bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of changes in waist circumference, waist-to-height ratio and weight-adjusted-waist index with multimorbidity among older Chinese adults: results from the Chinese longitudinal healthy longevity survey (CLHLS)
Authors: Chen Zi-Ting , Wang Xiao-Meng , Zhong Yi-Shi , Zhong Wen-Fang , Song Wei-Qi , Wu Xian-Bo 
Published: January 2024

Abstract
Background
The association of changes in waist circumference (WC), waist-to-height ratio (WHtR) and weight-adjusted-waist index (WWI) with subsequent risk of multimorbidity remains unclear among older Chinese adults. Therefore, we aimed to assess this association by utilizing data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS).

Methods
Our study was based on the 2011/2012 wave of the CLHLS whose follow-up surveys were conducted in 2014 and 2017/2018. A total of 2900 participants aged 65 and above at baseline were enrolled. WC, WHtR, and WWI were calculated from measured height, weight, and waist circumference. Multimorbidity refers to the coexistence of two or more of 18 chronic diseases. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs) to evaluate the effect of three-year changes in WC, WHtR, and WWI on the risk of multimorbidity.

Results
During a mean follow-up time of 4.2 (2.0) years, 906 multimorbidity cases were identified. Compared to participants in the persistently low WC group, those in the WC gain group and the persistently high WC group had a higher multimorbidity risk with adjusted HRs (95%CI) of 1.23 (1.01–1.50) and 1.34(1.14–1.58), respectively. Participants in the WHtR gain group and the persistently high WHtR group also had higher risks of multimorbidity with HRs (95%CI) of 1.35 (1.08–1.67) and 1.27 (1.05–1.53), respectively, relative to the persistently low WHtR group. Compared to the persistently low WWI group, those in the WWI loss group had a lower risk of multimorbidity with HRs (95%CI) of 0.80 (0.66–0.98). For every standard deviation increase in WC, WHtR, and WWI over three years, the risk of multimorbidity was higher by 12% (95%CI: 1.05–1.19), 13% (95%CI: 1.06–1.20), and 12% (95%CI: 1.05–1.20), respectively.

Conclusions
Associations of changes in WC, WHtR and WWI with multimorbidity are significant among older Chinese adults. The findings highlight the importance of evaluating changes in WC, WHtR, and WWI in screening and prevention of multimorbidity in older adults.
Assessment of the intrasinusidal volume before and after maxillary sinus augmentation using mri – a pilot study of eight patients
Authors: Flick K. , Smeets R. , Gosau M. , Meyer L. , Hanning U. , Kyselyova A. A. , Scheifele C. , Höhmann B. , Henningsen A. 
Published: January 2024

Abstract
Purpose
The purpose of this study was to evaluate the suitability, accuracy, and reliability of a non-invasive 3-Tesla magnetic resonance imaging technique (3 T-MRI) for the visualization of maxillary sinus grafts in comparison to conventional, X-ray-based, established standard imaging techniques.

Methods
A total of eight patients with alveolar bone atrophy who required surgical sinus floor augmentation in the course of dental implantation were included in this pilot study. Alongside pre-operative cone-beam computed tomography (CBCT), 3 T-MRI was performed before and 6 months after sinus floor augmentation. Two investigators measured the maxillary sinus volume preoperatively and after bone augmentation.

Results
In all cases, MRI demonstrated accurately the volumes of the maxillary sinus grafts. Following surgery, the bony structures suitable for an implant placement increased at an average of 4.89 cm3, corresponding with the decrease of the intrasinusidal volumes. In general, interexaminer discrepancies were low and without statistical significance.

Conclusion
In this preliminary study, we could demonstrate the feasibility of MRI bone volume measurement as a radiation-free alternative with comparable accuracy to CT/CBCT before procedures like sinus floor augmentation. Nevertheless, costs and artifacts, also present in MRI, have to be taken into account. Larger studies will be necessary to justify the practicability of MRI bone volume evaluation.
Analysis of five near-complete genome assemblies of the tomato pathogen Cladosporium fulvum uncovers additional accessory chromosomes and structural variations induced by transposable elements effecting the loss of avirulence genes
Authors: Zaccaron Alex Z. , Stergiopoulos Ioannis 
Published: January 2024

Abstract
Background
Fungal plant pathogens have dynamic genomes that allow them to rapidly adapt to adverse conditions and overcome host resistance. One way by which this dynamic genome plasticity is expressed is through effector gene loss, which enables plant pathogens to overcome recognition by cognate resistance genes in the host. However, the exact nature of these loses remains elusive in many fungi. This includes the tomato pathogen Cladosporium fulvum, which is the first fungal plant pathogen from which avirulence (Avr) genes were ever cloned and in which loss of Avr genes is often reported as a means of overcoming recognition by cognate tomato Cf resistance genes. A recent near-complete reference genome assembly of C. fulvum isolate Race 5 revealed a compartmentalized genome architecture and the presence of an accessory chromosome, thereby creating a basis for studying genome plasticity in fungal plant pathogens and its impact on avirulence genes.

Results
Here, we obtained near-complete genome assemblies of four additional C. fulvum isolates. The genome assemblies had similar sizes (66.96 to 67.78 Mb), number of predicted genes (14,895 to 14,981), and estimated completeness (98.8 to 98.9%). Comparative analysis that included the genome of isolate Race 5 revealed high levels of synteny and colinearity, which extended to the density and distribution of repetitive elements and of repeat-induced point (RIP) mutations across homologous chromosomes. Nonetheless, structural variations, likely mediated by transposable elements and effecting the deletion of the avirulence genes Avr4E, Avr5, and Avr9, were also identified. The isolates further shared a core set of 13 chromosomes, but two accessory chromosomes were identified as well. Accessory chromosomes were significantly smaller in size, and one carried pseudogenized copies of two effector genes. Whole-genome alignments further revealed genomic islands of near-zero nucleotide diversity interspersed with islands of high nucleotide diversity that co-localized with repeat-rich regions. These regions were likely generated by RIP, which generally asymmetrically affected the genome of C. fulvum.

Conclusions
Our results reveal new evolutionary aspects of the C. fulvum genome and provide new insights on the importance of genomic structural variations in overcoming host resistance in fungal plant pathogens.
The experience of albinism in France: a qualitative study on dyads of parents and their adult child with albinism
Authors: Fournier Hugo , Hasdenteufel Marie , Garrouteigt Constance , Perie Mathieu , Gliksohn Antoine , Jouanne Béatrice , Hadj-Rabia Smail , Arveiler Benoit , Morice-Picard Fanny , Quintard Bruno 
Published: January 2024

AbstractBackgroundTo date, almost no research on the psychosocial implications of albinism has been conducted in France and an exploration of albinism-related experiences could be beneficial, in order to better understand this condition. The aim of this study was to examine how French people with albinism and their parents live with and adapt to this condition in all the areas of their lives.MethodsSemi-structured phone interviews were conducted with 9 parent-child dyads, each participating separately. Participants were recruited by convenience sampling, thanks to the combined efforts of a patient association (Genespoir) and professionals from the partner medical referral centers involved in the project. Dyads in which the individual with albinism had any comorbidity were excluded. The interviews were then transcribed and subjected to in-depth thematic analysis. Two codebooks were constructed in a mirrored process: one for people with albinism; the other for their parents. They were finally merged at the end of the coding step.ResultsFour main categories were identified: personal perceptions and social representations of albinism, difficulties and obstacles encountered by people with albinism, resources and facilitators, and the importance of parent-child functioning. The results indicated that experiences of stigmatization during childhood and adolescence are common and that people with albinism face challenges in adapting to certain obstacles related to their visual impairments (VI) (e.g., inability to drive a car; eye strain...). Parents emerged as one, if not as the main, source of support for people with albinism throughout their development. Although external support systems exist to assist them in various aspects of their lives, some of them primarily rely on their own personal resources to cope.ConclusionsThis research highlights the importance of a systemic and transdisciplinary approach to make sure families receive the support that best meets their needs.
FastKnock: an efficient next-generation approach to identify all knockout strategies for strain optimization
Authors: Hassani Leila , Moosavi Mohammad R. , Setoodeh Payam , Zare Habil 
Published: January 2024

AbstractOverproduction of desired native or nonnative biochemical(s) in (micro)organisms can be achieved through metabolic engineering. Appropriate rewiring of cell metabolism is performed by making rational changes such as insertion, up-/down-regulation and knockout of genes and consequently metabolic reactions. Finding appropriate targets (including proper sets of reactions to be knocked out) for metabolic engineering to design optimal production strains has been the goal of a number of computational algorithms. We developed FastKnock, an efficient next-generation algorithm for identifying all possible knockout strategies (with a predefined maximum number of reaction deletions) for the growth-coupled overproduction of biochemical(s) of interest. We achieve this by developing a special depth-first traversal algorithm that allows us to prune the search space significantly. This leads to a drastic reduction in execution time. We evaluate the performance of the FastKnock algorithm using various Escherichia coli genome-scale metabolic models in different conditions (minimal and rich mediums) for the overproduction of a number of desired metabolites. FastKnock efficiently prunes the search space to less than 0.2% for quadruple- and 0.02% for quintuple-reaction knockouts. Compared to the classic approaches such as OptKnock and the state-of-the-art techniques such as MCSEnumerator methods, FastKnock found many more beneficial and important practical solutions. The availability of all the solutions provides the opportunity to further characterize, rank and select the most appropriate intervention strategy based on any desired evaluation index. Our implementation of the FastKnock method in Python is publicly available at https://github.com/leilahsn/FastKnock.
Genome-wide screen identifies new set of genes for improved heterologous laccase expression in Saccharomyces cerevisiae
Authors: Strawn Garrett , Wong Ryan W K , Young Barry P , Davey Michael , Nislow Corey , Conibear Elizabeth , Loewen Christopher J R , Mayor Thibault 
Published: January 2024

AbstractThe yeast Saccharomyces cerevisiae is widely used as a host cell for recombinant protein production due to its fast growth, cost-effective culturing, and ability to secrete large and complex proteins. However, one major drawback is the relatively low yield of produced proteins compared to other host systems. To address this issue, we developed an overlay assay to screen the yeast knockout collection and identify mutants that enhance recombinant protein production, specifically focusing on the secretion of the Trametes trogii fungal laccase enzyme. Gene ontology analysis of these mutants revealed an enrichment of processes including vacuolar targeting, vesicle trafficking, proteolysis, and glycolipid metabolism. We confirmed that a significant portion of these mutants also showed increased activity of the secreted laccase when grown in liquid culture. Notably, we found that the combination of deletions of OCA6, a tyrosine phosphatase gene, along with PMT1 or PMT2, two genes encoding ER membrane protein-O-mannosyltransferases involved in ER quality control, and SKI3, which encode for a component of the SKI complex responsible for mRNA degradation, further increased secreted laccase activity. Conversely, we also identified over 200 gene deletions that resulted in decreased secreted laccase activity, including many genes that encode for mitochondrial proteins and components of the ER-associated degradation pathway. Intriguingly, the deletion of the ER DNAJ co-chaperone gene SCJ1 led to almost no secreted laccase activity. When we expressed SCJ1 from a low-copy plasmid, laccase secretion was restored. However, overexpression of SCJ1 had a detrimental effect, indicating that precise dosing of key chaperone proteins is crucial for optimal recombinant protein expression. This study offers potential strategies for enhancing the overall yield of recombinant proteins and provides new avenues for further research in optimizing protein production systems.
PRDX6-iPLA2 aggravates neuroinflammation after ischemic stroke via regulating astrocytes-induced M1 microglia
Authors: Peng Li , Ji Yanyan , Li Yixin , You Yan , Zhou Yang 
Published: January 2024

AbstractThe crosstalk between astrocytes and microglia plays a pivotal role in neuroinflammation following ischemic stroke, and phenotypic distribution of these cells can change with the progression of ischemic stroke. Peroxiredoxin (PRDX) 6 phospholipase A2 (iPLA2) activity is involved in the generation of reactive oxygen species(ROS), with ROS driving the activation of microglia and astrocytes; however, its exact function remains unexplored. MJ33, PRDX6D140Amutation was used to block PRDX6-iPLA2 activity in vitro and vivo after ischemic stroke. PRDX6T177Amutation was used to block the phosphorylation of PRDX6 in CTX-TNA2 cell lines. NAC, GSK2795039, Mdivi-1, U0126, and SB202190 were used to block the activity of ROS, NOX2, mitochondrial fission, ERK, and P38, respectively, in CTX-TNA2 cells. In ischemic stroke, PRDX6 is mainly expressed in astrocytes and PRDX6-iPLA2 is involved in the activation of astrocytes and microglia. In co-culture system, Asp140 mutation in PRDX6 of CTX-TNA2 inhibited the polarization of microglia, reduced the production of ROS, suppressed NOX2 activation, and inhibited the Drp1-dependent mitochondrial fission following OGD/R. These effects were further strengthened by the inhibition of ROS production. In subsequent experiments, U0126 and SB202190 inhibited the phosphorylation of PRDX6 at Thr177 and reduced PRDX6-iPLA2 activity. These results suggest that PRDX6-iPLA2 plays an important role in the astrocyte-induced generation of ROS and activation of microglia, which are regulated by the activation of Nox2 and Drp1-dependent mitochondrial fission pathways. Additionally, PRDX6-iPLA2 activity is regulated by MAPKs via the phosphorylation of PRDX6 at Thr177 in astrocytes.
Severe COVID-19 and chronic kidney disease: bidirectional mendelian randomization study
Authors: Lin Haishan , Cao Bangwei 
Published: January 2024

AbstractTraditional observational research has revealed an association between severe COVID-19 and chronic kidney disease (CKD). It is unclear whether there is a causative connection between them. Our goal was to determine whether genetically predicted CKD is associated with the risk of critical COVID-19. We aimed to investigate potential underlying genetic mechanisms that could explain this relationship, paving the way for personalized risk assessment and targeted interventions to mitigate the effects of COVID-19 on individuals with CKD. Using combined data from a GWAS on European ancestry and CKD (n = 117,165) and critical COVID-19 (n = 1,059,456), bidirectional Mendelian randomization analysis was performed. Four single nucleotide polymorphisms (SNPs) were chosen from the genome as CKD instrumental variables (IVs). In addition to MR‒Egger regression, weighted mode approaches, and weighted medians, we employed the inverse-variance weighted estimate as our primary analytical method. A significant association of CKD with critical COVID-19 (OR = 1.28, 95% confidence interval [CI]: 1.04–1.58, p = 0.01811) was found. However, using 6 genome-wide significant SNPs as IVs for critical COVID‐19, we could not discover a meaningful correlation between severe COVID‐19 and CKD (OR = 1.03, 95% CI: 0.96–1.10, p = 0.3947). We found evidence to support a causal relationship between CKD and severe COVID-19 in European population. This underscores the need for comprehensive monitoring and specialized care strategies for individuals with CKD to mitigate the heightened risk and severity of COVID-19 complications.
Aseptic loosening around total joint replacement in humans is regulated by miR-1246 and miR-6089 via the Wnt signalling pathway
Authors: Deng Yi , Phillips Kate , Feng Zhi-Ping , Smith Paul N. , Li Rachel W. 
Published: January 2024

Abstract
Background
Total joint replacement for osteoarthritis is one of the most successful surgical procedures in modern medicine. However, aseptic loosening continues to be a leading cause of revision arthroplasty. The diagnosis of aseptic loosening remains a challenge as patients are often asymptomatic until the late stages. MicroRNA (miRNA) has been demonstrated to be a useful diagnostic tool and has been successfully used in the diagnosis of other diseases. We aimed to identify differentially expressed miRNA in the plasma of patients with aseptic loosening.

Methods
Adult patients undergoing revision arthroplasty for aseptic loosening and age- and gender-matched controls were recruited. Samples of bone, tissue and blood were collected, and RNA sequencing was performed in 24 patients with aseptic loosening and 26 controls. Differentially expressed miRNA in plasma was matched to differentially expressed mRNA in periprosthetic bone and tissue. Western blot was used to validate protein expression.

Results
Seven miRNA was differentially expressed in the plasma of patients with osteolysis (logFC >|2|, adj-P < 0.05). Three thousand six hundred and eighty mRNA genes in bone and 427 mRNA genes in tissue samples of osteolysis patients were differentially expressed (logFC >|2|, adj-P < 0.05). Gene enrichment analysis and pathway analysis revealed two miRNA (miR-1246 and miR-6089) had multiple gene targets in the Wnt signalling pathway in the local bone and tissues which regulate bone metabolism.

Conclusion
These results suggest that aseptic loosening may be regulated by miR-1246 and miR-6089 via the Wnt signalling pathway.
Gromwell ameliorates glucocorticoid-induced muscle atrophy through the regulation of Akt/mTOR pathway
Authors: Yoo Ahyoung , Kim Jung-In , Lee Hyunjung , Nirmala Farida S. , Hahm Jeong-Hoon , Seo Hyo Deok , Jung Chang Hwa , Ha Tae Youl , Ahn Jiyun 
Published: January 2024

Abstract
Background
Muscle atrophy is characterized by decreased muscle mass, function, and strength. Synthetic glucocorticoids, including dexamethasone (Dexa), are commonly used to treat autoimmune diseases. However, prolonged exposure of Dexa with high dose exerts severe side effects, including muscle atrophy. The purpose of this study was to investigate whether Gromwell root extract (GW) can prevent Dexa-induced muscle atrophy in C2C12 cells and mice and to characterize the composition of GW to identify bioactive compounds.

Methods
For in vitro experiments, GW (0.5 and 1 µg/mL) or lithospermic acid (LA, 5 and 10 µM) was added to C2C12 myotubes on day 4 of differentiation and incubated for 24 h, along with 50 µM Dexa. For in vivo experiment, four-week-old male C57BL/6 mice were randomly divided into the four following groups (n = 7/group): Con group, Dexa group, GW0.1 group, and GW0.2 group. Mice were fed experimental diets of AIN-93 M with or without 0.1 or 0.2% GW for 4 weeks. Subsequently, muscle atrophy was induced by administering an intraperitoneal injection of Dexa at a dose of 15 mg/kg/day for 38 days, in conjunction with dietary intake.

Results
In Dexa-induced myotube atrophy, treatment with GW increased myotube diameter, reduced the expression of muscle atrophy markers, and enhanced the expression of myosin heavy chain (MHC) isoforms in C2C12 cells. Supplementation with the GW improved muscle function and performance in mice with Dexa-induced muscle atrophy, evidenced in the grip strength and running tests. The GW group showed increased lean body mass, skeletal muscle mass, size, and myosin heavy chain isoform expression, along with reduced skeletal muscle atrophy markers in Dexa-injected mice. Supplementation with GW increased protein synthesis and decreased protein degradation through the Akt/mammalian target of rapamycin and glucocorticoid receptor/forkhead box O3 signaling pathways, respectively. We identified LA as a potential bioactive component of the GW. LA treatment increased myotube diameter and decreased the expression of muscle atrophy markers in Dexa-induced C2C12 cells.

Conclusions
These findings underscore the potential of the GW in preventing Dexa-induced skeletal muscle atrophy and highlight the contribution of LA to its effects.