bluuebunny/crossref_metadata_2025 huggingface dataset:
Remibrutinib (LOU064) inhibits neuroinflammation driven by B cells and myeloid cells in preclinical models of multiple sclerosis
Authors: Nuesslein-Hildesheim Barbara , Ferrero Enrico , Schmid Cindy , Huck Catherine , Smith Paul , Tisserand Sarah , Rubert Joelle , Bornancin Frederic , Eichlisberger Denis , Cenni Bruno
Published: August 2023

Background

Bruton’s tyrosine kinase (BTK) is a key signaling node in B cell receptor (BCR) and Fc receptor (FcR) signaling. BTK inhibitors (BTKi) are an emerging oral treatment option for patients suffering from multiple sclerosis (MS). Remibrutinib (LOU064) is a potent, highly selective covalent BTKi with a promising preclinical and clinical profile for MS and other autoimmune or autoallergic indications.

Methods

The efficacy and mechanism of action of remibrutinib was assessed in two different experimental autoimmune encephalomyelitis (EAE) mouse models for MS. The impact of remibrutinib on B cell-driven EAE pathology was determined after immunization with human myelin oligodendrocyte glycoprotein (HuMOG). The efficacy on myeloid cell and microglia driven neuroinflammation was determined in the RatMOG EAE. In addition, we assessed the relationship of efficacy to BTK occupancy in tissue, ex vivo T cell response, as well as single cell RNA-sequencing (scRNA-seq) in brain and spinal cord tissue.

Results

Remibrutinib inhibited B cell-dependent HuMOG EAE in dose-dependent manner and strongly reduced neurological symptoms. At the efficacious oral dose of 30 mg/kg, remibrutinib showed strong BTK occupancy in the peripheral immune organs and in the brain of EAE mice. Ex vivo MOG-specific T cell recall response was reduced, but not polyclonal T cell response, indicating absence of non-specific T cell inhibition. Remibrutinib also inhibited RatMOG EAE, suggesting that myeloid cell and microglia inhibition contribute to its efficacy in EAE. Remibrutinib did not reduce B cells, total Ig levels nor MOG-specific antibody response. In brain and spinal cord tissue a clear anti-inflammatory effect in microglia was detected by scRNA-seq. Finally, remibrutinib showed potent inhibition of in vitro immune complex-driven inflammatory response in human microglia.

Conclusion

Remibrutinib inhibited EAE models by a two-pronged mechanism based on inhibition of pathogenic B cell autoreactivity, as well as direct anti-inflammatory effects in microglia. Remibrutinib showed efficacy in both models in absence of direct B cell depletion, broad T cell inhibition or reduction of total Ig levels. These findings support the view that remibrutinib may represent a novel treatment option for patients with MS.
Levels of health literacy among people living with HIV in outpatient care: a cross-sectional study from Denmark
Authors: Rodkjaer Lotte Ørneborg , Storgaard Merete , Sørensen Nanna Toxvig , Schougaard Liv Marit Valen
Published: August 2023

Background

Low health literacy (HL) among people living with HIV (PLWHIV) encounter more disease related complications, more difficulty understanding health-related information and low adherence. Considering that, the HL levels among PLWHIV needs to be further investigated. The objective of this study was to investigate the levels of HL and patient involvement among PLWHIV in an outpatient clinic in Denmark. A second objective was to examine differences in HL levels across socio-demographic characteristics.

Methods

In 2019, a population of 682 PLWHIV from a Danish outpatient hospital clinic were enrolled in cross-sectional study. Patients who had a digital postbox received an electronic questionnaire including following domains; health literacy, patient involvement, and socio-demographic status. Health literacy was measured using the Health Literacy Questionnaire (HLQ) through scores on three subscales: social support for health (HLQ4), engaging with healthcare providers (HLQ6), and understanding health information (HLQ9). An unpaired t-test was used to investigate mean differences in the HLQ scores across socio-demographic variables.

Results

A total of 338 (55%) patients responded to the questionnaire. The included participants demonstrated high levels of HLQ4 (mean = 4.2) and HLQ6 (mean = 4.2), but lower for HLQ9 (mean = 2.9). In total 70–80% reported being involved in decisions about their health. We found a positive association between high level of HL (HLQ9) and living with a partner and higher levels of HL (HLQ4, HLQ6, and HLQ9) and employment.

Conclusion

PLWHIV in a Danish out-patient care population were found to have high levels of HL despite differences in demographic characteristics. Further research is needed to examine the levels of HL among non-responders to develop HL approaches and strategies to meet the needs of individuals with different HL skills.
Comparative effectiveness of hyaluronic acid, platelet-rich plasma, and platelet-rich fibrin in treating temporomandibular disorders: a systematic review and network meta-analysis
Authors: Xu Jingjing , Ren Hui , Zhao Shuwei , Li Qian , Li Ce , Bao Guangjie , Kang Hong
Published: August 2023

Objective

This study aims to compare the efficacy of intra-articular injections of hyaluronic acid (HA), platelet-rich plasma (PRP), and platelet-rich fibrin (PRF) for treating temporomandibular disorders (TMDs) and summarize their mechanisms of action.

Methods

Randomized controlled trials (RCTs) published until November 13, 2021, were identified using electronic and manual searches. Each study was evaluated for the risk of bias using the Cochrane risk of bias tool. The studies found via searches were categorized by follow-up time (1, 3, or 6 months). Evidence quality was graded according to the GRADE system.

Results

Twelve RCTs were included that involved 421 patients with TMD. The network meta-analysis showed that all treatment groups improved compared to the placebo groups in terms of pain and maximal mouth opening (MMO). For pain evaluated via the visual analog scale, PRF exhibited better analgesic effects than PRP or HA after 1 and 3 months. PRP appeared to be more effective than PRF was after 6 months but there were no statistically significant differences between the two. For MMO, the effect of PRP was superior to those of PRF and HA after 1 month. However, after 3 and 6 months, PRF provided more encouraging results in improving MMO.

Conclusion

PRP and PRF exhibited similar short-term efficacy in treating TMD, while PRF was more advantageous in terms of long-term efficacy. Therefore, PRF was recommended for treating TMD.
Plant disease prescription recommendation based on electronic medical records and sentence embedding retrieval
Authors: Ding Junqi , Qiao Yan , Zhang Lingxian
Published: August 2023

Background

In the era of Agri 4.0 and the popularity of Plantwise systems, the availability of Plant Electronic Medical Records has provided opportunities to extract valuable disease information and treatment knowledge. However, developing an effective prescription recommendation method based on these records presents unique challenges, such as inadequate labeling data, lack of structural and linguistic specifications, incorporation of new prescriptions, and consideration of multiple factors in practical situations.

Results

This study proposes a plant disease prescription recommendation method called PRSER, which is based on sentence embedding retrieval. The semantic matching model is created using a pre-trained language model and a sentence embedding method with contrast learning ideas, and the constructed prescription reference database is retrieved for optimal prescription recommendations. A multi-vegetable disease dataset and a multi-fruit disease dataset are constructed to compare three pre-trained language models, four pooling types, and two loss functions. The PRSER model achieves the best semantic matching performance by combining MacBERT, CoSENT, and CLS pooling, resulting in a Pearson coefficient of 86.34% and a Spearman coefficient of 77.67%. The prescription recommendation capability of the model is also verified. PRSER performs well in closed-set testing with Top-1/Top-3/Top-5 accuracy of 88.20%/96.07%/97.70%; and slightly worse in open-set testing with Top-1/Top-3/Top-5 accuracy of 82.04%/91.50%/94.90%. Finally, a plant disease prescription recommendation system for mobile terminals is constructed and its generalization ability with incomplete inputs is verified. When only symptom information is available without environment and plant information, our model shows slightly lower accuracy with Top-1/Top-3/Top-5 accuracy of 75.24%/88.35%/91.99% in closed-set testing and Top-1/Top-3/Top-5 accuracy of 75.08%/87.54%/89.84% in open-set testing.

Conclusions

The experiments validate the effectiveness and generalization ability of the proposed approach for recommending plant disease prescriptions. This research has significant potential to facilitate the implementation of artificial intelligence in plant disease treatment, addressing the needs of farmers and advancing scientific plant disease management.
Suprapatellar pouch effusion is associated with an increased risk of neglected osteochondral fractures in primary acute traumatic patellar dislocation: a consecutive series of 113 children
Authors: Miao Mingyuan , Cai Haoqi , Wang Zhigang , Hu Liwei , Bian Jingxia , Cai Haiqing
Published: August 2023

Background

The aim of this study was to investigate the risk factors of neglected osteochondral fractures in primary acute traumatic patellar dislocation in the pediatric population.

Methods

A total of 113 patients with primary acute traumatic patellar dislocation for whom coincident osteochondral fractures could not be confirmed by X-ray examination at initial diagnosis between January 2010 and February 2022 were retrospectively analyzed. Medical history, physical examination, and radiographic images were recorded in detail. The greatest dimension of the suprapatellar pouch (SP) effusion on radiograph was measured. Computed tomography and magnetic resonance imaging were used to confirm the presence of neglected osteochondral fractures and measure the fragment size. Potential risk factors were calculated and correlated with reference to the neglected osteochondral fractures and fragment size using multivariate linear regression analysis.

Results

Weight, walking ability, effusion grade, and SP measurement had a significant correlation with neglected osteochondral fractures in primary acute traumatic patellar dislocation (p = 0.046; p < 0.001; p = 0.048; p < 0.001). The cutoff point was 53.5 kg for weight and 18.45 mm for SP measurement. In the neglected fractures group, SP measurement was statistically significant with larger fragment size (beta value = 0.457; p < 0.001), and the cutoff point was 26.2 mm.

Conclusions

SP effusion is not only associated with an increased risk of neglected osteochondral fractures in primary acute traumatic patellar dislocation but also with larger fragment size. Knee radiograph, medical history, and physical examination can predict the need for further imaging examination and even surgery in primary acute traumatic patellar dislocation.
Prevalence of sleep disturbance among adolescents with substance use: a systematic review and meta-analysis
Authors: Phiri Doreen , Amelia Vivi Leona , Muslih Muhammad , Dlamini Lindelwa Portia , Chung Min-Huey , Chang Pi-Chen
Published: August 2023

Purpose

Sleep disturbance has become a major challenge among adolescents worldwide. Substance use is among the most common factors contributing to sleep disturbance. This systematic review and meta-analysis examined the prevalence and categories of sleep disturbance among adolescents with substance use.

Methods

We comprehensively searched for relevant studies published in the following databases from inception to August 2022: CINHAL (via EBSCOhost), PubMed, Scopus, Ovid Medline, Embase, ProQuest, and Web of Science. Data analysis was performed using Comprehensive Meta-Analysis version 3 software. We used a random-effects model to pool prevalence rates with 95% confidence intervals (CIs). Forest plots and p values for the Cochran Q statistic were used to evaluate heterogeneity among studies. Subgroup and meta-regression analyses were performed to compare the groups and identify the sources of heterogeneity.

Results

We examined 18 studies that reported insomnia, hypersomnolence, sleep-related breathing disorders as sleep disturbances among adolescents with the use of alcohol, smoking, marijuana, and coffee. The total sample was 124,554. The overall prevalence rate of sleep disturbance was 29% (95% CI: 0.201–0.403). Subgroup analysis revealed that the prevalence rates of insomnia and hypersomnolence were higher among alcohol users (31%; 95% CI: 0.100–0.654) and smokers (46%; 95% CI: 0.232–0.700). The study design and method of assessment groups were the significant moderators that showed the source of variation in the included studies.

Conclusion

Sleep disturbance is highly prevalent among adolescents with substance use. Insomnia and hypersomnolence are more prevalent among alcohol users and smokers, respectively. On the basis of our findings, health-care providers can develop effective targeted interventions to reduce substance use, prevent sleep disturbance, and promote healthy sleep habits among adolescents.
Dingkun pill alleviates metabolic abnormalities in polycystic ovary syndrome through brown adipose tissue activation
Authors: Gu Mengqing , Cai Han , Deng Weinan , Tang Yedong , Du Shuailin , Wang Peiran , Deng Wenbo , Wang Haibin , Sun Aijun , Kong Shuangbo
Published: August 2023

Background

Traditional Chinese medicine has been used for a long time to treat a variety of gynecological diseases. Among various traditional Chinese medicine, Dingkun Pill (DK) has been used for the treatment of female gynecological diseases. However, DK therapeutic effect on PCOS and the target tissue for its potential effect need to be explored. This study aims to explore the therapeutic effect of DK for PCOS in mice from three aspects: metabolism, endocrine and fertility, and determine whether the brown adipose tissue is the target organ to alleviate the PCOS phenotype.

Methods

PCOS mouse model was constructed by subcutaneous injection of DHEA. The estrous cycle, ovulation, and pregnancy outcome was examined in mice. The level of hormone including the LH, FSH, estrogen and testosterone in the serum were measured by ELISA. Both the glucose sensitivity and insulin sensitivity were determined in mice with different treatment. The histomorphology and lipid contents in the brown adipose tissue were analyzed. RNA-Seq was conducted for the brown adipose tissue and different expression of critical metabolism marker genes was confirmed by real-time PCR.

Results

The data showed that the fertility in PCOS mice with DK treatment was significantly increased, and the metabolic disorder was partially restored. Both the whiten of brown adipose tissue and reduced UCP1 expression induced by DHEA was rescued by the DK. The RNA-Seq data further demonstrated both the DHEA induced downregulation of lipolysis genes and oxidative phosphorylation genes were at least partially rescued by DK in the brown adipose tissue.

Conclusions

DK has therapeutic effect on PCOS in DHEA treated mice and the brown adipose tissue is at least one critical target organ to alleviate the PCOS. This is achieved by not only regulating the lipid mobilization of brown adipose, but also restoring its thermogenic function.
Mitophagy-related long non-coding RNA signature predicts prognosis and drug response in Ovarian Cancer
Authors: Wang Jiao , Zhang Xiaocui , Zheng Fei , Yang Qing , Bi Fangfang
Published: August 2023

Background

Ovarian cancer (OC) is the most malignant tumor with the worst prognosis in female reproductive system. Mitophagy and long non-coding RNAs (lncRNAs) play pivotal roles in tumorigenesis, development, and drug resistance. The effects of mitophagy-related lncRNAs on OC prognosis and therapeutic response remain unelucidated.

Methods

We retrieved OC-related RNA sequence, copy number variation, somatic mutation, and clinicopathological information from The Cancer Genome Atlas database and mitophagy-related gene sets from the Reactome database. Pearson’s correlation analysis was used to distinguish mitophagy-related lncRNAs. A prognostic lncRNA signature was constructed using UniCox, LASSO, and forward stepwise regression analysis. Individuals with a risk score above or below the median were classified as high- or low-risk groups, respectively. The risk model was analyzed using the Kaplan–Meier estimator, receiver operating characteristic curve, decision curve analysis, and Cox regression analysis and validated using an internal dataset. LINC00174 was validated in clinical samples and OC cell lines. We also reviewed reports on the role of LINC00174 in cancer. Subsequently, a nomogram model was constructed. Furthermore, the Genomics of Drug Sensitivity in Cancer database was used to explore the relationship between the risk model and anti-tumor drug sensitivity. Gene set variation analysis was performed to assess potential differences in biological functions between the two groups. Finally, a lncRNA prognostic signature-related competing endogenous RNA (ceRNA) network was constructed.

Results

The prognostic signature showed that patients in the high-risk group had a poorer prognosis. The nomogram exhibited satisfactory accuracy and predictive potential. LINC00174 mainly acts as an oncogene in cancer and is upregulated in OC; its knockdown inhibited the proliferation and migration, and promoted apoptosis of OC cells. High-risk patients were more insensitive to cisplatin and olaparib than low-risk patients. The ceRNA network may help explore the potential regulatory mechanisms of lncRNAs.

Conclusion

The mitophagy-related lncRNA signature can help estimate the survival and drug sensitivity, the ceRNA network may provide novel therapeutic targets for patients with OC.
Neuropsychological outcome after cardiac arrest: results from a sub-study of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial
Authors: Blennow Nordström Erik , Vestberg Susanna , Evald Lars , Mion Marco , Segerström Magnus , Ullén Susann , Bro-Jeppesen John , Friberg Hans , Heimburg Katarina , Grejs Anders M. , Keeble Thomas R. , Kirkegaard Hans , Ljung Hanna , Rose Sofia , Wise Matthew P. , Rylander Christian , Undén Johan , Nielsen Niklas , Cronberg Tobias , Lilja Gisela
Published: August 2023

Background

Cognitive impairment is common following out-of-hospital cardiac arrest (OHCA), but the nature of the impairment is poorly understood. Our objective was to describe cognitive impairment in OHCA survivors, with the hypothesis that OHCA survivors would perform significantly worse on neuropsychological tests of cognition than controls with acute myocardial infarction (MI). Another aim was to investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors following OHCA.

Methods

This was a prospective case–control sub-study of The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Eight of 61 TTM2-sites in Sweden, Denmark, and the United Kingdom included adults with OHCA of presumed cardiac or unknown cause. A matched non-arrest control group with acute MI was recruited. At approximately 7 months post-event, we administered an extensive neuropsychological test battery and questionnaires on anxiety, depression, fatigue, and insomnia, and collected information on the cardiovascular risk factors hypertension and diabetes.

Results

Of 184 eligible OHCA survivors, 108 were included, with 92 MI controls enrolled. Amongst OHCA survivors, 29% performed z-score ≤ − 1 (at least borderline–mild impairment) in ≥ 2 cognitive domains, 14% performed z-score ≤ − 2 (major impairment) in ≥ 1 cognitive domain while 54% performed without impairment in any domain. Impairment was most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed significantly worse than MI controls in episodic memory (mean difference, MD = − 0.37, 95% confidence intervals [− 0.61, − 0.12]), verbal (MD = − 0.34 [− 0.62, − 0.07]), and visual/constructive functions (MD = − 0.26 [− 0.47, − 0.04]) on linear regressions adjusted for educational attainment and sex. When additionally adjusting for anxiety, depression, fatigue, insomnia, hypertension, and diabetes, executive functions (MD = − 0.44 [− 0.82, − 0.06]) were also worse following OHCA. Diabetes, symptoms of anxiety, depression, and fatigue were significantly associated with worse cognitive performance.

Conclusions

In our study population, cognitive impairment was generally mild following OHCA. OHCA survivors performed worse than MI controls in 3 of 6 domains. These results support current guidelines that a post-OHCA follow-up service should screen for cognitive impairment, emotional problems, and fatigue.

Trial registration

ClinicalTrials.gov, NCT03543371. Registered 1 June 2018.
Haloperidol for the treatment of delirium in critically ill patients: an updated systematic review with meta-analysis and trial sequential analysis
Authors: Andersen-Ranberg Nina Christine , Barbateskovic Marija , Perner Anders , Oxenbøll Collet Marie , Musaeus Poulsen Lone , van der Jagt Mathieu , Smit Lisa , Wetterslev Jørn , Mathiesen Ole , Maagaard Mathias
Published: August 2023

Background

Haloperidol is frequently used in critically ill patients with delirium, but evidence for its effects has been sparse and inconclusive. By including recent trials, we updated a systematic review assessing effects of haloperidol on mortality and serious adverse events in critically ill patients with delirium.

Methods

This is an updated systematic review with meta-analysis and trial sequential analysis of randomised clinical trials investigating haloperidol versus placebo or any comparator in critically ill patients with delirium. We adhered to the Cochrane handbook, the PRISMA guidelines and the grading of recommendations assessment, development and evaluation statements. The primary outcomes were all-cause mortality and proportion of patients with one or more serious adverse events or reactions (SAEs/SARs). Secondary outcomes were days alive without delirium or coma, delirium severity, cognitive function and health-related quality of life.

Results

We included 11 RCTs with 15 comparisons (n = 2200); five were placebo-controlled. The relative risk for mortality with haloperidol versus placebo was 0.89; 96.7% CI 0.77 to 1.03; I2 = 0% (moderate-certainty evidence) and for proportion of patients experiencing SAEs/SARs 0.94; 96.7% CI 0.81 to 1.10; I2 = 18% (low-certainty evidence). We found no difference in days alive without delirium or coma (moderate-certainty evidence). We found sparse data for other secondary outcomes and other comparators than placebo.

Conclusions

Haloperidol may reduce mortality and likely result in little to no change in the occurrence of SAEs/SARs compared with placebo in critically ill patients with delirium. However, the results were not statistically significant and more trial data are needed to provide higher certainty for the effects of haloperidol in these patients.

Trial registration: CRD42017081133, date of registration 28 November 2017.
The effects of therapeutic virtual reality experience to promote mental well-being in older people living with physical disabilities in long-term care facilities
Authors: Kwan Rick Yiu Cho , Ng Fowie , Lam Linda Chiu Wa , Yung Rebecca Choy , Sin Olive Shuk Kan , Chan Sally
Published: August 2023

Background

Mental well-being is poor in long-term care facilities (LTCF) residents. Physical disabilities, impaired social engagement, and environmental stress are also common in LTCF which exacerbate the decline of the mental well-being of older people living in LTCF. Protective elements, including nature-based, reminiscence, outdoor, and group activities, are known to be effective to promote the mental well-being of older people living in LTCF. However, limited by their physical disabilities and poor social support, older people living in LTCF are not likely to benefit from these effective measures. Virtual reality has been proven to be feasible to be environmentally unrestricted to providing LTCF residents with all protective elements promoting mental well-being. However, its effects on the mental well-being of LTCF residents living with physical disabilities are unclear.

Methods

This study employs a single-blinded, two-parallel-group (intervention-to-control group ratio = 1:1), non-inferiority, randomized controlled trial. Eligible participants are aged 60 years or above, LTCF residents, and living with physical disabilities. The study will be conducted in LTCF. In the intervention group, participants will receive a 6-week VR experience program. In the control group, participants will receive the usual care provided by the LTCF. The primary outcome is mental well-being, as measured by World Health Organization Five Well-being Index at the time point of baseline (i.e., week 0) and after completion of the intervention (i.e., week 7). This study aims to recruit a total of 216 participants. Generalized estimating equations (GEE) will be used to examine the effects of the intervention.

Trial registration

The trial has been registered at ClinicalTrials.gov (Identifier: NCT05818579), Registered on April 5, 2023. The latest version of the protocol was published online on 19 April 2023. All items come from the World Health Organization Trial Registration Data Set. This study has been approved by the Research Ethics Committee of Tung Wah College, Hong Kong (reference number: REC2023158). The findings will be disseminated in peer-reviewed journals, presented at international and local conferences with related themes, and shared in local media.
Clinical manifestation for immunoglobulin A deficiency: a systematic review and meta-analysis
Authors: Vosughimotlagh Ahmad , Rasouli Seyed Erfan , Rafiemanesh Hosein , Safarirad Molood , Sharifinejad Niusha , Madanipour Atossa , Dos Santos Vilela Maria Marluce , Heropolitańska-Pliszka Edyta , Azizi Gholamreza
Published: August 2023

Objectives

Immunoglobulin A deficiency (IgAD) is a common disease with an unknown genetic defect, characterized by the decreased or absent IgA with other isotypes normal, normal subclasses, and specific antibodies. Patients with this disorder represent a spectrum of clinical manifestations including infections, autoimmune disorders, malignancy, and allergic diseases. The current study aimed to evaluate their prevalence and categorized them.

Methods

We searched PubMed, Web of Science, and Scopus databases to find eligible studies from the earliest available date to January 2022 with standard keywords. Pooled estimates of clinical manifestations prevalence and the corresponding 95% confidence intervals were calculated using random-effects models.

Results

The most prevalent clinical manifestations belonged to infection (64.8%) followed by allergic diseases (26.16%) and autoimmunity (22.0%), respectively. In selective IgA deficiency patients as the largest group of IgAD in current study, celiac disease (6.57%), Inflammatory bowel disease (4.01%), and rheumatoid arthritis (3.80%) were the most prevalent autoimmunity. Meanwhile, the most frequent infection was respiratory tract infection, fungal infection, and gastrointestinal infection at 50.74%, 18.48%, and 15.79%, respectively. In addition, the pooled prevalence of asthma, allergic rhinitis, and allergic conjunctivitis were 19.06%, 15.46%, and 11.68%, respectively which were reported as the most widespread allergic diseases.

Conclusions

Our results showed that apart from undiagnosed IgAD patients, IgAD patients represent a wide range of clinical manifestations. Infection, allergy, and autoimmunity are the most common clinical manifestations. The concurrent presence of IgA and IgG subtypes deficiency could be associated with increased susceptibility to infection. Considering the probability of developing new clinical complications during follow-up, periodic assessments of IgAD patients should be inspected.
Energy-efficient virtual machine placement in distributed cloud using NSGA-III algorithm
Authors: Gopu Arunkumar , Thirugnanasambandam Kalaipriyan , R Rajakumar , AlGhamdi Ahmed Saeed , Alshamrani Sultan S. , Maharajan K. , Rashid Mamoon
Published: August 2023

Cloud computing is the most widely adapted computing model to process scientific workloads in remote servers accessed through the internet. In the IaaS cloud, the virtual machine (VM) is the execution unit that processes the user workloads. Virtualization enables the execution of multiple virtual machines (VMs) on a single physical machine (PM). Virtual machine placement (VMP) strategically assigns VMs to suitable physical devices within a data center. From the cloud provider's perspective, the virtual machine must be placed optimally to reduce resource wastage to aid economic revenue and develop green data centres. Cloud providers need an efficient methodology to minimize resource wastage, power consumption, and network transmission delay. This paper uses NSGA-III, a multi-objective evolutionary algorithm, to simultaneously reduce the mentioned objectives to obtain a non-dominated solution. The performance metrics (Overall Nondominated Vector Generation and Spacing) of the proposed NSGA-III algorithm is compared with other multi-objective algorithms, namely VEGA, MOGA, SPEA, and NSGA-II. It is observed that the proposed algorithm performs 7% better that the existing algorithm in terms of ONVG and 12% better results in terms of spacing. ANOVA and DMRT statistical tests are used to cross-validate the results.
Data-intensive workflow scheduling strategy based on deep reinforcement learning in multi-clouds
Authors: Zhang Shuo , Zhao Zhuofeng , Liu Chen , Qin Shenghui
Published: August 2023

With the increase development of Internet of Things devices, the data-intensive workflow has emerged as a new kinds of representation for IoT applications. Because most IoT systems are structured in multi-clouds environment and the data-intensive workflow has the characteristics of scattered data sources and distributed execution requirements at the cloud center and edge clouds, it brings many challenges to the scheduling of such workflow, such as data flow control management, data transmission scheduling, etc. Aiming at the execution constraints of business and technology and data transmission optimization of data-intensive workflow, a data-intensive workflow scheduling method based on deep reinforcement learning in multi-clouds is proposed. First, the execution constraints, edge node load and data transmission volume of IoT data workflow are modeled; then the data-intensive workflow is segmented with the consideration of business constraints and the first optimization goal of data transmission; besides, taking the workflow execution time and average load balancing as the secondary optimization goal, the improved DQN algorithm is used to schedule the workflow. Based on the DQN algorithm, the model reward function and action selection are redesigned and improved. The simulation results based on WorkflowSim show that, compared with MOPSO, NSGA-II, GTBGA and DQN, the algorithm proposed in this paper can effectively reduce the execution time of IoT data workflow under the condition of ensuring the execution constraints and load balancing of multi-clouds.
Anthropogenic activities mediate stratification and stability of microbial communities in freshwater sediments
Authors: Zhou Xiaotian , Lennon Jay T. , Lu Xiang , Ruan Aidong
Published: August 2023

Background

Freshwater sediment microbes are crucial decomposers that play a key role in regulating biogeochemical cycles and greenhouse gas emissions. They often exhibit a highly ordered structure along depth profiles. This stratification not only reflects redox effects but also provides valuable insights into historical transitions, as sediments serve as important archives for tracing environmental history. The Anthropocene, a candidate geological epoch, has recently garnered significant attention. However, the human impact on sediment zonation under the cover of natural redox niches remains poorly understood. Dam construction stands as one of the most far-reaching anthropogenic modifications of aquatic ecosystems. Here we attempted to identify the ecological imprint of damming on freshwater sediment microbiome.

Results

We conducted a year-round survey on the sediment profiles of Lake Chaohu, a large shallow lake in China. Through depth-discrete shotgun metagenomics, metataxonomics, and geophysiochemical analyses, we unveiled a unique prokaryotic hierarchy shaped by the interplay of redox regime and historical damming (labeled by the 137Cs peak in AD 1963). Dam-induced initial differentiation was further amplified by nitrogen and methane metabolism, forming an abrupt transition governing nitrate–methane metabolic interaction and gaseous methane sequestration depth. Using a random forest algorithm, we identified damming-sensitive taxa that possess distinctive metabolic strategies, including energy-saving mechanisms, unique motility behavior, and deep-environment preferences. Moreover, null model analysis showed that damming altered microbial community assembly, from a selection-oriented deterministic process above to a more stochastic, dispersal-limited one below. Temporal investigation unveiled the rapid transition zone as an ecotone, characterized by high species richness, low community stability, and emergent stochasticity. Path analysis revealed the observed emergent stochasticity primarily came from the high metabolic flexibility, which potentially contributed to both ecological and statistical neutralities.

Conclusions

We delineate a picture in which dam-induced modifications in nutrient availability and sedimentation rates impact microbial metabolic activities and generate great changes in the community structure, assembly, and stability of the freshwater sediment microbiome. These findings reflect profound ecological and biogeochemical ramifications of human–Earth system interactions and help re-examine the mainstream views on the formation of sediment microbial stratification.
The endohyphal microbiome: current progress and challenges for scaling down integrative multi-omic microbiome research
Authors: Kelliher Julia M. , Robinson Aaron J. , Longley Reid , Johnson Leah Y. D. , Hanson Buck T. , Morales Demosthenes P. , Cailleau Guillaume , Junier Pilar , Bonito Gregory , Chain Patrick S. G.
Published: August 2023

As microbiome research has progressed, it has become clear that most, if not all, eukaryotic organisms are hosts to microbiomes composed of prokaryotes, other eukaryotes, and viruses. Fungi have only recently been considered holobionts with their own microbiomes, as filamentous fungi have been found to harbor bacteria (including cyanobacteria), mycoviruses, other fungi, and whole algal cells within their hyphae. Constituents of this complex endohyphal microbiome have been interrogated using multi-omic approaches. However, a lack of tools, techniques, and standardization for integrative multi-omics for small-scale microbiomes (e.g., intracellular microbiomes) has limited progress towards investigating and understanding the total diversity of the endohyphal microbiome and its functional impacts on fungal hosts. Understanding microbiome impacts on fungal hosts will advance explorations of how “microbiomes within microbiomes” affect broader microbial community dynamics and ecological functions. Progress to date as well as ongoing challenges of performing integrative multi-omics on the endohyphal microbiome is discussed herein. Addressing the challenges associated with the sample extraction, sample preparation, multi-omic data generation, and multi-omic data analysis and integration will help advance current knowledge of the endohyphal microbiome and provide a road map for shrinking microbiome investigations to smaller scales.
Countering the declining use of lithium therapy: a call to arms
Authors: Malhi Gin S. , Bell Erica , Jadidi Maedeh , Gitlin Michael , Bauer Michael
Published: August 2023

For over half a century, it has been widely known that lithium is the most efficacious treatment for bipolar disorder. Yet, despite this, its prescription has consistently declined over this same period of time. A number of reasons for this apparent disparity between evidence and clinical practice have been proposed, including a lack of confidence amongst clinicians possibly because of an absence of training and lack of familiarity with the molecule. Simultaneously, competition has grown within the pharmacological armamentarium for bipolar disorder with newer treatments promoting an image of being safer and easier to prescribe primarily because of not necessitating plasma monitoring, which understandably is appealing to patients who then exercise their preferences accordingly. However, these somewhat incipient agents are yet to reach the standard lithium has attained in terms of its efficacy in providing prophylaxis against the seemingly inevitable recrudescence of acute episodes that punctuates the course of bipolar disorder. In addition, none of these mimics have the additional benefits of preventing suicide and perhaps providing neuroprotection. Thus, a change in strategy is urgently required, wherein myths regarding the supposed difficulties in prescribing lithium and the gravity of its side-effects are resolutely dispelled. It is this cause to which we have pledged our allegiance and it is to this end that we have penned this article.
Relevance of multilamellar and multicompartmental vesicles in biological fluids: understanding the significance of proportional variations and disease correlation
Authors: Saadeldin Islam M. , Ehab Seif , Cho Jongki
Published: August 2023

Extracellular vesicles (EVs) have garnered significant interest in the field of biomedical science due to their potential applications in therapy and diagnosis. These vesicles participate in cell-to-cell communication and carry a diverse range of bioactive cargo molecules, such as nucleic acids, proteins, and lipids. These cargoes play essential roles in various signaling pathways, including paracrine and endocrine signaling. However, our understanding of the morphological and structural features of EVs is still limited. EVs could be unilamellar or multilamellar or even multicompartmental structures. The relative proportions of these EV subtypes in biological fluids have been associated with various human diseases; however, the mechanism remains unclear. Cryo-electron microscopy (cryo-EM) holds great promise in the field of EV characterization due to high resolution properties. Cryo-EM circumvents artifacts caused by fixation or dehydration, allows for the preservation of native conformation, and eliminates the necessity for staining procedures. In this review, we summarize the role of EVs biogenesis and pathways that might have role on their structure, and the role of cryo-EM in characterization of EVs morphology in different biological samples and integrate new knowledge of the alterations of membranous structures of EVs which could be used as biomarkers to human diseases.
Structuring reconstructions: recognising the advantages of interdisciplinary data in methodical research
Authors: Malcolm-Davies Jane
Published: August 2023

A theoretical framework for reconstruction as an integrated scholarly research method across a range of disciplines is long overdue. This paper discusses the usefulness of reconstructed textiles and dress as a template for it. It also argues that there is a need to integrate methods from the arts and humanities with analytical techniques from the natural sciences. The aim is to show how interdisciplinary research not only enriches a reconstruction but provides the mechanism through which cross-disciplinary collaboration takes place. Experimental remaking of historical textiles and dress has tended to be undertaken on an ad hoc basis. For reconstruction to be scientific, it must systematically employ soundly researched evidence from a variety of sources. The triangulation of data—well established in natural and social science—rigorously cross references primary evidence using a range of investigative methods. It produces a firm fix on the material under scrutiny and more credible results than those reliant on only one or two sources. The challenge is that different types of evidence demand specialist approaches, including quantitative and qualitative methods, which are not the traditional tools of dress history. Accurate reconstruction also demands interdisciplinary collaboration: the interrogation of fibres at the molecular level; the collection of observational data at the micro level; and the study of how garments were made and worn at the macro level. This calls for new ways of working with integrated methodologies in pragmatic multidisciplinary teams, which include experts from the humanities, sciences and craft.
Male sex is an independent risk factor for patellar osteochondral fractures following acute patellar dislocation in pediatric patients
Authors: Retzky Julia S. , Uppstrom Tyler J. , Chipman Danielle E. , Bovonratwet Patawut , Green Daniel W.
Published: August 2023

Purpose

Although most patellar dislocations are associated with medial patellofemoral ligament (MPFL) injury, many patients also sustain concomitant patellar osteochondral fractures following a patellar dislocation. Few prior studies have described or evaluated risk factors for patellar osteochondral fractures in pediatric patients. The purpose of the present study was to describe the incidenceand location of patellar osteochondral fractures following acute patellar dislocation in pediatric patients. In addition, we described risk factors for patellar osteochondral fractures in this population. We hypothesized that most fractures would occur at the inferomedial quadrant of the patella following a traumatic injury mechanism.

Methods

Following Institutional Review Board approval, the electronic medical record was queried to identify pediatric patients ≤ 18 years old who underwent MPFL reconstruction (MPFLR) or non‐operative treatment for patellar instability between July 2016 and February 2020. Osteochondral fractures were defined as full‐thickness chondral injuries with attached subchondral bone or purely osseous injuries measuring ≥ 3 mm (mm) in at least two magnetic resonance imaging (MRI) planes. Patients were included in the study if they had complete preoperative x‐ray and MRI studies with minimum 6‐month follow‐up. Patients were excluded if they had incomplete imaging, isolated chondral fractures, or less than 6 months follow‐up. Univariate analysis was used to identify patient factors associated with osteochondral fractures. Multivariate regression analysis was used to identify risk factors for osteochondral fractures.

Results

Sixty patients (63 knees) were included in the study, 15 (23.8%) of whom had a patellar osteochondral fracture. The majority of osteochondral fractures (87%) involved the inferomedial quadrant of the patella. Univariate analysis showed an association between male sex (p = 0.041), skeletal immaturity (p = 0.028), and decreased patellar tilt (p = 0.021) and patellar osteochondral fractures. Multivariate regression analysis identified male sex as an independent risk factor for osteochondral fractures (relative risk: 4.8, 95% confidence interval [CI]: 1.08–20.9, p = 0.039). No patients had recurrent dislocation at minimum 6‐month follow‐up. All patients with osteochondral fractures returned to sports at most recent follow up.

Conclusion

In this study, 23% of pediatric patients with acute patellar dislocations have a concomitant patellar osteochondral fracture. The majority of patellar osteochondral fractures involve the inferomedial quadrant of the patella. Male sex is an independent risk factor for patellar osteochondral fractures, and skeletal immaturity is associated with patellar osteochondral fractures in this population.

Level of evidence

Level III.
The FLY-project: study protocol for mixed methods research to explore the complex social dynamics of sustainable food-related lifestyles in youth in practical education
Authors: van Etten Soraya , Jansen Lonneke , Bal Michèlle , Dermody Brian J. , Müller Eggo , de Wit John , Stok Marijn
Published: August 2023

Background

The present-day food system is a key driver of climate change and biodiversity loss, making it imperative for populations to shift towards more sustainable diets. The involvement of youth in this transition is vital because they are in a formative period where their identities, values, and norms, including their food behaviours, are being shaped. Special attention should be paid to youth in practical education because they are often overlooked in existing studies, yet evidence suggests they may lack the necessary resources to support dietary changes, resulting in lower levels of pro-environmental food-related behaviours. The aim of the FLY (Food-related Lifestyles in Youth) project is to study how sustainable food-related lifestyles and underlying factors develop in early adolescence, particularly in Dutch youth in practical education, how these spread in social networks, and to develop community-level intervention strategies to support youths’ transition to sustainable food-related behaviours.

Methods/design

The FLY-project adopts a mixed-method approach. First, two literature reviews are conducted. A systematic review assesses how capabilities, opportunities and motivation are associated with sustainable food behaviours in youth, and how these elements interrelate in determining sustainable food-related lifestyles. A scoping review studies community-level interventions that target sustainable and healthy food-related behaviours. Second, focus groups are conducted to explore the barriers and facilitating factors concerning capabilities, opportunities, and motivations that Dutch youth in practical-level education experience to transition to more sustainable food-related lifestyles. Third, a cohort survey study is conducted to track the dynamic interplay between capabilities, opportunities, motivation, and changes in specific sustainable food behaviours over time, and to assess the diffusion of sustainable food-related lifestyles via social (media) networks. Fourth, an experimental research programme tests promising intervention approaches, some of which are co-created with youth, targeting relevant underlying factors.

Discussion

This paper describes the rationale, conceptual framework, design and methods of the FLY-project. The FLY-project contributes to an understanding of underlying factors of sustainable food-related behaviours in adolescence and results in a multi-component intervention toolkit, with a particular focus on youth in practical education programmes.
Usefulness of intraoperative transesophageal echocardiography for hemodynamic management of liver transplantation in a patient with massive polycystic liver disease: a case report
Authors: Ueda Yudai , Kawaji Takahiro , Komura Hidefumi , Hara Yoshitaka , Kuriyama Naohide , Nakamura Tomoyuki , Nishida Osamu
Published: August 2023

Background

Hemodynamic management during anesthesia in liver transplantation for patients with polycystic liver disease (PLD) can be more challenging because of the bleeding and hemodynamic alterations due to the markedly enlarged liver. We hereby report a case of PLD wherein transesophageal echocardiography (TEE) was employed for optimal hemodynamic monitoring during liver transplantation.

Case presentation

A 61-year-old man was scheduled to undergo liver transplantation for massive PLD. Hemodynamic instability was associated with mechanical displacement of the giant cystic liver. TEE results revealed the collapse of the inferior vena cava due to liver displacement. TEE also detected intrathoracic hemorrhage triggered by detachment from the markedly enlarged liver.

Conclusion

TEE is a valuable monitoring tool for sharing information with surgeons and diagnostic modality for finding the source of bleeding in liver transplantation for PLD and may contribute majorly to the quality of perioperative management.