bluuebunny/crossref_metadata_2025 huggingface dataset:
The potential of GPT-4 advanced data analysis for radiomics-based machine learning models
Authors: Foltyn-Dumitru Martha , Rastogi Aditya , Cho Jaeyoung , Schell Marianne , Mahmutoglu Mustafa Ahmed , Kessler Tobias , Sahm Felix , Wick Wolfgang , Bendszus Martin , Brugnara Gianluca , Vollmuth Philipp
Published: December 2024

Background

This study aimed to explore the potential of the Advanced Data Analytics (ADA) package of GPT-4 to autonomously develop machine learning models (MLMs) for predicting glioma molecular types using radiomics from MRI.

Methods

Radiomic features were extracted from preoperative MRI of n = 615 newly diagnosed glioma patients to predict glioma molecular types (IDH-wildtype vs IDH-mutant 1p19q-codeleted vs IDH-mutant 1p19q-non-codeleted) with a multiclass ML approach. Specifically, ADA was used to autonomously develop an ML pipeline and benchmark performance against an established handcrafted model using various MRI normalization methods (N4, Zscore, and WhiteStripe). External validation was performed on 2 public glioma datasets D2 (n = 160) and D3 (n = 410).

Results

GPT-4 achieved the highest accuracy of 0.820 (95% CI = 0.819-0.821) on the D3 dataset with N4/WS normalization, significantly outperforming the benchmark model’s accuracy of 0.678 (95% CI = 0.677-0.680) (P < .001). Class-wise analysis showed performance variations across different glioma types. In the IDH-wildtype group, GPT-4 had a recall of 0.997 (95% CI = 0.997-0.997), surpassing the benchmark’s 0.742 (95% CI = 0.740-0.743). For the IDH-mut 1p/19q-non-codel group, GPT-4’s recall was 0.275 (95% CI = 0.272-0.279), lower than the benchmark’s 0.426 (95% CI = 0.423-0.430). In the IDH-mut 1p/19q-codel group, GPT-4’s recall was 0.199 (95% CI = 0.191-0.206), below the benchmark’s 0.730 (95% CI = 0.721-0.738). On the D2 dataset, GPT-4’s accuracy was significantly lower (P < .001) than the benchmark’s, with N4/WS achieving 0.668 (95% CI = 0.666-0.671) compared with 0.719 (95% CI = 0.717-0.722) (P < .001). Class-wise analysis revealed the same pattern as observed in D3.

Conclusions

GPT-4 can autonomously develop radiomics-based MLMs, achieving performance comparable to handcrafted MLMs. However, its poorer class-wise performance due to unbalanced datasets shows limitations in handling complete end-to-end ML pipelines.
Prevalence and Patterns of Polysubstance Use (Tobacco and Other Substances) and Associated Factors: A Cross-Sectional Analysis in a High-Risk Cohort for Oral Cancer in Varanasi, India, With a Special Focus on Young Emerging Adults
Authors: Shruti Tulika , Sharma Priyanka , Khanna Divya , Ranjan Sudhir , Khan Aqusa , Gurushanth Keerthi , Singh Arjun Gurmeet , Mishra Aseem , Shetty Anupama , Birur Praveen , Chaturvedi Pankaj
Published: December 2024

Introduction

The dearth of population-based data on polysubstance use, especially in young emerging adults, presents a critical gap in understanding public health challenges, particularly in rural India, where tobacco use and oral cancer are prevalent. This study addresses this gap by investigating the prevalence and patterns of substance use, with a focus on young emerging adults (18–29 years) within a high-risk cohort for oral cancer in Varanasi, India.

Aims and Methods

The study involved a cross-sectional analysis of baseline data from 10 101 participants within a high-risk cohort in rural settings of the Varanasi district between December 2020 and June 2023. This region has high rates of tobacco use and oral cancer. Polysubstance use was defined as the lifetime concurrent use of two or more substances for at least a year. The study examined the prevalence of any substance use, polysubstance use, and associated sociodemographic factors. Univariable and multivariable analyses were employed to identify significant predictors.

Results

The prevalence of any substance use in the study population was 55.7%. Tobacco use was most prevalent (94.3%), followed by areca nut (44.8%), alcohol (6.6%), and cannabis (0.8%). Among young emerging adult substance users, the prevalence of polysubstance use was 42.6%. Predictors of polysubstance use included age, male gender, employment status, and income.

Conclusions

This study offers vital insights into substance use among rural Indian communities, particularly among young adults who are at a critical juncture in their lives. The findings underscore the urgent need for evidence-based strategies to address this region’s multifaceted public health challenge of polysubstance use.

Implications

Literature is scarce on population-based data for the prevalence and pattern of polysubstance (tobacco and other substances) use in India, both for the young and adult population. We studied the prevalence and pattern of substance use in a predominantly rural district of India, which reportedly has the second-highest burden of oral cancer among all Indian population-based cancer registries. We found that more than half (55.7%) of the study population used at least one substance; among them, nearly half (42.4%) used two or more substances. Tobacco use was the most prevalent form (94.3%), followed by areca nut use (44.8%), alcohol (6.6%), and cannabis (0.8%). Polysubstance use was prevalent among young emerging adult substance users. Age, male gender, employment, and income were predictors of polysubstance use. Distinct sociocultural factors shaping substance use in India necessitate research.
Prevalence and Multiple-Level Determinants of Smoking Among Women in the Workforce in China
Authors: Lin Hao , Liu Changping , Sun Yuying , Liu Yihua , Zhang Lanchao , Zhang Chengqian , Ji Ying , Cao Wangnan , Chang Chun
Published: December 2024

Introduction

To describe the prevalence of smoking among Chinese women in the workforce and to investigate its potential associated factors from a multilevel perspective.

Aims and Methods

The study was based on data collected from the “Asia Best Workplace” program in 2021. We obtained a sample of 6260 women in the workforce and collected the data using a self-administered questionnaire, including occupational characteristics, utilization of workplace health services, and mental health status. We employed univariate and multivariate logistic regression analyses to examine the associations between interested variables and the smoking status of women in the workforce.

Results

The prevalence of smoking among Chinese women in the workforce was 3.4%. After controlling for potential confounders, factors that were associated with smoking included field sales personnel (adjusted odds ratio, AOR = 3.45, 95% confidence interval, CI: 2.29–5.18, reference: white collar), mixed shift workers (AOR = 2.42, 95% CI: 1.66–3.53), working overtime every day (AOR = 2.27, 95% CI: 1.38–3.74, reference: no overtime work), having depressive (AOR = 1.10, 95% CI: 1.07–1.13) or anxiety symptoms (AOR = 1.25, 95% CI: 1.13–1.39), and daily exposure to secondhand smoke (AOR = 12.54, 95% CI: 8.70–18.05). Women with access to infirmaries (AOR = 0.38, 95% CI: 0.18–0.81) and fitness facilities (AOR = 0.60, 95% CI: 0.38–0.96) were less likely to smoke.

Conclusions

The prevalence of smoking among Chinese women in the workforce was low. Smoking cessation programs for women in the workforce may benefit from taking into account the nature of their work, whether there were night shifts and overtime working.

Implications

Smoking takes a huge toll on women, and women in the workforce face additional health challenges. Little is known about the specific factors associated with smoking among women in the workforce. Women who were field sales personnel, managers, working night or irregular shifts, and frequent overtime workers should be considered vulnerable subpopulations for smoking. Providing accessible workplace health services and resources is associated with a lower likelihood of smoking. Smoking cessation programs may consider the specific occupational and workplace factors that influence smoking behavior in this population, as well as address mental health needs.
Modification on Thermal Motion in Geant4 for Neutron Capture Simulation in Gadolinium Loaded Water
Authors: Hino Y , Abe K , Asaka R , Han S , Harada M , Ishitsuka M , Ito H , Izumiyama S , Kanemura Y , Koshio Y , Nakanishi F , Sekiya H , Yano T
Published: December 2024

Neutron tagging is a fundamental technique for electron anti-neutrino detection via the inverse beta decay channel. A reported discrepancy in neutron detection efficiency between observational data and simulation predictions prompted an investigation into neutron capture modeling in Geant4. The study revealed that an overestimation of the thermal motion of hydrogen atoms in Geant4 impacts the fraction of captured nuclei. By manually modifying the Geant4 implementation, the simulation results align with calculations based on evaluated nuclear data and show good agreement with observables derived from the SK-Gd data.
Incapacity planning under Swiss law in cross-border contexts
Authors: Weiss Kinga M , Börlin Lia
Published: December 2024

Incapacity planning in cross-border cases involves navigating non-harmonized legal frameworks. This analysis centers on the recognition and enforcement of ‘powers of representation’ under and outside the scope of the 2000 Hague Convention on the International Protection of Adults (2000 HCCH) in cross-border situations. A case study illustrates the complexities encountered when Swiss incapacity planning needs to be internationalized, particularly in relation to a non-contracting state, such as the United States.
Enhancing renal protection against cadmium toxicity: the role of herbal active ingredients
Authors: Safari Maleki Ahmad , Hayes A Wallace , Karimi Gholamreza
Published: December 2024

Background

Rapid industrialization globally has led to a notable increase in the production and utilization of metals, including cadmium (Cd), consequently escalating global metal pollution worldwide. Cd, characterized as a persistent environmental contaminant, poses significant health risks, particularly impacting human health, notably the functionality of the kidneys. The profound effects of Cd stem primarily from its limited excretion capabilities and extended half-life within the human body. Mechanisms underlying its toxicity encompass generating reactive oxygen species (ROS), disrupting calcium-signaling pathways and impairing cellular antioxidant defense mechanisms. This review focuses on the protective effects of various herbal active ingredients against Cd-induced nephrotoxicity.

Aim

This study aims to investigate the mechanisms of action of herbal active ingredients, including ant-oxidative, anti-inflammatory and anti-apoptotic pathways, to elucidate potential therapeutic strategies for reducing nephrotoxicity caused by Cd exposure.

Methods

A comprehensive search of scientific databases, including Web of Science, PubMed, Scopus and Google Scholar, used relevant keywords to identify studies published up to October 2024.

Results

Research illustrates that herbal active ingredients protect against Cd nephrotoxicity by reducing oxidative stress, enhancing antioxidant enzyme activity, inhibiting inflammation, preventing apoptosis, alleviating endoplasmic reticulum (ER) stress, enhancing autophagy and improving mitochondrial function in the kidney.

Conclusion

The present study indicates that an extensive understanding of the protective effects of herbal active ingredients holds promise for the development of innovative approaches to safeguard human health and environmental integrity against the detrimental effects of Cd exposure.
A Life Course Approach to Cardiovascular Disease Prevention
Authors: Hayman Laura L. , Braun Lynne T. , Muchira James M.
Published: December 2024

During the past 3 decades, life course socio-ecological frameworks have received considerable attention from clinical and public health professionals; developmental, social, and behavioral scientists; and scholars. Substantial evidence underscores the importance of a life course approach to prevention of cardiovascular (CV) disease and the promotion of optimal CV health. This article provides an overview of evidence on early origins and progression of CV disease (CVD) processes across the life course of individuals from diverse populations. Emphasis is placed on the evidence-based guidelines designed to prevent CVD and promote CV health with recommendations for implementation by CV health professionals and directions for future research in global CVD prevention.
Perceptions Among Mental Health Professionals Regarding the Intrusiveness of Coercive Measures
Authors: Birkeland Søren , Gildberg Frederik Alkier , Tingleff Ellen Boldrup , Pedersen Martin Locht , Lindekilde Camilla , Morsø Lars , Bogh Søren Bie
Published: December 2024

Background

Although hotly disputed, coercive measures are widely used in mental health services globally. In Denmark, to ensure the rights of patients, special psychiatric legislation that emphasizes the imperative to always use the least intrusive intervention has been implemented. This raises the question of which coercive measures are perceived as being less intrusive than others.

Aim

The aim of this study was to investigate the perceptions of Danish mental health professionals regarding the intrusiveness of various coercive measures used in mental health settings.

Methods

We conducted a web-based survey among 132 mental health professionals (response rate: 22%). The participants rated the intrusiveness of different coercive measures using the visual analog scale (VAS).

Results

Mental health professionals perceived mechanical restraint as being the most intrusive coercive intervention (belt and strap fixation received a VAS rating of 92 out of 100). Conversely, body searches and observation were perceived as being among the least intrusive measures, with VAS ratings of 35 and 50, respectively. Participants with different professional backgrounds, including general and forensic mental health workers, tended to perceive the coercive measures included in this study as being equally intrusive.

Conclusion

The participating mental health professionals generally perceived belt fixation as a highly intrusive measure, whereas seclusion, which is currently illegal under Danish law, was considered less intrusive. Because of the small sample size in this study, caution should be exercised when drawing conclusions based on the findings. Nevertheless, the study may add to how the principle of using the least intrusive measure is interpreted.
Fostering Informed Consent and Shared Decision-Making in Maternity Nursing With the Advancement of Artificial Intelligence
Authors: Penner Sara Bickweat , Mercado Nicholas R. , Bernstein Samantha , Erickson Elise , DuBois Melissa Anne , Dreisbach Caitlin
Published: December 2024

Artificial intelligence (AI), defined as algorithms built to reproduce human behavior, has various applications in health care such as risk prediction, medical image classification, text analysis, and complex disease diagnosis. Due to the increasing availability and volume of data, especially from electronic health records, AI technology is expanding into all fields of nursing and medicine. As the health care system moves toward automation and computationally driven clinical decision-making, nurses play a vital role in bridging the gap between the technological output, the patient, and the health care team. We explore the nurses' role in translating AI-generated output to patients and identify considerations for ensuring informed consent and shared decision-making throughout the process. A brief review of AI technology and informed consent, an identification of power dynamics that underly informed consent, and descriptions of the role of the nurse in various relationships such as nurse–AI, nurse–patient, and patient–AI are covered. Ultimately, nurses and physicians bear the responsibility of upholding and safeguarding the right to informed choice, as it is a fundamental aspect of safe and ethical patient-centered health care.
Antithrombin and Activated Protein C in Pediatric Sepsis: Prospective Observational Study of Outcome
Authors: Xoay Tran Dang , Tuan Ta Anh , Ha Nguyen Thi , Quan Thieu Quang , Duyen Nguyen Thi , My Tran Thi Kieu
Published: December 2024

Objectives:

To assess antithrombin and activated protein C (aPC) levels in relation to disseminated intravascular coagulation (DIC) and severe outcomes in pediatric sepsis.

Design:

Prospective, observational study conducted between April 2023 and October 2024. Coagulation profiles including conventional coagulation, antithrombin activity, and aPC were obtained at PICU admission.

Setting:

PICU in the Vietnam National Children’s Hospital, Hanoi, Vietnam.

Subjects:

PICU admissions, 1 month to 18 years old, with sepsis.

Interventions:

None.

Measurements and Main Results:

One hundred thirty children (78 males; median age 7.5 mo) with mortality 23/130 (17.7%). The prevalence of overt DIC was 37 of 130 (28.5%). Nonsurvival at 28 days, compared with survival, was associated with hemorrhage and/or thrombosis at presentation, and higher number of dysfunctional organs, and overt DIC. Those with overt DIC, compared with not, had longer activated partial thromboplastin time, higher international normalized ratio and d-dimer, and lower antithrombin, and aPC. Activity of antithrombin and aPC correlated inversely with the Vasoactive-Inotropic Score in survivors (p = 0.002 and 0.009, respectively). Patients with a cutoff value for antithrombin less than 63.5% had a mortality risk with area under the receiver operating characteristic (AUROC) curve 0.64, with sensitivity 0.51 and specificity 0.74, and positive predictive value 0.30. Regarding overt DIC, a cutoff value for antithrombin less than 55.5% had an AUROC 0.78, sensitivity 0.72 and specificity of 0.73, and positive predictive value 0.52.

Conclusions:

In this observational study of pediatric sepsis patients, first 24-hour coagulation data in those who did not-survive to 28 days, vs. survivors showed an associated prior lower level of antithrombin in nonsurvivors. Furthermore, using the outcome of overt DIC and nonovert DIC in the first 72 hours, we found that lower levels of antithrombin or aPC are each associated with overt DIC and nonovert DIC in pediatric sepsis. Further validation work is needed in larger case series of pediatric sepsis.
Outcomes of DCD Liver Transplant Using Sequential Normothermic Regional Perfusion and Normothermic Machine Perfusion or NRP Alone Versus Static Cold Storage
Authors: Croome Kristopher P. , Subramanian Vijay , Mathur Amit K. , Aqel Bashar , Mao Shennen A. , Clendenon Jacob N. , Perry Dana K. , Dhanireddy Kiran , Taner C. Burcin
Published: December 2024

Background.

The availability of in situ normothermic regional perfusion (NRP) or ex situ normothermic machine perfusion (NMP) has revolutionized donation after circulatory death (DCD) liver transplant (LT). While some have suggested that NRP and NMP may represent competing technologies for DCD LT, there are many scenarios where these technologies can function in a complementary manner.

Methods.

Between January 2022 and March 2024, 83 DCD LTs were performed using NRP (62 NRP alone and 21 NRP + NMP) and were compared with 297 static cold storage (SCS) DCD LTs. NRP + NMP was used in scenarios with (1) long travel distances, (2) complicated transplant recipients, or (c) the need for additional liver graft recovery in “marginal” cases.

Results.

Ischemic cholangiopathy was lower in the NRP alone group (0%) and the NRP + NMP group (0%) compared with the SCS group (16.8; P < 0.001 and P = 0.04, respectively). In addition, early allograft dysfunction, number of packed red blood cells transfused, and acute kidney injury were lower in the NRP alone and NRP + NMP groups compared with the SCS group. Graft survival was higher in cases where NRP was used than in cases where SCS was used (P = 0.016). In all the cases where lactate remained elevated at the end of NRP (mean 8.2 ± 2.0), it ultimately normalized at the end of NMP (0.92 ± 0.56).

Conclusions.

The present study demonstrates lower rates of ischemic cholangiopathy and improved graft survival with NRP alone or NRP + NMP compared with SCS when using liver grafts from DCD donors. It also demonstrates that excellent outcomes can be achieved with sequential NRP + NMP in cases with prolonged travel distances, complicated recipients, or when there is a need for additional liver recovery in “marginal” cases.
Quantum retrodiction
Authors: Jeffers John , Oi Daniel K. L. , Brougham Thomas
Published: December 2024

Quantum retrodiction, in which the state of a quantum system prior to a measurement is assigned based on the results of that measurement, has had a long history and has been used in quantum optics research for decades. Here we summarize the theory and point out some of the more interesting results, before applying the theory to state identification from multiple shots of an experiment. One surprising result is that we show that a photodetector with low quantum efficiency can discriminate between photonic states better than a detector with a higher efficiency.

This article is part of the theme issue ‘The quantum theory of light’.
Sir Rudolf Peierls and radiation pressure
Authors: Baxter C.
Published: December 2024

Towards the end of his life, Rudolf Peierls became interested in photon momentum and radiation pressure. He subsequently published a number of theoretical papers on the subject. Although the work of Peierls has neither been widely adopted nor developed, it did nevertheless have a provoking and fruitful effect on the radiation pressure research undertaken by Alan Gibson and Rodney Loudon at the University of Essex.

This article is part of the theme issue, ‘The quantum theory of light’.
Measurement with indefinite causal order and the Sagnac interferometer
Authors: Barnett S. M. , Croke S. , Franke-Arnold S.
Published: December 2024

It has been shown that measurements involving indefinite causal order can be superior to those in which a sequence of operations occurs in a specified order. In optics, such measurements are realized naturally in a Sagnac interferometer. We show that such an arrangement can measure the solid angle (on the Poincaré sphere) enclosed by a sequence of unitary transformations of the polarization. This is the Pancharatnam–Berry phase. Extension from the classical or single-photon treatment to a fully quantized treatment allows the analysis of the interferometer for arbitrary quantum states of light.

This article is part of the theme issue ‘The quantum theory of light’.
Differential effects of aging, Alzheimer’s pathology, andAPOE4on longitudinal functional connectivity and episodic memory in older adults
Authors: Fischer Larissa , Adams Jenna N. , Molloy Eóin N. , Vockert Niklas , Tremblay-Mercier Jennifer , Remz Jordana , Binette Alexa Pichet , Villeneuve Sylvia ,   PREVENT-AD Research Group, Maass Anne
Published: December 2024

INTRODUCTION

Both aging and Alzheimer’s disease (AD) affect episodic memory networks. How this relates to region-specific early differences in functional connectivity (FC), however, remains unclear.

METHODS

We assessed resting-state FC strength in the medial temporal lobe (MTL) - posteromedial cortex (PMC) - prefrontal network and cognition over two years in cognitively normal older adults from the PREVENT-AD cohort.

RESULTS

FC strength within PMC and between posterior hippocampus and inferomedial precuneus decreased in “normal” aging (amyloid- and tau-negative adults). Lower FC strength within PMC was associated with poorer longitudinal episodic memory performance. Increasing FC between anterior hippocampus and superior precuneus was related to higher baseline AD pathology. Higher FC strength was differentially associated with memory trajectories depending onAPOE4genotype.

DISCUSSION

Findings suggest differential effects of aging and AD pathology on longitudinal FC. MTL-PMC hypoconnectivity was related to aging and cognitive decline. Furthermore, MTL-PMC hyperconnectivity was related to early AD pathology and cognitive decline inAPOE4carriers.Graphical abstract.

A)“Normal aging” is characterized by a longitudinal decrease in functional connectivity.B)Cognitively unimpaired older adults with more Alzheimer’s pathology at baseline (measured via cerebrospinal fluid) exhibit a longitudinal increase in functional connectivity.
Dynamic Changes in Gene Expression Through Aging inDrosophila melanogasterHeads
Authors: Hanson Katherine M , Macdonald Stuart J
Published: December 2024

Work in many systems has shown large-scale changes in gene expression during aging. However, many studies employ just two, arbitrarily-chosen timepoints at which to measure expression, and can only observe an increase or a decrease in expression between “young” and “old” animals, failing to capture any dynamic, non-linear changes that occur throughout the aging process. We used RNA sequencing to measure expression in male head tissue at 15 timepoints through the lifespan of an inbredDrosophila melanogasterstrain. We detected >6,000 significant, age-related genes, nearly all of which have been seen in previous fly aging expression studies, and which include several known to harbor lifespan-altering mutations. We grouped our gene set into 28 clusters via their temporal expression change, observing a diversity of trajectories; some clusters show a linear change over time, while others show more complex, non-linear patterns. Notably, re-analysis of our dataset comparing the earliest and latest timepoints – mimicking a two-timepoint design – revealed fewer differentially-expressed genes (around 4,500). Additionally, those genes exhibiting complex expression trajectories in our multi-timepoint analysis were most impacted in this re-analysis; Their identification, and the inferred change in gene expression with age, was often dependent on the timepoints chosen. Informed by our trajectory-based clusters, we executed a series of gene enrichment analyses, identifying enriched functions/pathways in all clusters, including the commonly seen increase in stress- and immune-related gene expression with age. Finally, we developed a pair of accessible shiny apps to enable exploration of our differential expression and gene enrichment results.
Patient-derived Induced Pluripotent Stem Cells as a Model to Study Frontotemporal Dementia Pathologies
Authors: Infante-Tadeo Sonia , Barber Diane L.
Published: December 2024

The neurodegenerative disorder Frontotemporal Dementia (FTD) can be caused by a repeat expansion (GGGGCC; G4C2) in C9orf72. The function of wild-type C9orf72 and the mechanism by which the C9orf72-G4C2 mutation causes FTD, however, remain unresolved. Diverse disease models including human brain samples and differentiated neurons from patient-derived induced pluripotent stem cells (iPSCs) identified some hallmarks associated with FTD, but these models have limitations, including biopsies capturing only a static snapshot of dynamic processes and differentiated neurons being labor-intensive, costly, and post-mitotic. We find that patient-derived iPSCs, without being differentiated into neurons, exhibit established FTD hallmarks, including increased lysosome pH, decreased lysosomal cathepsin activity, cytosolic TDP-43 proteinopathy, and increased nuclear TFEB. Moreover, lowering lysosome pH in FTD iPSCs mitigates TDP-43 proteinopathy, suggesting a key role for lysosome dysfunction. RNA-seq reveals dysregulated transcripts in FTD iPSCs affecting calcium signaling, cell death, synaptic function, and neuronal development. We confirm differences in protein expression for some dysregulated genes not previously linked to FTD, including CNTFR (neuronal survival), Annexin A2 (anti-apoptotic), NANOG (neuronal development), and moesin (cytoskeletal dynamics). Our findings underscore the potential of FTD iPSCs as a model for studying FTD cellular pathology and for drug screening to identify therapeutics.

SIGNIFICANCE STATEMENT

Understanding the cellular pathology of Frontotemporal Dementia linked to a GGGGCC expansion in the C9orf72 gene remains a challenge.

This study shows that undifferentiated patient-derived iPSCs exhibit hallmark FTD characteristics, including lysosome dysfunction and TDP-43 proteinopathy, and identifies dysregulated genes related to neurodegeneration.

These findings highlight patient-derived iPSCs as a valuable model for studying FTD pathology and for drug screening, potentially guiding future research in therapeutic development.
Contrasting impacts of invasiveOpuntiacacti on mammal habitat use
Authors: Stewart Peter S. , Hill Russell A. , Oduor Ayub M. O. , Stephens Philip A. , Whittingham Mark J. , Dawson Wayne
Published: December 2024

Biological invasions impact ecosystems worldwide, including through changing the behaviour of native species. Here, we used camera traps to investigate the effects of invasiveOpuntiacacti on the habitat use of twelve mammal species in Laikipia County, Kenya, an internationally important region of mammalian biodiversity. We found thatOpuntiaimpacted mammal occupancy and activity, but the strength and direction of the effects varied among species and between seasons, and depended on the spatial scale at whichOpuntiawas considered. Notably, we observed consistent positive effects for olive baboons and elephants, two major consumers ofOpuntiafruit. We also observed seasonally varying effects on the occupancy of two key grazers: Grevy’s zebra and plains zebra. As well as having important implications for mammal conservation, ecosystem functioning, and the future spread ofOpuntia, our findings highlight behavioural changes in large mammals as a potentially important pathway through which invasive species impact ecosystems.
Kolmogorov-Smirnov and Shapiro-Wilk single distribution analysis methods in examining sample structure, strength of genetic background, and effects of interventions in lifespan and aging studies
Authors: Konopatov Alexander V. , Shidlovsky Yuli V. , Shtil Alexander A. , Bylino Oleg V.
Published: December 2024

The analysis of lifespan and ageing involves a variety of calculations based on survival data. One of these is the comparison of survival curves. However, inspection of survival curves provides little information about the frequency of phenotypes within samples. Here we propose to divide the distribution into intervals to obtain information about the sample structure. Then, we apply the normality criterion to the distributions using the Kolmogorov-Smirnov and Shapiro-Wilk tests. Using this approach, we reveal the destabilising effect of mutations on ontogenesis and lifespan, and estimate the strength of the genetic background of the lines. The proposed methodology allows effective estimation of sample structure and adds a new layer of information to longevity studies.
Stress-actuated Flexible Microelectrode Arrays for Activity Recording in 3D Neuronal Cultures
Authors: Serra João , Mateus José C. , Cardoso Susana , Ventura João , Aguiar Paulo , Leitao Diana C.
Published: December 2024

Microelectrode arrays (MEAs) are instrumental in monitoring electrogenic cell populations, such as neuronal cultures, allowing high precision measurements of electrical activity. Although three-dimensional neuronal cultures replicate the behavior ofin vivosystems better than two-dimensional models, conventional planar MEAs are not well suited to capture activity within such networks. Novel MEA geometries can overcome this difficulty, but often at the cost of increased fabrication complexity. Here, we used the stress mismatch between thin film layers to fabricate MEAs with vertical electrodes, using methods compatible with established microfabrication protocols. A micrometric SiO2hinge enables control over the bending angle of flexible polyimide structures with embedded electrodes. The performance of the patterned electrodes was assessed before and after stress actuation, through impedance measurements, voltage noise mapping, and neuronal activity recordings. 3D MEAs with 30×30 µm2electrodes showed an impedance of 0.96 ± 0.07 MΩ per electrode and detected neuronal activity spikes with amplitudes as high as 400 µV. These results demonstrate the potential of the developed methods to provide a scalable approach to fabricate 3D MEAs, enabling enhanced recording capabilities forin vitroneuronal cultures.
NRBP1 and TSC22D proteins impact distal convoluted tubule physiology through modulation of the WNK pathway
Authors: Magaña-Ávila Germán , Carbajal-Contreras Héctor , Amnekar Ramchandra , Dite Toby , Téllez-Sutterlin Michelle , García-Ávila Kevin , Marquina-Castillo Brenda , Lopez-Saavedra Alejandro , Vazquez Norma , Rojas-Ortega Eréndira , Delpire Eric , Ellison David H. , Alessi Dario R. , Gamba Gerardo , Castañeda-Bueno María
Published: December 2024

The With No lysine (WNK) kinases regulate processes such as cell volume and epithelial ion transport through the modulation of Cation Chloride Cotransporters such as the NaCl cotransporter, NCC, present in the distal convoluted tubule (DCT) of the kidney. Recently, the interaction of WNKs with Nuclear Receptor Binding Protein 1 (NRBP1) and Transforming Growth Factor β-Stimulated Clone 22 Domain (TSC22D) proteins was reported. Here we explored the effect of NRBP1 and TSC22Ds on WNK signaling in vitro and in the DCT. TSC22D1.1, TSC22D2, and NRBP1 are localized in DCT WNK bodies, which are cytoplasmic biomolecular condensates associated with WNK activation. In HEK293 cells, long TSC22D isoforms and NRBP1 increase WNK4 activity. DCT-specific NRBP1 knockout mice have reduced NCC phosphorylation and activate a compensatory response. Thus, NRBP1 and long TSC22D proteins are positive modulators of WNK signaling and modulate Na+reabsorption in the kidney. NRBP1 and TSC22Ds likely influence WNK signaling in other tissues, impacting various physiological processes.

Teaser

The pseudokinase NRBP1 and its associated TSC22D proteins modulate WNK kinases to regulate sodium reabsorption in the kidney.
Mechanisms of host exploitation by a microsporidian parasite
Authors: Silva Luís M. , Vallat Armelle , Koella Jacob C.
Published: December 2024

Parasites are masters at exploiting their hosts. In doing so, they often affect the development of co-infecting parasites. Such is the case of microsporidia andPlasmodium spp., which have been shown to have their development within the mosquito repressed in the presence of the former. Therefore, microsporidia hold significant potential as biological control agents for malaria. However, the mechanisms behind this repression remain unclear. Here, we characterised the mechanisms underpinning the infection by using evolved lines of the microsporidianVavraia culicisdiffering in their virulence upon infecting the mosquitoAnopheles gambiae, the main malaria vector. Through the use of host metallomics and energy quantification throughout infection progression, we were able to identify important parasite mechanisms of host exploitation of general and virulence-specific interest, namely iron. Our findings advance the fundamental understanding of microsporidia infections and provide important insights into the design of effective malaria control strategies.
Mechanisms for plastic landmark anchoring in zebrafish compass neurons
Authors: Tanaka Ryosuke , Portugues Ruben
Published: December 2024

Vision is a sensory modality particularly important for navigation, as it can inform animals of their current heading (i.e. visual landmarks) as well as its changes (i.e. optic flow). It has been shown that head direction (HD) neurons in various species incorporate the visual cues into their heading estimates. However, circuit mechanisms underlying this process remain still elusive in vertebrates. Here, we asked if and how the recently identified HD cells in the larval zebrafish – one of the smallest vertebrate models – incorporate visual information. By combining two-photon microscopy with a panoramic virtual reality setup, we demonstrate that the zebrafish HD cells can reliably track the orientation of multiple visual scenes, exploiting both landmark and optic flow cues. The mapping between landmark cues and the heading estimates is idiosyncratic across fish, and experience-dependent. Furthermore, we show that the landmark tracking requires the lateralized projection from the habenula to the interpeduncular nucleus (IPN), where the HD neuron processes innervate. The physiological and morphological parallels suggest that a Hebbian mechanism similar to the fly ring neuron is at work in the habenula axons. Overall, the observations that the hindbrain HD cells of the larval zebrafish lacking an elaborate visual telencephalon shed new light on the evolution of the navigation circuitry in vertebrates.
The inner integument controls embryo sac development and seed shape inArabidopsis thaliana
Authors: Mody Tejasvinee Atul , Schneitz Kay
Published: December 2024

The angiosperm ovule is characterized by the close association of the two generations, with the haploid female gametophyte or embryo sac being encapsulated by the diploid sporophyte, which usually forms two integuments. How the gametophyte and sporophyte coordinate their development has long been of interest. However, the function of the inner integument in embryo sac development has remained elusive. Here, we addressed this question. We applied a genetic ablation strategy to achieve an early block in inner integument outgrowth. We generated plants expressingBARNASEunder the control of an early acting endothelium-specific promoter. Corresponding lines carried ovules lacking most of the inner integument. The genetic and cell biological data revealed that in the near absence of an inner integument embryo sac development is blocked at the mono-nuclear embryo sac stage in most pre-fertilization ovules. Approximately 10 percent of the ovules developed a functional embryo sac and underwent fertilization. Subsequent embryo and endosperm development appeared unperturbed and viable seeds were produced albeit of altered shape. Our results show that the inner integument plays an important role in early embryo sac development as well as ovule and seed shape, but is dispensable for embryo and endosperm development. Key words: embryo sac, embryo, endothelium, female gametophyte, integument, seed development

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Genetic ablation of the inner integument demonstrates its role in embryo sac development and its irrelevance for embryogenesis.
The striatal compartments, striosome and matrix, are embedded in largely distinct resting state functional networks
Authors: Sadiq Alishba , Funk Adrian T. , Waugh Jeff L.
Published: December 2024

The striatum is divided into two interdigitated tissue compartments, the striosome and matrix. These compartments exhibit distinct anatomical, neurochemical, and pharmacological characteristics and have separable roles in motor and mood functions. Little is known about the functions of these compartments in humans. While compartment-specific roles in neuropsychiatric diseases have been hypothesized, they have yet to be directly tested. Investigating compartment-specific functions is crucial for understanding the symptoms produced by striatal injury, and to elucidating the roles of each compartment in healthy human skills and behaviors. We mapped the functional networks of striosome and matrix in humansin vivo. We utilized a diverse cohort of 674 healthy adults, derived from the Human Connectome Project, including all subjects with complete diffusion and functional MRI data and excluding subjects with substance use disorders. We identified striatal voxels with striosome-like and matrix-like structural connectivity using probabilistic diffusion tractography. We then investigated resting state functional connectivity (rsFC) using these compartment-like voxels as seeds. We found widespread differences in rsFC between striosome-like and matrix-like seeds (p< 0.05, FWE corrected for multiple comparisons), suggesting that striosome and matrix occupy distinct functional networks. Slightly shifting seed voxel locations (<4 mm) eliminated these rsFC differences, underscoring the anatomic precision of these networks. Striosome-seeded networks exhibited ipsilateral dominance; matrix-seeded networks had contralateral dominance. Next, we assessed compartment-specific engagement with the triple-network model (default mode, salience, and frontoparietal networks). Striosome-like voxels dominated rsFC with the default mode network bilaterally. The anterior insula (a primary node in the salience network) had higher rsFC with striosome-like voxels. The inferior and middle frontal cortices (primary nodes, frontoparietal network) had stronger rsFC with matrix-like voxels on the left, and striosome-like voxels on the right. Since striosome-like and matrix-like voxels occupy highly segregated rsFC networks, striosome-selective injury may produce different motor, cognitive, and behavioral symptoms than matrix-selective injury. Moreover, compartment-specific rsFC abnormalities may be identifiable before disease-related structural injuries are evident. Localizing rsFC differences provides an anatomic substrate for understanding how the tissue-level organization of the striatum underpins complex brain networks, and how compartment-specific injury may contribute to the symptoms of specific neuropsychiatric disorders.
Ultra-long sequencing for contiguous haplotype resolution of the human immunoglobulin heavy chain locus
Authors: Gornitzka Mari B. , Røsjø Egil , Jana Uddalok , Ford Easton E. , Tourancheau Alan , Lees William D. , Vanwinkle Zachary , Smith Melissa L. , Watson Corey T. , Lossius Andreas
Published: December 2024

Genetic diversity within the human immunoglobulin heavy chain (IGH) locus influences the expressed antibody repertoire and susceptibility to infectious and autoimmune diseases. However, repetitive sequences and complex structural variation pose significant challenges for large-scale characterization. Here, we introduce a method using Oxford Nanopore ultra-long sequencing and adaptive sampling, coupled with a bioinformatic pipeline, to generate haplotype-resolved single-contig IGH assemblies. We compared our method to a well-established IGH characterization framework using Pacific Biosciences HiFi sequencing in four donors and observed almost complete sequence congruence between our haplotype-resolved assemblies and the HiFi reads. Applying our approach to the HG002 reference material revealed no base differences to the Telomere-to-Telomere genome benchmark over the IGH locus. Importantly, among the four donors, our approach uncovered 30 novel alleles and previously uncharacterized large structural variants, including a 120 kb segmental duplication spanning IGHE to IGHA1 and an expanded seven-copy IGHV3-23 gene haplotype.
Predictive value of preclinical models for CAR-T cell therapy clinical trials: a systematic review and meta-analysis
Authors: Andreu-Sanz David , Gregor Lisa , Carlini Emanuele , Scarcella Daniele , Marr Carsten , Kobold Sebastian
Published: December 2024

Experimental mouse models are indispensable for the preclinical development of cancer immunotherapies, whereby complex interactions in the tumor microenvironment (TME) can be somewhat replicated. Despite the availability of diverse models, their predictive capacity for clinical outcomes remains largely unknown, posing a hurdle in the translation from preclinical to clinical success. This study systematically reviews and meta-analyzes clinical trials of chimeric antigen receptor (CAR-) T cell monotherapies with their corresponding preclinical studies. Adhering to PRISMA guidelines, a comprehensive search of PubMed andClinicalTrials.govwas conducted, identifying 422 clinical trials and 3157 preclinical studies. From these, 105 clinical trials and 180 preclinical studies, accounting for 44 and 131 distinct CAR constructs, respectively, were included.

Patientś responses varied based on the target antigen, expectedly with higher efficacy and toxicity rates in hematological cancers. Preclinical data analysis revealed homogenous and antigen-independent efficacy rates. Our analysis revealed that only 4 % (n = 12) of mouse studies used syngeneic models, highlighting their scarcity in research. Three logistic regression models were trained on CAR structures, tumor entities, and experimental settings to predict treatment outcomes. While the logistic regression model accurately predicted clinical outcomes based on clinical or preclinical features (Macro F1 and AUC > 0.8), it failed in predicting preclinical outcomes from preclinical features (Macro F1 < 0.5, AUC < 0.6), indicating that preclinical studies may be influenced by experimental factors not accounted for in the model.

These findings underscore the need for better understanding the experimental factors enhancing the predictive accuracy of mouse models in preclinical settings.
Modulating Cellular Deformability via 3D Dextran Hydrogel Cultivation to Regulate the Microcirculation of Mesenchymal Stem Cells in Murine Spleen and Liver
Authors: Zhu Xiaolu , Wang Zheng , Shi Yuanping , Yao Shuang , He Fengliang , Teng Fang
Published: December 2024

For mesenchymal stem cell (MSC) therapy to be effective, the vascular system may be used to deliver and steer the cells to the target tissue. However, the expanded MSCs in petri dishes are usually have a limited deformability and commonly excluded by the capillary networks when homing to the downstream organs via microcirculation. Here, we propose to utilize specially designed 3D dextran hydrogels and tuning the microscopic heterogeneity of hydrogel composition to make the administrated cells mechanically comply with the structure and mechanics of the capillary. The cell deformability in petri dishes, microcosmically homogeneous (HOM) and heterogeneous (HET) dextran hydrogels were investigated in vitro by measuring cell moduli through atomic force microscope (AFM), analyzing the expression of cytoskeletal protein via flow cytometry and fluorescent imaging. The in vitro experimental results demonstrate a progressive increase in cell deformability from 2D dishes, to HOM-hydrogel derived cells, and then to HET-hydrogel derived cells. The in vivo mouse experiment indicates the cells could deform accordingly and pass through easily with reduced resistance inside the mouse organs. It is suggested that the main destination of hMSC microcirculation could be selected between the spleen and liver of mice, by tuning cell mechanics that depends on the stimulus from microcosmically HOM or HET hydrogel, which lays a potential foundation for the mechanically modified MSC therapy for lesions in the organs.