bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unmasking the biological function and regulatory mechanism of NOC2L: a novel inhibitor of histone acetyltransferase
Authors: Lu Siyi , Chen Zhaoyu , Liu Zhenzhen , Liu Zhentao 
Published: January 2023

AbstractNOC2 like nucleolar associated transcriptional repressor (NOC2L) was recently identified as a novel inhibitor of histone acetyltransferase (INHAT). NOC2L is found to have two INHAT function domains and regulates histone acetylation in a histone deacetylases (HDAC) independent manner, which is distinct from other INHATs. In this review, we summarize the biological function of NOC2L in histone acetylation regulation, P53-mediated transcription, ribosome RNA processing, certain development events and carcinogenesis. We propose that NOC2L may be explored as a potential biomarker and a therapeutic target in clinical practice.
Transplanted human iPSC-derived vascular endothelial cells promote functional recovery by recruitment of regulatory T cells to ischemic white matter in the brain
Authors: Xu Bin , Shimauchi-Ohtaki Hiroya , Yoshimoto Yuhei , Sadakata Tetsushi , Ishizaki Yasuki 
Published: January 2023

Abstract
Background
Ischemic stroke in white matter of the brain induces not only demyelination, but also neuroinflammation. Peripheral T lymphocytes, especially regulatory T cells (Tregs), are known to infiltrate into ischemic brain and play a crucial role in modulation of inflammatory response there. We previously reported that transplantation of vascular endothelial cells generated from human induced pluripotent stem cells (iVECs) ameliorated white matter infarct. The aim of this study is to investigate contribution of the immune system, especially Tregs, to the mechanism whereby iVEC transplantation ameliorates white matter infarct.

Methods
iVECs and human Tregs were transplanted into the site of white matter lesion seven days after induction of ischemia. The egress of T lymphocytes from lymph nodes was sequestered by treating the animals with fingolimod (FTY720). The infarct size was evaluated by magnetic resonance imaging. Immunohistochemistry was performed to detect the activated microglia and macrophages, T cells, Tregs, and oligodendrocyte lineage cells. Remyelination was examined by Luxol fast blue staining.

Results
iVEC transplantation reduced ED-1+ inflammatory cells and CD4+ T cells, while increased Tregs in the white matter infarct. Treatment of the animals with FTY720 suppressed neuroinflammation and reduced the number of both CD4+ T cells and Tregs in the lesion, suggesting the importance of infiltration of these peripheral immune cells into the lesion in aggravation of neuroinflammation. Suppression of neuroinflammation by FTY720 per se, however, did not promote remyelination in the infarct. FTY720 treatment negated the increase in the number of Tregs by iVEC transplantation in the infarct, and attenuated remyelination promoted by transplanted iVECs, while it did not affect the number of oligodendrocyte lineage cells increased by iVEC transplantation. Transplantation of Tregs together with iVECs into FTY720-treated ischemic white matter did not affect the number of oligodendrocyte lineage cells, while it remarkably promoted myelin regeneration.

Conclusions
iVEC transplantation suppresses neuroinflammation, but suppression of neuroinflammation per se does not promote remyelination. Recruitment of Tregs by transplanted iVECs contributes significantly to promotion of remyelination in the injured white matter.
Acute phase response following pulmonary exposure to soluble and insoluble metal oxide nanomaterials in mice
Authors: Gutierrez Claudia Torero , Loizides Charis , Hafez Iosif , Brostrøm Anders , Wolff Henrik , Szarek Józef , Berthing Trine , Mortensen Alicja , Jensen Keld Alstrup , Roursgaard Martin , Saber Anne Thoustrup , Møller Peter , Biskos George , Vogel Ulla 
Published: January 2023

Abstract
Background
Acute phase response (APR) is characterized by a change in concentration of different proteins, including C-reactive protein and serum amyloid A (SAA) that can be linked to both exposure to metal oxide nanomaterials and risk of cardiovascular diseases. In this study, we intratracheally exposed mice to ZnO, CuO, Al2O3, SnO2 and TiO2 and carbon black (Printex 90) nanomaterials with a wide range in phagolysosomal solubility. We subsequently assessed neutrophil numbers, protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, Saa3 and Saa1 mRNA levels in lung and liver tissue, respectively, and SAA3 and SAA1/2 in plasma. Endpoints were analyzed 1 and 28 days after exposure, including histopathology of lung and liver tissues.

Results
All nanomaterials induced pulmonary inflammation after 1 day, and exposure to ZnO, CuO, SnO2, TiO2 and Printex 90 increased Saa3 mRNA levels in lungs and Saa1 mRNA levels in liver. Additionally, CuO, SnO2, TiO2 and Printex 90 increased plasma levels of SAA3 and SAA1/2. Acute phase response was predicted by deposited surface area for insoluble metal oxides, 1 and 28 days post-exposure.

Conclusion
Soluble and insoluble metal oxides induced dose-dependent APR with different time dependency. Neutrophil influx, Saa3 mRNA levels in lung tissue and plasma SAA3 levels correlated across all studied nanomaterials, suggesting that these endpoints can be used as biomarkers of acute phase response and cardiovascular disease risk following exposure to soluble and insoluble particles.
Study on geometry and morphology of proximal humerus in Northern Chinese population based on 3-D CT
Authors: Zhang Boyu , Guan Haitao , Ye Zhipeng , Zhang Yingze 
Published: January 2023

Abstract
Background
This study investigated the characteristics of humeral geometric and morphological parameters in northern Chinese population by three-dimensional measurements, and compared whether there were differences in humeral morphology among populations from different geographical regions.

Methods
Computed tomography scans of 80 humerus were obtained, reconstructed and measured. Differences in humeral morphological parameters between genders and sides were compared. Correlation analysis was used to explore possible correlations among the parameters. The differences in humeral geometric morphometric parameters between Western and East Asian populations were compared according to pool results of present and previous studies.

Results
The average (and standard deviation) of humeral head radius curvature, arc angle, diameter, and thickness was 151.79 ± 6.69°, 23.36 ± 2.08 mm, 44.83 ± 3.92 mm and 17.55 ± 1.84 mm in coronal humeral head plane, and 152.05 ± 8.82°, 21.81 ± 1.88 mm, 41.77 ± 3.44 mm and 16.52 ± 1.92 mm in transversal humeral head plane. The average of the humeral head medial offset and posterior offset was 7.34 ± 2.47 mm and 0.08 ± 1.72 mm. Humeral head inclination angle, arc angle and radius curvature of humeral neck-shaft averaged 137.69 ± 4.92°, 34.7 ± 5.29° and 55.76 ± 13.43 mm. Superior, inferior, anterior, posterior concave angle of humeral anatomical neck averaged 150.41 ± 10.91°, 146.55 ± 10.12°, 146.43 ± 13.53° and 149.33 ± 14.07°. The average of height of the greater tuberosity, height of the lesser tuberosity, depth, concave angle and volume of the intertubercular groove was 14.19 ± 1.7 mm, 8.9 ± 1.54 mm, 0.92 ± 0.31 mm3, 31.28 ± 9.61 mm, 4.98 ± 1.19 mm and 89.35 ± 17.62°. The upper angle of the greater tuberosity averaged 161.04 ± 7.84°, the upper angle of the greater tuberosity was 165.94 ± 3.6°. Differences in parameters of proximal humerus between genders and sides were found. There was no correlation between parameters of proximal humerus and age. Correlations were found among humeral morphological parameters. East Asian populations differed in proximal humeral morphology from Western populations.

Conclusions
This study will provide references for diagnosing and classifying shoulder disease, designing prosthesis and instrument, enhancing surgical precision and guiding patient recovery.
Association between age at menarche and bone mineral density in postmenopausal women
Authors: Yang Yimei , Wang Shanshan , Cong Hui 
Published: January 2023

Abstract
Background
Age at menarche (AAM) directly affects female estrogen levels, which play a vital role in bone metabolism. The exact relationship between bone mineral density (BMD) and AAM remains controversial. Thus, this study aimed to determine the association between AAM and lumbar spine (LS) BMD in postmenopausal women.

Methods
Our data were based on the National Health and Nutrition Examination Survey (NHANES) 2011–2018. AAM was divided into three categories including ≤ 12, 13–15, and ≥ 16 years, and the ≤ 12 years old category was used as the reference group. To examine the association between AAM and LS BMD, we used three weighted linear regression models, Model 1 (without adjustment), Model 2 (with adjustment for age, race, and body mass index [BMI]), and Model 3 (with adjustment for all covariates).

Results
This study included 1195 postmenopausal women aged 40–59 years. In the unadjusted model, a menarche age of ≥ 16 years compared with a menarche age of ≤ 12 years was associated with lower LS BMD (β = − 0.083, 95% CI − 0.117, − 0.048, P < 0.001). After adjusting for potential confounding factors, there was still a negative correlation in model 2 (β = − 0.078, 95% CI − 0.113, − 0.042, P < 0.001) and model 3 (β = − 0.065, 95% CI − 0.096, − 0.033, P < 0.001). Moreover, this significant relationship persisted after excluding participants who used female hormones (β = − 0.053, 95% CI − 0.089, − 0.016, P = 0.006).

Conclusion
Our study found that postmenopausal women with a menarche age of ≥ 16 years had significantly lower LS BMD than that had by those with a menarche age of ≤ 12 years. As a result of this study, postmenopausal women with a late menarche age may have a higher risk of lumbar osteoporotic fractures and need better bone health care.
Axonal membrane stretch suppresses neuronal excitability by activating mechanosensitive K2P channels at the node of Ranvier
Authors: Kanda Hirosato , Noguchi Koichi , Dai Yi 
Published: January 2023

AbstractSaltatory conduction is the propagation of action potentials along myelinated nerves, which enables fast propagation through the node of Ranvier. Recently, we demonstrated that K2P channels, TWIK-related K+ channel-1 (TREK-1), and TWIK-related arachidonic acid-activated K + channel (TRAAK), are highly expressed in the mammalian node of Ranvier of sensory nerves and have an important role in action potential repolarization instead of voltage-gated K+ channels. TREK-1/TRAAK channels are activated by membrane depolarization as well as various stimuli, such as temperature, pH, arachidonic acid, and mechanical membrane stretch. Although membrane mechanical stretch has been suggested to modulate action potential conduction, how membrane stretching modulates intrinsic electrophysiological properties at the node of Ranvier remains unclear. In the present study, we examined the effects of membrane stretch on neuronal membranes at the node of Ranvier in rat sciatic nerves. The single-channel conductance was approximately 90 pS at 80 mV. Membrane stretch increased the single-channel event numbers and open probability in a pressure-dependent manner. Consistent with single-channel activity, intra-pipette positive pressure increased outward leak currents and decreased membrane excitability in a whole-cell configuration. Furthermore, blockage of TREK-1/TRAAK channels by Ba2+ reversed the changes in the intrinsic electrophysiological properties induced by intra-pipette pressure. These results indicate that the activation of mechanosensitive TREK-1/TRAAK channels may suppress neuronal excitability following axonal stretch. Our findings suggest that TREK-1/TRAAK channels may play an important role in the prevention of ectopic action potential discharge at the axon by intense mechanical nerve stretch under physiological conditions.
A pH-dependent anti-CD47 antibody that selectively targets solid tumors and improves therapeutic efficacy and safety
Authors: Li Yulu , Liu Juan , Chen Wei , Wang Wei , Yang Fang , Liu Ximing , Sheng Yao , Du Kaixin , He Miaomiao , Lyu Xueyuan , Li Huiyu , Zhao Linlin , Wei Zhizhong , Wang Fengchao , Zheng Sanduo , Sui Jianhua 
Published: January 2023

Abstract
Background
The antiphagocytic molecule CD47 is overexpressed in a wide variety of cancer cells, and antibodies targeting CD47 for cancer therapies are currently under intensive investigation. However, owing to the ubiquitous expression of CD47 on healthy cells, anti-CD47 therapies often achieve only weak therapeutic benefits and can induce severe side effects. Here, we report the generation of a pH-dependent anti-CD47 antibody (BC31M4) which selectively binds to tumors under the acidic solid tumor microenvironment.

Methods
BC31M4 was generated using antibody phage display and a pH-dependent selection strategy. The pH-dependent binding and blocking activities of BC31M4 were verified using in vitro assays, and the structural basis of the pH-dependent binding property was characterized. BC31M4’s antitumor effect was confirmed by both phagocytosis assays and studies in xenograft models. The tumor selectivity, mechanism of action, PK properties, side effects, and therapeutic efficacy were further evaluated in humanized (hCD47 and its receptor hSIRPα) immunocompetent syngeneic mouse models.

Results
The crystal structure reveals that two histidines locate within the CDRs of the light chain directly contribute to the pH-dependent binding of BC31M4. BC31M4 promotes macrophage phagocytosis of tumor cells more potently at acidic-pH than at physiological-pH. Our hCD47/hSIRPα humanized syngeneic mouse model results demonstrated that BC31M4 selectively accumulates in tumors but not in normal tissues. BC31M4 causes minimal side effects and exhibits superior PK properties as compared to the other examined anti-CD47 antibodies. When combined with adoptive T cell transfer, BC31M4 efficiently promotes adaptive immune responses against tumors and also induces immune memory. Moreover, we show that BC31M4’s antitumor effects rely on an Fc that mediates strong effector functions.

Conclusions
Our study illustrates that the development of a tumor-selective, pH-dependent anti-CD47 antibody safely confers strong therapeutic effects against solid tumors, thus providing a promising therapeutic strategy to overcome the challenges of anti-CD47 therapy.
Association of red blood cells and plasma transfusion versus red blood cell transfusion only with survival for treatment of major traumatic hemorrhage in prehospital setting in England: a multicenter study
Authors: Tucker Harriet , Brohi Karim , Tan Joachim , Aylwin Christopher , Bloomer Roger , Cardigan Rebecca , Davenport Ross , Davies Edward D. , Godfrey Phillip , Hawes Rachel , Lyon Richard , McCullagh Josephine , Stanworth Simon , Thompson Julian , Uprichard James , Walsh Simon , Weaver Anne , Green Laura 
Published: January 2023

Abstract
Background
In-hospital acute resuscitation in trauma has evolved toward early and balanced transfusion resuscitation with red blood cells (RBC) and plasma being transfused in equal ratios. Being able to deliver this ratio in prehospital environments is a challenge. A combined component, like leukocyte-depleted red cell and plasma (RCP), could facilitate early prehospital resuscitation with RBC and plasma, while at the same time improving logistics for the team. However, there is limited evidence on the clinical benefits of RCP.

Objective
To compare prehospital transfusion of combined RCP versus RBC alone or RBC and plasma separately (RBC + P) on mortality in trauma bleeding patients.

Methods
Data were collected prospectively on patients who received prehospital transfusion (RBC + thawed plasma/Lyoplas or RCP) for traumatic hemorrhage from six prehospital services in England (2018–2020). Retrospective data on patients who transfused RBC from 2015 to 2018 were included for comparison. The association between transfusion arms and 24-h and 30-day mortality, adjusting for age, injury mechanism, age, prehospital heart rate and blood pressure, was evaluated using generalized estimating equations.

Results
Out of 970 recruited patients, 909 fulfilled the study criteria (RBC + P = 391, RCP = 295, RBC = 223). RBC + P patients were older (mean age 42 vs 35 years for RCP and RBC), and 80% had a blunt injury (RCP = 52%, RBC = 56%). RCP and RBC + P were associated with lower odds of death at 24-h, compared to RBC alone (adjusted odds ratio [aOR] 0.69 [95%CI: 0.52; 0.92] and 0.60 [95%CI: 0.32; 1.13], respectively). The lower odds of death for RBC + P and RCP vs RBC were driven by penetrating injury (aOR 0.22 [95%CI: 0.10; 0.53] and 0.39 [95%CI: 0.20; 0.76], respectively). There was no association between RCP or RBC + P with 30-day survival vs RBC.

Conclusion
Prehospital plasma transfusion for penetrating injury was associated with lower odds of death at 24-h compared to RBC alone. Large trials are needed to confirm these findings.
Variation in electroencephalography and neuroimaging for children receiving extracorporeal membrane oxygenation
Authors: Kohne Joseph G. , MacLaren Graeme , Shellhaas Renée A. , Benedetti Giulia , Barbaro Ryan P. 
Published: January 2023

AbstractBackgroundSeizures, strokes, and intracranial hemorrhage are common and feared complications in children receiving extracorporeal membrane oxygenation (ECMO) support. Researchers and clinicians have proposed and deployed methods for monitoring and detecting neurologic injury, but best practices are unknown. We sought to characterize clinicians’ approach to electroencephalography (EEG) and brain imaging modalities in children supported by ECMO.MethodsWe performed a retrospective observational cohort study among US Children’s Hospitals participating in the Pediatric Health Information System (PHIS) from 2016 to 2021. We identified hospitalizations containing ECMO support. We stratified these admissions by pediatric, neonatal, cardiac surgery, and non-cardiac surgery. We characterized the frequency of EEG, cranial ultrasound, brain computed tomography (CT), magnetic resonance imaging (MRI), and transcranial Doppler during ECMO hospitalizations. We reported key diagnoses (stroke and seizures) and the prescription of antiseizure medication. To assess hospital variation, we created multilevel logistic regression models.ResultsWe identified 8746 ECMO hospitalizations. Nearly all children under 1 year of age (5389/5582) received a cranial ultrasound. Sixty-two percent of the cohort received an EEG, and use increased from 2016 to 2021 (52–72% of hospitalizations). There was marked variation between hospitals in rates of EEG use. Rates of antiseizure medication use (37% of hospitalizations) and seizure diagnoses (20% of hospitalizations) were similar across hospitals, including high and low EEG utilization hospitals. Overall, 37% of the cohort received a CT and 36% received an MRI (46% of neonatal patients). Stroke diagnoses (16% of hospitalizations) were similar between high- and low-MRI utilization hospitals (15% vs 17%, respectively). Transcranial Doppler (TCD) was performed in just 8% of hospitalizations, and 77% of the patients who received a TCD were cared for at one of five centers.ConclusionsIn this cohort of children at high risk of neurologic injury, there was significant variation in the approach to EEG and neuroimaging in children on ECMO. Despite the variation in monitoring and imaging, diagnoses of seizures and strokes were similar across hospitals. Future work needs to identify a management strategy that appropriately screens and monitors this high-risk population without overuse of resource-intensive modalities.
KIN: a method to infer relatedness from low-coverage ancient DNA
Authors: Popli Divyaratan , Peyrégne Stéphane , Peter Benjamin M. 
Published: January 2023

AbstractGenetic kinship of ancient individuals can provide insights into their culture and social hierarchy, and is relevant for downstream genetic analyses. However, estimating relatedness from ancient DNA is difficult due to low-coverage, ascertainment bias, or contamination from various sources. Here, we present KIN, a method to estimate the relatedness of a pair of individuals from the identical-by-descent segments they share. KIN accurately classifies up to 3rd-degree relatives using at least 0.05x sequence coverage and differentiates siblings from parent-child pairs. It incorporates additional models to adjust for contamination and detect inbreeding, which improves classification accuracy.
Enhanced RNA knockdown efficiency with engineered fusion guide RNAs that function with both CRISPR-CasRx and hammerhead ribozyme
Authors: Zhan Yonghao , Cao Congcong , Li Aolin , Mei Hongbing , Liu Yuchen 
Published: January 2023

Abstract
Background
CRISPR-Cas13 is a newly emerging RNA knockdown technology that is comparable to RNAi. Among all members of Cas13, CasRx degrades RNA in human cells with high precision and effectiveness. However, it remains unclear whether the efficiency of this technology can be further improved and applied to gene therapy.

Results
In this study, we fuse CasRx crRNA with an antisense ribozyme to construct a synthetic fusion guide RNA that can interact with both CasRx protein and ribozyme and tested the ability of this approach in RNA knockdown and cancer gene therapy. We show that the CasRx-crRNA-ribozyme system (CCRS) is more efficient for RNA knockdown of mRNAs and non-coding RNAs than conventional methods, including CasRx, shRNA, and ribozyme. In particular, CCRS is more effective than wild-type CasRx when targeting multiple transcripts simultaneously. We next use bladder cancer as a model to evaluate the anticancer effects of CCRS targeting multiple genes in vitro and in vivo. CCRS shows a higher anticancer effect than conventional methods, consistent with the gene knockdown results.

Conclusions
Thus, our study demonstrates that CCRS expands the design ideas and RNA knockdown capabilities of Cas13 technology and has the potential to be used in disease treatment.