bluuebunny/crossref_metadata_2025 huggingface dataset:
A longitudinal exploration of self-reported TV behaviours as a surrogate for sedentary behaviour in older adults with an intellectual disability from the intellectual disability supplement to the Irish longitudinal study on aging (IDS-TILDA) study
Authors: Lynch Louise , McCarron Mary , McCallion Philip , Burke Eilish
Published: January 2024

This study presents the findings of an investigation into the self-reported TV habits of adults with an intellectual disability, where time watching TV was used as a proxy for sedentary behaviour (SB). Risk factors identified for the general and intellectual disability populations and standard covariates of age, sex, level of intellectual disability, living circumstances and BMI were explored to determine their viability as contributors to increased TV viewing and SB. Missing data was imputed using Multiple Imputation Chained Equation (MICE). Multinomial logistic regression and Chi-squared Automatic Interaction Detector Analysis (CHAID) analyses of risk factors for increased TV viewing were explored and compared. The Systems of Sedentary Behaviour (SOS) framework was used to structure results. Novel risk factors for increased TV viewing were identified.
Evaluation method for embedment stiffness of metal washers in bolted timber joints using torque gradient and nut factor
Authors: Matsubara Doppo , Teranishi Masaki , Mori Takuro
Published: January 2024

Assessing the residual performance of timber joints affected by decay is important for seismic diagnosis and reinforcement of timber structures. This study introduces a method to evaluate the embedment stiffness of metal washers in bolted timber joints using a torque wrench. Formulas for the embedment stiffness of metal washers using the torque gradient (the gradient of the tightening torque against the tightening rotation angle of the nut) and the nut factor are presented and the calculated values are compared with experimental values obtained by conducting tightening tests with a torque wrench and embedment tests of metal washers in bolted joints made from Japanese cedar, Hiba, and Japanese cypress. The results show that the experimental values of the embedment stiffness of metal washers in Japanese cedar and Hiba are generally within the range of the values calculated from the minimum and maximum values of the nut factor. However, for Japanese cypress, the values calculated from the maximum value of the nut factor exceed the experimental values. This was presumably due to locally large frictional forces generated on the bearing surface or threaded part.
Full-length isoform concatenation sequencing to resolve cancer transcriptome complexity
Authors: Wijeratne Saranga , Gonzalez Maria E. Hernandez , Roach Kelli , Miller Katherine E. , Schieffer Kathleen M. , Fitch James R. , Leonard Jeffrey , White Peter , Kelly Benjamin J. , Cottrell Catherine E. , Mardis Elaine R. , Wilson Richard K. , Miller Anthony R.
Published: January 2024

Background

Cancers exhibit complex transcriptomes with aberrant splicing that induces isoform-level differential expression compared to non-diseased tissues. Transcriptomic profiling using short-read sequencing has utility in providing a cost-effective approach for evaluating isoform expression, although short-read assembly displays limitations in the accurate inference of full-length transcripts. Long-read RNA sequencing (Iso-Seq), using the Pacific Biosciences (PacBio) platform, can overcome such limitations by providing full-length isoform sequence resolution which requires no read assembly and represents native expressed transcripts. A constraint of the Iso-Seq protocol is due to fewer reads output per instrument run, which, as an example, can consequently affect the detection of lowly expressed transcripts. To address these deficiencies, we developed a concatenation workflow, PacBio Full-Length Isoform Concatemer Sequencing (PB_FLIC-Seq), designed to increase the number of unique, sequenced PacBio long-reads thereby improving overall detection of unique isoforms. In addition, we anticipate that the increase in read depth will help improve the detection of moderate to low-level expressed isoforms.

Results

In sequencing a commercial reference (Spike-In RNA Variants; SIRV) with known isoform complexity we demonstrated a 3.4-fold increase in read output per run and improved SIRV recall when using the PB_FLIC-Seq method compared to the same samples processed with the Iso-Seq protocol. We applied this protocol to a translational cancer case, also demonstrating the utility of the PB_FLIC-Seq method for identifying differential full-length isoform expression in a pediatric diffuse midline glioma compared to its adjacent non-malignant tissue. Our data analysis revealed increased expression of extracellular matrix (ECM) genes within the tumor sample, including an isoform of the Secreted Protein Acidic and Cysteine Rich (SPARC) gene that was expressed 11,676-fold higher than in the adjacent non-malignant tissue. Finally, by using the PB_FLIC-Seq method, we detected several cancer-specific novel isoforms.

Conclusion

This work describes a concatenation-based methodology for increasing the number of sequenced full-length isoform reads on the PacBio platform, yielding improved discovery of expressed isoforms. We applied this workflow to profile the transcriptome of a pediatric diffuse midline glioma and adjacent non-malignant tissue. Our findings of cancer-specific novel isoform expression further highlight the importance of long-read sequencing for characterization of complex tumor transcriptomes.
Potential public health hazards related to consumption of poultry contaminated with antibiotic resistant Listeria monocytogenes in Egypt
Authors: Zakaria Amira Ibrahim , Sabala Rana Fahmi
Published: January 2024

Listeria monocytogenes is an important foodborne pathogen that incorporated into many serious infections in human especially immunocompromised individuals, pregnant women, the elderly, and newborns. The consumption of food contaminated with such bacteria is considered a source of potential risk for consumers. Therefore, a total of 250 poultry purchased in highly popular poultry stores besides 50 swabs from workers hands in the same stores, in Mansoura City had been tested for the L. monocytogenes prevalence, virulence genes, and antibiotic resistance profile illustrating the health hazards from such poultry. The L. monocytogenes were recovered from 9.6% of poultry samples while not detected from workers hand swabs. The antimicrobial susceptibility of 24 L. monocytogenes strains against 24 antibiotics of seven different classes revealed high susceptibility rates to erythromycin (79.17%), streptomycin (66.67%), gentamycin (66.67%), vancomycin (58.33%), chloramphenicol (58.33%) and cefotaxime (41.67%). The majority (79.2%) of L. monocytogenes were classified as multidrug resistant strains with high resistance to tetracyclines and β-lactams antibiotics while 16.7% of the strains were categorized as extensively resistant ones. The iap virulence-specific determination gene had been detected in all recovered L. monocytogenes isolates while 83.33 and 70.83% of the isolates harbored hylA and actA genes. In addition, the study confirmed the capability of most L. monocytogenes isolates for biofilm formation by moderate to strong production and the quantitative risk assessment illustrated the risk of developing listeriosis as the risk value exceeded 100. The current results illustrate that poultry meat can be a source of pathogenic antibiotic resistant strains that may cause infection with limited or no treatment in immunosuppressed consumers via the food chain.
Clinical factors associated with stable treatment of chronic constipation in Japanese patients
Authors: Ishibashi Kazuki , Urabe Yuji , Vu Nhu Thi Hanh , Miyauchi Shunsuke , Nakamura Takeo , Konishi Hirona , Mizuno Junichi , Fukuhara Motomitsu , Takigawa Hidehiko , Yuge Ryo , Quach Duc Trong , Oka Shiro , Hiyama Toru
Published: January 2024

Background/Aims

Chronic constipation (CC) is one of the most common gastrointestinal disorders in the general population. Although there are many treatment options, achieving a stable treatment for CC remains one of the challenges in clinical practice. This study aimed to evaluate the clinical factors associated with stable treatment for CC in Japanese patients.

Methods

A retrospective, cross-sectional, and multicenter study was carried out. Patients were eligible for inclusion if they fulfilled the Rome IV criteria for diagnosing CC and had been treated for at least one and a half years. Patients with up to two prescription modifications for CC in one year were defined as the stable treatment group, whereas those with three or more prescription changes were defined as the unstable treatment group. Univariate and multivariate analyses were carried out to identify factors associated with CC.

Results

A total of 114 patients have been recruited. There were 82 patients (77.0%) in the stable treatment group and 32 patients (23.0%) in the unstable treatment group. Based on multivariate likelihood analysis, only using acid-suppressive drugs contributed to stability treatment in CC patients (odds ratio: 2.81, 95% confidence interval: 1.12–7.08, p = 0.03).

Conclusion

Administration of acid-suppressive drugs was the only factor related to the stability of CC treatment. Further studies are needed to validate the results as well as clarify the causes.
Early encapsulation of peripancreatic fluid/necrosis collections on imaging (CECT) in acute pancreatitis: influential factors and clinical significance for prognosis
Authors: Ning Ning , Yu Congyi , Sun Wenwu , Wen Yi , Ni Tongtian , Sheng Huiqiu , Chen Ying , Ma Li , Chen Erzhen , Zhao Bing , Mao Enqiang
Published: January 2024

Background

To identify the factors influencing the early encapsulation of peripancreatic fluid/necrosis collections via contrast-enhanced computed tomography (CECT) and to determine the clinical significance of early encapsulation for determining the prognosis of acute pancreatitis (AP) patients.

Methods

AP patients who underwent CECT between 4 and 10 days after disease onset were enrolled in this study. Early encapsulation was defined as a continuous enhancing wall around peripancreatic fluid/necrosis collections on CECT. Univariate and multivariate logistic regression analyses were performed to assess the associations between the variables and early encapsulation. Clinical outcomes were compared between the non-encapsulation and early encapsulation groups with 1:1 propensity score matching.

Results

A total of 289 AP patients were enrolled. The intra-observer and inter-observer agreement were considered good (kappa statistics of 0.729 and 0.614, respectively) for identifying early encapsulation on CECT. The ratio of encapsulation increased with time, with a ratio of 12.5% on day 5 to 48.7% on day 9. Multivariate logistic regression analysis revealed that the longer time from onset to CECT examination (OR 1.55, 95% CI 1.23–1.97), high alanine aminotransferase level (OR 0.98, 95% CI 0.97–0.99), and high APACHE II score (OR 0.89, 95% CI 0.81–0.98) were found to be independent factors associated with delayed encapsulation. The incidence of persistent organ failure was significantly lower in the early encapsulation group after matching (22.4% vs 6.1%, p = 0.043). However, there was no difference in the incidence of infected pancreatic necrosis, surgical intervention, or in-hospital mortality.

Conclusions

AP patients without early encapsulation of peripancreatic fluid/necrosis collections have a greater risk of persistent organ failure. In addition to longer time, the high APACHE II score and elevated alanine aminotransferase level are factors associated with delayed encapsulation.
Effects of an integrated ambulatory care program on healthcare utilization and costs in older patients with multimorbidity: a propensity score-matched cohort study
Authors: Lo Yu-Tai , Chen Mei-Hua , Lu Tsung-Hsueh , Yang Ya-Ping , Chang Chia-Ming , Yang Yi-Ching
Published: January 2024

Background

Population aging has increased the prevalence of multimorbidity, jeopardizing the sustainability and efficiency of healthcare systems. This study aimed to evaluate the effects of an integrated ambulatory care program (IACP) on healthcare utilization and costs among older patients with multimorbidity while accounting for the confounding effects of frailty.

Methods

A retrospective cohort study using propensity matching including patients aged 65 or older with two or more chronic conditions attending the outpatient clinic at our hospital between June 1 and December 31, 2019, was conducted. Exposure was defined as receipt of IACP care. Patients not undergoing the IACP comprised the unexposed group and were matched at a ratio of 1:4 to patients undergoing the IACP group according to sex, age, Charlson Comorbidity Index score, multimorbidity frailty index score, and number of outpatient visits within 6 months before the index date. Outcomes were changes in healthcare utilization and related costs between 6 months before and after receiving IACP care. Multivariate regression analyses were used for data analysis and the Generalized Estimation Equation method was used to fit the regression models.

Results

A total of 166 (IACP) and 664 (non-exposed) patients were analyzed. The mean participant baseline ages were 77.15 ± 7.77 (IACP) and 77.28 ± 7.90 years (unexposed). In univariate analyses, the IACP group demonstrated greater reductions than the unexposed group in the frequency of outpatient visits (-3.16 vs. -1.36, p < 0.001), number of physicians visited (-0.99 vs. -0.17, p < 0.001), diagnostic fees (-1300 New Taiwan Dollar [NTD] vs. -520 NTD, p < 0.001), drug prescription fees (-250 NTD vs. -70 NTD, p < 0.001), and examination fees (-1620 NTD vs. -700 NTD, p = 0.014). Multivariate analyses demonstrated that patients in the IACP group experienced significant reduction in the frequency of outpatient visits (95% CI: -0.357 to -0.181, p < 0.001), number of physicians visited (95% CI: -0.334 to -0.199, p < 0.001), and overall outpatient costs (95% CI: -0.082 to -0.011, p = 0.01). However, emergency department utilization, hospitalization, and costs did not differ significantly.

Conclusions

Expanding IACPs may help patients with multimorbidity reduce their use of outpatient clinics at the 6-month follow-up, reduce care fragmentation, and promote sustainability of the healthcare system.
Factors affecting cognitive frailty improvement and progression in Taiwanese older adults
Authors: Suprawesta Lalu , Chen Sy-Jou , Liang Hui-Yu , Hwang Hei-Fen , Yu Wen-Yu , Lin Mau-Roung
Published: January 2024

Background

Knowledge of predictors of cognitive frailty (CF) trajectories is required to develop preventive strategies to delay or reverse the progression from CF to dementia and other adverse outcomes. This 2-year prospective study aimed to investigate factors affecting the progression and improvement of CF in older Taiwanese adults.

Methods

In total, 832 community-dwelling people aged ≥ 65 years were eligible. Fried’s five frailty criteria were used to measure prefrailty and frailty, while cognitive performance was assessed by the Clinical Dementia Rating and Mini-Mental State Examination. Each component of reversible CF and potentially reversible CF was assigned a score, with a total score ranging 0 to 5 points. Two annual follow-up CF assessments were conducted. The group-based trajectory model was applied to identify latent CF trajectory groups, and a multinomial logistic regression was used to examine relationships of explanatory variables with CF trajectories.

Results

According to data on 482 subjects who completed the two annual follow-ups, three CF trajectories of robust, improvement, and progression were identified. After adjusting for the baseline CF state, CF progression was significantly associated with an older age (odds ratio [OR] = 1.08; 95% confidence interval [CI], 1.02 ~ 1.14), a lower Tinetti balance score (OR = 0.72; 95% CI, 0.54 ~ 0.96), a slower gait (OR = 0.98; 95% CI, 0.97 ~ 0.99), and four or more comorbidities (OR = 2.65; 95% CI, 1.19 ~ 5.90), while CF improvement was not significantly associated with any variable except the baseline CF state. In contrast, without adjusting for the baseline CF state, CF progression was significantly associated with an older age, female sex, balance scores, gait velocity, regular exercise, the number of comorbidities, and depression, while CF improvement was significantly associated with female sex, balance scores, and the number of comorbidities.

Conclusions

The baseline CF state, an older age, poorer balance, slower gait, and a high number of comorbidities may contribute to CF progression, while the baseline CF state may account for associations of engaging in regular exercise and depression with CF development.
Prevalence of probable substance use disorders among children in Ugandan health facilities
Authors: Aber-Odonga Harriet , Babirye Juliet Ndimwibo , Engebretsen Ingunn Marie S. , Nuwaha Fred
Published: January 2024

Background

Globally, there is a concerning surge in the prevalence of substance use among adolescents and children, creating a substantial public health problem. Despite the magnitude of this issue, accessing healthcare explicitly for substance use remains challenging, even though many substance users frequently visit healthcare institutions for other health-related issues. To address this gap, proactive screening for substance use disorders has emerged as a critical strategy for identifying and engaging patients at risk of substance use. The purpose of this study was to investigate the prevalence of probable alcohol and other substance use disorders, and associated factors, among children aged 6 to 17 years old attending health facilities in Mbale, Uganda.

Methods

We conducted a health facility cross-sectional study, involving 854 children aged 6–17 years. The prevalence of probable alcohol and other substance use disorders was assessed using a validated Car, Relax, Alone, Forget, Friends, Trouble (CRAFFT) screening tool. Univariable and multivariable modified Poisson regression analyses were performed using STATA 15 software.

Results

The overall prevalence of probable alcohol use disorders (AUD) and other substance use disorders (SUD) was 27.8% (95% CI 1.24–1.31) while that of probable AUD alone was 25.3% (95% CI 1.22–1.28). Peer substance use (APR = 1.24, 95% CI 1.10–1.32), sibling substance use (APR = 1.14, 95% CI 1.06–1.23), catholic caregiver religion (APR = 1.07 95% CI 1.01–1.13), caregiver income of more than $128 (APR = 0.90, 95% CI 0.82–0.98), having no parental reprimand for substance use (APR = 1.05, 95% CI 1.01–1.10) and having no knowledge of how to decline an offer to use substances (APR = 1.06, 95% CI 1.01–1.12) were found to be significantly associated with probable AUD/SUD.

Conclusions

Our findings suggest a high prevalence of probable AUD and SUD among children and adolescents visiting healthcare facilities for other conditions, along with a strong link between AUD and SUD prevalence and social factors. The implication for our healthcare system is to actively screen for and treat these conditions at primary healthcare facilities.
COVID-19 information seeking and individuals’ protective behaviors: examining the role of information sources and information content
Authors: Zhang Xuefeng , Du Lin , Huang Yelin , Luo Xiao , Wang Fenglian
Published: January 2024

Background

Seeking COVID-19 information promotes individuals to adopt preventive behaviors, including wearing a mask, social distancing, staying away from risky places, and washing hands. This study aims to investigate which information and sources individuals relied on in seeking COVID-19 information and further examine their roles in individuals’ adoption of preventive behaviors.

Methods

Through a statistical analysis of 1027 valid responses from citizens in different Chinese cities in 2022 to the self-designed items in an online survey, this study identified individuals’ preferred information sources and content on COVID-19. Regarding the information sources and content, the study used multiple regression analysis to examine their associations with individuals’ preventive behaviors, and further applied fuzzy-set qualitative comparative analysis (fsQCA) to explore their configurations that increase the likelihood of individuals adopting preventive behaviors.

Results

Individuals preferred information about the newest prevention and control policies, precautions and treatment, and symptoms from the sources of workplace and community, social media, and social live streaming services. Additionally, individuals’ preventive behaviors were positively related to the workplace and community (β = 0.202, p <.001), social live streaming services (β = 0.089, p <.01), government department websites (β = 0.079, p <.05), television (β = 0.073, p <.05), and online news media (β = 0.069, p <.05), but were negatively associated with newspapers (β=-0.087, p <.05). Regarding information content, precautions and treatments (β = 0.211, p <.001), the newest prevention and control policies (β = 0.173, p <.001), symptoms (β = 0.152, p <.001), and official rumor-dispelling information (β = 0.082, p <.05) had a positive relationship with individuals’ preventive behaviors. In addition, fsQCA results presented eight configurations that promote individuals to adopt preventive behaviors. The total coverage and solution consistency values were 0.869 and 0.987, respectively. Furthermore, COVID-19 information content, the sources of social media and interpersonal sources, and official news media played an essential role in increasing the likelihood of individuals adopting preventive behaviors.

Conclusions

Our findings demonstrated that individuals seek various COVID-19 information from multiple sources. The direct and degree of association of information sources and content with individuals’ preventive behaviors vary from source to source and from content to content. Information sources and content could combinatorially promote individuals to adopt preventive behaviors through several configurations.
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

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

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

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

Background

To 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.

Methods

Semi-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.

Results

Four 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.

Conclusions

This 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

Overproduction 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

The 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

The 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

Traditional 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

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

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.
Development and prognostic validation of a three-level NHG-like deep learning-based model for histological grading of breast cancer
Authors: Sharma Abhinav , Weitz Philippe , Wang Yinxi , Liu Bojing , Vallon-Christersson Johan , Hartman Johan , Rantalainen Mattias
Published: January 2024

Background

Histological grade is a well-known prognostic factor that is routinely assessed in breast tumours. However, manual assessment of Nottingham Histological Grade (NHG) has high inter-assessor and inter-laboratory variability, causing uncertainty in grade assignments. To address this challenge, we developed and validated a three-level NHG-like deep learning-based histological grade model (predGrade). The primary performance evaluation focuses on prognostic performance.

Methods

This observational study is based on two patient cohorts (SöS-BC-4,N = 2421 (training and internal test); SCAN-B-Lund,N = 1262 (test)) that include routine histological whole-slide images (WSIs) together with patient outcomes. A deep convolutional neural network (CNN) model with an attention mechanism was optimised for the classification of the three-level histological grading (NHG) from haematoxylin and eosin-stained WSIs. The prognostic performance was evaluated by time-to-event analysis of recurrence-free survival and compared to clinical NHG grade assignments in the internal test set as well as in the fully independent external test cohort.

Results

We observed effect sizes (hazard ratio) for grade 3 versus 1, for the conventional NHG method (HR = 2.60 (1.18–5.70 95%CI,p-value = 0.017)) and the deep learning model (HR = 2.27, 95%CI 1.07–4.82,p-value = 0.033) on the internal test set after adjusting for established clinicopathological risk factors. In the external test set, the unadjusted HR for clinical NHG 2 versus 1 was estimated to be 2.59 (p-value = 0.004) and clinical NHG 3 versus 1 was estimated to be 3.58 (p-value < 0.001). For predGrade, the unadjusted HR for predGrade 2 versus 1 HR = 2.52 (p-value = 0.030), and 4.07 (p-value = 0.001) for preGrade 3 versus 1 was observed in the independent external test set. In multivariable analysis, HR estimates for neither clinical NHG nor predGrade were found to be significant (p-value > 0.05). We tested for differences in HR estimates between NHG and predGrade in the independent test set and found no significant difference between the two classification models (p-value > 0.05), confirming similar prognostic performance between conventional NHG and predGrade.

Conclusion

Routine histopathology assessment of NHG has a high degree of inter-assessor variability, motivating the development of model-based decision support to improve reproducibility in histological grading. We found that the proposed model (predGrade) provides a similar prognostic performance as clinical NHG. The results indicate that deep CNN-based models can be applied for breast cancer histological grading.