bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of incision healing status after transverse uterine fundal incision for cesarean delivery and postoperative pregnancy: a ten-year single-center retrospective study
Authors: Kotsuji Fumikazu , Shibata Takashi , Nakago Satoshi , Kato Hiroki , Hosono Sayoko , Fukuoka Yasunori , Nishijima Koji
Published: April 2024

Background

Transverse uterine fundal incision (TUFI) is a beneficial procedure for mothers and babies at risk due to placenta previa-accreta, and has been implemented worldwide. However, the risk of uterine rupture during a subsequent pregnancy remains unclear. We therefore evaluated the TUFI wound scar to determine the approval criteria for pregnancy after this surgery.

Methods

Between April 2012 and August 2022, we performed TUFI on 150 women. Among 132 of the 150 women whose uteruses were preserved after TUFI, 84 women wished to conceive again. The wound healing status, scar thickness, and resumption of blood flow were evaluated in these women by magnetic resonance imaging (MRI) and sonohysterogram at 12 months postoperatively. Furthermore, TUFI scars were directly observed during the Cesarean sections in women who subsequently conceived.

Results

Twelve women were lost to follow-up and one conceived before the evaluation, therefore 71 cases were analyzed. MRI scans revealed that the “scar thickness”, the thinnest part of the scar compared with the normal surrounding area, was ≥ 50% in all cases. The TUFI scars were enhanced in dynamic contrast-enhanced MRI except for four women. However, the scar thickness in these four patients was greater than 80%. Twenty-three of the 71 women conceived after TUFI and delivered live babies without notable problems until August 2022. Their MRI scans before pregnancy revealed scar thicknesses of 50–69% in two cases and ≥ 70% in the remaining 21 cases. And resumption of blood flow was confirmed in all patients except two cases whose scar thickness ≥ 90%. No evidence of scar healing failure was detected at subsequent Cesarean sections, but partial thinning was found in two patients whose scar thicknesses were 50–69%. In one woman who conceived seven months after TUFI and before the evaluation, uterine rupture occurred at 26 weeks of gestation.

Conclusions

Certain criteria, including an appropriate suture method, delayed conception for at least 12 months, evaluation of the TUFI scar at 12 months postoperatively, and cautious postoperative management, must all be met in order to approve a post-TUFI pregnancy. Possible scar condition criteria for permitting a subsequent pregnancy could include the scar thickness being ≥ 70% of the surrounding area on MRI scans, at least partially resumed blood flow, and no abnormalities on the sonohysterogram.

Trial registration

Retrospectively registered.
Associations between cardiovascular diseases and cancer mortality: insights from a retrospective cohort analysis of NHANES data
Authors: Ge Chenliang , Jiang Zhiyuan , Long Binghua , Lu Qingjian , He Yan
Published: April 2024

Background

This study explored the association of cardiovascular disease (CVD) with cancer mortality risk in individuals with or without a history of cancer, to better understand the interplay between CVD and cancer outcomes.

Methods

Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018, a retrospective cohort analysis was conducted. This analysis accounted for the survey’s complex design to ensure national representativeness. The association of CVD with cancer mortality was assessed through multivariable Cox proportional hazards models.

Results

The present study included 59,653 participants, of whom 54,095 did not have cancer and 5558 had a history of cancer. In individuals without cancer, heart failure (HF) was associated with an increased risk of mortality from cancer (HR, 1.36; 95% CI, 1.09–1.69; P = 0.005). In participants with cancer, HF correlated with a higher risk of mortality from cancer (HR, 1.76; 95% CI, 1.32–2.34; P < 0.001). Diabetes (DM), hypertension (HBP) and coronary heart disease (CHD) were not significantly associated with an increased risk of mortality from cancer. Significant differences were observed in the interaction between cancer and CHD (HR, 0.68; 95% CI, 0.53–0.87; P = 0.002). For cancer and HBP, a similar trend was noted (HR, 0.75; 95% CI, 0.62–0.91; P = 0.003). No significant differences were found in interactions between HF, DM and cancer.

Conclusions

HF was associated with an increased risk of mortality from cancer, regardless of cancer history, while HBP, CHD and DM showed no significant association. These findings underscore the importance of understanding the mechanisms behind the increased risk of cancer mortality following HF.
Latent tuberculosis infection and infection-associated risk factors for miner workers with silicosis in eastern China
Authors: Hu Xinsong , Chen Cheng , Gao Qianqian , Zhou Lang , Shao Yan , Li Guoli , Song Honghuan , Liu Qiao , Han Lei , Zhu Limei
Published: April 2024

Objectives

Silicosis people are at high risk of developing pulmonary tuberculosis. Whether silica exposure increases the likelihood of latent tuberculosis infection (LTBI) was not well understood, and potential factors involved in LTBI risk among silicosis people were not evaluated before. Thus, LTBI among silicosis people and potential risk factors for LTBI among silicosis people were evaluated in this study.

Methods

A cross-sectional study was undertaken for 130 miner workers with silicosis. The QFT-GIT was performed for LTBI detection.

Results

The LTBI was high to 31.6% (36/114) for silicosis participants, and 13.1% (13/99) had a history of tuberculosis. Drinking was associated with LTBI risk (OR = 6.92, 95%CI, 1.47–32.66, P = 0.015). Meanwhile, tunneling work was associated with an increased risk of LTBI compared with other mining occupations (OR = 3.91,95%CI,1.20–12.70, P = 0.024).

Conclusions

The LTBI rate of silicosis participants was high and more than 10% had a history of tuberculosis. Drinking alcohol and tunneling were independent risk factors for LTBI in silicosis participants.
A new dressing system for accelerating wound recovery after primary total knee arthroplasty: a feasibility study
Authors: Lei Pengfei , Gao Fawei , Qi Jun , Li Zhigang , Zhong Da , Su Shilong
Published: April 2024

Purpose

Currently, postoperative wound infection and poor healing of total knee arthroplasty have been perplexing both doctors and patients. We hereby innovatively invented a new dressing system to reduce the incidence of postoperative wound complications.

Methods

We enrolled 100 patients who received primary unilateral total knee arthroplasty and then applied the new dressing system. The data collected included the number of dressing changes, postoperative hospital stay, Visual Analogue Scale score (VAS), the Knee Society Score (KSS), the Knee Injury and Osteoarthritis Outcome Score (KOOS), ASEPSIS scores, The Stony Brook Scar Evaluation Scale (SBSES), wound complications, dressing cost, the frequency of shower and satisfaction. Subsequently, a statistical analysis of the data was performed.

Results

Our findings demonstrated the average number of postoperative dressing changes was 1.09 ± 0.38, and the average postoperative hospital stay was 3.72 ± 0.98 days. The average cost throughout a treatment cycle was 68.97 ± 12.54 US dollars. Collectively, the results of VAS, KSS, and KOOS revealed that the pain and function of patients were continuously improved. The results of the four indexes of the ASEPSIS score were 0, whereas the SBSES score was 3.58 ± 0.52 and 4.69 ± 0.46 at two weeks and one month after the operation, respectively. We observed no wound complications until one month after the operation. Remarkably, the satisfaction rate of the patients was 91.85 ± 4.99% one month after the operation.

Conclusion

In this study, we invented a new dressing system for surgical wounds after total knee arthroplasty and further confirmed its clinical feasibility and safety.

Chinese clinical trial registry

ChiCTR2000033814, Registered 13/ June/2020.
Biomechanical behavior of implant retained prostheses in the posterior maxilla using different materials: a finite element study
Authors: Aboelfadl Ahmad , Keilig Ludger , Ebeid Kamal , Ahmed Mohamed Abdel Moniem , Nouh Ingy , Refaie Ashraf , Bourauel Christoph
Published: April 2024

Background

The aim of this study is to evaluate the biomechanical behavior of the mesial and distal off-axial extensions of implant-retained prostheses in the posterior maxilla with different prosthetic materials using finite element analysis (FEA).

Methods

Three dimensional (3D) finite element models with three implant configurations and prosthetic designs (fixed-fixed, mesial cantilever, and distal cantilever) were designed and modelled depending upon cone beam computed tomography (CBCT) images of an intact maxilla of an anonymous patient. Implant prostheses with two materials; Monolithic zirconia (Zr) and polyetherketoneketone (PEKK) were also modeled .The 3D modeling software Mimics Innovation Suite (Mimics 14.0 / 3-matic 7.01; Materialise, Leuven, Belgium) was used. All the models were imported into the FE package Marc/Mentat (ver. 2015; MSC Software, Los Angeles, Calif). Then, individual models were subjected to separate axial loads of 300 N. Von mises stress values were computed for the prostheses, implants, and bone under axial loading.

Results

The highest von Mises stresses in implant (111.6 MPa) and bone (100.0 MPa) were recorded in distal cantilever model with PEKK material, while the lowest values in implant (48.9 MPa) and bone (19.6 MPa) were displayed in fixed fixed model with zirconia material. The distal cantilever model with zirconia material yielded the most elevated levels of von Mises stresses within the prosthesis (105 MPa), while the least stresses in prosthesis (35.4 MPa) were recorded in fixed fixed models with PEKK material.

Conclusions

In the light of this study, the combination of fixed fixed implant prosthesis without cantilever using a rigid zirconia material exhibits better biomechanical behavior and stress distribution around bone and implants. As a prosthetic material, low elastic modulus PEKK transmitted more stress to implants and surrounding bone especially with distal cantilever.
Construction and application of the core competence course training system for infectious disease specialist nurses
Authors: Wu Chao , Zhang Hongli , Lin Yawei , Yuan Weiyun , He Jing , Li Lu , Jiang Donglei , Ji Zhaohua , Lang Hongjuan
Published: April 2024

Objectives

This study aims to construct and apply a training course system which was scientific and comprehensive to foster the core competence of infectious disease specialist nurses.

Design

A two-round Delphi consultation survey was carried out to collect feedback from experts on constructing the training course system of core competence for infectious disease specialist nurses. Besides, a non-randomized controlled experimental study was adopted to check the application effect of the courses.

Methods

This study adopted a series of methods including group discussion, theoretical analysis and Delphi consultation to draft the training course content of core competence of infectious disease specialist nurses. Twenty-one Chinese experts were invited to participate in the Delphi consultation from November 2021 to December 2021. From October 2022 to January 2023, a total of 105 infectious disease specialist nurses from two training bases were selected by the convenience sampling method, of which the nurses in one training base were the control group and the nurses in the other training base were the observation group. The observation group was trained by the constructed core competence training course. Questionnaire evaluation was used to compare the core competence of infectious disease specialist nurses and the training effect.

Results

The experts, regarded as the authorities on the subject, were highly motivated in this study. Besides, they reached a consensus on the results. The final training course system of core competence for infectious disease specialist nurses focused on 5 competence modules and was composed of 12 categories of courses with 66 classes and corresponding objectives. The core competence scores of the observation group were significantly higher than those in the control group after training (P < 0.05), which proved the training system can effectively enhance the core competence of infectious disease specialist nurses.

Conclusions

The research methods embodied scientific and precise properties. The course system was comprehensive in content and reliable in results. It could serve as a reference for training infectious disease specialist nurses.
Perceived HRM and turnover intentions of elderly care workers: perspective from person-job fit and institutional ownership
Authors: Wu Fang , Chen Wei , Wan Ruyi , Lu Jiatong , Yu Qianqian , Tu Qilei
Published: April 2024

Background

Although the phenomenon of high turnover rate in the elderly care industry has existed for a long time, there are few studies that have constructed frameworks to comprehensively analyze the strength of the effects of various factors on the turnover intention of elderly care workers.. This study analyzed the impact of different types of perceived human resource management practices on elderly care workers’ turnover intentions and whether this relationship is moderated by person-job fit and ownership of elderly care institutions.

Methods

This is a cross-sectional and regional survey study. The study included questionnaire survey data from a total of 305 elderly care workers from 42 elderly care institutions in 21 provinces in China during June to September 2021. Descriptive statistics, Pearson correlation coefficient, multiple regression, and heterogeneity analyses were performed.

Results

Perceived work environment ($$\beta$$
β
=-0.5164, p< 0.01), perceived occupational protection ($$\beta$$
β
=-0.3390, p< 0.01), perceived welfare benefits ($$\beta$$
β
= -0.2620, p< 0.01) and perceived competency training ($$\beta$$
β
= -0.1421, p< 0.1) were all significantly and negatively related to turnover intentions, the quality of perceived work environment has the greatest impact on elderly care workers’ turnover intentions. Under the moderating effects of person-job fit and ownership of elderly care institutions, there existed heterogeneity between perceived human resource management and turnover intentions among elderly care workers. High level of person-job fit and elderly care institutions’ public feature can effectively weaken the negative impact of each type of perceived human resource management on turnover intention among elderly care workers.

Conclusions

The managers of elderly care institutions should optimize the management mechanism, typically pay attention to elderly care workers’ working environment, formulate and improve the professional standards and job requirements for elderly care workers, promote the public welfare value of nursing care services, and strengthen the sense of honor and responsibility of elderly care workers to reduce the turnover rate.
Life expectancy, long-term care demand and dynamic financing mechanism simulation: an empirical study of Zhejiang Pilot, China
Authors: Xu Xueying , Li Yichao , Mi Hong
Published: April 2024

Background

China has piloted Long-Term Care Insurance (LTCI) to address increasing care demand. However, many cities neglected adjusting LTCI premiums since the pilot, risking the long-term sustainability of LTCI. Therefore, using Zhejiang Province as a case, this study simulated mortality-adjusted long-term care demand and the balance of LTCI funds through dynamic financing mechanism under diverse life expectancy and disability scenarios.

Methods

Three-parameter log-quadratic model was used to estimate the mortality from 1990 to 2020. Mortality with predicted interval from 2020 to 2080 was projected by Lee-Carter method extended with rotation. Cohort-component projection model was used to simulate the number of older population with different degrees of disability. Disability data of the older people is sourced from China Health and Retirement Longitudinal Study 2018. The balance of LTCI fund was simulated by dynamic financing actuarial model.

Results

Life expectancy of Zhejiang for male (female) is from 80.46 (84.66) years in 2020 to 89.39 [86.61, 91.74] (91.24 [88.90, 93.25]) years in 2080. The number of long-term care demand with severe disability in Zhejiang demonstrates an increasing trend from 285 [276, 295] thousand in 2023 to 1027 [634, 1657] thousand in 2080 under predicted mean of life expectancy. LTCI fund in Zhejiang will become accumulated surplus from 2024 to 2080 when annual premium growth rate is 5.25% [4.20%, 6.25%] under various disability scenarios, which is much higher than the annual growth of unit cost of long-term care services (2.25%). The accumulated balance of LTCI fund is sensitive with life expectancy.

Conclusions

Dynamic growth of LTCI premium is essential in dealing with current deficit around 2050 and realizing Zhejiang’s LTCI sustainability in the long-run. The importance of dynamic monitoring disability and mortality information is emphasized to respond immediately to the increase of premiums. LTCI should strike a balance between expanding coverage and controlling financing scale. This study provides implications for developing countries to establish or pilot LTCI schemes.
Systemic IL-26 correlates with improved asthma control in children sensitized to dog allergen
Authors: Kovach Melissa A. , Käck Ulrika , Che Karlhans F , Brundin Bettina , Konradsen Jon R. , Lindén Anders
Published: April 2024

Background

Interleukin (IL)-26 is produced by T helper type 17 (Type 17) cells and exerts immunomodulatory plus antimicrobial effects. Previous studies show that local IL-26 concentrations in the airways are higher in patients with uncontrolled than in those with controlled asthma, and that this intriguing cytokine bears biomarker potential. Here, we determined how systemic IL-26 relates to allergen sensitization, asthma severity, and to IL-17 A in children.

Methods

Serum samples were obtained from children with (n = 60) and without (n = 17) sensitization to dog allergen, and IL-26 and IL-17 A protein concentrations were measured using ELISA. Self-reported history, including medication use and validated symptom-based questionnaire scores, was recorded.

Results

The serum concentrations of IL-26 were enhanced in allergen-sensitized subjects and correlated with those of IL-17 A in a positive manner. However, the IL-26 concentrations did not markedly differ between allergen-sensitized subjects with and without asthma, eczema, allergic rhinitis, or a history of food allergy. Notably, IL-26 concentrations correlated with increasing Asthma Control Test (ACT) scores in a positive manner and with inhaled corticosteroid in a negative manner, amongst sensitized subjects with asthma. Moreover, subjects with asthma requiring ≥ 1 course of oral corticosteroids in the preceding 12 months had decreased IL-26 concentrations.

Conclusion

This study forwards evidence that systemic IL-26, just like IL-17 A, is involved in allergen sensitization among children. The association of systemic IL-26 with improved asthma control is compatible with the cellular sources being recruited into the airways in severe asthma, which supports that this kinocidin bears potential as a biomarker and therapeutic target.
Optimizing microbioreactor cultivation strategies for Trichoderma reesei: from batch to fed-batch operations
Authors: Rohr Katja , Gremm Lisa , Geinitz Bertram , Jourdier Etienne , Wiechert Wolfgang , Ben Chaabane Fadhel , Oldiges Marco
Published: April 2024

Background

Filamentous fungi have long been recognized for their exceptional enzyme production capabilities. Among these, Trichoderma reesei has emerged as a key producer of various industrially relevant enzymes and is particularly known for the production of cellulases. Despite the availability of advanced gene editing techniques for T. reesei, the cultivation and characterization of resulting strain libraries remain challenging, necessitating well-defined and controlled conditions with higher throughput. Small-scale cultivation devices are popular for screening bacterial strain libraries. However, their current use for filamentous fungi is limited due to their complex morphology.

Results

This study addresses this research gap through the development of a batch cultivation protocol using a microbioreactor for cellulase-producing T. reesei strains (wild type, RutC30 and RutC30 TR3158) with offline cellulase activity analysis. Additionally, the feasibility of a microscale fed-batch cultivation workflow is explored, crucial for mimicking industrial cellulase production conditions. A batch cultivation protocol was developed and validated using the BioLector microbioreactor, a Round Well Plate, adapted medium and a shaking frequency of 1000 rpm. A strong correlation between scattered light intensity and cell dry weight underscores the reliability of this method in reflecting fungal biomass formation, even in the context of complex fungal morphology. Building on the batch results, a fed-batch strategy was established for T. reesei RutC30. Starting with a glucose concentration of 2.5 g l$$^{-1}$$

-
1

in the batch phase, we introduced a dual-purpose lactose feed to induce cellulase production and prevent carbon catabolite repression. Investigating lactose feeding rates from 0.3 to 0.75 g (l h)$$^{-1}$$

-
1

, the lowest rate of 0.3 g (l h)$$^{-1}$$

-
1

revealed a threefold increase in cellobiohydrolase and a fivefold increase in $$\upbeta$$
β
-glucosidase activity compared to batch processes using the same type and amount of carbon sources.

Conclusion

We successfully established a robust microbioreactor batch cultivation protocol for T. reesei wild type, RutC30 and RutC30 TR3158, overcoming challenges associated with complex fungal morphologies. The study highlights the effectiveness of microbioreactor workflows in optimizing cellulase production with T. reesei, providing a valuable tool for simultaneous assessment of critical bioprocess parameters and facilitating efficient strain screening. The findings underscore the potential of microscale fed-batch strategies for enhancing enzyme production capabilities, revealing insights for future industrial applications in biotechnology.
Unlocking the genome of the non-sourdough Kazachstania humilis MAW1: insights into inhibitory factors and phenotypic properties
Authors: Mielecki Damian , Detman Anna , Aleksandrzak-Piekarczyk Tamara , Widomska Małgorzata , Chojnacka Aleksandra , Stachurska-Skrodzka Anna , Walczak Paulina , Grzesiuk Elżbieta , Sikora Anna
Published: April 2024

Background

Ascomycetous budding yeasts are ubiquitous environmental microorganisms important in food production and medicine. Due to recent intensive genomic research, the taxonomy of yeast is becoming more organized based on the identification of monophyletic taxa. This includes genera important to humans, such as Kazachstania. Until now, Kazachstania humilis (previously Candida humilis) was regarded as a sourdough-specific yeast. In addition, any antibacterial activity has not been associated with this species.

Results

Previously, we isolated a yeast strain that impaired bio-hydrogen production in a dark fermentation bioreactor and inhibited the growth of Gram-positive and Gram-negative bacteria. Here, using next generation sequencing technologies, we sequenced the genome of this strain named K. humilis MAW1. This is the first genome of a K. humilis isolate not originating from a fermented food. We used novel phylogenetic approach employing the 18 S-ITS-D1-D2 region to show the placement of the K. humilis MAW1 among other members of the Kazachstania genus. This strain was examined by global phenotypic profiling, including carbon sources utilized and the influence of stress conditions on growth. Using the well-recognized bacterial model Escherichia coli AB1157, we show that K. humilis MAW1 cultivated in an acidic medium inhibits bacterial growth by the disturbance of cell division, manifested by filament formation. To gain a greater understanding of the inhibitory effect of K. humilis MAW1, we selected 23 yeast proteins with recognized toxic activity against bacteria and used them for Blast searches of the K. humilis MAW1 genome assembly. The resulting panel of genes present in the K. humilis MAW1 genome included those encoding the 1,3-β-glucan glycosidase and the 1,3-β-glucan synthesis inhibitor that might disturb the bacterial cell envelope structures.

Conclusions

We characterized a non-sourdough-derived strain of K. humilis, including its genome sequence and physiological aspects. The MAW1, together with other K. humilis strains, shows the new organization of the mating-type locus. The revealed here pH-dependent ability to inhibit bacterial growth has not been previously recognized in this species. Our study contributes to the building of genome sequence-based classification systems; better understanding of K.humilis as a cell factory in fermentation processes and exploring bacteria-yeast interactions in microbial communities.
Micropeptides: potential treatment strategies for cancer
Authors: Zhou He , Wu Yan , Cai Ji , Zhang Dan , Lan Dongfeng , Dai Xiaofang , Liu Songpo , Song Tao , Wang Xianyao , Kong Qinghong , He Zhixu , Tan Jun , Zhang Jidong
Published: April 2024

Some noncoding RNAs (ncRNAs) carry open reading frames (ORFs) that can be translated into micropeptides, although noncoding RNAs (ncRNAs) have been previously assumed to constitute a class of RNA transcripts without coding capacity. Furthermore, recent studies have revealed that ncRNA-derived micropeptides exhibit regulatory functions in the development of many tumours. Although some of these micropeptides inhibit tumour growth, others promote it. Understanding the role of ncRNA-encoded micropeptides in cancer poses new challenges for cancer research, but also offers promising prospects for cancer therapy. In this review, we summarize the types of ncRNAs that can encode micropeptides, highlighting recent technical developments that have made it easier to research micropeptides, such as ribosome analysis, mass spectrometry, bioinformatics methods, and CRISPR/Cas9. Furthermore, based on the distribution of micropeptides in different subcellular locations, we explain the biological functions of micropeptides in different human cancers and discuss their underestimated potential as diagnostic biomarkers and anticancer therapeutic targets in clinical applications, information that may contribute to the discovery and development of new micropeptide-based tools for early diagnosis and anticancer drug development.
Machine-learning analysis reveals an important role for negative selection in shaping cancer aneuploidy landscapes
Authors: Jubran Juman , Slutsky Rachel , Rozenblum Nir , Rokach Lior , Ben-David Uri , Yeger-Lotem Esti
Published: April 2024

Background

Aneuploidy, an abnormal number of chromosomes within a cell, is a hallmark of cancer. Patterns of aneuploidy differ across cancers, yet are similar in cancers affecting closely related tissues. The selection pressures underlying aneuploidy patterns are not fully understood, hindering our understanding of cancer development and progression.

Results

Here, we apply interpretable machine learning methods to study tissue-selective aneuploidy patterns. We define 20 types of features corresponding to genomic attributes of chromosome-arms, normal tissues, primary tumors, and cancer cell lines (CCLs), and use them to model gains and losses of chromosome arms in 24 cancer types. To reveal the factors that shape the tissue-specific cancer aneuploidy landscapes, we interpret the machine learning models by estimating the relative contribution of each feature to the models. While confirming known drivers of positive selection, our quantitative analysis highlights the importance of negative selection for shaping aneuploidy landscapes. This is exemplified by tumor suppressor gene density being a better predictor of gain patterns than oncogene density, and vice versa for loss patterns. We also identify the importance of tissue-selective features and demonstrate them experimentally, revealingKLF5as an important driver for chr13q gain in colon cancer. Further supporting an important role for negative selection in shaping the aneuploidy landscapes, we find compensation by paralogs to be among the top predictors of chromosome arm loss prevalence and demonstrate this relationship for one paralog interaction. Similar factors shape aneuploidy patterns in human CCLs, demonstrating their relevance for aneuploidy research.

Conclusions

Our quantitative, interpretable machine learning models improve the understanding of the genomic properties that shape cancer aneuploidy landscapes.
Powerful and accurate detection of temporal gene expression patterns from multi-sample multi-stage single-cell transcriptomics data with TDEseq
Authors: Fan Yue , Li Lei , Sun Shiquan
Published: April 2024

We present a non-parametric statistical method called TDEseq that takes full advantage of smoothing splines basis functions to account for the dependence of multiple time points in scRNA-seq studies, and uses hierarchical structure linear additive mixed models to model the correlated cells within an individual. As a result, TDEseq demonstrates powerful performance in identifying four potential temporal expression patterns within a specific cell type. Extensive simulation studies and the analysis of four published scRNA-seq datasets show that TDEseq can produce well-calibrated p-values and up to 20% power gain over the existing methods for detecting temporal gene expression patterns.
Overflow metabolism provides a selective advantage to Escherichia coli in mixed cultures
Authors: Yasir Muhammad , Thomson Nicholas M. , Turner A. Keith , Webber Mark A. , Charles Ian G.
Published: April 2024

Purpose

It has previously been shown that organic acids produced by Escherichia coli suppress the growth of Pseudomonas aeruginosa in co-cultures under conditions of glucose excess, due to overflow metabolism. Inactivation of genes involved in central carbon metabolism favours fermentation of glucose over respiration and therefore increases production of organic acid by-products such as acetate and lactate. We sought to extend and refine the list of genes known to contribute to the metabolic balance between respiration and fermentation, to better understand the role of overflow metabolism in competitive survival of E. coli.

Methods

We confirmed the previous finding that E. coli excludes P. aeruginosa from co-cultures by producing organic acids in the presence of glucose. Using a genome-wide transposon screen we identified E. coli genes that are important for survival in co-cultures with P. aeruginosa, both with and without glucose supplementation.

Results

Central carbon metabolism was the dominant gene function under selection in our experimental conditions, indicating that the observed inhibition is a side-effect of overflow metabolism adopted by E. coli as a response to high glucose concentrations. The presence of a competing species increased the selective pressure for central carbon metabolism genes, with 31 important for growth in the presence of P. aeruginosa and glucose, while only 9 were significant for pure E. coli cultures grown with glucose. In our experiments, each transposon mutant was competed against all others in the pool, suggesting that overflow metabolism provides benefits to individual E. coli cells in addition to competitive inhibition derived from acidification of the growth medium.

Conclusion

Co-culture assays using transposon mutant libraries can provide insight into the selective pressures present in mixed species competition. This work demonstrates central carbon metabolism is the dominant gene function under selection in E. coli for aerobic growth in glucose and a side-effect of this is overflow metabolism which can inhibit growth of bystander species.
Zombie cheminformatics: extraction and conversion of Wiswesser Line Notation (WLN) from chemical documents
Authors: Blakey Michael , Pearman-Kanza Samantha , Frey Jeremy G.
Published: April 2024

Purpose

Wiswesser Line Notation (WLN) is a old line notation for encoding chemical compounds for storage and processing by computers. Whilst the notation itself has long since been surpassed by SMILES and InChI, distribution of WLN during its active years was extensive. In the context of modernising chemical data, we present a comprehensive WLN parser developed using the OpenBabel toolkit, capable of translating WLN strings into various formats supported by the library. Furthermore, we have devised a specialised Finite State Machine l, constructed from the rules of WLN, enabling the recognition and extraction of chemical strings out of large bodies of text. Available open-access WLN data with corresponding SMILES or InChI notation is rare, however ChEMBL, ChemSpider and PubChem all contain WLN records which were used for conversion scoring. Our investigation revealed a notable proportion of inaccuracies within the database entries, and we have taken steps to rectify these errors whenever feasible.

Scientific contribution

Tools for both the extraction and conversion of WLN from chemical documents have been successfully developed. Both the Deterministic Finite Automaton (DFA) and parser handle the majority of WLN rules officially endorsed in the three major WLN manuals, with the parser showing a clear jump in accuracy and chemical coverage over previous submissions. The GitHub repository can be found here: https://github.com/Mblakey/wiswesser.
Mind your prevalence!
Authors: Guesné Sébastien J. J. , Hanser Thierry , Werner Stéphane , Boobier Samuel , Scott Shaylyn
Published: April 2024

Multiple metrics are used when assessing and validating the performance of quantitative structure–activity relationship (QSAR) models. In the case of binary classification, balanced accuracy is a metric to assess the global performance of such models. In contrast to accuracy, balanced accuracy does not depend on the respective prevalence of the two categories in the test set that is used to validate a QSAR classifier. As such, balanced accuracy is used to overcome the effect of imbalanced test sets on the model’s perceived accuracy. Matthews' correlation coefficient (MCC), an alternative global performance metric, is also known to mitigate the imbalance of the test set. However, in contrast to the balanced accuracy, MCC remains dependent on the respective prevalence of the predicted categories. For simplicity, the rest of this work is based on the positive prevalence. The MCC value may be underestimated at high or extremely low positive prevalence. It contributes to more challenging comparisons between experiments using test sets with different positive prevalences and may lead to incorrect interpretations. The concept of balanced metrics beyond balanced accuracy is, to the best of our knowledge, not yet described in the cheminformatic literature. Therefore, after describing the relevant literature, this manuscript will first formally define a confusion matrix, sensitivity and specificity and then present, with synthetic data, the danger of comparing performance metrics under nonconstant prevalence. Second, it will demonstrate that balanced accuracy is the performance metric accuracy calibrated to a test set with a positive prevalence of 50% (i.e., balanced test set). This concept of balanced accuracy will then be extended to the MCC after showing its dependency on the positive prevalence. Applying the same concept to any other performance metric and widening it to the concept of calibrated metrics will then be briefly discussed. We will show that, like balanced accuracy, any balanced performance metric may be expressed as a function of the well-known values of sensitivity and specificity. Finally, a tale of two MCCs will exemplify the use of this concept of balanced MCC versus MCC with four use cases using synthetic data.

Scientific contribution

This work provides a formal, unified framework for understanding prevalence dependence in model validation metrics, deriving balanced metric expressions beyond balanced accuracy, and demonstrating their practical utility for common use cases. In contrast to prior literature, it introduces the derived confusion matrix to express metrics as functions of sensitivity, specificity and prevalence without needing additional coefficients. The manuscript extends the concept of balanced metrics to Matthews' correlation coefficient and other widely used performance indicators, enabling robust comparisons under prevalence shifts.
Effects of yeast culture on in vitro ruminal fermentation and microbial community of high concentrate diet in sheep
Authors: Wang Hongze , Liu Guiqiong , Zhou Aimin , Yang Huiguo , Kang Kun , Ahmed Sohail , Li Biao , Farooq Umar , Hou Fuqing , Wang Chaoli , Bai Xue , Chen Yan , Ding Yi , Jiang Xunping
Published: April 2024

This research aimed to investigate effects of different yeast culture (YC) levels on in vitro fermentation characteristics and bacterial and fungal community under high concentrate diet. A total of 5 groups were included in the experiment: control group without YC (CON), YC1 (0.5% YC proportion of substrate dry matter), YC2 (1%), YC3 (1.5%) and YC4 (2%). After 48 h of fermentation, the incubation fluids and residues were collected to analyze the ruminal fermentation parameters and bacterial and fungal community. Results showed that the ruminal fluid pH of YC2 and YC4 groups was higher (P < 0.05) than that of CON group. Compared with CON group, the microbial protein, propionate and butyrate concentrations and cumulative gas production at 48 h of YC2 group were significantly increased (P < 0.05), whereas an opposite trend of ammonia nitrogen and lactate was observed between two groups. Microbial analysis showed that the Chao1 and Shannon indexes of YC2 group were higher (P < 0.05) than those of CON group. Additionally, YC supplementation significantly decreased (P < 0.05) Succinivibrionaceae_UCG-001, Streptococcus bovis and Neosetophoma relative abundances. An opposite tendency of Aspergillus abundance was found between CON and YC treatments. Compared with CON group, the relative abundances of Prevotella, Succiniclasticum, Butyrivibrio and Megasphaera elsdenii were significantly increased (P < 0.05) in YC2 group, while Apiotrichum and unclassified Clostridiales relative abundances were decreased (P < 0.05). In conclusion, high concentrate substrate supplemented with appropriate YC (1%) can improve ruminal fermentation and regulate bacterial and fungal composition.
Disordered GPR43/NLRP3 expression in peripheral leukocytes of patients with atrial fibrillation is associated with intestinal short chain fatty acids levels
Authors: Fang Chen , Zuo Kun , Liu Zheng , Xu Li , Yang Xinchun
Published: April 2024

Background

Atrial fibrillation (AF) is associated with circulating inflammation. Short-chain fatty acids (SCFAs) derived from gut microbiota (GM) regulate leukocyte function and inhibit the release of inflammatory cytokines, which are partly mediated by the G-protein-coupled receptor 43 (GPR43) signaling. This study aimed to investigate the expression of GPR43/NOD-like receptors family pyrin domain containing 3 (NLRP3) in leukocytes and the interaction with intestinal SCFAs levels in AF patients.

Methods

Expressions of GPR43 and NLRP3 mRNA in peripheral blood leukocytes from 23 AF patients and 25 non-AF controls were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Expressions of leukocyte GPR43 and NLRP3 protein were evaluated by western blot analysis. The levels of plasma IL-1β were measured by enzyme-linked immunosorbent assay (ELISA). The fecal SCFAs levels based on GC/MS metabolome of corresponding 21 controls and 14 AF patients were acquired from our published dataset. To evaluate the expression of NLRP3 and GPR43 and the release of IL-1β, human THP-1 cells were stimulated with or without SCFAs (acetate, propionate, and butyrate), lipopolysaccharide (LPS), and nigericin in vitro, respectively.

Results

Compared to the controls, the mRNA expression in peripheral leukocytes was significantly reduced in AF patients (P = 0.011) coupled with the increase in downstream leukocyte NLRP3 mRNA expression (P = 0.007) and plasma IL-1β levels (P < 0.001), consistent with changes in GPR43 and NLRP3 protein expression. Furthermore, leukocyte GPR43 mRNA levels were positively correlated with fecal GM-derived acetic acid (P = 0.046) and negatively correlated with NLRP3 mRNA expression (P = 0.024). In contrast to the negative correlation between left atrial diameter (LAD) and GPR43 (P = 0.008), LAD was positively correlated with the leukocyte NLRP3 mRNA levels (P = 0.024). Subsequent mediation analysis showed that 68.88% of the total effect of intestinal acetic acid on AF might be mediated by leukocyte GPR43/NLRP3. The constructed GPR43–NLRP3 score might have a predictive potential for AF detection (AUC = 0.81, P < 0.001). Moreover, SCFAs treatment increased GPR43 expression and remarkably reduced LPS/nigericin-induced NLRP3 expression and IL-1β release in human THP-1 cells in vitro.

Conclusions

Disrupted interactions between GPR43 and NLRP3 expression in peripheral blood leukocytes, associated with reduced intestinal GM-derived SCFAs, especially acetic acid, may be involved in AF development and left atrial enlargement by enhancing circulating inflammation.
Asymptotically consistent and computationally efficient modeling of short-ranged molecular interactions between curved slender fibers undergoing large 3D deformations
Authors: Grill Maximilian J. , Wall Wolfgang A. , Meier Christoph
Published: April 2024

This article proposes a novel computational modeling approach for short-ranged molecular interactions between curved slender fibers undergoing large 3D deformations, and gives a detailed overview how it fits into the framework of existing fiber or beam interaction models, either considering microscale molecular or macroscale contact effects. The direct evaluation of a molecular interaction potential between two general bodies in 3D space would require to integrate molecule densities over two 3D volumes, leading to a sixfold integral to be solved numerically. By exploiting the short-range nature of the considered class of interaction potentials as well as the fundamental kinematic assumption of undeformable fiber cross-sections, as typically applied in mechanical beam theories, a recently derived, closed-form analytical solution is applied for the interaction potential between a given section of the first fiber (slave beam) and the entire second fiber (master beam), whose geometry is linearly expanded at the point with smallest distance to the given slave beam section. This novel approach based on a pre-defined section–beam interaction potential (SBIP) requires only one single integration step along the slave beam length to be performed numerically. In addition to significant gains in computational efficiency, the total beam–beam interaction potential resulting from this approach is shown to exhibit an asymptotically consistent angular and distance scaling behavior. Critically for the numerical solution scheme, a regularization of the interaction potential in the zero-separation limit as well as the finite element discretization of the interacting fibers, modeled by the geometrically exact beam theory, are presented. In addition to elementary two-fiber systems, carefully chosen to verify accuracy and asymptotic consistence of the proposed SBIP approach, a potential practical application in form of adhesive nanofiber-grafted surfaces is studied. Involving a large number of helicoidal fibers undergoing large 3D deformations, arbitrary mutual fiber orientations as well as frequent local fiber pull-off and snap-into-contact events, this example demonstrates the robustness and computational efficiency of the new approach.
Interactive driving of electrostatic film actuator by proximity motion of human body
Authors: Okuno Akira , Yoshimoto Shunsuke , Yamamoto Akio
Published: April 2024

A built-in capacitive proximity sensing method for a charge-induction electrostatic film actuator is proposed. This actuator consists of two thin sheets that function as a stator and a slider. A stator is an insulating sheet with many strips of electrodes in it, whereas a slider is a dielectric sheet that has slight conductivity on its surface. By applying actuation voltage on stator electrodes, the slider that is placed on the stator is driven by electrostatic force. This research realized the simultaneous actuation and proximity sensing using the same electrodes by integrating a resonance-based capacitance measurement circuit into a driving circuit. The study investigated the impact of having a slider on sensing performance, confirming the feasibility of simultaneous sensing and driving. The implemented system achieved an interactive actuation that changed driving velocity according to the proximity distance of the human hand.
Multiplexing near- and far-field functionalities with high-efficiency bi-channel metasurfaces
Authors: Dai Changhong , Liu Tong , Wang Dongyi , Zhou Lei
Published: April 2024

Propagating waves and surface waves are two distinct types of light-transporting modes, the free control of which are both highly desired in integration photonics. However, previously realized devices are bulky in sizes, inefficient, and/or can only achieve one type of light-manipulation functionality with a single device. Here, we propose a generic approach to design bi-channel meta-devices, constructed by carefully selected meta-atoms possessing reflection phases of both structural-resonance and geometric origins, which can exhibit two distinct light-manipulation functionalities in near-field (NF) and far-field (FF) channels, respectively. After characterizing the scattering properties of basic meta-atoms and briefly stating the theoretical strategy, we design/fabricate three different meta-devices and experimentally characterize their bi-channel wave-control functionalities in the telecom regime. Our experiments show that the first two devices can multiplex the generations of NF and FF optical vortices with different topological charges, while the third one exhibits anomalous surface plasmon polariton focusing in the NF and hologram formation in the FF simultaneously. Our results expand the wave-control functionalities of metasurfaces to all wave-transporting channels, which may inspire many exciting applications in integration optics.
Understanding PI3K/Akt/mTOR signaling in squamous cell carcinoma: mutated PIK3CA as an example
Authors: Zheng Shutao , He Shuo , Liang Yan , Tan Yiyi , Liu Qing , Liu Tao , Lu Xiaomei
Published: April 2024

Compared with those in adenocarcinoma, PIK3CA mutations are more common in squamous cell carcinoma (SCC), which arises from stratified squamous epithelia that are usually exposed to adverse environmental factors. Although hotspot mutations in exons 9 and 20 of PIK3CA, including E542K, E545K, H1047L and H1047R, are frequently encountered in the clinic, their clinicopathological meaning remains to be determined in the context of SCC. Considering that few reviews on PIK3CA mutations in SCC are available in the literature, we undertook this review to shed light on the clinical significance of PIK3CA mutations, mainly regarding the implications and ramifications of PIK3CA mutations in malignant cell behavior, prognosis, relapse or recurrence and chemo- or radioresistance of SCC. It should be noted that only those studies regarding SCC in which PIK3CA was mutated were cherry-picked, which fell within the scope of this review. However, the role of mutated PIK3CA in adenocarcinoma has not been discussed. In addition, mutations occurring in other main members of the PI3K-AKT-mTOR signaling pathway other than PIK3CA were also excluded.