bluuebunny/crossref_metadata_2025_split huggingface dataset:
Walleye Dermal Sarcoma Virus Cyclin Interacts with Components of the Mediator Complex and the RNA Polymerase II Holoenzyme
Authors: Rovnak Joel , Quackenbush Sandra L. 
Published: July 2002

ABSTRACT
Walleye dermal sarcoma virus (WDSV) encodes an accessory protein, OrfA, with sequence homology to cyclins (retrovirus cyclin). In cells transfected with an expression construct, OrfA was localized to the nucleus and was concentrated in interchromatin granule clusters (IGCs), sites where splicing factors are concentrated. Other proteins identified in IGCs include transcription factors, the large subunit of RNA polymerase II (Pol II), and cyclin-dependent kinase 8 (cdk8). cdk8 is the kinase partner of cyclin C and a component of the mediator complex, associated with the Pol II holoenzyme. cdk8 and cyclin C can regulate transcription via phosphorylation of cyclin H and the carboxy-terminal domain of Pol II. OrfA in transfected HeLa cells was found to colocalize and copurify with hyperphosphorylated forms of Pol II (Pol IIO) in IGCs, and OrfA was coimmunoprecipitated from lysates of transfected cells with an antibody against Pol IIO. Likewise, Pol IIO could be coprecipitated with an antibody against OrfA. A survey with antibodies against several different cdks resulted in coimmunoprecipitation of OrfA with anti-cdk8, and antiserum against OrfA was able to coprecipitate cdk8 from lysates of cells that express OrfA. Coprecipitation of OrfA with anti-cyclin C demonstrated that it was included in complexes with OrfA and cdk8. OrfA has sequence and structural similarities to cyclin C, and, functionally, OrfA appears to have the capacity to both enhance and inhibit the activity of promoters in a cell-specific manner, similar to functions of the mediator complex. These data suggest that WDSV OrfA functions through its interactions with these large, transcription complexes. Further investigations will clarify the role of the retrovirus cyclin in control of virus expression and transformation.
Brucella suis
S2 strain inhibits IRE1/caspase-12/caspase-3 pathway-mediated apoptosis of microglia HMC3 by affecting the ubiquitination of CALR
Authors: Wang Zhao , Wang Yanbai , Yang Shulong , Wang Zhenhai , Yang Qian 
Published: February 2025

ABSTRACT

Neurobrucellosis represents a severe complication of brucellosis, posing a considerable risk to human health and quality of life. This condition arises from an increased susceptibility to chronic
Brucella
infection, a significant clinical challenge. One key factor contributing to chronic neurobrucellosis is the regulation of microglial apoptosis by
Brucella
; however, the exact molecular mechanisms remain largely unresolved. In this study, human microglial clone 3 (HMC3) cells were infected with
Brucella suis
vaccine strain S2 (
B. suis
S2) at varying multiplicity of infection (MOI) and durations to assess its effects on the IRE1/caspase-12/caspase-3 signaling pathway. Following the suppression of this pathway by
B. suis
S2, calreticulin (CALR) was identified through ubiquitin-modified proteomics (data accessible via ProteomeXchange, identifier PXD056006). To further investigate, CALR-overexpression and knockdown HMC3 cell lines were infected with
B. suis
S2 to elucidate the mechanism by which
B. suis
S2 inhibits apoptosis in HMC3 cells. In conclusion, our findings demonstrate that
B. suis
S2 suppresses HMC3 cell apoptosis via the IRE1/caspase-12/caspase-3 pathway by modulating CALR ubiquitination. This study provides a theoretical basis for exploring the mechanisms of neurobrucellosis and offers insights into its clinical treatment.

IMPORTANCE

Neurobrucellosis is a severe complication impacting the central nervous system (CNS) due to neurological deficits caused by
Brucella
, with primary clinical features including meningitis, encephalitis, brain abscesses, and demyelinating lesions. These nonspecific symptoms often lead to misdiagnosis or delayed diagnosis, increasing the risk of recurrent or chronic neurobrucellosis infections. Consequently, persistent infection and relapse are critical challenges in the clinical management of neurobrucellosis, which are closely linked to
Brucella
’s survival and replication within microglia. Interestingly,
Brucella
may inhibit microglia apoptosis by mitigating endoplasmic reticulum (ER) stress, though the precise molecular mechanisms remain largely unexplored. Thus, this study will elucidate the specific mechanisms by which
Brucella
suppresses microglial apoptosis and provide deeper insights into the molecular pathogenesis and clinical treatment of neurobrucellosis.
Bridging assessment and treatment for repeat suicidality in prisons: development and validation of a risk model
Authors: Fazel Seena , Heathcote Leanne , Farouki Leen , Senior Jane , Perry Amanda , Fanshawe Thomas R , Shaw Jenny 
Published: February 2025

BackgroundSuicidal thoughts and behaviours are common in people in prison and associated with poor health outcomes, including suicide, injury and repeat self-harm.ObjectiveTo develop and validate a model to stratify risk of repeat suicidality up to 3 months in people in prison.MethodsIn seven English prisons, we identified 754 people aged over 17 who had been placed on a suicide risk management plan after a self-harm episode or elevated risk. We developed a multivariable model to stratify risk of repeat suicidality at 3 months using routinely collected sociodemographic, clinical and prison-related factors, which were tested using Cox proportional HR models. In a prospective validation sample of 390 people from 13 prisons, we tested this model to assess risk of repeat suicidality at 3 months across a range of performance measures.FindingsOf the overall sample of 1144 people in prison (n=966 men or 84%, mean age 33 years), 22% had the outcome of repeat suicidality over 3 months. The final risk model consisted of nine factors, including sex, calendar age and features of recent suicidal behaviour. Calibration and discrimination were similar in both development and validation samples, with O:E ratio=1.09 (95% CI 0.88 to 1.35) and c-statistic=0.66 (95% CI 0.60 to 0.72) in external validation. At a 25% cut-off, sensitivity was 58% (50 to 66) and specificity was 72% (68 to 75) in external validation. The tool (Risk Assessment for people in Prison at risk of Self-harm and Suicide, RAPSS) is available as an online risk calculator athttps://oxrisk.com/rapsstrial/.InterpretationA novel assessment approach for repeat suicidality can provide an evidence-based approach to stratify risk and better allocate resources.
Sleep disorders and the association with frailty among community-dwelling older adults in Northwest China: a cross-sectional study
Authors: Yu Xingfeng , Wang Dan , Yao Lipei , Shi Zhengyan , Liu Xiaomei , Wu Hongjuan , Jiang Jia , Zhang Yulian , He Qianfeng 
Published: February 2025

ObjectivesTo investigate the status of sleep disorders and their association with comprehensive frailty in the community-dwelling older adults.DesignA cross-sectional study.SettingSix community healthcare centres in Xi’an City, Northwest China.ParticipantsA total of 2647 community-dwelling older adults completed the study.Primary and secondary outcome measuresThe primary outcomes included frailty and sleep disorders, measured with the Comprehensive Frailty Assessment Instrument and Pittsburgh Sleep Quality Index (PSQI), respectively. The secondary outcomes were potential factors associated with frailty.ResultsThe participants averaged 5.23±2.94 in the total score of the PSQI, with a poor sleep quality prevalence of 19.9%. Individuals with poor sleep quality are more likely to have mild and high frailty, with an OR of 1.64 and 2.81, respectively. Both shortened (<5 hours) and prolonged (>8 hours) sleep duration are associated with higher level of frailty. Poor overall sleep, poor subjective sleep quality, extended sleep latency, sleep disturbances, use of sleeping medication and daytime dysfunction were associated with higher level of frailty (with a correlational coefficient of 0.237, 0.201, 0.223, 0.197, 0.087 and 0.378, respectively).ConclusionSleep disorders are common problems among community-dwelling older adults, the severity of which rises with the increase in frailty level. Poor overall sleep quality, poor subjective sleep quality, extended sleep latency, sleep disturbances, daytime dysfunction and abnormal sleep duration are associated with frailty.
Frizzled-7-targeting antibody-derived bifunctional protein retargets NK cells against triple-negative breast cancer cells via MICA-NKG2D axis
Authors: Wang Chenyue , Wu Lisha , Li Xingxing , Mao Shuyang , Wang Zitong , Xie Haiyan , Xu Jing , Li Danfang , Yang Hao , Wang Tong , Huang Qingqing , Yang Lin , Zhang Xiaofei , Liu Yuxia , Wang Jin , Huang Gang , Xie Wei 
Published: February 2025

BackgroundHypoxia is associated with the evasion of triple-negative breast cancer (TNBC) from immune surveillance. Hypoxia increases the subpopulation of putative TNBC stem-like cells (TNBCSCs) through activating Wnt/β-Catenin signaling. The shedding of MHC class I-related chain A (MICA) is particularly noteworthy in cancer stem cells (CSCs), promoting the resistance of CSCs to natural killer (NK) cell cytotoxicity. To reestablish MICA/NKG2D-mediated immunosurveillance, we proposed the design of a fusion protein (SHH002-hu1-MICA) which consists of Frizzled-7 (Fzd7)-targeting antibody and MICA, serving as an engager retargeting NK cells against TNBCs, especially TNBCSCs.MethodsOpal multicolor immunohistochemistry staining was used to validate the expression of membrane MICA (mMICA) and existence of NK cells in TNBC tumors; flow cytometry (FCM) assay was used to detect the expression of Fzd7/mMICA on TNBCs. Biolayer interferometry (BLI) and surface plasmon resonance (SPR) assays were executed to assess the affinity of SHH002-hu1-MICA towards rhFzd7/rhNKG2D; near-infrared imaging assay was used to evaluate the targeting capability. A cytotoxicity assay was conducted to assess the effects of SHH002-hu1-MICA on NK cell-mediated killing of TNBCs, and FCM assay to analyze the effects of SHH002-hu1-MICA on the degranulation of NK cells. Finally, TNBC cell-line-derived xenografts were established to evaluate the anti-tumor activities of SHH002-hu1-MICA in vivo.ResultsThe expression of mMICA is significantly downregulated in hypoxic TNBCs and TNBCSCs, leading to the evasion of immune surveillance exerted by NK cells. The expression of Fzd7 is significantly upregulated in TNBCSCs and exhibits a negative correlation with the expression of mMICA and infiltration level of NK cells. On accurate assembly, SHH002-hu1-MICA shows a strong affinity for rhFzd7/rhNKG2D, specifically targets TNBC tumor tissues, and disrupts Wnt/β-Catenin signaling. SHH002-hu1-MICA significantly enhances the cytotoxicity of NK cells against hypoxic TNBCs and TNBCSCs by inducing the degranulation of NK cells and promotes the infiltration of NK cells in CD44highregions within TNBC xenograft tumors, exhibiting superior anti-tumor activities than SHH002-hu1.ConclusionsSHH002-hu1-MICA maintains the targeting property of SHH002-hu1, successfully activates and retargets NK cells against TNBCs, especially TNBCSCs, exhibiting superior antitumor activities than SHH002-hu1. SHH002-hu1-MICA represents a promising new engager for NK cell-based immunotherapy for TNBC.
Impact of iron deficiency on congestion and postdischarge survival in patients recently hospitalised for decompensated heart failure: a multicentre, prospective, observational analysis of the FERIC-RO study
Authors: Margineanu Cornelia , Antohi Laura , Ambrosy Andrew , Bartos Daniela , Collins Sean , Sinescu Crina , Tatu Chitoiu Gabriel , Lighezan Daniel , Vinereanu Dragos , Pop Dana , Pang PS , Butler Javed , Chioncel Ovidiu 
Published: February 2025

BackgroundIron deficiency (ID) is a highly prevalent comorbidity in patients with chronic and acute heart failure and is associated with worse clinical outcomes. We aimed to evaluate the prevalence and clinical characteristics of ID and its association with in-hospital congestion and postdischarge outcomes.MethodsFiER deficit in Insuficienta Cardiaca in Romania was a prospective, multicentric study, enrolling 163 patients hospitalised for worsening chronic heart failure (WCHF) irrespective of left ventricular ejection fraction. ID was evaluated at discharge and defined as ferritin<100 ng/mL or ferritin 100–299 ng/mL with transferrin saturation<20%. Patients were classified based on ID status. In-hospital changes of clinical signs of congestion and natriuretic peptides (NT-proBNP) were reported and correlated with ID status. Additionally, survival analysis at 30 and 90 days was performed and compared between patients with ID+ and ID−.ResultsThe prevalence of ID was 54.6% (N=89) among 163 eligible patients. Patients with ID+ had more clinical signs of congestion and advanced New York Heart Association functional class at discharge (classes III and IV 58.4% vs 31.1%; p 0.002). NT-proBNP values at admission were higher in ID+ (9288 pg/dL vs 4414 pg/dL, p<0.001), with lower NT-proBNP decrease during hospitalisation (−45.7% vs −63.3%, p 0.003). Additionally, there was no difference in ID prevalence between discharge and 30 days after (54.6% vs 51.3%, p 0.782). Postdischarge all-cause mortality did not differ between ID+ and ID− at 30 days (5.6%% vs 2.7%, p 0.361), but at 90 days, it was higher in ID+ group (30.9% ID+ vs 9.6% ID−, p 0.005).ConclusionsPatients hospitalised for WCHF and ID had more residual congestion, higher absolute values and significantly lower in-hospital change of NT-proBNP. A significant difference in survival between the two ID groups emerged within 90 days of hospital discharge.
EducAR: implementing a multicomponent strategy to improve therapeutic adherence in rheumatoid arthritis
Authors: Ahijón Lana María , Sivera Mascaró Francisca , Fernández-Nebro Antonio , Muntadas Castelló Sara , Pérez Marina , Otón Teresa , García de Yébenes María Jesús , Carmona Loreto 
Published: February 2025

IntroductionThe EULAR points to consider (PtC) for reducing non-adherence need implementation.ObjectivesTo design, implement and evaluate a strategy based on the PtC to improve treatment adherence in rheumatoid arthritis (RA).MethodsA multidisciplinary panel cocreated an intervention that was subsequently tested in a cluster trial, where centres were randomised to access the developed intervention or follow the standard of care (SOC). 6-month initiation and implementation adherence were measured in consecutive patients with <2 years of RA. The results were discussed among the centres assigned to the intervention to explore barriers and facilitators to implementation.ResultsThe intervention was a two-sided website. The items on the patient site mainly addressed disease and treatment education, self-management and peer support. The healthcare professional site has tutorials on communication to improve trust and adherence, plus shared decision-making aids. It was tested in 141 RA patients (67 control and 74 intervention). Both groups increased adherence at 6 months, mainly in the control group (48% to 67% vs 42% to 47% in the intervention group). Implementation had been very low in relation to barriers identified as lack of time, inadequate focus (exclusively for nurses) and consideration of the current SOC as adequate.ConclusionDespite designing an intervention based on the best evidence, the results were inconclusive; the lack of a detected effect could be explained by the limited implementation, which was insufficient for the complexity of the changes required (change of culture).Trial register numberClinicalTrials.gov IDNCT05425485.
Optical, physical and structural study of cadmium sodium bismuth borate glasses system
Authors: Maan Deepika , Nain Deepika , Sonia  , Pilania Ravita , Rao A. S. , Meenakshi  
Published: February 2025

The classic melt-quench method was used to make unique transparent cadmium sodium bismuth borate glasses with a composition of [Formula: see text] (18[Formula: see text] Na2[Formula: see text]Bi2O[Formula: see text]B2O3; for ([Formula: see text], 6, 8, 10, 12). Different analytical equipment such as XRD, UV-Vis-NIR, Raman, DSC, and FTIR were employed to characterize and analyze the manufactured glass samples. The density and oxygen packing density of produced glass samples increased linearly with CdO addition, whereas the molar volume decreased. The X-ray diffraction method was employed to anticipate the amorphous nature of the prepared glass samples. The structural alterations of the generated glasses were investigated using FTIR and RAMAN spectra. DSC was employed to assess the thermal characteristics related to the crystallization temperature ([Formula: see text] and glass transition temperature ([Formula: see text]. DSC demonstrates the result that CdO content contributes most to enhancing the thermal stability of glasses. The ([Formula: see text] values increased while ([Formula: see text] values decreased as CdO substitution increased. Infrared and Raman spectroscopy were used to conduct a thorough examination of structure, which revealed that these glasses were comprised of both symmetric and asymmetric stretched vibrations of bonds. The absorption spectra in the ultraviolet-visible range of the samples indicated a reduction in the optical bandgap as CdO content increased. All the findings indicate that the CdO level in glass samples acts as a network modulator, while BO4 does not.
Revisiting GPS Spoofing in Phasor Measurement: Real-World Exploitation and Practical Detection in Power Grids
Authors: Kim Chunghyo , Noh Juhwan , Ghahremani Esmaeil , Kim Yongdae 
Published: February 2025

Phasor Measurement Units (PMUs) are critical devices in modern power grids, providing precise voltage and current phasor measurements (synchrophasors) for real-time monitoring, fault detection, and stability assessment. While previous research suggested that arbitrary time manipulation through GPS spoofing could disrupt grid operations, our study reveals that successful attacks require specific conditions, contrary to earlier assumptions.

Through careful analysis of the synchrophasor data specification (IEEE Standard C37.118.x), we demonstrate that arbitrary time manipulation
does not
directly lead to phase manipulation. Instead, arbitrary manipulations can cause GPS holdover (loss of lock), alert operators with erroneous timing, and ultimately invalidate the received synchrophasors. An experiment with a commercial PMU confirms our specification analysis. We identify the time spoofing conditions to avoid GPS holdover and discover that nanosecond-scale signal alignment (approximately 375 ns error) and gradual time manipulation (around 50 ns/s error) are required.

Experiments on a commercial Wide Area Monitoring System (WAMS) testbed demonstrate that GPS spoofing meeting the identified criteria results in a 500-microsecond time error (10.8-degree phase error) after 12 hours without triggering alarms. Given that a 60-degree phase variation is considered a fault, triggering protection mechanisms, this GPS spoofing technique could potentially induce false faults within 70 hours.
To counter this threat, we propose a practical method to distinguish GPS spoofing-induced false faults from actual faults caused by events like lightning strikes or ground shorts. Analysis of 10 real-world incidents from the past six months demonstrates that genuine faults consistently exhibit instantaneous phase variations within three electrical cycles, providing a basis for differentiation.
Electrostatically-Assisted Removal of Charged Bumpy and Rough Particles in Turbulent Airflows
Authors: Khanmohammadi Abbas , Ahmadi Goodarz 
Published: February 2025

Abstract
The detachment of charged, bumpy, and rough particles from rough surfaces in turbulent airflow in an electric field was studied. Electrostatic forces between the charged particles and the conductive surface were evaluated for various electric fields. Particles with corona ion charges, Boltzmann charge distribution, and saturation charges were considered. The enhanced JKR model was used to determine the adhesion force between micro-particle bumps and surfaces with fine roughness. Attention was given to particle rolling detachment in turbulent airflows when electrostatic forces contribute to the removal process. That is, the electrostatic Coulomb+ force points away from the surface, and hydrodynamic drag force and moment led to the rolling detachment of particles from the surface. The corresponding critical shear velocities for particle resuspension from a substrate were evaluated and compared against the experimental data. The effects of particle size, irregularity, and surface roughness for particle removal were studied. It was shown that appropriate electric fields could significantly reduce the shear velocity needed for particle removal. In fact, a sufficiently high electric field intensity could electrostatically remove the particle in the absence of airflow. Finally, the theoretical findings showed that the electrostatic effects could significantly improve the particle removal and surface cleaning processes.
Phase II trial of atezolizumab and bevacizumab for treatment of HPV-positive unresectable or metastatic squamous cell carcinoma of the anal canal
Authors: Morris Van K. , Liu Suyu , Lin Kangyu , Zhu Haifeng , Prasad Seema , Mahvash Armeen , Bhosale Priya , Sun Baohua , Parra Edwin R. , Wistuba Ignacio , Peddireddy Arjun , Yao James , Mendoza-Perez Julia , Knafl Mark , Woodman Scott E. , Eng Cathy , Halperin Daniel 
Published: February 2025

Abstract
Background: Anti-PD-(L)1 antibodies are associated with responses in &lt;25% of patients with metastatic human papillomavirus (HPV)-associated malignancies. VEGF signaling causes intratumoral immune evasion and immune suppression. We evaluated the anti-PD-L1 antibody atezolizumab and anti-VEGF antibody bevacizumab for patients with unresectable, advanced anal cancer. Patients and methods: For this phase II study, participants with previously treated, immunotherapy-naïve anal cancer received atezolizumab (1200 mg) and bevacizumab (15 mg/kg) intravenously every 21 days. Responses were evaluated every 9 weeks (RECIST v1.1). The primary endpoint was best radiographic response. Median survival was estimated by Kaplan-Meier and compared for selected biomarkers (including paired pretreatment/on-treatment biopsies) using a log-rank test. Results: Among 20 participants, the overall response rate was 11% (95% confidence interval (CI): 1.2-32). Median PFS and OS were 4.1 months (95% CI: 2.6-not assessable) and 11.6 months (95% CI, 9.5-20), respectively. One grade 5 bevacizumab-related bowel perforation occurred. Analyses of 16 paired biopsies linked increases in interferon gamma (P=.03) and inflammatory response (P =.02) gene expression signatures with prolonged PFS, as did rises in CD3+CD8+PD1+ (P=.02) cells and decreases in CD3+FoxP3+ cells (P=.04) from 10 paired biopsies with multiplex immunoflorescence. A subgroup of anal cancers characterized by the SBS31 “prior-platinum” signature demonstrated shorter OS (HR 6.3, 95% CI 1.2-32; P=.01). Conclusions: Atezolizumab and bevacizumab demonstrate activity similar to anti-PD-1 monotherapy for unresectable anal cancer. Our translational data identify undescribed chromosomal and transcriptomic biomarkers associated with survival. These correlative findings warrant confirmation and further validation in larger, prospective immunotherapy trials for advanced anal cancer.