bluuebunny/crossref_metadata_2025_split huggingface dataset:
A study on tomato brown rugose fruit virus longevity in soil and virion susceptibility to various pH treatments contributes to optimization of a soil disinfection protocol
Authors: Molad Ori , Smith Elisheva , Luria Neta , Bakelman Elena , Lachman Oded , Reches Meital , Dombrovsky Aviv 
Published: January 2024

AbstractBackground and aimsTobamoviruses are highly stable soil-borne pathogens posing a challenge to a monoculture practice. Biochemical and physical properties of tobamovirus virions were studied by analyses of tobacco mosaic virus (TMV). Little is known about tomato brown rugose fruit tobamovirus (ToBRFV) regarding longevity in soil and virion stability. Our aims were to determine ToBRFV longevity in naturally-contaminated soil and study virion stability in a range of acidic and alkaline conditions to promote new strategies for soil remediation.MethodsToBRFV longevity in naturally-contaminated soil was tested by collecting an earth pile after a growth-cycle of ToBRFV-infected tomato plants. The soil was sampled at different time points and root-truncated tomato seedlings were planted. Virion stability at a range of pH values was determined by testing virus infectivity onNicotiana glutinosa; by amplifying large genome segments using RT-PCR; and by transmission electron microscopy (TEM) visualization.ResultsToBRFV-infectivity in naturally-contaminated soil was profoundly reduced by day 184 of pile-age and was abolished between 205-385 days of pile-age. Virion stability and genome integrity were preserved over the pH range of 2-10. At pH 1, ToBRFV-infectivity and efficiency of large genome segment amplifications were reduced. At pH values above 10, modified particle morphologies were visualized by TEM, and virus infectivity was abolished. Treatment of ToBRFV-contaminated soil with an alkaline chlorinated-trisodium phosphate solution profoundly reduced soil-mediated virus infection of root-truncated tomato seedlings.ConclusionspH values above 10, compromised ToBRFV particle morphology genome integrity and virus infectivity. Alkaline disinfectant enhanced soil remediation following natural ToBRFV contamination.
Efficient CRISPR genome editing and integrative genomic analyses reveal the mosaicism of Cas-induced mutations and pleiotropic effects ofscarletgene in an emerging model system
Authors: Xu Sen , Neupane Swatantra , Wang Hongjun , Pham Thinh Phu , Snyman Marelize , Huynh Trung V. , Wang Li 
Published: January 2024

AbstractDespite the revolutionary impacts of CRISPR-Cas gene editing systems, the effective and widespread use of CRISPR technologies in emerging model organisms still faces significant challenges. These include the inefficiency in generating heritable mutations at the organismal level, limited knowledge about the genomic consequences of gene editing, and an inadequate understanding of the inheritance patterns of CRISPR-Cas-induced mutations. This study addresses these issues by 1) developing an efficient microinjection delivery method for CRISPR editing in the microcrustaceanDaphnia pulex; 2) assessing the editing efficiency of Cas9 and Cas12a nucleases, examining mutation inheritance patterns, and analyzing the local and global mutation spectrum in thescarletmutants; and 3) investigating the transcriptomes ofscarletmutants to understand the pleiotropic effects ofscarletunderlying their swimming behavior changes. Our reengineered CRISPR microinjection method results in efficient biallelic editing with both nucleases. While indels are dominant in Cas-induced mutations, a few on-site large deletions (>1kb) are observed, most likely caused by microhomology-mediated end joining repair. Knock-in of a stop codon cassette to thescarletlocus was successful, despite complex induced mutations surrounding the target site. Moreover, extensive germline mosaicism exists in some mutants, which unexpectedly produce different phenotypes/genotypes in their asexual progenies. Lastly, our transcriptomic analyses unveil significant gene expression changes associated with scarlet knock-out and altered swimming behavior in mutants, including several genes (e.g., NMDA1, ABAT, CNTNAP2) involved in human neurodegenerative diseases. This study expands our understanding of the dynamics of gene editing in the tractable model organismDaphniaand highlights its promising potential as a neurological disease model.
Harnessing the regenerative potential ofinterleukin11to enhance heart repair
Authors: Shin Kwangdeok , Rodriguez-Parks Anjelica , Kim Chanul , Silaban Isabella M. , Xia Yu , Sun Jisheng , Dong Chenyang , Keles Sunduz , Wang Jinhu , Cao Jingli , Kang Junsu 
Published: January 2024

ABSTRACTBalancing between regenerative processes and fibrosis is crucial for heart repair, yet strategies regulating this balance remain a barrier to developing therapies. While Interleukin11 (IL11) is known as a fibrotic factor, its contribution to heart regeneration is poorly understood. We uncovered thatil11a, an Il11homolog in zebrafish, can trigger robust regenerative programs in zebrafish hearts, including cardiomyocytes proliferation and coronary expansion, even in the absence of injury. However, prolongedil11ainduction in uninjured hearts causes persistent fibroblast emergence, resulting in fibrosis. While deciphering the regenerative and fibrotic effects ofil11a, we found thatil11-dependent fibrosis, but not regeneration, is mediated through ERK activity, suggesting to potentially uncoupleil11adual effects on regeneration and fibrosis. To harness theil11a’s regenerative ability, we devised a combinatorial treatment throughil11ainduction with ERK inhibition. This approach enhances cardiomyocyte proliferation with mitigated fibrosis, achieving a balance between regenerative processes and fibrosis. Thus, we unveil the mechanistic insights into regenerativeil11roles, offering therapeutic avenues to foster cardiac repair without exacerbating fibrosis.
Application of the thermal death time model in predicting thermal damage accumulation in plants
Authors: Faber Andreas H , Ørsted Michael , Ehlers Bodil Kirstine 
Published: January 2024

AbstractThe thermal death time (TDT) model suggests that the duration an organism can tolerate thermal stress decreases exponentially as the intensity of the temperature becomes more extreme. This model has been used to predict damage accumulation in ectotherm animals and plants under fluctuating thermal conditions. However, the critical assumption of the TDT model, which is additive damage accumulation, remains unverified for plants.We assessed thermal damage inThymus vulgarisunder different heat and cold treatments and used TDT models to predict time to thermal failure of PSII. Additionally, thermal tolerance estimates from previous studies were used to create TDT models to assess the applicability of this framework in plants.We show that thermal damage obtained at different stress intensities and durations is additive for both heat and cold stress, and that the TDT model can predict damage accumulation at both temperature extremes. Data from previous studies indicate a broad applicability of this approach across species, traits, and environments.The TDT framework reveals a thermal tolerance landscape describing the exponential relationship between exposure duration, stress intensity and damage accumulation in plants. This thermal sensitivity emphasizes the potential impact of future thermal extremes on the mortality and distribution of plant species.HighlightThis study highlights the applicability of the thermal death time model to plants, unveiling a distinct thermal tolerance landscape, extending across species and traits for assessing thermal stress impacts.
AC-BioSD : A biomolecular signal differentiator module with enhanced performance (extended version)
Authors: Alexis Emmanouil , Avalos José L. , Cardelli Luca , Papachristodoulou Antonis 
Published: January 2024

AbstractTemporal gradient estimation is a pervasive phenomenon in natural biological systems and holds great promise for synthetic counterparts with broad-reaching applications. Here, we advance the concept ofBioSD(Biomolecular Signal Differentiators) by introducing a novel biomolecular topology, termedAutocatalytic-BioSDorAC-BioSD. Its structure allows for insensitivity to input signal changes and high precision in terms of signal differentiation, even when operating far from nominal conditions. Concurrently, disruptive high-frequency signal components are effectively attenuated. In addition, the usefulness of our topology in biological regulation is highlighted via a PID (Proportional-Integral-Derivative) bio-control scheme withset point weightingand filtered derivative action in both the deterministic and stochastic domains.
From small to tall: breed-varied household pet dogs can be trained to detect Parkinson’s Disease
Authors: Holt Lisa , Johnston Samuel V 
Published: January 2024

ABSTRACTObjectiveParkinson’s Disease (PD) is a clinically diagnosed disease that carries a reported misdiagnosis rate of 10–20%. Recent scientific discoveries have provided evidence of volatile organic compounds in sebum that are unique to patients with PD. The purpose of this study was to determine if companion dogs could be trained to distinguish between sebum samples provided by PD-positive patients and PD-negative human controls.MethodsThis was a randomized, handler-blind, controlled study. Twenty-three canines of varying breeds, ages, and environmental backgrounds were included. The two-year study period reported here was the final two years of a seven-year program which started in January of 2016. This study encompassed 200 total working session days from 2021 and 2022.ResultsWhen averaged as a group over two years, the 23 dogs were 89% sensitive and 87% specific to an olfactory distinction between PD-positive and PD-negative human donor samples. Ten of the twenty-three dogs averaged 90% or higher in both sensitivity and specificity.In 161 separate instances, dogs were presented with both unique PD-positive and PD-negative samples (the dogs had not previously encountered any of the samples presented). For these first-time exposures, the 23 dogs collectively averaged 86% sensitivity and 89% specificity.When comparing the sensitivity and specificity of PD-positive samples from donors who reported levodopa usage to PD-positive samples from donors who reported no levodopa usage, the dogs showed no statistical difference in sensitivity or specificity at the 95% significance level, indicating levodopa usage is not a factor in PD canine detection. Other factors investigated as part of this study included sample donor gender, canine breed, age, duration of time in the program, and training.ConclusionsCompanion dogs can be trained with reward-biased detection methodologies to distinguish between PD-positive and PD-negative donor sebum samples in a controlled setting. This study provides further evidence of one or more volatile organic compounds in the sebum of PD-positive patients that can be detected by canines. Summarily, study findings support the application of trained companion dogs for the screening of PD-positive and PD-negative samples in which numbers of samples are limited and the dogs are worked in short intervals, followed by recovery training.
The interaction of relative age with maturation and body size in female handball talent selection based on only sport-specific criteria
Authors: Tróznai Zsófia , Utczás Katinka , Pápai Júlia , Pálinkás Gergely , Szabó Tamás , Petridis Leonidas 
Published: January 2024

AbstractTalent identification is often affected by the relative age effects (RAEs) and/or maturation. Previous research has suggested that talent selection should include sport-specific technical tasks instead of body size and/or physical test measurements, assuming that the technical tasks are less influenced by interindividual variability in maturation. Our purpose was to examine the prevalence of RAEs and how biological maturity, body size, and body composition in relation to relative age affect talent selection among female handball players. Handball-specific drills and in-game performance were the criteria of a single talent selection program. Birth distribution of U14 female (N= 3198) handball players were analyzed. Body size, body composition, and bone age were assessed on 264 selected and 266 not-selected players. Body composition was assessed with InBody 720, whereas biological age from bone age. Chi-square was used to examine quartile distributions, and logistic regression to determine the effects of the predictors on the selection. In terms of all registered players, there was no difference in birth distribution. RAEs appeared at the first selection level and were evident at all levels. Quartiles differed only between the first and the last quartiles in body size and muscle mass. Only bone age differed between consecutive quartile or semi-year groups. Body size, body composition, and maturity had a significant, but of moderate power, effect on the selection. Larger body height increased selection odds by about 12%, larger muscle mass by 12% to 25%, larger percent body fat decreased selection odds by 7%, while larger bone age by 3.5-4 times. RAEs affected talent selection when applying sport-specific drills as selection criteria. Relative age was connected to bone age, but not convincingly to body size and muscle mass. Bone age had the largest effect on the selection, but this was not associated with larger body size or muscle mass.
A vagal influence on schizophrenia? A nationwide retrospective cohort of vagotomized individuals
Authors: Richter Cornelia F , Skibicka Karolina P , Meyer Urs , Rohrmann Sabine , Krieger Jean-Philippe 
Published: January 2024

AbstractBackground and ObjectivesEmerging preclinical evidence suggests that vagal signals contribute to the development of schizophrenia-related abnormalities in brain and behavior. Whether vagal communication in general, and its impairment in particular, is a risk factor for schizophrenia in humans remains, however, unclear. Vagotomy, the surgical lesion of the vagus nerve, was routinely performed as a treatment for peptic ulcer before modern treatment options were available. Hence, the primary aim of this study was to investigate whether vagotomy modulates the subsequent risk of developing schizophrenia. Moreover, given the existence of diverse vagotomy techniques (i.e., “truncal” or “selective”), our secondary goal was to test whether the extent of denervation modulates the risk of schizophrenia.MethodsUsing a nationwide retrospective matched cohort design, we identified 8,315 vagotomized individuals from the Swedish National Patient Register during the period 1970-2020 and 40,855 non-vagotomized individuals matching for age, sex and type of peptic ulcer. The risk of being diagnosed with schizophrenia and associated psychoses (ICD10 codes F20-29) was analyzed using Cox proportional hazards regression models, including death as competing risk.ResultsWhen considering all types of vagotomy together, vagotomy was not significantly associated with schizophrenia (HR: 0.91 [0.72; 1.16]). However, truncal vagotomy (which denervates all subdiaphragmatic organs) significantly increased the risk of developing schizophrenia by 69% (HR: 1.69 [1.08; 2.64]), whereas selective vagotomy (which only denervates the stomach) showed no significant association (HR: 0.80 [0.61; 1.04]).DiscussionOur results provide epidemiological support for the hypothesis that impairments in vagal functions could increase the risk of schizophrenia. Notably, the finding that truncal but not selective vagotomy is associated with an increased risk of schizophrenia raises the possibility that the activity of subdiaphragmatic non-gastric vagal branches may be of particular relevance for the development of schizophrenia.
Derivation, External Validation and Clinical Implications of a deep learning approach for intracranial pressure estimation using non-cranial waveform measurements
Authors: Gulamali Faris , Jayaraman Pushkala , Sawant Ashwin S. , Desman Jacob , Fox Benjamin , Chang Annie , Soong Brian Y. , Arivazaghan Naveen , Reynolds Alexandra S. , Duong Son Q , Vaid Akhil , Kovatch Patricia , Freeman Robert , Hofer Ira S. , Sakhuja Ankit , Dangayach Neha S. , Reich David S. , Charney Alexander W , Nadkarni Girish N. 
Published: January 2024

AbstractImportanceIncreased intracranial pressure (ICP) is associated with adverse neurological outcomes, but needs invasive monitoring.ObjectiveDevelopment and validation of an AI approach for detecting increased ICP (aICP) using only non-invasive extracranial physiological waveform data.DesignRetrospective diagnostic study of AI-assisted detection of increased ICP. We developed an AI model using exclusively extracranial waveforms, externally validated it and assessed associations with clinical outcomes.SettingMIMIC-III Waveform Database (2000-2013), a database derived from patients admitted to an ICU in an academic Boston hospital, was used for development of the aICP model, and to report association with neurologic outcomes. Data from Mount Sinai Hospital (2020-2022) in New York City was used for external validation.ParticipantsPatients were included if they were older than 18 years, and were monitored with electrocardiograms, arterial blood pressure, respiratory impedance plethysmography and pulse oximetry. Patients who additionally had intracranial pressure monitoring were used for development (N=157) and external validation (N=56). Patients without intracranial monitors were used for association with outcomes (N=1694).ExposuresExtracranial waveforms including electrocardiogram, arterial blood pressure, plethysmography and SpO2.Main Outcomes and MeasuresIntracranial pressure > 15 mmHg. Measures were Area under receiver operating characteristic curves (AUROCs), sensitivity, specificity, and accuracy at threshold of 0.5. We calculated odds ratios and p-values for phenotype association.ResultsThe AUROC was 0.91 (95% CI, 0.90-0.91) on testing and 0.80 (95% CI, 0.80-0.80) on external validation. aICP had accuracy, sensitivity, and specificity of 73.8% (95% CI, 72.0%-75.6%), 99.5% (95% CI 99.3%-99.6%), and 76.9% (95% CI, 74.0-79.8%) on external validation. A ten-percentile increment was associated with stroke (OR=2.12; 95% CI, 1.27-3.13), brain malignancy (OR=1.68; 95% CI, 1.09-2.60), subdural hemorrhage (OR=1.66; 95% CI, 1.07-2.57), intracerebral hemorrhage (OR=1.18; 95% CI, 1.07-1.32), and procedures like percutaneous brain biopsy (OR=1.58; 95% CI, 1.15-2.18) and craniotomy (OR = 1.43; 95% CI, 1.12-1.84;P< 0.05 for all).Conclusions and RelevanceaICP provides accurate, non-invasive estimation of increased ICP, and is associated with neurological outcomes and neurosurgical procedures in patients without intracranial monitoring.
Identification and characterization of a potentially novel dorsal cutaneous muscle in rodents
Authors: Petruska Jeffrey C. 
Published: January 2024

ABSTRACTIn the course of performing a detailed dissection of adult rat to map the cutaneous nerves of cervical, thoracic, and lumbar levels a small and unexpected structure was isolated. It appeared to be a cutaneous striated muscle and was observed in both male and female rats and in mice but absent from cats and humans. With the skin reflected laterally from midline, the muscle lies closely apposed to the lateral border of the Thoracic Trapezius (Spinotrapezius) muscle and is easily missed in standard gross dissections. Focussed prosections were performed to identify the origin, insertion, and course of gross innervation. Identification of each of these elements showed them to be distinct from the nearby Trapezius and Cutaneous Trunci (Cutaneous Maximus in mouse) muscles. The striated muscle nature of the structure was validated with whole-mount microscopy.Consulting a range of published rodent anatomical atlases and gross anatomical experts revealed no prior descriptions. This preliminary report is an opportunity for the anatomical and research communities to provide input to either confirm the novelty of this muscle or refer to prior published descriptions in rodents or other species while the muscle, its innervation, and function are further characterized. Presuming this muscle is indeed novel, the name “Cutaneous Scapularis muscle” is proposed in accord with general principles of the anatomical field.
Event-Related Potential markers of Subjective Cognitive Decline and Mild Cognitive Impairment during a sustained visuo-attentive task
Authors: Vergani A. A. , Mazzeo S. , Moschini V. , Burali R. , Lassi M. , Amato L. G. , Carpaneto J. , Salve-strini G. , Fabbiani C. , Giacomucci G. , Morinelli C. , Emiliani F. , Scarpino M. , Bagnoli S. , Ingannato A. , Nacmias B. , Padiglioni S. , Sorbi S. , Bessi V. , Grippo A. , Mazzoni A. 
Published: January 2024

AbstractSubjective cognitive decline (SCD), mild cognitive impairment (MCI), or severe Alzheimer’s disease stages are still lacking clear electrophysiological correlates. In 178 individuals (119 SCD, 40 MCI, and 19 healthy subjects (HS)), we analysed event-related potentials recorded during a sustained visual attention task, aiming to distinguish biomarkers associated with clinical conditions and task performance. We observed condition-specific anomalies in event-related potentials (ERPs) during visual encoding (P1/N1/P2) and decision-making (P300/P600/P900): SCD individuals showed attenuated dynamics compared to HS, while MCI individuals showed amplified dynamics, except for P300, which matched clinical severity. ERP features confirmed a non-monotonic trend, with MCI showing higher neural resource recruitment. Moreover, task performance correlated with condition-specific ERP gain and latencies across early and late ERP components. These findings enhanced the understanding of the neural mechanisms underlying cognitive decline in SCD and MCI and suggested potential biomarkers for early diagnosis and intervention.HighlightsIn encoding (P1/N1/P2) and decision (P600/P900) ERPs, SCD individuals showed attenuated dynamics compared to HS, while MCI individuals exhibited amplified dynamics compared to SCD.P300 dynamics matched clinical severity.MCI individuals demonstrated higher recruitment of neural resources, indicating a non-monotonic trend in ERP features between clinical conditions.Task performance correlated with condition-specific gain and latencies across multiple ERP components.
GMMA can stabilize proteins across different functional constraints
Authors: Daffern Nicolas , Johansson Kristoffer E. , Baumer Zachary T. , Robertson Nicholas R. , Woojuh Janty , Bedewitz Matthew A. , Davis Zoë , Wheeldon Ian , Cutler Sean R. , Lindorff-Larsen Kresten , Whitehead Timothy A. 
Published: January 2024

ABSTRACTStabilizing proteins without otherwise hampering their function is a central task in protein engineering and design. PYR1 is a plant hormone receptor that has been engineered to bind diverse small molecule ligands. We sought a set of generalized mutations that would provide stability without affecting functionality for PYR1 variants with diverse ligand-binding capabilities. To do this we used a global multi-mutant analysis (GMMA) approach, which can identify substitutions that have stabilizing effects and do not lower function. GMMA has the added benefit of finding substitutions that are stabilizing in different sequence contexts and we hypothesized that applying GMMA to PYR1 with different functionalities would identify this set of generalized mutations. Indeed, conducting FACS and deep sequencing of libraries for PYR1 variants with two different functionalities and applying a GMMA analysis identified 5 substitutions that, when inserted into four PYR1 variants that each bind a unique ligand, provided 2-6°C in increased thermal stability and no decrease in functionality.