bluuebunny/crossref_metadata_2025 huggingface dataset:
The sequence of regional structural disconnectivity due to multiple sclerosis lesions
Authors: Tozlu Ceren , Olafson Emily , Jamison Keith W , Demmon Emily , Kaunzner Ulrike , Marcille Melanie , Zinger Nicole , Michaelson Nara , Safi Neha , Nguyen Thanh , Gauthier Susan , Kuceyeski Amy
Published: December 2023

Prediction of disease progression is challenging in multiple sclerosis as the sequence of lesion development and retention of inflammation within a subset of chronic lesions is heterogeneous among patients. We investigated the sequence of lesion-related regional structural disconnectivity across the spectrum of disability and cognitive impairment in multiple sclerosis. In a full cohort of 482 multiple sclerosis patients (age: 41.83 ± 11.63 years, 71.57% females), the Expanded Disability Status Scale was used to classify patients into (i) no or mild (Expanded Disability Status Scale <3) versus (ii) moderate or severe disability groups (Expanded Disability Status Scale ≥3). In 363 out of 482 patients, quantitative susceptibility mapping was used to identify paramagnetic rim lesions, which are maintained by a rim of iron-laden innate immune cells. In 171 out of 482 patients, Brief International Cognitive Assessment was used to identify subjects as being cognitively preserved or impaired. Network Modification Tool was used to estimate the regional structural disconnectivity due to multiple sclerosis lesions. Discriminative event-based modelling was applied to investigate the sequence of regional structural disconnectivity due to (i) all representative T2 fluid-attenuated inversion recovery lesions, (ii) paramagnetic rim lesions versus non-paramagnetic rim lesions separately across disability groups (‘no to mild disability’ to ‘moderate to severe disability’), (iii) all representative T2 fluid-attenuated inversion recovery lesions and (iv) paramagnetic rim lesions versus non-paramagnetic rim lesions separately across cognitive status (‘cognitively preserved’ to ‘cognitively impaired’). In the full cohort, structural disconnection in the ventral attention and subcortical networks, particularly in the supramarginal and putamen regions, was an early biomarker of moderate or severe disability. The earliest biomarkers of disability progression were structural disconnections due to paramagnetic rim lesions in the motor-related regions. Subcortical structural disconnection, particularly in the ventral diencephalon and thalamus regions, was an early biomarker of cognitive impairment. Our data-driven model revealed that the structural disconnection in the subcortical regions, particularly in the thalamus, is an early biomarker for both disability and cognitive impairment in multiple sclerosis. Paramagnetic rim lesions–related structural disconnection in the motor cortex may identify the patients at risk for moderate or severe disability in multiple sclerosis. Such information might be used to identify people with multiple sclerosis who have an increased risk of disability progression or cognitive decline in order to provide personalized treatment plans.
Non-motor symptoms in motor neuron disease: prevalence, assessment and impact
Authors: Beswick Emily , Forbes Deborah , Johnson Micheala , Newton Judith , Dakin Rachel , Glasmcher Stella , Abrahams Sharon , Carson Alan , Chandran Siddharthan , Pal Suvankar
Published: December 2023

People with motor neuron disease often experience non-motor symptoms that may occur secondary to, or distinct from, motor degeneration and that may significantly reduce quality of life, despite being under-recognized and evaluated in clinical practice. Non-motor symptoms explored in this population-based study include pain, fatigue, gastrointestinal issues, poor sleep, low mood, anxiety, problematic saliva, apathy, emotional lability, cognitive complaints and sexual dysfunction. People registered on the Clinical Audit Research and Evaluation of motor neuron disease platform, the Scottish Motor Neuron Disease Register, were invited to complete a questionnaire on non-motor symptoms and a self-reported Amyotrophic Lateral Sclerosis Functional Rating Scale. The questionnaire comprised a pre-defined list of 11 potential non-motor symptoms, with the opportunity to list additional symptoms. A total of 120 individuals participated in this cross-sectional study, a 39% response rate of those sent questionnaires (n = 311); 99% of participants recruited (n = 120) experienced at least one non-motor symptom, with 72% (n = 120) reporting five or more. The symptoms most often reported were pain and fatigue (reported by 76% of participants, respectively). The symptoms reported to be most impactful were gastrointestinal issues (reported as ‘severe’ by 54% of participants who experienced them), followed by pain and problematic saliva (51%, respectively). Lower Amyotrophic Lateral Sclerosis Functional Rating Scale scores, indicating more advanced disease and being a long survivor [diagnosed over 8 years ago; Black et al. (Genetic epidemiology of motor neuron disease-associated variants in the Scottish population. Neurobiol Aging. 2017;51:178.e11-178.e20.)], were significantly associated with reporting more symptoms; 73% of respondents were satisfied with the frequency that non-motor symptoms were discussed in clinical care; 80% of participants indicated they believe evaluation of non-motor symptom is important to include as outcomes in trials, independent of their personal experience of these symptoms. The preferred method of assessment was completing questionnaires, at home. The overwhelming majority of people with motor neuron disease report non-motor symptoms and these frequently co-occur. Pain, fatigue, gastrointestinal issues, sleep, mood, anxiety, problematic saliva, apathy, emotional lability, cognitive complaints and sexual dysfunction are prevalent. People with motor neuron disease who had worse physical function and those who were long survivors were more likely to report more symptoms. Where reported, these symptoms are frequent, impactful and a priority for people with motor neuron disease in clinical care and trial design.
Mapping microarchitectural degeneration in the dilated ascending aorta with ex vivo diffusion tensor imaging
Authors: Wang Mofei , Ching-Johnson Justin A , Yin Hao , O’Neil Caroline , Li Alex X , Chu Michael W A , Bartha Robert , Pickering J Geoffrey
Published: December 2023

Aims

Thoracic aortic aneurysms (TAAs) carry a risk of catastrophic dissection. Current strategies to evaluate this risk entail measuring aortic diameter but do not image medial degeneration, the cause of TAAs. We sought to determine if the advanced magnetic resonance imaging (MRI) acquisition strategy, diffusion tensor imaging (DTI), could delineate medial degeneration in the ascending thoracic aorta.

Methods and results

Porcine ascending aortas were subjected to enzyme microinjection, which yielded local aortic medial degeneration. These lesions were detected by DTI, using a 9.4 T MRI scanner, based on tensor disorientation, disrupted diffusion tracts, and altered DTI metrics. High-resolution spatial analysis revealed that fractional anisotropy positively correlated, and mean and radial diffusivity inversely correlated, with smooth muscle cell (SMC) and elastin content (P < 0.001 for all). Ten operatively harvested human ascending aorta samples (mean subject age 61.6 ± 13.3 years, diameter range 29–64 mm) showed medial pathology that was more diffuse and more complex. Nonetheless, DTI metrics within an aorta spatially correlated with SMC, elastin, and, especially, glycosaminoglycan (GAG) content. Moreover, there were inter-individual differences in slice-averaged DTI metrics. Glycosaminoglycan accumulation and elastin degradation were captured by reduced fractional anisotropy (R2 = 0.47, P = 0.043; R2 = 0.76, P = 0.002), with GAG accumulation also captured by increased mean diffusivity (R2 = 0.46, P = 0.045) and increased radial diffusivity (R2 = 0.60, P = 0.015).

Conclusion

Ex vivo high-field DTI can detect ascending aorta medial degeneration and can differentiate TAAs in accordance with their histopathology, especially elastin and GAG changes. This non-destructive window into aortic medial microstructure raises prospects for probing the risks of TAAs beyond lumen dimensions.
Clinical profiling and outcomes of viral myocarditis manifesting with ventricular arrhythmias
Authors: Peretto Giovanni , Sala Simone , Carturan Elisa , Rizzo Stefania , Villatore Andrea , De Luca Giacomo , Campochiaro Corrado , Palmisano Anna , Vignale Davide , De Gaspari Monica , Dagna Lorenzo , Esposito Antonio , Basso Cristina , Camici Paolo Guido , Della Bella Paolo
Published: December 2023

Aims

Clinical features and risk stratification of patients with viral myocarditis (VM) complicated by ventricular arrhythmias (VA) are incompletely understood. We aim to describe arrhythmia patterns and outcomes in patients with VM and early-onset VA.

Methods and results

We present a single-centre study, enrolling patients with VM proven by endomyocardial biopsy, and evidence of VA within 24 h of hospitalization. The incidence of major adverse events (MAE), including all-cause death, severe heart failure, advanced atrioventricular blocks, or major VA, was evaluated during a 24-month follow-up (FU) and compared with a matched group of virus-negative myocarditis. Of patients with VM (n = 74, mean age 47 ± 16 years, 66% males, and left ventricular ejection fraction 51 ± 13%), 20 (27%) presented with major VA [ventricular tachycardia/ventricular fibrillation (VT/VF)], and 32 (44%) had polymorphic VA. Patients with polymorphic VA more commonly had evidence of ongoing systemic infection (24/32 vs. 10/42, P = 0.004) and experienced greater occurrence of MAE at discharge (15/32 vs. 2/42, P < 0.001). However, the incidence of MAE during FU was higher in patients with monomorphic VA compared to those with polymorphic VA (17/42 vs. 2/28, P = 0.002). Patients with monomorphic VA displayed frequently signs of chronic cardiomyopathy and had outcomes comparable with virus-negative myocarditis (log rank P = 0.929). Presentation with VT/VF was independently associated with MAE [at discharge: hazard ratio (HR) 4.7, 95% confidence interval (CI) 1.6–14.0, P = 0.005; during FU: HR 6.3, 95% CI 2.3–17.6, P < 0.001].

Conclusion

In patients with VM, polymorphic VA point to ongoing systemic infection and early adverse outcomes, whereas monomorphic VA suggest chronic cardiomyopathy and greater incidence of MAE during FU. Presentation with VT/VF is independently associated with MAE.
Lack of temporal correlations between COVID pandemic waves and the occurrence of malignant ventricular arrhythmias
Authors: Foltran Deborah , Guilbeau-Frugier Céline , Marimpouy Nathan , Beneyto Maxime , Cherbi Miloud , Bongard Vanina , Maury Philippe
Published: December 2023

Aims

Correlations between malignant ventricular arrhythmias and the COVID waves have never been investigated.

Methods and results

Prevalence of malignant ventricular arrhythmias/sudden cardiac death has been correlated to the four COVID waves between the onset of pandemic and end 2021. No significant correlation was present in the temporal evolution of both COVID patients/positive tests and incidence of malignant ventricular arrhythmias, which tended to decrease after vaccination onset.

Conclusion

We present evidence of complex higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex vivo human hearts. We infer that the oscillation of the calcium cycling machinery is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability and may provide targets for substrate-based ablation of VF.
Transmembrane protein 120A (TMEM-120A/TACAN) coordinates with PIEZO channel during Caenorhabditis elegans reproductive regulation
Authors: Bai Xiaofei , Golden Andy
Published: December 2023

Membrane protein TMEM120A (also known as TACAN) was presumed to be both a mechanically activated molecule and a lipid-modifying enzyme. TMEM120A has been identified as a negative regulator of the essential excitatory mechanosensitive protein PIEZO2. However, the extent to which TMEM120A mediates PIEZO2's activity during physiological processes remains largely unknown. In this study, we used the Caenorhabditis elegans reproductive tract to explore the functional contribution of tmem-120, the sole TMEM120A/B ortholog, and its genetic interaction with pezo-1 in vivo. tmem-120 was expressed throughout the C. elegans development, particularly in the germline, embryos, and spermatheca. A tmem-120 mutant with a full-length deletion (tmem-120Δ) displayed deformed germline, maternal sterility, and a reduced brood size. In vivo live imaging revealed that pinched zygotes were frequently observed in the uterus of tmem-120Δ mutant animals, suggesting damage during spermathecal contraction. We then employed the auxin-inducible degradation system to degrade TMEM-120 protein in all somatic tissues or the germline, both of which resulted in reduced brood sizes. These findings suggested that multiple inputs of tmem-120 from different tissues regulate reproduction. Lastly, the loss of tmem-120 alleviated the brood size reduction and defective sperm navigation behavior in the pezo-1Δ mutant. Overall, our findings reveal a role for tmem-120 in regulating reproductive physiology in C. elegans, and suggest an epistatic interaction between pezo-1 and tmem-120 when governing proper reproduction.
Theoretical, numerical and experimental investigation into vibration characteristics for composite structures of an annular membrane internally connected with a piezoceramic disk
Authors: Ji Ming , Zhong Jia-Jin , Huang Yu-Hsi , Wu Yi-Chuang
Published: December 2023

This work analyzed the vibration characteristics of an annular membrane internally connected with a piezoceramic disk theoretically, numerically and experimentally. The general solution for the free vibration of an annular membrane under uniform tension was derived. Then, the displacement solutions for the piston modes and coupled modes of an annular membrane internally connected with a piezoceramic disk were derived. Two plate theories, Kirchhoff and Mindlin plate theories, were used to simulate the piezoceramic disk. The theoretical results are compared with the numerical results obtained from two finite element software packages: ABAQUS and COMSOL. The amplitude-fluctuation electronic speckle pattern interferometry was used to measure the resonant frequencies and associated mode shapes of five different type specimens with different sizes. Good agreements of dynamic characteristics determined by theoretical analysis, experimental measurements, and numerical calculation are presented for the annular membrane internally connected with piezoceramic disk structures.
Non-linear magnetic buoyancy instability and turbulent dynamo
Authors: Qazi Yasin , Shukurov Anvar , Tharakkal Devika , Gent Frederick A , Bendre Abhijit B
Published: December 2023

Stratified discs with strong horizontal magnetic fields, are susceptible to magnetic buoyancy instability (MBI). Modifying the magnetic field and gas distributions, this can play an important role in galactic evolution. The MBI and the Parker instability, in which MBI is exacerbated by cosmic rays, are often studied using an imposed magnetic field. However, in galaxies and accretion discs, the magnetic field is continuously replenished by a large-scale dynamo action. Using non-ideal MHD equations, we model a section of the galactic disc (we neglect rotation and cosmic rays considered elsewhere), in which the large-scale field is generated by an imposed α-effect of variable intensity to explore the interplay between dynamo instability and MBI. The system evolves through three distinct phases: the linear (kinematic) dynamo stage, the onset of linear MBI when the magnetic field becomes sufficiently strong and the non-linear, statistically steady state. Non-linear effects associated with the MBI introduce oscillations which do not occur when the field is produced by the dynamo alone. The MBI initially accelerates the magnetic field amplification but the growth is quenched by the vertical motions produced by MBI. We construct a 1D model, which replicates all significant features of 3D simulations to confirm that magnetic buoyancy alone can quench the dynamo and is responsible for the magnetic field oscillations. Unlike similar results obtained with an imposed magnetic field, the non-linear interactions do not reduce the gas scale height, so the consequences of the magnetic buoyancy depend on how the magnetic field is maintained.
Radiato-thermal self-similar funnel jets
Authors: Fukue J
Published: December 2023

Steady axisymmetric two-dimensional flows driven by radiation and gas pressures in the conical funnel formed by the supercritical accretion disc are examined using the fully self-similar treatment. The effect of alpha-viscosity is also considered. The self-similar solutions are found to be classified into three types: successful outflows of hollow-conical or funnel-filled solutions, failed inflows, which are gravitationally bound, and unphysical cases, where the flow meets the singularity or the radiation energy density becomes negative.
Examining quasar absorption-line analysis methods: the tension between simulations and observational assumptions key to modelling clouds
Authors: Marra Rachel , Churchill Christopher W , Kacprzak Glenn G , Nielsen Nikole M , Trujillo-Gomez Sebastian , Lewis Emmy A
Published: December 2023

A key assumption in quasar absorption-line studies of the circumgalactic medium (CGM) is that each absorption component maps to a spatially isolated ‘cloud’ structure that has single valued properties (e.g. density, temperature, metallicity). We aim to assess and quantify the degree of accuracy underlying this assumption. We used adaptive mesh refinement hydrodynamic cosmological simulations of two z = 1 dwarf galaxies and generated synthetic quasar absorption-line spectra of their CGM. For the Si ii λ1260 transition, and the C iv λλ1548, 1550 and O vi λλ1031, 1037 fine-structure doublets, we objectively determined which gas cells along a line of sight (LOS) contribute to detected absorption. We implemented a fast, efficient, and objective method to define individual absorption components in each absorption profile. For each absorption component, we quantified the spatial distribution of the absorbing gas. We studied a total of 1302 absorption systems containing a total of 7755 absorption components. 48  per cent of Si ii, 68  per cent of C iv, and 72  per cent of O vi absorption components arise from two or more spatially isolated ‘cloud’ structures along the LOS. Spatially isolated ‘cloud’ structures were most likely to have cloud–cloud LOS separations of 0.03Rvir (1.3 kpc), 0.11Rvir (4.8 kpc), and 0.13Rvir (5.6 kpc) for Si ii, C iv, and O vi, respectively. There can be very little overlap between multiphase gas structures giving rise to absorption components. If our results reflect the underlying reality of how absorption lines record CGM gas, they place tension on current observational analysis methods as they suggest that component-by-component absorption-line formation is more complex than is assumed and applied for chemical-ionization modelling.
3D models of fungal chromosomes to enhance visual integration of omics data
Authors: Poinsignon Thibault , Gallopin Mélina , Grognet Pierre , Malagnac Fabienne , Lelandais Gaëlle , Poulain Pierre
Published: December 2023

The functions of eukaryotic chromosomes and their spatial architecture in the nucleus are reciprocally dependent. Hi-C experiments are routinely used to study chromosome 3D organization by probing chromatin interactions. Standard representation of the data has relied on contact maps that show the frequency of interactions between parts of the genome. In parallel, it has become easier to build 3D models of the entire genome based on the same Hi-C data, and thus benefit from the methodology and visualization tools developed for structural biology. 3D modeling of entire genomes leverages the understanding of their spatial organization. However, this opportunity for original and insightful modeling is underexploited. In this paper, we show how seeing the spatial organization of chromosomes can bring new perspectives to omics data integration. We assembled state-of-the-art tools into a workflow that goes from Hi-C raw data to fully annotated 3D models and we re-analysed public omics datasets available for three fungal species. Besides the well-described properties of the spatial organization of their chromosomes (Rabl conformation, hypercoiling and chromosome territories), our results highlighted (i) in Saccharomyces cerevisiae, the backbones of the cohesin anchor regions, which were aligned all along the chromosomes, (ii) in Schizosaccharomyces pombe, the oscillations of the coiling of chromosome arms throughout the cell cycle and (iii) in Neurospora crassa, the massive relocalization of histone marks in mutants of heterochromatin regulators. 3D modeling of the chromosomes brings new opportunities for visual integration of omics data. This holistic perspective supports intuition and lays the foundation for building new concepts.
Risk Factors for Hospitalization and Effect of Immunosuppression on Clinical Outcomes Among an Urban Cohort of Patients With Mpox
Authors: Garneau William M , Jones Joyce L , Dashler Gabriella M , Mostafa Heba H , Judson Seth D , Kwon Nathan , Hamill Matthew M , Gilliams Elizabeth A , Rudolph David S , Keruly Jeanne C , Fall Amary , Klein Eili Y , Hansoti Bhakti , Gebo Kelly A
Published: December 2023

Background

During the 2022 mpox outbreak most patients were managed as outpatients, but some required hospitalization. Uncontrolled human immunodeficiency virus (HIV) has been identified as a risk factor for severe mpox.

Methods

Patients with mpox diagnosed or treated within the Johns Hopkins Health System between 1 June and 15 December 2022 were included. The primary outcome of interest was risk of hospitalization. Demographic features, comorbid conditions, treatment, and clinical outcomes were determined.

Results

A total of 353 patients were tested or treated for mpox; 100 had mpox diagnosed or treated (median age, 35.3 years; 97.0% male; 57.0% black and 10.0% Hispanic; 46.0% people with HIV [PWH]). Seventeen patients (17.0%) required hospitalization, 10 of whom were PWH. Age >40 years, race, ethnicity, HIV status, insurance status, and body mass index >30 (calculated as weight in kilograms divided by height in meters squared) were not associated with hospitalization. Eight of 9 patients (88.9%) with immunosuppression were hospitalized. Immunosuppression was associated with hospitalization in univariate (odds ratio, 69.3 [95% confidence interval, 7.8–619.7]) and adjusted analysis (adjusted odds ratio, 94.8 [8.5–1060.1]). Two patients (11.8%) who were hospitalized required intensive care unit admission and died; both had uncontrolled HIV infection and CD4 T-cell counts <50/µL. Median cycle threshold values for the first positive mpox virus sample did not differ between those who were hospitalized and those who were not.

Conclusions

Immunosuppression was a significant risk factor for hospitalization with mpox. PWH with CD4 T-cell counts <50/µL are at high risk of death due to mpox infection. Patients who are immunosuppressed should be considered for early and aggressive treatment of mpox, given the increased risk of hospitalization.
Conscience and the continuum of constitutionalism: John Calvin on civil government
Authors: Lee Constance
Published: December 2023

This article examines John Calvin’s theology on its own terms with the aim of appreciating the normative basis and implications of his political theory. Although the claim that Calvin’s account of civil government falls within the category of political ‘theology’ is less controversial, the normative implications of his theological ontology for political actors are more commonly contested. Calvin seminally wrote ‘on Civil Government’ in Book IV, Chapter xx of the Institutes of the Christian Religion. In contrast, his accounts of conscience and natural law are far less systemized.1 This article contends that this reticence is not due to lack of importance but rather, due to its foundational nature. Indeed, the opening statement of the Institutes is indicative of the coherence of the Reformer’s thoughts wherein any emerging polity is composed of what this article refers to as the ‘spheres-of-influence’ scheme—a normative system originating inward from the vertical relationship every human agent has with the divine, and then extending horizontally outwards to bind the collective in a common system of values. Such an ontology is predicated on the concepts of conscience and the divine image, which renders all persons, who possess this natural repository of moral knowledge, accountable to transcendent standards of virtue. It follows that when we overlay this ‘continuum’2 onto a constitutional framework, we place the priority, not on the individual rights of the citizen, but on the responsibilities of all political actors whereby others precede the self and the common good prevails over self-interest.
Temperature shapes language sonority: Revalidation from a large dataset
Authors: Wang Tianheng , Wichmann Søren , Xia Quansheng , Ran Qibin
Published: December 2023

Multiple factors of the natural environment have been found to impact and mold the phonetic patterns of human speech, among which the potential correlation between sonority and temperature has garnered significant attention. We leverage a large database containing basic vocabularies of 5,293 languages and calculate the average sonority for each language by adopting a universal sonority scale. Our findings confirm a positive correlation between sonority and temperature across macroareas and language families, whereas this relationship cannot be discerned within language families. We suggest that the adaptation of the distribution of speech sounds within languages is a slow process which is moreover insensitive to minor differences in temperature experienced by speakers as they carry their languages to new regions. Nevertheless, at the global level a solid relationship emerges. Furthermore, we delve deeper into the nature of the relationship and contend that it is mainly due to cold temperatures having a weakening effect on sonority. This research provides compelling additional evidence that climatic factors contribute to shaping language and its evolution.
Systematic assessment of transcriptomic and metabolic reprogramming by blue light exposure coupled with aging
Authors: Huang Jia , Zhou Fan , Zhou Huanchan , Zheng Xiaoqi , Huo Zhengyi , Yang Meng , Xu Zihe , Liu Runzhou , Wang Luoluo , Wang Xiaoyun
Published: December 2023

The prevalent use of light-emitting diodes (LEDs) has caused revolutionary changes in modern life, but the potential hazards to health of blue light are poorly understood. N6-methyladenosine (m6A) is the most prevalent posttranscriptional modification in eukaryotes and can modulate diverse physiological processes by regulating mRNA fate. Here, to understand the effects and molecular mechanisms of daily low-intensity blue light exposure (BLE) and ascertain whether m6A methylation plays a role in BLE-induced phenotypes, we constructed a series of Drosophila models under different durations of daily low-intensity BLE and obtained multiomics profiles. Our results revealed that BLE could induce transcriptomic, m6A epitranscriptomic, and metabolomic reprogramming in Drosophila along with aging process. Importantly, the m6A methylation sites enriched in the 5′ untranslated regions (UTRs) of Drosophila transcripts showed strong age specificity and could be altered by BLE. We experimentally validated that aging-related gene Tor and circadian rhythm-related gene per were regulated by 5′ UTR-enriched m6A methylation. Overall, our study provides a systematic assessment of m6A RNA methylome reprogramming by BLE and aging in Drosophila model.
The Complete and Gapless Genome Sequence of the Sugarbeet Pathogen Cercospora beticola
Authors: Wyatt Nathan A. , Spanner Rebecca E. , Bolton Melvin D.
Published: December 2023

Cercospora beticola, causal agent of Cercospora leaf spot of sugarbeet ( Beta vulgaris subsp. vulgaris), is the most economically damaging foliar pathogen inhibiting sugarbeet production. Despite the global importance of C. beticola, significant knowledge gaps exist pertaining to pathogen virulence and adaptation to management practices that include the use of resistant host varieties and the application of different fungicide chemistries. The lack of a high-quality reference genome for C. beticola has hindered research progression addressing these critical knowledge gaps. Here, we report the complete and gapless genome assembly and annotation of the reference C. beticola isolate Cb09-40. We identified misassembled regions in the previous reference genome and annotated previously missing protein-coding genes. This work establishes a high-quality reference genome that can serve as the foundation for future comparative genomic, population genetic, and evolutionary studies into the virulence and evolution of this important plant pathogen.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Association Between Doula Use on a Digital Health Platform and Birth Outcomes
Authors: Karwa Smriti , Jahnke Hannah , Brinson Alison , Shah Neel , Guille Constance , Henrich Natalie
Published: December 2023

OBJECTIVE:

To examine the association between the use of virtual doula appointments on a comprehensive digital health platform and users' mode of birth and their birth experiences, among all platform users and Black platform users.

METHODS:

Data for this retrospective cohort study were extracted from individuals who enrolled in a comprehensive digital health platform, between January 1, 2020, and April 22, 2023. Multivariable logistic regression models were used to estimate the association between number of virtual doula appointments completed on the digital health platform and odds of cesarean birth and user-reported birth experience outcomes, which included help deciding a birth preference, receiving a high level of support during pregnancy, learning medically accurate information about pregnancy complications and warning signs, and managing mental health during pregnancy, stratified by parity. The interaction of doula utilization by race for each outcome was also tested.

RESULTS:

Overall 8,989 platform users were included. The completion of at least two appointments with a virtual doula on the digital health platform was associated with a reduction in odds of cesarean birth among all users (adjusted odds ratio [aOR] 0.80, 95% CI, 0.65–0.99) and among Black users (aOR 0.32, 95% CI, 0.14–0.72). Among platform users with a history of cesarean birth, completion of any number of doula visits was associated with a reduction in odds of repeat cesarean birth (one visit: aOR 0.35, 95% CI, 0.17–0.72; two or more visits: aOR 0.37, 95% CI, 0.17–0.83). Analyses among all users indicated dose–response associations between increased virtual doula use and greater odds of users reporting support in deciding a birth preference (one visit: aOR 2.35, 95% CI, 2.02–2.74; two or more visits: aOR 3.67, 95% CI, 3.03–4.44), receiving a high level of emotional support during pregnancy (one visit: aOR 1.99, 95% CI, 1.74–2.28; two or more visits: aOR 3.26, 95% CI, 2.70–3.94), learning medically accurate information about pregnancy complications and warning signs (one visit: aOR 1.26, 95% CI, 1.10–1.44; two or more visits: aOR 1.55, 95% CI, 1.29–1.88), and help managing mental health during pregnancy (one visit: aOR 1.28, 95% CI, 1.05–1.56; two or more visits: aOR 1.78, 95% CI, 1.40–2.26).

CONCLUSION:

This analysis demonstrates that virtual doula support on a digital health platform is associated with lower odds of cesarean birth and an improved birth experience. Positive findings among Black users and users with vaginal birth after cesarean suggest that doula support is critical for patient advocacy, and that digital health may play a meaningful role in increasing health equity in birth outcomes.
A mobile health application for prostate cancer antigen dosage: is it time to say goodbye to classic screening methods?
Authors: Di Bello Francesco , di Mauro Ernesto , Fusco Giovanni Maria , Falcone Alfonso , Pezone Gabriele , Ruvolo Claudia Collà , Califano Gianluigi , Fraia Agostino , Passaro Francesco , Pepillo Francesco , Ranieri Alessandro , Alvino Pierluigi , Mastrangelo Francesco , Turco Carmine , Cirillo Luigi , Franzese Corrado Aniello , La Rocca Roberto , Creta Massimiliano , Longo Nicola , Napolitano Luigi
Published: December 2023

Objective

To evaluate the quality of apps for prostate cancer antigen (PSA) dosage, available for downloading on the iOS and Android platforms, discussing the potential role of mobile health applications (MHAs) in update the screening protocol.

Methods

An observational cross-sectional descriptive study of all smartphone apps for PSA dosage was performed through the most used platforms (iOS and Android). On 10 February 2023, a total of 457 apps were found according to the search criteria. Mobile Application Rating Scale (MARS) was adopted to assess apps’ quality. Then, MARS items were analyzed through descriptive statistics and bivariate correlations between study variables with Pearson’s coefficient.

Results

Of all samples, 24 MHAs were included in the final analysis: 12% (n = 3) from the iTunes App Store and 88% (n = 21) from the Google Play Store. According to the MARS quality assessment, the mean values 2.61, 2.94, 3.11, 2.97, 2.94, and 2.63 were measured for the engagement, functionality, aesthetics, information, overall mean score, and subjective quality, respectively.

Conclusion

The MHAs for PSA were under the acceptability threshold and future improvements are required. Moreover, MHAs appropriately developed could play an active role in PSA screening campaign and adherence of follow-up regimens. Finally, the virtual instrument could both reduce the social divide of access to care for patients in rural areas and improve PCA detection, speeding up the active treatment.
Incidence and Clinical Features of Immunologic Rejection After Deep Anterior Lamellar Keratoplasty
Authors: Kasamatsu Hirotsugu , Yamaguchi Takefumi , Yagi-Yaguchi Yukari , Nishisako Sota , Tomida Daisuke , Akiyama Masato , Murata Toshinori , Shimazaki Jun
Published: December 2023

Purpose:

The aim of this study was to investigate the incidence and clinical features of immunologic rejection after deep anterior lamellar keratoplasty (DALK).

Methods:

This study included 411 patients (464 eyes, median age [interquartile range; IQR] 55.8 years [36.1–69.5]) who underwent DALK at Tokyo Dental College between June 1997 and 2021. Of 411 patients, 24 (24 eyes [5.2%], 51.9 years [IQR 31.6–65.4]) developed immunologic rejection. We characterized the clinical features, risk factors associated with immunologic rejection, and prognosis.

Results:

The interval between DALK and immunologic rejection was 14.5 (range, 5–78) months. Immunologic rejection occurred after cessation/reduction of topical steroid in 9 (47.4%) and suture removal in 4 eyes (21.1%). The postoperative duration of topical steroid use in eyes with immunologic rejection was significantly shorter (10.0 months, [IQR 6.0–14.0]) than those without immunologic rejection (28.3 [IQR 15.8–42.7], P = 0.001). Immunologic rejection manifested as stromal edema in 19 (100.0%), ciliary hyperemia in 17 (89.5%), keratic precipitates in 13 (68.4%), epithelial edema in 13 (68.4%), infiltration in 9 (47.4%), corneal opacity in 4 (21.1%), and Descemet membrane detachment in 2 eyes (10.5%). After treatment, corneal clarity was restored in 17 eyes (89.5%); however, immunologic rejection led to corneal endothelial decompensation in 2 eyes (10.5%). Endothelial cell density decreased from 1795.7 ± 722.6 to 1651.6 ± 655.6 cells/mm2 after immunologic rejection (P = 0.074).

Conclusions:

Post-DALK immunologic rejection was associated with specific clinical triggers such as reduction/cessation of topical steroids or suture removal.
Successful robotic kidney transplantation for surgeons with no experience in minimally invasive surgery: a single institution experience
Authors: Kim Hyun Jeong , Jeong Wooju , Lee Juhan , Yang Seok Jeong , Lee Jong Soo , Na Joon Chae , Han Woong Kyu , Huh Kyu Ha
Published: December 2023

Background:

Robotic kidney transplantation (RKT) is a novel and welcomed innovation yielding good surgical outcomes. However, data on the feasibility and safety of performing RKT by surgeons with a lack of prior minimally invasive surgery (MIS) experience are limited. The authors aimed to evaluate the surgical and functional results of RKT and present the learning curves (LC) of RKT by a single surgeon with no prior experience in MIS.

Materials and methods:

This was a retrospective study of all RKT performed between November 2019 and April 2023 at Severance Hospital in Seoul, South Korea. The authors analyzed surgical and functional outcomes, as well as complication rates of RKT in comparison to open kidney transplantation (OKT). The authors evaluated LCs using the cumulative summation method to describe the number of cases associated with the competency of a single surgeon.

Results:

A total of 50 patients who underwent RKT and 104 patients who underwent OKT were included in this study. In RKT group, the median surgical console time was 193 min (interquartile range, 172–222) and the median vascular anastomoses time was 38 min (35–44). Total operation time was 323 min (290–371) and rewarming time was 62.5 min (56.0–70.0) in RKT group compared to 210 min (190–239) and 25 min (21–30), respectively, in OKT group. Despite extended surgical durations with a robotic technique, both groups had comparable intraoperative and postoperative outcomes, as well as renal function. Estimated blood loss and post-transplant hospital stays were significantly lower in RKT group than in OKT group. LC analysis of RKT by the single surgeon revealed that surgical competence was achieved after 15 cases.

Conclusion:

Even if surgeons do not have prior experience with MIS, they can rapidly overcome the LC and safely perform RKT with adequate preparation and acquisition of basic robotic surgical techniques.
Leveraging artificial intelligence for perioperative cancer risk assessment of oral potentially malignant disorders
Authors: Adeoye John , Su Yu-Xiong
Published: December 2023

Oral potentially malignant disorders (OPMDs) are mucosal conditions with an inherent disposition to develop oral squamous cell carcinoma. Surgical management is the most preferred strategy to prevent malignant transformation in OPMDs, and surgical approaches to treatment include conventional scalpel excision, laser surgery, cryotherapy, and photodynamic therapy. However, in reality, since all patients with OPMDs will not develop oral squamous cell carcinoma in their lifetime, there is a need to stratify patients according to their risk of malignant transformation to streamline surgical intervention for patients with the highest risks. Artificial intelligence (AI) has the potential to integrate disparate factors influencing malignant transformation for robust, precise, and personalized cancer risk stratification of OPMD patients than current methods to determine the need for surgical resection, excision, or re-excision. Therefore, this article overviews existing AI models and tools, presents a clinical implementation pathway, and discusses necessary refinements to aid the clinical application of AI-based platforms for cancer risk stratification of OPMDs in surgical practice.
Predictors and mortality of new onset postoperative atrial fibrillation after STAAD surgery: a retrospective cohort study
Authors: Li Dongjie , Fang Zhou , Liu Maomao , Li Haibin , Zhang Hongjia , Li Haiyang , Liu Yuyong , Jiang Wenjian
Published: December 2023

Background:

Data on new onset postoperative atrial fibrillation (POAF) after Stanford type A dissection (STAAD) surgery was limited. This study aimed to detect the risk factors for developing POAF after STAAD procedures and the association between POAF and in-hospital mortality.

Methods:

A total of 1354 patients who underwent surgical treatment for STAAD in Beijing Anzhen hospital were enrolled in this single-center retrospective study from January 2015 to October 2020. POAF were defined as atrial fibrillation/flutter requiring treatment after surgery procedure. Logistic model was conducted to detect the predictors of POAF, and inverse probability of treatment weighting (IPTW) and subgroup analysis were used to compare the mortality of POAF and non-POAF groups.

Results:

There were 176 patients (13.0%) diagnosed with POAF according to the definition. Multivariate logistics analyses revealed that advanced age [odds ratio (OR), 1.07; 95% CI: 1.05–1.08; P<0.001)], creatinine (OR, 1.00; 95% CI: 1.00–1.01; P=0.001) and cross-clamp time (OR, 1.00; 95% CI: 1.00–1.01; P=0.021) were independent risk factors of developing POAF in STAAD patients. POAF patients were associated with significantly higher in-hospital mortality compared with non-POAF patients (6.5 vs. 19.9%, OR, 3.60; 95% CI: 2.30–5.54; P<0.001), IPTW and subgroup analysis had reached consistent conclusions.

Conclusions:

The incidence of POAF was 13.0% after STAAD surgery, advanced age, creatinine, and cross-clamp time were independent risk factors of developing POAF in STAAD patients. POAF is associated with increased mortality after STAAD procedures.
Pharmacists Colocated With Primary Care Physicians
Authors: Hawes Emily M. , Page Cristen , Galloway Evan , McClurg Mary Roth , Lombardi Brianna
Published: December 2023

Background:

While evidence supports interprofessional primary care models that include pharmacists, the extent to which pharmacists are working in primary care and the factors associated with colocation is unknown.

Objectives:

This study aimed to analyze the physical colocation of pharmacists with primary care providers (PCPs) and examine predictors associated with colocation.

Research Design:

This is a retrospective cross-sectional study of pharmacists and PCPs with individual National Provider Identifiers in the National Plan and Provider Enumeration System’s database. Pharmacist and PCP practice addresses of the health care professionals were geocoded, and distances less than 0.1 miles were considered physically colocated.

Subjects:

In all, 502,373 physicians and 221,534 pharmacists were included.

Results:

When excluding hospital-based pharmacists, 1 in 10 (11%) pharmacists were colocated with a PCP. Pharmacists in urban settings were more likely to be colocated than those in rural areas (OR=1.32, CI: 1.26–1.38). Counties with the highest proportion of licensed pharmacists per 100,000 people in the county had higher colocation (OR=1.38, CI: 1.32–1.45). Colocation was significantly higher in states with an expanded scope of practice (OR 1.37, CI: 1.32–1.42) and those that have expanded Medicaid (OR 1.07, CI: 1.03–1.11). Colocated pharmacists more commonly worked in larger physician practices.

Conclusion:

Although including pharmacists on primary care teams improves clinical outcomes, reduces health care costs, and enhances patient and provider experience, colocation appears to be unevenly dispersed across the United States, with lower rates in rural areas. As the integration of pharmacists in primary care continues to expand, knowing the prevalence and facilitators of growth will be helpful to policymakers, researchers, and clinical administrators.
The clinical utility of three frailty measures in identifying HIV-associated neurocognitive disorders
Authors: Moore David J. , Sun-Suslow Ni , Nichol Ariadne A. , Paolillo Emily W. , Saloner Rowan , Letendre Scott L. , Iudicello Jennifer , Morgan Erin E.
Published: December 2023

Objective:

Frailty measures vary widely and the optimal measure for predicting HIV-associated neurocognitive disorders (HAND) is unclear.

Design:

A study was conducted to examine the clinical utility of three widely used frailty measures in identifying HIV-associated neurocognitive disorders.

Methods:

The study involved 284 people with HIV (PWH) at least 50 years enrolled at UC San Diego's HIV Neurobehavioral Research Program. Frailty measurements included the Fried Phenotype, the Rockwood Frailty Index, and the Veterans Aging Cohort Study (VACS) Index. HAND was diagnosed according to Frascati criteria. ANOVAs examined differences in frailty severity across HAND conditions. ROC analyses evaluated sensitivity and specificity of each measure to detect symptomatic HAND [mild neurocognitive disorder (MND) and HIV-associated dementia (HAD)] from no HAND.

Results:

Across all frailty measures, frailty was found to be higher in HAD compared with no HAND. For Fried and Rockwood (not VACS), frailty was significantly more severe in MND vs. no HAND and in HAD vs. ANI (asymptomatic neurocognitive impairment). For discriminating symptomatic HAND from no HAND, Fried was 37% sensitive and 92% specific, Rockwood was 85% sensitive and 43% specific, and VACS was 58% sensitive and 65% specific.

Conclusion:

These findings demonstrate that Fried and Rockwood outperform VACS in predicting HAND. However, ROC analyses suggest none of the indices had adequate predictive validity in detecting HAND. The results indicate that the combined use of the Rockwood and Fried indices may be an appropriate alternative.
Promising Therapeutic Activity of 177Lu-PSMA-617 in Synchronous High-Volume Metastatic Hormone-Sensitive Prostate Cancer
Authors: Satapathy Swayamjeet , Yadav Madhav Prasad , Ballal Sanjana , Sahoo Ranjit Kumar , Bal Chandrasekhar
Published: December 2023

Purpose

177Lu-PSMA-617 has been shown to improve survival outcomes in patients with end-stage metastatic castration-resistant prostate cancer. However, data in earlier lines remain limited. In this study, we intended to evaluate the efficacy and safety of 177Lu-PSMA-617 in patients with synchronous high-volume metastatic hormone-sensitive prostate cancer (mHSPC).

Patients and Methods

Hormone-sensitive prostate cancer patients with synchronous high-volume metastases (defined as ≥4 skeletal metastases with ≥1 extra-axial site or any visceral metastasis) showing high PSMA expression on 68Ga-PSMA-11 PET/CT and ineligible/unwilling for conventional chemohormonal treatment options were selected. Approximately, ~5.55–7.4 GBq of 177Lu-PSMA-617 was administered intravenously at 8–12 weeks intervals, up to 6 cycles. All patients underwent concomitant androgen deprivation therapy/orchiectomy. The outcome measures included the proportion of patients achieving an undetectable serum prostate-specific antigen (PSA) (ie, ≤0.2 ng/mL) at any time point after therapy, best PSA response rate, objective radiographic response rate, radiographic progression-free survival, overall survival, and adverse events.

Results

Ten patients with high-volume mHSPC received a median cumulative activity of 32.4 GBq (range, 7.4–44.4) of 177Lu-PSMA-617 over 1–6 cycles. Five patients (50%) achieved an undetectable PSA with 9 patients (90%) showing a ≥50% decline in PSA from baseline. Nine patients underwent radiological follow-up, of which 7 (77.8%) had an objective response. The median radiographic progression-free survival was 24 months (95% confidence interval, 18–30), whereas the median overall survival was not reached. None of the patients had any grade 3/4 adverse event.

Conclusions

177Lu-PSMA-617 seems to be a promising efficacious and safe treatment option for patients with synchronous high-volume mHSPC.