bluuebunny/crossref_metadata_2025 huggingface dataset:
Human-Centered Design in Graduate Nursing Education
Authors: Holt Jeana M. , Talsma AkkeNeel , Lloren Jan Irene C. , Eljarrah Imteyaz , Woehrle Lynne , Avdeev Ilya
Published: December 2024

Background:

Many nursing curricula lack human-centered design (HCD) learning opportunities, and minimal evidence exists about HCD educational outcomes.

Purpose:

The study explored the effects of HCD experiential learning activities on graduate nursing students.

Methods:

The quasi-experimental mixed-method design employed an explanatory approach. Pre- and posttest surveys were administered during an HCD workshop. Descriptive and inferential statistics assessed gains in the measures. Qualitative data were collected once, post-intervention, and analyzed using thematic analysis.

Results:

Sixty-four students provided complete responses. A linear mixed-effects regression model indicated statistically significant gains in creative self-efficacy, psychological empowerment, and traits of design thinkers. Qualitative themes contextualized the quantitative findings.

Conclusions:

The results indicated that HCD experiential learning influenced the study’s constructs. These results set the stage for multi-site studies investigating the long-term outcomes of HCD interventions in nursing curricula.
Timing is Everything: Using a Phased Toolkit Approach in Large-Scale Education
Authors: Buckner Jessica B. , Kirkman Allyson , Tripp Heather , Fencl Jennifer
Published: December 2024

Purpose

This article aims to share an innovative way to use virtual toolkits in large-scale education.

Description of Program

An incredible number of educational needs exist at any time in the hospital setting. Sharing information with hundreds of nurses in different departments or campuses is a vast undertaking for the clinical nurse specialist (CNS). At times, the material required for a single educational endeavor can be substantial, presenting another challenge for the CNS. Based on principles from Cognitive Load Theory and microlearning, a toolkit methodology allows in-depth education to be broken down into manageable portions for leaders, CNSs, and/or nursing professional development practitioners to effectively share with staff. The toolkit educational strategy utilizes calendar reminders with educational flyers, links, and content attached, making education accessible and easy to share.

Outcome

This method is an effective way to educate staff without requiring traditional class time.

Conclusion

CNSs, nursing professional development practitioners, and leaders alike can use the toolkit strategy for rolling out large initiatives in smaller portions over time, which can lead to better uptake and retention of information.
MR-Guided PET Reconstruction
Authors: Huellner Martin W. , Maurer Alexander , Spangler-Bickell Matthew
Published: December 2024

We report a case of a 33-year-old man with epilepsy and equivocal EEG, MRI signs of mesiotemporal sclerosis, and nondiagnostic standard FDG-PET imaging. The patient underwent repeat FDG-PET/MRI to clarify the sidedness of the epileptogenic focus and to confirm the suspected MTS. The standard PET reconstruction using block sequential regularized expectation maximization failed to provide evidence of a clear epileptogenic focus. However, using MR-guided PET reconstruction, circumscribed hypometabolism was observed in the right-sided entorhinal cortex, compatible with the epileptogenic focus. The MR-guided PET reconstruction provided significantly improved gray/white matter differentiation, enhancing confidence in imaging interpretation.
Evaluation of Situs Inversus Combined With Plastic Surgery–Related Malformations in a Chinese Clinic Population
Authors: Jia Ying , Zhang Ziming , Gao Shangjie , Jiang Fengli , Wang Yuhao , Su Xueshang , Zhuang Jun , Li Jingjing , Hu Jintian , Zhan Sien
Published: December 2024

Background

Situs inversus is a congenital malformation that occurs in one or multiple organs simultaneously and can be accompanied by malformations in other body parts. We analyzed the prevalence and phenotype of patients with situs inversus and comorbidities associated with other plastic surgery–related malformations to enhance the knowledge of its related disorders and facilitate treatment.

Methods

We recruited patients with situs inversus who were seen at our institution from February 2015 to July 2023. They underwent ultrasound and physical examinations to investigate deformity in other body parts. Fisher's exact test was used to analyze the laterality between hemifacial microsomia and situs inversus type.

Results

All 14 patients with situs inversus had plastic surgery–related malformations—three congenital and three developmental. Nine (65%) patients had hemifacial microsomia (right side, n = 8; bilateral, n = 1). The laterality of hemifacial microsomia was associated with the situs inversus type, with a significant difference (P < 0.05), and hemifacial microsomia occurred ipsilaterally in patients with right-sided hearts.

Conclusions

Early situs inversus diagnosis is clinically important for patients and plastic surgeons. Further studies on anomalies associated with situs inversus will improve our understanding of their etiology.
Comprehensive Validation of the German Version of the LIMB-Q
Authors: Besmens Inga S. , Watson Jennifer A. , Akyildiz Efe , Mundy Lily R. , Giovanoli Pietro , Calcagni Maurizio , Lindenblatt Nicole
Published: December 2024

Objective

Lower extremity trauma significantly impacts patients' lives, requiring a nuanced approach to evaluate outcomes beyond clinical measures. The LIMB-Q, a patient-reported outcome measure (PROM), assesses the multifaceted impacts of lower extremity trauma, including physical and emotional dimensions, from the patient's perspective. This study validates the German version of the LIMB-Q.

Methods

We relied on the translation of the LIMB-Q that had followed the International Society for Pharmacoeconomics and Outcomes Research best practice guidelines. Sixty patients who had undergone reconstructive surgery or amputation of the lower limb completed the LIMB-Q, Lower Extremity Functional Scale (LEFS), and Short Form Health Survey (SF-36). Internal consistency of the German LIMB-Q was determined by Cronbach's alpha, and reliability was assessed using the intraclass correlation coefficient. Construct validity was analyzed using Pearson correlation coefficients between the LIMB-Q, LEFS, and SF-36.

Results

Validation involved 60 patients. Internal consistency in a test-retest subset of 5 patients was good to excellent (α: 0.891 to 0.965). The intraclass correlation coefficient for these scales ranged from 0.821 to 1. The LIMB-Q domains significantly correlated with the corresponding domains of the SF-36 and LEFS, confirming excellent construct validity.

Conclusions

The German version of the LIMB-Q is conceptually equivalent to the original English version. It is a reliable and valid PROM for assessing physical and psychological impairments in patients who have undergone lower extremity reconstructive surgery or amputation.
A Physician-Centered Craniofacial Asymmetry Index for the Severity of Plagiocephaly
Authors: Lee Chien-Han , Lin Ting-Hsuan , Chen Shih-Heng , Chen Meng-Tse , Chen Pin-Ru , Shih Albert J. , Lee Chang-Chun , Chou Pang-Yun
Published: December 2024

Background

Plagiocephaly, wherein infants' head exhibits a diagonal asymmetry, is currently diagnosed based on physicians' subjective judgment. Discrepancies between physician and parent perspectives may result in dissatisfaction with treatment outcomes. This problem highlights the need for an objective assessment system aligning with physician-made clinical diagnoses.

Methods

Infant heads were modeled using 3-dimensional scanning techniques. We developed a craniofacial asymmetric index (CAI) based on 10 height planes of heads with varying weight. CAI and traditional craniofacial vault asymmetry index (CVAI) of 10 infants undergoing helmet therapy were compared with 11 craniofacial surgeons' judgment. The Pearson correlation coefficient and Bland-Altman plot were used to determine the correlations and agreement between physicians' judgment and the aforementioned assessment methods. The adjusted intraclass correlation coefficient was calculated to evaluate the reliability of between-physician agreement.

Results

All 10 infants were divided into the following 3 severity groups: severe, moderate, and mild groups based on craniofacial surgeons' judgment. Notably in CAI, front/back halves of skull and multiangular weighting factors were evaluated. The evaluation revealed perfect alignment in severity classification between the CAI and physicians' judgment, whereas both the CVAI score and MATLAB analysis show varying degrees of difference, 6 and 4 distinct results, respectively. Coefficients of the correlations of physician-assigned scores with the MATLAB analysis, CVAI score, and CAI score were 0.500, 0.833, and 1.000, respectively. Furthermore, Bland-Altman plots revealed the best agreement between CAI and physician-assigned scores.

Conclusions

CAI closely aligns with the subjective judgment of craniofacial surgeons' assessing the severity of plagiocephaly in infants.
Optimal Treatment for Post-Surgical Cicatricial Alopecia: Autologous Hair Transplantation?
Authors: Zhu Ling , Niu Yanchao , Chi Longjun , Zhang Jian , Wang Jing , Ren Ci
Published: December 2024

Background and Rationale:

Scarring alopecia significantly impacts patients’ appearance and psychological well-being. Surgery is a common cause of scarring alopecia, making positive treatment crucial for patients’ overall health.

Objective:

To investigate the clinical efficacy of autologous follicular unit extraction (FUE) transplantation for postoperative secondary stable scarring alopecia and evaluate its effectiveness.

Methods:

A retrospective descriptive study was conducted, including 14 patients with postoperative secondary scarring alopecia. All patients underwent initial autologous FUE hair transplantation, and postoperative complications were monitored. Patient satisfaction surveys were also conducted.

Results:

Satisfaction assessments were performed for all 14 patients. Two patients (14.3%) reported being very satisfied, 6 patients expressed satisfaction (35.7%), 4 patients reported being somewhat satisfied (28.6%), and 3 patients were dissatisfied (21.4%). Aesthetic complications included low follicular density post-transplantation, uneven density, and unnatural appearance.

Conclusion:

Solely using a single FUE hair transplantation for treating postoperative secondary scarring alopecia has limited effectiveness and may not always meet expectations, potentially requiring multiple transplantations. Further research is necessary to guide and improve follicular transplantation survival rates to ensure surgical efficacy.
Rouvière’s Sulcus as a Landmark for a Safe Laparoscopic Cholecystectomy: An Interim Analysis of a Multicenter Cross-sectional Study on the Prevalence and Morphologic Type of Rouvière’s Sulcus in the Italian Population
Authors: Cirocchi Roberto , Properzi Luca , Matteucci Matteo , Artico Marco , Vettoretto Nereo , Desiderio Jacopo , Di Cintio Antonio , Di Nardo Domenico , Farinacci Federico , Gemini Alessandro , Guerci Lorenzo , Mazzetti Stefano , Ricci Francesco , Trastulli Stefano , Avenia Stefano , Boselli Carlo , Cirillo Bruno , Brachini Gioia , Fedeli Piergiorgio , Montori Giulia , Ursi Pietro , Iandoli Ruggero , Bergamini Carlo , Giordano Alessio , Santoro Alberto , Mingoli Andrea , Antipas Pavlos , Tebala Giovanni Domenico
Published: December 2024

Background:

Laparoscopic cholecystectomy is the gold standard in the treatment of symptomatic gallstones. The large number of gallbladders removed every year is not fully consistent with the excessively high incidence of iatrogenic bile duct injury (IBDI). Several strategies have been suggested to reduce this risk. Among them, the use of extra biliary anatomic structures, such as the Rouvière’s sulcus, as a landmark to guide the surgeon during dissection has been proposed as a means to prevent IBDI. The main aim of the present paper is the evaluation of the prevalence of Rouvière’s sulcus (RS) and its anatomic variants in a given population.

Materials and Methods:

This observational, cross-sectional, and multicenter study has been conducted at the Department of Digestive and Emergency Surgery of the “Azienda Ospedaliera Santa Maria,” Terni (Italy), at the Department of Surgical Sciences of the “Azienda Ospedaliera Perugia,” Perugia (Italy) and at the Department of Emergency and Trauma Surgery of the “Policlinico Umberto I,” Rome (Italy). Intraoperative images of 111 patients undergoing laparoscopic cholecystectomy were analyzed to identify the presence and type of RS, according to the Singh-Prasad classification and the Dahmane classification.

Results:

RS was present in 93 (83.8%) patients. Singh-Prasad type 1A is present in 48.4% of patients, type 1B in 25.8%, type 2 in 12.9% and type 3 in 12.9%. Dahmane’s open type is present in 48.4% of patients and fused type in 51.6%.

Conclusion:

Due to its high prevalence, RS can be used as an anatomic landmark and probably reduces the incidence of IBDI during laparoscopic cholecystectomy.
Anxiety-like behaviors in rats exposed to the single and combined program of running exercise and environmental enrichment
Authors: Ghayourbabaei Farnaz , Farzin Mohaya , Keshavarzi Zakieh , Saburi Ehsan , Khodadadegan Mohammad Amin , Hajali Vahid
Published: December 2024

Exercise (Ex) and environmental enrichment (EE) as the nondrug solutions have positive effects on cognitive behaviors and also increase the ability to cope with anxiety, fear, and stress. In this research, we decided to investigate the simultaneous effect of Ex and EE on anxiety-like behaviors and hippocampal neurogenesis markers in healthy rats. A total of 40 male Wistar rats were divided into four treatment groups: control, EE, Ex, and EE + Ex. Animals in EE groups were housed in large cages (50 × 50 × 50 cm) equipped with toys and objects of different shapes for 3 weeks. Ex-animals were forced to run on a treadmill once a day for 3 consecutive weeks. Open field (OF) and elevated plus maze (EPM) tests were used to evaluate anxiety behaviors. The hippocampal expression of early neurogenesis markers, doublecortin, and sex determining region Y-box 2, were measured using real-time-PCR. Ex and EE animals separately did not show any significant performance in reducing anxiety levels, neither in EPM nor in OF compared with the control group. When animals were treated with EE and Ex simultaneously, they showed significantly reduced anxiety in both EPM and OF tests compared with the control as well as Ex and EE groups separately. Both treatments in combination were also more effective than individual groups in increasing the neurogenesis molecular markers within the hippocampus. This study proposes that Ex in combination with cognitive engagement is more efficient in alleviating anxiety responses and that can develop a nonpharmacological and multidomain policy that may prevent or delay psychophysiological symptoms.
Insights into the genome of Azotobacter sp. strain CWF10, isolated from an agricultural field in Central India, India
Authors: Roy Arindam , Ghosh Anwesha , Yash Yash , Mehra Prateeksha , Roy Sumit , Bhadury Punyasloke
Published: December 2024

Azotobacter sp. strain CWF10, an aerobic gram negative, oval shaped and motile bacterium, was isolated from a lateritic agricultural soil of Madhya Pradesh, India. The draft genome of the isolate is 5.7 Mb in size, consisting of 14 contigs with 65.09 % G+C content. Average nucleotide identity (94.66%) and digital DNA-DNA hybridization (62%) calculation with closest reference strains underpin the bacterium as a potential novel species. The bacterium has a plethora of plant growth promoting genes that point towards potential ability for enhancement of available nitrogen, biosynthesis of folic acid, among others. Siderophores such as vibrioferrin and crochelin A are also present in the genome which are known to regulate iron uptake. Overall, mining of the genome of Azotobacter sp. strain CWF10 has revealed the potential of this strain for application in regenerative agriculture and sustaining soil health.
Clinical Utility of Bone Turnover Markers in Chronic Kidney Disease
Authors: Srisuwarn Praopilad , Eastell Richard , Salam Syazrah
Published: December 2024

Chronic kidney disease (CKD) often leads to mineral and bone disorders (CKD-MBDs), which are nearly universal in patients undergoing dialysis. CKD-MBD includes abnormal calcium-phosphate metabolism, vascular and soft tissue calcification, and bone abnormalities (renal osteodystrophy [ROD]). Bone fragility in CKD occurs due to low bone mass and poor bone quality, and patients with CKD have higher fracture and mortality rates. Bone histomorphometry is the gold standard for ROD diagnosis; however, it is labor-intensive and expensive. The Kidney Disease Improving Global Outcomes clinical practice guidelines on CKD-MBD suggest serum parathyroid hormone (PTH) and bone-specific alkaline phosphatase (bone ALP) for predicting bone turnover in ROD. In this review, we focus on the role of PTH and bone turnover markers, intact procollagen type N-terminal propeptide of type I collagen, bone ALP, and tartrate-resistant acid phosphatase 5b in diagnosing ROD, predicting fractures, and guiding treatment in patients with CKD.
Unraveling Hepatic and Caval Flow to Improve Surgical Planning and Assessment in Fontan Patients via Novel 4D Flow CMR and CFD Methods
Authors: Sahni Akshita , Kannojiya Vikas , St. Clair Nicole , Hoganson David M. , Hammer Peter E. , del Nido Pedro J. , Rathod Rahul H. , Govindarajan Vijay
Published: December 2024

The Fontan procedure, a palliative surgery for single-ventricle heart defects, creates a non-physiological circulation that often leads to complications such as pulmonary arteriovenous malformations (PAVMs), thrombosis, and energy loss. As the number of Fontan patients surviving into adulthood continues to grow, precise understanding and improved monitoring of patient-specific hemodynamics is critical for long-term management. Two key challenges hinder progress: 1) the lack of a reliable method to quantify hepatic flow distribution (HFD) from post-operative imaging, a critical determinant of outcomes, and 2) the absence of a validated, patient-specific computational fluid dynamics (CFD) workflow to guide surgical personalization.

This study addresses these gaps by integrating a novel 4D Flow CMR-based particle tracking algorithm with an image-based CFD workflow to quantify and predict Fontan hemodynamics, including HFD, validated with in-vivo data. The 4D Flow-based particle tracking algorithm offers a precise, non-invasive tool for visualizing HFD, demonstrating excellent agreement with phase-contrast MRI (< 5% deviation). Patient-specific CFD models further predicted flow dynamics with high accuracy, validated against in vivo data (< 8% deviation).

Using this integrated workflow, we uncovered uneven mixing between the inferior vena cava and hepatic blood flow, challenging assumptions of uniform mixing and highlighting the critical role of local flow dynamics in determining long-term outcomes. By enabling non-invasive assessment and improved surgical planning, this validated CFD workflow, combined with 4D Flow particle tracking, offers immediate clinical application. With CFD-based surgical planning gaining traction, this approach establishes a new standard for personalized management for patients undergoing treatment for congenital heart diseases.

This study presents a validated workflow integrating 4D Flow CMR and patient-specific CFD to accurately quantify hepatic flow distribution and enhance surgical planning, addressing key challenges in the treatment and long-term management of Fontan patients with single-ventricle disease.
Magnetically induced magnetosome chain (MAGiC): A biogenic magnetic-particle-imaging tracer with high performance and navigability
Authors: Li Lei , Zhao Chan , Zhao Zhiyuan , Han Dou , Liao Yidong , Liu Yanjun , Liu Sijia , Jia Xiaohua , Tian Jiesheng , Liu Qing , Feng Xin , Tian Jie
Published: December 2024

Magnetic particle imaging (MPI) enables real-time, sensitive and quantitative visualization of magnetic tracers’ spatial distribution, augmenting the capability of in vivo imaging technologies. Previous tracer studies in MPI have primarily focused on superparamagnetic nanoparticles; however, their non-ideal sigmoidal magnetization response limits the spatial resolution. Here we demonstrate the utilization of magnetically induced magnetosome chain (MAGiC) as a novel superferromagnetic MPI tracer, exhibiting a 25-fold improvement in resolution and a 91-fold enhancement in signal intensity compared to the commercial tracer VivoTrax+™. The spatial resolution of MPI was pushed to an unprecedented 80 μm under a 4 T/m gradient field. Additionally, MAGiC can be precisely controlled using magnetic fields, enabling it to function as a MPI trackable microrobot. We provided a theoretical model elucidating MAGiC’s unique properties, and validated its imaging and actuation performance through phantom studies and in vivo experiments. As a high-performance MPI tracer and magnetic microrobot with exceptional capabilities, MAGiC holds tremendous potential for diverse applications including cell tracking, targeted drug delivery as well as therapeutic interventions.
Going beyond cell clustering and feature aggregation: Is there single cell level information in single-cell ATAC-seq data?
Authors: Kwok Aaron Wing Cheung , Shim Heejung , McCarthy Davis J
Published: December 2024

1

Single-cell Assay for Transposase Accessible Chromatin with sequencing (scATAC-seq) has become a widely used method for investigating chromatin accessibility at single-cell resolution. However, the resulting data is highly sparse with most data entries being zeros. As such, currently available computational methods for scATAC-seq feature a range of transformation procedures to extract meaningful information from the sparse data. Most notably, these transformations can be categorized into: 1) feature aggregation with known biological associations, 2) pseudo-bulking cells of similar biology, and 3) binarisation of count data. These strategies beg the question of whether or not scATAC-seq data actually has usable single-cell and single-region information as intended from the assay. If we can go beyond aggregated features and pooled cells, it opens up the possibility of more complex statistical tasks that require that degree of granularity. To reach the finest possible resolution of single-cell, single-region information there are inevitably many computational challenges to overcome. Here, we review the major data analysis challenges lying between raw data readout and biological discovery, and discuss the limitations of current data analysis approaches. Lastly, we conclude that chromatin accessibility profiling at true single-cell resolution is not yet achieved with current technology, but that it may be achieved with promising developments in optimising the efficiency of scATAC-seq assays.
New insight into erythema reduction induced by quercetin metal ions chelates
Authors: Bolaño Alvarez Alain , Arvesen Kristian B. , Hjuler Kasper F. , Bjerring Peter , Petersen Steffen B.
Published: December 2024

In dermatology, chelates play a significant role in skin care and treatment of skin diseases. Chelates involve coordination bonding between metal ions and organic molecules such as flavonoids. Quercetin (Q) is an extensively studied natural flavonoid with proven safety and anti-inflammatory properties. This study shows the role of two biocompatible metal ions, Iron (Fe2+) and Copper (Cu2+) in coordination bonding withQin 2-Propanol 50% and 80% at 1:1 stoichiometry. Our results show that chelation involves the hydroxyl groups and occurs by coordination ofCu2+toQfor the Ring A-B (Benzoyl group) resulting in a fluorescence emission peak at 530nm from the Ring B-C (Cinnamoyl group). This chelatesQ+Cu2+reduces mechanically induced erythema in the skin (Tanned type). A similar effect was observed in the chelateQ+Fe2+where the coordination ofFe2+toQoccurs for the cinnamoyl group resulting in an emission peak at 425nm from Benzoyl group ofQ. The statistical analysis shows significant differences in the effects ofQ+Cu2+(p-value = 0.00001),Q+Fe2+(p-value = 0.0003) respect toQas well as between them (p-value =0.0029). Our results suggest that the interaction betweenQand metal ions plays a central role in the inflammatory pathway. We conclude that the anti-inflammatory properties ofQwere enhanced by bothQ+Fe2+andQ+Cu2+chelates, highlighting the effect ofQ+Fe2+where the hydroxyl groups available in the cinnamoyl group of theQmolecule are the main intermediates to interact withFe2+, which is a requirement to trigger the anti-inflammatory molecular events ofQmolecules.
Differing genetics of saline and cocaine self-administration in the hybrid mouse diversity panel
Authors: Khan Arshad H. , Bagley Jared R. , LaPierre Nathan , Gonzalez-Figueroa Carlos , Spencer Tadeo C. , Choudhury Mudra , Xiao Xinshu , Eskin Eleazar , Jentsch James D. , Smith Desmond J.
Published: December 2024

To identify genes involved in regulating the behavioral and brain transcriptomic response to the potentially addictive drug cocaine, we performed genome-wide association studies (GWASs) for intravenous self-administration of cocaine or saline (as a control) over 10 days using a panel of inbred and recombinant inbred mice. A linear mixed model increased statistical power for these longitudinal data and identified 145 loci for responding when saline only was delivered, compared to 17 for the corresponding cocaine GWAS. Only one locus overlapped. Transcriptome-wide association studies (TWASs) using RNA-Seq data from the medial frontal cortex and nucleus accumbens identified5031434O11RikandZfp60as significant for saline self-administration. Two other genes,Myh4andNpc1, were nominated based on proximity to loci for multiple endpoints or acislocus regulating expression. All four genes have previously been implicated in locomotor activity. Our results indicate distinct genetic bases for saline and cocaine self-administration, and suggest some common genes for saline self-administration and locomotor activity.
Neurotransmitter loaded DNA nanocages as potential therapeutics for α-synuclein based neuropathies in cells andin vivo
Authors: Vaswani Payal , Kansara Krupa , Kumar Ashutosh , Bhatia Dhiraj
Published: December 2024

Parkinson’s disease is one of the neuropathies characterized by accumulation of α-synuclein protein, leading to motor dysfunction. Levodopa is the gold standard treatment, however, in long term usage, it leads to levodopa induced dyskinesia (LID). New therapeutic options are need of the hour to treat the α-synuclein based neuropathies. The role of imbalance of neurotransmitters other than dopamine has been underestimated in α-synuclein based neuropathies. Here, we explore the role of serotonin, epinephrine and norepinephrine as a therapeutic moiety. For the efficientin vivodelivery, we use DNA nanotechnology-based DNA tetrahedra that has shown the potential to cross the biological barriers. In this study, we explore the use of DNA nanodevices, particularly DNA tetrahedron functionalized with neurotransmitters, as a novel therapeutic approach for MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced Parkinson’s disease in PC12 cellular system. We first establish the effect of these nanodevices on clearance of α-synuclein protein in cells. We follow the study by understanding the various cellular processes like ROS, iron accumulation and lipid peroxidation. We also explore the effect of the neurotransmitter loaded nanodevices inin vivozebrafish model. We show that neurotransmitter loaded DNA nanocages can potentially clear the MPTP induced α-synuclein aggregates in cells andin vivo. The findings of these work open up new avenues for use of DNA nanotechnology by functionalizing it with neurotransmitters for future therapeutics in treatment of neurodegenerative diseases such as Parkinson’s disease.

TOC

TD:NT can clear α-synuclein by targeting the ferroptosis pathway.
Human genetic variation reveals FCRL3 is a lymphocyte receptor forYersinia pestis
Authors: Keener Rachel M. , Shi Sam , Dalapati Trisha , Wang Liuyang , Reinoso-Vizcaino Nicolás M , Luftig Micah A. , Miller Samuel I. , Wilson Timothy J. , Ko Dennis C.
Published: December 2024

Yersinia pestisis the gram-negative bacterium responsible for plague, one of the deadliest and most feared diseases in human history. This bacterium is known to infect phagocytic cells, such as dendritic cells and macrophages, but interactions with non-phagocytic cells of the adaptive immune system are frequently overlooked despite the importance they likely hold for human infection. To discover human genetic determinants ofY. pestisinfection, we utilized nearly a thousand genetically diverse lymphoblastoid cell lines in a cellular genome-wide association study method called Hi-HOST (High-throughput Human in-vitrO Susceptibility Testing). We identified a nonsynonymous SNP, rs2282284, inFc receptor like 3 (FCRL3) associated with bacterial invasion of host cells (p=9×10-8).FCRL3belongs to the immunoglobulin superfamily and is primarily expressed in lymphocytes. rs2282284 is within a tyrosine-based signaling motif, causing an asparagine-to-serine mutation (N721S) in the most common FCRL3 isoform. Overexpression of FCRL3 facilitated attachment and invasion of non-opsonizedY. pestis.Additionally, FCRL3 colocalized withY. pestisat sites of cellular attachment, suggesting FCRL3 is a receptor forY. pestis.These properties were variably conserved across the FCRL family, revealing molecular requirements of attachment and invasion, including an Ig-like C2 domain and a SYK interaction motif. Direct binding was confirmed with purified FCRL5 extracellular domain. Following attachment, invasion ofY. pestiswas dependent on SYK and decreased with the N721S mutation. Unexpectedly, this same variant is associated with risk of chronic hepatitis C virus infection in BioBank Japan. Thus,Y. pestishijacks FCRL proteins, possibly taking advantage of an immune receptor to create a lymphocyte niche during infection.
Ultrasensitive tuning of cytoplasmic viscosity via active noise
Authors: Zhao Ziming , Lin Jie
Published: December 2024

The mechanical properties of cytoplasm are crucial for cellular functions. While active processes significantly alter cytoplasmic viscoelasticity, the physical mechanisms remain elusive. Here, we model the cytoplasm as a colloidal suspension subject to passive and active noise, coarse-grained as an effective temperature. We show that a jammed cytoplasm transitions from a solid to a liquid phase at a critical effective temperature. Intriguingly, the simulated complex shear modulus at the critical state exhibits a 1/2 power-law scaling with frequency and quantitatively matches the experimental data of live cells without fitting parameters, given that the cytoplasmic volume fraction is slightly above the jamming transition. We further reveal the biological significance for the cytoplasm to be slightly above jamming: it is a regime in which the viscosity is ultrasensitive to changes in the effective temperature. Our results suggest that cells actively regulate their volume fractions in the sensitive regime in which they can tune cytoplasmic viscosity efficiently via active processes.
Dispersal evolution can only rescue a limited set of species from climate change
Authors: Kamal Peter , Thompson Patrick L. , Lewis Natalie , Fronhofer Emanuel A.
Published: December 2024

LAY SUMMARY

Global biodiversity is under threat from climate change. A key process for understanding species’ responses to climate change is dispersal: the movement of an individual to reproduce somewhere other than its birthplace. Dispersal allows species to shift their range to more suitable habitats when conditions change. In addition, dispersal can evolve rapidly, especially during such range shifts. Here, we explore whether rapid dispersal evolution can save species from climate change. We identify a small set of cases in which this is theoretically possible. Our results outline general characteristics of species and their environments that make such rescue possible and therefore aid both with our fundamental understanding and applied conservation measures.
NicheTrans: Spatial-aware Cross-omics Translation
Authors: Wang Zhikang , Lin Senlin , Zou Qi , Cui Yan , Han Chuangyi , Li Yida , Li Jianmin , Zhao Yi , Gao Rui , Song Jiangning , Yuan Zhiyuan
Published: December 2024

Spatial omics technologies have revolutionized our studies on tissue architecture and cellular interactions at single-cell resolution. While spatial multi-omics approaches offer unprecedented insights into complex biological systems, their widespread adoption is hindered by technical challenges, specialized requirements, and limited accessibility. To address these limitations, we present NicheTrans, the first spatially-aware cross-omics translation method and a flexible Transformer-based multi-modal deep learning framework. Unlike existing single-cell (non-spatial) translation methods, NicheTrans uniquely incorporates both cellular microenvironment information and flexible integration of multi-modal data, such as morphology and prior knowledge. We validated NicheTrans across diverse biological cases: Parkinson’s Disease (PD), Alzheimer’s Disease (AD), breast cancer, and lymph nodes. Our approach demonstrated superior performance compared to existing single-cell methods, highlighting the crucial role of spatial and multi-modal information in cross-omics translation. Through NicheTrans, we uncovered spatial multi-omics domains that were not detectable through single-omics analysis alone. Model interpretation revealed key molecular relationships, including gene programs associated with dopamine metabolism and amyloid β-associated cell states. Additionally, using translated protein markers as spatial landmarks, we quantified the spatial organization of key glial cell subtypes in the AD brain. NicheTrans represents a powerful tool for generating comprehensive spatial multi-omics insights from more accessible single-omics measurements, making multi-omics analysis more feasible for the broader research community.
Time-of-day related fluctuations of self-belief formation
Authors: Mayer Annalina V. , Schröder Alexander , Czekalla Nora , Müller-Pinzler Laura , Rosenbusch Laura , Paulus Frieder M. , Oster Henrik , Sayk Clara , Kammerer Mathias , Wilhelm-Groch Ines , Krach Sören
Published: December 2024

Time of day influences a variety of human cognitive processes, including attention, executive functions and memory formation, as well as affective experiences and mood. However, circadian modulations of self-related learning and belief formation, which are highly affected by emotional states, remain poorly understood.

Here, we present results from exploratory post-hoc analyses on data aggregated from five studies assessing the formation of self-related ability beliefs. A total ofN=242 healthy participants completed a validated learning task at different times of the day, during which they continuously received feedback on their performance. Computational modeling was applied to quantify participants’ learning behavior during the task.

Results suggest an association between time-of-day and self-belief formation, showing that participants who were tested in the evening (7:00-9:59 p.m.) updated their self-beliefs more strongly in response to the received feedback compared to those tested in the afternoon (1:00-3:59 p.m.). Evidence from additional models indicated that these differences were driven by non-linear, rhythmic changes in self-belief formation across different times of the day.

Future studies should systematically examine within-subject fluctuations in self-belief formation across the day and address the influence of individual factors such as chronotype, age, mood and sleep quality. Understanding circadian modulations of self-related belief formation could contribute to optimized interventions for conditions characterized by maladaptive self-beliefs, such as depression, as well as in academic contexts.
Humoral correlate of vaccine-mediated protection from tuberculosis identified in humans and non-human primates
Authors: Kelkar Natasha S. , Curtis Nicholas C. , Lahey Timothy P. , Wieland-Alter Wendy , Stout Jason E. , Larson Erica C. , Jauro Solomon , Scanga Charles A. , Darrah Patricia A. , Roederer Mario , Seder Robert A. , von Reyn C. Fordham , Lee Jiwon , Ackerman Margaret E.
Published: December 2024

Development of an effective tuberculosis (TB) vaccine has been challenged by incomplete understanding of specific factors that provide protection againstMycobacterium tuberculosis(Mtb) and the lack of a known correlate of protection (CoP). Using a combination of samples from a vaccine showing efficacy (DarDar [NCT00052195]) and Bacille Calmette-Guerin (BCG)- immunized humans and nonhuman primates (NHP), we identify a humoral CoP that translates across species and vaccine regimens. Antibodies specific to the DarDar vaccine strain (M. obuense) sonicate (MOS) correlate with protection from the efficacy endpoint of definite TB. In humans, antibodies to MOS also scale with vaccine dose, are elicited by BCG vaccination, are observed during TB disease, and demonstrate cross-reactivity with Mtb; in NHP, MOS-specific antibodies scale with dose and serve as a CoP mediated by BCG vaccination. Collectively, this study reports a novel humoral CoP and specific antigenic targets that may be relevant to achieving vaccine-mediated protection from TB.
Parkinson’s disease-associated Pink1 loss disrupts vesicle trafficking in Ensheathing glia causing dopaminergic neuron synapse loss
Authors: Ghezzi Lorenzo , Pech Ulrike , Schoovaerts Nils , Poovathingal Suresh , Davie Kristofer , Lamote Jochen , Praschberger Roman , Verstreken Patrik
Published: December 2024

Parkinson’s disease (PD) is commonly associated with the loss of dopaminergic neurons in thesubstantia nigra, but many other cell types are affected even before neuron loss occurs. Recent studies have linked oligodendrocytes to early stages of PD, though their precise role is still unclear.Pink1is mutated in familial PD and through unbiased single-cell sequencing of the entire brain ofDrosophila Pink1models, we observed significant gene deregulation in ensheathing glia (EG); cells that share functional similarities with oligodendrocytes. We found that the loss ofPink1leads to the activation of EG, similar to the reactive response of EG seen upon nerve injury. Using cell-type specific transcriptomics, we identified deregulated genes in EG as potential functional modifiers. Specifically, downregulating two trafficking factors, Rab7 and Vps13, also mutated in PD, or the direct regulators of Rab7, Mon1 and Ccz1, specifically in EG was sufficient to rescue neuronal function and protect against dopaminergic synapse loss. Our findings demonstrate that Pink1 loss in neurons triggers an injury response in EG, and that Pink1 loss in EG in turn disrupts neuronal function. Vesicle trafficking components, which regulate membrane interactions between organelles within EG, play a crucial role in maintaining neuronal health and preventing dopaminergic synapse loss. Our work highlights the essential role of glial support cells in the pathogenesis of PD and identifies vesicle trafficking within these cells as a key point of convergence in disease progression.
Early identification of Family Medicine residents at risk of failure using Natural Language Processing and Explainable Artificial Intelligence
Authors: Joshi Abhisht , Mortezaagha Pouria , Inkpen Diana , Seale Edward , Archibald Douglas , Noel Kendall , Rahgozar Arya
Published: December 2024

Background

During residency, each resident is observed and receives feedback based on their performance. Residency training is demanding, with a few residents struggling in their academic performance. A competency-based residency training program’s success depends on its ability to identify residents with difficulty during their first year of post-graduate education and to provide them with timely intervention and support.

Objective

In large training programs such as Family Medicine, identifying residents at risk of failing their certification exams is difficult. We develop a AI system using state-of-the-art technologies in Machine Learning (ML), Deep Learning (DL), Natural Language Processing (NLP) and Explainable AI (XAI) to detect at-risk residents automatically.

Methods

We implemented ML, DL and NLP models for the prediction and its performance analysis. The target variable chosen for the prediction was the determination of whether the resident would fail or pass their certification exam. XAI was used to enhance the understanding of the model’s inner workings.

Results

In total, there were 1382 data points of residents. The champion model, Support Vector Machine (SVM), achieved an accuracy of 89.05% and an F1 score of 74.54 for the multiclass classification when multimodal (text and tabular) data was used. This model outperformed the models that only used qualitative or quantitative data exclusively.

Conclusion

Combining qualitative and quantitative data represents a novel approach and has provided better classification results. This research demonstrates the feasibility of an automated AI system for the early identification of residents at risk of academic struggle.
Optimal Control Strategies for Mitigating Antibiotic Resistance: Integrating Virus Dynamics for Enhanced Intervention Design
Authors: Dere Zainab , Cogan N. G. , Karamched Bhargav R.
Published: December 2024

Given the global increase in antibiotic resistance, new effective strategies must be developed to treat bacteria that do not respond to first or second line antibiotics. One novel method uses bacterial phage therapy to control bacterial populations. Phage viruses replicate and infect bacterial cells and are regarded as the most prevalent biological agent on earth. This paper presents a comprehensive model capturing the dynamics of wild-type bacteria (S), antibiotic-resistant bacteria (R), and infective (I) strains, incorporating virus inclusion. Our model integrates biologically relevant parameters governing bacterial birth rates, death rates, and mutation probabilities and incorporates infection dynamics via contact with a virus. We employ an optimal control approach to study the influence of virus inclusion on bacterial population dynamics. Through numerical simulations, we establish insights into the stability of various system equilibria and bacterial population responses to varying infection rates. By examining the equilibria, we reveal the impact of virus inclusion on population trajectories, describe a medical intervention for antibiotic-resistant bacterial infections through the lense of optimal control theory, and discuss how to implement it in a clinical setting. Our findings underscore the necessity of considering virus inclusion in antibiotic resistance studies, shedding light on subtle yet influential dynamics in bacterial ecosystems.
Effectiveness of the PAS Scale for Diagnosing the Severity of Acute Appendicitis in Children: A Cohort Study
Authors: Edgar Sucso-Noa
Published: December 2024

What’s Known on This Subject

Appendicitis is an acute inflammatory process that affects the appendix, one of the common causes of abdominal pain in children in emergency. Being one of the most common conditions faced by surgeons.

The PAS scale, a clinical score for acute appendicitis, is among the most popular for use in children for diagnosis. The severity of appendicitis subclassified as simple appendicitis (congested or suppurated) vs complicated appendicitis (gangrenous or perforated) could be predicted with a PAS scale ≥8.

What This Study Adds

Tests logistic regression models as a basis for developing more complex models to improve prediction of complicated acute appendicitis in children.

Background

The Pediatric Appendicitis Score (PAS) is a highly utilized diagnostic tool for acute appendicitis in pediatric patients. The severity of appendicitis subclassified as simple appendicitis (congested or suppurated) vs complicated appendicitis (gangrenous or perforated) could be predicted with a PAS scale ≥8.

Methods

The type of study of the present research, according to Altman Douglas, is: Observational, Retrospective y Longitudinal. The design is cohort-type. The population was evaluated, 86 children aged 4-14 years with a preoperative diagnosis of appendicitis, grouped into 2 groups: complicated appendicitis (43) and simple appendicitis (43) exposed to the PAS≥8 or PAS 8.

Results

The effectiveness of the PAS≥8 scale for diagnosing the severity of appendicitis showed a predictive diagnostic accuracy of 59.3% and increases the likelihood of severity by 2.246 times (CI:95% 0.917-5.50 p=0.077) in the predictive model. There were statistically significant differences in cough/hop/percussion Tenderness, migration of pain, anorexia, leukocytosis and neutrophilia, between scale PAS≥8 vs PAS<8.

Conclusion

The PAS≥8 scale alone is not sufficient to diagnose the severity of acute appendicitis, with 59.3% predictive diagnostic accuracy and increasing the likelihood of presenting the severity of appendicitis by 2.246 times.
The ratio of plasma pTau217 to Aβ42 outperforms individual measurements in detecting brain amyloidosis
Authors: Lehmann Sylvain , Gabelle Audrey , Duchiron Marie , Busto Germain , Morchikh Mehdi , Delaby Constance , Hirtz Christophe , Mondesert Etienne , Cristol Jean-Paul , Barnier-Figue Genevieve , Perrein Florence , Turpinat Cédric , Jurici Snejana , Bennys Karim ,   the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: December 2024

IMPORTANCE

Early detection of brain amyloidosis (Aβ+) is pivotal for diagnosing Alzheimer’s disease (AD) and optimizing patient management, especially in light of emerging treatments. While plasma biomarkers are promising, their combined diagnostic value through specific ratios remains underexplored.

OBJECTIVE

To evaluate the diagnostic accuracy of plasma pTau isoform (pTau181 and pTau217) to Aβ42 ratios in detecting Aβ+ status.

DESIGN, SETTING, AND PARTICIPANTS

This study included 423 participants from the multicenter prospective ALZAN cohort, recruited for cognitive complaints. Aβ+ status was determined using cerebrospinal fluid (CSF) biomarkers. Validation of the key findings was performed in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort, where Aβ+ status was determined using PET imaging.

EXPOSURES

Plasma biomarkers (pTau181, pTau217, Aβ40, Aβ42) were measured using immunoassays and mass spectrometry, with specific ratios calculated. In the ALZAN cohort, the impact of confounding factors such as age, renal function, ApoE4 status, body mass index, and the delay between blood collection and processing was also evaluated to assess their influence on biomarker concentrations and diagnostic performance.

MAIN OUTCOMES AND MEASURES

The primary outcome was the diagnostic performance of plasma biomarkers and their ratios for detecting Aβ+ status. Secondary outcomes included the proportion of patients classified as low, intermediate, or high risk for Aβ+ using a two-cutoff approach.

RESULTS

The pTau181/Aβ42 ratio matched the diagnostic performance of pTau217 with AUC of 0.911 (0.880-0.936). The pTau217/Aβ42 ratio demonstrated the highest diagnostic accuracy in the ALZAN cohort, with an AUC of 0.927 (0.898-0.950), outperforming individual biomarkers. Both ratios effectively mitigated confounding factors, such as variations in renal function, and were particularly excellent in identifying Aβ+ status in individuals with early cognitive decline. Validation in the ADNI cohort confirmed these findings, with consistent performance across different measurement methods. The two-cutoff workflow using pTau217/Aβ42 reduced the intermediate-risk zone from 16% to 8%, enhancing stratification for clinical decision-making.

CONCLUSIONS AND RELEVANCE

The pTau217/Aβ42 ratio offers superior diagnostic accuracy for detecting Aβ+ compared to individual biomarkers and reduces diagnostic uncertainty. These findings highlight the clinical utility of plasma biomarker ratios for early AD detection, paving the way for broader implementation in clinical and research settings.