bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of life improvement after radiotherapy for bone metastases assessed using real-world data: a secondary analysis of a Nationwide Multicenter Cohort Study
Authors: Utsumi Nobuko , Saito Tetsuo , Shikama Naoto , Takahashi Takeo , Harada Hideyuki , Nakamura Naoki , Ueno Shuichi , Notsu Akifumi , Shirato Hiroki , Yamada Kazunari , Uezono Haruka , Koide Yutaro , Kubota Hikaru , Yamazaki Takuya , Ito Kei , Heianna Joichi , Okada Yukinori , Tonari Ayako , Katoh Norio , Wada Hitoshi , Ejima Yasuo , Yoshida Kayo , Kosugi Takashi , Takahashi Shigeo , Komiyama Takafumi , Uchida Nobue , Miwa Misako , Watanabe Miho , Nagakura Hisayasu , Ikeda Hiroko , Asakawa Isao , Shigematsu Naoyuki
Published: October 2024

Objective

Single-center studies or randomized controlled trials have evaluated the impact of radiotherapy for bone metastases on quality of life (QOL). We investigated the real-world impact of radiotherapy for bone metastases on QOL using nationwide multicenter cohort data.

Methods

We conducted a prospective observational study at 26 centers in Japan. Of 333 patients who received radiotherapy for bone metastases between December 2020 and March 2021, 232 (70%) were enrolled in the study. Patient-reported QOL was evaluated at enrollment and at two- and six-month follow-up using the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 15-Palliative and the EORTC QOL Questionnaire Bone Metastases module (QLQ-BM22). Possible predictors (patient-, tumor -, and treatment-related factors) of QOL improvement were screened using logistic regression models.

Results

QOL scores showed significant improvement at two-month follow-up in seven (global health status/QOL, emotional functioning, pain, insomnia, painful sites, pain characteristics and functional interference) of the 14 scales. Of these seven scales, mean improvement ≥ the minimal clinically important difference (defined by a change of 10 or more on the 0 to 100 scale) was seen in four scales (pain, insomnia, pain characteristics and functional interference). We did not find any predictors of QOL improvement in the functional interference scale of QLQ-BM22.

Conclusion

Radiotherapy for bone metastases performed in daily practice is effective in improving some scales of QOL.
Enhancing 3D planetary atmosphere simulations with a surrogate radiative transfer model
Authors: Tahseen Tara P A , Mendonça João M , Yip Kai Hou , Waldmann Ingo P
Published: October 2024

This work introduces an approach to enhancing the computational efficiency of 3D atmospheric simulations by integrating a machine-learned surrogate model into the oasis global circulation model (GCM). Traditional GCMs, which are based on repeatedly numerically integrating physical equations governing atmospheric processes across a series of time-steps, are time-intensive, leading to compromises in spatial and temporal resolution of simulations. This research improves upon this limitation, enabling higher resolution simulations within practical time frames. Speeding up 3D simulations holds significant implications in multiple domains. First, it facilitates the integration of 3D models into exoplanet inference pipelines, allowing for robust characterization of exoplanets from a previously unseen wealth of data anticipated from JWST and post-JWST instruments. Secondly, acceleration of 3D models will enable higher resolution atmospheric simulations of Earth and Solar system planets, enabling more detailed insights into their atmospheric physics and chemistry. Our method replaces the radiative transfer module in oasis with a recurrent neural network-based model trained on simulation inputs and outputs. Radiative transfer is typically one of the slowest components of a GCM, thus providing the largest scope for overall model speed-up. The surrogate model was trained and tested on the specific test case of the Venusian atmosphere, to benchmark the utility of this approach in the case of non-terrestrial atmospheres. This approach yields promising results, with the surrogate-integrated GCM demonstrating above 99.0 per cent accuracy and factor of 147 speed-up of the entire simulation executed on one graphics processing unit (GPU) compared to using the matched original GCM under Venus-like conditions.
SSBD: an ecosystem for enhanced sharing and reuse of bioimaging data
Authors: Kyoda Koji , Itoga Hiroya , Yamagata Yuki , Fujisawa Emi , Wang Fangfang , Miranda-Miranda Miguel , Yamamoto Haruna , Nakano Yasue , Tohsato Yukako , Onami Shuichi
Published: October 2024

SSBD (https://ssbd.riken.jp) is a platform for the sharing and reuse of bioimaging data. As part of efforts to build a bioimaging data ecosystem, SSBD has recently been updated to a two-tiered data resource comprising SSBD:repository, a public repository for the sharing of all types of bioimaging data reported in journals, and SSBD:database, an added-value database for the sharing of curated, highly reusable, metadata-rich data. This update addresses the conflicting demands of rapid data publication and sharing of richly annotated data, thereby promoting bioimaging data sharing and reuse. With this update, SSBD is now positioned as a core repository and database within the foundingGIDE, an international consortium working to establish a global image data ecosystem. Harmonizing metadata between data resources enables cross-searching and data exchange with data resources from other countries and regions.
Primed to persevere: Hypoxia regulation from epigenome to protein accumulation in plants
Authors: Gibbs Daniel J , Theodoulou Frederica L , Bailey-Serres Julia
Published: October 2024

Plant cells regularly encounter hypoxia (low-oxygen conditions) as part of normal growth and development, or in response to environmental stresses such as flooding. In recent years, our understanding of the multi-layered control of hypoxia-responsive gene expression has greatly increased. In this Update, we take a broad look at the epigenetic, transcriptional, translational, and post-translational mechanisms that regulate responses to low-oxygen levels. We highlight how a network of post-translational modifications (including phosphorylation), secondary messengers, transcriptional cascades, and retrograde signals from the mitochondria and endoplasmic reticulum (ER) feed into the control of transcription factor activity and hypoxia-responsive gene transcription. We discuss epigenetic mechanisms regulating the response to reduced oxygen availability, through focussing on active and repressive chromatin modifications and DNA methylation. We also describe current knowledge of the co- and post-transcriptional mechanisms that tightly regulate mRNA translation to coordinate effective gene expression under hypoxia. Finally, we present a series of outstanding questions in the field and consider how new insights into the molecular workings of the hypoxia-triggered regulatory hierarchy could pave the way for developing flood-resilient crops.
Ultrasound-mediated cardiovascular thrombolysis: from Sonothrombolysis to Sonoperfusion
Authors: Jiang Zhixin , Jiang Nan , Wang Zhiwen , Deng Qing , Zhou Qing , Hu Bo
Published: October 2024

The incidence of coronary artery disease has been increasing in recent years, with acute myocardial infarction as its most severe onset. The major aim for clinical treatment is to restore myocardial blood supply with the recanalization of coronary circulation as early as possible, while the still existed issue of microcirculation thromboembolism has become a serious obstacle. Thus, thrombus elimination in coronary microcirculation is crucial and essential to improve the treatment outcome of acute myocardial infarction. In recent years, from sonothrombolysis to sonoperfusion, ultrasound-mediated cardiovascular thrombolysis can effectively solve the problem of vascular thromboembolism, including microcirculation thromboembolism, and the treatment method is expected to obtain satisfied thrombolytic treatment effect with microthrombus elimination in coronary microvessels and function recovery of terminal microcirculation, which has potential clinical value for the establishment of novel treatment for coronary thromboembolism. Therefore, this paper reviews ultrasound-mediated cardiovascular thrombolysis including sonothrombolysis and sonoperfusion for the application exploration in the treatment of coronary artery thromboembolism, the mechanism of action, and its research progress.
Common and divergent neuroimaging features in major depression, posttraumatic stress disorder, and their comorbidity
Authors: Jiang Jing , Ferraro Stefania , Zhao Youjin , Wu Baolin , Lin Jinping , Chen Taolin , Gao Jin , Li Lei
Published: October 2024

Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are common stress-related psychiatric disorders. Genetic and neurobiology research has supported the viewpoint that PTSD and MDD may possess common and disorder-specific underlying mechanisms. In this systematic review, we summarize evidence for the similarities and differences in brain functional and structural features of MDD, PTSD, and their comorbidity, as well as the effects of extensively used therapies in patients with comorbid PTSD and MDD (PTSD + MDD). These functional magnetic resonance imaging (MRI) studies highlight the (i) shared hypoactivation in the prefrontal cortex during cognitive and emotional processing in MDD and PTSD; (ii) higher activation in fear processing regions including amygdala, hippocampus, and insula in PTSD compared to MDD; and (iii) distinct functional deficits in brain regions involved in fear and reward processing in patients with PTSD + MDD relative to those with PTSD alone. These structural MRI studies suggested that PTSD and MDD share features of reduced volume in focal frontal areas. The treatment effects in patients with PTSD + MDD may correlate with the normalization trend of structural alterations. Neuroimaging predictors of repetitive transcranial magnetic stimulation response in patients with PTSD + MDD may differ from the mono-diagnostic groups. In summary, neuroimaging studies to date have provided limited information about the shared and disorder-specific features in MDD and PTSD. Further research is essential to pave the way for developing improved diagnostic markers and eventually targeted treatment approaches for the shared and distinct brain alterations presented in patients with MDD and PTSD.
Expectations and Learning from Prices
Authors: Bastianello Francesca , Fontanier Paul
Published: October 2024

We study mislearning from equilibrium prices, and contrast this with mislearning from exogenous fundamentals. We micro-found mislearning from prices with a psychologically founded theory of “Partial Equilibrium Thinking” (PET), where traders learn fundamental information from prices, but fail to realize others do so too. PET leads to over-reaction, and upward sloping demand curves, thus contributing to more inelastic markets. The degree of individual-level over-reaction and the extent of inelasticity vary with the composition of traders, and with the informativeness of new information. More generally, unlike mislearning from fundamentals, mislearning from prices (i) generates a two-way feedback between prices and beliefs that can provide an arbitrarily large amount of amplification and (ii) can rationalize both over-reaction and more inelastic markets. The two classes of biases are not mutually exclusive. Instead, they interact in very natural ways, and mislearning from prices can vastly amplify mislearning from fundamentals.
Dermal Microcoring for Skin Laxity, Rhytides, and Scars
Authors: Hashemi David A. , Tao Joy , Wang Jordan V. , Munavalli Girish , Geronemus Roy G.
Published: October 2024

BACKGROUND

Dermal microcoring extracts cores of skin that are small enough to allow healing in a scarless fashion. Its use has been reported in the treatment of skin laxity, rhytides, and textural abnormalities.

OBJECTIVE

To report the authors' clinical experience using dermal microcoring in a variety of cases.

MATERIALS AND METHODS

A retrospective chart review was performed looking at dermal microcoring cases for any indication between August 2022 and March 2024.

RESULTS

Thirty-eight patients were treated. Overall, 32 (84.2%) patients were women, with median age of 67 years (R: 20–80 years). Fitzpatrick skin types I to V were represented. Among patients with adequate photographs for review, improvements of grade 3 and 4 (good and excellent) were seen in 85.7% (n = 18/21) treated for skin laxity and rhytides, 50.0% (n = 3/6) treated for acne scars, 66.7% (n = 2/3) treated for traumatic or surgical scars, and 100.0% (n = 3/3) treated for foreign material. Six (15.4%) patients experienced erythema or hyperpigmentation lasting more than 4 weeks, and 2 (5.1%) patients experienced temporary focal scarring, which improved with intralesional therapy and laser treatment. No patients experienced permanent dyspigmentation, prolonged edema, or infection.

CONCLUSION

Dermal microcoring has been demonstrated to safely and effectively treat skin laxity, rhytides, scars, and foreign material.
Predisposing Factors, Treatment, and Pathophysiology of Retronychia in China: A Retrospective Study of 107 Cases
Authors: Chen Liang , Wang Wei , Wang Heng , Dong Dong , Liu Tianyi
Published: October 2024

BACKGROUND

Retronychia, a condition marked by abnormal nail growth, is frequently underdiagnosed and misinterpreted, with a few reported cases in the literature.

OBJECTIVE

To investigate the pathophysiology, identify contributing factors, and assess the outcomes of surgical and nonsurgical treatments for retronychia.

METHODS AND MATERIALS

A retrospective review of 107 retronychia cases diagnosed at the center between January 2021 and July 2022 was conducted.

RESULTS

Predisposing factors were identified in 93.46% of cases, with 88.79% of patients reporting a habit of wearing socks during sleep before symptom onset. Noninvasive treatments targeting these factors led to full recovery in 79.55% of cases, while 13.64% experienced partial improvement, inducing reduced proximal nail fold inflammation. Nail avulsion, which involves removing the entire nail, achieved a relapse-free cure rate of 90.91%. When the innermost nail plate was preserved, the cure rate rose to 96.67%.

CONCLUSION

Chronic mechanical forces, frequently overlooked, play a pivotal role in retronychia onset and progression. Conservative management targeting these mechanical factors is recommended for patients with mild cases.
A Pivotal Study on the Safety and Effectiveness of a Targeted Alkali Thermolysis Patch for Treatment of Primary Axillary Hyperhidrosis or Excessive Axillary Sweating
Authors: Smith Stacy , Glaser Dee Anna , Green Lawerence J. , Kaminer Micheal S. , Tims Erin , Pariser David M.
Published: October 2024

BACKGROUND

One-third of US adults are bothered by excessive sweating, approximately 5% are diagnosed with hyperhidrosis. A topical patch using targeted alkali thermolysis (TAT) was developed for treatment of this condition.

OBJECTIVE

This study was intended to assess the efficacy and safety of the TAT-Patch for axillary sweat reduction.

MATERIALS AND METHODS

A randomized, multicenter, double-blind, sham-controlled, pivotal trial enrolled 120 subjects to a bilateral axillary treatment with a TAT patch (63 subjects) or sham patch (57 subjects).

RESULTS

The primary end point was achieved; 64% of TAT-treated versus 44% of sham-treated subjects (p = .0332) improved from Hyperhidrosis Disease Severity Scale (HDSS) 3/4 to HDDS 1/2 at 4 weeks. Targeted alkali thermolysis treatment also showed a statistically significant improvement over sham treatment for all secondary end points, including gravimetric sweat production and subject-reported quality-of-life (QoL) assessments. The duration of effect is approximately 3 months, determined by the time to return to baseline HDSS. Mild-to-moderate treatment-site adverse events (AEs) were reported in 22% of TAT patch subjects. No serious or severe AEs were reported.

CONCLUSION

HDSS, GSP, and QoL findings confirm clinically meaningful sweat reduction and a significant improvement in quality of life following a single TAT patch treatment. This device has potential to offer a new, noninvasive treatment option that is well tolerated with minimal downtime.
Development of Undergraduate Competencies in Caring for People Experiencing Homelessness
Authors: Richmond Rachel , Noone Joanne , Voss Heather , Hale Aina , Gran-Moravec Marilyn
Published: October 2024

Background:

Nurses play a critical role in reducing health inequities in people experiencing homelessness (PEH), a key social determinant of health. Health disparities specific to PEH are exacerbated by numerous factors, including bias, stigma, and a lack of nursing competency in caring for PEH.

Purpose:

The purpose of this study was to validate registered nurse key competencies; associated knowledge, skills, and attitudes; and concepts, content, and learning activities to serve as an educational framework in providing care for PEH.

Methods:

Twenty-four nursing experts on the care of PEH rated draft competency and subcompetency statements for relevance and clarity, proposed revisions and missing competencies, and identified essential and useful content, concepts, and learning activities.

Results:

Four key competencies, 38 subcompetencies, and associated concepts, content, and learning activities were validated by the experts.

Conclusions:

This framework can be used to guide curricular development across nursing programs to advance health equity for PEH.
Qualitatively Assessing ChatGPT Responses to Frequently Asked Questions Regarding Sexually Transmitted Diseases
Authors: Moothedan Elijah , Jhumkhawala Vama , Burgoa Sara , Martinez Lisa , Sacca Lea
Published: October 2024

Background

ChatGPT, a large language model artificial intelligence platform that uses natural language processing, has seen its implementation across a number of sectors, notably in health care. However, there remains limited understanding regarding the efficacy of ChatGPT in addressing commonly asked questions on public health subjects. This study aimed to investigate whether ChatGPT could appropriately answer frequently asked questions related to sexually transmitted diseases (STDs).

Methods

Ten frequently asked questions on STDs were gathered from 25 different government agency websites. The questions were inputted into ChatGPT, and subsequent responses were analyzed for accuracy, clarity, and appropriateness using an evidence-based approach on a 4-point grading scale.

Results

Of the responses provided by ChatGPT, 4 were determined to be excellent requiring no clarification and 6 requiring minimal clarification. No responses were graded as unsatisfactory. Additionally, the responses appropriately emphasized consulting a health care specialist.

Conclusion

Although the majority of responses required minimal clarification, ChatGPT has the potential to be an effective supplementary tool for patient education. Additional research is necessary to explore possible public health strategies that incorporate artificial intelligence to address concerns related to STDs.
Analysis of 2019 Ohio Disease Intervention Specialist Records for Syphilis Cases Using Clustering Algorithms
Authors: Chakraborty Payal , Ning Xia , McNeill Mary , Kline David M. , Shoben Abigail B. , Miller William C. , Norris Turner Abigail
Published: October 2024

Background

Developments in natural language processing and unsupervised machine learning methodologies (e.g., clustering) have given researchers new tools to analyze both structured and unstructured health data. We applied these methods to 2019 Ohio disease intervention specialist (DIS) syphilis records, to determine whether these methods can uncover novel patterns of co-occurrence of individual characteristics, risk factors, and clinical characteristics of syphilis that are not yet reported in the literature.

Methods

The 2019 disease intervention specialist syphilis records (n = 1996) contain both structured data (categorical and numerical variables) and unstructured notes. In the structured data, we examined case demographics, syphilis risk factors, and clinical characteristics of syphilis. For the unstructured text, we applied TF-IDF (term frequency multiplied by inverse document frequency) weights, a common way to convert text into numerical representations. We performed agglomerative clustering with cosine similarity using the CLUTO software.

Results

The cluster analysis yielded 6 clusters of syphilis cases based on patterns in the structured and unstructured data. The average internal similarities were much higher than the average external similarities, indicating that the clusters were well formed. The factors underlying 3 of the clusters related to patterns of missing data. The factors underlying the other 3 clusters were sexual behaviors and partnerships. Notably, 1 of the 3 consisted of individuals who reported oral sex with male or anonymous partners while intoxicated, and one comprised mainly of males who have sex with females.

Conclusions

Our analysis resulted in clusters that were well formed mathematically, but did not reveal novel epidemiological information about syphilis risk factors or transmission that were not already known.
Extranodal Mantle Cell Lymphoma Presented as Bilateral Adrenal Masses on 18F-FDG PET/CT and 68Ga-DOTATATE PET/CT
Authors: Filizoglu Nuh , Ozguven Salih , Ones Tunc , Turoglu Halil Turgut , Erdil Tanju Yusuf
Published: October 2024

Mantle cell lymphoma (MCL) is a rare type of B-cell non-Hodgkin lymphoma that commonly presents with constitutional symptoms, lymphadenopathy, and laboratory abnormalities. Although less common, extranodal involvement of MCL may be seen at initial presentation and most commonly occurs in the spleen, liver, bone marrow, and gastrointestinal tract. Adrenal involvement in MCL is extremely rare, and only a few cases have been reported in the literature. Herein, we present 18F-FDG PET/CT and 68Ga-DOTATATE PET/CT findings of a unique case of primary extranodal MCL with gastric and adrenal involvement.
After 30 Years of Remission, Recurrence With Renal Cell Carcinoma Metastasis Mimicking Pancreatic Neuroendocrine Tumor on 18F-FDG and 68Ga-DOTATATE PET/CT
Authors: Aydinbelge Dizdar Nur , Erdem Karaoglu Aysenur , Ozmen Ozlem , Kaya Ozge
Published: October 2024

A 75-year-old man with a previous history of left nephrectomy for clear cell renal cell carcinoma in remission was underwent 68Ga-DOTATATE PET/CT imaging for evaluation of pancreatic body lesion. It showed a mass with intense 68Ga-DOTATATE uptake in the pancreatic corpus. During the follow-up of the patient who did not want to undergo surgery, 18F-FDG PET/CT scan was performed due to the increase in the size of the mass, and mild FDG uptake was detected in the pancreatic corpus lesion, and histopathological examination was confirmed as renal cell carcinoma metastasis.
UnCOT-AD: Unpaired Cross-Omics Translation Enables Multi-Omics Integration for Alzheimer’s Disease Prediction
Authors: Abir Abrar Rahman , Dip Sajib Acharjee , Zhang Liqing
Published: October 2024

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder, posing a growing public health challenge. Traditional machine learning models for AD prediction have relied on single omics data or phenotypic assessments, limiting their ability to capture the disease’s molecular complexity and resulting in poor performance. Recent advances in high-throughput multi-omics have provided deeper biological insights. However, due to the scarcity of paired omics datasets, existing multi-omics AD prediction models rely on unpaired omics data, where different omics profiles are combined without being derived from the same biological sample, leading to biologically less meaningful pairings and causing less accurate predictions. To address these issues, we proposeUnCOT-AD, a novel deep learning framework forUnpairedCross-OmicsTranslation enabling effective multi-omics integration forADprediction. Our method introduces the first-ever cross-omics translation model trained on unpaired omics datasets, using two coupled Variational Autoencoders and a novel cycle consistency mechanism to ensure accurate bidirectional translation between omics types. We integrate adversarial training to ensure that the generated omics profiles are biologically realistic. Moreover, we employ contrastive learning to capture the disease specific patterns in latent space to make the cross-omics translation more accurate and biologically relevant. We rigorously validate UnCOT-AD on both cross-omics translation and AD prediction tasks. Results show thatUnCOT-ADempowers multi-omics based AD prediction by combining real omics profiles with corresponding omics profiles generated by our cross-omics translation module and achieves state-of-the-art performance in accuracy and robustness. Source code is available athttps://github.com/abrarrahmanabir/UnCOT-AD
LCL: Contrastive Learning for Lineage Barcoded scRNA-seq Data
Authors: Yang Shizhao Joshua , Wang Yixin , Lin Kevin Z
Published: October 2024

Single-cell lineage tracing technology has advanced the investigation of progenitor cells’ development using static, inheritable barcodes. It can determine temporal dynamics in progenitor-progeny relationships through single-cell RNA-sequencing (scRNA-seq) data. However, studying fate commitment from scRNA-seq can be difficult since the gene expression profiles are confounded with information about many cell processes beyond fate commitment. This paper demonstrates a novel framework to specifically isolate lineage signals driving cell fate, allowing us to learn the gene pathways that differentiate different lineages based on their eventual fates.

Our novel approach, LCL (Lineage-aware Contrastive Learning), is a contrastive-learning deep learning model for analyzing lineage-tracing scRNA-seq data. Using two lineage-tracing datasets, one about reprogramming embryonic fibroblasts and the other about hematopoietic progenitor cells, we demonstrate that LCL can produce low-dimensional representations that effectively isolate fate-determining signals from other key biological signals. We evaluate the quality of LCL embeddings and demonstrate that they perform well in out-of-sample evaluation, both in terms of predicting the lineage and cell type compositions at a future time point. LCL also enables us to identify differential genes stably expressed within a lineage and visualize the fate-determining landscape using self-organizing maps based on the results from LCL. Lastly, we demonstrate the consistency of our approach across datasets of varying complexity using a series of pseudo-real datasets. In conclusion, our results demonstrate that LCL allows researchers to explore fate commitment in single-cell lineage-tracing data and uncover lineage-specific gene pathways.
Linguistic and Affective Prosody – A Unifying Perspective: A Systematic Review and ALE Meta-Analysis of the Cortical Organization of Prosody
Authors: Themistocleous Charalambos
Published: October 2024

Prosody is a cover term referring to the melodic aspects of speech, with linguistic and affective (a.k.a. emotional) meanings. This review provides an overview of linguistic and affective prosody, testing two hypotheses on healthy individuals’ linguistic and affective prosody. The first hypothesizes that the biological nature of affective prosody triggers activations unrelated to language (biological hypothesis), and the second that the aspects of affective prosody have been grammaticalized, i.e., incorporated into the language (linguistic hypothesis). We employed a systematic ALE metanalytic approach to identify neural correlates of prosody from the literature. Specifically, we assessed papers that report brain coordinates from healthy individuals selected using systematic research from academic databases, such as PubMed (NLM), Scopus, and Web of Science. We found that affective and linguistic prosody activate bilateral frontotemporal regions, like the Superior Temporal Gyrus (STG). A key difference is that affective prosody involves subcortical structures like the amygdala, and linguistic prosody activates linguistic areas and brain areas of social cognition and engagement. The shared activations, therefore, suggest that linguistic and affective meanings are combined, involving shared underlying brain connectivity mechanisms and acoustic manifestations. We propose the “prosodic blending hypothesis” to account for the findings. The hypothesis unifies the linguistic and affective prosody distinction, suggesting that prosody incorporates affective, social, and linguistic meanings in the acoustic signal and involves selective bilateral neural contributions. Although brain regions responsible for core emotions can be activated, those meanings are produced through a coordinated and structured linguistic manner, accounting for the gradient expression of non-linguistic and categorical linguistic aspects. We argue that the process is similar to speech, lexicon, and grammar domains, as they, too, convey affective, social, and linguistic meanings without their explicit separation into linguistic and affective. Therefore, our blending hypothesis views prosody as a unified system that combines affective and linguistic functions.
Neural mechanisms underlying robust target selection in response to microstimulation of the oculomotor system
Authors: Rakhshan Mohsen , Schafer Robert J , Moore Tirin , Soltani Alireza
Published: October 2024

Despite its prevalence in studying the causal roles of different brain circuits in cognitive processes, electrical microstimulation often results in inconsistent behavioral effects. These inconsistencies are assumed to be due to multiple mechanisms, including habituation, compensation by other brain circuits, and contralateral suppression. Considering the presence of reinforcement in most experimental paradigms, we hypothesized that interactions between reward feedback and microstimulation could contribute to inconsistencies in behavioral effects of microstimulation. To test this, we analyzed data from electrical microstimulation of the frontal eye field of male macaques during a value-based decision-making task and constructed network models to capture choice behavior. We found evidence for microstimulation-dependent adaptation in saccadic choice, such that in stimulated trials, monkeys’ choices were biased toward the target in the response field of the microstimulated site (Tin). In contrast, monkeys showed a bias away fromTinin non-stimulated trials following microstimulation. Critically, this bias slowly decreased as a function of the time since the last stimulation. Moreover, microstimulation-dependent adaptation was influenced by reward outcomes in preceding trials. Despite these local effects, we found no evidence for the global effects of microstimulation on learning and sensitivity to the reward schedule. By simulating choice behavior across various network models, we found a model in which microstimulation and reward-value signals interact competitively through reward-dependent plasticity can best account for our observations. Our findings indicate a reward-dependent compensatory mechanism that enhances robustness to perturbations within the oculomotor system and could explain the inconsistent outcomes observed in previous microstimulation studies.
Using a Deep Learning Approach for Model-based Control of Deep Brain Stimulation
Authors: Saradhi Srikar , Tian Yupeng , Rezaei Mohammed R. , Lankarany Milad
Published: October 2024

Deep brain stimulation (DBS) has been developed as a treatment method for various neurological disorders, including Parkinson’s disease, essential tremor and depression. Although DBS is effective, it often loses efficacy over sustained periods because a constant stimulation is applied without adapting to the patient’s current clinical state. In contrast, an adaptive closed-loop DBS system can offer more tailored stimulation in real-time based on a feedback biomarker. In early 2024, we developed a model-based DBS control framework that consists of three main functions: (1) a biophysically reasonable encoding model, (2) a simple decoding model, and (3) a controller. We used a polynomial fit function in the decoding model to approximate the neural-motor relationship, from DBS-induced Vim neural activity to muscle fiber electromyography (EMG). Despite promising results, the polynomial method is inaccurate in capturing the full representation of the neural-motor (EMG) function across different DBS frequencies. In this work, to capture the nonlinear intricate relationship between the neural and EMG patterns, we developed a one-dimensional convolutional neural network (1-D CNN) as a decoding model to predict the EMG signal directly from the DBS-induced Vim neural activity. The 1-D CNN network outputted a high R2value of 0.997 which significantly outperformed the polynomial method (R2= 0.277) and a deep learning approach based on long short-term memory (R2= 0.296). We anticipate that our work highlights the need for a data-driven approach that can reliably map neural activities to symptomatic signals like EMG for better adjusting DBS parameters.
Promiscuous and unbiased recombination underlies the sequence-discrete species of the SAR11 lineage in the deep ocean
Authors: Zhao Jianshu , Pachiadaki Maria , Conrad Roth E. , Hatt Janet K. , Bristow Laura A. , Rodriguez-R Luis M. , Rossello-Mora Ramon , Stewart Frank J. , Konstantinidis Konstantinos T.
Published: October 2024

Surveys of microbial communities (metagenomics) or isolate genomes have revealed sequence-discrete species. That is, members of the same species usually show >95% Average Nucleotide Identity (ANI) of shared genes among themselves vs. <83% ANI to members of other species while genome pairs showing between 83-95% ANI are comparatively rare. In these surveys, aquatic bacteria of the ubiquitous SAR11 clade (ClassAlphaproteobacteria), which play a major role in carbon cycling, are an outlier and often do not exhibit discrete species boundaries, suggesting the potential for alternate modes of genetic differentiation. To explore evolution in SAR11, we analyzed high-quality, single-cell amplified genomes (SAGs) and companion metagenomes from an oxygen minimum zone (OMZ) in the Eastern Tropical Pacific Ocean, where the SAR11 make up ∼20% of the total microbial community. Our results show that SAR11 do form several sequence-discrete species, but their ANI range of discreteness is shifted to lower identities between 86-91%, with intra-species ANI ranging between 91-100%. Measuring recent gene exchange among these genomes based on a newly developed methodology revealed higher frequency of homologous recombination within compared to between species that affects sequence evolution at least twice as much as diversifying point mutation across the genome. Recombination in SAR-11 appears to be more promiscuous compared to other prokaryotic species and has facilitated the spreading of adaptive mutations within the species, further promoting the high intra-species diversity observed. These results implicate rampant, genome-wide homologous recombination as the mechanism that underlies the evolution of SAR11 into discrete species.

Significance

Distinguishing “species” is a pressing issue in microbiology, partly because the mechanisms that create and maintain clusters of genetically similar microbes are sparsely documented for natural populations. By leveraging high quality single-cell genomic data and a novel method for assessing homologous recombination, we show that rampant homologous recombination maintains species-level clusters of genomes for the most abundant order of marine bacteria, suggesting that these genomes may be evolving sexually to a much greater extent than previously thought. Therefore, our results identify a mechanism explaining the evolution of species in a major microbial group and have implications for understanding microbial diversity and the species concept more broadly.
Geometric tortuosity at invaginating rod synapses slows glutamate diffusion and shapes synaptic responses: insights from anatomically realistic Monte Carlo simulations
Authors: Thoreson Wallace B. , Bartol Thomas M. , Conoan Nicholas H. , Diamond Jeffrey S.
Published: October 2024

At the first synapse in the vertebrate retina, rod photoreceptor terminals form deep invaginations occupied by multiple second-order rod bipolar and horizontal cell (RBP and HC) dendrites. Synaptic vesicles are released into this invagination at multiple sites beneath an elongated presynaptic ribbon. We investigated the impact of this complex architecture on the diffusion of synaptic glutamate and activity of postsynaptic receptors. We obtained serial electron micrographs of mouse retina and reconstructed four rod terminals along with their postsynaptic RBP and HC dendrites. We incorporated these structures into an anatomically realistic Monte Carlo simulation of neurotransmitter diffusion and receptor activation. We compared passive diffusion of glutamate in these realistic structures to existing, geometrically simplified models of the synapse and found that glutamate exits anatomically realistic synapses ten times more slowly than previously predicted. By comparing simulations with electrophysiological recordings, we modeled synaptic activation of EAAT5 glutamate transporters in rods, AMPA receptors on HC dendrites, and metabotropic glutamate receptors (mGluR6) on RRBP dendrites. Our simulations suggested that ~3,000 EAAT5 transporters populate the rod presynaptic membrane and that, while uptake by surrounding glial Müller cells retrieves much of the glutamate released by rods, binding and uptake by EAAT5 influences RBP response kinetics. The long lifetime of glutamate within the cleft allows mGluR6 on RBP dendrites to temporally integrate the steady stream of vesicles released at this synapse in darkness. Glutamate’s tortuous diffusional path through realistic synaptic geometry confers quantal variability, as release from nearby ribbon sites exerts larger effects on RBP and HC receptors than release from more distant sites. While greater integration may allow slower sustained release rates, added quantal variability complicates the challenging task of detecting brief decreases in release produced by rod light responses at scotopic threshold.
Specific origin selection and excess functional MCM2-7 loading in ORC-deficient cells
Authors: Shibata Yoshiyuki , Peycheva Mihaela , Shibata Etsuko , Malzl Daniel , Pavri Rushad , Dutta Anindya
Published: October 2024

The six subunit Origin Recognition Complex (ORC) loads excess MCM2-7 on chromosomes to promote initiation of DNA replication and is believed to be important for origin specification. Mapping of origins in cancer cell lines engineered to delete three of the subunits,ORC1,ORC2orORC5shows that specific origins are still used and are mostly at the same sites in the genome as in wild type cells. The few thousand origins that were up-regulated in the absence of ORC suggest that GC/TA skewness and simple repeat sequences facilitate, but are not essential for, origin selection in the absence of the six-subunit ORC. Despite the lack of ORC, excess MCM2-7 is still loaded at comparable rates in G1 phase to license dormant origins and is also repeatedly loaded in the same S phase to permit re-replication. Thus, origin specification and excess MCM2-7 loading on origins do not require the six-subunit ORC in human cancer cell lines.
The Causal Role of Beta Band Desynchronization: Individualized High-Definition Transcranial Alternating Current Stimulation Improves Bimanual Motor Control
Authors: Van Hoornweder Sybren , Mora Diego Andres Blanco , Nuyts Marten , Cuypers Koen , Verstraelen Stefanie , Meesen Raf
Published: October 2024

Objective

To unveil if 3 mA peak-to-peak high-definition β transcranial alternating current stimulation (tACS) applied over C4 –the area overlaying the right sensorimotor cortex– enhances bimanual motor control and affects movement-related β desynchronization (MRβD), thereby providing causal evidence for the polymorphic role of MRβD in motor control.

Methods

In this sham-controlled, crossover study, 36 participants underwent 20 minutes of fixed 20 Hz tACS; tACS individualized to peak β activity during motor planning at baseline; and sham tACS randomized over three consecutive days. Before, during, and after tACS, participants performed a bimanual tracking task (BTT) and 64-channel electroencephalography (EEG) data was measured. Spatiotemporal and temporal clustering statistics with underlying linear mixed effect models were used to test our hypotheses.

Results

Individualized tACS significantly improved bimanual motor control, both online and offline, and increased online MRβD during motor planning compared to fixed tACS. No offline effects of fixed and individualized tACS on MRβD were found compared to sham, although tACS effects did trend towards the hypothesized MRβD increase. Throughout the course of the study, MRβD and bimanual motor performance improved. Exclusively during motor planning, MRβD was positively associated to bimanual motor performance improvements, emphasizing the functionally polymorphic role of MRβD. tACS was well tolerated and no side-effects occurred.

Conclusion

Individualized β-tACS improves bimanual motor control and enhances motor planning MRβD online. These findings provide causal evidence for the importance of MRβD when planning complex motor behavior.
Herpes simplex virus type 1 origin binding protein UL9 tethers and loops origin- and non-origin-DNA intra- and intermolecularly
Authors: Meier Anita F. , Vuckovic Jan , Girvan Paul , Cutts Erin , Brophy Theodora , Ambrose Benjamin , Rueda David S.
Published: October 2024

Herpesviruses are ubiquitous human pathogens, which are the causative agent of mild to severe symptoms ranging from cold sore to nasopharyngeal carcinoma. Even though replication of the linear dsDNA genome has been studied for decades, we still lack a complete molecular understanding of its mechanism. It has been proposed, but never shown directly, that the HSV-1 origin binding protein UL9 binds two closely located binding sites within the oriS origin sequence, thereby mediating origin looping, which in turn facilitates replication initiation. Here, we used an array of single-molecule approaches to test this long-standing hypothesis directly. Surprisingly, the data show that UL9 does not loop oriS efficiently. However, we demonstrate that UL9 can form large DNA loops at non-origin sequences very efficiently, as well as tether two oriS DNA molecules intermolecularly. Contrary to the origin bending hypothesis, our findings indicate that UL9 does not loop oriS DNA, but rather may play an alternative role in replication initiation, such as tethering two separate molecules to facilitate recombination.
Biosynthesis of mitis group streptococcal glycolipids and their roles in physiology and antibiotic susceptibility
Authors: Wei Yahan , Chen Guan H. , Yaqub Muneer , Kim Elice , Tillett Lily E , Joyce Luke R. , Dillon Nicholas , Palmer Kelli L. , Guan Ziqiang
Published: October 2024

Bacterial cell surface components such as lipoteichoic acids (LTAs) play critical roles in host-microbe interactions and alter host responses based on their chemical structures. Mitis group streptococci have commensal and pathogenic interactions with the human host and produce Type IV LTAs that are slightly different in chemical structures between species. To reveal the molecular bases for the intricate interactions between MGS and human hosts, a detailed understanding of the structure and biosynthetic process of MGS LTAs is needed. In this study, we used genomic and lipidomic techniques to elucidate the biosynthetic processes of Type IV LTA and its associated glycolipid anchors, monohexosyl-diacylglycerol and dihexosyl-diacyglycerol, in the infectious endocarditis isolateStreptococcussp. strain 1643. Through establishing a murine sepsis model, we validated the essentiality of these glycolipids in the full virulence ofS. mitis. Additionally, we found that these glycolipids play an important role in protecting the bacteria from antimicrobials. Overall, results obtained through this study both confirm and dispute aspects of the existing model of glycolipids biosynthesis, provide insights into the fundamental roles of bacterial glycolipids, as well as suggest the potential of targeting glycolipids for developing antimicrobial therapeutics.

Significance/Importance

Glycolipids and glycolipid-anchored LTAs are common and essential membrane components in Gram-positive bacteria. Yet, the biosynthesis and functions of LTAs have not been fully understood for many significant Gram-positive pathogens. Through genomic, lipidomic, and animal infection model analyses, as well as antimicrobial susceptibility assays, this study advances our understanding of Type IV LTA biosynthesis and the physiological roles of glycolipids in mitis group streptococci. Overall, our work establishes the essentiality of glycolipids in both bacterial virulence and defense against antimicrobials.
Rod inputs arrive at horizontal cell somas in mouse retina solely via rod-cone coupling
Authors: Thoreson Wallace B. , Sladek Asia L. , Barta Cody L. , Townsend Lou E.
Published: October 2024

Rod and cone photoreceptor cells selectively contact different compartments of axon-bearing retinal horizontal cells in the retina. Cones synapse exclusively on the soma whereas rods synapse exclusively on a large axon terminal compartment. The possibility that rod signals can travel down the axon from terminal to soma has been proposed to allow spectrally opponent interactions between rods and cones, but there is conflicting data about whether this actually occurs. Because of spectral overlap between rod and cone visual pigments in mouse, we analyzed photoreceptor inputs into horizontal somata by selectively expressing channelrhodopsin in rods and/or cones. Optogenetic stimulation of rods and cones both evoked large fast inward currents in horizontal cell somata. Cone-driven responses were abolished by eliminating synaptic release in a cone-specific knockout of the exocytotic calcium sensor, synaptotagmin 1. However, rod-driven responses in horizontal somata were unchanged after eliminating synaptic release from rods but abolished by eliminating release from both rods and cones. This suggests that cones transmit rod signals that arrive via rod-cone gap junctions. Consistent with this, eliminating Cx36 gap junctions between rods and cones also abolished rod-driven optogenetic responses in horizontal cell somata. These results show that rod signals reach the somas of B-type horizontal cells exclusively via gap junctions with cones and not by traveling down the axon from the axon terminal.

Significance

Rods and cones contact different compartments of retinal horizontal cells: cones contact the soma whereas rods contact a large axon terminal. Cone signals can travel through the axon from soma to terminal, but it is not clear whether rod signals travel the other direction. This latter pathway has been proposed to mediate opponent interactions between rods and cones that could shape vision in dim lights. However, our results show that rod signals cannot travel from axon terminal to soma, but mix with cone signals via gap junctions between the two cell types. This finding limits mechanisms for explaining opponent rod-cone interactions in color and contrast perception.