bluuebunny/crossref_metadata_2025 huggingface dataset:
Tomato Brown Rugose Fruit Virus Nextstrain Build Version 4: Pathways of Introduction and Local Spread
Authors: de Koning Pier P. M. , Fowkes Aimee R. , Zisi Zafeiro , Beris Despoina , Oplaat Carla , McGreig Sam , Skelton Anna , Adams Ian P. , van Gemert Jerom , de Krom Christel , Visser Michael , Westenberg Marcel , van de Vossenberg Bart T. L. H. , Varveri Christina , Roenhorst Johanna W. , Schenk Martijn , Matthijnssens Jelle , Fox Adrian , Botermans Marleen
Published: October 2024

Tomato brown rugose fruit virus (ToBRFV; Tobamovirus fructirugosum) is a harmful virus significantly reducing yield and fruit quality in tomato. It was first detected in Israel and Jordan in 2015 and quickly reached a near-global distribution. Following the outbreak of ToBRFV in the Netherlands in 2019, the Dutch National Plant Protection Organization (NPPO-NL) created a Nextstrain build, which was updated in 2021 and 2023. Here, we announce the release of 82 new (near) complete ToBRFV genomes with associated metadata and the fourth version of the ToBRFV Nextstrain build, which has expanded from 179 to 336 (near) complete genomes. This ToBRFV Nextstrain build is a powerful tool for gaining more insight into the epidemiology of ToBRFV, i.e., on pathways of introduction and the spread and possible origin of the rapidly emerging clade 7 sequence type isolates. The ToBRFV Nextstrain build is available at https://nextstrain.nrcnvwa.nl/ToBRFV/20240205 .

[Formula: see text] Copyright © 2025 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Bridging the gap: neurodevelopmental disorder risks in inborn errors of immunity
Authors: Kurup Devika , FitzPatrick Amy M. , Badura Aleksandra , Serra Ines
Published: October 2024

Purpose of review

The aim of this review is to examine published reports of neurodevelopmental phenotypes in patients with inborn errors of immunity (IEI). We briefly discuss potential interactions between the immune and the central nervous system and the implications of this crosstalk for current clinical management guidelines.

Recent findings

An increasing number of reports have described neurodevelopmental disorders (NDDs) comorbid with immune-mediated signs. However, the prevalence of this association in IEIs remains unknown.

IEIs comprise a group of clinically heterogeneous disorders associated with a number of nonimmune comorbidities. Although certain neurological conditions such as microcephaly are recognized as associated features of some IEIs, NDDs are less well described. We reviewed published clinical descriptions of IEIs and found a number of comorbid NDDs in these patients, including autism spectrum disorder (ASD), behavioral deficits, and intellectual disability. Given the lack of uniform assessments for NDDs, we suspect they may be underdiagnosed in IEIs. As NDDs manifest early and can result in life-long cognitive and emotional deficits, which diminish quality of life and increase healthcare utilization, we hope to elucidate relevant pathomechanisms and raise clinician awareness of these comorbidities so appropriate and timely interventions are sought.
Bioequivalence and Pharmacokinetics of Intravenous Calcium during Cesarean Delivery
Authors: Ansari Jessica R. , Conti Daniel J. , Michel Guillermina , Yarmosh Alla , Cole Naida M. , Shafer Steven L.
Published: October 2024

Background:

Few studies have assessed the dose ratio of calcium gluconate to calcium chloride or defined the time course of change in serum ionized calcium concentration after intravenous injection.

Methods:

In a bioequivalence (dose ratio) trial, parturients undergoing cesarean delivery were randomly assigned to receive calcium chloride (0.5 g) or calcium gluconate (1.5 or 2 g) by 10-min intravenous infusion. Venous serum ionized calcium concentration was measured before calcium infusion and approximately 5, 10, 15, 30, and 60 min after infusion start. These data were combined with serum ionized calcium concentration measurements in parturients who received 1 g calcium chloride or saline placebo in two recent clinical trials to define the pharmacokinetics of intravenous calcium over the first hour during and after drug administration.

Results:

The bioequivalence study enrolled 34 participants, from whom were collected 181 serum ionized calcium concentration measurements. The dose ratio of calcium gluconate to calcium chloride was 3.11 (95% CI, 2.77 to 3.48). Population pharmacokinetics of calcium were determined using 311 serum ionized calcium concentration measurements from 70 parturients. The pharmacokinetics of intravenous calcium were described by a two-compartment model with systemic clearance of 0.18 (95% CI, 0.07 to 0.27) l/min, distributional clearance of 1.25 (95% CI, 1.03 to 1.56) l/min, central volume of 10.9 (95% CI, 9.3 to 12.6) l, and peripheral volume of 16.5 (95% CI, 12.5 to 24.7) l. After adjusting for the dose ratio, calcium gluconate and calcium chloride had identical time courses. A 1-g infusion of calcium chloride resulted in a peak increase in serum ionized calcium concentration of 0.39 (0.38 to 0.42 mM), which decreased by half (29 [23 to 40] min) after initiation of the 10-min infusion.

Conclusions:

This study confirmed a 3:1 dose ratio of calcium gluconate to calcium chloride and estimated the pharmacokinetics over the first hour after intravenous delivery. These data inform clinical care and may guide future trials assessing calcium efficacy to reduce bleeding in obstetric patients.
Association Among Surgeon Volume, Surgical Approach, and Uterine Size for Hysterectomy for Benign Indications
Authors: Santiago Sarah , Richardson Darington , Kamdar Neil , Till Sara R. , As-Sanie Sawsan , Hong Christopher X.
Published: October 2024

OBJECTIVE:

To assess the relationship between surgeon volume and surgical approach for patients undergoing hysterectomy for benign indications among uteri of varying sizes.

METHODS:

This was a retrospective cohort study of patients who underwent hysterectomy for benign indications from 2012 to 2021 within the Michigan Surgical Quality Collaborative registry. For each hysterectomy, the relative annual volume of the performing surgeon was assessed by calculating the proportion of hysterectomy cases contributed by the surgeon each calendar year relative to the total number of hysterectomies in the registry for that year. Hysterectomies were stratified into tertiles: those performed by low-volume surgeons, intermediate-volume surgeons, and high-volume surgeons. Uterine size was represented by the uterine specimen weight and categorized to facilitate clinical interpretation. Multivariable logistic regression models were developed incorporating interaction terms for surgeon volume and uterine size to explore potential effect modification.

RESULTS:

A total of 54,150 hysterectomies were included. Hysterectomies performed by intermediate- and high-volume surgeons were more likely to be performed through a minimally invasive approach compared with those performed by low-volume surgeons (intermediate-volume: adjusted odds ratio [aOR] 1.68, 95% CI, 1.47–1.92; high-volume: aOR 2.14, 95% CI, 1.87–2.46). Moreover, this likelihood increased with increasing uterine weight. For uteri weighing between 1,000 g and 1,999 g, the odds of minimally invasive approach was significantly higher among intermediate-volume surgeons (aOR 3.38, 95% CI, 2.04–5.12) and high-volume (aOR 9.26, 95% CI, 5.64–15.2) surgeons, compared with low-volume surgeons. After including an interaction term for uterine weight and surgeon volume, we identified effect modification of surgeon volume on the relationship between uterine size and choice of minimally invasive surgery.

CONCLUSION:

For uteri up to 3,000 g in weight, hysterectomies performed by high-volume surgeons have a higher likelihood of being performed through a minimally invasive approach compared with those performed by low-volume surgeons.
A Comparative Analysis of Postoperative Single Fraction of 9.5 Gy Versus 10 Gy for Ear Keloids
Authors: Kang Daihun , Ha Boram , Park Tae Hwan
Published: October 2024

BACKGROUND

The optimal radiotherapy doses for postoperative treatment of ear keloids are currently a topic of debate.

OBJECTIVE

The authors compared the efficacy of 9.5-Gy and 10-Gy single-fraction electron beam radiation therapy after surgical excision and evaluated the impact of radiation timing on outcomes.

MATERIALS AND METHODS

This study was conducted on patients with ear keloid who underwent surgical excision and postoperative electron beam radiotherapy between May 2021 and June 2024. Patients were divided into groups based on radiation dose (9.5 vs 10) and timing (within 8 hours vs 24 hours postoperatively). Recurrence rates and complications were also compared.

RESULTS

The study included 182 patients (21 men and 161 women). The overall recurrence rate was 3.3% (6/182). The 10-Gy group had a significantly lower recurrence rate than the 9.5-Gy group (0.81% vs 8.47%; p = .014). Radiation timing did not significantly influence recurrence rates (2.59% vs 3.80%, p = 1). Complications were not significantly different.

CONCLUSION

A postoperative single dose of 10 Gy is the most effective low-dose single fractional electron beam radiotherapy for preventing ear keloid recurrence. Once administered within 24 hours after surgery, the timing of radiotherapy has no significant impact on treatment outcomes.
Norharmane potentiated anxiolytic- and antidepressant-like responses induced by imipramine and citalopram: an isobologram analysis
Authors: Khakpai Fatemeh
Published: October 2024

β-carboline compounds display a therapeutic property for treating depression and anxiety behaviors. Imipramine and citalopram play an important role in the modulation of anxiety and depression behaviors. We investigated the effects of norharmane, imipramine, and citalopram on anxiety- and depression-like effects and their interactions. Elevated plus maze and forced swimming test were used for the assessment of anxiety- and depression-like behaviors in male mice. The results revealed that intraperitoneal (i.p.) administration of norharmane (10 mg/kg) increased percentage of open arm time (%OAT) in the elevated plus maze test and decreased immobility time in the forced swimming test, proposing anxiolytic- and antidepressant-like effects. Injection of imipramine (5 mg/kg; i.p.) enhanced %OAT and decreased immobility time, suggesting anxiolytic- and antidepressant-like effects. Moreover, norharmane potentiated the anxiolytic- and antidepressant-like responses induced by imipramine by increasing %OAT and decreasing immobility time. The results revealed additive anxiolytic- and antidepressant-like effects between norharmane and imipramine in mice. Alone, the administration of citalopram (5 mg/kg; i.p.) enhanced %OAT and reduced immobility time, causing anxiolytic- and antidepressant-like effects. When citalopram and norharmane were coinjected, norharmane augmented the anxiolytic- and antidepressant-like effects induced by citalopram by increasing %OAT and reducing immobility time. These results indicated additive anxiolytic- and antidepressant-like effects between norharmane and antidepressant drugs such as imipramine and citalopram on the modulation of anxiety and depression processes in mice.
Scaphocapitate Arthrodesis for Wrist Deformities: A Systematic Review
Authors: Deptula Peter , McCullough Meghan , Brown Theodore , Singh Dylan , Kuschner Stuart , Kulber David
Published: October 2024

Background:

Scaphocapitate arthrodesis (SCA) is a described technique for chronic wrist pathology such as Kienbock disease and carpal instability. The technique aims to preserve motion, while maintaining carpal height, preserving the radioscaphoid articulation, and offloading the lunate. Limited case series evaluate the outcomes of this previously described technique. We aim to determine if the collective, updated literature on outcomes of SCA support its continued application by the wrist surgeon. Furthermore, we investigated if any technical variations offer an advantage in improving patient-reported outcomes after SCA.

Methods:

A literature search was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles selected for critical review were examined for patient demographic data, functional outcomes, radiographic outcomes, and complications. A qualitative analysis was then performed to synthesize the available date.

Results:

A total of 18 unique articles published between 1991 and 2022 were identified, representing a total of 285 individual cases of SCA. Nonunion rate ranged 0%–22%. Preoperative visual analog scale pain scores ranged from 3.2 to 10, whereas postoperative visual analog scale pain scores ranged from 0 to 4. Patient-reported outcomes are reported by validated instruments, including the Disabilities of the Arm, Shoulder, and Hand, QuickDASH, Patient-rated Wrist Evaluation, and Mayo Wrist Score.

Conclusions:

SCA is a viable treatment option for patients with Kienbock disease. SCA offers reliable improvements in patient pain, grip strength, and patient-reported outcomes.
Accelerated Agony
Authors: Kattamuri Lakshmi Prasanna Vaishnavi , Senapati Sidhartha Gautam , Vulisha Abhinav , Rao Sheldon
Published: October 2024

This case report discusses a 39-year-old male with advanced HIV infection presenting with fever, weight loss, and respiratory symptoms, ultimately succumbing to fulminant pulmonary coccidioidomycosis. Despite initial empirical treatment for bacterial pneumonia and Pneumocystis jirovecii, the patient's condition rapidly deteriorated, highlighting the diagnostic challenges posed by this fungal infection, especially in immunocompromised individuals. Diagnostic confirmation was complicated by nonspecific clinical features, overlapping symptoms with other opportunistic infections, and unreliable serological tests. Radiological findings resembled those of other pulmonary infections, further complicating timely diagnosis. Delayed recognition of disseminated coccidioidomycosis contributed to the patient's poor prognosis. Antifungal therapy, primarily azoles, remains the cornerstone of management, with prognosis worsening with additional dissemination sites and advanced HIV illness. This case underscores the importance of considering pulmonary coccidioidomycosis in immunocompromised patients presenting with respiratory symptoms, particularly in endemic regions.
Mobility Loss in Hospitalized Adults Predicts Poor Clinical Outcomes
Authors: Rogers Stephanie E. , Mulvey Jade , Turingan Roniela , Coco L. Maurine , Hubbard Colin C. , Binford Sasha , Harrison James D.
Published: October 2024

Background:

The Johns Hopkins Activity and Mobility Program is a systematic approach to measure and improve patient mobility.

Purpose:

The purpose of this study was to evaluate the relationship between mobility loss and quality outcomes.

Methods:

A retrospective cohort study design was used. Patients were categorized into 3 groups (gain, loss, no change in mobility) using the Johns Hopkins Highest Level of Mobility (JH-HLM) scores. The association between mobility loss and falls risk, in-hospital mortality, delirium, discharge to a facility, length of stay, and 30 day readmissions were assessed.

Results:

Those who lost mobility were more at risk of being a high fall risk, in-hospital mortality, delirium, discharging to a facility, and had 48% longer lengths of stay. There was no association between mobility loss and 30-day readmissions.

Conclusions:

Loss of mobility assessed using JH-HLM scores is associated with worse patient outcomes.
Effects of Hurricanes and the Coronavirus Disease 2019 (COVID-19) Pandemic on Cervical Cancer Diagnosis in Puerto Rico
Authors: Santiago-Rodríguez Eduardo J. , Ramos Tonatiuh Suárez , Ramos-Cartagena Jeslie M. , Torres-Cintrón Carlos R. , Deshmukh Ashish A. , Ortiz-Ortiz Karen J. , Ortiz Ana P.
Published: October 2024

This cross-sectional study evaluated the effects of hurricanes and the coronavirus disease 2019 (COVID-19) pandemic on the diagnosis of cervical cancer in Puerto Rico. Interrupted time series analysis was performed on monthly counts of cases diagnosed between January 2012 and December 2021. Before the hurricanes, the number of cases diagnosed per month was stable, at an average of 20 (95% CI, 18–22). After the hurricanes (end of September 2017), diagnosed cases dropped by 62.1% and reached prehurricane levels in the subsequent 5 months. After the COVID-19 restrictions (April 2020), only one case was reported. In the subsequent months and up to the end of the study period (December 2021), an upward trend of diagnosed cases was observed, but cases did not reach pre–COVID-19 levels. Major events affected the diagnosis of cervical cancer in Puerto Rico. Potential detection delays warrant further evaluation.
Integrating Clay Modeling in Implant Fabrication for Craniofacial Defect
Authors: Fukuyama Sotatsu , Tang Pei-Chun , Lo Lun-Jou
Published: October 2024

Manufacturing craniofacial implants using 3-dimensional (3D) methods and computed tomography data has become popular. The image object for the defect is produced as the first step, followed by several methods to create the implant. The authors have used a novel method that combines clay modeling with 3D scanning to create implants for craniofacial contour reconstruction. This approach does not require complicated resources. The method allows for high customization and immediate modifications, resulting in implants that achieve an accurate fit and high patient satisfaction. It is particularly beneficial for addressing complex defects and achieving aesthetic improvements. In addition, it reduces the need for cumbersome digital processing and expensive materials, making it a practical and feasible solution for a wide range of craniofacial deformities.
Precise Localization of the Posterior Clinoid Process in the Fetal Skull Base
Authors: Öztürk Cansu , Şencan Zeynep , İnce Rümeysa , Çalişir Ebru Sena , Cihan Ömer Faruk , Beger Orhan
Published: October 2024

Objective:

To determine the precise position of the posterior clinoid process (PCP) in fetuses.

Materials and Methods:

Skull bases of 32 fetuses (11 males/21 females) aged 17 to 32 weeks in utero were included in the study. The distances of PCP to certain reference points were measured.

Results:

The distances of PCP to the foramen ovale, foramen rotundum, superior orbital fissure, anterior clinoid process, foramen magnum, and crista galli were measured as 7.70±1.86 mm, 6.99±1.65 mm, 6.07±1.85 mm, 3.85±1.10 mm, 15.34±3.38 mm, and 14.49±2.65 mm, respectively. All parameters were similar for both sides (P>0.05). Apart from the distance of PCP to the foramen magnum, the remaining parameters were similar for both genders. This parameter was greater in males than females (P=0.001). All parameters were greater in the third-trimester fetuses than the second-trimester fetuses. All parameters increased with advancing gestational weeks (P<0.001). Linear functions were calculated for the distances of PCP to the crista galli (y = 1.311 + 0.551 × age), to the foramen magnum (y = 0.086 + 0.638 × age), to the anterior clinoid process (y = −0.303 + 0.174 × age), to the superior orbital fissure (y = − 2.013 + 0.338 × age), to the foramen rotundum (y = 1.803 + 0.217 × age), and to the foramen ovale (y = 0.760 + 0.290 × age).

Conclusion:

The measured distances increased with growth. The linear functions displaying the growth dynamics of PCP-related parameters may be used to estimate the distances.
Correct patient identification and matching of adults in an ambulatory care setting: a best practice implementation project
Authors: Tran Louise Dung , Neil Bronwyn , Taylor Christine
Published: October 2024

Introduction:

Ambulatory care settings are at high risk for errors when identifying patients and matching them to their intended care.

Objective:

The objective of this project was to improve correct and consistent patient identification and matching to their intended care by nurses in ambulatory care settings.

Methods:

The seven-phase JBI Evidence Implementation Framework was used to guide this project. JBI tools were used to audit current practices and implement best practices in four ambulatory care units. The implementation plan included a baseline audit and two follow-up audits. Feedback was obtained through interviews with ambulatory care nursing staff, educational sessions were conducted for nursing staff, and unit guidelines were developed.

Results:

In the baseline audit, compliance with best practice criteria for patient matching and identification was below 62% for 7/13 criteria. After conducting education sessions and other strategies, 1/3 pre- and post-clinical intervention criteria improved in compliance, while 2 were unchanged. For blood product administration criteria, 2/5 improved, 1 was unchanged, and 2 were lower than baseline. Nurses’ education in patient identification procedures improved (1/1) and knowing where to access relevant policies remained unchanged at 100%. Criteria for patients knowing the importance of patient identification (2/2) and the identification band following national standards (1/1) improved from baseline.

Conclusions:

The results support the use of education sessions and infrastructure changes to promote and sustain change in evidence-based practice in ambulatory care units. Not all criteria improved, and the audit team identified strategies to improve the implementation of evidence-based practice in ambulatory care units.

Spanish abstract:

http://links.lww.com/IJEBH/A275
Ultrastructural Organization of the Honeybee Blood-Brain Barrier and Comparison with Age
Authors: Quigley Tyler , Amdam Gro
Published: October 2024

The blood-brain barrier is an essential feature of the most animal nervous systems, adapted to maintain brain homeostasis across species occupying unique and dynamic environments. Understanding the structural and functional diversity of animal blood-brain barriers can aid our understanding of how this structure contributes to important areas of neuroscience such as behavior, health, and disease. The honeybee worker is a well-established model for exploring these dimensions of brain function, however, the honeybee worker blood-brain barrier has yet to be described. Here, we present the first global anatomic analysis and description of the honeybee worker blood-brain barrier and compare key ultrastructural features between two age groups. We describe the cellular makeup of the honeybee worker blood-brain barrier, patterns of heterogeneity in barrier structure throughout the brain, and highlight important areas of further study.
Prenatal exposure to genocide accelerates epigenetic aging as measured in second-generation clocks among young adults
Authors: Uwizeye Glorieuse , Rivera Luisa M. , Stolrow Hannah G. , Christensen Brock C. , Rutherford Julienne N. , Thayer Zaneta M.
Published: October 2024

Prenatal exposure to trauma, including genocide and maternal rape, and adverse childhood experiences (ACEs), are associated with lifespan reduction. We evaluated whether prenatal exposure to genocide or genocidal rape, and ACEs among individuals conceived during the 1994 genocide against Tutsi in Rwanda were associated with differences in age acceleration in three first-generation (Horvath, Hannum, PhenoAge) and four second-generation epigenetic aging clocks (GrimAge, DunedinPace, YingDamAge, YingAdaptAge), given the association between biological aging and mortality. No differences in age acceleration were observed with first-generation age clocks. However, age acceleration was associated with prenatal exposure to extreme stress for all second-generation clocks, with the greatest acceleration observed in the genocidal rape conception group. For YingDamAge clock, acceleration effects were strengthened after inclusion of ACEs. We suggest that prenatal trauma exposure is associated with epigenetic age acceleration. Second-generation clocks may more accurately capture these relationships.
Role of MicroRNAs in Autosomal Dominant Polycystic Kidney Disease: Expression Profiles and Pathway Analysis
Authors: Devi Chandra , Ranjan Prashant , Mishra Jitendra Kumar , Singh Shivendra , Das Parimal
Published: October 2024

This study investigates the role of specific microRNAs (miRNAs) in autosomal dominant polycystic kidney disease (ADPKD). Network analysis using Cytoscape 3.10.1 revealed 28 miRNAs that target two or more PKD related genes, while 14 miRNAs interacted with three or more genes. Pathway analysis of these 14 miRNAs, conducted via the miRPath V4.0 tool, utilized various resources such as KEGG, GO terms, Pfam, and MSigDB, highlighting their functional roles in ADPKD. Among these 14 miRNAs, four were prioritized for further analysis based on the higher number of target genes and existing evidence of their expression in blood. These miRNAs were analyzed for fold change expression levels using qRT-PCR on blood-derived RNA samples from ADPKD patients (n=19) and healthy controls (n=5). These four miRNAs—hsa-miR20a-5p, hsa-miR27b-3p, hsa-miR3613-3p, and hsa-miR181a-5p— showed significant upregulation with p-values of 0.0179, 0.0002, 0.0166, and 0.0402 respectively. The functional enrichment of miRNAs involved in PKD evidently suggests that these play diverse roles in regulating key processes such as cell cycle progression, mTOR signaling, autophagy, EMT, and cellular responses to hypoxia thus playing crucial role in the pathogenesis of ADPKD and could serve as potential biomarkers or therapeutic targets.
Knowledge, Attitude, and Practice of Vasoactive Agents Infusions : Development and Psychometric Properties of a Questionnaire with Chinese Clinical Nurses
Authors: Huang Yanfang , Chen Yi , Fang Yaping , Mou Junjie , Li Shiqin , Lei Xianying , Li Yuxin , Ai Zhongping
Published: October 2024

Background

Inconsistencies with guidelines or standards regarding nurses’ practice of vasoactive agent infusion have been documented. Adequate knowledge and positive attitudes are critical for compliance. However, there are currently no validated tools specifically designed to measure the knowledge and attitudes related to vasoactive agent infusions among nurses.

Objective

The aim of this study was to develop and test the validity and reliability of the Chinese mainland version of Knowledge, Attitude, and Practice of Vasoactive Agents Infusions Questionnaire among nurses.

Methods

The initial questionnaire items were developed through a comprehensive literature review, expert consultation, and pilot study. From February to June 2024, cross-sectional data were collected using convenience sampling from 538 nurses across 9 hospitals in Sichuan Province, China. The reliability and validity of the scale were evaluated through internal consistency reliability, inter-rater reliability, exploratory factor analysis, and confirmatory factor analysis.

Results

The final version of the questionnaire included 33 items across 3 dimensions, explaining 78.04% of the variance, with item loadings ranging from 0.56 to 0.89. The content validity index ranged from 0.91 to 1.00, and the scale-level content validity index was 0.98. The overall Cronbach’s α for the questionnaire was 0.96, with Cronbach’s α for each dimension ranging from 0.96 to 0.98. The test-retest reliability for the entire questionnaire was 0.90, and for each dimension, it ranged from 0.90 to 0.94 (p < 0.05). The confirmatory factor analysis demonstrated acceptable fit indices for the three-dimensional model: χ²/(df) = 1.135, p = 0.200, RMSEA = 0.024, CFI = 0.986, TLI = 0.985, GFI = 0.884, and NFI = 0.895.

Conclusion

The Knowledge, Attitude, and Practice of Vasoactive Agents Infusions Questionnaire demonstrates good reliability and validity, making it a reliable measurement tool for assessing nurses’ attitudes and knowledge related to vasoactive agents’ infusions. This version will facilitate further research and advancements in this specific field of study.
Sciphy: A Bayesian phylogenetic framework using sequential genetic lineage tracing data
Authors: Seidel Sophie , Zwaans Antoine , Regalado Samuel , Choi Junhong , Shendure Jay , Stadler Tanja
Published: October 2024

CRISPR-based lineage tracing offers a promising avenue to decipher single cell lineage trees, especially in organisms that are challenging for microscopy. A recent advancement in this domain is lineage tracing based on sequential genome editing, which not only records genetic edits but also the order in which they occur. To capitalize on this enriched data, we introduce SciPhy, a simulation and inference tool integrated within the BEAST 2 framework. SciPhy utilizes a Bayesian phylogenetic approach to estimate time-scaled phylogenies and cell population parameters. After validating SciPhy using simulations, we apply it to lineage tracing data obtained from a monoclonal culture of HEK293T cells for which we estimate time-scaled trees together with cell proliferation rates. We compare SciPhy to the lineage reconstruction based on a widely used clustering method, UPGMA, and find that the UPGMA-reconstructed lineage trees differ from SciPhy trees in some key aspects of tree structure; in particular, SciPhy trees stand out for their later estimated cell division times. In addition, SciPhy reports uncertainty as well as proliferation rates, neither of which are available within a UPGMA analysis. This study showcases the application of advanced phylogenetic and phylodynamic tools to explore and quantify cell lineage trees, laying the groundwork for enhanced and confident analyses to decode the complexities of biological development in multicellular organisms. SciPhy’s codebase is publicly available athttps://github.com/azwaans/SciPhy.
IgBlend: Unifying 3D Structures and Sequences in Antibody Language Models
Authors: Malherbe Cedric , Uçar Talip
Published: October 2024

Large language models (LLMs) trained on antibody sequences have shown significant potential in the rapidly advancing field of machine learning-assisted antibody engineering and drug discovery. However, current state-of-the-art antibody LLMs often overlook structural information, which could enable the model to more effectively learn the functional properties of antibodies by providing richer, more informative data. In response to this limitation, we introduce IgBlend, which integrates both the 3D coordinates of backbone atoms (C-alpha, N, and C) and antibody sequences. Our model is trained on a diverse dataset containing over 4 million unique structures and more than 200 million unique sequences, including heavy and light chains as well as nanobodies. We rigorously evaluate IgBlend using established benchmarks such as sequence recovery, complementarity-determining region (CDR) editing and inverse folding and demonstrate that IgBlend consistently outperforms current state-of-the-art models across all benchmarks. Furthermore, experimental validation shows that the model’s log probabilities correlate well with measured binding affinities.
Camera traps unable to determine whether plasticine models of caterpillars reliably measure bird predation
Authors: Schillé Laura , Plat Nattan , Barbaro Luc , Jactel Hervé , Raspail Frédéric , Rivoal Jean-Baptiste , Castagneyrol Bastien , Mrazova Anna
Published: October 2024

Sampling methods that are both scientifically rigorous and ethical are cornerstones of any experimental biological research. Since its introduction 30 years ago, the method of using plasticine prey to quantify predation pressure has become increasingly popular in biology. However, recent studies have questioned the accuracy of the method, suggesting that misinterpretation of predator bite marks and the artificiality of the models may bias the results. Yet, biasper semight not be a methodological issue as soon as its statistical distribution in the samples is even, quantifiable, and thus correctable in quantitative analyses. In this study, we focus on avian predation of lepidopteran larvae models, which is one of the most extensively studied predator-prey interactions across diverse ecosystems worldwide. We compared bird predation on plasticine caterpillar models to that on dead caterpillars of similar size and color, using camera traps to assess actual predation events and to evaluate observer accuracy in identifying predation marksa posteriori. The question of whether plasticine models reliably measure insectivorous bird predation remained unanswered, for two reasons: (1) even the evaluation of experienced observers in the posterior assessment of predation marks on plasticine models was subjective to some extent, and (2) camera traps failed to reflect predation rates as assessed by observers, partly because they could only record evidence of bird presence rather than actual predation events. Camera traps detected more evidence of bird presence than predation clues on plasticine models, suggesting that fake prey may underestimate the foraging activity of avian insectivores. The evaluation of avian predation on real caterpillar corpses was probably also compromised by losses to other predators, likely ants. Given the uncertainties and limitations revealed by this study, and in the current absence of more effective monitoring methods, it remains simpler, more cost-effective, ethical, and reliable to keep using plasticine models to assess avian predation. However, it is important to continue developing improved monitoring technologies to better evaluate and refine these methods in order to advance research in this field.
Ternary complex formation of VCP, VCPIP1 and p47 facilitates Golgi reassembly
Authors: Shah Binita , Hunkeler Moritz , Bratt Ariana , Yue Hong , Jaen Maisonet Isabella , Fischer Eric S. , Buhrlage Sara J.
Published: October 2024

VCP/p97 regulates a wide range of cellular processes, including post-mitotic Golgi reassembly. In this context, VCP is assisted by p47, an adapter protein, and VCPIP1, a deubiquitinase (DUB). However, how they organize into a functionally competent complex and promote reassembly remains unknown. Here, we use cryo-EM to characterize VCP-VCPIP1 and VCP-VCPIP1-p47 complexes. We show that VCPIP1 engages VCP through two interfaces: one involving the N-domain of VCP and the UBX domain of VCPIP1, and the other involving the VCP D2 domains and a region of VCPIP1 we refer to as VCPID. The p47 UBX domain competitively binds to the VCP N-domain, while not affecting VCPID binding. We show that VCPID is critical for VCP-mediated enhancement of DUB activity and Golgi reassembly.
Fully Hyperbolic Neural Networks: A Novel Approach to Studying Aging Trajectories
Authors: Ramirez Hugo , Tabarelli Davide , Brancaccio Arianna , Belardinelli Paolo , Marsh Elisabeth B. , Funke Michael , Mosher John C. , Maestu Fernando , Xu Mengjia , Pantazis Dimitrios
Published: October 2024

Characterizing age-related alterations in brain networks is crucial for understanding aging trajectories and identifying deviations indicative of neurodegenerative disorders, such as Alzheimer’s disease. In this study, we developed a Fully Hyperbolic Neural Network (FHNN) to embed functional brain connectivity graphs derived from magnetoencephalography (MEG) data into low dimensions on a Lorentz model of hyperbolic space. Using this model, we computed hyperbolic embeddings of the MEG brain networks of 587 individuals from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) dataset. Notably, we leveraged a unique metric—the radius of the node embeddings—which effectively captures the hierarchical organization of the brain, to characterize subtle hierarchical organizational changes in various brain subnetworks attributed to the aging process. Our findings revealed that a considerable number of subnetworks exhibited a reduction in hierarchy during aging, with some showing gradual changes and others undergoing rapid transformations in the elderly. Moreover, we demonstrated that hyperbolic features outperform traditional graph-theoretic measures in capturing age-related information in brain networks. Overall, our study represents the first evaluation of hyperbolic embeddings in MEG brain networks for studying aging trajectories, shedding light on critical regions undergoing significant age-related alterations in the large cohort of the Cam-CAN dataset.
Digital Light Processing 3D Printing enables High Throughput Fabrication of Human Engineered Heart Tissues for Disease Modeling
Authors: Dhand Abhishek P. , Juarros Miranda A. , Martin Thomas G. , Rodriguez-Rivera Gabriel J. , Hunt Dakota R. , Obenreder Mackenzie C. , Crosby Cody O. , Meurer-Zeman Bianca , McAfee Quentin , Valle-Ayala Henry , Zlotnick Hannah M. , Goddard Declan N. , Ebmeier Christopher C. , Burdick Jason A. , Leinwand Leslie A.
Published: October 2024

3Din vitroengineered heart tissue (EHT) models recapitulate aspects of native cardiac physiology but are often limited by scalability, cost, and reproducibility. Here, we report a simple, one-step method for rapid (∼minutes) fabrication of molds using digital light processing (DLP)-based 3D printing that support the formation of EHTs by human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) with high reproducibility (>95% efficiency) and varied designs (e.g., length, aspect ratio). Compared to 2D iPSC-CMs, 3D EHTs display enhanced maturity, including increased expression of β-oxidation genes, higher concentrations of sarcomeric myosins, improved sarcomere density and alignment, and enrichment of cardiac pathways (e.g., upregulation of sodium channels, action potentials, contraction). The technology is applied to model pathological cardiac hypertrophyin vitro, using either (i) acute adrenergic agonism or (ii) chronic culture within stiff hydrogel molds. Treated EHTs exhibit increased levels of pathology-associated gene expression and activation of signaling cascades involved in pathological remodeling compared to untreated controls or treated 2D iPSC-CMs. Thus, our method results in robust yet simpler, cheaper, and faster EHTs to study cardiac disease.
TheC. elegansLON-1 protein requires its CAP domain for function in regulating body size and BMP signaling
Authors: Serrano Maria Victoria , Cottier Stephanie , Wang Lianzijun , Moreira-Antepara Sergio , Nzessi Anthony , Liu Zhiyu , Williams Byron , Lee Myeongwoo , Schneiter Roger , Liu Jun
Published: October 2024

The CAP (Cysteine-rich secretory proteins, Antigen-5, Pathogenesis-Related) proteins are widely expressed and have been implicated to play diverse roles ranging from mammalian reproduction to plant immune response. Increasing evidence supports a role of CAP proteins in lipid binding. TheC. elegansCAP protein LON-1 is known to regulate body size and Bone Morphogenetic Protein (BMP) signaling. LON-1 is a secreted protein with a conserved CAP domain and a C-terminal unstructured domain with no homology to other proteins. In this study, we report that the C-Terminal Domain (CTD) of LON-1 is dispensable for its function. Instead, key conserved residues located in the CAP domain are critical for LON-1 function in vivo. We further showed that LON-1 is capable of binding sterol, but not fatty acid, in vitro, and that certain key residues implicated in LON-1 function in vivo are also important for LON-1 sterol binding in vitro. These findings suggest a role of LON-1 in regulating body size and BMP signaling via sterol binding.

ARTICLE SUMMARY

TheC. elegansLON-1 protein is known to regulate body size and Bone Morphogenetic Protein (BMP) signaling. However, its molecular mode of action remains elusive. This study shows that LON-1 can bind sterol, but not fatty acid, in vitro. Furthermore, key conserved residues in the CAP domain of LON-1 are required for LON-1 function in vivo. These findings suggest a role of LON-1 in regulating body size and BMP signaling via sterol binding.
Structural basis for saxitoxin congener binding and neutralization by anuran saxiphilins
Authors: Zakrzewska Sandra , Nixon Samantha A. , Chen Zhou , Hajare Holly S. , Park Elizabeth R. , Mulcahy John V. , Arlinghaus Kandis M. , Neu Eduard , Konovalov Kirill , Provasi Davide , Leighfield Tod A. , Filizola Marta , Bois J. Du , Minor Daniel L.
Published: October 2024

Dinoflagellates and cyanobacteria in harmful ‘red tide’ algal blooms produce saxitoxin (STX) and ∼50 congeners that block voltage-gated sodium channel (NaV) function and disrupt bioelectrical signals1–4. Consuming seafood carrying these lethal toxins causes paralytic shellfish poisoning (PSP), a growing public health hazard due to climate change5–7that motivates efforts to detect these toxins and counteract their noxious effects. Although structural studies of NaVs8,9and anuran soluble STX binding proteins known as saxiphilins (Sxphs)10,11revealed convergent binding modes for the bis-guanidinium STX core10,11, the structural basis for STX congener recognition is unknown. Here, we show that American bullfrog (Rana catesbeiana)RcSxph10,11and High Himalaya frog (Nanorana parkeri)NpSxph10use a pre-organized pocket to sequester STX congeners through a binding mode shared with STX. This ‘lock and key’ recognition yields a tradeoff between a relatively rigid high-affinity toxin binding site in which bound waters are crucial and the ability of Sxphs to accommodate STX congener modifications. Importantly, functional studies show that Sxphs act as ‘toxin sponges’ that reverse NaVblock by multiple STX congeners and can detect these bis-guanidinium toxins in a radioligand receptor binding assay (RBA) for PSP toxin environmental testing12,13. Our findings establish how Sxphs sequester diverse neurotoxins and reveal structural factors underlying STX congener binding differences between Sxphs and NaVs that are rooted in the distinct toxin binding orientations on these two targets. These insights expand the molecular foundation required for understanding toxin sponge action and for guiding development of new means to monitor PSTs and mitigate their harmful effects.
Assessing Quantitative Performance and Expert Review of Multiple Deep Learning-Based Frameworks for Computed Tomography-based Abdominal Organ Auto-Segmentation
Authors: Ram Udbhav S. , Pogue Joel A. , Soike Michael , Pfister Neil T. , Jacob Rojymon , Cardenas Carlos E.
Published: October 2024

Segmentation of abdominal organs in clinical oncological workflows is crucial for ensuring effective treatment planning and follow-up. However, manually generated segmentations are time-consuming and labor-intensive in addition to experiencing inter-observer variability. Many deep learning (DL) and Automated Machine Learning (AutoML) frameworks have emerged as a solution to this challenge and show promise in clinical workflows. This study presents a comprehensive evaluation of existing AutoML frameworks (Auto3DSeg, nnU-Net) against a state-of-the-art non-AutoML framework, the Shifted Window U-Net Transformer (SwinUNETR), each trained on the same 122 training images, taken from the Abdominal Multi-Organ Segmentation (AMOS) grand challenge. Frameworks were compared using Dice Similarity Coefficient (DSC), Surface DSC (sDSC) and 95th Percentile Hausdorff Distances (HD95) on an additional 72 holdout-validation images. The perceived clinical viability of 30 auto-contoured test cases were assessed by three physicians in a blinded evaluation. Comparisons show significantly better performance by AutoML methods. nnU-Net (average DSC: 0.924, average sDSC: 0.938, average HD95: 4.26, median Likert: 4.57), Auto3DSeg (average DSC: 0.902, average sDSC: 0.919, average HD95: 8.76, median Likert: 4.49), and SwinUNETR (average DSC: 0.837, average sDSC: 0.844, average HD95: 13.93). AutoML frameworks were quantitatively preferred (13/13 OARs p>0.0.5 in DSC and sDSC, 12/13 OARs p>0.05 in HD95, comparing Auto3DSeg to SwinUNETR, and all OARs p>0.05 in all metrics comparing SwinUNETR to nnU-Net). Qualitatively, nnU-Net was preferred over Auto3DSeg (p=0.0027). The findings suggest that AutoML frameworks offer a significant advantage in the segmentation of abdominal organs, and underscores the potential of AutoML methods to enhance the efficiency of oncological workflows.
Association of Amygdala, Hippocampus, and Entorhinal cortex with thyroid function in older adults: Stratification’s value and relevance of bilateral volumetric analyses
Authors: Hallab Asma ,   Alzheimer’s Disease Neuroimaging Initiative
Published: October 2024

Introduction

Thyroid hormones modulate the brain structure during neurogenesis and impact cognition and emotions during the lifetime. It is, therefore, important to understand their association with relevant brain structures during the aging process.

Methods

A subset of 1348 older adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) was included. Linear regression was used to study the association between serum thyroid stimulating hormone (TSH) and the Amygdala, Hippocampus, and Entorhinal cortex volumes. Sex and neurodegeneration-related stratifications and comparative bilateral volumetric analyses were performed.

Results

Females represented 667 (49%) of included cases, and 522 (38.72 %) were healthy controls (HC). A significant positive association was observed between TSH and total Hippocampus volume in mild cognitive impairment (MCI) (adj.ß=92 (23, 161),p- value=0.009), while a negative association in dementia participants remained statistically significant (ß=-177 (−295, −60),p-value=0.003 and adj.ß=-141 (−250, −32),p-value=0.012). There was a significant association between TSH and total Entorhinal cortex volume in the total study population (ß=44 (3.9, 85),p-value=0.032 and adj.ß=40 (5.1, 75),p-value=0.025). Stratification showed significant associations only in MCI (ß=80 (21, 138),p-value=0.007, and adj.ß=83 (27, 138),p-value=0.003), and males (adj.ß=54 (1.9, 106),p-value=0.042). Similar statistically significant associations were found only in the left Entorhinal cortex. The association between TSH and total Amygdala volume was positive in HC (ß=37 (1.6, 73),p- value=0.041) and negative in dementia participants (ß=-67 (−128, −6.4),p-value=0.030). None of those results remained statistically significant after adjusting the models. The bilateral volumetric analysis showed significant results only in the right Amygdala and dementia group.

Conclusions

Depending on the stratum and side of the volumetric analysis, significant associations were observed between TSH and Hippocampus, Amygdala, and Entorhinal cortex volumes. It is, therefore, crucial to consider the role of sex, neurodegeneration, and laterality when exploring the thyroid-brain interaction in older adults.

Highlights

Higher TSH levels are associated with lower Hippocampus volume on both sides in the dementia group.

Lower TSH levels are associated with lower left Entorhinal cortex volume in the mild cognitive impairment and male strata.

Higher TSH levels are associated with lower right Amygdala volume in the dementia group.

Graphical abstract