bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of cell factory through combinatorial metabolic engineering for efficient production of itaconic acid
Authors: Feng Jiao , Li Chunqiu , He Hao , Xu Sheng , Wang Xin , Chen Kequan
Published: December 2022

Background

Itaconic acid, an unsaturated C5 dicarbonic acid, has significant market demand and prospects. It has numerous biological functions, such as anti-cancer, anti-inflammatory, and anti-oxidative in medicine, and is an essential renewable platform chemical in industry. However, the development of industrial itaconic acid production by Aspergillus terreus, the current standard production strain, is hampered by the unavoidable drawbacks of that species. Developing a highly efficient cell factory is essential for the sustainable and green production of itaconic acid.

Results

This study employed combinatorial engineering strategies to construct Escherichia coli cells to produce itaconic acid efficiently. Two essential genes (cis-aconitate decarboxylase (CAD) encoding gene cadA and aconitase (ACO) encoding gene acn) employed various genetic constructs and plasmid combinations to create 12 recombination E. coli strains to be screened. Among them, E. coli BL-CAC exhibited the highest titer with citrate as substrate, and the induction and reaction conditions were further systematically optimized. Subsequently, employing enzyme evolution to optimize rate-limiting enzyme CAD and synthesizing protein scaffolds to co-localize ACO and CAD were used to improve itaconic acid biosynthesis efficiency. Under the optimized reaction conditions combined with the feeding control strategy, itaconic acid titer reached 398.07 mM (51.79 g/L) of engineered E. coli BL-CAR470E-DS/A-CS cells as a catalyst with the highest specific production of 9.42 g/g(DCW) among heterologous hosts at 48 h.

Conclusions

The excellent catalytic performance per unit biomass shows the potential for high-efficiency production of itaconic acid and effective reduction of catalytic cell consumption. This study indicates that it is necessary to continuously explore engineering strategies to develop high-performance cell factories to break through the existing bottleneck and achieve the economical commercial production of itaconic acid.
Achieving optimal heath data impact in rural African healthcare settings: measures to barriers in Bukomansimbi District, Central Uganda
Authors: Miiro Chraish , Ndawula Josephine Caren , Musudo Enoch , Nabuuma Olivia Peace , Mpaata Charles Norman , Nabukenya Shamim , Akaka Alex , Bebembeire Olivia , Sanya Douglas
Published: December 2022

Background

Health data is one of the most valuable assets in health service delivery yet one of the most underutilized in especially low-income countries. Health data is postulated to improve health service delivery through availing avenues for optimal patient management, facility management, and public health surveillance and management. Advancements in information technology (IT) will further increase the value of data, but will also call for capacity readiness especially in rural health facilities.

We aimed to understand the current knowledge, attitudes and practices of health workers towards health data management and utilization.

Methods

We conducted key informant interviews (KII) for health workers and data staff, and focus group discussions (FGD) for the village health teams (VHTs). We used both purposive and convenience sampling to recruit key informants, and convenience sampling to recruit village health teams. Interviews and discussions were audiotaped and transcribed verbatim. We manually generated the codes and we used thematic analysis to identify the themes. We also developed a reflexivity journal.

Results

We conducted a total of 6 key informant interviews and 3 focus group discussions of 29 participants. Our analysis identified 7 themes: One theme underscored the health workers’ enthusiasm towards an optimal health data management setting. The rest of the six themes resonated around working remedies to the systemic challenges that grapple health data management and utilization at facilities in rural areas. These include: Building human resource capacity; Equipping the facilities; Improved coordination with partners; Improved data quality assurance; Promotion of a pull supply system and Reducing information relay time.

Conclusion

Our findings reveal a plethora of systematic challenges that have persistently undercut optimal routine health data management and utilization in rural areas and suggest possible working remedies. Health care workers express enthusiasm towards an optimal health management system but this isn’t matched by their technical capacity, facility readiness, systems and policy willingness. There is an urgent need to build rural lower facilities’ capacity in health data management and utilization which will also lay a foundation for exploitation of information technology in health.
Association between liver fibrosis and thrombotic or bleeding events in acute coronary syndrome patients
Authors: Liu Yupeng , Song Jingjing , Wang Wenyao , Zhang Kuo , Yang Jie , Wen Jun , Meng Xiangbin , Gao Jun , Wang Jingjia , Shao Chunli , Tang Yi-Da
Published: December 2022

Background

The prognostic implication of liver fibrosis in acute coronary syndrome (ACS) patients are scarce. We sought to evaluate whether liver fibrosis scores (LFS) were associated with thrombotic or bleeding events in patients with acute coronary syndrome.

Methods

We included 6386 ACS patients who underwent percutaneous coronary intervention (PCI). This study determined liver fibrosis with aspartate aminotransferase to platelet ratio index (APRI), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio), Forns score, and nonalcoholic fatty liver disease fibrosis score (NFS). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality (ACM), myocardial infarction (MI), and ischemic stroke (IS).

Results

During the follow-up, 259 (4.06%) MACCE and 190 (2.98%) bleeding events were recorded. As a continuous variable or a categorical variable stratified by the literature-based cutoff, LFS was positively associated with MACCE (p > 0.05) but not with bleeding events. Compared with subjects with low APRI scores, AST/ALT ratio scores, Forns scores, and NFS scores, subjects with high scores had a 1.57- to 3.73-fold increase risk of MACCE after adjustment (allp < 0.05). The positive relationship between LFS and MACCE was consistent in different subgroups.

Conclusions

In ACS patients, increased LFS predicted an elevated risk of thrombotic events but not bleeding. LFS may contribute to thrombotic risk stratification after ACS.
Effects of incentive-based population policies on sustainability of China’s recent maternity insurance system reform: a system dynamics simulation
Authors: Zhang Xiaotian , Liu Xiaoyun , Wang Wanxin , Zhou Lulin , Wang Yang , Li Mingyue
Published: December 2022

Background

This paper seeks to assess the sustainability of the reformed maternity insurance system and the extent to which China’s current maternity insurance system can support different levels of fertility incentives in the future. Our findings will serve as a reference for countries in a similar demographic predicament and those about to face it.

Methods

This study used a combination of qualitative and quantitative methods. In the qualitative assessment, we used a grounded theory model to generalize the factors influencing the sustainability of maternity insurance funds. For the quantitative analysis, we used a novel and comprehensive system dynamics model to visualize the status of the combined operation of maternity and health insurance. Data are mainly derived from the historical data of the Statistical Yearbook of Jiangsu Province and the National Bureau of Statistics of China.

Results

In the short term, fertility incentive payments can be set to motivate people to have children. It is therefore recommended that when the scope of the fertility incentive policy is limited to two children, and an average amount above RMB 10 000 could be set, it would be prudent to set the amount at a level not exceeding RMB 10 000 when the scope of the fertility incentive policy is for all newborns. In the long term, a system of incentives for childbirth should be built from education policy, house price regulation, tax relief and childcare services.

Conclusion

Our research not only highlights the significance of improving the resilience of maternity insurance by combining maternity insurance and health insurance funds, but also suggests a way to economically incentivize beneficiaries to have children so as to mitigate the decline in China’s birth rate and cope with the crisis of an ageing population.
miR-4443 promotes radiation resistance of esophageal squamous cell carcinoma via targeting PTPRJ
Authors: Shi Xiaobo , Liu Xiaoxiao , Huang Shan , Hao Yu , Pan Shupei , Ke Yue , Guo Wei , Wang Yuchen , Ma Hongbing
Published: December 2022

Background

Radiotherapy is one of the main treatments for esophageal squamous cell carcinoma (ESCC), but its efficacy is limited by radioresistance. MicroRNAs play a crucial role in posttranscriptional regulation, which is linked to the cancer response to radiation.

Methods

We successfully established a radioresistant cell line model by using fractionated irradiation. qRT-PCR was adopted to detect the expression of miR-4443 in human normal esophageal cell lines, tumor cells, and radioresistant cells. Next, CCK-8, colony formation, apoptosis, and cell cycle assays were used to assess the biological effect of miR-4443. Weighted gene coexpression network analysis (WGCNA) was performed to identify potential radiosensitivity-related genes. Additionally, we predicted the probable targets of the miRNA using bioinformatic methods and confirmed them using Western blot.

Results

miR-4443 was significantly upregulated in radioresistant ESCC cells. Enhancement of miR-4443 further decreased the radiosensitivity of ESCC cells, while inhibition of miR-4443 increased the radiosensitivity of ESCC cells. Notably, miR-4443 modulated radiosensitivity by influencing DNA damage repair, apoptosis, and G2 cycle arrest. By using WGCNA and experimental validation, we identified PTPRJ as a key target for miRNA-4443 to regulate radiosensitivity. The effects of miR-4443 overexpression or inhibition could be reversed by increasing or decreasing PTPRJ expression.

Conclusion

In this study, miR-4443 is found to promote radiotherapy resistance in ESCC cells by regulating PTPRJ expression, which provides a new perspective and clue to alleviate radioresistance.
KPNA2 promotes angiogenesis by regulating STAT3 phosphorylation
Authors: Jia Yujie , Wang Qi , Liang Minglu , Huang Kai
Published: December 2022

Purpose

Angiogenesis is involved in many pathological and physiological processes and is mainly driven by hypoxia. Karyopherin subunit alpha 2 (KPNA2), a member of the nuclear transport protein family, was recently shown to be induced by hypoxia in various types of tumours, so we aimed to investigate the role and mechanism of KPNA2 in angiogenesis under hypoxia.

Materials and methods

After overexpression or knockdown of KPNA2 in human umbilical vein endothelial cells (HUVEC) by adenovirus vector infection, the tube formation, proliferation and migration of HUVEC under hypoxia were detected by tubule formation assay, 5-ethynyl-2′-deoxyuridine (EdU) staining and Transwell assay, respectively. After overexpression or knockdown of KPNA2 in a murine hindlimb ischemia model by local injection of purified adenovirus vector into the gastrocnemius muscle, blood flow changes were examined with a laser Doppler system. Changes in KPNA2-binding proteins under hypoxia were detected by immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP). The effect of KPNA2 on signal transducer and activator of transcription 3 (STAT3) was detected by Western blotting and quantitative RT‒PCR.

Results

KPNA2 was upregulated in the HUVEC hypoxia model and murine hindlimb ischemia model. Overexpression of KPNA2 increased the proliferation, migration and tube formation of HUVEC under hypoxia, while knockdown of KPNA2 reduced the proliferation, migration and tube formation of HUVEC. Overexpression of KPNA2 promoted the restoration of blood flow in the murine hindlimb ischemia model, while knockout of KPNA2 inhibited the restoration of blood flow in the murine hindlimb ischemia model. Mechanistically, hypoxia promoted the binding of STAT3 to KPNA2. Overexpression of KPNA2 promoted STAT3 phosphorylation and then upregulated vascular endothelial growth factor (VEGF) and angiopoietin 2(ANGPT2), whereas knockdown of KPNA2 inhibited STAT3 phosphorylation and then downregulated VEGF and ANGPT2.

Conclusion

Our study demonstrates that hypoxia promotes the binding of STAT3 to KPNA2 and KPNA2 promotes angiogenesis under hypoxia by promoting the binding of STAT3 and JAK1 and regulating STAT3 phosphorylation.
An exploratory study to understand how people use Twitter to share experiences or information about spinal stenosis
Authors: Li Lillian L. C. , Wong Arnold Y. L. , Kawchuk Gregory N.
Published: December 2022

Background

Spinal stenosis is a narrowing of the spinal canal that may compress neurological tissues resulting in pain and disability. Although previous qualitative studies have solicited data regarding the life experience of patients with spinal stenosis or their opinions on relevant non-surgical treatments, their data was collected from participants in a controlled setting. Therefore, it remains unclear whether patients’ or caregivers’ concerns/opinions about spinal stenosis would be different in a non-experimental environment. Since Twitter is a popular online platform for people to share information and interact, it may reveal people’s thoughts and attitudes about spinal stenosis. This study aimed to identify tweets that are related to spinal stenosis on Twitter, and to categorize them into common themes.

Methods

A social media monitoring and analysis software program (TalkWalker) was used to search relevant tweets using the keywords 'spinal stenosis' and 'stenosis' between 29 May 2019 and 24 June 2020. Two independent reviewers screened and conducted content analysis of the tweets and classified the tweets into different themes.

Results

Of 510 identified tweets, 362 tweets met the selection criteria. Five themes were identified: (1) compromised physical, psychological, and social wellbeing (n = 173); (2) diverse treatment options (n = 69); (3) coping strategies (n = 30); (4) dissemination of scientific information (n = 86); and (5) health policy (n = 4). Most of the tweets revealed negative impacts of spinal stenosis on patients' physical and psychosocial wellbeing. People with spinal stenosis shared their experiences and sought helps from others, while some people used Twitter to disseminate relevant information and research findings.

Conclusions

This is the first study exploring Twitter using an online analytical tool to identify themes related to spinal stenosis. The approach not only helps understand people’s concerns about spinal stenosis in an uncontrolled environment, but also can be adopted to monitor influences of diseases or public health education on Twitter users.
Antimicrobial effect of methylene blue in microbiologic culture to diagnose periprosthetic joint infection: an in vitro study
Authors: Liu Kan , Luo Yanping , Hao Libo , Chen Jiying
Published: December 2022

Background

As one of the major diagnostic criteria in Musculoskeletal Infection Society, the microbiological diagnosis of periprosthetic joint infection (PJI) performed by analyzing periprosthetic tissue culture is recommended. The goal of this study was to determine if methylene blue (MB) has antibacterial effects that might interfere with microbial culture in vitro.

Methods

Eight isolates of reference strains of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Streptococcus pyogenes, and Candida albicans were incubated appropriately on blood agar, China blue agar, or Sabouraud’s agar plates at 35 ℃. (Streptococci were cultured in a CO2-rich atmosphere.) Each bacterial suspension was formed by 50-fold dilution before the test MB was added. For each strain, bacterial suspension was divided into 3 groups (5 samples each) exposed either MB 0.1%, MB 0.05% or sterile non-bacteriostatic 0.45% saline. The antimicrobial property of MB was determined by measuring the bacterial density on agar plates incubated for 24 h and comparing it with controls unexposed to MB.

Results

Exposure to MB 0.1% or MB 0.05% negatively affected microbial viability in vitro. Of the diluted form of MB exposure, reference strains of S. hominis and A. baumannii resulted in fewer colony-forming units compared with the sterile saline control. MB concentration was significantly negatively correlated with CFU counts of S. hominis and A. baumannii strains. The antibacterial property of MB 0.1% or MB 0.05% appears to affect the ability to culture the organism in in vitro assays.

Conclusion

MB 0.1% or MB 0.05% has strong antimicrobial activities against some commonly encountered bacterial strains in PJI in vitro. To further evaluate its potential antibacterial usefulness in clinical applications, the next studies are needed to assess the ability of MB to affect the ability to culture the pathogens in vivo, especially in periprosthetic tissue.
Mutational analysis of epidermolysis bullosa in Taiwan by whole-exome sequencing complemented by RNA sequencing: a series of 77 patients
Authors: Tu Wei-Ting , Hou Ping-Chen , Chen Peng-Chieh , Chen Wan-Rung , Huang Hsin-Yu , Wang Jing-Yu , Huang Yi-Ting , Wu Yi-Huei , Su Chun-Lin , Tang Yen-An , Iwata Hiroaki , Natsuga Ken , Chao Sheau-Chiou , Sun H. Sunny , Tang Ming-Jer , Lee Julia Yu-Yun , McGrath John A. , Hsu Chao-Kai
Published: December 2022

Background

Epidermolysis bullosa (EB) is a heterogeneous group of hereditary skin diseases characterized by skin fragility. Primary data on Taiwanese population remain scarce.

Methods

We gathered clinical information from EB patients at National Cheng Kung University Hospital from January, 2012, to June, 2021. Diagnostic tests including transmission electron microscopy, immunofluorescence studies, and whole-exome sequencing (WES) were performed. The pathogenicity of novel splice-site mutations was determined through reverse transcriptase-PCR of skin mRNA followed by Sanger and/or RNA sequencing.

Results

Seventy-seven EB patients from 45 families were included: 19 EB simplex, six junctional EB, and 52 dystrophic EB. Pathogenic variants were identified in 37 of 38 families (97.4%), in which WES was used as a first-line tool for mutational analysis; RNA sequencing determined pathogenic variants in the remaining one family. A total of 60 mutations in EB-related genes were identified, including 22 novel mutations. The mutations involved KRT5, KRT14, PLEC, COL17A1, LAMB3, LAMA3, ITGB4, and COL7A1. Over one-quarter of DEB patients had EB pruriginosa.

Conclusions

The distinct clinical presentation and molecular pathology of EB in Taiwan expand our understanding of this disorder. WES was an effective first-line diagnostic tool for identifying EB-associated variants. RNA sequencing complemented WES when multiple potentially pathogenic splice-site mutations were found.
The effect of virtual specialist conferences between endocrinologists and general practitioners about type 2 diabetes: study protocol for a pragmatic randomized superiority trial
Authors: Prætorius Thim , Baymler Lundberg Anne Sofie , Søndergaard Esben , Tang Knudsen Søren , Sandbæk Annelli
Published: December 2022

Background

To support the primary care sector in delivering high-quality type 2 diabetes (T2D), literature reviews emphasize the need for implementing models of collaboration that in a simple and effective way facilitate clinical dialogue between general practitioners (GPs) and endocrinologists. The overall aim of the project is to evaluate if virtual specialist conferences between GPs and endocrinologists about patients living with T2D is clinically effective and improves diabetes competences and organization in general practice in comparison to usual practice.

Methods

A prospective, pragmatic, and superiority RCT with two parallel arms of general practices in the Municipality of Aarhus, Denmark. All general practices are invited (n = 100). The intervention runs for 12 months and consists of four virtual conferences between endocrinologists and an individual general practice. Before the first conference, an introductory webinar teaches GPs about how to use an IT-platform to identify and manage T2D patients. The main analysis (month 12) concerns the difference between the intervention and control arm. It is expected that the virtual conferences at the patient level will improve adherence to international recommendations on diabetes medication for T2D patients and improve the risk profile with a reduction in glycated haemoglobin, blood pressure, and cholesterol. The study design allows for identifying a significant difference between the intervention (n = 15) and control group (n = 15) regarding the three primary clinical outcomes with a power of 0.8870–0.9941. At the general practice level, it is expected that general practitioners and practice staff in the intervention group will improve self-reported diabetes competence and organization. The control arm will get the intervention when the primary intervention ends (months 12–24), and the intervention arm transitions to a maintenance phase.

Discussion

The potential of virtual conferences is yet to be fully tapped because of methodological limitations. Studies have also not yet systematically evaluated virtual conferences in the context of chronic care using a high-quality research design. Given the nature of this real-life intervention, general practitioners and endocrinologists cannot be blinded to their allocation to either the intervention or comparison arm.

Trial registration

ClinicalTrials.gov, United States National Institutes of Health trial ID: NCT05268081. Registered on 4 March 2022.
Consumer perspectives on simplified, layered consent for a low risk, but complex pragmatic trial
Authors: Symons Tanya J. , Straiton Nicola , Gagnon Rosie , Littleford Roberta , Campbell Anita J. , Bowen Asha C. , Stewart Adam G. , Tong Steven Y. C. , Davis Joshua S.
Published: December 2022

Background

For decades, the research community has called for participant information sheets/consent forms (PICFs) to be improved. Recommendations include simplifying content, reducing length, presenting information in layers and using multimedia. However, there are relatively few studies that have evaluated health consumers’ (patients/carers) perspectives on the type and organisation of information, and the level of detail to be included in a PICF to optimise an informed decision to enter a trial.

We aimed to elicit consumers’ views on a layered approach to consent that provides the key information for decision-making in a short PICF (layer 1) with additional optional information that is accessed separately (layer 2). We also elicited consumers’ views on the optimal content and layout of the layered consent materials for a large and complex Bayesian adaptive platform trial (the SNAP trial).

Methods

We conducted a qualitative multicentre study (4 focus groups and 2 semi-structured interviews) involving adolescent and adult survivors of Staphylococcus aureus bloodstream infection (22) and their carers (2). Interview transcripts were examined using inductive thematic analysis.

Results

Consumers supported a layered approach to consent. The primary theme that emerged was the value of agency; the ability to exert some control over the amount of information read before the consent form is signed. Three other themes emerged; the need to prioritise participants’ information needs; the importance of health literacy; the importance of information about a trial’s benefits (over its risks) for decision-making and the interplay between the two.

Conclusions

Our findings suggest that consumers may challenge the one-size-fits-all approach currently applied to the development of PICFs in countries like Australia. Consumers supported a layered approach to consent that offers choice in the amount of information to be read before deciding whether to enter a trial. A 3-page PICF was considered sufficient for decision-making for the SNAP trial, provided that further information was available and accessible.
Safety and microbiological activity of phage therapy in persons with cystic fibrosis colonized with Pseudomonas aeruginosa: study protocol for a phase 1b/2, multicenter, randomized, double-blind, placebo-controlled trial
Authors: Tamma Pranita D. , Souli Maria , Billard Michael , Campbell Joseph , Conrad Douglas , Ellison Damon W. , Evans Beth , Evans Scott R. , Greenwood-Quaintance Kerryl E. , Filippov Andrey A. , Geres Holly S. , Hamasaki Toshimitsu , Komarow Lauren , Nikolich Mikeljon P. , Lodise Thomas P. , Nayak Seema U. , Norice-Tra Carmelle , Patel Robin , Pride David , Russell Janie , Van Tyne Daria , Chambers Henry F. , FowlerJr Vance G. , Schooley Robert T. ,   for the Antibacterial Resistance Leadership Group
Published: December 2022

Background

Bacteriophages (phages) are a promising anti-infective option for human disease. Major gaps remain in understanding their potential utility.

Methods

This is a randomized, placebo-controlled, double-blind study of a single dose of intravenous phage in approximately 72 clinically stable adult cystic fibrosis volunteers recruited from up to 20 US sites with Pseudomonas aeruginosa airway colonization. The single dose of phage consists of a mixture of four anti-pseudomonal phages. Six sentinel participants will be sequentially enrolled with dose escalation of the phage mixture by one log10 beginning with 4 × 107 plaque-forming units in an unblinded stage 1. If no serious adverse events related to the study product are identified, the trial will proceed to a double-blinded stage 2. In stage 2a, 32 participants will be randomly assigned to one of three phage dosages or placebo in a 1:1:1:1 allocation. An interim analysis will be performed to determine the phage dosage with the most favorable safety and microbiological activity profile to inform phage dosing in stage 2b. During stage 2b, up to 32 additional volunteers will be randomized 1:1 to the phage or placebo arm. Primary outcomes include (1) the number of grade 2 or higher treatment-emergent adverse events, (2) change in log10P. aeruginosa total colony counts in sputum, and (3) the probability of a randomly selected subject having a more favorable outcome ranking if assigned to receive phage therapy versus placebo. Exploratory outcomes include (1) sputum and serum phage pharmacokinetics, (2) the impact of phage on lung function, (3) the proportion of P. aeruginosa isolates susceptible to the phage mixture before and after study product administration, and (4) changes in quality of life.

Discussion

This trial will investigate the activity of phages in reducing P. aeruginosa colony counts and provide insights into the safety profile of phage therapy.

Trial registration

ClinicalTrials.gov NCT05453578. Registered on 12 July 2022.
Response letter to “Latent class analysis of 216 patients with adult-onset Still’s disease” by Sugiyama et al.
Authors: Delplanque Marion , Mekinian Arsène , Georgin-Lavialle Sophie
Published: December 2022

Sugiyama et al. recently described in “Latent class analysis of 216 patients with adult-onset Still’s disease,” baseline characteristics, laboratory tests, treatment, relapse, and death of adult-onset Still’s disease (AOSD) patients from a Japanese hospital. They identified two subgroups: Class 1 (n=155) with a younger age and typical symptoms of AOSD and Class 2 (n=61) with older patients and fewer typical symptoms of AOSD. In 2022, VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, an established X-linked disease associated with a somatic mutation in UBA1, is considered as a differential diagnosis for AOSD particularly in elderly. These patients from Class 2 could benefit from more explorations for mild myelodysplasia and VEXAS.
Maintenance of methylation profile in imprinting control regions in human induced pluripotent stem cells
Authors: Pham A. , Selenou C. , Giabicani E. , Fontaine V. , Marteau S. , Brioude F. , David L. , Mitanchez D. , Sobrier M. L. , Netchine I.
Published: December 2022

Background

Parental imprinting is an epigenetic mechanism that leads to monoallelic expression of a subset of genes depending on their parental origin. Imprinting disorders (IDs), caused by disturbances of imprinted genes, are a set of rare congenital diseases that mainly affect growth, metabolism and development. To date, there is no accurate model to study the physiopathology of IDs or test therapeutic strategies. Human induced pluripotent stem cells (iPSCs) are a promising cellular approach to model human diseases and complex genetic disorders. However, aberrant hypermethylation of imprinting control regions (ICRs) may appear during the reprogramming process and subsequent culture of iPSCs. Therefore, we tested various conditions of reprogramming and culture of iPSCs and performed an extensive analysis of methylation marks at the ICRs to develop a cellular model that can be used to study IDs.

Results

We assessed the methylation levels at seven imprinted loci in iPSCs before differentiation, at various passages of cell culture, and during chondrogenic differentiation. Abnormal methylation levels were found, with hypermethylation at 11p15 H19/IGF2:IG-DMR and 14q32 MEG3/DLK1:IG-DMR, independently of the reprogramming method and cells of origin. Hypermethylation at these two loci led to the loss of parental imprinting (LOI), with biallelic expression of the imprinted genes IGF2 and DLK1, respectively. The epiPS™ culture medium combined with culturing of the cells under hypoxic conditions prevented hypermethylation at H19/IGF2:IG-DMR (ICR1) and MEG3/DLK1:IG-DMR, as well as at other imprinted loci, while preserving the proliferation and pluripotency qualities of these iPSCs.

Conclusions

An extensive and quantitative analysis of methylation levels of ICRs in iPSCs showed hypermethylation of certain ICRs in human iPSCs, especially paternally methylated ICRs, and subsequent LOI of certain imprinted genes. The epiPS™ culture medium and culturing of the cells under hypoxic conditions prevented hypermethylation of ICRs in iPSCs. We demonstrated that the reprogramming and culture in epiPS™ medium allow the generation of control iPSCs lines with a balanced methylation and ID patient iPSCs lines with unbalanced methylation. Human iPSCs are therefore a promising cellular model to study the physiopathology of IDs and test therapies in tissues of interest.
Prenatal diagnosis of fetal midgut volvulus: a case report
Authors: Jain Neelam , Awal Sandeep Singh , Biswas Som , Ghosh Tanushree
Published: December 2022

Background

Fetal midgut volvulus is an uncommon yet potentially life-threatening condition. Prenatal diagnosis may pose a challenge, due to the paucity of specific signs and symptoms. Timely prenatal diagnosis of this condition is imperative to prevent fetal mortality and morbidity.

Case presentation

We present a rare case report of fetal midgut volvulus, malrotation, and intestinal obstruction at 32 weeks of gestation in a 31-year-old multigravida Indian patient who presented with decreased fetal movements. Fetal ultrasound revealed midgut volvulus with proximal bowel obstruction and polyhydramnios. The patient underwent emergency surgery, which revealed intestinal malrotation and confirmed the diagnosis of midgut volvulus. Untwisting of the volvulus was done followed by Ladd’s procedure. Follow-up postoperative ultrasound was unremarkable.

Conclusions

Delay in the diagnosis of fetal midgut volvulus leads to poor fetal and maternal outcomes. Hence, it is vital for radiologists, sonologists, and obstetricians to be aware of this condition while performing fetal sonography. Prompt diagnosis and surgical intervention are vital to reduce the morbidity and mortality associated with this condition.
Effect of the initial pH on the anaerobic digestion process of dairy cattle manure
Authors: Castro-Ramos Job Jonathan , Solís-Oba Aida , Solís-Oba Myrna , Calderón-Vázquez Carlos Ligne , Higuera-Rubio Jesús Mireya , Castro-Rivera Rigoberto
Published: December 2022

Anaerobic digestion (AD) has recently been studied to obtain products of greater interest than biogas, such as volatile fatty acids (VFAs) and phytoregulators. The effect of the initial pH of cow manure and the fermentation time of the AD on the microbial composition, VFAs, indole-3-acetic acid (IAA) and gibberellic acid (GA3) production was evaluated. The cow manure (7% solids) was adjusted to initial pH values of 5.5, 6.5, 7.5, and 8.5, and the AD products were analyzed every four days until day 20. The initial pH and the fermentation time had an important effect on the production of metabolites. During AD, only the hydrolytic and acidogenic stages were identified, and the bacteria found were from the phyla Firmicutes, Bacteroidetes, Actinobacteria, and Spirochaetes. The most abundant genera produced in the four AD were Caproiciproducens, Clostridium sensu stricto 1, Romboutsia, Paeniclostridium, Turicibacter, Peptostreptococcaceae, Ruminococcaceae and Fonticella. The highest amount of VFAs was obtained at pH 8.5, and the production of the acids was butyric > acetic > propionic. The maximum production of GA3 and IAA was at an initial pH of 6.5 on day 20 and a pH of 5.5 on day 4, respectively. There was a strong correlation (> 0.8) between the most abundant microorganisms and the production of VFAs and GA3. The anaerobic digestion of cow manure is a good alternative for the production of VFAs, GA3 and IAA.
Transcriptomic and enzymatic analysis reveals the roles of glutamate dehydrogenase in Corynebacterium glutamicum
Authors: Ge Fanglan , Sun Jingkun , Ren Yao , He Bing , Li Jiao , Yang Sen , Li Wei
Published: December 2022

Glutamate dehydrogenase (Gdh), catalyzing the reversible conversion between 2-oxoglutarate and glutamate, plays an important role in the connection of nitrogen and carbon metabolism. Yet little is known about these enzymes in the amino acid-manufacturing Corynebacterium glutamicum. In the present study, we firstly identified the enzymatic characteristics of two Gdhs (GdhA and GdhB). The results showed that both GdhA and GdhB prefers NADPH as a coenzyme and have higher affinity for 2-OG than glutamate. The growth characteristics of gdhAΔ mutant and gdhBΔ mutant, gdhABΔ mutant showed GdhA serves as the main conduit for ammonium assimilation, and GdhB is the main glutamate- metabolizing enzyme in C. glutamicum. The full-genome transcriptomic analysis was used to investigate physiological response of C. glutamicum to the glutamate as nitrogen source, and gdh deletion. The results showed that the nitrogen starvation response was elicited when glutamine served as the sole nitrogen source. gdhAΔBΔ double deletion trigger a partially deregulated nitrogen starvation response, in which genes involved in nitrogen assimilation showed obviously upregulated in a certain extent. On the other hand, the genes of phosphotransferase system (PTS) and glycolysis pathway, most genes in pentose phosphate pathway were significantly upregulated, indicating that gdh deficiency initiated the enhancement of the absorption and metabolism of carbon sources. We believed that our results in this study will give new insights on the molecular mechanism of Gdh activity cross-talks with carbon and nitrogen metabolism, also setting a new background for further flux redistribution applied research of biotechnological interest.
Performance analysis on the speed spectrum estimation based on dual-HFM waveform
Authors: Wei Runyu , Li Xuan , Fu Yubin , Ma Xiaochuan
Published: December 2022

Real-time Doppler estimation of sonar signals is of great significance to underwater communication and detection. The Hyperbolic-Frequency-Modulated (HFM) waveform-based speed spectrum estimation is one of the modern methods for underwater Doppler estimation, and this paper presents a detailed analyses of the derivation and the performance of this method. The analyzing results show the robustness of the method on multipath channels and multi-highlight targets and provide the main lobe width of the speed spectrum. Moreover, the paper examines the spectral properties of the HFM signal from the frequency-domain Doppler invariance property, which could provide insights for better understanding and utilization of this Doppler invariant waveform.
Hemodiafiltration combined with polymyxin B-immobilized fiber column direct hemoperfusion is effective for acute postoperative exacerbation of interstitial pneumonia: a case report
Authors: Yokoyama Tatsuro , Tamura Takahiro , Nakashima Harunori , Ando Morihide , Kikkawa Koshiro , Ito Ryohei
Published: December 2022

Background

Postoperative acute exacerbation of interstitial pneumonia has a high mortality rate; however, its treatment methods have not been standardized.

Case presentation

A 72-year-old man with rheumatoid arthritis developed acute respiratory failure about 3 weeks after lung cancer surgery. There were increased diffuse frosted shadows in both lung fields. His condition was diagnosed as an acute exacerbation of interstitial pneumonia associated with rheumatoid arthritis, and he was started on steroid pulse therapy; however, his respiratory condition deteriorated. He was urgently intubated and started on veno-venous extracorporeal membrane oxygenation. Further, intensive care, including blood purification therapy, was initiated. The blood purification therapy comprised a combination of hemodiafiltration and 6-h polymyxin B-immobilized fiber column direct hemoperfusion. The patient was weaned off veno-venous extracorporeal membrane oxygenation, extubated, and discharged from the intensive care unit on the ninth day.

Conclusions

Blood purification therapy was effective for acute exacerbation of interstitial pneumonia.
Gap selection and steering during obstacle avoidance in pigeons
Authors: Pérez-Campanero Antolín Natalia , Taylor Graham K.
Published: December 2022

The ability of birds to fly through cluttered environments has inspired biologists interested in understanding its underlying mechanisms, and engineers interested in applying its underpinning principles. To analyse this problem empirically, we break it down into two distinct, but related, questions: How do birds select which gaps to aim for? And how do they steer through them? We answered these questions using a combined experimental and modelling approach, in which we released pigeons (Columbia livia domestica) inside a large hall with an open exit separated from the release point by a curtain creating two vertical gaps – one of which was obstructed by an obstacle. We tracked the birds using a high-speed motion capture system, and found that their gap choice seemed to be biased by their intrinsic handedness, rather than determined by extrinsic cues such as the size of the gap or its alignment with the destination. We modelled the pigeons' steering behaviour algorithmically by simulating their flight trajectories under a set of six candidate guidance laws, including those used previously to model target-oriented flight behaviours in birds. We found that their flights were best modelled by delayed proportional navigation commanding turning in proportion to the angular rate of the line-of-sight from the pigeon to the midpoint of the gap. Our results are consistent with this being a two-phase behaviour, in which the pigeon heads forward from the release point before steering towards the midpoint of whichever gap it chooses to aim for under closed-loop guidance. Our findings have implications for the sensorimotor mechanisms that underlie clutter negotiation in birds, uniting this with other kinds of target-oriented behaviours including aerial pursuit.
Χημεία στην Καθημερινή Ζωή
Authors: Kotsali Ilia , Kavouras Ermis
Published: December 2022

Αντικείμενο της παρούσας έρευνας, την οποία πραγματοποιήσαμε στο πλαίσιο του μαθήματος της Χημείας  στην Γ΄ τάξη  Γυμνασίου, αποτέλεσε η ασφαλής και ποιοτική επιλογή της οδοντόκρεμας για τη διατήρηση και βελτίωση της στοματικής  υγείας και αισθητικής,  καθώς και η άποψη των φίλων και μαθητών του σχολείου μας για το ζήτημα αυτό. Η ομάδα μας επέλεξε να ασχοληθεί με το θέμα: «Πόσο καλά γνωρίζετε την οδοντόκρεμά σας;» γιατί είναι ένα ζήτημα το οποίο άπτεται της στοματικής υγιεινής και της ευημερίας των ατόμων, ενώ συγχρόνως  έχει και περιβαλλοντικές συνέπειες. Το κεντρικό ερευνητικό μας ερώτημα  ήταν: Πως μπορούμε να ξεχωρίσουμε ποια οδοντόκρεμα είναι κατάλληλη για εμάς; Αναζητήσαμε πληροφορίες, κυρίως μέσω του διαδικτύου, σχετικά με τη  χημική σύσταση των σκευασμάτων οδοντόκρεμας   και τις βασικές  κατηγορίες στις οποίες διαχωρίζονται. Διερευνήσαμε κατά πόσο είναι ασφαλείς για τον ανθρώπινο οργανισμό και τον βαθμό στον οποίο το υλικό της συσκευασίας τους  επιβαρύνει το περιβάλλον. Με βάση τη γνώση που αποκομίσαμε, διεξήγαμε  μία  ενδεικτική κοινωνική  έρευνα, χρησιμοποιώντας τα μέσα κοινωνικής δικτύωσης, προκειμένου να καταγράψουμε  τα κριτήρια με τα οποία  οι περισσότεροι άνθρωποι επιλέγουν την οδοντόκρεμα που χρησιμοποιούν. Παράλληλα πραγματοποιήσαμε μέτρηση pH του σιέλου πριν και μετά τη χρήση οδοντόκρεμας, έτσι ώστε να εμπλουτίσουμε τη γνώση μας  και εμπειρικά.
Παιχνιδοποίηση στην Εκπαίδευση
Authors: Κυριάκου Έλενα , Κλιάμπα Μελίνα , Σταυροπούλου Σταυροπούλου , Κορκολή Θεοφανία , Πριονιστής Γιάννης
Published: December 2022

Η παιχνιδοποίηση (gamification) είναι μια σύγχρονη έννοια και αφορά τη χρήση μηχανισμών παιχνιδιού σε μη παιγνιώδεις καταστάσεις. Μέσω διάφορων τεχνικών που μιμούνται τα παιχνίδια, αποσκοπεί να βελτιώσει την μαθησιακή εμπειρία, να ενισχύσει τον βαθμό εμπλοκής με το μάθημα και να ενδυναμώσει την αίσθηση του σκοπού και της οικειότητας στις διάφορες διαδικασίες. Στην έρευνά μας δημιουργήσαμε ένα ερωτηματολόγιο για να εξετάσουμε τις αντιλήψεις των μαθητών σχετικά με την παιχνιδοποίηση στην εκπαίδευση. Στη συνέχεια, δημιουργήσαμε ένα εκπαιδευτικό παιχνίδι, το οποίο δοκίμασαν μαθητές του σχολείου μας και συλλέξαμε σχόλια ανατροφοδότησης από τους μαθητές.
Αρχαία Ελληνική Κληρονομιά και Σύγχρονος Ψηφιακός Κόσμος
Authors: Γεωργοπούλου Νικόλ , Πελέκη Χάιντι , Σούτου Ανθή , Φωσκίνη Αντιγόνη
Published: December 2022

Ο αρχαίος ελληνικός πολιτισμός, η ελληνική αρχαιότητα αποτελεί αναμφίβολα το θεμέλιο του σύγχρονου κόσμου. Ο αρχαίος ελληνικός πολιτισμός είναι παντού γύρω μας, γιατί έχει διαμορφώσει τη σύγχρονη σκέψη στον πυρήνα της. Θεμελίωσε τον ορθολογισμό, τη φιλοσοφία, τις επιστήμες. Και όμως η ελληνική αρχαιότητα δεν είναι απλώς ο θεμελιωτής όλων αυτών των κατορθωμάτων, είναι συγχρόνως και ο μόνιμος συνομιλητής του νεότερου και σύγχρονου πολιτισμού, του ψηφιακού κόσμου. Ο ανθρωποκεντρικός και κοινωνιοκεντρικός πολιτισμός της ελληνικής αρχαιότητας αποτελεί καίριο αντίβαρο στη σύγχρονη τεχνοκρατία, καθώς θέτει στο κέντρο της προσέγγισης τον ίδιο τον άνθρωπο. Και είναι αυτό ακριβώς το μεγαλύτερο στοίχημα του σύγχρονου ψηφιακού κόσμου, να τεθεί στην υπηρεσία και στην ουσιαστική πρόοδο και ευτυχία του ανθρώπου.
ΝΕΕΣ ΜΟΡΦΕΣ ΕΝΕΡΓΕΙΑΣ: ΠΡΟΣ ΤΗΝ ΠΥΡΗΝΙΚΗ ΣΥΝΤΗΞΗ
Authors: Μπλάνας Σωκράτης , Παπαδογιάννης Έκτορας , Ποταμιάς Ηλίας
Published: December 2022

Με τον πόλεμο να μαίνεται στην Ουκρανία και την ενεργειακή κρίση να κορυφώνεται ραγδαία, ανάγεται σε μείζων ζήτημα η ενεργειακή απεξάρτηση της Ευρώπης από τα ορυκτά καύσιμα και η ούτως ή άλλως περιβαλλοντικά απαραίτητη στροφή προς καθαρότερες πηγές ενέργειας. Στην παρούσα εργασία γίνεται αναφορά στο ενεργειακό προφίλ της Ελλάδας, στην μεγάλη - αν και ολοένα μειούμενη -  εξάρτηση της χώρας μας από τον λιγνίτη,  και στο αναγκαίο  πέρασμα της στην μεταλιγνιτική εποχή.  Από τις ανανεώσιμες πηγές ενέργειας δίνεται ιδιαίτερη έμφαση στην πυρηνική σύντηξη, διαδικασία «παραγωγής» καθαρής ενέργειας (που πραγματοποιείται ανεμπόδιστα στον ήλιο), με ελάχιστο περιβαλλοντικό αποτύπωμα, εξαιρετικά πλεονεκτήματα αλλά και μεγάλες δυσκολίες αξιοποίησής της στις συνθήκες της γης.  Μέσα από μία μεγάλη πορεία δοκιμών, τα τελευταία επιτεύγματα ανάβουν το πράσινο φως και δημιουργούν υψηλές προσδοκίες για το άμεσο μέλλον.
ELEMENTS COMPOSING THE YIELD OF SPRING WHEAT OF THE YOLDYZ VARIETY, DEPENDING ON THE DEFEAT OF ROOT ROT IN THE CONDITIONS OF THE PRE-KAMA REGION OF THE REPUBLIC OF TATARSTAN
Authors: Garaev Razil , Shaykhutdinov Farit , Serzhanov Igor , Serzhanova Al'bina
Published: December 2022

The research was carried out to study the effect of the infestation of spring wheat plants of the Yoldyz variety by root rot on individual elements of the crop structure. During 2018-2019, experiments were conducted at the experimental field of the Kazan State Agrarian University on the basis of the Agrobiotechnopark, laboratory analyses were conducted at the Center for agroecological Research of the Institute of Agrobiotechnologies and Land Use. Experiments have shown that the survival rate of spring wheat plants in growing conditions was the lower, the higher the degree of their root rot disease. In the germination phase, 13.2-15.6% of plants were affected, and by wax ripeness, the lesion increased by 9.3-19.1%. Against the background of mineral nutrition N123P73K108, the lesion was 11.2% lower than against the background without fertilizers. With an increase in the degree of the disease, the ear of the ear decreases. In healthy plants, the number of grains in the ear was 21.4-25.3 pieces, and in severely affected plants – 8.0-13.4 pieces. Grain yield losses from root rot amounted to 0.54-0.69 t/ha. On the fertilized background of nutrition, losses were less by 0.15 tons per 1 ha, which is undoubtedly due to an increase in the resistance of spring wheat plants to root rot. The potential of spring wheat of the Yoldyz variety was realized through three main elements of the crop structure: a productive stem per unit area, the ear of the ear and the mass of 1000 grains. The effect of root rot on the elements of the structure of the spring wheat crop depends on the degree of root rot damage. The disease reduces the productive stem, the ear of the ear and the mass of 1000 grains more significantly with a 3-point lesion. Reducing the degree of damage to the root rot of spring wheat under conditions of application of calculated doses of fertilizers contributes to improving the elements of the crop structure and obtaining a high yield of grain of this crop.