bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying inpatient hospitalizations with continuous electroencephalogram monitoring from administrative data
Authors: Fernandes Marta , Westover M. Brandon , Zafar Sahar F. 
Published: November 2023

Abstract
Background
Continuous electroencephalography (cEEG) is increasingly utilized in hospitalized patients to detect and treat seizures. Epidemiologic and observational studies using administrative datasets can provide insights into the comparative and cost effectiveness of cEEG utilization. Defining patient cohorts that underwent acute inpatient cEEG from administrative datasets is limited by the lack of validated codes differentiating elective epilepsy monitoring unit (EMU) admissions from acute inpatient hospitalization with cEEG utilization. Our aim was to develop hospital administrative data-based models to identify acute inpatient admissions with cEEG monitoring and distinguish them from EMU admissions.

Methods
This was a single center retrospective cohort study of adult (≥ 18 years old) inpatient admissions with a cEEG procedure (EMU or acute inpatient) between January 2016-April 2022. The gold standard for acute inpatient cEEG vs. EMU was obtained from the local EEG recording platform. An extreme gradient boosting model was trained to classify admissions as acute inpatient cEEG vs. EMU using administrative data including demographics, diagnostic and procedure codes, and medications.

Results
There were 9,523 patients in our cohort with 10,783 hospital admissions (8.5% EMU, 91.5% acute inpatient cEEG); with average age of 59 (SD 18.2) years; 46.2% were female. The model achieved an area under the receiver operating curve of 0.92 (95% CI [0.91–0.94]) and area under the precision-recall curve of 0.99 [0.98–0.99] for classification of acute inpatient cEEG.

Conclusions
Our model has the potential to identify cEEG monitoring admissions in larger cohorts and can serve as a tool to enable large-scale, administrative data-based studies of EEG utilization.
Transcription dosage compensation does not occur in Down syndrome
Authors: Hunter Samuel , Hendrix Jo , Freeman Justin , Dowell Robin D. , Allen Mary A. 
Published: November 2023

Abstract
Background
The increase in DNA copy number in Down syndrome (DS; caused by trisomy 21) has led to the DNA dosage hypothesis, which posits that the level of gene expression is proportional to the gene’s DNA copy number. Yet many reports have suggested that a proportion of chromosome 21 genes are dosage compensated back towards typical expression levels (1.0×). In contrast, other reports suggest that dosage compensation is not a common mechanism of gene regulation in trisomy 21, providing support to the DNA dosage hypothesis.

Results
In our work, we use both simulated and real data to dissect the elements of differential expression analysis that can lead to the appearance of dosage compensation, even when compensation is demonstrably absent. Using lymphoblastoid cell lines derived from a family with an individual with Down syndrome, we demonstrate that dosage compensation is nearly absent at both nascent transcription (GRO-seq) and steady-state RNA (RNA-seq) levels. Furthermore, we link the limited apparent dosage compensation to expected allelic variation in transcription levels.

Conclusions
Transcription dosage compensation does not occur in Down syndrome. Simulated data containing no dosage compensation can appear to have dosage compensation when analyzed via standard methods. Moreover, some chromosome 21 genes that appear to be dosage compensated are consistent with allele specific expression.
Determination of reference values for tear production and intraocular pressure in Pygoscelis penguins of the Antarctic Peninsula
Authors: Bayram Latife Cakir , Isler Cafer Tayer , Ekebas Görkem 
Published: November 2023

AbstractBackgroundAccording to the literature review, this is the first study investigating tear production (TP) and intraocular pressure (IOP) in thePygoscelispenguins living in their natural habitat. The study aimed to establish normal values for standard ocular tests in the genusPygoscelis, namely, the Adélie (Pygoscelis adeliae), gentoo (Pygoscelis papua), and chinstrap (Pygoscelis antarctica) penguins, in four different islands of Antarctica. Sampling was made by specifically using the left eye of the penguins. The Schirmer's tear test type I (STT-I) and the Tonovet® (rebound tonometer) were used to measure the TP and the IOP, respectively.ResultsThe mean TP and IOP values of 129 Adélie,chinstrap, gentoo, and 120 adult Adélie,gentoo penguins were determined as 10.2 ± 4.0 mm/min and 38.9 ± 13.2 mmHg, respectively. No statistical difference was detected between the penguin species for the mean IOP values, while the difference was determined in all the locations. However, statistical differences in the mean TP values were determined between all locations.ConclusionThe results of this study provide a reference range of Schirmer's tear test (STT) and IOP values inPygoscelispenguins and show that the IOP is significantly affected by locations. This result can be attributed to the harsh climatic conditions of the Antarctic Peninsula that change very quickly. The described data may help diagnose clinical pathological findings in Pygoscelis penguins.The STT and rebound tonometry appears to be safe and reproducible methods inPygoscelispenguins, as the results were obtained quickly and were well tolerated by the birds.Based on our results, we propose that similar studies can be initiated in crowded colonies of three penguin species of this genus on the Antarctic Peninsula, the southern Shetland Islands, and other frequently visited islands in Antarctica.
Panax notoginseng: derived exosome-like nanoparticles attenuate ischemia reperfusion injury via altering microglia polarization
Authors: Li Shiyi , Zhang Ru , Wang Anni , Li Yang , Zhang Miaomiao , Kim Jisu , Zhu Ying , Wang Qizheng , Zhang Yue , Wei Ying , Wang Jianxin 
Published: November 2023

AbstractCerebral ischemia/reperfusion (CI/R) injury is a clinical conundrum during the treatment of ischemic stroke. Cell-derived exosomes (CDE) were proved to be therapeutically effective for CI/R injury. However, production of CDE is time and effort consuming. Increasing studies reported that plants can also generate exosome-like nanoparticles (ELN) which are therapeutically effective and have higher yield compared with CDE. In this study, a commonly used Chinese herb Panax notoginseng (PN), whose active ingredients were well-documented in the treatment of CI/R injury, was chosen as a source of ELNs. It was found that Panax notoginseng derived exosome like nanoparticles (PDN) could enter the brain without modification and ameliorate cerebral infarct volume, improve behavior outcome and maintained the integrity of BBB. PDNs attenuated CI/R injury by altering the phenotype of microglia from “pro-inflammation” M1 type to “anti-inflammation” M2 type. Also, we found that lipids from PDNs were the major therapeutic effective component. As a mechanism of action, PDN was proved to exert therapeutic effect via activating pI3k/Akt pathway.
Graphical Abstract
Unveiling the potential effects of acetylsalicylic acid: insights into regeneration in endometrial stem cells
Authors: Park Se-Ra , Kim Soo-Rim , Min Eun-Kyung , Oh Byung-Chul , Jung YunJae , Kim Yong Ho , Lee Hwa-Yong 
Published: November 2023

Abstract
Background
Although acetylsalicylic acid has been widely used for decades to treat and prevent various diseases, its potential effects on endometrial receptivity and subsequent pregnancy rates are still controversial due to conflicting data: many reports have shown positive effects of acetylsalicylic acid, whereas others have found that it has no effect. Furthermore, the direct effects of acetylsalicylic acid on various functions of normal endometrial cells, especially endometrial stem cells, and their underlying molecular mechanisms have not yet been proven. Recently, studies have revealed that a reduced number of active stem/progenitor cells within endometrial tissue limits cyclic endometrial regeneration and subsequently decreases pregnancy success rates, suggesting that endometrial stem cells play a critical role in endometrial regeneration and subsequent endometrial receptivity.

Methods
We assessed whether aspirin treatment can inhibit various endometrial stem cell functions related to regenerative capacity, such as self-renewal, migration, pluripotency/stemness, and differentiation capacity, in vitro. Next, we evaluated whether SERPINB2 regulates the effects of aspirin on endometrial stem cell functions by depleting SERPINB2 expression with specific shRNA targeting SERPINB2. To further investigate whether aspirin also inhibits various endometrial stem cell functions in vivo, aspirin was administered daily to mice through intraperitoneal (i.p.) injection for 7 days.

Results
In addition to its previously identified roles, to the best of our knowledge, we found for the first time that acetylsalicylic acid directly inhibits various human endometrial stem cell functions related to regenerative capacity (i.e., self-renewal, migration, differentiation, and capacity) through its novel target gene SERPINB2 in vitro. Acetylsalicylic acid exerts its function by suppressing well-known prosurvival pathways, such as Akt and/or ERK1/2 signaling, through a SERPINB2 signaling cascade. Moreover, we also found that acetylsalicylic acid markedly inhibits regenerative capacity-related functions in endometrial stem cells within tissue.

Conclusions
We have found that acetylsalicylic acid has diverse effects on various endometrial stem cell functions related to regenerative capacity. Our findings are a critical step toward the development of more effective therapeutic strategies to increase the chances of successful pregnancy.
Leveraging circulating microbiome signatures to predict tumor immune microenvironment and prognosis of patients with non-small cell lung cancer
Authors: Zhou Xiaohan , You Liting , Xin Zhaodan , Su Huiting , Zhou Juan , Ma Ying 
Published: November 2023

Abstract
Background
Accumulating evidence supports the significant role of human microbiome in development and therapeutic response of tumors. Circulating microbial DNA is non-invasive and could show a general view of the microbiome of host, making it a promising biomarker for cancers. However, whether circulating microbiome is associated with prognosis of non-small cell lung cancer (NSCLC) and its potential mechanisms on tumor immune microenvironment still remains unknown.

Methods
The blood microbiome data and matching tumor RNA-seq data of TCGA NSCLC patients were obtained from Poore’s study and UCSC Xena. Univariate and multivariate Cox regression analysis were used to identify circulating microbiome signatures associated with overall survival (OS) and construct the circulating microbial abundance prognostic scoring (MAPS) model. Nomograms integrating clinical characteristics and circulating MAPS scores were established to predict OS rate of NSCLC patients. Joint analysis of blood microbiome data and matching tumor RNA-seq data was used to deciphered the tumor microenvironment landscape of patients in circulating MAPS-high and MAPS-low groups. Finally, the predictive value of circulating MAPS on the efficacy of immunotherapy and chemotherapy were assessed.

Results
A circulating MAPS prediction model consisting of 14 circulating microbes was constructed and had an independent prognostic value for NSCLC. The integration of circulating MAPS into nomograms may improve the prognosis predictive power. Joint analysis revealed potential interactions between prognostic circulating microbiome and tumor immune microenvironment. Especially, intratumor plasma cells and humoral immune response were enriched in circulating MAPS-low group, while intratumor CD4 + Th2 cells and proliferative related pathways were enriched in MAPS-high group. Finally, drug sensitivity analysis indicated the potential of circulating MAPS as a predictor of chemotherapy efficacy.

Conclusion
A circulating MAPS prediction model was constructed successfully and showed great prognostic value for NSCLC. Our study provides new insights of interactions between microbes, tumors and immunity, and may further contribute to precision medicine for NSCLC.
Human Wharton’s jelly-derived mesenchymal stromal cells promote bone formation in immunodeficient mice when administered into a bone microenvironment
Authors: Cabrera-Pérez Raquel , Ràfols-Mitjans Alexis , Roig-Molina Ángela , Beltramone Silvia , Vives Joaquim , Batlle-Morera Laura 
Published: November 2023

Abstract
Background
Wharton’s Jelly (WJ) Mesenchymal Stromal Cells (MSC) have emerged as an attractive allogeneic therapy for a number of indications, except for bone-related conditions requiring new tissue formation. This may be explained by the apparent recalcitrance of MSC,WJ to differentiate into the osteogenic lineage in vitro, as opposed to permissive bone marrow (BM)-derived MSCs (MSC,BM) that readily commit to bone cells. Consequently, the actual osteogenic in vivo capacity of MSC,WJ is under discussion.

Methods
We investigated how physiological bone environments affect the osteogenic commitment of recalcitrant MSCs in vitro and in vivo. To this end, MSC of BM and WJ origin were co-cultured and induced for synchronous osteogenic differentiation in vitro using transwells. For in vivo experiments, immunodeficient mice were injected intratibially with a single dose of human MSC and bone formation was evaluated after six weeks.

Results
Co-culture of MSC,BM and MSC,WJ resulted in efficient osteogenesis in both cell types after three weeks. However, MSC,WJ failed to commit to bone cells in the absence of MSC,BM’s osteogenic stimuli. In vivo studies showed successful bone formation within the medullar cavity of tibias in 62.5% of mice treated with MSC, WJ. By contrast, new formed trabeculae were only observed in 25% of MSC,BM-treated mice. Immunohistochemical staining of human COXIV revealed the persistence of the infused cells at the site of injection. Additionally, cells of human origin were also identified in the brain, heart, spleen, kidney and gonads in some animals treated with engineered MSC,WJ (eMSC,WJ). Importantly, no macroscopic histopathological alterations, ectopic bone formation or any other adverse events were detected in MSC-treated mice.

Conclusions
Our findings demonstrate that in physiological bone microenvironment, osteogenic commitment of MSC,WJ is comparable to that of MSC,BM, and support the use of off-the-shelf allogeneic MSC,WJ products in bone repair and bone regeneration applications.
The incidence, risk factors and outcomes of impaired cerebral autoregulation in aortic arch surgery: a single-center, retrospective cohort study
Authors: Peng Ling , Guo Dan , Shi Yinhui , Yang Jiapei , Wei Wei 
Published: November 2023

Abstract
Background
Impairment of cerebral autoregulation (CA) has been observed in patients undergoing cardiopulmonary bypass (CPB), but little is known about its risks and associations with outcomes. The cerebral oximetry index (COx), which is a moving linear correlation coefficient between regional cerebral oxygen saturation (rScO2) and mean blood pressure (MAP), may reflect CA function. When COx approaches 1, it implies that CA is damaged, whereas the CA is functional when the COx value approaches 0. The objective of this study was to analyze the incidence and risks of impaired CA, based on COx assessment, in patients undergoing total aortic arch replacement under systemic moderate hypothermia and circulatory arrest of the lower body (MHCA). We also evaluated the association between impaired CA and patient outcomes.

Methods
One hundred and fifty-four adult patients who underwent total aortic arch replacement with stented elephant trunk implantation under MHCA at our hospital were retrospectively analyzed. Patients were defined as having new-onset impaired CA if pre-CPB COx < 0.3 and post-CPB COx > 0.3. Pre- and intraoperative factors were tested for independent association with impaired CA. Postoperative outcomes were compared between patients with normal and impaired CA.

Results
In our 154 patients, 46(29.9%) developed new-onset impaired CA after CPB. Multivariable analysis revealed a prolonged low rScO2 (rScO2 < 55%) independently associated with onset of impaired CA, and receiver operating charactoristic curve showed a cutoff value at 40 min (sensitivity, 89.5%; specificity, 68.0%). Compared with normal CA patients, those with impaired CA showed a significantly higher rates of in-hospital mortality and postoperative complications.

Conclusions
Prolonged low rScO2 (rScO2 < 55%) during aortic arch surgery was closely related to onset of impaired CA. Impaired CA remained associated with the increased rates of postoperative complications and in-hospital mortality.

Trial registration
ChiCTR1800014545 with registered date 20/01/2018.
Crizotinib combined with bronchoscopic interventional treatment in ALK-positive inflammatory myofibroblastic tumor of left main stem bronchus: a case report
Authors: Zhang Peng , Wang Chenchen , Lv Zechao , Du Mingxiang , Xu Ruixin 
Published: November 2023

Abstract
Background
Inflammatory myofibroblastic tumor (IMT), also known as an inflammatory pseudotumor, is a unique type of intermediate soft tissue tumor that commonly occurred in the lung. Its unclear etiology and cellular activity brought about the confusion not only in naming of it, but also in diagnosis and treatment.

Case presentation
We reported the case of an 18-year-old male student who suffered from shortness of breath, chest tightness and chest pain. Chest computed tomography scan showed a spherical neoplasm blocking left main stem bronchus. After fiberoptic bronchoscopy procedure, the results of histopathological and immunohistochemical analysis indicated an IMT. The targeted next generation sequencing based genomic profiling of the tumor using formalin-fixed and paraffin embedded tissue was performed and a EML4-ALK fusion was detected. The patient began to receive Crizotinib, a ALK tyrosine kinase inhibitor, at a dose of 250 mg twice daily orally. The patient has recovered well after the operation, and no recurrence or metastasis has been found after 12 months’ follow-up.

Conclusion
By means of the diagnosis and treatment of this case, the characteristics and therapies of IMT are illustrated. In addition, it also provides a reference for the therapeutic strategy of IMT in the future.
Statistical learning quantifies transposable element-mediated cis-regulation
Authors: Pulver Cyril , Grun Delphine , Duc Julien , Sheppard Shaoline , Planet Evarist , Coudray Alexandre , de Fondeville Raphaël , Pontis Julien , Trono Didier 
Published: November 2023

Abstract
Background
Transposable elements (TEs) have colonized the genomes of most metazoans, and many TE-embedded sequences function as cis-regulatory elements (CREs) for genes involved in a wide range of biological processes from early embryogenesis to innate immune responses. Because of their repetitive nature, TEs have the potential to form CRE platforms enabling the coordinated and genome-wide regulation of protein-coding genes by only a handful of trans-acting transcription factors (TFs).

Results
Here, we directly test this hypothesis through mathematical modeling and demonstrate that differences in expression at protein-coding genes alone are sufficient to estimate the magnitude and significance of TE-contributed cis-regulatory activities, even in contexts where TE-derived transcription fails to do so. We leverage hundreds of overexpression experiments and estimate that, overall, gene expression is influenced by TE-embedded CREs situated within approximately 500 kb of promoters. Focusing on the cis-regulatory potential of TEs within the gene regulatory network of human embryonic stem cells, we find that pluripotency-specific and evolutionarily young TE subfamilies can be reactivated by TFs involved in post-implantation embryogenesis. Finally, we show that TE subfamilies can be split into truly regulatorily active versus inactive fractions based on additional information such as matched epigenomic data, observing that TF binding may better predict TE cis-regulatory activity than differences in histone marks.

Conclusion
Our results suggest that TE-embedded CREs contribute to gene regulation during and beyond gastrulation. On a methodological level, we provide a statistical tool that infers TE-dependent cis-regulation from RNA-seq data alone, thus facilitating the study of TEs in the next-generation sequencing era.
Impact of insulin resistance on mild cognitive impairment in type 2 diabetes mellitus patients with non-alcoholic fatty liver disease
Authors: Zhang Hui , Fareeduddin Mohammed Farooqui Huzaifa , Zhu Wenwen , Niu Tong , Zhang Zhen , Zhang Haoqiang 
Published: November 2023

Abstract
Aims
Insulin resistance (IR) is a pivotal factor in the pathogenesis of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Nevertheless, the impact of IR on cognitive dysfunction in T2DM patients with NAFLD remains inadequately understood. We aim to investigate the effect of IR on mild cognitive impairment (MCI) in T2DM individuals with NAFLD.

Materials and methods
143 T2DM individuals were categorized into Non-MCI and MCI groups, as well as Non-NAFLD and NAFLD groups. Clinical parameters and cognitive preference test outcomes were compared. Correlation and regression analyses were executed to explore the interconnections between IR and cognitive details across all T2DM patients, as well as within the subgroup of individuals with NAFLD.

Results
In comparison to the Non-MCI group, the MCI group displayed elevated HOMA-IR levels. Similarly, the NAFLD group exhibited higher HOMA-IR levels compared to the Non-NAFLD group. Additionally, a higher prevalence of MCI was observed in the NAFLD group as opposed to the Non-NAFLD group. Notably, HOMA-IR levels were correlated with Verbal Fluency Test (VFT) and Trail Making Test-B (TMTB) scores, both related to executive functions. Elevated HOMA-IR emerged as a risk factor for MCI in the all patients. Intriguingly, increased HOMA-IR not only correlated with TMTB scores but also demonstrated an influence on TMTA scores, reflecting information processing speed function in patients with NAFLD.

Conclusion
IR emerges as a contributory factor to cognitive dysfunction in T2DM patients. Furthermore, it appears to underlie impaired executive function and information processing speed function in T2DM individuals with NAFLD.
Magnetic resonance imaging and next-generation sequencing for the diagnosis of cystic echinococcosis in the intradural spine: a case report
Authors: Lao Xiaojie , Hu Diefei , Ji Lei , Zhan Tingzheng , Li Tiantian , Luo Shuming , Xu Xianli , Zhang Chunlan , Chen Maowei 
Published: November 2023

Abstract
Background
Cystic echinococcosis (CE) is a parasitic zoonotic disease caused by the larval stage of Echinococcus granulosus. The liver and lungs are the most common sites for infection. Infection of the intradural spine is rare.

Case presentation
A 45-year-old woman of Han ethnicity presented with a chronic history of recurrent lumbar pain. Magnetic resonance imaging of the lumbar spine revealed the classical characteristic of multiple cystic lesions of variable sizes, manifesting a “bunch of grapes” appearance, localized within the spinal canal at the L4–L5 vertebral level. In the meanwhile, metagenomic next-generation sequencing identified Echinococcosis granulosa. The patient underwent surgery to remove the cyst entirely and subsequently took albendazole 400 mg orally twice daily for 6 months.

Conclusion
Spinal CE should be suspected in patients with multiple spinal cystic lesions and zoonotic exposure. metagenomic next-generation sequencing serves as a robust diagnostic tool for atypical pathogens, particularly when conventional tests are inconclusive. Prompt and aggressive treatment for spinal cystic echinococcosis is imperative, and further research is warranted for improved diagnostic and therapeutic strategies.