bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-nucleotide-resolution genomic maps of O6-methylguanine from the glioblastoma drug temozolomide
Authors: Kubitschek Jasmina , Takhaveev Vakil , Mingard Cécile , Rochlitz Martha I , Reinert Patricia B , Keller Giulia , Kloter Tom , Fernández Cereijo Raúl , Huber Sabrina M , McKeague Maureen , Sturla Shana J 
Published: January 2025

Abstract
Temozolomide kills cancer cells by forming O6-methylguanine (O6-MeG), which leads to cell cycle arrest and apoptosis. However, O6-MeG repair by O6-methylguanine-DNA methyltransferase (MGMT) contributes to drug resistance. Characterizing genomic profiles of O6-MeG could elucidate how O6-MeG accumulation is influenced by repair, but there are no methods to map genomic locations of O6-MeG. Here, we developed an immunoprecipitation- and polymerase-stalling-based method, termed O6-MeG-seq, to locate O6-MeG across the whole genome at single-nucleotide resolution. We analyzed O6-MeG formation and repair across sequence contexts and functional genomic regions in relation to MGMT expression in a glioblastoma-derived cell line. O6-MeG signatures were highly similar to mutational signatures from patients previously treated with temozolomide. Furthermore, MGMT did not preferentially repair O6-MeG with respect to sequence context, chromatin state or gene expression level, however, may protect oncogenes from mutations. Finally, we found an MGMT-independent strand bias in O6-MeG accumulation in highly expressed genes. These data provide high resolution insight on how O6-MeG formation and repair are impacted by genome structure and nucleotide sequence. Further, O6-MeG-seq is expected to enable future studies of DNA modification signatures as diagnostic markers for addressing drug resistance and preventing secondary cancers.
‘Splice-at-will’ Cas12a crRNA engineering enabled direct quantification of ultrashort RNAs
Authors: Fei Xinrui , Lei Chao , Ren Wei , Liu Chenghui 
Published: January 2025

Abstract
We present a robust ‘splice-at-will’ CRISPR RNA (crRNA) engineering mechanism that overcomes the limitations of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system in directly detecting ultrashort RNAs. In this strategy, an intact Cas12a crRNA can be split from almost any site of the spacer region to obtain a truncated crRNA (tcrRNA) that cannot activate Cas12a even after binding an auxiliary DNA activator. While splicing tcrRNAs with a moiety of ultrashort RNA, the formed combination can work together to activate Cas12a efficiently, enabling ‘splice-at-will’ crRNA engineering. Importantly, the ‘splice-at-will’ crRNA exhibits almost the same trans-cleavage activation efficiency as that of a conventional intact crRNA. Therefore, by rationally designing a DNA auxiliary activator with a conserved tcrRNA-complementary sequence and an arbitrary short RNA-of-interest recognition domain, a general sensing system is established that directly utilizes traditional DNA-activated Cas12a to detect ultrashort RNAs. This ‘splice-at-will’ crRNA engineering strategy could faithfully detect ultrashort RNA sequences as short as 6–8 nt, which cannot be achieved by conventional Cas12a and Cas13a systems. Additionally, through flexible splicing site design, our method can precisely distinguish single-base differences in microRNA and other short RNA sequences. This work has significantly expanded the Cas12a-based diagnostic toolbox and opened new avenues for ultrashort RNA detection.
An integrated approach for the accurate detection of HERV-K HML-2 transcription and protein synthesis
Authors: Gleason Charles , Terry Sandra N , Hernandez Matthew M , Jacob Samson , Fenyo David , Johnson Jeffrey R , Deikus Gintaras , Francoeur Nancy , Hahn Aana , Sebra Robert , Zamarin Dmitriy , Molina Henrik , Simon Viviana , Mulder Lubbertus C F 
Published: January 2025

Abstract
Human endogenous retroviruses (HERVs) occupy a large portion of the human genome. Most HERVs are transcriptionally silent, but they can be reactivated during pathological states such as viral infection and certain cancers. The HERV-K HML-2 clade includes elements that recently integrated have in the human germ line and often contain intact open reading frames that possibly support peptide and protein expression. Understanding HERV–K-host interactions and their potential as biomarkers is problematic due to the high similarity among different elements. Previously, we described a long-read single molecule real-time sequencing (PacBio) strategy to analyze HERV-K RNA expression profiles in different cell types. However, identifying HERV-K HML-2 proteins accurately is difficult without robust and reliable methods and reagents. Here we present a new approach to characterize the HML-2 elements that (a) are being translated and (b) produce enough protein to be detected and identified by mass spectrometry. Our data reveal that RNA expression profiling alone cannot accurately predict which HML-2 elements are responsible for protein production, as we observe several differences between the highest expressed RNAs and the elements that are the predominant source of HERV-K HML-2 protein synthesis. These studies represent an important advance toward untangling the complexity of HERV–K-host interactions.
Navigating vagueness: Rule-following and the scope of trust
Authors: Israel Eli Benjamin 
Published: January 2025

Abstract
In this paper, I address a fundamental challenge in the philosophy of trust: how to account for trustee discretion in scenarios that fall outside explicitly defined expectations. I argue that this challenge reveals vagueness as an inherent feature of trusting relationships, often leading to disagreements between trustors and trustees. To resolve this, I propose a novel account of trust grounded in rule-following, shifting the object of trust from particular actions to adherence to rules constitutive of relationships. By focusing on relationships and their constitutive rules, I provide here a framework for understanding and minimizing disagreements through communication and engaged practice. Furthermore, I argue this framework sheds light on the dynamics of trust-related reactive attitudes, in particular, distinguishing between betrayal and mere disappointment.
Cognitive and neural underpinnings of friend-prioritization in a perceptual matching task
Authors: Gao Tianyu , Zhou Yuqing , Pan Xinyue , Li Wenxin , Han Shihui 
Published: January 2025

Abstract
Previous findings of better behavioral responses to self- over other-related stimuli suggest prioritized cognitive processes of self-related information. However, it is unclear whether the processing of information related to important others (e.g.friends) may be prioritized over that related to the self in certain subpopulations and, if yes, whether friend-prioritization and self-prioritization engage distinct cognitive and neural mechanisms. We collected behavioral and electroencephalography (EEG) data from a large sample (N = 1006) during learning associations between shapes and person labels (self or a friend). Analyses of response times and sensitivities revealed two subpopulations who performed better to friend–shape or self–shape associations, respectively (N = 216 for each group). Drift diffusion model (DDM) analyses unraveled faster information acquisition for friend–shape (vs. self–shape) associations in the friend-prioritization group but an opposite pattern in the self-prioritization group. Trial-by-trial regression analyses of EEG data showed that the greater amplitudes of a frontal/central activity at 180–240 ms poststimulus were correlated with faster information acquisition from friend–shape associations in the friend-prioritization group but from self-shape associations in the self-prioritization group. However, the frontal/central neural oscillations at 8–18 Hz during perceptual learning were specifically associated with speed of information acquisition from friend–shape associations in the friend–prioritization-group. Our findings provide evidence for friend-prioritization in perceptual learning in a subpopulation of adults and clarify the underlying cognitive and neural mechanisms.
Validation of the ANDON KD-7920 wrist blood pressure monitor in general population according to the ISO 81060-2:2018+AMD1:2020 protocol
Authors: Li Duan , Li Yiming , Li Jiaheng , Gu Yuan , Shang Fujun 
Published: January 2025

Objective
This study aimed to evaluate the accuracy of the ANDON KD-7920 oscillometric wrist blood pressure monitor in general population according to the ISO 81060-2:2018+AMD1:2020.

Methods
The same arm sequential method was used for blood pressure measurement among qualified participants according to the ISO 81060-2:2018+AMD1:2020. The validation results were assessed following the criteria of the protocol, and the Bland–Altman scatter plot was used to present the difference between the test device and reference results.

Results
A total of 90 participants were included in the study. According to criterion 1 of the validation protocol, the mean ± SD of the differences between the test device and reference readings was 0.76 ± 6.23 mmHg and −0.13 ± 5.57 mmHg for systolic and diastolic blood pressure, respectively, which met the requirements of less than 5 ± 8 mmHg. According to the criterion 2, the average differences between the test device and reference readings per participant were 0.76 ± 5.56 mmHg and −0.13 ± 5.27 mmHg for systolic and diastolic blood pressure, respectively, which also met the requirements.

Conclusion
The ANDON KD-7920 wrist blood pressure monitor passed all the requirements of the ISO 81060-2:2018+AMD1:2020 and can be recommended for clinical use and self-measurement in general population.
Reimagining apnea monitoring in the neonatal ICU
Authors: Jeanne Emily , Alvaro Ruben , Shalish Wissam 
Published: January 2025

Purpose of review
This review outlines the prevalence and complications of apneas and intermittent hypoxemic events in preterm infants, examines current monitoring limitations in neonatal ICUs (NICUs), and explores emerging technologies addressing these challenges.

Recent findings
New evidence from the Prematurity-Related Ventilatory Control (Pre-Vent) study, which analyzed cardiorespiratory data from 717 extremely preterm infants, exposes the varying frequency, duration, and severity of apneas, intermittent hypoxemia, bradycardias, and periodic breathing during hospitalization, and highlights the negative impact of intermittent hypoxemia on pulmonary outcomes at discharge. Although traditional monitoring methods cannot differentiate between apnea types and quantify their burden, recent advancements in sensor technologies and data integration hold promise for improving real-time detection and evaluation of apneas in the NICU. Notably, small wearable mechano-acoustic sensors could improve apnea monitoring through continuous detection of airflow and respiratory efforts. Additionally, integrating bedside physiological data with modalities such as near-infrared spectroscopy, diaphragmatic activity, and electrical impedance tomography could help predict adverse outcomes by monitoring regional oxygen saturation and lung function in relation to apneas.

Summary
Enhancing our understanding of neonatal apneas and overcoming the current limitations in apnea monitoring through advanced sensor technologies and data integration could lead to more personalized management and improved outcomes for preterm infants.
Utilizing preterm infant body composition assessments to guide neonatal nutrition
Authors: Buck Catherine O. 
Published: January 2025

Purpose of review
The use of body composition to assess the quality of infant growth may add valuable information to pediatric clinical care. Preterm infants have differences in their fat and muscle mass development compared with infants born at term, which may be related to their early nutritional exposures. This review focuses on recent studies examining early nutrition in preterm infants and related body composition outcomes in the newborn period and beyond.

Recent findings
Overall, the evidence shows that early nutrient delivery in parenteral nutrition and through formula supplementation or human milk fortification is associated with increased fat-free mass or lean mass in early life. However, future research is needed to fully understand the link between these body composition changes and longitudinal outcomes in preterm infants.

Summary
Inclusion of body composition assessments in preterm infant nutrition research is critical to understand the factors associated with differences in adiposity and lean mass development in preterm infants. Medical fragility in preterm infants limits the routine use of body composition assessment tools which are currently validated, and additional studies are needed to thoroughly assess other methods which may be more feasible to integrate into bedside routine.
Long-term impact of early identification of cerebral palsy
Authors: Rojas Ana-Marie 
Published: January 2025

Purpose of review
Early identification of cerebral palsy (CP), as in all neurologic conditions, has a profound impact on the ability to initiate interventions, support the education and empowerment of parents, ameliorate the effect of the conditions, and importantly identifies cohorts for neuroprotection or repair to address the primary injury. CP is a life span condition. Rapid initiation of services, support and anticipatory guidance is essential to maximize functional outcomes, prevent or manage complications and improve quality of life.

Recent findings
CP diagnosis should not be delayed. Early imaging as well as motor and neurologic evaluation can aid in early detection of CP before age 5 months. Early therapeutic intervention can influence function and assist in prevention of complications that can impact abilities. There is important ongoing research with efforts to prevent CP or alter the phenotype of the condition.

Summary
Literature review provides evidence to change in standard of care in diagnosing CP. There are published guidelines on how to pursue the diagnosis during early infancy. Early identification results in early intervention with the purpose of enhancing functional skill development, prevention of complications, and establishing parental support. Early identification provides an optimistic view and opportunity to intervene immediately in hopes to have an impact in the functional outcome and improving quality of life.
Reducing Employee Injuries from Aggressive Patient Behavior at Children’s Hospital by Implementing a Behavioral Response Team
Authors: Martorana Julia A. , Griffith Debrea M. , Eiger Carmel , Maurer James J. , Burnside Amanda , Janssen Aron C. , Pergjika Alba , Hoffmann Jennifer A. 
Published: January 2025

Background:
Among hospitalized children, episodes of aggressive patient behavior place healthcare staff at risk for serious injuries. By implementing a behavioral response team at a children’s hospital, we aimed to reduce monthly employee injuries related to aggressive patient behavior from 3.4 to 2.4 per 1,000 acute care visits during 12 months.

Methods:
At a children’s hospital, a multidisciplinary team used quality improvement methodology to implement a behavioral response team that provided proactive and reactive support to staff caring for children at risk for aggressive behavior. Full-scale implementation occurred in July 2022. We measured days between Occupational Health and Safety Administration (OSHA)-recordable employee injuries related to aggressive patient behavior and total monthly employee injuries related to aggressive patient behavior per 1,000 acute care visits (emergency department visits and/or hospitalizations) by patients 3 years of age or older.

Results:
In the year after full-scale implementation, an average of 101 BRT rounds and 17 reactive responses occurred per month. The maximum number of days between OHSA-recordable employee injuries related to aggressive patient behavior increased from 163 days in the year before full-scale implementation to 271 days in the following year. Monthly employee injuries related to aggressive patient behavior decreased from 3.4 to 1.7 injuries per 1,000 acute care visits by patients 3 years of age or older.

Conclusions:
The BRT model, which provides proactive and reactive support to hospital staff caring for children at risk for aggressive behavior, should be considered a strategy to reduce employee injuries and promote workplace safety.
Trypstatin as a Novel TMPRSS2 Inhibitor with Broad-Spectrum Efficacy Against Corona and Influenza Viruses
Authors: Lawrenz Jan , Wettstein Lukas , Alfonso Armando Rodríguez , Nchioua Rayhane , von Maltitz Pascal , Albers Dan P.J. , Zech Fabian , Vandeput Julie , Naesens Lieve , Fois Giorgio , Preising Nico , Schmierer Emilia , Almeida-Hernandez Yasser , Petersen Moritz , Ständker Ludger , Wiese Sebastian , Braubach Peter , Frick Manfred , Barth Eberhard , Sauter Daniel , Kirchhoff Frank , Sanchez-Garcia Elsa , Stevaert Annelies , Münch Jan 
Published: January 2025

AbstractRespiratory viruses, such as SARS-CoV-2 and influenza, exploit host proteases like TMPRSS2 for entry, making TMPRSS2 a prime antiviral target. Here, we report the identification and characterization of Trypstatin, a 61-amino acid Kunitz-type protease inhibitor derived from human hemofiltrate. Trypstatin inhibits TMPRSS2 and related proteases, with IC50values in the nanomolar range, comparable to the small molecule inhibitor camostat mesylate.In vitroassays demonstrated that Trypstatin effectively blocks spike-driven entry of SARS-CoV-2, SARS-CoV-1, MERS-CoV, and hCoV-NL63, as well as hemagglutinin-mediated entry of influenza A and B viruses. In primary human airway epithelial cultures, Trypstatin significantly reduced SARS-CoV-2 replication and retained activity in the presence of airway mucus.In vivo, intranasal administration of Trypstatin to SARS-CoV-2-infected Syrian hamsters reduced viral titers and alleviated clinical symptoms. These findings highlight Trypstatin’s potential as a broad-spectrum antiviral agent against TMPRSS2-dependent respiratory viruses.Abstract Figure
Single-cell morphological profiling reveals insights into cell death
Authors: Frey Benjamin , Holmberg David , Byström Petter , Bergman Ebba , Georgiev Polina , Johansson Martin , Hennig Patrick , Rietdijk Jonne , Rosén Dan , Carreras-Puigvert Jordi , Spjuth Ola 
Published: January 2025

AbstractAnalysis of single-cell data has emerged as a powerful tool for studying biological processes and response to perturbations. However, its application in morphological profiling is less explored. In this study we profile six cell death subtypes induced by 50 small molecule drugs across six concentrations using the Cell Painting assay. We evaluate the performance of three feature extraction methods at single-cell and aggregated level and apply supervised and unsupervised analyses to uncover factors contributing to cell death mechanisms. Our results show that a bagged LightGBMXT model, trained on single-cell DeepProfiler achieved classification accuracy of 77.23%, with a top overall performance of 89.97% for corresponding aggregated profiles. Furthermore, self-supervised learning using the transformer-based DINO network revealed highly resolved and biologically meaningful subpopulations, shedding light on perturbation- and concentration-specific molecular targets and dose-dependant morphological changes. Our findings demonstrate the potential of studying phenomic data on single-cell level to enhance the characterization of cell death pathways, advancing our understanding of perturbation effects at a granular level.
3D-Printed Magnetic Levitation Device with Deep Learning-Assisted Particle Tracking and Analysis for High-Throughput Sorting
Authors: Ramarao Malavika , Ozaltin Alfa , Yaman Sena , Ozbozduman Kaan , Loc Irem , Ertok Nil , Gao Aria , Unlu Mehmet Burcin , Durmus Naside Gozde 
Published: January 2025

AbstractIntrinsic density-based particle separation is fundamental to biomedical research and materials science. Magnetic levitation offers an accessible and label-free approach; however, current platforms are limited by throughput, complex fabrication requirements, and manual analysis methods. Here, we demonstrate a high-throughput magnetic levitation-based microfluidic device fabricated using commercial 3D printing, integrated with dual automated analysis systems. The device features optimized magnet configurations and wide channel design (1 mm × 1 mm) that enables gentle separation (<1 PSI) at throughputs of 66 mL/hr–– a ten-fold improvement over existing levitation platforms. We developed two complementary analysis tools: “Phase” for static levitation height measurements, and a deep learning pipeline combining CNN-based particle classification (>95% accuracy) with SORT (Simple Online and Realtime Tracking) algorithm for dynamic analysis. The automated system showed excellent correlation with manual counting (Pearson coefficients: 0.91-0.99, p<0.001). Through systematic optimization of magnet spacing and paramagnetic medium concentration (150 mM Gd), the platform achieved robust continuous-flow sorting while maintaining exceptional purity (>90%) and resolving density differences as small as 0.03 g/mL. This work establishes a versatile platform for particle sorting, enabling sophisticated analysis without specialized facilities or extensive operator training, with broad applications in biomedical research and diagnostics.
IL-27 limits HSPC differentiation during infection and protects from stem cell exhaustion
Authors: Aldridge Daniel L. , Lanzar Zachary , Phan Anthony T. , Christian David A. , Pardy Ryan , Min Booki , Kedl Ross M. , Hunter Christopher A. 
Published: January 2025

AbstractMany inflammatory stimuli can induce progenitor cells in the bone marrow to produce increased numbers of myeloid cells as part of the process of emergency myelopoiesis. These events are associated with innate training and can have long-term impacts on hematopoietic stem and progenitor cell (HSPC) development but can also compromise their function. While many cytokines support emergency myelopoiesis, less is known about the mechanisms that temper these events. When mice that lack the cytokine IL-27 were infected withToxoplasma gondii, there was enhanced generation of monocyte progenitors and increased numbers of inflammatory monocytes. In the bone marrow of infected mice there was increased production of IL-27 that localized with HSPCs and a survey of cytokine receptor expression highlighted that HSPCs were uniquely poised to respond to IL-27. Furthermore, the use ofin vitrodifferentiation assays and mixed bone marrow chimeras revealed that HSPCs from IL-27 deficient mice are pre-disposed towards the monocyte lineage. Additional studies highlighted that after infection loss of the IL-27R resulted in reduced HSPC fitness that manifested as reduced proliferative responses and a decreased ability to reconstitute the hematopoietic system. Thus, the ability of IL-27 to act on HSPC provides a regulatory brake on differentiation to limit monocyte induction and preserve HSPC stemness.