bluuebunny/crossref_metadata_2025 huggingface dataset:
Auditory aversive generalization learning prompts threat-specific changes in alpha-band activity
Authors: Farkas Andrew H , Ward Richard T , Gilbert Faith E , Pouliot Jourdan , Chiasson Payton , McIlvanie Skylar , Traiser Caitlin , Riels Kierstin , Mears Ryan , Keil Andreas
Published: March 2024

Pairing a neutral stimulus with aversive outcomes prompts neurophysiological and autonomic changes in response to the conditioned stimulus (CS+), compared to cues that signal safety (CS−). One of these changes—selective amplitude reduction of parietal alpha-band oscillations—has been reliably linked to processing of visual CS+. It is, however, unclear to what extent auditory conditioned cues prompt similar changes, how these changes evolve as learning progresses, and how alpha reduction in the auditory domain generalizes to similar stimuli. To address these questions, 55 participants listened to three sine wave tones, with either the highest or lowest pitch (CS+) being associated with a noxious white noise burst. A threat-specific (CS+) reduction in occipital–parietal alpha-band power was observed similar to changes expected for visual stimuli. No evidence for aversive generalization to the tone most similar to the CS+ was observed in terms of alpha-band power changes, aversiveness ratings, or pupil dilation. By-trial analyses found that selective alpha-band changes continued to increase as aversive conditioning continued, beyond when participants reported awareness of the contingencies. The results support a theoretical model in which selective alpha power represents a cross-modal index of continuous aversive learning, accompanied by sustained sensory discrimination of conditioned threat from safety cues.
Distinct and common mechanisms of cross-model semantic conflict and response conflict in an auditory relevant task
Authors: Xu Honghui , Yang Guochun , Göschl Florian , Nolte Guido , Ren Qiaoyue , Li Zhenghan , Wu Haiyan , Engel Andreas K , Li Qi , Liu Xun
Published: March 2024

The mechanisms of semantic conflict and response conflict in the Stroop task have mainly been investigated in the visual modality. However, the understanding of these mechanisms in cross-modal modalities remains limited. In this electroencephalography (EEG) study, an audiovisual 2–1 mapping Stroop task was utilized to investigate whether distinct and/or common neural mechanisms underlie cross-modal semantic conflict and response conflict. The response time data showed significant effects on both cross-modal semantic and response conflicts. Interestingly, the magnitude of semantic conflict was found to be smaller in the fast response time bins than in the slow response time bins, whereas no such difference was observed for response conflict. The EEG data demonstrated that cross-modal semantic conflict specifically increased the N450 amplitude. However, cross-modal response conflict specifically enhanced theta band power and theta phase synchronization between the medial frontal cortex (MFC) and lateral prefrontal electrodes as well as between the MFC and motor electrodes. In addition, both cross-modal semantic conflict and response conflict led to a decrease in P3 amplitude. Taken together, these findings provide cross-modal evidence for domain-specific mechanism in conflict detection and suggest both domain-specific and domain-general mechanisms exist in conflict resolution.
Quantification of mediation effects of white matter functional characteristics on cognitive decline in aging
Authors: Li Muwei , Schilling Kurt G , Gao Fei , Xu Lyuan , Choi Soyoung , Gao Yurui , Zu Zhongliang , Anderson Adam W , Ding Zhaohua , Landman Bennett A , Gore John C
Published: March 2024

Cognitive decline with aging involves multifactorial processes, including changes in brain structure and function. This study focuses on the role of white matter functional characteristics, as reflected in blood oxygenation level-dependent signals, in age-related cognitive deterioration. Building on previous research confirming the reproducibility and age-dependence of blood oxygenation level-dependent signals acquired via functional magnetic resonance imaging, we here employ mediation analysis to test if aging affects cognition through white matter blood oxygenation level-dependent signal changes, impacting various cognitive domains and specific white matter regions. We used independent component analysis of resting-state blood oxygenation level-dependent signals to segment white matter into coherent hubs, offering a data-driven view of white matter’s functional architecture. Through correlation analysis, we constructed a graph network and derived metrics to quantitatively assess regional functional properties based on resting-state blood oxygenation level-dependent fluctuations. Our analysis identified significant mediators in the age-cognition relationship, indicating that aging differentially influences cognitive functions by altering the functional characteristics of distinct white matter regions. These findings enhance our understanding of the neurobiological basis of cognitive aging, highlighting the critical role of white matter in maintaining cognitive integrity and proposing new approaches to assess interventions targeting cognitive decline in older populations.
Bacterial diversity in a continuum from supraglacial habitats to a proglacial lake on the Tibetan Plateau
Authors: Xing Tingting , Liu Keshao , Ji Mukan , Chen Yuying , Liu Yongqin
Published: March 2024

Mountain glaciers are frequently assessed for their hydrological connectivity from glaciers to proglacial lakes. Ecological process on glacier surfaces and downstream ecosystems have often been investigated separately, but few studies have focused on the connectivity between the different glacial habitats. Therefore, it remains a limited understanding of bacterial community assembly across different habitats along the glacier hydrological continuum. In this study, we sampled along a glacial catchment from supraglacial snow, cryoconite holes, supraglacial runoff, ice-marginal moraine and proglacial lake on the Tibetan Plateau. The bacterial communities in these habitats were analyzed using high-throughput DNA sequencing of the 16S rRNA gene to determine the bacterial composition and assembly. Our results showed that each habitat hosted unique bacterial communities, with higher bacterial α-diversity in transitional habitats (e.g. runoff and ice-marginal moraine). Null model analysis indicated that deterministic processes predominantly shaped bacterial assembly in snow, cryoconite holes and lake, while stochastic process dominantly governed bacterial community in transitional habitats. Collectively, our findings suggest that local environment play a critical role in filtering bacterial community composition within glacier habitats. This study enhances our understanding of microbial assembly process in glacier environments and provides valuable insights into the factors governing bacterial community compositions across different habitats along the glacial hydrological continuum.
Evolution and genetics of accessory gland transcriptome divergence between Drosophila melanogaster and D. simulans
Authors: Majane Alex C , Cridland Julie M , Blair Logan K , Begun David J
Published: March 2024

Studies of allele-specific expression in interspecific hybrids have provided important insights into gene-regulatory divergence and hybrid incompatibilities. Many such investigations in Drosophila have used transcriptome data from complex mixtures of many tissues or from gonads, however, regulatory divergence may vary widely among species, sexes, and tissues. Thus, we lack sufficiently broad sampling to be confident about the general biological principles of regulatory divergence. Here, we seek to fill some of these gaps in the literature by characterizing regulatory evolution and hybrid misexpression in a somatic male sex organ, the accessory gland, in F1 hybrids between Drosophila melanogaster and D. simulans. The accessory gland produces seminal fluid proteins, which play an important role in male and female fertility and may be subject to adaptive divergence due to male–male or male–female interactions. We find that trans differences are relatively more abundant than cis, in contrast to most of the interspecific hybrid literature, though large effect-size trans differences are rare. Seminal fluid protein genes have significantly elevated levels of expression divergence and tend to be regulated through both cis and trans divergence. We find limited misexpression (over- or underexpression relative to both parents) in this organ compared to most other Drosophila studies. As in previous studies, male-biased genes are overrepresented among misexpressed genes and are much more likely to be underexpressed. ATAC-Seq data show that chromatin accessibility is correlated with expression differences among species and hybrid allele-specific expression. This work identifies unique regulatory evolution and hybrid misexpression properties of the accessory gland and suggests the importance of tissue-specific allele-specific expression studies.
Reconceptualizing the Nation in Sanctuary Practices: Toward a Progressive, Relational National Politics?
Authors: Wyn Edwards Catrin , Dafydd Jones Rhys
Published: March 2024

This article explores sanctuary in Wales, focusing on the Welsh Government’s recent declaration to become a Nation of Sanctuary (NoS), and identifying how the national scale provides an alternative locus for progressive sanctuary measures. In revealing the nation’s emergence as another crucial site of sanctuary, the work reconceptualizes the nation’s place in sanctuary policies and practices in two ways: (i) it locates sanctuary through a national scale, thus moving beyond the city/state dichotomy that has dominated explanations of sanctuary, and (ii) it shows the importance of decoupling the nation-state compound while simultaneously integrating the nation(al) into discussions on sanctuary without being bound to the state or xenophobic populism. In showing how “nations against the state” can participate in sanctuary measures, we expand the current understanding of where sanctuary can be found, and capture the various forms of national belonging and identities that exist within plurinational states, including alternative, progressive forms of civic belonging. This is particularly significant in light of the tightening of state immigration policies, greater regulation of immigrant entry at state borders, and continuation of restrictive citizenship policies witnessed in recent years, which have ignited sanctuary measures aimed at creating safe spaces beyond the reach of state measures.
Blockchain as a database—proposal for a new test for the criterion of ‘independence’ in the legal definition of a database for the purposes of copyright and the sui generis right
Authors:  Ari Ilsu Erdem
Published: March 2024

Technology’s exponential growth often outpaces that of the law. The persistence of outdated legal concepts that were not drafted with new technology in mind leads to legal uncertainty. This article focuses on one example of such a friction between old law and new technology, namely the eligibility of blockchain as a‘database’ for protection under the EU Database Directive, as implemented into UK copyright law. The most problematic requirement for blockchain as a candidate is that the material inside the database be ‘independent’. This can pose a significant hurdle for blockchain to succeed as the immutability of blockchain is ensured by the ‘linked-list’ structure in between the blocks and the combinational hashing of data within the individual block. This article examines this issue and proposes a solution to this quandary: to divide the data recorded on a blockchain into ‘content’ and ‘structure’, and confine the criterion of ‘independence’ to the former. In reaching this solution, the author examines previous literature on the different types of data that can be found in databases, as well as how the concept of ‘independence’ is understood by judges and academics. This article will be of practical significance for developers of non-open source blockchain applications who wish to protect their products as a database.
Mechanism of oxalate decarboxylase Oxd_S12 from Bacillus velezensis BvZ45-1 in defence against cotton verticillium wilt
Authors: Sun Ying , Yang Na , Li Sirui , Chen Fei , Xie Yijing , Tang Canming
Published: March 2024

Verticillium wilt, a soilborne vascular disease caused by Verticillium dahliae, strongly affects cotton yield and quality. In this study, an isolated rhizosphere bacterium, designated Bacillus velezensis BvZ45-1, exhibited >46% biocontrol efficacy against cotton verticillium wilt under greenhouse and field conditions. Moreover, through crude protein extraction and mass spectrometry analyses, we found many antifungal compounds present in the crude protein extract of BvZ45-1. The purified oxalate decarboxylase Odx_S12 from BvZ45-1 inhibited the growth of V. dahliae Vd080 by reducing the spore yield, causing mycelia to rupture, spore morphology changes, cell membrane rupture, and cell death. Subsequently, overexpression of Odx_S12 in Arabidopsis significantly improved plant resistance to V. dahliae. Through studies of the resistance mechanism of Odx_S12, V. dahliae was shown to produce oxalic acid (OA), which has a toxic effect on Arabidopsis leaves. Odx_S12 overexpression reduced Arabidopsis OA content, enhanced tolerance to OA, and improved resistance to verticillium wilt. Transcriptomics and quantitative real-time PCR analysis revealed that Odx_S12 promoted a reactive oxygen species burst and a salicylic acid- and abscisic acid-mediated defence response in Arabidopsis. In summary, this study not only identified B. velezensis BvZ45-1 as an efficient biological control agent, but also identified the resistance gene Odx_S12 as a candidate for cotton breeding against verticillium wilt.
Imaging and spectroscopic observations of a confined solar filament eruption with two-stage evolution
Authors: Xu Zhe , Yan Xiaoli , Yang Liheng , Xue Zhike , Wang Jincheng , Zhou Yian
Published: March 2024

Solar filament eruptions are often characterized by stepwise evolution due to the involvement of multiple mechanisms, such as magnetohydrodynamic instabilities and magnetic reconnection. In this article, we investigated a confined filament eruption with a distinct two-stage evolution by using the imaging and spectroscopic observations from the Interface Region Imaging Spectrograph and the Solar Dynamics Observatory. The eruption originated from a kinked filament thread that separated from an active region filament. In the first stage, the filament thread rose slowly and was obstructed due to flux pile-up in its front. This obstruction brought the filament thread into reconnection with a nearby loop-like structure, which enlarged the flux rope and changed its connectivity through the foot-point migration. The newly formed flux rope became more kink unstable and drove the rapid eruption in the second stage. It ascended into the upper atmosphere and initiated the reconnection with the overlying field. Finally, the flux rope was totally disintegrated, producing several solar jets along the overlying field. These observations demonstrate that the external reconnection between the flux rope and overlying field can destroy the flux rope, thus playing a crucial role in confining the solar eruptions.
The bicoherence study of quasi-periodic oscillations in MAXI J1535−571
Authors: Zhu Ziyuan , Chen Xiao , Wang Wei
Published: March 2024

Bicoherence is a way to measure the phase coupling of triplets of Fourier frequencies. We use this method to analyse quasi-periodic oscillations (QPOs) in the black hole X-ray binary MAXI J1535−571 during its 2017 September–October outburst. The bicoherence provides an interesting new diagnostic to uncover QPO behaviour and the relationships between QPO harmonics and broad-band noise. The bicoherence pattern of type-C QPOs starts as a ‘web’ pattern and changes to a ‘hypotenuse’ pattern after the presence of type-B QPOs, indicating that MAXI J1535−571 is a low-inclination source. The intensity of bicoherence also exhibits variations across different energy bands. We try to explain the bicoherence results in the scenario of a dual-corona geometry.
Long-term persistence to onabotulinumtoxinA to prevent chronic migraine: results from 11 years of patient data from a tertiary headache center
Authors: Moskatel Leon S , Graber-Naidich Anna , He Zihuai , Zhang Niushen
Published: March 2024

Objective

To determine if patients with chronic migraine continue onabotulinumtoxinA (onabotA) long-term.

Methods

We performed a retrospective cohort analysis using aggregated, de-identified patient data from the Stanford Headache Center. We included patients in California who received at least one prescription for onabotA during the years of 2011–2021. The primary outcome was the number of onabotA treatments each patient received. Secondary outcomes included sex, age, race, ethnicity, body mass index (BMI), distance to the treatment facility, and zip code income quartile.

Results

A total of 1551 patients received a mean of 7.60 ± 7.26 treatments and a median of 5 treatments, with 16.2% of patients receiving only one treatment and 10.6% receiving at least 19. Time-to-event survival analysis suggested 26.0% of patients would complete at least 29 treatments if able. Younger age and female sex were associated with statistically significant differences between quartile groups of number of onabotA treatments (P = .007, P = .015). BMI, distance to treatment facility, and zip code income quartile were not statistically significantly different between quartile groups (P > .500 for all). Prescriptions of both triptans and non-onabotA preventive medications showed a statistically significant increase with each higher quartile of number of onabotA treatments (P < .001; P < .001).

Discussion

We show long-term persistence to onabotA is high and that distance to treatment facility and income are not factors in continuation. Our work also demonstrates that as patients continue onabotA over time, there may be an increased need for adjunctive or alternative treatments.
Bond Price Fragility and the Structure of the Mutual Fund Industry
Authors: Giannetti Mariassunta , Jotikasthira Chotibhak
Published: March 2024

We conjecture that mutual funds with large shares of outstanding bond issues are more inclined to internalize the negative price spillovers of fire sales and thus sell their holdings in those issues, to a lower extent, when they experience redemptions. We provide evidence consistent with this conjecture and further show that ownership concentration limits bonds’ exposures to flow-induced fire sales. We exploit variation in negative spillovers arising from the Fed’s SMCCF to confirm the economic mechanism and explore our findings’ implications for fund performance and fire-sale spillovers to other funds.
Unveiling the distinctive ossification patterns of diffuse idiopathic skeletal hyperostosis and ankylosing spondylitis using computed tomography three-dimensional reconstruction
Authors: Liao Simin , Zhu Jian , Cheng Liuquan , Zhao Zheng , Ji Xiaojian , Zhang Jianglin , Huang Feng
Published: March 2024

Objective

To quantitatively analyse the morphological characteristics of osteophytes in DISH and syndesmophytes in AS, and summarize different ossification patterns to help identify the two diseases. Associated factors for new bone formation would be investigated.

Methods

Fifty patients with DISH and 50 age-, sex-, CT examination site-matched patients with AS were enrolled. Radiographic and clinical data were reviewed. Osteophytes (syndesmophytes) in front of each vertebral body and the corresponding intervertebral disc space were defined as vertebral osteophytes unit (VOU). The volume, angle and location (contralateral, ipsilateral, bilateral) of osteophytes in each VOU were measured and compared between DISH and AS groups.

Results

In each VOU, the volume and angle of osteophytes in DISH were significantly larger. The best osteophytes volume and angle cutoff value in predicting DISH was 0.59 cm3 and 40.15°. Contralateral, bilateral, ipsilateral osteophytes were recorded in 59.32%, 36.38%, 4.3% of assessed VOUs in patients with DISH and 64.78%, 29.31%, 5.91% in AS (P < 0.001), respectively. As to ipsilateral osteophytes, the volume was inversely correlated with the centre of the vertebral body to the centre of the descending aorta (DISH: r = −0.45, P = 0.01; AS: r = −0.83, P < 0.001). Advanced age, disease duration, smoking and overweight contribute to the progression of osteophytes and syndesmophytes.

Conclusion

Morphological features of osteophytes are helpful to distinguish DISH with AS. Aortic pulsations inhibit or hinder new bone formation in both DISH and AS. Maintaining normal BMI could postpone osteophytes formation.
Improvement of high-density lipoprotein atheroprotective properties in patients with systemic lupus erythematosus after belimumab treatment
Authors: Dedemadi Anastasia-Georgia , Gkolfinopoulou Christina , Nikoleri Dimitra , Nikoloudaki Myrto , Ruhanen Hanna , Holopainen Minna , Käkelä Reijo , Christopoulou Georgia , Bournazos Stavros , Constantoulakis Pantelis , Sidiropoulos Prodromos , Bertsias George , Chroni Angeliki
Published: March 2024

Objective

Chronic inflammatory diseases, like Systemic Lupus Erythematosus (SLE), carry an increased risk for atherosclerosis and cardiovascular events, accompanied by impairment of atheroprotective properties of high-density lipoprotein (HDL). In SLE, serum B cell-activating factor (BAFF), a cytokine implicated in disease progression, has been correlated with subclinical atherosclerosis. We investigated the impact of treatment with belimumab -an anti-BAFF monoclonal antibody- on HDL atheroprotective properties and composition in SLE patients.

Methods

Serum samples were collected from 35 SLE patients with active disease despite conventional therapy, before and after 6-month add-on treatment with belimumab, and 26 matched healthy individuals. We measured cholesterol efflux and antioxidant capacities, paraoxonase-1 (PON1) activity, serum amyloid A1 (SAA1), myeloperoxidase (MPO) and lipid peroxidation product levels of HDL. LC-MS/MS was performed to analyse the HDL lipidome.

Results

Following treatment with belimumab, cholesterol efflux and antioxidant capacities of HDL were significantly increased in SLE patients and restored to levels of control subjects. HDL-associated PON1 activity was also increased, whereas lipid peroxidation products were decreased following treatment. HDL cholesterol efflux and antioxidant capacities correlated negatively with the disease activity. Changes were noted in the HDL lipidome of SLE patients following belimumab treatment, as well as between SLE patients and healthy individuals, and specific changes in lipid species correlated with functional parameters of HDL.

Conclusions

HDL of SLE patients with active disease displays impaired atheroprotective properties accompanied by distinct lipidomic signatures compared with controls. Belimumab treatment may improve the HDL atheroprotective properties and modify the HDL lipidomic signature in SLE patients, thus potentially mitigating atherosclerosis development.
Quantitative cross-species comparison of serum albumin binding of per- and polyfluoroalkyl substances from five structural classes
Authors: Starnes Hannah M , Jackson Thomas W , Rock Kylie D , Belcher Scott M
Published: March 2024

Per- and polyfluoroalkyl substances (PFAS) are a class of over 8000 chemicals, many of which are persistent, bioaccumulative, and toxic to humans, livestock, and wildlife. Serum protein binding affinity is instrumental in understanding PFAS toxicity, yet experimental binding data is limited to only a few PFAS congeners. Previously, we demonstrated the usefulness of a high-throughput, in vitro differential scanning fluorimetry assay for determination of relative binding affinities of human serum albumin for 24 PFAS congeners from 6 chemical classes. In the current study, we used this assay to comparatively examine differences in human, bovine, porcine, and rat serum albumin binding of 8 structurally informative PFAS congeners from 5 chemical classes. With the exception of the fluorotelomer alcohol 1H, 1H, 2H, 2H-perfluorooctanol (6:2 FTOH), each PFAS congener bound by human serum albumin was also bound by bovine, porcine, and rat serum albumin. The critical role of the charged functional headgroup in albumin binding was supported by the inability of albumin of each species tested to bind 6:2 FTOH. Significant interspecies differences in serum albumin binding affinities were identified for each of the bound PFAS congeners. Relative to human albumin, perfluoroalkyl carboxylic and sulfonic acids were bound with greater affinity by porcine and rat serum albumin, and the perfluoroalkyl ether acid congener bound with lower affinity to porcine and bovine serum albumin. These comparative affinity data for PFAS binding by serum albumin from human, experimental model, and livestock species reduce critical interspecies uncertainty and improve accuracy of predictive bioaccumulation and toxicity assessments for PFAS.
Marfan syndrome
Authors: Spencer Michelle
Published: March 2024

This article provides a comprehensive review of Marfan Syndrome (MFS), covering its epidemiology, etiology, clinical presentations, diagnostics, complications, and treatment modalities. The Ghent II Nosology of MFS criteria are crucial in MFS diagnosis, guiding clinicians in identifying high-risk patients. Nursing implications underscore the importance of screenings, assessments, and close follow-ups to optimize the continuum of care for individuals with MFS.
Posttraumatic Cubitus Varus: Respect the Columns
Authors: Schlauch Adam M. , Manske Mary Claire , Leshikar Holly B. , Davids Jon R.
Published: March 2024

Posttraumatic cubitus varus is a multiplanar deformity that results from an improperly reduced supracondylar humerus fracture. The prevention of posttraumatic cubitus varus hinges on the stable restoration of all 3 columns of the distal humerus while avoiding malrotation. The collapse of any column leads to varying degrees of deformity in the coronal, sagittal, and/or axial plane. The purpose of this article is to explain the pattern of the deformity and use this to summarize preventative tactics for avoiding its described sequelae. We also summarize, illustrate, and present case examples for the various osteotomies used to correct the deformity, and speculate future directions.
Chinese expert consensus on anti-thrombotic therapy for pan-vascular diseases (2023 edition)
Authors:   Chinese College of Cardiovascular Physicians
Published: March 2024

Pan-vascular disease is a systemic condition characterized by vascular lesions, with atherosclerosis comprising 95% of cases, manifesting as coronary artery disease, cerebrovascular disease, peripheral artery disease, or combinations thereof, known as multivascular disease. In China, the burden of pan-vascular diseases is substantial, necessitating urgent improvements in patient prognosis. Despite being managed by different disciplines, pan-vascular diseases often share common risk factors and pathophysiological mechanisms, underscoring the need for standardized treatment strategies. Anti-thrombotic therapy for pan-vascular diseases primarily involves antiplatelet and anticoagulant therapy. Currently, there is a lack of unified guidance across various disciplines for patients with differing ischemic and bleeding risks and disease stages. Recognizing the pivotal role of standardized anti-thrombotic therapy in pan-vascular disease treatment, the Chinese College of Cardiovascular Physicians organized a consensus working group comprising 33 senior experts from cardiology, vascular surgery, neurology, and endocrinology. The “Chinese expert consensus on anti-thrombotic therapy for pan-vascular diseases (2023 Edition)” was developed based on specific treatment needs in China, incorporating published clinical research evidence, specialized guidelines and consensus, and recommendations from the consensus expert group. The primary aim of this consensus is to standardize the application of anti-thrombotic therapy in pan-vascular diseases, thereby optimizing clinical outcomes, improving patient prognosis, and mitigating the economic and societal burdens associated with pan-vascular disease.
Cranial nerve involvement, visual complications and headache syndromes in Lyme disease
Authors: McEntire Caleb R.S. , Chwalisz Bart K.
Published: March 2024

Purpose of review

To provide a summary of the visual manifestations and cranial neuropathies seen in Lyme disease.

Recent findings

Lyme facial palsy remains the most common manifestation of Lyme neuroborreliosis. Recent investigations show likely evidence of vagal involvement in Lyme disease.

The literature on Lyme neuroborreliosis continues to evolve. Lyme disease can affect nearly any cranial nerve in addition to causing various headache syndromes. The most common manifestation is Lyme disease facial palsy, occurring in up to 5–10% of patients with documented Lyme disease. Headache syndromes are common in the context of facial palsy but can occur in isolation, and more specific headache syndromes including trigeminal and geniculate neuralgias can occur rarely. Signs and symptoms indicative of vestibulocochlear nerve involvement are relatively common, although it could be that these represent other vestibular involvement rather than a specific cranial neuropathy. Optic neuritis is a controversial entity within Lyme disease and is likely overdiagnosed, but convincing cases do exist. Physicians who see any cranial neuropathy, including optic neuritis, in an endemic area can consider Lyme disease as a possible cause.
State-of-the-Art Hybrid Imaging of Neuroendocrine Neoplasms
Authors: Ambrosini Valentina , Fortunati Emilia , Fanti Stefano , Ursprung Stephan , Asmundo Luigi , O'Shea Aileen , Kako Bashar , Lee Susanna , Furtado Felipe S. , Blake Michael , Goiffon Reece J. , Najmi Zahra , Hesami Mina , Murakami Takaaki , Domachevsky Liran , Catalano Onofrio A.
Published: March 2024

Neuroendocrine neoplasms (NENs) may be challenging to diagnose due to their small size and diverse anatomical locations. Hybrid imaging techniques, specifically positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI), represent the current state-of-the-art for evaluating NENs. The preferred radiopharmaceuticals for NEN PET imaging are gallium-68 (68Ga) DOTA-peptides, which target somatostatin receptors (SSTR) overexpressed on NEN cells. Clinical applications of [68Ga]Ga-DOTA-peptides PET/CT include diagnosis, staging, prognosis assessment, treatment selection, and response evaluation. Fluorodeoxyglucose-18 (18F-FDG) PET/CT aids in detecting low-SSTR-expressing lesions and helps in patient stratification and treatment planning, particularly in grade 3 neuroendocrine tumors (NETs). New radiopharmaceuticals such as fluorine-labeled SSTR agonists and SSTR antagonists are emerging as alternatives to 68Ga-labeled peptides, offering improved detection rates and favorable biodistribution. The maturing of PET/MRI brings advantages to NEN imaging, including simultaneous acquisition of PET and MRI images, superior soft tissue contrast resolution, and motion correction capabilities. The PET/MRI with [68Ga]Ga-DOTA-peptides has demonstrated higher lesion detection rates and more accurate lesion classification compared to PET/CT. Overall, hybrid imaging offers valuable insights in the diagnosis, staging, and treatment planning of NENs. Further research is needed to refine response assessment criteria and standardize reporting guidelines.
The Impact of Rapid On-site Evaluation on Diagnostic Performance of Computed Tomography–Guided Core Needle Biopsy in Lung Cancer
Authors: Magnini Andrea , Lorini Chiara , Calistri Linda , Calcagni Francesca , Giuntoli Federico , Foxi Prassede , Nardi Cosimo , Colagrande Stefano
Published: March 2024

Purpose

Rapid on-site-evaluation (ROSE) is a technique aimed at improving the diagnostic performance of computed tomography (CT)–guided core needle biopsy (CNB) in lung cancer. The aim of this retrospective study was to investigate the impact of ROSE on the rate of nondiagnostic specimens and on accuracy computed on diagnostic specimens.

Materials and Methods

During a 3-year period, 417 CT-guided CNBs were performed at our center. The biopsies were retrospectively classified into 2 groups: 141 procedures were assisted by ROSE and 276 were not. All of them were reviewed for clinical, procedural, and pathological data. Pathology results were classified as diagnostic (positive or negative for malignancy) or nondiagnostic. The results were compared with the final diagnosis after surgery or clinical follow-up. Nondiagnostic rate, sensitivity/specificity/negative predictive value/positive predictive value for the ROSE and non-ROSE groups were calculated. Finally, procedural complications and the adequacy of the specimens for the molecular analysis were recorded.

Results

The study evaluated 417 CNBs (mean patients' age 71 years, 278 men). Nondiagnostic rates with and without ROSE were 4% (6/142) and 11% (29/276), respectively (P = 0.028). Sensitivity/specificity/negative predictive value/positive predictive value with and without ROSE did not show statistically significant differences, and no difference in major/minor complication rates was observed between the 2 groups. The adequacy of specimen for subsequent molecular analysis was 100% with (42/42) and 82% without ROSE (51/62).

Conclusions

Rapid on-site-evaluation reduced the rate of nondiagnostic specimens by 50% with no change in complication rates or accuracy and increased by 20% the chances of a successful subsequent molecular analysis.
CHRONIC CRITICAL ILLNESS-INDUCED MUSCLE ATROPHY: INSIGHTS FROM A TRAUMA MOUSE MODEL AND POTENTIAL MECHANISM MEDIATED VIA SERUM AMYLOID A
Authors: Lei Mingxing , Feng Taojin , Zhang Mingming , Chang Feifan , Liu Jiang , Sun Baisheng , Chen Ming , Li Yi , Zhang Licheng , Tang Peifu , Yin Pengbin
Published: March 2024

Background: Chronic critical illness (CCI), which was characterized by persistent inflammation, immunosuppression, and catabolism syndrome (PICS), often leads to muscle atrophy. Serum amyloid A (SAA), a protein upregulated in critical illness myopathy, may play a crucial role in these processes. However, the effects of SAA on muscle atrophy in PICS require further investigation. This study aims to develop a mouse model of PICS combined with bone trauma to investigate the mechanisms underlying muscle weakness, with a focus on SAA. Methods: Mice were used to examine the effects of PICS after bone trauma on immune response, muscle atrophy, and bone healing. The mice were divided into two groups: a bone trauma group and a bone trauma with cecal ligation and puncture group. Tibia fracture surgery was performed on all mice, and PICS was induced through cecal ligation and puncture surgery in the PICS group. Various assessments were conducted, including weight change analysis, cytokine analysis, hematological analysis, grip strength analysis, histochemical staining, and immunofluorescence staining for SAA. In vitro experiments using C2C12 cells (myoblasts) were also conducted to investigate the role of SAA in muscle atrophy. The effects of inhibiting receptor for advanced glycation endproducts (RAGE) or JAK2 on SAA-induced muscle atrophy were examined. Bioinformatic analysis was conducted using a dataset from the GEO database to identify differentially expressed genes and construct a coexpression network. Results: Bioinformatic analysis confirmed that SAA was significantly upregulated in muscle tissue of patients with intensive care unit–induced muscle atrophy. The PICS animal models exhibited significant weight loss, spleen enlargement, elevated levels of proinflammatory cytokines, and altered hematological profiles. Evaluation of muscle atrophy in the animal models demonstrated decreased muscle mass, grip strength loss, decreased diameter of muscle fibers, and significantly increased expression of SAA. In vitro experiment demonstrated that SAA decreased myotube formation, reduced myotube diameter, and increased the expression of muscle atrophy–related genes. Furthermore, SAA expression was associated with activation of the FOXO signaling pathway, and inhibition of RAGE or JAK2/STAT3-FOXO signaling partially reversed SAA-induced muscle atrophy. Conclusions: This study successfully develops a mouse model that mimics PICS in CCI patients with bone trauma. Serum amyloid A plays a crucial role in muscle atrophy through the JAK2/STAT3-FOXO signaling pathway, and targeting RAGE or JAK2 may hold therapeutic potential in mitigating SAA-induced muscle atrophy.
THE RELATIONSHIP BETWEEN CIRCULATING IMMUNE CELL PHENOTYPES AND SEPSIS: A MENDELIAN RANDOMIZATION STUDY
Authors: Liu Hongmei , Liu Hai , Zhou Li , Wen Shu , Liu Tiankuang , Ju Linqin , Liu Yiwen
Published: March 2024

Objective: The role of immune cells in sepsis remains unclear, and there is some controversy. Here, we aim to systematically assess whether distinct immune cell phenotypes impact the susceptibility to sepsis. Methods: In this study, we harnessed publicly available summary-level data from genome-wide association studies (GWASs). The selection of genetic variations strongly associated with 731 phenotypes of circulating immune cells served as instrumental variables (IVs). Using a two-sample Mendelian randomization (MR) analysis, we investigated the relationships between different immunophenotypes and the occurrence of sepsis, as well as the 28-day mortality. The MR study utilized the inverse variance weighting (IVW) method as the main analytical approach. In addition, we incorporated four other MR methods for supplementary causal inference, including weighted median (WME), MR-Egger regression, simple mode, and weighted mode. Furthermore, the robustness of the results was affirmed through multiple sensitivity analyses. Results: The results of the IVW method indicated that a total of 36 immunophenotypes are associated with the risk of sepsis. We also identified 34 immunophenotypes with a causal association with the 28-day mortality. Interestingly, before multiple testing corrections, 11 immunophenotypes were determined to have consistent causal relationships with both the occurrence of sepsis and the 28-day mortality. Notably, after false discovery rate (FDR) correction, four immunophenotypes were found to be significantly correlated with susceptibility to sepsis: CD45RA− CD4+ %CD4+ (odds ratio [OR], 1.355; 95% confidence interval [CI], 1.139~1.611; P < 0.001, P
FDR = 0.192), HLA DR on HLA DR+ NK (OR, 0.818; 95% CI, 0.726~0.922; P = 0.001, P
FDR = 0.192), IgD+ CD24+ %B cell (OR, 0.626; 95% CI, 0.473~0.828; P = 0.001, P
FDR = 0.192), and TD DN (CD4− CD8−) AC (OR, 0.655; 95% CI, 0.510~0.840; P < 0.001, P
FDR = 0.192). Following FDR correction, only one immunophenotype was confirmed to be negatively correlated with the 28-day mortality: CD39 on CD39+ CD8br (OR, 0.820; 95% CI, 0.737~0.912; P < 0.001, P
FDR = 0.184). Conclusion: This study, for the first time, has uncovered indicative evidence of a causal relationship between circulating immune cell phenotypes and varying degrees of sepsis through genetic means. These findings underscore the significance of immune cells in the pathogenesis of sepsis.
Is Time Scheduling Important? An Analysis of Donor Heart Cross-clamp Times During Heart Transplantation
Authors: Gouchoe Doug A. , Ganapathi Asvin M. , Cui Ervin Y. , Henn Matthew C. , Yim Wai Yen , Geng Bingchuan , Whitson Bryan A. , Zhu Hua
Published: March 2024

Background.

Outcomes in heart transplantation are affected by a variety of variables and patient factors. However, the impact of circadian rhythms, gene expression, and transcription remain underexplored. We thus evaluated the potential role of donor heart cross-clamp times on short-term and long-term outcomes after heart transplantation.

Methods.

A total of 31 713 heart transplants were identified from the United Network for Organ Sharing Database. Patients were first stratified on the basis of time of donor procurement: 12 am to 12 pm or 12 pm to 12 am. To evaluate a possible effect of circadian rhythms, donor time was further divided into 5 groups based on preclinical data: 4 am to 8 am; 8 am to 11 am; 11 am to 5 pm; 5 pm to 10 pm; 10 pm to 4 am. Groups were assessed with comparative statistics. Long-term survival was evaluated using Kaplan-Meier methods and a multivariate Cox proportional hazard model.

Results.

Patients who received hearts recovered between 12 am and 12 pm had significantly higher survival than those who received hearts recovered between 12 pm and 12 am. This survival difference was observed in both unadjusted (P = 0.002) and adjusted analyses (hazard ratio [HR]: 0.93; 95% confidence interval [CI], 0.89-0.97; P < 0.001). On unadjusted analysis, the survival difference among the 5 groups was insignificant (P = 0.07). Following adjustment, the periods of 11 am to 5 pm (HR: 1.09, 95% CI, 1.02-1.17; P = 0.012), 5 pm to 10 pm (HR: 1.11; 95% CI, 1.04-1.19; P = 0.002), and 10 pm to 4 am (HR: 1.07; 95% CI, 1.01-1.15; P = 0.034), were all independently associated with increased long-term mortality. Notably, the time of 8 am to 11 am was not associated with a change in survival (HR: 1.04; 95% CI, 0.96-1.14; P = 0.3).

Conclusions.

Given the independent association of donor timing and survival after adjustment in a large national cohort, further investigation into the role of donor circadian rhythm and donor procurement time is warranted in preclinical and clinical studies. Understanding the underlying mechanisms of this observation could potentially lead to the development of effective treatments and donor procurement processes that prepare the organs for transplantation in a better condition.
Multiple novel Caliciviruses identified from stoats (Mustela erminea) in the United Kingdom
Authors: Hinds Joseph , Apaa Ternenge , Parry Rhys H. , Withers Amy J. , MacKenzie Laura , Staley Ceri , Morrison Joshua , Bennett Malcolm , Bremner-Harrison Samantha , Chadwick Elizabeth A. , Hailer Frank , Harrison Stephen W.R. , Lambin Xavier , Loose Matthew , Mathews Fiona , Tarlinton Rachael , Blanchard Adam
Published: March 2024

The Caliciviridae family, comprising positive-sense RNA viruses, is characterised by its non-enveloped, small virions, broad host range, and notable tendency for host switching. These viruses are primarily associated with gastroenteric disease, though they can lead to haemorrhagic or respiratory infections. Our study employed a metagenomics analysis of faecal samples from Stoats (Mustela erminea), identifying two novel Calicivirus species, tentatively named Stoat vesivirus and Stoat valovirus. Stoat vesivirus was identified in three samples (ST008, ST006, ST004), exhibiting a genome wide nucleotide identity of approximately 92%. The complete coding sequences of these samples were 8471 (ST004) and 8322 (ST006) nucleotides in length, respectively. Each comprised three open reading frames (ORF), closely resembling the Vesivirus mink calicivirus (China/2/2016), with 70-72% similarity in ORF1, 61-62% in ORF2 and 71% in ORF3. Phylogenetic analysis robustly supported Stoat vesivirus as belonging within the Vesivirus genus. The second Calivicirus (Stoat valovirus), detected solely in sample ST008, was 6527 nucleotides in length and with complete coding sequences present. It shared highest similarity with St-Valerien swine virus and Marmot norovirus HT16, showing 39.5% and 38.8% protein identity with ORF1 and 43.3% and 42.9% for VP1. Phylogenetic analysis suggested that while Stoat valovirus is borderline for new genus demarcation criteria, with greater than 60% divergence at ORF1, it clusters basally within the Valovirus genus, supporting its inclusion in this genus.
Characterizing and targeting glioblastoma neuron-tumor networks with retrograde tracing
Authors: Tetzlaff Svenja Kristin , Reyhan Ekin , Bengtson C. Peter , Schroers Julian , Wagner Julia , Schubert Marc Cicero , Layer Nikolas , Puschhof Maria C. , Faymonville Anton J. , Drewa Nina , Pramatarov Rangel L. , Wissmann Niklas , Alhalabi Obada , Heuer Alina , Sivapalan Nirosan , Campos JoaquÍn , Boztepe Berin , Scheck Jonas G. , Villa Giulia , Schröter Manuel , Sahm Felix , Forsberg-Nilsson Karin , Breckwoldt Michael O. , Acuna Claudio , Suchorska Bogdana , Heiland Henrik Dieter , Saez-Rodriguez Julio , Venkataramani Varun
Published: March 2024

Glioblastomas are heterogeneous brain tumors, notorious for their invasive behavior and resistance to therapy. Neuron-to-glioma synapses have been identified to promote glioblastoma invasion and proliferation. However, a comprehensive characterization of tumor-connected neurons has been hampered by a lack of technologies. Here, we adapted retrograde tracing with a modified rabies virus system to characterize and manipulate connected neuron-tumor networks. Glioblastoma rapidly integrated into neural circuits across the brain engaging in widespread functional communication, with acetylcholinergic and glutamatergic neurons driving glioblastoma progression. We uncovered patient-specific and tumor cell state-dependent differences in synaptogenic gene expression driving neuron-tumor connectivity and subsequent invasivity. Importantly, radiotherapy enhanced neuron-tumor connectivity by increased neuronal activity. In turn, simultaneous inhibition of AMPA receptors and radiotherapy showed increased therapeutic effects, indicative of a role for neuron-to-glioma synapses in contributing to therapeutic resistance. Lastly, rabies-mediated genetic ablation of tumor-connected neurons halted glioblastoma progression, offering a novel viral strategy to target glioblastoma. Together, this study provides a comprehensive framework for basic research and clinical translation of synaptic neuron-cancer interactions to target glioblastoma.
Structural insight into bacterial co-transcriptional translation initiation
Authors: Yokoyama Takeshi , Murayama Yuko , Uchikubo-Kamo Tomomi , Tomabechi Yuri , Nagao Asuteka , Suzuki Tsutomu , Shirouzu Mikako , Sekine Shun-ichi
Published: March 2024

In bacteria, transcription and translation are tightly coupled, forming a transcription-translation complex (TTC) between RNA polymerase (RNAP) and the ribosome. As nascent mRNA emerging from RNAP is susceptible to ribonuclease digestion, undesired RNA folding, and R-loop formation, immediate TTC formation is important. Here, we report the cryo-electron microscopy structures that capture the translation initiation complex assembly on transcribing RNAP. As a short mRNA emerging from RNAP, the 30S ribosomal subunit binds the RNAP on its inter-subunit side, interacting with the mRNA 5’-region and the initiator tRNA. The RNAP could relocate to the canonical mRNA-entry site of 30S, threading the mRNA into a path formed between RNAP and 30S. The subsequent 50S joining establishes a TTC. These structures illustrate the transcription-coupled translation initiation, while protecting mRNA.

One-Sentence Summary

Cryo-EM captures the ribosome assembly on transcribing RNA polymerase in the presence of translation initiation factors.