐epileptic effects.
Molecular mechanisms underlying oesophageal cancer development triggered by chronic alcohol consumption
Authors: Chen Huai Yi , Por Chia Rou , Hong Yong Kai , Kong Eason Qi Zheng , Subramaniyan Vetriselvan
Published: December 2024

This review explores the mechanisms underlying alcohol‐induced oesophageal carcinogenesis, including DNA damage, oxidative stress, and nutritional deficiencies. Alcohol metabolism primarily involves alcohol dehydrogenase (ADH) converting ethanol to acetaldehyde, which can cause DNA damage, inhibit repair mechanisms, and form DNA adducts thus inhibiting DNA replication. Plus, it delves into the epidemiological evidence, genetic susceptibility, epigenetic modifications, biomarkers, and preventive strategies associated with alcohol‐related oesophageal cancers. Consumption of alcohol increases the risk of gastroesophageal reflux disease thus compromising mucosal integrity of the oesophagus as dysregulation of cytokines such as IL‐18, TNFA, GATA3, TLR4, and CD68 expands the intercellular spaces of epithelial cells. Genetic variants, such as ADH1B rs1229984 and ALDH2 rs671, significantly influence susceptibility to alcohol‐related oesophageal cancers, with these variations affecting acetaldehyde metabolism and cancer risk. Understanding these factors is crucial for early detection, effective treatment, and the development of targeted prevention strategies. Biomarkers, such as miRNA and metabolite markers, offer non‐invasive methods for early detection, while advanced endoscopic techniques provide better diagnostic accuracy. Pharmacological interventions, such as statins and proton pump inhibitors, also show potential for reducing cancer progression in high‐risk individuals. Despite advances, late‐stage oesophageal cancer diagnoses are still common, highlighting the need for better screening and prevention. Further research, including this study, should aim to improve early detection, personalise prevention, and explore new treatments to reduce cases and enhance outcomes in alcohol‐related oesophageal cancers.
Unveiling the effects of landscape–fire interactions on functional diversity in a Southern European mountain
Authors: Campos João C. , Albuquerque Beatriz , Civantos Emilio , Honrado João P. , Regos Adrián
Published: December 2024

Climate and land‐use changes are contributing to impacts on global ecosystem functioning. These effects are particularly severe in areas undergoing land abandonment and extreme wildfire events, such as the Mediterranean regions of the Iberian Peninsula. Previous studies have evaluated the impacts of land management on fire mitigation and biodiversity (species distribution and species richness), but how such strategies influence functional diversity remains unexplored. This study investigates how alternative land‐fire management strategies may affect functional diversity. We modeled for 2050 for the Transboundary Biosphere Reserve Gerês‐Xurés (Portugal‐Spain). Land‐use scenarios simulated processes of land abandonment (“business‐as‐usual”—BAU) and the implementation of EU rural policies (“high nature value farmlands”—HNVf), and were combined with three fire suppression levels. Species distribution models (102 vertebrates) were projected to each scenario, and functional diversity indices were consequently calculated. The highest functional richness was predicted for BAU scenarios, probably representing the benefits to unique species that deliver singular functions. The HNVf scenarios provided the highest functional divergence, probably indicating a high niche differentiation and low resource competition amongst agricultural communities. HNVf was the most beneficial scenario for ecosystem functioning, while fire suppression did not affect functional diversity. Despite the proneness to burn of our study area and the effects of firefighting on its fire regime, land‐use policies are expected to have greater influence than fire suppression effects on functional diversity. These findings suggest that different facets of functional diversity will be unevenly influenced by fire–landscape dynamics driven by the land‐use policies to be implemented in the upcoming decades.
Individuality Through Ecology: Rethinking the Evolution of Complex Life From an Externalist Perspective
Authors: Bourrat Pierrick , Takacs Peter , Doulcier Guilhem , Nitschke Matthew C. , Black Andrew J. , Hammerschmidt Katrin , Rainey Paul B.
Published: December 2024

The evolution of complex life forms, exemplified by multicellular organisms, can be traced through a series of evolutionary transitions in individuality, beginning with the origin of life, followed by the emergence of the eukaryotic cell, and, among other transitions, culminating in the shift from unicellularity to multicellularity. Several attempts have been made to explain the origins of such transitions, many of which have been internalist (i.e., based largely on internal properties of ancestral entities). Here, we show how externalist perspectives can shed new light on questions pertaining to evolutionary transitions in individuality. We do this by presenting the ecological scaffolding framework in which properties of complex life forms arise from an external scaffold. Ultimately, we anticipate that progress will come from recognition of the importance of both the internalist and externalist modes of explanation. We illustrate this by considering an extension of the ecological scaffolding model in which cells modify the environment that later becomes the scaffold giving rise to multicellular individuality.
Extensive Tracking of Nomadic Waterbird Movements Reveals an Inland Flyway
Authors: McGinness Heather M. , Jackson Micha V. , Lloyd‐Jones Luke , Robinson Freya , Langston Art , O'Neill Louis G. , Rapley Shoshana , Piper Melissa , Davies Micah , Hodgson Jessica , Martin John M. , Kingsford Richard , Brandis Kate , Doerr Veronica , Mac Nally Ralph
Published: December 2024

Waterbirds are highly mobile and have the ability to respond to environmental conditions opportunistically at multiple scales. Mobility is particularly crucial for aggregate‐nesting species dependent on breeding habitat in arid and semi‐arid wetlands, which can be ephemeral and unpredictable. We aimed to address knowledge gaps about movement routes for aggregate‐nesting nomadic waterbird species by tracking them in numbers sufficient to make robust assessment of their movement patterns. We hypothesised that analysis of long‐distance movements would identify common routes with consistent environmental features that would be useful as context for conservation management. We used GPS satellite telemetry to track the movements of 73 straw‐necked ibis (Threskiornis spinicollis) and 42 royal spoonbills (Platalea regia) over 7 years (2016‐2023). We used these data to identify long‐distance movements and to demarcate and characterise movement routes. We identified common routes used by both species, including a ‘flyway’ over 2000 km long, spanning Australia's Murray–Darling Basin from the south‐west to the north‐east. This flyway connects important breeding sites and is characterised by flat, open/unforested areas with low elevations of < 350 m and mid to high rainfall. The flyway corresponds to an area west of Australia's Great Dividing Range, which appears to act as a low‐permeability barrier to the movement of both species. Identification of an inland flyway for waterbirds in Australia provides important context for multi‐jurisdictional cooperation and strategic management. Where resources are limited, water and wetland management efforts (e.g., environmental watering) should be preferentially located within this route. Similarly, targeting threat mitigation within common movement routes may have disproportionate importance for long‐term population viability. Given the widespread distribution of similar species globally, there are likely to be other flyways worthy of scientific and conservation management attention that could be identified using our approach.
The Origin of the Matter Matters: The Influence of Terrestrial Inputs on Coastal Benthic Microeukaryote Communities Revealed by eDNA
Authors: Meyneng Mathisse , Siano Raffaele , Mouras Naïna , Ansquer Dominique , Laporte‐Magoni Christine , Antypas Florence , Haize Thomas , Lemonnier Hugues
Published: December 2024

Estuaries are a key component of the land‐sea continuum, and their microbial diversity depends on the connection with terrestrial ecosystems. This work aimed to demonstrate that the terrestrial matter carried by rivers influences the structuration of microeukaryote communities of superficial (0–3 cm) sediments collected at the interface between the land and marine coastal areas. To demonstrate this hypothesis, we have chosen the main island of New Caledonia as a study site, a French overseas territory located in the South West Pacific. Using amplicon sequencing of the 18S‐V4 rDNA extracted from sediments, we analyzed microeukaryote community composition in relation to numerous environmental parameters. Samples were collected in five bays influenced by riverine inputs and corresponding to distinct geological features of the watersheds, as revealed by high variations in metal concentrations released from specific minerals in the sediment. Particularly, the influence of ultramafic soils was highlighted by higher nickel concentration (correlated to Co, Cr, Mn, and Fe). Diatoms were the dominant taxonomic group, especially the classes of Bacillariophyceae and Mediophyceae. Then Apicomplexa, Ciliophora, Dinoflagellata, and Cercozoa followed. The metallic composition of the sediment explained 18.46% of the community spatial variability. The selection of ASVs based on their contribution to beta diversity and their correlation with metallic concentrations enabled us to identify spatial patterns. This information could lead to identifying microeukaryote bioindicators of terrestrial influences, particularly of ultramafic origin. We hypothesized that the association between microeukaryotes and metallic compositions is linked to selection processes, given the resistance of some microeukaryotes to some high metallic concentrations. In vitro experiments are needed to confirm this hypothesis. Our results emphasized the role of terrestrial inputs in shaping estuarine diversity and the need to consider the entire land–sea continuum for studying these ecosystems.
Identification of health trajectories of patients with persistent spinal pain syndrome type 2 using latent class trajectory methods
Authors: Ounajim Amine , Billot Maxime , Babin Etienne , Goudman Lisa , Moens Maarten , Roulaud Manuel , Lorgeoux Bertille , Baron Sandrine , Nivole Kevin , Many Mathilde , Lampert Lucie , Borel Sarah , David Romain , Rigoard Philippe
Published: December 2024

Background

Persistent spinal pain syndrome Type 2 (PSPS‐T2) is a long‐lasting condition that consists of persistent pain following spinal surgery. Although this condition has long‐term effects, it is currently studied at a given time point or over a limited period of time, which does not reflect the true impact of pain patients. To bridge this gap, we used latent class trajectory models to extract clusters with different trajectories of patients with PSPS‐T2.

Materials and Methods

Data from the PREDIBACK study, an observational, multicentric, and longitudinal investigation carried out prospectively, were used. This study focuses on patients with PSPS‐T2, tracking their outcomes at 3‐month intervals over a one‐year period. Health status was evaluated using a novel multidimensional clinical response index (MCRI). The trajectories of patients' health status were extracted using mixture of mixed effect models.

Results

Two hundred (200) PSPS‐T2 patients were included. Two clusters were identified, including ‘persistent low health’ trajectories (63.1%) and ‘improving health’ trajectories (36.9%). Regarding the factors associated with these trajectories, our results showed that lower age, lower body mass index, lower pain intensity, lower functional disability, lower anxiety and less extended pain surface were associated with improving health status.

Conclusion

Clustering methods provide an opportunity to identify two distinct clusters of pain‐related health trajectories of PSPS‐T2 patients. Persistence of the symptoms was not observed in one third of the PSPS‐T2 study patients, who belong to the improving pain‐related health cluster, while the other two thirds did not achieve improved health over a 1‐year follow‐up.

Significance Statement

Our study findings suggest that the use of trajectory‐based methods could improve patient evaluation and pain management as it allows for obtaining a global view of patients during their care pathway compared to conventional methods, which only focus on specific visits. Our study also advocates for multidimensional assessment and management of pain by targeting not only pain intensity but also the psychological distress, functional capacity and pain surface at an early stage of pain onset after spine surgery.
ILAE genetic literacy series: Focal cortical dysplasia
Authors: Macdonald‐Laurs Emma , Leventer Richard J. ,   the ILAE Genetics Commission* and the ILAE Genetics Literacy Taskforce**
Published: December 2024

Focal cortical dysplasia (FCD) is a common cause of drug‐resistant focal epilepsy in children and young adults and is often surgically remediable. The genetics of FCD are increasingly understood due to the ability to perform genomic testing including deep sequencing of resected FCD tissue specimens. There is clear evidence that FCD type II occurs secondary to both germline and somatic mTOR pathway variants, while emerging literature supports the role of SLC35A2, a glycosylation gene, in mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE). Herein, we provide a review of FCDs focusing on their clinical phenotypes, genetic basis, and management considerations when performing genetic testing in this patient group.
Study on the Influence of Scaling‐Up in the Transesterification Process for the Synthesis of Biodegradable Monoglycerides of Fatty Acids
Authors: Nagy Roland , Bejczi Rebeka
Published: December 2024

Fatty acids and monoglycerides from vegetable oils or animal fats are crucial in various industries. Monoglycerides, with their hydrophilic and hydrophobic properties, act as effective non‐ionic surfactants for oil‐in‐water emulsions. Scaling‐up the synthesis of biodegradable non‐ionic surfactants from natural sources presents challenges in maintaining physicochemical properties. This study investigates the scale‐up synthesis of biodegradable non‐ionic surfactants using sunflower oil and glycerol, focusing on properties like kinematic viscosity, acid number, and active matter content. Comparative experiments were conducted using different reactor sizes and configurations, evaluating the effects of reactor size, length‐to‐diameter (L/D) ratio, and mixer type. The results indicate that larger reactors generally reduce kinematic viscosity and active matter content. The geometric characteristics of the reactor significantly impact surfactant properties with variations in the RD/RH ratio affecting the active matter content and changes in the MPD/RD ratio influencing the water number. Based on our findings, the highest active matter content was achieved with an RD/RH ratio of 0.49 and an MPD/RD ratio of 0.95. A strong correlation was found between the active matter content and water solubility. The study underscores the importance of reactor design in optimizing surfactant properties when scaling‐up.
Yogurt Supplementation Can Ameliorate Fatty Liver Diseases and Metabolic Syndrome in High Fat‐Induced Conditions in Mice
Authors: Hasan Sohel , Amin Md Aminul Islam , Mia Masum , Khatun Sumaiya , Arafat Yesir , Gofur Md Royhan , Islam Md Mahmudul , Hosen Md Eram , Almaary Khalid S. , Fentahun Wondmie Gezahign , Islam Amirul , Rahman Matiar , Bourhia Mohammed
Published: December 2024

Hepatic steatosis/non‐alcoholic fatty liver disease is a major public health delinquent caused by the excess deposition of lipid into lipid droplets (LDs) as well as metabolic dysregulation. Hepatic cells buildup with more fat molecules when a person takes high fat diet that is excessive than the body can handle. At present, millions of people in the world are affected by this problem. So, it is very important to know the effects of factors responsible for the disease. Here, the role of lipid droplet (LD) biogenesis and metabolism was analyzed and intended to investigate if defects in biogenesis/metabolic enzymes are responsible for the accumulation of lipids other than LDs in fatty liver disease in high‐fat‐induced conditions in mice model. To explore it, high‐fat diet (HFD), fast food (FF), and soft drinks (SD) were administered to wild‐type Swiss albino mice for 14 weeks following yogurt supplementation. After experimental period, glucose tolerance, enzyme function, lipid profile, plasma biochemistry, and other analytical tests were analyzed by auto‐analyzer including different oxidative stress markers. Lipids from hepatic tissues were extracted, and purified by Floatation Assay and subsequently analyzed by different biochemical and chromatographic techniques. Histological architecture of hepatocytes was performed using Zeiss microscope. Finally, increased amount of lipids biogenesis/accumulation was found in liver tissues that causes Fatty liver disease. Significantly, HFD, FF, and SD were identified as factors for the increased LD biogenesis and or lipid metabolic disorder. Nevertheless, yogurt supplementation can homeostasis those LD formation and metabolic syndrome as it increases the down regulation of lipid biogenesis as well as lipid metabolic rate. So, yogurt supplementation was considered as a novel agent for decreasing LD biogenesis as well as excessive accumulation of fat in hepatocytes which can be used as therapeutics for the treatment of NAFLD.
Techno‐Economic Analysis of Glycerol Steam Reforming with Amine‐Based Carbon Capture for Blue Hydrogen Production: A Rate‐Based Kinetic Model Approach
Authors: Rosha Pali , Sajjadi Mohammad , Ibrahim Hussameldin
Published: December 2024

This study outlines a comprehensive process design utilising glycerol‐steam reforming for an H2‐enriched gas stream, coupled with carbon dioxide removal via a chemical absorption system, followed by a techno‐economic analysis. The Aspen Plus economic analyser assesses the developed model, incorporating simulation results and literature data. Initially, the CO2 capture unit was planned with a standalone absorber and stripper, later integrated for solvent makeup calculation. Findings reveal that as catalyst loading increased from 5 to 50 kg, glycerol conversion and product molar fraction improved. For a targeted H2 production of 10 t/day, optimal reactor dimensions are 3.2 m diameter and 30 m length, corresponding to a reactant flow of 105 t/day and a 2.52 MW heat duty at stoichiometry conditions. To capture 95% CO2 from the reformed product stream, absorber and stripper packing heights of 12 and 7 m, respectively, with column diameters of 1.25 and 2.71 m are necessary. The production cost of H2 is determined to be $3.8 per kg, as revealed by the techno‐economic analysis. Calculated values for net present value, discounted payback period, and internal rate of return stand at $30 million, 5 years, and 25.0%, respectively. © 2024 Society of Chemical Industry and John Wiley & Sons, Ltd.
Clotted Apheresis Hematopoietic Stem Cell Product
Authors: Zhuang Lefan , Woo Jennifer , Francisco Franchesca , Bertram Rickey , Wang Shirong , Jackson Ryan , Yuan Shan
Published: December 2024

The majority of the time hematopoietic progenitor cells (HPC) are collected through leukapheresis, where anticoagulants are necessary to prevent clotting of the apheresis circuit and HPC product. Although clotting of the product is a possible rare complication surrounding the HPC cryopreservation process, there have been no reports of clotting of fresh HPC product after collection. We report a case of progressive clotting of a fresh matched unrelated donor HPC product. Upon initial receipt, thin thread‐like white clots were seen in the bag. In an attempt to isolate the clot, the product was aseptically aliquoted into 50 mL syringes. Within the next 60 minutes the small clots coalesced into a pink cylindrical jelly‐like blood clot surrounded by serum. In the future, an anticoagulant can be added into the product prior to isolation of the clot.
Tumor‐Derived GDF15 Induces Tumor Associated Fibroblast Transformation From BMSCs and Fibroblasts in Oral Squamous Cell Carcinoma
Authors: Zhao Jingjing , Li Yahui , Huang Yingying , Su Peng , Nie Fujiao , Yang Pishan , Yang Chengzhe
Published: December 2024

Cancer associated fibroblasts (CAFs) are the predominant stromal cell‐type in the solid tumor microenvironment, originating from various cell types and playing a crucial role in promoting tumor progression and metastasis The generation of CAFs is influenced by complex factors secreted by tumor cells, with particular emphasis on transforming growth factor‐β (TGF‐β). However, it remains largely unknown whether growth/differentiation factor‐15 (GDF15), as a member of the TGF‐β superfamily, exerts similar effects to TGF‐β in oral squamous cell carcinoma (OSCC). In this study, we investigated the impact of GDF15 derived from tumor cells on CAF transformation and elucidated the underlying mechanisms. Exogenous GDF15 and OSCC cells induced the transformation of bone marrow mesenchymal stem cells (BMSCs) and human gingival fibroblasts (HGFs) into CAFs, as evidenced by α‐smooth muscle actin (α‐SMA) as a phenotypic marker and TGF‐β, interleukin 6 (IL‐6), and vascular endothelial‐derived growth factor (VEGF) as functional markers. Conversely, knockdown of GDF15 in OSCC cells reversed CAF transformation. Mechanistically, extracellular signal‐regulated kinases 1/2(ERK1/2) pathway was associated with GDF15‐mediated promotion of CAF transformation. Furthermore, OSCC‐induced CAFs enhanced migration and invasion abilities of OSCC cells; but this pro‐cancer effect was abolished upon knockdown of GDF15 in OSCC cells. Subcutaneous coinjection of OSCC cells with BMSCs or HGFs into mice revealed the promoted tumor growth along with increased expression levels of α‐SMA and Ki67 compared with alone OSCC cells injection; these effects were attenuated when GDF15 was knocked down in OSCC cells. Collectively, our findings suggest that tumor‐derived GDF15 contributes to the progression of OSCC by promoting CAF transformation through activation of the ERK1/2 pathway.
Feature Engineering for the Prediction of Scoliosis in 5q‐Spinal Muscular Atrophy
Authors: Vu‐Han Tu‐Lan , Sunkara Vikram , Bermudez‐Schettino Rodrigo , Schwechten Jakob , Runge Robin , Perka Carsten , Winkler Tobias , Pokutta Sebastian , Weiß Claudia , Pumberger Matthias
Published: December 2024

Background

5q‐Spinal muscular atrophy (SMA) is now one of the 5% treatable rare diseases worldwide. As disease‐modifying therapies alter disease progression and patient phenotypes, paediatricians and consulting disciplines face new unknowns in their treatment decisions. Conclusions made from historical patient data sets are now mostly limited, and new approaches are needed to ensure our continued best standard‐of‐care practices for this exceptional patient group. Here, we present a data‐driven machine learning approach to a rare disease data set to predict spinal muscular atrophy (SMA)‐associated scoliosis.

Methods

We collected data from 84 genetically confirmed 5q‐SMA patients who have received novel SMA therapies. We performed expert domain knowledge‐directed feature engineering, correlation and predictive power score (PPS) analyses for feature selection. To test the predictive performance of the selected features, we trained a Random Forest Classifier and evaluated model performance using standard metrics.

Results

The SMA data set consisted of 1304 visits and over 360 variables. We performed feature engineering for variables related to ‘interventions’, ‘devices’, ‘orthosis’, ‘ventilation’, ‘muscle contractures’ and ‘motor milestones’. Through correlation and PPS analysis paired with expert domain knowledge feature selection, we identified relevant features for scoliosis prediction in SMA that included disease progression markers: Hammersmith Functional Motor Scale Expanded ‘HFMSE’ (PPS = 0.27) and 6‐Minute Walk Test ‘6MWT’ scores (PPS = 0.44), ‘age’ (PPS = 0.41) and ‘weight’ (PPS = 0.49), ‘contractures’ (PPS = 0.17), the use of ‘assistive devices’ (PPS = 0.39, ‘ventilation’ (PPS = 0.16) and the presence of ‘gastric tubes’ (PPS = 0.35) in SMA patients. These features were validated using expert domain knowledge and used to train a Random Forest Classifier with an observed accuracy of 0.82 and an average receiver operating characteristic (ROC) area of 0.87.

Conclusion

The introduction of disease‐modifying SMA therapies, followed by the implementation of SMA in newborn screenings, has presented physicians with never‐seen patients. We used feature engineering tools to overcome one of the main challenges when using data‐driven approaches in rare disease data sets. Through predictive modelling of this data, we defined disease progression markers, which are easily assessed during patient visits and can help anticipate scoliosis onset. This highlights the importance of progressive features in the drug‐induced revolution of this rare disease and further supports the ongoing efforts to update the SMA classification. We advocate for the consistent documentation of relevant progression markers, which will serve as a basis for data‐driven models that physicians can use to update their best standard‐of‐care practices.
Usefulness of simplified comprehensive geriatric assessment as a pre‐ERCP screening for the elderly
Authors: Nomura Shuzo , Saito Kei , Fujisawa Mariko , Kitahara Mai , Kuniyoshi Noriyuki , Imazu Hiroo , Kogure Hirofumi
Published: December 2024

Background

Endoscopic retrograde cholangiopancreatography (ERCP) is often performed in elderly patients for stone removal and biliary drainage following common bile duct stones or malignant biliary obstruction. Safety in ERCP should be considered in elderly patients due to complications and decreased activities of daily living (ADL), but there are no adequate pretest evaluation criteria. In recent years, the usefulness of the comprehensive geriatric assessment (CGA) for planning treatment and predicting prognosis has been reported.

Methods

We retrospectively analyzed consecutive patients who underwent ERCP at our institution between October 2021 and June 2023. The relationship between CGA and ERCP outcomes was examined by dividing CGA scores into three groups (Group A; score 0, Group B; score 1–4, Group C; score 5–7) among patients 65 years of age and older. Risk factors for prolonged hospitalization were identified using univariate and multivariate analysis.

Results

Of the 388 patients, 290 were 65 or older with a CGA score. The median length of hospital stay was significantly longer in the higher CGA7 scores group (5 vs. 8 vs. 15 days, p < .01). There was no significant difference in the rate of adverse events (p = .54) and median total procedure time (p = .35). In univariate and multivariate analysis, higher CGA score groups were significant risk factors for a prolonged hospital stay.

Conclusions

CGA appears to be a valuable tool for preadmission screening in elderly patients undergoing ERCP.
Retention on antiretroviral therapy and drivers of lost‐to‐follow up in the Central African Republic: a longitudinal analysis
Authors: Tekpa Gaspard , Inikoutiyo Jules , Yonli Christian , Noguera Celia , Lujwiro Pierre Prince , Gigout Laure , Hachimou Aboubacar , Romaric Sydney , Mabaïlao Raphaël , Banthas Marie Charlotte , Mbia Larissa Bertille , Mbay Paulette Rose , Romuald Kevin , Sana Alain , Roberte Florida , Moretó‐Planas Laura , Goemaere Eric , Mekiedje Calorine , Ouanekpone Stella , Núñez‐Andrés Maria Amparo , Hoibak Sarah , Vallès Xavier
Published: December 2024

Introduction

The retention in care of patients undergoing antiretroviral therapy (ART) is a cornerstone for preventing AIDS‐associated morbidity and mortality, as well as further transmission of HIV. Adherence to ART poses particular challenges in conflict‐affected settings like the Central African Republic (CAR). The study objective was to estimate the rate of lost‐to‐follow‐up (LTFU) and determine factors associated with LTFU among patients living with HIV under ART in CAR.

Methods

A retrospective cohort analysis was conducted using data from patients being managed at 42 representative ART dispensing sites (i.e. management of ≥200 patients) in the seven health regions of CAR which started ART between January 2019 to September 2021 and followed up to December 2021. The outcome of LTFU was defined as a failure of a patient to attend a scheduled ART refill appointment for at least 90 days from the last appointment. Patients were censored at the first LTFU event.

Results

A total of 6844 patients enrolled in ART care were included in the analysis, of whom 67.5% were females. The mean age (standard deviation) was 35.3 years (10.5). Forty‐two per cent (n = 2874/6844) had an LTFU event during the follow‐up period. However, 23.2% (n = 666/2874) returned to care after LTFU. Overall retention in antiretroviral care at 12 months was 64.2% (CI 63.0−65.5), which ranged from 76.1% in the capital to 48.2% in the inner country region. Risk factors related to LTFU were being male (adjusted hazard ratio [aHR] 1.33; CI 1.1−1.5), age < 25 (aHR 1.46; CI 1.1−1.9), living in regions outside the capital (aHR 1.83; CI 1.6−2.3) and undernutrition (aHR 1.13; CI 1.0−1.3).

Conclusions

Retention to care in CAR is suboptimal, especially in the inner country. Our results underline the difficulties involved in retaining patients in ART in complex settings, the interplay between poor retention, social unrest, stigma, food insecurity and HIV epidemic control, and the need for tailored programming and interventions like differentiated treatment strategies and complementary food provision.
Declining Prevalence of Human Papillomavirus Co‐Infections Among Young Japanese Women With Cervical Cancer and Its Precursors
Authors: Yoshiizumi Eri , Onuki Mamiko , Kukimoto Iwao , Takahashi Fumiaki , Matsui Tomoya , Hamasaki Kyoko , Kanao Hiroyuki , Nio Ai , Yahata Hideaki , Goda Mayuko , Yokoyama Takanori , Hisa Tsuyoshi , Tasaki Kazuto , Tenjimbayashi Yuri , Saji Haruya , Kudaka Wataru , Takei Yuji , Shigeta Shogo , Motohara Takeshi , Matsumiya Hiroko , Nakamura Keiichiro , Yoshida Hiroyuki , Ishikawa Mitsuya , Hamanishi Junzo , Nakai Hidekatsu , Mori‐Uchino Mayuyo , Hirashima Yasuyuki , Sekizawa Akihiko , Yoshikawa Hiroyuki , Yaegashi Nobuo , Matsumoto Koji ,   the MINT Study Group
Published: December 2024

Co‐infections with human papillomavirus (HPV) of multiple genotypes mainly occur due to increased sexual activity. To address the prevalence and trend of HPV co‐infections in Japan, HPV‐type‐specific data from Japanese women (n = 8128) aged < 40 years and newly diagnosed with cervical abnormalities at 24 hospitals between 2012 and 2023 were analyzed. These included cervical intraepithelial neoplasia grade 1/2 (CIN1/2, n = 2745), CIN3/adenocarcinoma in situ (AIS) (n = 3953), and invasive cervical cancer (ICC, n = 1430). For women enrolled in this study since 2019, information on sexual behaviors was collected via a self‐administered questionnaire. Time‐trend analyses by disease category showed significant declines in the prevalence of multiple HPV infections in CIN1/2 (49.1%−38.3%, ptrend = 0.0004), CIN3/AIS (44.7%–31.5%, ptrend = 0.0002), and ICC (26.7%–10.5%, ptrend < 0.0001) during the last decade. When these data were analyzed separately for women aged 20–29 and 30–39 years, similar declining trends were observed in each disease category. Using data from 2111 women for whom information on sexual history was available, the number of sexual partners was strongly associated with increased multiple HPV infections (p < 0.0001). In conclusion, the declining prevalence of HPV co‐infections in cervical cancer and its precursors may reflect a decrease in sexual activity among Japanese women of reproductive age.
Systems Immunology Approaches to Understanding Immune Responses in Acute Infection of Yellow Fever Patients
Authors: Gonçalves André N. A. , Costa Priscilla R. , Thomazella Mateus V. , Correia Carolina A. , Marmorato Mariana P. , Dias Juliana Z. C. , Silveira Cassia G. T. , Maestri Alvino , Cerqueira Natalia B. , Moreira Carlos H. V. , Buccheri Renata , Félix Alvina C. , Martins Felipe M. , Maso Vanessa E. , Ferreira Frederico M. , Araújo José D. A. , Vasconcelos Amanda P. , Gonzalez‐Dias Patrícia , Pelletier Adam‐Nicolas , Sékaly Rafick‐Pierre , Cabral‐Marques Otavio , Coelho‐dos‐Reis Jordana G. A. , Ferreira Daniela M. , Kallas Esper G. , Nakaya Helder I.
Published: December 2024

In the 2018 yellow fever (YF) outbreak in Brazil, we generated new transcriptomic data and combined it with clinical and immunological data to decode the pathogenesis of YF. Analyzing 79 patients, we found distinct gene expression patterns between acute YF, other viral infections, and the milder YF‐17D vaccine infection. We identified a critical role for low‐density, immature neutrophils in severe outcomes, marked by the downregulation of genes essential for neutrophil migration and maturation, such as PADI4, CSF3R, and ICAM1, in deceased patients. Our study also revealed complex interactions among inflammation‐related genes, including increased CXCL10 and IL1R2 expression and decreased IL‐1b expression in the acute phase. The diminished expression of HLA class II genes indicates impaired antigen presentation. These findings highlight the delicate balance of immune responses in YF pathogenesis and lay the groundwork for future therapeutic and diagnostic advancements.
Analytical Performance of a Novel Nanopore Sequencing for SARS‐CoV‐2 Genomic Surveillance
Authors: Maimaiti Mulatijiang , Kong Lingjun , Yu Qi , Wang Ziyi , Liu Yiwei , Yang Chenglin , Guo Wenhu , Jin Lijun , Yi Jie
Published: December 2024

The genomic analysis of SARS‐CoV‐2 has served as a crucial tool for generating invaluable data that fulfils both epidemiological and clinical necessities. Long‐read sequencing technology (e.g., ONT) has been widely used, providing a real‐time and faster response when necessitated. A novel nanopore‐based long‐read sequencing platform named QNome nanopore has been successfully used for bacterial genome sequencing and assembly; however, its performance in the SARS‐CoV‐2 genomic surveillance is still lacking. Synthetic SARS‐CoV‐2 controls and 120 nasopharyngeal swab (NPS) samples that tested positive by real‐time polymerase chain reaction were sequenced on both QNome and MGI platforms in parallel. The analytical performance of QNome was compared to the short‐read sequencing on MGI. For the synthetic SARS‐CoV‐2 controls, despite the increased error rates observed in QNome nanopore sequencing reads, accurate consensus‐level sequence determination was achieved with an average mapping quality score of approximately 60 (i.e., a mapping accuracy of 99.9999%). For the NPS samples, the average genomic coverage was 89.35% on the QNome nanopore platform compared with 90.39% for MGI. In addition, fewer consensus genomes from QNome were determined to be good by Nextclade compare with MGI (p < 0.05). A total of 9004 mutations were identified using QNome sequencing, with substitutions being the most prevalent, in contrast, 10 997 mutations were detected on MGI (p < 0.05). Furthermore, 23 large deletions (i.e., deletions≥ 10 bp) were identified by QNome while 19/23 were supported by evidence from short‐read sequencing. Phylogenetic analysis revealed that the Pango lineage of consensus genomes for SARS‐CoV‐2 sequenced by QNome concorded 83.04% with MGI. QNome nanopore sequencing, though challenged by read quality and accuracy compared to MGI, is overcoming these issues through bioinformatics and computational advances. The advantage of structure variation (SV) detection capabilities and real‐time data analysis renders it a promising alternative nanopore platform for the surveillance of the SARS‐CoV‐2.
Rainfall From Brazilian Flying Rivers: Evaluating the Effectiveness of Precipitation Gridded Databases
Authors: Amaral e Silva Arthur , de Assis Leonardo Campos , dos Santos Vitor Juste , de Andrade Laura Coelho , Lorentz Juliana Ferreira , Henriques Bruno Silva , Calijuri Maria Lucia , Ferreira Italo Oliveira
Published: December 2024

The uneven global distribution of rainfall significantly impacts water resources and environmental sustainability, emphasising the need for reliable climate prediction models. Accurate predictions are vital for sectors such as food security, urban planning and disaster management. Data from ground stations, radars and satellites are essential, despite challenges like instrumental errors. Satellites, with their comprehensive sensors, are crucial for atmospheric observations, aiding in the prediction of large‐scale climatic events. Climate models such as CHIRPS, GLDAS, TerraClimate, and PERSIANN use different approaches to analyse precipitation data, which is key to understanding its spatial and temporal variability. This study evaluated (rainfall data) from these four climate models over 20 years (within the Brazilian territory), focusing on the spatiotemporal behaviour of rainfall using statistical metrics such as R
2, RMSE, and MAPE. The findings showed that CHIRPS had the best performance (R
2 = 0.843; RMSE = 42.83; MAPE = 0.09%), excelling in both overall database and extreme event analyses. TerraClimate, initially the lowest‐performing model (R
2 = 0.413; RMSE = 91.56; MAPE = 0.23%), improved significantly when combined with elevation through multiple linear regression (MLR), achieving R
2 of 0.718, RMSE of 31.14, and MAPE of 9.56%. This made TerraClimate a viable model for studying the Flying Rivers. The study highlights that model selection should align with the specific characteristics of the area under consideration, with CHIRPS being particularly suitable for the studied region. This research enhances the understanding of the effectiveness of these models in estimating rainfall compared to in situ measurements, which is crucial for various applications. The authors advocate for further studies to advance research on the Flying Rivers, their significance, and the impacts of climate change on them.
The ASPEN Rhoads Research Foundation: Supporting and advancing clinical nutrition research
Authors: Winkler Marion , Tappenden Kelly A. , McMahon M. Molly , Spangenburg Michelle , Compher Charlene
Published: December 2024

The vision of the ASPEN Rhoads Research Foundation is to promote innovation and research discovery to improve nutrition care and health. The Foundation was launched in 1993, incorporated in 2002, and established as a nonprofit 501(c)(3) organization in 2007. On the occasion of American Society for Parenteral and Enteral Nutrition (ASPEN)'s 50th anniversary, this article examines the creation of the Foundation, the state of clinical nutrition research funding, the Foundation's philanthropic mission, and the return on investment of Foundation grant support. To date, 114 investigators have received 2.78 million dollars in funding. The article examines the success of ASPEN research programs and Foundation grant support in career development, leadership, and mentorship. It is important to document a historical account of the ASPEN Rhoads Research Foundation and encourage innovation and discovery and ongoing financial support.
Associations between the Dietary Inflammatory Index and fractional exhaled nitric oxide among United States adults: A cross‐sectional study
Authors: Wang Yinghong , Song Xiaolian , Tan Min
Published: December 2024

Background

Fractional exhaled nitric oxide (FeNo) is a convenient and noninvasive test that measures the concentration of nitric oxide in exhalation as a surrogate biomarker of airway inflammation. This cross‐sectional study aimed to determine the associations between Dietary Inflammatory Index (DII) and FeNo in US adults.

Methods

Adults participating in the 2007–2012 cycles of the US National Health and Nutrition Examination Survey with complete information and available measurement data of DII and FeNo were included. Associations between DII and FeNo were assessed using univariable and multivariable logistic regression models, restricted cubic spline analysis, stratified analysis, and sensitivity analysis.

Results

A total of 7677 participants (mean age 45.68 years, 53.03% men) with a mean DII of 1.28 and FeNo of 17.33 ppb were included. The multivariable‐adjusted linear regression analysis showed that a one‐unit increase in DII was associated with a 0.283‐ppb reduction in FeNo level. The beta and 95% CI for the second, third, and fourth DII quartile groups were −1.19 (−2.04 to −0.35), −1.07 (−2.26 to 0.12), and −1.60 (−2.85 to −0.36), respectively (P for trend = 0.04), with the lowest quartile group as the reference. The restricted cubic spline curve showed an inversely linear relationship between DII and FeNo. The study result is robust and did not appear to be affected by the participant's age, sex, race, body mass index, physical activity, diabetes status, or white blood cell or eosinophil counts.

Conclusion

A proinflammatory diet, as indicated by a higher DII, is cross‐sectionally associated with lower FeNo levels in US adults.
Navigated versus conventionally instrumented total knee arthroplasty techniques: No difference in functional alignment or balance
Authors: Russell Shane P. , Keyes Sarah , Grobler Grant , Harty James A.
Published: December 2024

Purpose

Much debate exists about the superiority of navigated versus conventional instrumentation for achieving optimal balance and alignment during total knee arthroplasty (TKA). Recent registry data indicate no long‐term survivorship benefit for TKAs performed using technology assistance, despite the added resource and financial costs. However, outcome comparisons are confounded by varying surgeon techniques and targets for ideal balance and alignment. This study aimed to investigate alignment or balance outcome differences between navigated and conventionally instrumented TKAs performed using an identical operative sequence and alignment strategy.

Methods

Fifty navigated and 50 conventionally instrumented primary TKAs, using an identical inverse kinematic alignment strategy, were included. Navigation equipment was used intraoperatively to ‘post‐cut’ record the conventionally instrumented TKAs. Intraoperative balance, range, and alignment; and post‐operative radiographic accuracy for restoration of constitutional alignment were compared.

Results

Forty‐nine navigated and 49 conventionally instrumented TKAs were compared (n = 2 excluded due to inadequate radiographs). No preoperative demographic or deformity severity differences existed. No intraoperative balance, range or alignment difference existed. Neither technique was more accurate for restoration of constitutional alignment.

Conclusion

Whilst large registry data may be confounded by uncaptured variables such as surgeon balancing techniques or surgeon alignment strategy preferences, this study found no alignment or balance differences between navigated versus conventionally instrumented TKA techniques for a surgeon and technique‐controlled study. Although the increased resources necessary for technology assistance are not justified by this study, further studies may identify significance using larger samples or comparison of alternative outcomes.

Level of Evidence

Level II.