bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pros and cons of a bone-conduction device implanted in the worse hearing ear of patients with asymmetric hearing loss
Authors: Kurihara Sho , Ganaha Akira , Nakamura Takeshi , Kubuki Kan , Saruwatari Emi , Matsui Koudai , Takahashi Kuniyuki , Tono Tetsuya 
Published: February 2024

PurposeBone-conduction devices can be considered a viable treatment option for patients experiencing asymmetric hearing loss (AHL), especially those with severe to profound hearing loss (HL) present in one ear. However, there are only a few reports on the effects of bone-anchored hearing aids (BAHAs) on patients with AHL. This retrospective study analyzed in detail the effects of BAHA on softer sounds than other hearing aids and identified situations in which BAHA had a negative effect.MethodsPatients with AHL, characterized by severe to profound hearing loss in one ear with a difference of ≥45 dB from that of the contralateral ear, underwent BAHA implantation in the ear with worse hearing. The BAHA effects were evaluated by assessing the word recognition score (WRS) and speech reception threshold (SRT) using the Japanese Oldenburg Sentence Test for various signal settings and noise directions. For a subjective analysis, the Speech, Spatial and Qualities of Hearing Scale (SSQ12) score was determined.ResultsThirteen patients who underwent BAHA implantation at the Miyazaki University Hospital between 2007 and 2021 were included. The BAHA demonstrated a significant improvement in the WRS from 40 to 70 dB sound pressure levels. Although the SRT showed significant improvement in noisy environments when speech was presented to the BAHA-wearing side, it worsened significantly when noise was presented to this side. In the survey of subjective hearing ability, both the total and subscale SSQ12 scores improved significantly after wearing the BAHA.ConclusionThis study identified scenarios in which BAHAs were beneficial and detrimental to individuals with AHL. Generally used audiological tests, such as the WRS with fixed sound pressure, may underestimate the effectiveness of BAHAs for softer sounds. In addition, depending on the direction of the noise, BAHAs may have adverse effects. These results could help patients comprehend the potential benefits and limitations of bone-conduction devices for their hearing.
Subthalamic nucleus dynamics track microlesion effect in Parkinson’s disease
Authors: Peng Chunkai , Wang Zhuyong , Sun Yujia , Mo Yixiang , Hu Kai , Li Qingqing , Hou Xusheng , Zhu Zhiyuan , He Xiaozheng , Xue Sha , Zhang Shizhong 
Published: February 2024

Parkinson’s Disease (PD) is characterized by the temporary alleviation of motor symptoms following electrode implantation (or nucleus destruction), known as the microlesion effect (MLE). Electrophysiological studies have explored different PD stages, but understanding electrophysiological characteristics during the MLE period remains unclear. The objective was to examine the characteristics of local field potential (LFP) signals in the subthalamic nucleus (STN) during the hyperacute period following implantation (within 2 days) and 1 month post-implantation. 15 patients diagnosed with PD were enrolled in this observational study, with seven simultaneous recordings of bilateral STN-LFP signals using wireless sensing technology from an implantable pulse generator. Recordings were made in both on and off medication states over 1 month after implantation. We used a method to parameterize the neuronal power spectrum to separate periodic oscillatory and aperiodic components effectively. Our results showed that beta power exhibited a significant increase in the off medication state 1 month after implantation, compared to the postoperative hyperacute period. Notably, this elevation was effectively attenuated by levodopa administration. Furthermore, both the exponents and offsets displayed a decrease at 1 month postoperatively when compared to the hyperacute postoperative period. Remarkably, levodopa medication exerted a modulatory effect on these aperiodic parameters, restoring them back to levels observed during the hyperacute period. Our findings suggest that both periodic and aperiodic components partially capture distinct electrophysiological characteristics during the MLE. It is crucial to adequately evaluate such discrepancies when exploring the mechanisms of MLE and optimizing adaptive stimulus protocols.
Trehalose promotes atherosclerosis regression in female mice
Authors: Robichaud Sabrina , Rochon Valérie , Emerton Christina , Laval Thomas , Ouimet Mireille 
Published: February 2024

IntroductionAtherosclerosis is a chronic inflammatory disease caused by the deposition of lipids within the artery wall. During atherogenesis, efficient autophagy is needed to facilitate efferocytosis and cholesterol efflux, limit inflammation and lipid droplet buildup, and eliminate defective mitochondria and protein aggregates. Central to the regulation of autophagy is the transcription factor EB (TFEB), which coordinates the expression of lysosomal biogenesis and autophagy genes. In recent years, trehalose has been shown to promote TFEB activation and protect against atherogenesis. Here, we sought to investigate the role of autophagy activation during atherosclerosis regression.Methods and resultsAtherosclerosis was established in C57BL/6N mice by injecting AAV-PCSK9 and 16 weeks of Western diet feeding, followed by switching to a chow diet to induce atherosclerosis regression. During the regression period, mice were either injected with trehalose concomitant with trehalose supplementation in their drinking water or injected with saline for 6 weeks. Female mice receiving trehalose had reduced atherosclerosis burden, as evidenced by reduced plaque lipid content, macrophage numbers and IL-1β content in parallel with increased plaque collagen deposition, which was not observed in their male counterparts. In addition, trehalose-treated female mice had lower levels of circulating leukocytes, including inflammatory monocytes and CD4+ T cells. Lastly, we found that autophagy flux in male mice was basally higher than in female mice during atherosclerosis progression.ConclusionsOur data demonstrate a sex-specific effect of trehalose in atherosclerosis regression, whereby trehalose reduced lipid content, inflammation, and increased collagen content in female mice but not in male mice. Furthermore, we discovered inherent differences in the autophagy flux capacities between the sexes: female mice exhibited lower plaque autophagy than males, which rendered the female mice more responsive to atherosclerosis regression. Our work highlights the importance of understanding sex differences in atherosclerosis to personalize the development of future therapies to treat cardiovascular diseases.
When all computers shut down: the clinical impact of a major cyber-attack on a general hospital
Authors: Abbou Benyamine , Kessel Boris , Ben Natan Merav , Gabbay-Benziv Rinat , Dahan Shriki Dikla , Ophir Anna , Goldschmid Nimrod , Klein Adi , Roguin Ariel , Dudkiewicz Mickey 
Published: February 2024

ImportanceHealthcare organizations operate in a data-rich environment and depend on digital computerized systems; thus, they may be exposed to cyber threats. Indeed, one of the most vulnerable sectors to hacks and malware is healthcare. However, the impact of cyberattacks on healthcare organizations remains under-investigated.ObjectiveThis study aims to describe a major attack on an entire medical center that resulted in a complete shutdown of all computer systems and to identify the critical actions required to resume regular operations.SettingThis study was conducted on a public, general, and acute care referral university teaching hospital.MethodsWe report the different recovery measures on various hospital clinical activities and their impact on clinical work.ResultsThe system malfunction of hospital computers did not reduce the number of heart catheterizations, births, or outpatient clinic visits. However, a sharp drop in surgical activities, emergency room visits, and total hospital occupancy was observed immediately and during the first postattack week. A gradual increase in all clinical activities was detected starting in the second week after the attack, with a significant increase of 30% associated with the restoration of the electronic medical records (EMR) and laboratory module and a 50% increase associated with the return of the imaging module archiving. One limitation of the present study is that, due to its retrospective design, there were no data regarding the number of elective internal care hospitalizations that were considered crucial.Conclusions and relevanceThe risk of ransomware cyberattacks is growing. Healthcare systems at all levels of the hospital should be aware of this threat and implement protocols should this catastrophic event occur. Careful evaluation of steady computer system recovery weekly enables vital hospital function, even under a major cyberattack. The restoration of EMR, laboratory systems, and imaging archiving modules was found to be the most significant factor that allowed the return to normal clinical hospital work.
Prediction of permeability in a tight sandstone reservoir using a gated network stacking model driven by data and physical models
Authors: Shi Pengyu , Shi Pengda , Bie Kang , Han Chuang , Ni Xiaowei , Mao Zhiqiang , Zhao Peiqiang 
Published: February 2024

Introduction: Permeability is one of the most important parameters for reservoir evaluation. It is commonly measured in laboratories using underground core samples. However, it cannot describe the entire reservoir because of the limited number of cores. Therefore, petrophysicists use well logs to establish empirical equations to estimate permeability. This method has been widely used in conventional sandstone reservoirs, but it is not applicable to tight sandstone reservoirs with low porosity, extremely low permeability, and complex pore structures.Methods: Machine learning models can identify potential relationships between input features and sample labels, making them a good choice for establishing permeability prediction models. A stacking model is an ensemble learning method that aims to train a meta-learner to learn an optimal combination of expert models. However, the meta-learner does not evaluate or control the experts, making it difficult to interpret the contribution of each model. In this study, we design a gate network stacking (GNS) model, which is an algorithm that combines data and model-driven methods. First, an input log combination is selected for each expert model to ensure the best performance of the expert model and selfoptimization of the hyperparameters. Petrophysical constraints are then added to the inputs of the expert model and meta-learner, and weights are dynamically assigned to the output of the expert model. Finally, the overall performance of the model is evaluated iteratively to enhance its interpretability and robustness.Results and discussion: The GNS model is then used to predict the permeability of a tight sandstone reservoir in the Jurassic Ahe Formation in the Tarim Basin. The case study shows that the permeability predicted by the GNS model is more accurate than that of other ensemble models. This study provides a new approach for predicting the parameters of tight sandstone reservoirs.
Engaging kindergarten pre-service teachers in the design and implementation of STEM lessons
Authors: Evagorou Maria 
Published: February 2024

IntroductionEngaging young students in integrated STEM early on can support them to develop their competences linked to problem solving and critical thinking. Despite the importance of STEM education in younger ages, teachers still lack the skills and competences to implement STEM in their classes. The purpose of this study is to explore how pre-service kindergarten teachers (PSTs) understand STEM education, how they design lesson plans to teach STEM and how they implement STEM in their teaching.MethodsParticipants of the study were 21, 3rd, and 4th year students studying to become kindergarten teachers. The participants of the current study attended a Science Methods Course for Kindergarten which is a 36 h long course. Data collected included questionnaires, reflections, lesson plans, interviews, and classroom observations.ResultsFindings for the first research question reveal that kindergarten PSTs were not familiar with STEM education and did not have any previous experience with STEM education either as school students or during their studies at the university. Another important finding is that teachers’ views on STEM education improved after the theoretical introduction to STEM, but considerable improvement and understanding of STEM education was evident after they engaged as learners in a STEM lesson specially designed for kindergarten students.DiscussionFindings from the lesson plans designed by the PSTs showed that when working in groups PSTs designed lessons which offered integration between two subjects, mainly math and science. Finally, when implementing STEM lessons PSTs had similar difficulties as when designing lessons. Additionally, PSTs reported that they did not have support from their mentors, or their mentors did not act as role models during the implementation of their designs. What this study supports is the need for teacher preparation programs to prepare kindergarten teachers in understanding what STEM is, but also supporting them in the process of designing and implementing STEM lessons. Implications from this study include the design of a teacher training course to support PSTs during their studies and in their early career, but also include mentors as part of the training course to support them to act as positive role models.
Identification of new variants in patients with mucopolysaccharidosis in consanguineous Iranian families
Authors: Zabihi Rezvan , Zamani Mina , Aminzadeh Majid , Chamanrou Niloofar , Kiani Fatemeh Zahra , Seifi Tahere , Zeighami Jawaher , Yadegari Tahere , Sedaghat Alireza , Saberi Alihossein , Hamid Mohammad , Shariati Gholamreza , Galehdari Hamid 
Published: February 2024

Introduction: Mucopolysaccharidoses are a group of lysosomal storage disorders that include seven types that are classified based on the enzymes that are disrupted. Malfunction of these enzymes leads to the accumulation of glycosaminoglycans (GAGs) in various tissues. Due to genetic and clinical heterogeneity, diagnosing and distinguishing the different types is challenging. Genetic methods such as whole exome sequencing (WES) and Sanger sequencing are accurate methods for detecting pathogenic variants in patients. Methods: Thirty-two cases of mucopolysaccharidosis, predominantly from families with consanguineous marriages, were genetically examined. Out of these, fourteen cases underwent targeted sequencing, while the rest underwent WES. The results of WES were analyzed and the pathogenicity of the variants was examined using bioinformatics tools. In addition, a segregation analysis within families was carried out.Results: In most cases, a pathogenic or likely pathogenic variant was detected. Sixteen previously reported variants and six new variants were detected in the known IDS (c.458G&gt;C, c.701del, c.920T&gt;G), GNS (c.1430A&gt;T), GALNS (c.1218_1221dup), and SGSH (c.149T&gt;C) genes. Furthermore, we discovered a c.259G&gt;C substitution in the NAGLU gene for the first time in three homozygous patients. This substitution was previously reported as heterozygous. Except for the variants related to the IDS gene, which were hemizygous, all the other variants were homozygous.Discussion: It appears that the high rate of consanguineous marriages in the families being studied has had a significant impact on the occurrence of this disease. Overall, these findings could expand the spectrum of pathogenic variants in mucopolysaccharidoses. Genetic methods, especially WES, are very accurate and can be used alone or in conjunction with other diagnostic methods for a more precise and rapid diagnosis of mucopolysaccharidoses. Additionally, they could be beneficial for family screening and disease prevention.
Crosstalk between keratinocytes and neutrophils shapes skin immunity against S. aureus infection
Authors: Focken Jule , Schittek Birgit 
Published: February 2024

IntroductionStaphylococcus aureus (S. aureus) infection of the skin leads to a rapid initial innate immune response with keratinocytes in the epidermis as the initial sensors. Polymorphonuclear neutrophils (PMNs) are the first innate immune cells to infiltrate infection sites where they provide an effective first-line of defense. Previous work of our group showed that in inflamed skin a crosstalk between PMNs and keratinocytes results in enhanced S. aureus skin colonization.MethodsIn this work, we used an in vitro co-culture model to studied the crosstalk between primary human keratinocytes (PHKs) and PMNs in a sterile environment and upon S. aureus infection. We investigated the influence of PHKs on PMN activation by analyzing PMN lifespan, expression of degranulation markers and induction of proinflammatory cytokines. Furthermore, we analyzed the influence of PMNs on the inflammatory response of PHKs. Finally, we investigated the influence of the skin microbiome on PMN-mediated skin inflammation.ResultsWe show that co-culture of PMNs with PHKs induces activation and degranulation of PMNs and significantly enhances their lifespan compared to PMN cultivation alone by an IL-8 mediated mechanism and, furthermore, primes PMNs for enhanced activity after S. aureus infection. The prolonged incubation with PMNs also induces inflammatory responses in PHKs which are further exacerbated in the presence of S. aureus and induces further PMN recruitment thus fueling skin inflammation. Interestingly, infection of PHKs with the skin commensal S. epidermidis reduces the inflammatory effects of PMNs in the skin and exhibits an anti-inflammatory effect.DiscussionOur data indicate that skin infiltrating PMNs and PHKs influence each other in such a way to enhance skin inflammation and that commensal bacteria are able to reduce the inflammatory effect.
Regulation mechanisms of disulfidptosis-related genes in ankylosing spondylitis and inflammatory bowel disease
Authors: Li Lin , Fang Haixin , Li Fuzhen , Xie Kunpeng , Zhou Pengyi , Zhu Haiyan , Jin Xuemin , Song Ruifeng , Yang Peizeng , Liping Du 
Published: February 2024

IntroductionDisulfidptosis is a recently identified form of cell death that contributes to maintaining the internal environment balance of an organism. However, the molecular basis of disulfidptosis in ulcerative colitis (UC), ankylosing spondylitis (AS), and Crohn’s disease (CD) has not been thoroughly explored.MethodsFirstly, the differentially expressed genes (DEGs) and disulfidptosis-associated genes (DAGs) were obtained through differential analysis between diseases (AS, CD, and UC) and control groups. After the disulfidptosis score was acquired using the single-sample gene set enrichment analysis (ssGSEA) algorithm, the DE-DAGs were screened by overlapping DAGs and DEGs of the three diseases. Next, the feature genes were selected through a combination of machine learning algorithms, receiver operating characteristic (ROC) curves, and expression analysis. Based on these feature genes, nomograms were created for AS, CD and UC. The co-feature genes were then identified by taking the intersections of the genes featured in all three diseases. Meanwhile, single-gene set enrichment analysis (GSEA) and the TF-mRNA-miRNA network were utilized to investigate the molecular mechanisms of the co-feature genes. To validate the expression differences of the co-feature genes between healthy controls and patients (AS and IBD), RT-PCR was performed. Lastly, mendelian randomization (MR) analysis was utilized to explore the causality between genetic variants of S100A12 with AS, UC and CD.ResultsIn this study, 11 DE-DAGs were obtained. Functional enrichment analysis revealed their involvement in cytokine production and fatty acid biosynthesis. Latterly, AS/CD/UC -feature genes were derived, and they all had decent diagnostic performance. Through evaluation, the performance of the nomogram was decent for three diseases. Then, 2 co-feature genes (S100A12 and LILRA5) were obtained. The GSEA enrichment results indicated that the co-feature genes were mainly enriched in the cytokine-cytokine receptor interaction and drug metabolism cytochrome P450. As shown by functional experiments, there was a correlation between the mRNA expression of S100A12 with AS, UC and CD. Additionally, a causal connection between S100A12 and IBD was detected through MR analysis.DiscussionIn this study, 2 co-feature genes (S100A12 and LILRA5) were screened, and their functions were investigated in AS, CD and UC, providing a basis for further research into diagnosis and treatment.
Brucella abortus triggers the differential expression of immunomodulatory lncRNAs in infected murine macrophages
Authors: Flores-Concha Manuel , Gómez Leonardo A. , Soto-Shara Rodrigo , Molina Raúl E. , Coloma-Rivero Roberto F. , Montero David A. , Ferrari Ítalo , Oñate Ángel 
Published: February 2024

IntroductionThe lncRNAs (long non-coding RNAs) are the most diverse group of non-coding RNAs and are involved in most biological processes including the immune response. While some of them have been recognized for their influence on the regulation of inflammatory activity, little is known in the context of infection by Brucella abortus, a pathogen that presents significant challenges due to its ability to manipulate and evade the host immune system. This study focuses on characterize the expression profile of LincRNA-cox2, Lethe, lincRNA-EPS, Malat1 and Gas5 during infection of macrophages by B. abortus.MethodsUsing public raw RNA-seq datasets we constructed for a lncRNA expression profile in macrophages Brucella-infected. In addition, from public RNA-seq raw datasets of RAW264.7 cells infected with B. abortus we constructed a transcriptomic profile of lncRNAs in order to know the expression of the five immunomodulating lncRNAs studied here at 8 and 24 h post-infection. Finally, we performed in vitro infection assays in RAW264.7 cells and peritoneal macrophages to detect by qPCR changes in the expression of these lncRNAs at first 12 hours post infection, a key stage in the infection cycle where Brucella modulates the immune response to survive.ResultsOur results demonstrate that infection of macrophages with Brucella abortus, induces significant changes in the expression of LincRNA-Cox2, Lethe, LincRNA-EPS, Gas5, and Malat1.DiscussionThe change in the expression profile of these immunomodulatory lncRNAs in response to infection, suggest a potential involvement in the immune evasion strategy employed by Brucella to facilitate its intracellular survival.