bluuebunny/crossref_metadata_2025 huggingface dataset:
Water channel protein AQP1 in cytoplasm is a critical factor in breast cancer local invasion
Authors: Guo Zhifang , Zhang Huikun , Liu Xiaoli , Zhao Yawen , Chen Yongzi , Jin Jiaqi , Guo Caixia , Zhang Ming , Gu Feng , Ma Yongjie
Published: February 2023

Background

Metastasis of breast cancer grows from the local invasion to the distant colonization. Blocking the local invasion step would be promising for breast cancer treatment. Our present study demonstrated AQP1 was a crucial target in breast cancer local invasion.

Methods

Mass spectrometry combined with bioinformatics analysis was used to identify AQP1 associated proteins ANXA2 and Rab1b. Co-immunoprecipitation, immunofluorescence assays and cell functional experiments were carried out to define the relationship among AQP1, ANXA2 and Rab1b and their re-localization in breast cancer cells. The Cox proportional hazards regression model was performed toward the identification of relevant prognostic factors. Survival curves were plotted by the Kaplan–Meier method and compared by the log-rank test.

Results

Here, we show that the cytoplasmic water channel protein AQP1, a crucial target in breast cancer local invasion, recruited ANXA2 from the cellular membrane to the Golgi apparatus, promoted Golgi apparatus extension, and induced breast cancer cell migration and invasion. In addition, cytoplasmic AQP1 recruited cytosolic free Rab1b to the Golgi apparatus to form a ternary complex containing AQP1, ANXA2, and Rab1b, which induced cellular secretion of the pro-metastatic proteins ICAM1 and CTSS. Cellular secretion of ICAM1 and CTSS led to the migration and invasion of breast cancer cells. Both in vivo assay and clinical analysis data confirmed above results.

Conclusions

Our findings suggested a novel mechanism for AQP1-induced breast cancer local invasion. Therefore, targeting AQP1 offers promises in breast cancer treatment.
“I loved it, absolutely loved it” a qualitative study exploring what student podiatrists learn volunteering as part of an interprofessional medical team at a marathon
Authors: Otter Simon , Whitham Deborah , Riley Paula , Coughtrey James , Whitham Sophia
Published: February 2023

Background

Final year podiatry students volunteer annually as part of the wider interprofessional medical team at both the Brighton and London Marathon race events, supervised by qualified podiatrists, allied health professionals and physicians. Volunteering has been reported to be a positive experience for all participants and a way of developing a range of professional, transferable, and where appropriate, clinical skills. We sought to explore the lived experience of 25 students who volunteered at one of these events and aimed to: i) examine the experiential learning reported by students while volunteering in a dynamic and demanding clinical field environment; ii) determine whether there were elements of learning that could be translated to the traditional teaching environment in a pre‐registration podiatry course.

Methods

A qualitative design framework informed by the principles of interpretative phenomenological analysis, was adopted to explore this topic. We used IPA principles to enable analysis of four focus groups over a two‐year period to generate findings. Focus group conversations were led by an external researcher, recorded, independently transcribed verbatim and anonymised prior to analysis by two different researchers. To enhance credibility, data analysis was followed by independent verification of themes, in addition to respondent validation.

Results

In total, five themes were identified: i) a new inter‐professional working environment, ii) identification of unexpected psychosocial challenges, iii) the rigors of a non‐clinical environment, iv) clinical skill development, and v) learning in an interprofessional team.

Throughout the focus group conversations, a range of positive and negative experiences were reported by the students. This volunteering opportunity fills a gap in learning as perceived by students, particularly around developing clinical skills and interprofessional working. However, the sometimes‐frantic nature of a Marathon race event can both facilitate and impede learning. To maximize learning opportunities, particularly in the interprofessional environment, preparing students for new or different clinical settings remains a considerable challenge.
Impact of virtual supervised tooth brushing on caries experience and quality of life among primary school children: study protocol for a randomized controlled trial
Authors: Alayadi Haya , Alsiwat Areej , AlAkeel Haifa , Alaskar Munirah , Alwadi Maram , Sabbah Wael
Published: February 2023

Background

Dental caries is one of the most common diseases affecting children world widely as well as in the Kingdom of Saudi Arabia. Supervised tooth brushing programs are implemented throughout the world to provide young children’s developing teeth with additional fluoride as a form of dental caries prevention. While school-based supervised tooth brushing programs have been proven to improve young children’s oral health, virtual supervised teeth brushing programs have not been assessed. The purpose of this protocol is to assess the impact of virtual supervised tooth brushing on caries experience and quality of life among primary school students in Riyadh, Saudi Arabia.

Methods

This is a cluster randomized controlled trial comparing a virtual supervised tooth brushing program against no intervention applied. A total of 1192 (596 in each group) 8–9-year-old children in Riyadh primary schools, Saudi Arabia, will be recruited for the trial. Schools (cluster) will be randomly selected and allocated to either group. Clinical assessment for caries experience will be conducted in six points (baseline, + 3 months, + 6 months, + 12 months, + 24 months, + 36 months) by dental hygienists using the World Health Organization criteria. Data on sociodemographic behavioral factors and children’s quality of life will be collected with every clinical assessment through a structured questionnaire. The primary outcome is the change in caries experience (the number of teeth with untreated dental caries, filled and missing teeth) in both primary and permanent teeth over 36 months.

Discussion

Virtual education as well as some health consultation through the pandemic period had enabled an effective IT infrastructure in Saudi Arabia. Virtual supervised tooth brushing is a proposed initiative. It is also an opportunity for targeting a large portion of the population with a high level of disease as a quarter of the Saudi population is younger than 15 years. This project should provide high level evidence on the effectiveness of virtual supervised tooth brushing. The findings should potentially inform policies related to the continuation/implementation of school-based programs in Saudi Arabia.

Trial registration

ClinicalTrials.gov, ID: NCT05217316. Registered on 19 January 2022.
Proportion of clinical holistic responders in patients with persistent spinal pain syndrome type II treated by subthreshold spinal cord stimulation compared to best medical treatment: a study protocol for a multicentric randomised controlled trial (TRADITION)
Authors: Goudman Lisa , Putman Koen , Van Doorslaer Leen , Billot Maxime , Roulaud Manuel , Rigoard Philippe ,   TRADITION consortium, Billet Bart , Bryon Bart , Plazier Mark , Raymaekers Vincent , Vangeneugden Johan , Moens Maarten
Published: February 2023

Background

Integrating information on bodily functions, pain intensity and quality of life into one composite measure of a holistic responder has recently been proposed as a useful method to evaluate treatment efficacy of spinal cord stimulation (SCS) in patients with therapy-refractory persistent spinal pain syndrome type II (PSPS-T2). Previous studies already demonstrated the efficacy of standard SCS over best medical treatment (BMT) and the superiority of new subthreshold (i.e. paresthesia free) SCS paradigms compared to standard SCS. Nevertheless, the efficacy of subthreshold SCS compared to BMT has not yet been investigated in patients with PSPS-T2, neither with unidimensional outcomes nor with a composite measure. The current objective is to examine whether subthreshold SCS, compared to BMT, provided to patients with PSPS-T2 results in a different proportion of clinical holistic responders (as composite measure) at 6 months.

Methods

A two-arm multicentre randomised controlled trial will be conducted whereby 114 patients will be randomised (1:1) to (a) BMT or (b) paresthesia-free SCS. After a follow-up period of 6 months (primary time endpoint), patients receive the opportunity to cross over towards the other treatment group. The primary outcome is the proportion of clinical holistic responders at 6 months (i.e. a composite measure of pain intensity, medication, disability, health-related quality of life and patient satisfaction). The secondary outcomes are work status, self-management, anxiety, depression and healthcare expenditure.

Discussion

Within the TRADITION project, we propose to shift the focus from a unidimensional outcome measure towards a composite measure as primary outcome measure to evaluate the efficacy of currently used subthreshold SCS paradigms. The lack of methodologically rigorous trials exploring the clinical efficacy and socio-economic consequences of subthreshold SCS paradigms is pressing, especially in light of the growing burden of PSPS-T2 on the society.

Trial registration

ClinicalTrials.gov NCT05169047. Registered on December 23, 2021
TREM2 splice isoforms generate soluble TREM2 species that disrupt long-term potentiation
Authors: Moutinho Miguel , Coronel Israel , Tsai Andy P. , Di Prisco Gonzalo Viana , Pennington Taylor , Atwood Brady K. , Puntambekar Shweta S. , Smith Daniel C. , Martinez Pablo , Han Seonggyun , Lee Younghee , Lasagna-Reeves Cristian A. , Lamb Bruce T. , Bissel Stephanie J. , Nho Kwangsik , Landreth Gary E.
Published: February 2023

Background

TREM2 is a transmembrane receptor expressed by myeloid cells and acts to regulate their immune response. TREM2 governs the response of microglia to amyloid and tau pathologies in the Alzheimer’s disease (AD) brain. TREM2 is also present in a soluble form (sTREM2), and its CSF levels fluctuate as a function of AD progression. Analysis of stroke and AD mouse models revealed that sTREM2 proteins bind to neurons, which suggests sTREM2 may act in a non-cell autonomous manner to influence neuronal function. sTREM2 arises from the proteolytic cleavage of the membrane-associated receptor. However, alternatively spliced TREM2 species lacking a transmembrane domain have been postulated to contribute to the pool of sTREM2. Thus, both the source of sTREM2 species and its actions in the brain remain unclear.

Methods

The expression of TREM2 isoforms in the AD brain was assessed through the analysis of the Accelerating Medicines Partnership for Alzheimer’s Disease Consortium transcriptomics data, as well as qPCR analysis using post-mortem samples of AD patients and of the AD mouse model 5xFAD. TREM2 cleavage and secretion were studied in vitro using HEK-293T and HMC3 cell lines. Synaptic plasticity, as evaluated by induction of LTP in hippocampal brain slices, was employed as a measure of sTREM2 actions.

Results

Three distinct TREM2 transcripts, namely ENST00000373113 (TREM2230), which encodes the full-length transmembrane receptor, and the alternatively spliced isoforms ENST00000373122 (TREM2222) and ENST00000338469 (TREM2219), are moderately increased in specific brain regions of patients with AD. We provide experimental evidence that TREM2 alternatively spliced isoforms are translated and secreted as sTREM2. Furthermore, our functional analysis reveals that all sTREM2 species inhibit LTP induction, and this effect is abolished by the GABAA receptor antagonist picrotoxin.

Conclusions

TREM2 transcripts can give rise to a heterogeneous pool of sTREM2 which acts to inhibit LTP. These results provide novel insight into the generation, regulation, and function of sTREM2 which fits into the complex biology of TREM2 and its role in human health and disease. Given that sTREM2 levels are linked to AD pathogenesis and progression, our finding that sTREM2 species interfere with LTP furthers our understanding about the role of TREM2 in AD.
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

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

Background

miRNAs 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.

Results

Patients’ 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.

Conclusions

This 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

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

Rational 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

The 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

Bacterial 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

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

Honeypot 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

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

This 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

Gene 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

Eating 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.
Stigma in people living with bipolar disorder and their families: a systematic review
Authors: Latifian Maryam , Abdi Kianoush , Raheb Ghoncheh , Islam Sheikh Mohammed Shariful , Alikhani Rosa
Published: February 2023

Background

Stigma affects different life aspects in people living with bipolar disorder and their families. This study aimed to examining the experience of stigma and evaluating predictors, consequences and strategies to combat stigma in people with bipolar disorder and their families.

Methods

We conducted a systematic review according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) in 2022. We extensively reviewed six online databases (PubMed, Scopus, Medline, EMBASE, Web of Science and Google Scholar). Articles published in the English language about stigma in people living with bipolar disorders and their families were included.

Results

A total of 42,763 articles were retrieved, of which 40 articles from 14 countries were included in this study (n = 7417 participants). Of the 40 articles, 29 adopted quantitative methods (72.5%), two used mixed-methods (5%), eight used qualitative (20%) methods, and one was a case series (2.5%). The results of the studies were categorized into four themes: 1. Stigma experienced by people living with bipolar disorders and their families, 2. Predictors of stigma in people living with bipolar disorders and their families, 3. Consequences of stigma in people living with bipolar disorders and their families, 4. Effective interventions and strategies to reduce stigma in people living with bipolar disorders and their families.

Conclusion

The results of this study might be useful to design psychiatric cognitive interventions to reduce stigma in people living with bipolar disorders and their families and designing community-based interventions to normalize bipolar disorder at the community level.
Spanish adaptation of the Burden Assessment Scale in family caregivers of people diagnosed with borderline personality disorder
Authors: García-Alandete Joaquín , Fernández-Felipe Isabel , Fonseca-Baeza Sara , Fernández Irene , Pérez Sandra , Marco José H. , Guillén Verónica
Published: February 2023

Background

Caregiving is a strong source of stress and leads the family caregiver to experience the burden of being responsible for the care of a severely mentally ill family member. The Burden Assessment Scale (BAS) assesses burden in family caregivers. This study aimed to analyze the psychometric properties of the BAS in a sample of family caregivers of people diagnosed with Borderline Personality Disorder (BPD).

Methods

Participants were 233 Spanish family caregivers (157 women and 76 men aged between 16–76 years old, M = 54.44, SD = 10.09) of people diagnosed with BPD. The BAS, the Multicultural Quality of Life Index, and the Depression Anxiety Stress Scale-21 were used.

Results

An exploratory analysis resulted in a three-factor 16-item model (Disrupted Activities; Personal and Social Dysfunction; Worry, Guilt, and Being Overwhelmed) with an excellent fit (χ2(101) = 56.873, p = 1.000, CFI = 1.000, TLI = 1.000, RMSEA = .000, SRMR = .060), good internal consistency (ω = .93), a negative correlation with quality of life, and a positive correlation with anxiety, depression, and stress.

Conclusion

The model obtained for the BAS is a valid, reliable, and useful tool for assessing burden in family caregivers of relatives diagnosed with BPD.
Advances and key considerations of liquid chromatography–mass spectrometry for porcine authentication in halal analysis
Authors: Dewi Kifayati Rosiyanti , Ismayati Maya , Solihat Nissa Nurfajrin , Yuliana Nancy Dewi , Kusnandar Feri , Riantana Handy , Heryani Heryani , Halim Abdul , Acter Thamina , Uddin Nizam , Kim Sunghwan
Published: February 2023

The halal food industries are rapidly expanding to fulfill global halal demands. Non-halal substances such as porcine proteins are often added intentionally or unintentionally to products. The development of highly selective and sensitive analytical tools is necessary, and liquid chromatography–mass spectrometry is a powerful tool that can cope with the challenge. The LC–MS method has great potential for halal authentication, because it has high sensitivity and low detection limit and detects several species markers and different tissue origins at once within one species. This article provides an understanding of recent advances in the application of LC–MS for the improvement of porcine authentication. Sample preparation, marker selection, separation and mass spectrometry conditions, quantitative assessment, and data processing for protein identification were all covered in detail to choose the most suitable method for the analytical needs.
Fatal and non-fatal firearm-related injuries in Canada, 2016–2020: a population-based study using three administrative databases
Authors: Toigo Stephanie , Pollock Nathaniel J. , Liu Li , Contreras Gisèle , McFaull Steven R. , Thompson Wendy
Published: February 2023

Background

Firearms are a substantial cause of injury-related morbidity and mortality in Canada and globally, though evidence from contexts other than the USA is relatively limited. We examined deaths, hospitalizations and emergency department (ED) visits due to firearm-related injuries in Canada to identify population groups at increased risk of fatal and non-fatal outcomes.

Methods

We conducted a population-based study using three national administrative databases on deaths, hospitalizations, and ED visits. ICD-10 codes were used to identify firearm-related injuries from January 1, 2016, through December 31, 2020. Fatal and non-fatal firearm injuries were classified as suicide/self-harm, homicide/assault, unintentional, undetermined or legal intervention injuries. We analyzed the data with counts, rates and proportions, stratified by sex, age group, province/territory, and year.

Results

Over the 5-year period, we identified 4005 deaths, 3169 hospitalizations, and 2847 ED visits related to firearm injuries in various jurisdictions in Canada. Males comprised the majority of fatal and non-fatal injury cases. The highest rates of fatal and non-fatal firearm injuries were among 20- to 34-year-olds. The leading cause of fatal firearm injuries was self-harm (72.3%). For non-fatal firearm hospitalizations and ED visits, assault (48.8%) and unintentional injuries (62.8%) were the leading causes of injury. Rates varied by province and territory.

Conclusions

Our results showed that males comprised the majority of fatal and non-fatal firearm injuries in Canada. The rates of both fatal and non-fatal firearm injuries were highest among the 20- to 34-year-old age group. This comprehensive overview of the epidemiology of firearm injuries in Canada provides baseline data for ongoing surveillance and policy evaluation related to public health interventions.
Imported diseases in travellers presenting to the emergency department after a stay in a malaria-endemic country: a retrospective observational study
Authors: Desmet Sofie , Henckaerts Liesbet , Ombelet Sien , Damanet Benjamin , Vanbrabant Peter
Published: February 2023

Background

We aimed to investigate the aetiology and outcomes of illnesses in patients presenting to an emergency department after travelling to a malaria-endemic country, in order to raise awareness of both tropical and cosmopolitan diseases.

Methods

A retrospective chart review was performed for all patients who underwent blood smear testing for malaria at the Emergency Department of the University Hospitals Leuven from 2017 to 2020. Patient characteristics, results of laboratory and radiological examinations, diagnoses, disease course and outcome were collected and analysed.

Results

A total of 253 patients were included in the study. The majority of ill travellers returned from Sub-Saharan Africa (68.4%) and Southeast Asia (19.4%). Their diagnoses fell into three major syndrome categories: systemic febrile illness (30.8%), inflammatory syndrome of unknown origin (23.3%) and acute diarrhoea (18.2%). Malaria (15.8%) was the most common specific diagnosis in patients with systemic febrile illness, followed by influenza (5.1%), rickettsiosis (3.2%), dengue (1.6%), enteric fever (0.8%), chikungunya (0.8%) and leptospirosis (0.8%). The presence of hyperbilirubinemia and thrombocytopenia increased the probability of malaria, with a likelihood ratio of 4.01 and 6.03, respectively. Seven patients (2.8%) were treated in the intensive care unit, and none died.

Conclusion

Systemic febrile illness, inflammatory syndrome of unknown origin and acute diarrhoea were the three major syndromic categories in returning travellers presenting to our emergency department after a stay in a malaria-endemic country. Malaria was the most common specific diagnosis in patients with systemic febrile illness. None of the patients died.
Interindividual Variability in Mental Fatigue-Related Impairments in Endurance Performance: A Systematic Review and Multiple Meta-regression
Authors: Habay Jelle , Uylenbroeck Robin , Van Droogenbroeck Ruben , De Wachter Jonas , Proost Matthias , Tassignon Bruno , De Pauw Kevin , Meeusen Romain , Pattyn Nathalie , Van Cutsem Jeroen , Roelands Bart
Published: February 2023

Background

The negative effect of mental fatigue (MF) on physical performance has recently been questioned. One reason behind this could lie in the interindividual differences in MF-susceptibility and the individual features influencing them. However, the range of individual differences in mental fatigue-susceptibility is not known, and there is no clear consensus on which individual features could be responsible for these differences.

Objective

To give an overview of interindividual differences in the effects of MF on whole-body endurance performance, and individual features influencing this effect.

Methods

The review was registered on the PROSPERO database (CRD42022293242). PubMed, Web of Science, SPORTDiscus and PsycINFO were searched until the 16th of June 2022 for studies detailing the effect of MF on dynamic maximal whole-body endurance performance. Studies needed to include healthy participants, describe at least one individual feature in participant characteristics, and apply at least one manipulation check. The Cochrane crossover risk of bias tool was used to assess risk of bias. The meta-analysis and regression were conducted in R.

Results

Twenty-eight studies were included, with 23 added to the meta-analysis. Overall risk of bias of the included studies was high, with only three presenting an unclear or low rating. The meta-analysis shows the effect of MF on endurance performance was on average slightly negative (g = − 0.32, [95% CI − 0.46; − 0.18], p < 0.001). The multiple meta-regression showed no significant influences of the included features (i.e. age, sex, body mass index and physical fitness level) on MF-susceptibility.

Conclusions

The present review confirmed the negative impact of MF on endurance performance. However, no individual features influencing MF-susceptibility were identified. This can partially be explained by the multiple methodological limitations such as underreporting of participant characteristics, lack of standardization across studies, and the restricted inclusion of potentially relevant variables. Future research should include a rigorous description of multiple different individual features (e.g., performance level, diet, etc.) to further elucidate MF mechanisms.