bluuebunny/crossref_metadata_2025 huggingface dataset:
A Cost–Utility Analysis of the Use of −125 mm Hg Closed-incision Negative Pressure Therapy in Oncoplastic Breast Surgery
Authors: Bloom Joshua A. , Wareham Carly , Chahine Elsa , Singhal Dhruv , Lin Samuel J. , Lee Bernard T. , Nardello Salvatore , Homsy Christopher , Persing Sarah M. , Chatterjee Abhishek
Published: October 2024

Background:

Closed-incision negative pressure therapy (ciNPT) decreases the rate of wound complications in oncoplastic breast surgery (OBS) but at a fiscal cost. Our aim was to examine the cost-utility of ciNPT in OBS.

Methods:

A literature review was performed to obtain the probabilities and outcomes for the treatment of unilateral breast cancer with OBS with ciNPT versus without. Reported utility scores in the literature were used to calculate quality-adjusted life years (QALYs) for each health state. A decision analysis tree was constructed with rollback analysis to determine the more cost-effective strategy. An incremental cost–utility ratio was calculated. Sensitivity analyses were performed.

Results:

OBS with ciNPT is associated with a higher clinical effectiveness (QALY) of 33.43 compared to without (33.42), and relative cost increase of $667.89. The resulting incremental cost-utility ratio of $57432.93/QALY favored ciNPT. In one-way sensitivity analysis, ciNPT was the more cost-effective strategy if the cost of ciNPT was less than $1347.02 or if the probability of wound dehiscence without was greater than 8.2%. Monte Carlo analysis showed a confidence of 75.39% that surgery with ciNPT is more cost effective.

Conclusion:

Despite the added cost, surgery with ciNPT is cost-effective. This finding is a direct result of decreased overall wound complications with ciNPT.
ChatGPT Virtual Assistant for Breast Reconstruction: Assessing Preferences for a Traditional Chatbot versus a Human AI VideoBot
Authors: Kim Trudy S. , Yu Catherine T. , Hinson Chandler , Fung Ethan , Allam Omar , Nazerali Rahim S. , Ayyala Haripriya S.
Published: October 2024

Background:

Recent advancements in artificial intelligence (AI) have reshaped telehealth, with AI chatbots like Chat Generative Pretrained Transformer (ChatGPT) showing promise in various medical applications. ChatGPT is capable of offering basic patient education on procedures in plastic and reconstructive surgery (PRS), yet the preference between human AI VideoBots and traditional chatbots in plastic and reconstructive surgery remains unexplored.

Methods:

We developed a VideoBot by integrating ChatGPT with Synthesia, a human AI avatar video platform. The VideoBot was then integrated into Tolstoy to create an interactive experience that answered four of the most asked questions related to breast reconstruction. We used Zapier to develop a ChatGPT-integrated chatbot. A 16-item survey adapted from the 2005 validated measurement of online trust by Corritore et al was distributed online to female participants via Amazon Mechanical Turk.

Results:

A total of 396 responses were gathered. Participants were 18 to 64 years old. Perceptions of truthfulness, believability, content expertise, ease of use, and safety were similar between the VideoBot and chatbot. Most participants preferred the VideoBot compared with the traditional chatbot (63.5% versus 28.1%), as they found it more captivating than the text-based chatbot. Of the participants, 77% would have preferred to see someone who they identified with in terms of gender and race.

Conclusions:

Both the VideoBot and text-based chatbot show comparable effectiveness, usability, and trust. Nonetheless, the VideoBot’s human-like qualities enhance interactivity. Future research should explore the impact of race and gender concordance in telehealth to provide a more personalized experience for patients.
Value of Factor V in the diagnosis of early graft dysfunction after liver transplantation: Internal validation
Authors: Sanchez-Gonzalez Claudia , Fernández Aguilar José L. , Sánchez Pérez Belinda , Santoyo Santoyo Julio
Published: October 2024

Primary graft dysfunction is a major early complication following liver transplantation, potentially leading to retransplantation or patient death. Coagulation Factor V (FV) and ALT have emerged as important biomarkers in assessing liver function, yet their role as early predictors of graft loss has not been fully validated. The aim of this study is to conduct an internal validation of published results on the applicability of FV and ALT for diagnosing graft dysfunction and its predictive ability for graft loss within the first 90 days. We conducted a retrospective cohort study including 513 adult recipients from 2012 to 2023 at the Regional University Hospital of Málaga. FV and ALT levels were measured on postoperative day 2, and patients were categorized based on FV <37.5 and ALT >1539. The association with 90-day graft loss was analyzed. Graft loss occurred in 43 patients (8.4%) within the first 90 days. The combination of FV <37.5 and ALT >1539 on postoperative day 2 demonstrated a specificity of 99% and a test efficiency of 94% in predicting graft loss. Patients meeting both criteria had a 74-fold increased risk of graft loss, with most losses occurring within the first week, and a median survival of 4 days. These findings suggest that FV and ALT on postoperative day 2 are reliable early markers for predicting graft loss, enabling risk stratification and guiding critical decisions regarding early retransplantation in the immediate postoperative period.
K-means clustering-based young users’ kitchen needs analysis and personalized design strategy
Authors: Xu Liye , Ren Tori Hui , Zhu Jie
Published: October 2024

Objectives:

This study aimed to understand the kitchen use behaviors and design preferences that cater to the needs of young people, encouraging their intention to cook and promoting healthy living.

Methods:

This study conducted a survey with 310 young people (aged 18–40) and applied the K-means clustering method for analysis. The silhouette coefficient feature in R was used to automatically assess the impact of different K-values on the clustering outcome, thereby determining the ideal number of clusters. After identifying the optimal number of clusters, K-means clustering was performed in R to segment the survey data and identify the primary user personas.

Results:

The analysis identified 2 user categories: (1) health-convenience advocates, that is, young people with a high level of education who seek efficient lifestyles but due to their busy schedules, have a significant need for quick and healthy dietary solutions; (2) cooking explorers, typically modern, educated young individuals who are passionate about cooking, viewing it not only as a necessity but also as a personal interest and a realm for exploration.

Conclusions:

This study provides valuable guidance for kitchen designers and home product developers to better understand the actual needs and preferences of young users, highlighting the importance of excellent kitchen design in promoting a healthy lifestyle and improving quality of life.
Outcomes of a policy to prioritize populations with expected healthcare barriers for subsidized preexposure prophylaxis care in Amsterdam, the Netherlands
Authors: Wijstma Eline , Jongen Vita W. , Boyd Anders , de Vries Henry J.C. , Schim van der Loeff Maarten F. , Prins Maria , Hoornenborg Elske
Published: October 2024

Objective:

The Dutch HIV preexposure prophylaxis (PrEP) pilot provided subsidized PrEP care to maximum 2900 individuals at a time in Amsterdam. Populations with expected barriers to accessing PrEP elsewhere were prioritized for program inclusion. We evaluated their prior sexual health service engagement and PrEP need.

Design:

Cross-sectional analysis using enrolment data.

Methods:

We included individuals ever enrolled in the PrEP program at the Center for Sexual Health (CSH) Amsterdam between 2019 and 2023. We calculated the proportion belonging to higher-priority groups (i.e., <25 years old, transgender, sex worker, uninsured or migrant). We defined classes of sexual health service engagement in the 12 months preceding enrolment using latent class analysis (LCA). We compared engagement classes, sexual behavior and positivity of HIV and sexually transmitted infections (STI) between higher- and lower-priority groups.

Results:

2004/4075 (49%) individuals enrolled belonged to higher-priority groups. LCA showed three classes of prior engagement: “newly engaged” (14%, n = 551) were new to the CSH-Amsterdam; “PrEP initiators” (40%, n = 1642) previously visited the CSH-Amsterdam but had not used PrEP; “PrEP experienced” individuals (46%, n = 1882) previously accessed PrEP. Higher-priority groups were more often “newly engaged” or “PrEP-initiators” than “PrEP-experienced”. Higher-priority groups less often had condomless anal sex with casual partners or chemsex in the prior 6 months. Positivity of bacterial STI was similar between higher-priority (n = 300/2004, 15.0%) and lower-priority (n = 315/2071, 15.2%) groups. 13/14 HIV diagnoses at enrolment were in higher-priority groups.

Conclusion:

Higher-priority populations had less often previously used sexual health services and accounted for most new HIV diagnoses at enrolment. Engaging these populations in sexual healthcare, including PrEP, should be stressed.
Real-world Decision-making Process for Stereotactic Body Radiotherapy Versus Minimally Invasive Surgery in Early-stage Lung Cancer Patients
Authors: Vanstraelen Stijn , Tan Kay See , Adusumilli Prasad S. , Bains Manjit S. , Bott Matthew J. , Downey Robert J. , Gomez Daniel R. , Gray Katherine D. , Huang James , Isbell James M. , Molena Daniela , Park Bernard J. , Rimner Andreas , Rusch Valerie W. , Shaverdian Narek , Sihag Smita , Wu Abraham J. , Jones David R. , Rocco Gaetano
Published: October 2024

Objective:

To generate a prediction model for selection of treatment modality for early-stage non-small cell lung cancer (NSCLC).

Summary Background Data:

Stereotactic body radiotherapy (SBRT) and minimally invasive surgery (MIS) are used in the local treatment of early-stage NSCLC. However, selection of patients for either SBRT or MIS remains challenging, due to the multitude of factors influencing the decision-making process.

Methods:

We analyzed 1291 patients with clinical stage I NSCLC treated with intended MIS or SBRT from January 2020 to July 2023. A prediction model for selection for SBRT was created based on multivariable logistic regression analysis. The receiver operating characteristic curve analysis stratified the cohort into 3 treatment-related risk categories. Post-procedural outcomes, recurrence and overall survival (OS) were investigated to assess the performance of the model.

Results:

In total, 1116 patients underwent MIS and 175 SBRT. The prediction model included age, performance status, previous pulmonary resection, MSK-Frailty score, FEV1 and DLCO, and demonstrated an area-under-the-curve of 0.908 (95%CI, 0.876–0.938). Based on the probability scores (n=1197), patients were stratified into a low-risk (MIS, n=970 and SBRT, n=28), intermediate-risk (MIS, n=96 and SBRT, n=53) and high-risk category (MIS, n=10 and SBRT, n=40). Treatment modality was not associated with OS (HR of SBRT, 1.67 [95%CI: 0.80-3.48]; P=0.20).

Conclusion:

Clinical expertise can be translated into a robust predictive model, guiding the selection of stage I NSCLC patients for MIS versus SBRT and effectively categorizing them into three distinct risk groups. Patients in the intermediate category could benefit most from multidisciplinary evaluation.
Real-time hybrid testing using iterative control for periodic oscillations
Authors: Beregi S. , Barton D. A. W. , Rezgui D. , Neild S. A.
Published: October 2024

Real-time hybrid testing is a method in which a substructure of the system is realized experimentally and the rest numerically. The two parts interact in real time to emulate the dynamics of the full system. Such experiments, however, are often difficult to realize as the actuators and sensors, needed to ensure compatibility and force–equilibrium conditions at the interface, can seriously affect the predicted dynamics of the system and result in stability and fidelity issues. The traditional approach of using feedback control to overcome the additional unwanted dynamics is challenging due to the presence of an outer feedback loop, passing interface displacements or forces to the numerical substructure. We, therefore, advocate for an alternative approach, removing the problematic interface dynamics with an iterative scheme to minimize interface errors, thus, capturing the response of the true assembly. The technique is examined by hybrid testing of a bench-top four-storey building with different interface configurations, where using conventional hybrid measurement techniques is very challenging. A case where the physical part exhibits nonlinear restoring force characteristics is also considered. These tests show that the iterative approach is capable of handling even scenarios which are theoretically infeasible with feedback control.
Swimming through sand: using accelerometers to observe the cryptic, pre-emergence life-stage of sea turtle hatchlings
Authors: Dor David , Booth David T. , Schwanz Lisa E.
Published: October 2024

Animals that hatch within a subterranean nest, such as turtle hatchlings, expend some of their limited energy reserves digging out through sand or soil to reach the surface. In sea turtles, this emergence process can take the hatchlings 3–7 days. However, we have a poor understanding of this process as it is difficult to observe what is occurring underground. Here, we utilize a novel method to characterize digging-out behaviour: affixing an accelerometer directly to newly hatched green turtles (
Chelonia mydas
) to record movement until nest emergence. Our data revealed that buried hatchlings maintained a head-up orientation but did not move in the expected left and right swaying motion associated with alternating limb crawling. Rather, they moved using dorsal–ventral heaving and pitching as if swimming vertically through the sand to the surface. Movement activity was irregular and brief, interspersed by many short periods of inactivity, mostly lasting less than 10 min. The first 24 h of head-up activity displayed no diel patterns, but the last 24 h prior to emergence involved more intense movement during night-time hours compared with daytime hours. Thus, our results add valuable new insight, and in some cases change previous assumptions, regarding the digging behaviours during the egg-to-emergence life stage in sea turtles.
Microbial genetic potential differs among cryospheric habitats of the Damma glacier
Authors: Feng Maomao , Robinson Serina , Qi Weihong , Edwards Arwyn , Stierli Beat , van der Heijden Marcel , Frey Beat , Varliero Gilda
Published: October 2024

Climate warming has led to glacier retreat worldwide. Studies on the taxonomy and functions of glacier microbiomes help us better predict their response to glacier melting. Here, we used shotgun metagenomic sequencing to study the microbial functional potential in different cryospheric habitats, i.e. surface snow, supraglacial and subglacial sediments, subglacial ice, proglacial stream water and recently deglaciated soils. The functional gene structure varied greatly among habitats, especially for snow, which differed significantly from all other habitats. Differential abundance analysis revealed that genes related to stress responses (e.g. chaperones) were enriched in ice habitat, supporting the fact that glaciers are a harsh environment for microbes. The microbial metabolic capabilities related to carbon and nitrogen cycling vary among cryospheric habitats. Genes related to auxiliary activities were overrepresented in the subglacial sediment, suggesting a higher genetic potential for the degradation of recalcitrant carbon (e.g., lignin). As for nitrogen cycling, genes related to nitrogen fixation were more abundant in barren proglacial soils, possibly due to the presence of Cyanobacteriota in this habitat. Our results deepen our understanding of microbial processes in glacial ecosystems, which are vulnerable to ongoing global warming, and they have implications for downstream ecosystems.
A depth map of visual space in the primary visual cortex
Authors: He Yiran , Colas Nieto Antonio , Blot Antonin , Znamenskiy Petr
Published: October 2024

Depth perception is essential for visually-guided behavior. Computer vision algorithms use depth maps to encode distances in three-dimensional scenes but it is unknown whether such depth maps are generated by animal visual systems. To answer this question, we focused on motion parallax, a depth cue relying on visual motion resulting from movement of the observer. As neurons in the mouse primary visual cortex (V1) are broadly modulated by locomotion, we hypothesized that they may integrate vision- and locomotion-related signals to estimate depth from motion parallax. Using recordings in a three-dimensional virtual reality environment, we found that conjunctive coding of visual and self-motion speeds gave rise to depth-selective neuronal responses. Depth-selective neurons could be characterized by three-dimensional receptive fields, responding to specific virtual depths and retinotopic locations. Neurons tuned to a broad range of virtual depths were found across all sampled retinotopic locations, showing that motion parallax generates a depth map of visual space in V1.
Latent-TGF-β has a domain swapped architecture
Authors: Jin Mingliang , Seed Robert , Shing Tiffany , Cheng Yifan , Nishimura Stephen L.
Published: October 2024

The multifunctional cytokine TGF-β is produced in a latent form (L-TGF-β) where a RGD containing homodimeric prodomain forms a “ring” encircling mature TGF-β shielding it from its receptors. Thus L-TGF-β must be activated to function, a process driven by dynamic allostery resulting from integrin binding the L-TGF-β RGD motif. Here we provide critical evidence that defines a domain-swapped architecture of L-TGF-β, an essential component in the dynamic allostery mechanism of L-TGF-β activation.
Clioquinol improves catalytic activity of PHGDH and shows antiseizure efficacy in patients
Authors: Thevissen Karin , Ny Annelii , Copmans Daniëlle , Tits Jana , Kamata Kenichi , Gielis Eva , Longin Kevin , Sourbron Jo , Thergarajan Peravina , Tan Tracie Huey-Lin , Ali Idrish , Jones Nigel C. , O’Brien Terence J. , Monif Mastura , Semple Bridgette D. , Germeys Christine , Frizzi Benedetta , Minniti Virginia , Perrone Sebastian , Linster Carole L. , Elia Ilaria , Van Den Bosch Ludo , Cammue Bruno P.A. , Voet Arnout , Lagae Lieven , de Witte Peter
Published: October 2024

Drug-resistant epilepsy (DRE) affects over 25 million people worldwide and is associated with neuroinflammation. We identified haloquinolines from a drug repurposing library as potent activators of phosphoglycerate dehydrogenase (PHGDH) enzyme, which converts 3-phosphoglycerate to generate serine and the neurotransmitter glycine, and steers anti-inflammatory responses. The most promising haloquinoline clioquinol can increase the catalytic activity of PHGDH up to 2.5-fold, thereby increasing de novo glycine biosynthesis and resulting in reduced glutamate levels. Moreover, we show that clioquinol has PHGDH-dependent antiseizure activity as well as anti-inflammatory propertiesin vivousing various zebrafish and mouse epilepsy models. Finally, we demonstrate the efficacy of clioquinol as add-on treatment in severe DRE patients. Therefore, increasing activity of PHGDH is a promising new approach to treat DRE.
Hypoxia threatens coral and sea anemone early life stages
Authors: Glass Benjamin H. , Barott Katie L.
Published: October 2024

Seawater hypoxia is increasing globally and can drive declines in organismal performance across a wide range of marine taxa. However, the effects of hypoxia on early life stages (e.g., larvae and juveniles) are largely unknown, and it is unclear how evolutionary and life histories may influence these outcomes. Here, we addressed this question by comparing hypoxia responses across early life stages of three cnidarian species representing a range of life histories: the reef-building coralGalaxea fascicularis, a broadcast spawner with horizontal transmission of endosymbiotic algae (family Symbiodiniaceae); the reef-building coralPorites astreoides, a brooder with vertical endosymbiont transmission; and the estuarine sea anemoneNematostella vectensis, a non-symbiotic broadcast spawner. Transient exposure of larvae to hypoxia (dissolved oxygen < 2 mg L-1for 6 h) led to decreased larval swimming and growth for all three species, which resulted in impaired settlement for the corals. Coral-specific responses also included larval swelling, depressed respiration rates, and decreases in symbiont densities and function. These results indicate both immediate and latent negative effects of hypoxia on cnidarian physiology and coral-algal mutualisms specifically. In addition,G. fascicularisandP. astreoideswere sensitized to heat stress following hypoxia exposure, suggesting that the combinatorial nature of climate stressors will lead to declining performance for corals. However, sensitization to heat stress was not observed inN. vectensisexposed to hypoxia, suggesting that this species may be more resilient to combined stressors. Overall, these results emphasize the importance of reducing anthropogenic carbon emissions to limit further ocean deoxygenation and warming.
LightMed: A Light-weight and Robust FFT-Based Model for Adversarially Resilient Medical Image Segmentation
Authors: Pham Viet Tien , Ha Minh Hieu , Bui Bao V. Q. , Hy Truong Son
Published: October 2024

Accurate and reliable medical image segmentation is essential for computer-aided diagnosis and formulating appropriate treatment plans. However, real-world challenges such as suboptimal image quality and computational resource constraints hinder the effective deployment of deep learning-based segmentation models. To address these issues, we propose LightMed, a novel efficient neural architecture based on Fast Fourier Transform (FFT). Different from prior works, our model directly learns on the frequency domain, harnessing its resilience to noise and un-even brightness, which common artifacts found in medical images. By focusing on low-frequency image components, we significantly reduce computational complexity while preserving essential image features. Our deep learning architecture extracts discriminative features directly from the Fourier domain, leading to improved segmentation accuracy and robustness compared to traditional spatial domain methods. Additionally, we propose a new benchmark incorporating various levels of Gaussian noise to assess susceptibility to noise attacks. The experimental results demonstrate that LightMed not only effectively eliminates noise and consistently achieves accurate image segmentation but also shows robust resistance to imperceptible adversarial attacks compared to other baseline models. Our new benchmark datasets and source code are publicly available athttps://github.com/HySonLab/LightMed.
Tracing Cellular Senescence in Bone: Time-Dependent Changes in Osteocyte Cytoskeleton Mechanics and Morphology
Authors: Tilton Maryam , Liao Junhan , Kim Chanul , Shaygani Hossein , Potes Maria Astudillo , Cordova Domenic , Kirkland James L. , Miller Kyle M.
Published: October 2024

Aging-related bone loss significantly impacts the growing elderly population globally, leading to debilitating conditions such as osteoporosis. Senescent osteocytes play a crucial role in the aging process of bone. This longitudinal study examines the impact of continuous local and paracrine exposure to senescence-associated secretory phenotype (SASP) factors on senescence-associated biophysical and biomolecular markers in osteocytes. We found significant cytoskeletal stiffening in irradiated osteocytes, accompanied by expansion of F-actin areas and a decline in dendritic integrity. These changes, correlating with alterations in pro-inflammatory cytokine levels and osteocyte-specific gene expression, support the reliability of biophysical markers for identifying senescent osteocytes. Notably, local accumulation of SASP factors had a more pronounced impact on osteocyte properties than paracrine effects, suggesting that the interplay between local and paracrine exposure could substantially influence cellular aging. This study underscores the importance of osteocyte mechanical and morphological properties as biophysical markers of senescence, highlighting their time-dependence and differential effects of local and paracrine SASP exposure. Collectively, our investigation into biophysical senescence markers offer unique and reliable functional hallmarks for non-invasive identification of senescent osteocytes, providing insights that could inform therapeutic strategies to mitigate aging-related bone loss.
A new spin on chemotaxonomy using non-proteogenic amino acids as a test case
Authors: Gibson Makenzie , Thives Santos William , Oyler Alan R. , Busta Lucas , Schenck Craig A.
Published: October 2024

Premise

Specialized metabolites serve various roles for plants and humans. Unlike core metabolites, specialized metabolites are restricted to certain lineages. Thus, in addition to their ecological functions, specialized metabolites can serve as diagnostic markers of plant lineages.

Methods

We investigate the phylogenetic distribution of plant metabolites using non-proteogenic amino acids (NPAA). Species-NPAA associations for eight NPAAs were identified from the existing literature and placed within a phylogenetic context using R packages and interactive tree of life. To confirm and extend the literature-based NPAA distribution we selected azetidine-2-carboxylic acid (Aze) and screened over 70 diverse plants using GC-MS.

Results

Literature searches identified > 900 NPAA-relevant articles, which were manually inspected to identify 560 species-NPAA associations. NPAAs were mapped at the order and genus level, revealing that some NPAAs are restricted to single orders, whereas others are present across divergent taxa. The distribution of Aze across plants suggests a convergent evolutionary history.

Discussion

The reliance on chemotaxonomy has decreased over the years. Yet, there is still value in placing metabolites within a phylogenetic context to understand the evolutionary processes of plant chemical diversification. This approach can be applied to metabolites present in any organism and compared at a range of taxonomic levels.
Test-Retest Reliability and Repeatability of Behavioral and Electrophysiological Markers in an Eriksen Flanker Task
Authors: Bogdanov Mario , Scott Jason N. , Esfand Shiba M. , Boyle Brian W. , Lees Ty , Li Mohan , Woronko Sarah E. , Linton Samantha R. , Miller Courtney , Li Shuang , Bolton Paula , Meisner Robert C. , Pizzagalli Diego A.
Published: October 2024

Cognitive control processes, specifically interference control and error monitoring, are often impaired across neuropsychiatric disorders and have been proposed as transdiagnostic markers of psychopathology and important treatment targets. Accurately probing them, however, requires understanding the psychometric properties of the measures used to assess cognitive control, including their intra- and interindividual stability over time. Using an Eriksen Flanker Task, we tested behavioral and electrophysiological readouts of cognitive control in 36 healthy individuals (26 female, 10 male,Mage±SD=33.18±14.49, range=19–68) and evaluated their test-retest reliability across 48 hours by calculating Pearson correlations and Intraclass Correlation Coefficients (ICCs) to assess group-level stability. Moreover, we assessed repeatability through Coefficients of Variation (CVs) and Bland-Altman statistics, to investigate the degree of change in participants’ absolute scores. We found satisfactory-to-excellent test-retest reliability for most cognitive control measures, with condition-specific metrics generally being more reliable than difference scores. Regarding repeatability, we observed considerable intraindividual variability in absolute scores over time, which differed widely between participants. These results demonstrate that measurements of cognitive control may display substantial intraindividual variability across sessions despite demonstrating high test-retest reliability and vice versa. Our findings expand the current literature by providing novel information about the stability of behavioral and physiological markers of cognitive control over time. Moreover, they may have important implications for the application and evaluation of clinical interventions by highlighting the usefulness of considering repeatability measures in addition to the more commonly reported test-retest reliability metrics, when tracking changes over time in clinically relevant processes within single individuals.
Characterization of Autophagy Cargo Profiles during Starvation and Exercise with a Novel Autophagosome Isolation Method
Authors: Farhan Mohd , Nguyen Trezze P , Zhang Dakai , Liang Hong , Zhou Yong , Yang Hongyuan , Du Guangwei , Liu Yang
Published: October 2024

Autophagy is a cellular process to clear unwanted and dysfunctional cellular cargoes, which are sequestered in autophagosomes before their delivery to lysosomes for degradation. Autophagy cargo selection, mediated by cargo receptors, varies across cell types and conditions. Understanding the cargo features is essential for elucidating autophagy’s function in specific physiological or pathological contexts. Here we present a simple and rapid method for isolating LC3B-positive autophagosomes from the tissues of GFP-LC3 transgenic mice, a widely used autophagy reporter model. When combined with quantitative proteomics, this approach enables efficient in vivo characterization of autophagy cargoes. We applied this method to establish autophagy cargo profiles in skeletal muscle during starvation and exercise-two physiological conditions that activate autophagy-and identified distinct cargo selection patterns, with significantly higher levels of ER-phagy and ribophagy observed during starvation. We further revealed the ER-phagy receptors TEX264 and FAM134B as potential mediators of the elevated ER-phagy under starvation. In summary, we report an efficient workflow for in vivo autophagy cargo characterization and provide detailed analysis and comparison of cargo profiles under starvation and exercise conditions.
Long-Term Effects of Early Adolescent Second-Generation Antipsychotic Exposure on Body Weight, Caloric Intake, and Metabolism-Associated Gene Expression
Authors: Soto Paul L. , Young Michael E. , Nguyen Serena , Federoff Megan , Goodson Mia , Morrison Christopher D. , Batdorf Heidi M. , Burke Susan J. , Collier J. Jason
Published: October 2024

The use of second-generation antipsychotic (SGA) medications in pediatric patients raises concerns about potential long-term adverse outcomes. The current study evaluated the long-term effects of treatment with risperidone or olanzapine on body weight, caloric intake, serum insulin, blood glucose, and metabolism-associated gene expression in C57Bl/6J female mice. Compared to mice treated with vehicle, female mice treated with risperidone or olanzapine gained weight at higher rates during treatment and maintained higher body weights for months following treatment cessation. During high-fat diet feeding, some groups of treated mice gained weight at higher rates than their respective control groups, but the finding was not consistent across experiments. Finally, female mice previously treated with olanzapine also exhibited increased expression of genes associated with inflammation and lipogenesis. These findings suggest that pediatric use of SGA medications that induce excess weight gain during treatment may exert persistent effects on body weight and gene expression and such outcomes may form an important aspect of assessing risk-to-benefit ratios in prescribing decisions.
Phytochemical Analysis and Nematicidal Activity of Medicinal Plants AgainstMeloidogyne javanica
Authors: Maher Saima , Naheed Nadra , Khan Noureen , Ishtiaq Hina , Solangi Ghulam Sarwar , karim Aasia , Imran Muhammad , Iqbal Erum , Mukhtar Farah , Bakhshi Mahganj , Mina Gul , Alarfaji Saleh S
Published: October 2024

This study examined the nematicidal potential of ethanol extracts derived from four plants, namelyActinidia deliciosa(Chev.),Carica papaya, Citrus paradise, andRaphanus sativus, against the root-knot nematodeMeloidogyne javanica. Experimental results indicated a significant reduction in the survival of second-stage juveniles ofM. javanicawhen exposed to these plant extracts. Notably, concentrations of 2% and 1% were found to be more effective in comparison to 0.5% and 0.25%, yielding statistically significant outcomes. Furthermore, the mortality rate of the nematodes exhibited a direct correlation with the duration of exposure for most plant extracts. The fruit extracts obtained fromA. deliciosa, C. papaya, C. paradise, andR. sativusdemonstrated a substantial decrease in nematode infestation compared to the control group. The nematicidal activity of KI3a (BuOH) significant from 0.1356 to 1.9076 over 72 hours, while P-KI-2a (EtOAc) showed rose from 0.1206 to 0.6456. In compare, GF-3 (EtOAc) and Carbofuran to 0.0179 and 0.0098, respectively. PA-1 (MeOH) and RS-3 (EtOAc) showed modest nematicidal potential. This research emphasizes the efficacy of plant extract in mitigating root-knot nematode infestation, offering a promising alternative to chemical managements. Additionally, comprehensive phytochemical analysis should be achieved to recognize the active chemical constituents responsible for their effects. Exploring synergistic effects between these compounds and other natural or synthetic agents could further improve their potential applications in sustainable agriculture, improving crop protection and promoting eco-friendly practices.
Complex motion trajectories are represented by a population code from the ensemble activity of multiple motion-sensitive descending interneurons in locusts
Authors: Zhang Sinan , Gray John R.
Published: October 2024

Adaptive locust flight relies on rapid detection and processing of objects moving in the visual field. One identified neural pathway, comprised of the lobula giant movement detector (LGMD) and the descending contralateral movement detector (DCMD), responds preferentially to approaching objects. The LGMD receives retinotopic inputs from ipsilateral ommatidia and generates spikes in a 1:1 ratio in the DCMD, which synapses contralaterally with multiple locomotion-related neurons. Other motion-sensitive neurons have also been identified in locusts but are not as well characterized. To better understand how locusts process visual information, we used multichannel neural recordings within a stimulus arena and presented various complex visual stimuli to investigate the neural encoding of complex object motion. We found multiple discriminated units that responded uniquely to visual motion and categorized the responses. More units responded to motion trajectories with a looming component, compared to translations across the visual field. Dynamic factor analysis (DFA) of discriminated units revealed common trends that reflect the activity of neural ensembles. The numbers and types of common trends varied among motion trajectories. These results increase the understanding of complex visual motion processing in this tractable system.
Design and evaluation of an automated real-time SOFA score calculator in an electronic health record system, for early sepsis diagnosis
Authors: Smitt Einarson Gustaf , Nordqvist Hampus , Marking Ulrika , Jonmarker Sandra , Parke Åsa , Unge Christian , Yu David , Sundén-Cullberg Jonas , Strålin Kristoffer
Published: October 2024

Background

In patients with infections, the Sequential Organ Failure Assessment (SOFA) score should be used to diagnose sepsis. However, manual SOFA calculation is time consuming. Thus, we developed an automated real-time SOFA score application that has been fully implemented into the major electronic health record (EHR) system (TakeCare) in Stockholm. We aimed to describe the method and evaluate its performance for detection of sepsis.

Method

We developed an automated SOFA application that presents a total score (SOFATotal) over time and a baseline score (SOFAChronic) based on outpatient data prior to hospital admission. We evaluated its performance on 583 sepsis alert patients in an emergency department, including 472 with sepsis according to manually calculated SOFA (SOFAManual). SOFATotal at 30 minutes and 3 hours, and quick-SOFA (qSOFA) were compared with SOFAManual for detection of sepsis. The acute SOFA score (SOFAAcute) was calculated by subtracting SOFAChronic from SOFATotal.

Results

SOFATotal at 3 hours showed moderate-good agreement with SOFAManual (R² = 0.76). Areas under receiver operating characteristic curves for sepsis detection were 0.83 at 30 minutes, 0.94 at 3 hours for SOFATotal, and 0.67 for qSOFA. Among patients with SOFAChronic ≥1 (21% of cases), SOFATotal of ≥2 was observed in 90% of cases (mortality 13.5%), although SOFAAcute of ≥2 was noted in 63% (mortality 16.7%).

Conclusion

The automated SOFA score demonstrated effectiveness in early sepsis detection, outperforming qSOFA, but adjustments for chronic baseline scores were necessary to avoid over-diagnosis. Further studies on broader patient populations would be useful to validate its clinical use.
Risk of cardiovascular disease in patients with classical Hodgkin lymphoma: a Danish nationwide register-based cohort study
Authors: Godtfredsen Sissel J. , Yonis Harman , Baech Joachim , Al-Hussainy Nour R. , Riddersholm Signe , Kober Lars , Schou Morten , Christensen Jacob Haaber , Hutchings Martin , Dahl-Sørensen Rasmus Bo , Kamper Peter , Dietrich Caroline E. , Andersen Mikkel Porsborg , Torp-Pedersen Christian , Sogaard Peter , El-Galaly Tarec Christoffer , Kragholm Kristian H.
Published: October 2024

Aim

To describe the risk of cardiovascular disease (CVD) in patients with classical Hodgkin lymphoma (cHL) undergoing contemporary treatment.

Methods

Including all patients with cHL ≥18 years at diagnosis treated with doxorubicin-containing chemotherapy between 2000-2022. Patients were matched with comparators in a 1:5 ratio on birth year, sex, and Charlson Comorbidity Index at time of matching (score of 0 or ≥1). A composite of CVDs including coronary artery disease, heart failure, valvular stenoses, restrictive pericarditis, arrythmias, or any procedures related to these was the primary outcome. Follow-up started on date of cHL diagnosis (i.e., the matching date). The cause-specific cumulative incidence and 95% confidence intervals (CIs) were computed with all-cause death and lymphoma relapse as competing events using the Aalen-Johansen estimator.

Results

A total of 1,905 patients with cHL and 9,525 comparators were included. Median age was 39 years (interquartile range, [IQR]: 27-56), 58% were males, most were treated with ABVD (83%), and the median cumulative doxorubicin dose was 250 mg/m2(IQR: 200-300). Median follow-up was 10 years (IQR: 5.9-17.4). The cumulative incidences of CVD were 4.7% (95% CI: 3.6-5.7) for patients vs. 2.6% (95% CI: 2.3-2.9) for comparators at 5 years, 8.9% (95% CI: 7.2-10.5) vs. 5.5% (95% CI: 4.9-6.0) at 10 years, and 17.0% (95% CI: 14.1-19.9) vs. 8.2% (95% CI: 7.4-9.0) at 15 years.

Conclusions

CVD remains a substantial late effect after contemporary treatment for cHL, suggesting that awareness of cardiac symptoms and a low threshold for referral to diagnostic examination are still important measures during survivorship.
The neurodevelopmental spectrum ofCASK-related disorder
Authors: Martin Jessica , Mavrogalou-Foti Alkistis , Eck Josefine , Hattersley Laura , Baker Kate
Published: October 2024

Background

PathogenicCASKvariants are associated with neurodevelopmental disorders of variable severity including X-linked intellectual disability (XLID) and microcephaly with pontocerebellar hypoplasia (MICPCH). Although the number of diagnosed cases is rising, current understanding of theCASK-related neurodevelopmental spectrum is limited. Here, we systematically review the published characteristics of individuals withCASK-related disorder, and compare these to a more recently-diagnosed group. We provide quantitative information about the ranges of adaptive abilities, motor function, visual function and social-emotional-behavioural characteristics, and explore within-group associations.

Methods

151 individuals withCASKvariants were identified in published literature. 31 children and young people withCASKvariants were recruited to the UK-based Brain and Behaviour in Neurodevelopmental disorder of Genetic Origin (BINGO) project. BINGO-participating caregivers completed a bespoke medical history questionnaire and battery of standardised neurodevelopmental measures.

Results

Comparing the recently diagnosed BINGOCASK-related disorder group to previously reported individuals, we found consistent prevalence of tone abnormalities, sensorineural hearing loss and epilepsy, but lower prevalence of severe/profound ID, MICPCH, optic atrophy and nystagmus. Areas of frequent difficulty not highlighted in previous reports include sleep difficulties and cerebral visual impairment (CVI). Neurodevelopmental characteristics were highly variable within the BINGOCASK-related disorder group, and group-wide patterns were similar to those observed in other rare genetic conditions. Within the BINGOCASK-related group, epilepsy is significantly associated with ID severity, after controlling for age. Sub-groups with MICPCH or microcephaly only have equivalent ranges of adaptive function, but MICPCH may be associated with more severe motor difficulties.

Conclusion

The spectrum of neurodevelopmental characteristics associated withCASK-related disorder appears to be broadening with increased access to genome-wide diagnostic testing. Further studies are needed to elucidate the relationships betweenCASKvariants, structural brain development, epilepsy, and neurodevelopmental characteristics.
Nucleoporin Nup153 docks the splicing machinery to the nuclear pore for efficient mRNA processing
Authors: de Castro IJ , Schuster L , Patiño-Gomez C , Glavas D , Udupa A , Ríos Vázquez M , Symens T , Tulcan G , Heinze J , de las Heras J , Reinhardt Robert , Trojanowski Jorge , Harz H , Stumberger G , Leonhardt H , Schirmer E , Saka S , Laketa V , Lusic M
Published: October 2024

The nuclear pore complex (NPC), composed of proteins termed nucleoporins (Nups), intercalates the nuclear envelope, and is primarily involved in protein trafficking and mRNA export. At the nuclear basket, Nups have been associated with chromatin organization and postulated to function as transcriptional hubs, working in tandem with mRNA export machinery. However, little is known about the intermediate process of RNA splicing at the NPC. Here, we used BioID to screen for interactors of basket-Nups Nup153 and TPR and discovered the enrichment of splicing proteins across all spliceosome complexes (E, A, B, B*, P). The peripheral nature of the interaction between Nup153 and selected splicing components was confirmed byin-situproximity ligation assay and STED microscopy. The presence of splicing components at the NPC, reduced upon splicing inhibition, is partly dependent on Nup153 and functionally correlated to the splicing of Nup153-bound genes. Assessed by DamID, Nup153-bound genes (∼500) are characterized by multiple long introns with lower-than-average GC content. Positioned at the periphery but distinct from the neighbouring lamina-associated domain (LADs) in chromatin signatures and expression levels, these genes showed Nup153-dependent splicing defect, suggesting that splicing occurs at the NPC.

Altogether, our data substantiates the gene gating theory bringing transcription and export, now accompanied by speckle-distant splicing events, at the level of the NPC.
High-throughput diversification of protein-ligand surfaces to discover chemical inducers of proximity
Authors: Shaum James B. , Steen Erica A. , Muñoz i Ordoño Miquel , Wenge Daniela V. , Cheong Hakyung , Hunkeler Moritz , Bilotta Eric M. , Rutter Zoe , Barta Paige A. , Milosevich Natalia , Hargis Lauren M. , Janowski Jordan , Bishop Timothy R. , Carter Trever R. , da Camara Bryce , Hinterndorfer Matthias , Dada Lucas , He Wen-Ji , Offensperger Fabian , Furihata Hirotake , Schweber Sydney R. , Hatton Charlie , Wen Yanhe , Cravatt Benjamin F. , Engle Keary M. , Melillo Bruno , Kitamura Seiya , Ciulli Alessio , Armstrong Scott A. , Fischer Eric S. , Winter Georg E. , Erb Michael A.
Published: October 2024

Chemical inducers of proximity (CIPs) stabilize biomolecular interactions, often causing a privileged rewiring of cellular biochemistry. While rational design strategies can expedite the discovery of heterobifunctional CIPs, molecular glues have predominantly been discovered by serendipity. Envisioning a prospective approach to discover molecular glues for a pre-selected target, we hypothesized that pre-existing ligands could be systematically decorated with chemical modifications to discover protein-ligand surfaces that are tuned to cooperatively engage another protein interface. Using high-throughput chemical synthesis to diversify a ligand for the transcriptional coactivator ENL with 3,163 structurally diverse chemical building blocks, we discovered a compound dHTC1 that elicits potent, selective, and stereochemistry-dependent degradation of ENL by induced binding to CRL4CRBN. Unlike prior CRBN-based degraders, dHTC1 binds the ligase with high affinity only after forming the ENL:dHTC1 complex, relying on a hybrid interface of protein-protein and protein-ligand contacts. Altogether, this study points toward an expanded chemical space for co-opting the therapeutically important substrate receptor, CRBN, and a second proof-of-concept extending this approach to BRD4 further validates high-throughput chemistry as a facile tool to discover new degraders.
Independent evolution of atypical sperm morphology in a passerine bird, the red-browed finch (Neochmia temporalis temporalis)
Authors: Rowe Melissah , Hooper Daniel M. , Hofgaard Antje , Hurley Laura L. , McDiarmid Callum S. , Pataraia Ioanna , Lifjeld Jan T. , Griffith Simon C.
Published: October 2024

Spermatozoa exhibit striking morphological variation across the animal kingdom. In passerine birds, sperm exhibit considerable variation in size, yet the basic sperm phenotype is highly conserved; sperm are filiform, the head is corkscrew-shaped, and the midpiece is elongated and twisted around the flagellum. A significant departure from this typical sperm morphology has been reported in the sister species, the Eurasian bullfinch (Pyrrhula pyrrhula) and Azores bullfinch (P. murina). Here, we report a second evolutionary shift in passerine sperm phenotype in the nominate subspecies of the red-browed finch (Neochmia temporalis temporalis); sperm are non-filiform, with an ellipsoid head, and an extremely short midpiece restricted to the nuclear-axoneme junction. Additionally, we show that the sperm phenotype of the red-browed finch is similar to the putatively neotenous sperm described in the two bullfinch species. Using whole-genome data, we found no evidence that the unusual sperm phenotype of the red-browed finch is associated with reduced genetic variation or a population bottleneck. In contrast, we find some support for the hypothesis that relaxed post-copulatory sexual selection may, at least in part, explain the unusual sperm of the red-browed finch. We also discuss the possible roles of mutation, genetic drift, and genetic hitchhiking, in the evolutionary origins and maintenance of neotenous sperm phenotypes. Finally, we suggest that these dramatic evolutionary shifts in sperm phenotype warrant further investigation and highlight the need for a greater understanding of the developmental and genomic basis of sperm phenotype.