bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synchronous online focus groups in health research: application and further development of methodology based on experiences from two mixed-methods research projects
Authors: Lander Jonas , Altawil Hala , Dilger Elise-Marie , Bruett Anna Levke , Fricke Lara Marleen , Hoekstra Dyon , John Cosima , Krauth Christian , Krüger Kathrin , Schaubert Kristina , von Sommoggy Julia , Thiele Annett , Dierks Marie-Luise 
Published: February 2023

Abstract
Objectives
Focus groups used for data collection in health research are increasingly conducted online. In two multi-center health research projects, we applied available methodological instructions for synchronous online focus groups (SOFGs). We describe necessary changes and specifications regarding the planning (recruitment, technology, ethics, appointments) and conduct (group composition, moderation, interaction, didactics) to enhance knowledge about the planning and conduct of SOFGs.

Results
Recruiting online proved to be challenging and necessitated direct and analogue recruiting, too. To ensure participation, less digital and more individual formats may be offered, e.g. telephone calls. Explaining verbally the specifics of data protection and anonymity in an online setting can foster participants’ confidence to actively engage in the discussion. Two moderators, one moderating, one supporting technically, are advisable in SOFGs, however, due to limited nonverbal communication, roles and tasks need to be defined beforehand. Participant interaction is central to focus groups in general, but sometimes difficult to achieve online. Hence, smaller group size, sharing of personal information and moderators increased attention to individual reactions appeared helpful. Lastly, digital tools such as surveys and breakout rooms should be used with caution, as they easily inhibit interaction.
A miRNA screening identifies miR-192-5p as associated with response to azacitidine and lenalidomide therapy in myelodysplastic syndromes
Authors: Mongiorgi Sara , De Stefano Alessia , Ratti Stefano , Indio Valentina , Astolfi Annalisa , Casalin Irene , Pellagatti Andrea , Paolini Stefania , Parisi Sarah , Cavo Michele , Pession Andrea , McCubrey James A. , Suh Pann-Ghill , Manzoli Lucia , Boultwood Jacqueline , Finelli Carlo , Cocco Lucio , Follo Matilde Y. 
Published: February 2023

AbstractBackgroundmiRNAs are small non-coding RNAs that regulate gene expression and are linked to cancer development and progression. miRNA profiles are currently studied as new prognostic factors or therapeutic perspectives. Among hematological cancers, myelodysplastic syndromes at higher risk of evolution into acute myeloid leukemia are treated with hypomethylating agents, like azacitidine, alone or in combination with other drugs, such as lenalidomide. Recent data showed that, during azacitidine and lenalidomide therapy, the concurrent acquisition of specific point mutations affecting inositide signalling pathways is associated with lack or loss of response to therapy. As these molecules are implicated in epigenetic processes, possibly involving miRNA regulation, and in leukemic progression, through the regulation of proliferation, differentiation and apoptosis, here we performed a new miRNA expression analysis of 26 high-risk patients with myelodysplastic syndromes treated with azacitidine and lenalidomide at baseline and during therapy. miRNA array data were processed, and bioinformatic results were correlated with clinical outcome to investigate the translational relevance of selected miRNAs, while the relationship between selected miRNAs and specific molecules was experimentally tested and proven.ResultsPatients’ overall response rate was 76.9% (20/26 cases): complete remission (5/26, 19.2%), partial remission (1/26, 3.8%), marrow complete remission (2/26, 7.7%), hematologic improvement (6/26, 23.1%), hematologic improvement with marrow complete remission (6/26, 23.1%), whereas 6/26 patients (23.1%) had a stable disease. miRNA paired analysis showed a statistically significant up-regulation of miR-192-5p after 4 cycles of therapy (vs baseline), that was confirmed by real-time PCR analyses, along with an involvement of BCL2, that was proven to be a miR-192-5p target in hematopoietic cells by luciferase assays. Furthermore, Kaplan–Meier analyses showed a significant correlation between high levels of miR-192-5p after 4 cycles of therapy and overall survival or leukemia-free survival, that was stronger in responders, as compared with patients early losing response and non-responders.ConclusionsThis study shows that high levels of miR-192-5p are associated with higher overall survival and leukemia-free survival in myelodysplastic syndromes responding to azacitidine and lenalidomide. Moreover, miR-192-5p specifically targets and inhibits BCL2, possibly regulating proliferation and apoptosis and leading to the identification of new therapeutic targets.
Internal carotid artery aneurysm with incomplete isolated oculomotor nerve palsy: a case report
Authors: Zheng Jing , Wan Yue 
Published: February 2023

Abstract
Background
Oculomotor nerve palsy is a common and well-described disease with diverse etiologies. Clinicians should quickly and correctly diagnose and treat oculomotor nerve palsy according to its characteristics and the accompanying symptoms and signs. Intracranial aneurysm is an important and frequent cause of oculomotor nerve palsy. Considering the catastrophic consequences of rupture, the possibility of an urgent, life-threatening disease should always be considered.

Case presentation
A 63-year-old Chinese woman presented with intermittent left ptosis and diplopia and painless incomplete oculomotor nerve palsy without pupil involvement. She manifested no mydriasis or extraocular muscle weakness, and the light reflex was normal. Other cranial nerves and somatosensory and somatomotor examinations were normal. The neostigmine experiment and electromyography were normal, so the diagnosis of myasthenia gravis was excluded. Brain magnetic resonance angiography showed a 4-mm aneurysm located at the cavernous segment of the left internal carotid artery. Unfortunately, the patient refused digital subtraction angiography and was discharged home without further treatment.

Conclusion
Neuroimaging must be performed to exclude intracranial aneurysms in oculomotor nerve palsy regardless of whether the pupils are involved, as aneurysm rupture carries substantial morbidity and mortality.
DrugEx v3: scaffold-constrained drug design with graph transformer-based reinforcement learning
Authors: Liu Xuhan , Ye Kai , van Vlijmen Herman W. T. , IJzerman Adriaan P. , van Westen Gerard J. P. 
Published: February 2023

AbstractRational drug design often starts from specific scaffolds to which side chains/substituents are added or modified due to the large drug-like chemical space available to search for novel drug-like molecules. With the rapid growth of deep learning in drug discovery, a variety of effective approaches have been developed for de novo drug design. In previous work we proposed a method named DrugEx, which can be applied in polypharmacology based on multi-objective deep reinforcement learning. However, the previous version is trained under fixed objectives and does not allow users to input any prior information (i.e. a desired scaffold). In order to improve the general applicability, we updated DrugEx to design drug molecules based on scaffolds which consist of multiple fragments provided by users. Here, a Transformer model was employed to generate molecular structures. The Transformer is a multi-head self-attention deep learning model containing an encoder to receive scaffolds as input and a decoder to generate molecules as output. In order to deal with the graph representation of molecules a novel positional encoding for each atom and bond based on an adjacency matrix was proposed, extending the architecture of the Transformer. The graph Transformer model contains growing and connecting procedures for molecule generation starting from a given scaffold based on fragments. Moreover, the generator was trained under a reinforcement learning framework to increase the number of desired ligands. As a proof of concept, the method was applied to design ligands for the adenosine A2A receptor (A2AAR) and compared with SMILES-based methods. The results show that 100% of the generated molecules are valid and most of them had a high predicted affinity value towards A2AAR with given scaffolds.
Micafungin effect on Pseudomonas aeruginosa metabolome, virulence and biofilm: potential quorum sensing inhibitor
Authors: Hijazi Duaa M. , Dahabiyeh Lina A. , Abdelrazig Salah , Alqudah Dana A. , Al-Bakri Amal G. 
Published: February 2023

AbstractThe prevalence of antibiotic resistance in Pseudomonas aeruginosa places a heavy burden on the health care sectors urging the need to find alternative, non-antibiotic strategies. The interference with the P. aeruginosa quorum sensing (QS) system represents a promising alternative strategy to attenuate the bacterial virulency and its ability to form biofilms. Micafungin has been reported to impede the pseudomonal biofilm formation. However, the influences of micafungin on the biochemical composition and metabolites levels of P. aeruginosa have not been explored. In this study, the effect of micafungin (100 µg/mL) on the virulence factors, QS signal molecules and the metabolome of P. aeruginosa was studied using exofactor assay and mass spectrometry-based metabolomics approaches. Furthermore, confocal laser scanning microscopy (CLSM) using the fluorescent dyes ConA-FITC and SYPRO® Ruby was used to visualize micafungin disturbing effects on the pseudomonal glycocalyx and protein biofilm-constituents, respectively. Our findings showed that micafungin significantly decreased the production of various QS-controlled virulence factors (pyocyanin, pyoverdine, pyochelin and rhamnolipid), along with a dysregulation in the level of various metabolites involved in QS system, lysine degradation, tryptophan biosynthesis, TCA cycle, and biotin metabolism. In addition, the CLSM examination showed an altered matrix distribution. The presented findings highlight the promising role of micafungin as a potential quorum sensing inhibitor (QSI) and anti-biofilm agent to attenuate P. aeruginosa pathogenicity. In addition, they point to the promising role of metabolomics study in investigating the altered biochemical pathways in P. aeruginosa.
mltG gene deletion mitigated virulence potential of Streptococcus mutans: An in-vitro, ex-situ and in-vivo study
Authors: Zaidi Sahar , Ali Khursheed , Chawla Yadya M. , Khan Asad U. 
Published: February 2023

AbstractBacterial cells are surrounded by a peptidoglycan (PG) cell wall, which is essential for cell integrity and intrinsic biogenesis pathways; hence, the cell wall is a potential target for several antibiotics. Among several lytic transglycosylases (LTs), the mltG gene plays a crucial role in the synthesis of peripheral PG. It localises the re-modelled PGs for septum formation and cleavage across the bacterial cell wall during daughter cells separation. However, the role of mltG gene in bacterial virulence, particularly in Gram-positive bacteria during dentine biofilm and caries development, has remained unexplored. Hence, we exploited Gram-positive Streptococcus mutans cells for the very first time to construct a mltG knock-out bacterial strain, e.g., ΔmltG S. mutans. Systematic comparative investigations revealed that doubling time (Td), survival, enzymatic efficiencies, pH tolerance, bio-synthesise of lipid, proteins and DNA, biofilm formation and dentine lesions were significantly (p < 0.001) compromised in case of ΔmltG S. mutans than wild type strain. The qRT-PCR based gene expression profiling revealed that transcriptional expression of critically important genes involved in biofilm, metabolism, and stress response were dysregulated in the mutant. Besides, an incredible reduction in dentine caries development was found in the molar teeth of Wistar rats and also in human extracted teeth. Concisely, these trends obtained evidently advocated the fact that the deletion of mltG gene can be a potential target to impair the S. mutans virulence through severe growth retardation, thereby reducing the virulence potential of S. mutans.
Graphical Abstract
A patient-derived mutation of epilepsy-linked LGI1 increases seizure susceptibility through regulating Kv1.1
Authors: Zhou Lin , Wang Kang , Xu Yuxiang , Dong Bin-Bin , Wu Deng-Chang , Wang Zhao-Xiang , Wang Xin-Tai , Cai Xin-Yu , Yang Jin-Tao , Zheng Rui , Chen Wei , Shen Ying , Wei Jian-She 
Published: February 2023

Abstract
Background
Autosomal dominant lateral temporal epilepsy (ADLTE) is an inherited syndrome caused by mutations in the leucine-rich glioma inactivated 1 (LGI1) gene. It is known that functional LGI1 is secreted by excitatory neurons, GABAergic interneurons, and astrocytes, and regulates AMPA-type glutamate receptor-mediated synaptic transmission by binding ADAM22 and ADAM23. However, > 40 LGI1 mutations have been reported in familial ADLTE patients, more than half of which are secretion-defective. How these secretion-defective LGI1 mutations lead to epilepsy is unknown.

Results
We identified a novel secretion-defective LGI1 mutation from a Chinese ADLTE family, LGI1-W183R. We specifically expressed mutant LGI1W183R in excitatory neurons lacking natural LGI1, and found that this mutation downregulated Kv1.1 activity, led to neuronal hyperexcitability and irregular spiking, and increased epilepsy susceptibility in mice. Further analysis revealed that restoring Kv1.1 in excitatory neurons rescued the defect of spiking capacity, improved epilepsy susceptibility, and prolonged the life-span of mice.

Conclusions
These results describe a role of secretion-defective LGI1 in maintaining neuronal excitability and reveal a new mechanism in the pathology of LGI1 mutation-related epilepsy.
A new dynamic security defense system based on TCP_REPAIR and deep learning
Authors: Tang Jianxun , Chen Mingsong , Chen Haoyu , Zhao Shenqi , Huang Yu 
Published: February 2023

AbstractHoneypot is an active defense mechanism, which attracts attackers to interact with virtual resources in the honeypot mainly by simulating real working scenarios and deploying decoy targets, so as to prevent real resources from being damaged and collect attackers’ attack processes and analyze potential system vulnerabilities to proactively respond to similar attacks. Because of the existing honeypot system has defects such as the inability to deploy specific honeypots to induce attacks based on complex attacks, the inability to select the best honeypot for dynamic response based on honeypot deployment and maintenance costs during attack interactions, and insufficient ability to identify variants of known attack methods. Although hybrid honeypots can solve some of these problems by deploying low-interaction honeypots and high-interaction honeypots, they cannot really be applied to real production scenarios because of their slow TCP connection switching speed and inability to efficiently identify encrypted malicious traffic. In this paper, we propose a new dynamic security defense system based on the combination of TCP_REPAIR-based dynamic honeypot selection architecture and a deep learning-based intelligent firewall. The system accurately distributes encrypted or non-encrypted attack traffic and its variants through the intelligent firewall. The normal traffic is sent to the actual system, and the marked malicious traffic dynamically selects honeypots to respond according to the attack process.The experimental result indicated that the system can select honeypots for targeted responses according to the actual network situation quickly and dynamically and covertly, effectively improving the utilization rate of honeypot clusters as well as the ability to decoy.
Impact of left atrial appendage morphology on thrombus formation in TAVI patients with atrial fibrillation
Authors: Abanador-Kamper N. , Bepperling J. , Seyfarth M. , Haage P. , Kamper L. 
Published: February 2023

Abstract
Purpose
We aimed to correlate left atrial appendage (LAA) morphology with thrombus formation in patients with severe aortic valve stenosis and atrial fibrillation.

Methods
We analyzed LAA morphology and the prevalence of a thrombus in 231 patients with atrial fibrillation and severe aortic valve stenosis that were referred for pre-interventional CT scan before trans-catheter aortic valve implantation (TAVI) between 2016 and 2018. In addition, we documented neuro-embolic events depending on the presence of LAA thrombus within a follow-up of 18 months.

Results
The overall distribution of different LAA morphologies was chicken-wing 25.5%, windsock 51.5%, cactus 15.6% and cauliflower 7.4%. Compared to chicken-wing morphology, patients with non-chicken-wing morphology showed a significantly higher thrombus rate (OR: 2.48, 95%; CI 1.05 to 5.86, p = 0.043). Within the 50 patients with a LAA thrombus, we observed chicken-wing (14.0%), windsock (62.0%), cactus (16.0%) and cauliflower (8.0%) configuration. In patients with LAA thrombus those with chicken-wing configuration have a higher risk (42.9%) to develop neuro-embolic events compared to non-chicken-wing configuration (20.9%).

Conclusion
We found a lower LAA thrombus rate in patients with chicken-wing morphology compared to patients with non-chicken-wing configuration. However, in the presence of thrombus, those patients with chicken-wing morphology showed a doubled risk for neuro-embolic events compared to patients with non-chicken-wing morphology.
These results must be confirmed in larger trials but underline the importance of LAA evaluation in thoracic CT scans and could have an impact on the anticoagulation management.
Experimental Investigation on the Effect of Curing Condition and Admixture on Meso-Structure of Recycled Aggregate Concrete Based on X-ray CT
Authors: Chen Yuzhi , Ning Yingjie , Chen Xudong , Xuan Weihong , Guo Yuzhu 
Published: February 2023

AbstractThis study addresses the meso-structure of recycled aggregate concrete with different admixture and c;uring condition. The RCA (Recycled concrete aggregate) with admixture of slag power and fly ash and curing condition of steam was casted. X-ray CT (Computed tomography) was used to obtain meso-structure of RCA, and the pore structure, aggregate, and interface traction zone were analyzed. The results show that steam curing not only increases the pore volume but also makes the pore morphology more complex, the fractal dimension increases, the proportion of spherical pores decreases, and the pores develop from spherical to flat and slender with the increase of steam curing temperature. The porosity of micron pores in recycled aggregate concrete is about 2.3%, in which the pores with aperture less than 300 μm accounts for more than 85%. The thickness of the interface area between recycled aggregate and new mortar is about 200 μm, and the crack width in recycled aggregate is about 300– 400 μm.
Breast cancer cells that preferentially metastasize to lung or bone are more glycolytic, synthesize serine at greater rates, and consume less ATP and NADPH than parent MDA-MB-231 cells
Authors: Jekabsons Mika B. , Merrell Mollie , Skubiz Anna G. , Thornton Noah , Milasta Sandra , Green Douglas , Chen Taosheng , Wang Yan-Hong , Avula Bharathi , Khan Ikhlas A. , Zhou Yu-Dong 
Published: February 2023

AbstractGene expression signatures associated with breast cancer metastases suggest that metabolic re-wiring is important for metastatic growth in lungs, bones, and other organs. However, since pathway fluxes depend on additional factors such as ATP demand, allosteric effects, and post-translational modification, flux analysis is necessary to conclusively establish phenotypes. In this study, the metabolic phenotypes of breast cancer cell lines with low (T47D) or high (MDA-MB-231) metastatic potential, as well as lung (LM)- and bone (BoM)-homing lines derived from MDA-MB-231 cells, were assessed by 13C metabolite labeling from [1,2-13C] glucose or [5-13C] glutamine and the rates of nutrient and oxygen consumption and lactate production. MDA-MB-231 and T47D cells produced 55 and 63%, respectively, of ATP from oxidative phosphorylation, whereas LM and BoM cells were more glycolytic, deriving only 20–25% of their ATP from mitochondria. ATP demand by BoM and LM cells was approximately half the rate of the parent cells. Of the anabolic fluxes assessed, nucleotide synthesis was the major ATP consumer for all cell lines. Glycolytic NADH production by LM cells exceeded the rate at which it could be oxidized by mitochondria, suggesting that the malate-aspartate shuttle was not involved in re-oxidation of these reducing equivalents. Serine synthesis was undetectable in MDA-MB-231 cells, whereas 3–5% of glucose was shunted to serine by LM and BoM lines. Proliferation rates of T47D, BoM, and LM lines tightly correlated with their respiration-normalized NADPH production rates. In contrast, MDA-MB-231 cells produced NADPH and GSH at higher rates, suggesting this line is more oxidatively stressed. Approximately half to two-thirds of NADPH produced by T47D, MDA-MB-231, and BoM cells was from the oxidative PPP, whereas the majority in LM cells was from the folate cycle. All four cell lines used the non-oxidative PPP to produce pentose phosphates, although this was most prominent for LM cells. Taken together, the metabolic phenotypes of LM and BoM lines differed from the parent line and from each other, supporting the metabolic re-wiring hypothesis as a feature of metastasis to lung and bone.
Renal and electrolyte complications in eating disorders: a comprehensive review
Authors: Puckett Leah 
Published: February 2023

AbstractEating disorders are psychiatric disorders with significant and widespread medical complications, including renal disorders. Renal disease is not uncommon in patients with eating disorders but is often unrecognized. It includes both acute renal injury and progression to chronic kidney disease requiring dialysis. Electrolyte abnormalities including hyponatremia, hypokalemia, and metabolic alkalosis are common in eating disorders and vary depending on whether patients engage in purging behaviors. Chronic hypokalemia due to purging in patients with anorexia nervosa-binge purge subtype or bulimia nervosa can lead to hypokalemic nephropathy and chronic kidney disease. Additional electrolyte derangements are seen during refeeding, including hypophosphatemia, hypokalemia, and hypomagnesemia. Patients can also develop Pseudo-Bartter’s syndrome which leads to edema and rapid weight gain in patients who cease purging behavior. Clinicians and patients should be aware of these complications in order to provide education and early detection and prevention.