bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal DNA methylation within HPA-axis genes years after paediatric critical illness
Authors: Coppens Grégoire , Vanhorebeek Ilse , Güiza Fabian , Derese Inge , Wouters Pieter J. , Téblick Arno , Dulfer Karolijn , Joosten Koen F. , Verbruggen Sascha C. , Van den Berghe Greet 
Published: February 2024

Abstract
Background
Critically ill children suffer from impaired physical/neurocognitive development 2 years later. Glucocorticoid treatment alters DNA methylation within the hypothalamus–pituitary–adrenal (HPA) axis which may impair normal brain development, cognition and behaviour. We tested the hypothesis that paediatric-intensive-care-unit (PICU) patients, sex- and age-dependently, show long-term abnormal DNA methylation within the HPA-axis layers, possibly aggravated by glucocorticoid treatment in the PICU, which may contribute to the long-term developmental impairments.

Results
In a pre-planned secondary analysis of the multicentre PEPaNIC-RCT and its 2-year follow-up, we identified differentially methylated positions and differentially methylated regions within HPA-axis genes in buccal mucosa DNA from 818 former PICU patients 2 years after PICU admission (n = 608 no glucocorticoid treatment; n = 210 glucocorticoid treatment) versus 392 healthy children and assessed interaction with sex and age, role of glucocorticoid treatment in the PICU and associations with long-term developmental impairments. Adjusting for technical variation and baseline risk factors and correcting for multiple testing (false discovery rate < 0.05), former PICU patients showed abnormal DNA methylation of 26 CpG sites (within CRHR1, POMC, MC2R, NR3C1, FKBP5, HSD11B1, SRD5A1, AKR1D1, DUSP1, TSC22D3 and TNF) and three DNA regions (within AVP, TSC22D3 and TNF) that were mostly hypomethylated. These abnormalities were sex-independent and only partially age-dependent. Abnormal methylation of three CpG sites within FKBP5 and one CpG site within SRD5A1 and AKR1D1 was partly attributable to glucocorticoid treatment during PICU stay. Finally, abnormal methylation within FKBP5 and AKR1D1 was most robustly associated with long-term impaired development.

Conclusions
Two years after critical illness in children, abnormal methylation within HPA-axis genes was present, predominantly within FKBP5 and AKR1D1, partly attributable to glucocorticoid treatment in the PICU, and explaining part of the long-term developmental impairments. These data call for caution regarding liberal glucocorticoid use in the PICU.
Ileo-ileal knot causing acute gangrenous small bowel obstruction: a case report
Authors: Molla Yohannis Derbew , Mequanint Melese Birara , Bisrat Solomon Hailesilassie , Workneh Gebrehiwot Aderaw , Alemu Hirut Tesfahun 
Published: February 2024

Abstract
Background
Ileo-ileal knotting is a very rare cause of small bowel obstruction, and only a few reports have been published. Small bowel obstruction (SBO) is one of the most common emergency surgical conditions that require urgent evaluation and treatment and is one of the leading causes of emergency surgical admission. There are many causes of SBO that are known in general surgical practice, and these causes are different in the developing and developed worlds.

Clinical presentation
In this article, we present a case of acute gangrenous SBO secondary to ileo-ileal knotting in a 37-year-old Ethiopian female patient after she presented with severe abdominal cramp, vomiting, and abdominal distension of 4 hours duration. The patient was operated on intraoperatively; she had gangrenous small bowel obstruction caused by ileo-ileal knotting. Later, the patient was discharged and improved after 12 days of hospital stay.

Conclusion
Ileo-ileal knotting should always be considered in the differential diagnosis of acute small-bowel obstruction. The diagnostic difficulty and the need for urgent treatment of this condition to yield optimal results are discussed.
Sustained control of recalcitrant chronic spontaneous urticaria after initiation of inflammatory airway diseases treatment: two case reports
Authors: Nguyen Doanh , Deitiker Philip 
Published: February 2024

Abstract
Background
Current classification of chronic urticaria is primarily based on clinical presentation of skin manifestations. Hence, therapeutic treatment is primarily aimed locally for immediate symptom relief. We reason that limiting therapeutic strategies to the skin pathology might be inadequate since cellular activation and inflammation might be triggered remotely.

Case presentation
In this series two patients had exhausted all current treatments for recalcitrant urticaria but remained symptomatic. The first case was 26-year-old Caucasian female and the second was 63-year-old African American female. Both cases had frequent breakthrough urticaria requiring frequent pulsating courses of prednisone to control urticaria despite treatment with omalizumab and antihistamines. When inflammatory airway disease was discovered and managed with inhaled corticosteroid, urticaria is controlled much faster without the need of high dose immunosuppression over several years of observation. Coincidentally, autoimmune thyroiditis and anti-immunogobulin-E immunoglobulin-G titers dropped significantly in one case with sustained inhaled corticosteroid therapy.

Conclusions
We suggest a novel approach of controlling remote epithelial site inflammation in these two cases that resulted in sustained-control of urticaria symptoms without the need for systemic corticosteroids or immunosuppressant. The changes of autoimmune antibodies might be the consequences of tolerance breaking from chronic lower airway inflammation as observed in other epithelial inflammatory condition like in celiac disease and rheumatoid arthritis.
New threats in the recovery of large carnivores inhabiting human-modified landscapes: the case of the Cantabrian brown bear (Ursus arctos)
Authors: Balseiro Ana , Herrero-García Gloria , García Marín Juan Francisco , Balsera Ramón , Monasterio Juana María , Cubero David , de Pedro Gabriel , Oleaga Álvaro , García-Rodríguez Alberto , Espinoza Israel , Rabanal Benjamín , Aduriz Gorka , Tuñón José , Gortázar Christian , Royo Luis José 
Published: February 2024

AbstractUnderstanding mortality causes is important for the conservation of endangered species, especially in small and isolated populations inhabiting anthropized landscapes where both natural and human-caused mortality may hinder the conservation of these species. We investigated the mortality causes of 53 free-ranging brown bears (Ursus arctos) found dead between 1998 and 2023 in the Cantabrian Mountains (northwestern Spain), a highly human-modified region where bears are currently recovering after being critically threatened in the last century. We detected natural traumatic injuries in 52.63% and infectious diseases in 39.47% of the 38 bears for which the mortality causes were registered, with 21.05% of these cases presenting signs of both infectious diseases and traumas. More specifically, almost 30% of the bears died during or after intraspecific fights, including sexually selected infanticide (10.53%). In addition, primary infectious diseases such as infectious canine hepatitis, distemper, clostridiosis and colibacillosis caused the death of 15.79% of the bears. The number of direct human-caused deaths (i.e., shooting, poisoning, snare) decreased over the study period. This study also reveals three new mortality causes triggered by pathogens, two of which—Clostridium novyi and verotoxigenic Escherichia coli—not previously described in ursids, and the other one, canine distemper virus, never reported in brown bears as cause of death. New management strategies for the conservation of Cantabrian bears, which are urgently needed due to the rapid expansion of the population, should consider the mortality causes described in this study and must promote further research to elucidate how the high prevalence of infectious diseases may threaten the current recovery of the population.
Synergistic enhancement of the mouse Pramex1 and Pramel1 in repressing retinoic acid (RA) signaling during gametogenesis
Authors: Yang Mingyao , Diaz Francisco , Krause Ana Rita T. , Lei Yuguo , Liu Wan-Sheng 
Published: February 2024

Abstract
Background
PRAME constitutes one of the largest multi-copy gene families in Eutherians, encoding cancer-testis antigens (CTAs) with leucine-rich repeats (LRR) domains, highly expressed in cancer cells and gametogenic germ cells. This study aims to elucidate genetic interactions between two members, Pramex1 and Pramel1, in the mouse Prame family during gametogenesis using a gene knockout approach.

Result
Single-gene knockout (sKO) of either Pramex1 or Pramel1 resulted in approximately 7% of abnormal seminiferous tubules, characterized by a Sertoli-cell only (SCO) phenotype, impacting sperm count and fecundity significantly. Remarkably, sKO female mice displayed normal reproductive functions. In contrast, Pramex1/Pramel1 double knockout (dKO) mice exhibited reduced fecundity in both sexes. In dKO females, ovarian primary follicle count decreased by 50% compared to sKO and WT mice, correlating with a 50% fecundity decrease. This suggested compensatory roles during oogenesis in Pramex1 or Pramel1 sKO females. Conversely, dKO males showed an 18% frequency of SCO tubules, increased apoptotic germ cells, and decreased undifferentiated spermatogonia compared to sKO and WT testes. Western blot analysis with PRAMEX1- or PRAMEL1-specific antibodies on sKO testes revealed compensatory upregulation of each protein (30–50%) in response to the other gene’s deletion. Double KO males exhibited more severe defects in sperm count and litter size, surpassing Pramex1 and Pramel1 sKO accumulative effects, indicating a synergistic enhancement interaction during spermatogenesis. Additional experiments administering trans-retinoic acid (RA) and its inhibitor (WIN18,446) in sKO, dKO, and WT mice suggested that PRAMEX1 and PRAMEL1 synergistically repress the RA signaling pathway during spermatogenesis.

Conclusion
Data from sKO and dKO mice unveil a synergistic interaction via the RA signaling pathway between Pramex1 and Pramel1 genes during gametogenesis. This discovery sets the stage for investigating interactions among other members within the Prame family, advancing our understanding of multi-copy gene families involved in germ cell formation and function.
Association between frailty and clinical outcomes in patients undergoing craniotomy—systematic review and meta-analysis of observational studies
Authors: Licina Ana , Silvers Andrew , Thien Christopher 
Published: February 2024

Abstract
Background
Frailty in patients undergoing craniotomy may affect perioperative outcomes. There have been a number of studies published in this field; however, evidence is yet to be summarized in a quantitative review format. We conducted a systematic review and meta-analysis to examine the effects of frailty on perioperative outcomes in patients undergoing craniotomy surgery.

Methods
Our eligibility criteria included adult patients undergoing open cranial surgery. We searched MEDLINE via Ovid SP, EMBASE via Ovid SP, Cochrane Library, and grey literature. We included retrospective and prospective observational studies. Our primary outcome was a composite of complications as per the Clavien–Dindo classification system. We utilized a random-effects model of meta-analysis. We conducted three preplanned subgroup analyses: patients undergoing cranial surgery for tumor surgery only, patients undergoing non-tumor surgery, and patients older than 65 undergoing cranial surgery. We explored sources of heterogeneity through a sensitivity analysis and post hoc analysis.

Results
In this review of 63,159 patients, the pooled prevalence of frailty was 46%. The odds ratio of any Clavien–Dindo grade 1–4 complication developing in frail patients compared to non-frail patients was 2.01 [1.90–2.14], with no identifiable heterogeneity and a moderate level of evidence. As per GradePro evidence grading methods, there was low-quality evidence for patients being discharged to a location other than home, length of stay, and increased mortality in frail patients.

Conclusion
Increased frailty was associated with increased odds of any Clavien–Dindo 1-4 complication. Frailty measurements may be used as an integral component of risk-assessment strategies to improve the quality and value of neurosurgical care for patients undergoing craniotomy surgery.

Ethics and dissemination
Formal ethical approval is not needed, as primary data were not collected.

Systematic review registration
PROSPERO identification number: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=405240
Unified ensemble federated learning with cloud computing for online anomaly detection in energy-efficient wireless sensor networks
Authors: Gayathri S. , Surendran D. 
Published: February 2024

AbstractAnomaly detection in Wireless Sensor Networks (WSNs) is critical for their reliable and secure operation. Optimizing resource efficiency is crucial for reducing energy consumption. Two new algorithms developed for anomaly detection in WSNs—Ensemble Federated Learning (EFL) with Cloud Integration and Online Anomaly Detection with Energy-Efficient Techniques (OAD-EE) with Cloud-based Model Aggregation. EFL with Cloud Integration uses ensemble methods and federated learning to enhance detection accuracy and data privacy. OAD-EE with Cloud-based Model Aggregation uses online learning and energy-efficient techniques to conserve energy on resource-constrained sensor nodes. By combining EFL and OAD-EE, a comprehensive and efficient framework for anomaly detection in WSNs can be created. Experimental results show that EFL with Cloud Integration achieves the highest detection accuracy, while OAD-EE with Cloud-based Model Aggregation has the lowest energy consumption and fastest detection time among all algorithms, making it suitable for real-time applications. The unified algorithm contributes to the system's overall efficiency, scalability, and real-time response. By integrating cloud computing, this algorithm opens new avenues for advanced WSN applications. These promising approaches for anomaly detection in resource constrained and large-scale WSNs are beneficial for industrial applications.
The effect of oral supplementation of Paricalcitol on C-reactive protein levels in chronic kidney disease patients: GRADE-assessed systematic review and dose-response meta-analysis of data from randomized controlled trials
Authors: Arabi Seyyed Mostafa , Shahraki-Jazinaki Mostafa , Chambari Mahla , Bahrami Leila Sadat , Sabeti Sara , Gubari Mohammaed Ibrahim Mohaildeen , Roufogalis Basil D. , Sahebkar Amirhossein 
Published: February 2024

Abstract
Background
Previous studies investigating the effect of oral supplementation of paricalcitol on reactive protein levels in chronic kidney disease (CKD) patients reported inconsistent findings. In this systematic review and meta-analysis, we have analyzed and interpreted the results obtained from previous randomized clinical trials on the effect of paricalcitol on C-reactive protein in CKD patients in the literature.

Methods
MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science databases were searched until January 2023 and related articles were obtained through a careful screening process allowing extraction of required data from selected articles. The effect size was calculated using a random effect model and weighted mean differences (WMD) and 95% confidence intervals (CI). Heterogeneity among studies was evaluated using Cochran’s Q test and I2.

Results
Amongst the 182 articles obtained from the initial search, 4 studies (6 arms) were finally included in the meta-analysis. Pooled analysis shows that C-reactive protein levels significantly decrease after oral supplementation with paricalcitol (WMD: -2.55 mg/L, 95% CI (-4.99 to -0.11; P = 0.04). The studies used in this meta-analysis showed significant heterogeneity (I2 = 66.3% and P = 0.01).

Conclusion
Oral paricalcitol supplementation in CKD patients can significantly reduce C-reactive protein levels, which may prevent CKD progression.
Pharmacovigilance study of BCR-ABL1 tyrosine kinase inhibitors: a safety analysis of the FDA adverse event reporting system
Authors: Zhao Dehua , Long Xiaoqing , Wang Jisheng 
Published: February 2024

Abstract
Background
With the increased use of BCR-ABL1 tyrosine kinase inhibitors (TKIs) in cancer patients, adverse events (AEs) have garnered considerable interest. We conducted this pharmacovigilance study to evaluate the AEs of BCR-ABL1 TKIs in cancer patients using the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods
To query AE reports from the FAERS database, we used OpenVigil 2.1. Descriptive analysis was then employed to describe the characteristics of TKIs-associated AE reports. We also utilized the disproportionality analysis to detect safety signals by calculating the proportional reporting ratio (PRR) and reporting odds ratios (ROR).

Results
From the FAERS database, a total of 85,989 AE reports were retrieved, with 3,080 significant AE signals identified. Specifically, imatinib, nilotinib, dasatinib, bosutinib, and ponatinib had significant AE signals of 1,058, 813, 232, 186, and 791, respectively. These significant signals were further categorized into 26 system organ classes (SOCs). The AE signals of imatinib and ponatinib were primarily associated with general disorders and administration site conditions. On the other hand, nilotinib, dasatinib, and bosutinib were mainly linked to investigations, respiratory, thoracic and mediastinal disorders, and gastrointestinal disorders, respectively. Notably, new signals of 245, 278, 47, 55, and 253 were observed in imatinib, nilotinib, dasatinib, bosutinib, and ponatinib, respectively.

Conclusions
The results of this study demonstrated that AE signals differ among the five BCR-ABL1 TKIs. Furthermore, each BCR-ABL1 TKI displayed several new signals. These findings provide valuable information for clinicians aiming to reduce the risk of AEs during BCR-ABL1 TKI treatment.
Synchronization on higher-order networks
Authors: Liu Haoran , Zhou Jin , Li Bo , Huang Meng , Lu Jun-an , Shi Dinghua 
Published: February 2024

Abstract
Network science has already been fruitful and confirmed effective on the description of real-world or abstract systems. An increasing number of researches and instances have successfully verified, however, that interactions in systems may occur among three, four, or even more components. The introduction of higher-order perspective brings a revolution on network science, and refreshes researchers’ understanding of synchronization. Hence, an overview is presented here in regard of synchronization on higher-order networks. We start from an introduction of how the higher-order networks are represented using algebraic tools. Then a series of landmark researches on synchronization is reviewed under circumstances of whether or not the dynamics contains control. Finally, we summarize our conclusions and propose our outlooks on expectations of future works.
Quantitative Assessment of Hemodynamics Associated With Embolization Degree in Brain Arteriovenous Malformations
Authors: You Wei , Meng Xiangyu , Chen Ting , Ye Wanxing , Wang Yanwen , Lv Jian , Li Yuanjie , Sui Yutong , Zhang Yifan , Gong Wentao , Sun Yong , Jin Hengwei , Li Youxiang 
Published: February 2024

BACKGROUND AND OBJECTIVES:
Grading systems, including the novel brain arteriovenous malformation endovascular grading scale (NBAVMES) and arteriovenous malformation embocure score (AVMES), predict embolization outcomes based on arteriovenous malformation (AVM) morphological features. The influence of hemodynamics on embolization outcomes remains unexplored. In this study, we investigated the relationship between hemodynamics and embolization outcomes.

METHODS:
We conducted a retrospective study of 99 consecutive patients who underwent transarterial embolization at our institution between 2012 and 2018. Hemodynamic features of AVMs were derived from pre-embolization digital subtraction angiography sequences using quantitative digital subtraction angiography. Multivariate logistic regression analysis was performed to determine the significant factors associated with embolization outcomes.

RESULTS:
Complete embolization (CE) was achieved in 17 (17.2%) patients, and near-complete embolization was achieved in 18 (18.2%) patients. A slower transnidal relative velocity (TRV, odds ratio [OR] = 0.71, P = .002) was significantly associated with CE. Moreover, higher stasis index of the drainage vein (OR = 16.53, P = .023), shorter transnidal time (OR = 0.15, P = .013), and slower TRV (OR = 0.9, P = .049) were significantly associated with complete or near-complete embolization (C/nCE). The area under the receiver operating characteristic curve for predicting CE was 0.87 for TRV, 0.72 for NBAVMES scores (ρ = 0.287, P = .004), and 0.76 for AVMES scores. The area under the receiver operating characteristic curve for predicting C/nCE was 0.77 for TRV, 0.61 for NBAVMES scores, and 0.75 for AVMES scores. Significant Spearman correlation was observed between TRV and NBAVMES scores and AVMES scores (ρ = 0.512, P < .001).

CONCLUSION:
Preoperative hemodynamic factors have the potential to predict the outcomes of AVM embolization. A higher stasis index of the drainage vein, slower TRV, and shorter transnidal time may indicate a moderate blood flow status or favorable AVM characteristics that can potentially facilitate embolization.
Tracking cell layer contribution during repair of the tympanic membrane
Authors: Dinwoodie Olivia M. , Tucker Abigail S. , Fons Juan M. 
Published: February 2024

ABSTRACT
The tympanic membrane (i.e. eardrum) sits at the interface between the middle and external ear. The tympanic membrane is composed of three layers: an outer ectoderm-derived layer, a middle neural crest-derived fibroblast layer with contribution from the mesoderm-derived vasculature, and an inner endoderm-derived mucosal layer. These layers form a thin sandwich that is often perforated following trauma, pressure changes or middle ear inflammation. During healing, cells need to bridge the perforation in the absence of an initial scaffold. Here, we assessed the contribution, timing and interaction of the different layers during membrane repair by using markers and reporter mice. We showed that the ectodermal layer is retracted after perforation, before proliferating away from the wound edge, with keratin 5 basal cells migrating over the hole to bridge the gap. The mesenchymal and mucosal layers then used this scaffold to complete the repair, followed by advancement of the vasculature. Finally, differentiation of the epithelium led to formation of a scab. Our results reveal the dynamics and interconnections between the embryonic germ layers during repair and highlight how defects might occur.