bluuebunny/crossref_metadata_2025_split huggingface dataset:
The evaluation of a novel single-lead biopotential device for home sleep testing
Authors: Massie Frederik , Vits Steven , Verbraecken Johan , Bergmann Jeroen 
Published: October 2024

Abstract

Study Objectives
This paper reports on the clinical evaluation of the sleep staging performance of a novel single-lead biopotential device.

Methods
One hundred and thirty-three patients suspected of obstructive sleep apnea were included in a multi-site cohort. All patients underwent polysomnography and received the study device, a single-lead biopotential measurement device attached to the forehead. Clinical endpoint parameters were selected to evaluate the device’s ability to determine sleep stages. Finally, the device’s performance was compared to the clinical study results of comparable devices.

Results
Concurrent PSG and study device data were successfully acquired for 106 of the 133 included patients. The results of this study demonstrated significant similarity in overall sleep staging performance (five-stage Cohen’s Kappa of 0.70) to the best-performing reduced-lead biopotential device to which it was compared (five-stage Cohen’s Kappa of 0.73). Contrary to the comparator devices, the study device reported a higher Cohen’s Kappa for rapid eye movement (REM) (0.78) compared to N3 (0.61), which can be explained by its particular measuring electrode placement (diagonally across the lateral cross-section of the eye). This placement was optimized to ensure the polarity of rapid eye movements could be adequately captured, enhancing the capacity to discriminate between N3 and REM sleep when using only a single-lead setup.

Conclusions
The results of this study demonstrate the feasibility of incorporating a single-lead biopotential extension in a reduced-channel home sleep apnea testing setup. Such incorporation could narrow the gap in the functionality of reduced-channel home sleep testing and in-lab polysomnography without compromising the patient’s ease of use and comfort.

Clinical Trials
NCT05035992, A Validation Study of the NightOwl Head Sensor
https://clinicaltrials.gov/ct2/show/NCT05035992
Dissecting the role of transcription factor AP2‐M in Babesia asexual replication
Authors: Wang Jinming , Chai Yijun , Yang Jifei , Ye Yuxin , Luo Jianxun , Yin Hong , Guan Guiquan 
Published: October 2024

AbstractBabesia spp. are obligate intracellular parasites that invade host cells to complete their asexual development and transmission. Here, we identified a transcription factor AP2‐M (BXIN_0799) in Babesia sp. Xinjiang (Bxj), a member of the Apicomplexan AP2 family, which regulates gene expression related to red blood cell (RBC) invasion and cell cycle progression. Our genome‐wide analysis of (Cut‐Tag) data shows that AP2‐M specifically recognized DNA motifs in the promoters of target genes. AP2‐M target genes included other AP2 gene family members and epigenetic markers, which could modulate gene expression involved in RBC invasion, merozoite morphology, and cell cycle phases, as indicated by RNA sequencing, proteomics, and single‐cell RNA sequencing (scRNA‐seq) data from an ap2‐m gene disrupted strain (AP2‐M (−)). We conclude that AP2‐M appeared to contribute to the process of red blood cell invasion, maintain merozoite morphology, and cell cycle progression through GS and MS phases.
m6A demethylase FTO transcriptionally activated by SP1 improves ischemia reperfusion‐triggered acute kidney injury by activating Ambra1/ULK1‐mediated autophagy
Authors: Chen Yan , Liu Yuanfei , Tu Weiping , Chen Yanxia , Xu Chengyun , Huang Chong 
Published: October 2024

AbstractIschemia reperfusion (I/R) was considered as one of main causes of acute kidney injury (AKI). However, the exact mechanism remains unclear. Here, this study aimed to investigate the role and mechanism of the m6A demethylase fat mass and obesity‐associated (FTO) protein in I/R‐induced AKI. HK‐2 cells and SD rats were utilized to establish hypoxia/reoxygenation (H/R) or I/R induced AKI models. The changes of RNAs and proteins were quantified using RT‐qPCR, western blot, and immunofluorescence assays, respectively. Cell proliferation and apoptosis were assessed by CCK‐8 and flow cytometry. Interactions between molecules were investigated using RIP, ChIP, Co‐IP, RNA pull‐down, and dual luciferase reporter assays. Global m6A quantification was evaluated by kits. TUNEL and HE staining were employed for histopathological examinations. Oxidative stress‐related indicators and renal function were determined using ELISA assays. The FTO expression was downregulated in H/R‐induced HK‐2 cells and renal tissues from I/R‐induced rats. Overexpression of FTO improved the cell viability but repressed apoptosis and oxidative stress in H/R‐treated HK‐2 cells, as well as enhanced renal function and alleviated kidney injury in I/R rats. Notably, the FTO overexpression significantly increased autophagy‐related LC3 and ULK1 levels. When autophagy was inhibited, the protective effects of FTO in AKI were diminished. Notably, Ambra1, a crucial regulator of autophagy, was repressed in H/R‐induced HK‐2 cells. However, the FTO overexpression restored the Ambra1 expression by reducing m6A modification of its mRNA. SP1, acting as an upstream transcription factor, directly interacts with the FTO promoter to enhance FTO expression. Knockdown of SP1 or Ambra1 suppressed the beneficial effects of FTO upregulation on autophagy and oxidative stress injury in H/R‐stimulated cells. FTO, transcriptionally activated by SP1, promoted autophagy by upregulating Ambra1/ULK1 signaling, thereby inhibiting oxidative stress and kidney injury. These findings may provide some novel insights for AKI treatment.
Surgical Management of Early Metacarpophalangeal Joint Silicone Implant Fracture in Patient With Rheumatoid Arthritis
Authors: Pasha Mehreen , Baldino Joshua B. , Rodner Craig M. 
Published: October 2024

Introduction:
Metacarpophalangeal (MCP) joint arthroplasty is a common treatment modality to correct ulnar drift, pain, and functional deficits in patients with rheumatoid arthritis, an autoimmune condition targeting the synovium of joints. While silicone MCP joint implants are susceptible to revision in the long term, there is a lack of literature discussing their early breakage. The present case illustrates silicone implant fracture only 10 weeks after MCP arthroplasty—the first instance in the literature to the authors’ knowledge.

Materials and Methods:
The patient is a 64-year-old female with stage 4 rheumatoid arthritis who underwent right index and middle finger MCP joint arthroplasties using 0-degree silicone implants, radial sagittal band imbrication on these digits, and right ring and small finger extensor tendon centralization at the MCP joint.

Results:
During the 10th postoperative week, the patient presented with atraumatic middle finger pain and ulnar deviation. Imaging revealed a right middle finger MCP implant fracture at the distal stem, which underwent successful revision using a 30-degree flexed implant and index and middle extensor tendon centralization.

Discussion:
Nineteen months after revision surgery, the patient continues to have no pain and an improved range of motion. Ultimately, we are hopeful that the flexed silicone implant will last the patient's lifetime.
Long-Term Prospective Quality-of-Life Outcomes in 445 Patients with Sporadic Vestibular Schwannoma
Authors: Carlson Matthew L. , Babajanian Eric E. , Lohse Christine M. , Tombers Nicole M. , Link Michael J. 
Published: October 2024

Objective
To evaluate the long-term changes in sporadic vestibular schwannoma (VS) disease-specific quality-of-life (QOL) outcomes.

Study Design
Prospective longitudinal study using the Penn Acoustic Neuroma Quality of Life (PANQOL) Scale.

Setting
National survey.

Patients
Patients with sporadic VS who completed a baseline survey before treatment and at least one follow-up survey recruited through the authors’ center and through the Acoustic Neuroma Association.

Interventions
Observation, microsurgery, radiosurgery.

Main Outcome Measures
Changes in PANQOL scores from baseline to most recent survey.

Results
Among 445 eligible patients the mean duration of follow-up was 4.4 (SD, 2.3) years, including 122, 218, and 105 in the observation, microsurgery, and radiosurgery groups, respectively. Patients managed with observation (p = 0.03) or microsurgery (p < 0.001) demonstrated improvement in anxiety scores. Changes in facial function scores differed significantly by management group (p = 0.01), with patients undergoing microsurgery demonstrating a mean decline of 10 points in facial function scores compared with mean declines of 3 for those managed with observation or radiosurgery. Hearing loss scores decreased similarly over time for all three groups (p = 0.3). There were minimal changes in total PANQOL scores over time across all management groups (p = 0.5).

Conclusions
Long-term changes in total QOL among VS management groups are not significantly different. Microsurgery may continue to confer an advantage regarding improvement in anxiety postoperatively, but with a greater decline in facial function when compared to observation or radiosurgery. Long-term declines in hearing loss scores were not statistically significantly different among groups.
Residual Vestibular Schwannomas: Proposed Age-Tumor-Residual (ATR) Staging System to Predict Future Growth
Authors: Totten Douglas J. , Cumpston Evan C. , Schneider William , Yates Charles W. , Shah Mitesh V. , Nelson Rick F. 
Published: October 2024

Objective
To assess growth rates of residual vestibular schwannoma after subtotal and near-total surgical resection and establishing staging system for risk of residual tumor growth.

Study Design
Retrospective cohort study.

Setting
Tertiary referral center.

Patients
Patients with residual vestibular schwannoma after surgical resection from 2011 to 2023 identified on postoperative MRI defined as near-total resection (NTR, less than 5 mm of remaining tumor), subtotal resection (STR; 5–10 mm) and debulking (>10 mm).

Main Outcome Measures
Tumor growth of 2 mm or more after subtotal or near-total surgical resection of vestibular schwannoma.

Results
A total of 56 patients (54% female; mean, standard deviation [SD] age 51 [17] yr) had residual tumor. Mean preoperative tumor size was 3.0 (1.1) cm, and residual tumors involved both sides with similar frequency (right: 52%). Quantitatively, 29% were NTR, 32% were STR, and 39% were debulking. With an average follow-up of 27 (SD 31) months, tumor growth occurred in 11 (20%), tumor shrinkage occurred in 16 (29%), and tumors were unchanged in 29 (51%) cases. Growing residual tumors were treated with radiation (7 patients) or a second surgical resection (4 patients). Multivariable analysis identified lower patient age, larger preoperative tumor size, and larger residual tumor size in risk of residual growth. A residual VS tumor staging system (Age, Tumor, Residual [ATR]) is proposed with most tumors in stage II (22, 42%) or stage III (23, 44%), whereas 7 (14%) tumors are stage I.

Conclusions
Approximately 80% of residual VS are stable or shrink in size. Initial observation is advocated after incomplete resection and long-term follow up is needed. Patient age less than 55 years, larger preoperative tumor size, and larger postoperative residual tumor size appear predictive of residual tumor growth.
Level of Evidence: 4
Rag2Mol: Structure-based drug design based on Retrieval Augmented Generation
Authors: Zhang Peidong , Peng Xingang , Han Rong , Chen Ting , Ma Jianzhu 
Published: October 2024

ABSTRACTArtificial intelligence (AI) has brought tremendous progress to drug discovery, yet identifying hit and lead compounds with optimal physicochemical and pharmacological properties remains a significant challenge. Structure-based drug design (SBDD) has emerged as a promising paradigm, but the inherent data biases and ignorance of synthetic accessibility render SBDD models disconnected from practical drug discovery. In this work, we explore two methodologies, Rag2Mol-G and Rag2Mol-R, both based on retrieval-augmented generation (RAG) to design small molecules to fit a 3D pocket. These two methods involve searching for similar small molecules that are purchasable in the database based on the generated ones, or creating new molecules from those in the database that can fit into a 3D pocket. Experimental results demonstrate that Rag2Mol methods consistently produce drug candidates with superior binding affinities and drug-likeness. We find that Rag2Mol-R provides a broader coverage of the chemical landscapes and more precise targeting capability than advanced virtual screening models. Notably, both workflows identified promising inhibitors for the challenging target PTPN2, which was considered undruggable because of structural characteristics of phosphatases. Our highly extensible framework can integrate diverse SBDD methods, marking a significant advancement in AI-driven SBDD. The codes are available at:https://github.com/CQ-zhang-2016/Rag2Mol.
Cultivation protocols for the rhodophytes,Devaleraea mollisandPalmaria hecatensisfrom Alaska
Authors: Dittrich Muriel C. , Meyer Lindsay , Stekoll Michael , Kelley Amanda , Umanzor Schery 
Published: October 2024

AbstractSpecies diversification is crucial for the long-term viability, competitiveness, and sustainability of the seaweed farming industry in the United States. This study investigated the effects that temperature (4, 8 and 12°C), photoperiod (8L:16D, 12L:12D and 16L:8D), and irradiance (20, 40, 100 ± 10 µmol photons m−2s−1) had on the specific growth rate (SGR) ofDevaleraea mollisandPalmaria hecatensisfrom Alaska. Outputs were used to adjust indoor cultivation protocols forD. mollisand develop the first protocols forP. hecatensis. This study also explored the use of two low-cost commercial nutrient products (F/2 and Jack’s Special 25-5-15) as alternatives to the recommended nutrient medium, von Stosch Enrichment. Assessments determined whether their use resulted in similar SGRs without compromising biomass quality or raising production costs. Results showed that both species responded differently to each factor, indicating distinct ecological and physiological adaptations.D. mollisexhibited higher growth rates in warmer temperatures and responded to higher irradiance levels with spore release but showed no clear preference between neutral and long-day photoperiods. In contrast,P. hecatensisdemonstrated higher growth rates in cooler environments with a long-day photoperiod promoting the most growth without spore release. Nutrient supplementation revealed that growth inD. molliswas affected by nutrient formulation, whileP. hecatensisshowed no significant growth variation. These findings underscore the importance of species and geographic-specific protocols for seaweed farming. Further research is needed to optimize the potential cultivation protocols provided here. Cultivation protocols would also benefit from exploring the ecological and physiological nuances of both species.
All-trans retinoic acid-mediated ADAR1 degradation synergizes with PD-1 blockade to suppress pancreatic cancer
Authors: Li Ching-Fei , Bai Li-Yuan , Wei Yongkun , Lee Heng-Huan , Yang Riyao , Yao Jun , Wang Huamin , Wang Ying-Nai , Chang Wei-Chao , Shen Yi-Chun , Wang Shao-Chun , Chou Cheng-Wei , Fu Jie , Ling Jianhua , Chu Yu-Yi , Chiu Chang-Fang , Wang Michael , Yu Dihua , Chiao Paul J , Liang Han , Maitra Anirban , Ying Haoqiang , Hung Mien-Chie 
Published: October 2024

AbstractAs a double-stranded RNA–editing enzyme and an interferon-stimulated gene, double-stranded RNA-specific adenosine deaminase (ADAR1) suppresses interferon signaling and contributes to immunotherapy resistance. Suppression of ADAR1 overcomes immunotherapy resistance in preclinical models, but has not yet been translated to clinical settings. By conducting a screening of a subset of the FDA-approved drugs, we found that all-trans retinoic acid (ATRA, also known as tretinoin) caused ADAR1 protein degradation through ubiquitin-proteasome pathways and concomitantly increased PD-L1 expression in pancreatic and breast cancers. In addition, the combination of ATRA and PD-1 blockade reprogrammed the tumor microenvironment and unleashed antitumor immunity and thereby impeded tumor growth in pancreatic cancer mouse models. In a pilot clinical trial, a higher dose of ATRA plus the anti-PD-1 antibody nivolumab prolonged median overall survival in patients with chemotherapy-resistant pancreatic cancer compared to a lower dose of the same regimen. In this study, ATRA was the first drug to be found to cause ADAR1 degradation. We propose translation of a promising 2-pronged antitumor strategy using ATRA and nivolumab to convert immunologically “cold” into “hot” tumors susceptible to immune checkpoint blockade.
Enhancing Radiation-induced Reactive Oxygen Species Generation Through Mitochondrial Transplantation in Human Glioblastoma
Authors: Marshall Kent L , Velayutham Murugesan , Khramtsov Valery V. , Mizener Alan , Cifarelli Christopher P 
Published: October 2024

AbstractGlioblastoma (GBM) is the most aggressive primary brain malignancy in adults, with high recurrence rates and resistance to standard therapies. This study explores mitochondrial transplantation as a novel method to enhance the radiobiological effect (RBE) of ionizing radiation (IR) by increasing mitochondrial density in GBM cells, potentially boosting reactive oxygen species (ROS) production and promoting radiation-induced cell death. Using cell-penetrating peptides (CPPs), mitochondria were transplanted into GBM cell lines U3020 and U3035. Transplanted mitochondria were successfully incorporated into recipient cells, increasing mitochondrial density significantly. Mitochondrial chimeric cells demonstrated enhanced ROS generation post-irradiation, as evidenced by increased electron paramagnetic resonance (EPR) signal intensity and fluorescent ROS assays. The transplanted mitochondria retained functionality and viability for up to 14 days, with mitochondrial DNA (mtDNA) sequencing confirming high transfection and retention rates. Notably, mitochondrial transplantation was feasible in radiation-resistant GBM cells, suggesting potential clinical applicability. These findings support mitochondrial transplantation as a promising strategy to overcome therapeutic resistance in GBM by amplifying ROS-mediated cytotoxicity, warranting further investigation into its efficacy and mechanismsin vivo.
Nested admixture during and after the Trans-Atlantic Slave Trade on the island of São Tomé
Authors: Ciccarella Marta , Laurent Romain , Szpiech Zachary A. , Patin Etienne , Dessarps-Freichey Françoise , Utgé José , Lémée Laure , Semo Armando , Rocha Jorge , Verdu Paul 
Published: October 2024

AbstractHuman admixture history is rarely a simple process in which distinct populations, previously isolated for a long time, come into contact once to form an admixed population. In this study, we aim to reconstruct the complex admixture histories of the population of São Tomé, an island in the Gulf of Guinea that was the site of the first slave-based plantation economy, and experienced successive waves of forced and deliberate migration from Africa. We examined 2.5 million SNPs newly genotyped in 96 São Toméans and found that geography alone cannot explain the observed patterns of genetic differentiation within the island. We defined five genetic groups in São Tomé based on the hypothesis that individuals sharing the most haplotypes are more likely to share similar genetic histories. Using Identical-by-Descent and different local ancestry inference methods, we inferred shared ancestries between 70 African and European populations and each São Toméan genetic group. We identified admixture events between admixed groups that were previously isolated on the island, showing how recently admixed populations can be themselves the sources of other admixture events. This study demonstrates how complex admixture and isolation histories during and after the Transatlantic Slave-Trade shaped extant individual genetic patterns at a local scale in Africa.
Cannabidiol reverses microglia activation and loss of parvalbumin interneurons and perineuronal nets in a mouse model of schizophrenia
Authors: Rodrigues da Silva Naielly , Gobbo Davide , Gomes Felipe V. , Scheller Anja , Kirchhoff Frank , Del Bel Elaine , Silveira Guimarães Francisco 
Published: October 2024

AbstractCannabidiol (CBD) has shown potential for treating schizophrenia (SCZ) by targeting its positive, negative, and cognitive symptoms. In this study, we investigated if CBD could reverse the memory impairment observed after chronic administration of the NMDA receptor antagonist. MK-801 treatment (0.5 mg/kg i.p., twice a day, for 14 days) resulted in short- and long-term memory deficits and decreased relative power of γ oscillation in freely moving animals. CBD administration (60 mg/kg i.p. daily for seven days after the MK-801 treatment period) reversed these changes. The positive cognitive effects of CBD were prevented by a 5-HT1A, but not a CB2, receptor antagonist. On the cellular level, CBD reversed MK-801-induced reduced number of parvalbumin-positive neurons and their associated perineuronal nets in the prelimbic medial prefrontal cortex (mPFC) and ventral hippocampus (vHip). This neuroprotective effect was mediated by 5-HT1A and CB2 receptors in the vHip but was independent of these receptors in the mPFC. Additionally, CBD reversed MK-801-induced microglial activation in both mPFC and vHip, again through 5-HT1A and CB2 receptors. These findings suggest that CBD modulates multiple pathways affected in SCZ-like conditions, offering a promising therapeutic avenue for SCZ treatment.Chemical compounds studied in this articleCBD (PubChem CID: 644019), MK-801 (PubChem CID: 180081), AM630 (PubChem CID: 4302963), WAY100635 (PubChem CID: 11957721).
Transcutaneous Vagus Nerve Stimulation Boosts Post-Error Accuracy During Perceptual Decision-Making
Authors: Su Shiyong , Vanvoorden Thomas , Le Denmat Pierre , Zénon Alexandre , Braconnier Clara , Duque Julie 
Published: October 2024

AbstractThe locus coeruleus-norepinephrine (LC-NE) system is a well-established regulator of behavior, yet its precise role remains unclear. Animal studies predominantly support a “gain” hypothesis, suggesting that the LC-NE system enhances sensory processing, while human studies have proposed an alternative “urgency” hypothesis, postulating that LC-NE primarily accelerates responses. To address this discrepancy, we administered transcutaneous vagus nerve stimulation (tVNS) in two experiments involving 43 participants. In the first experiment, we showed that 4-second tVNS trains reliably induced greater pupil dilation compared to SHAM condition, indicating increased LC-NE activity. In the second experiment, we applied tVNS during a random dot motion task to assess its impact on perceptual decision-making. Notably, tVNS improved accuracy without affecting reaction times, which appears inconsistent with the “urgency” hypothesis. Drift-diffusion model analyses further supported the “gain” hypothesis, revealing that tVNS increased the drift rate, indicative of enhanced evidence accumulation. Accuracy and drift-rate improvements were especially pronounced following errors and in less proficient participants, who otherwise exhibited post-error declines in these measures under SHAM condition. Our findings suggest that the influence of the LC-NE system adapts to task demands, becoming especially beneficial in challenging contexts. Overall, this study underscores the potential of tVNS as a non-invasive tool to investigate the causal role of the LC-NE system in human behavior.