Miracle-dz/UniFAR-FTUs huggingface dataset:
Pregnancy-associated systemic gene expression compared to a pre-pregnancy baseline, among healthy women with term pregnancies

Background Pregnancy is known to induce extensive biological changes in the healthy mother. Little is known, however, about what these changes are at the molecular level. We have examined systemic expression changes in protein-coding genes and long non-coding (lnc) RNAs during and after pregnancy, compared to before pregnancy, among healthy women with term pregnancies. Methods Blood samples were collected from 14 healthy women enrolled in our prospective pregnancy cohort at 7 time-points (before, during and after pregnancy). Total RNA from frozen whole blood was used for RNA sequencing. Following raw read alignment and assembly, gene-level counts were obtained for protein-coding genes and long non-coding RNAs. At each time-point, cell type proportions were estimated using deconvolution. To examine associations between pregnancy status and gene expression over time, Generalized Estimating Equation (GEE) models were fitted, adjusting for age at conception, and with and without adjusting for changes in cell type proportions. Fold-changes in expression at each trimester were examined relative to the pre-pregnancy baseline. Results Numerous immune-related genes demonstrated pregnancy-associated expression, in a time-dependent manner. The genes that demonstrated the largest changes in expression included several that were neutrophil-related (over-expressed) and numerous immunoglobulin genes (under-expressed). Estimated cell proportions revealed a marked increase in neutrophils, and less so of activated CD4 memory T cells, during pregnancy, while most other cell type proportions decreased or remained unchanged. Adjusting for cell type proportions in our model revealed that although most of the expression changes were due to changes in cell type proportions in the bloodstream, transcriptional regulation was also involved, especially in down-regulating expression of type I interferon inducible genes. Conclusion Compared to a pre-pregnancy baseline, there were extensive systemic changes in cell type proportions, gene expression and biological pathways associated with different stages of pregnancy and postpartum among healthy women. Some were due to changes in cell type proportions and some due to gene regulation. In addition to providing insight into term pregnancy among healthy women, these findings also provide a “normal” reference for abnormal pregnancies and for autoimmune diseases that improve or worsen during pregnancy, to assess deviations from normal.
Fungal strain and crop cultivar affect growth of sweet pepper plants after root inoculation with entomopathogenic fungi

As endophytes, entomopathogenic fungi can protect plants against biotic and abiotic stresses and at the same time promote plant growth and plant health. To date, most studies have investigated whether Beauveria bassiana can enhance plant growth and plant health, while only little is known about other entomopathogenic fungi. In this study, we evaluated whether root inoculation of the entomopathogenic fungi Akanthomyces muscarius ARSEF 5128, B. bassiana ARSEF 3097 and Cordyceps fumosorosea ARSEF 3682 can promote plant growth of sweet pepper (Capsicum annuum L.), and whether effects are cultivar-dependent. Plant height, stem diameter, number of leaves, canopy area, and plant weight were assessed four weeks following inoculation in two independent experiments using two cultivars of sweet pepper (cv. ‘IDS RZ F1’ and cv. ‘Maduro’). Results showed that the three entomopathogenic fungi were able to enhance plant growth, particularly canopy area and plant weight. Further, results showed that effects significantly depended on cultivar and fungal strain, with the strongest fungal effects obtained for cv. ‘IDS RZ F1’, especially when inoculated with C. fumosorosea. We conclude that inoculation of sweet pepper roots with entomopathogenic fungi can stimulate plant growth, but effects depend on fungal strain and crop cultivar.
Immune-related adverse effects of checkpoint immunotherapy and implications for the treatment of patients with cancer and autoimmune diseases

During the past decade, there has been a revolution in cancer therapeutics by the emergence of antibody-based immunotherapies that modulate immune responses against tumors. These therapies have offered treatment options to patients who are no longer responding to classic anti-cancer therapies. By blocking inhibitory signals mediated by surface receptors that are naturally upregulated during activation of antigen-presenting cells (APC) and T cells, predominantly PD-1 and its ligand PD-L1, as well as CTLA-4, such blocking agents have revolutionized cancer treatment. However, breaking these inhibitory signals cannot be selectively targeted to the tumor microenvironment (TME). Since the physiologic role of these inhibitory receptors, known as immune checkpoints (IC) is to maintain peripheral tolerance by preventing the activation of autoreactive immune cells, IC inhibitors (ICI) induce multiple types of immune-related adverse effects (irAEs). These irAEs, together with the natural properties of ICs as gatekeepers of self-tolerance, have precluded the use of ICI in patients with pre-existing autoimmune diseases (ADs). However, currently accumulating data indicates that ICI might be safely administered to such patients. In this review, we discuss mechanisms of well established and newly recognized irAEs and evolving knowledge from the application of ICI therapies in patients with cancer and pre-existing ADs.
Transcriptome analysis reveals the high ribosomal inhibitory action of 1,4-naphthoquinone on Meloidogyne luci infective second-stage juveniles

The root-knot nematode (RKN) Meloidogyne luci presents a threat to the production of several important crops. This nematode species was added to the European Plant Protection Organization Alert list in 2017. The scarce availability of efficient nematicides to control RKN and the phasing out of nematicides from the market have intensified the search for alternatives, such as phytochemicals with bionematicidal properties. The nematicidal activity of 1,4-naphthoquinone (1,4-NTQ) against M. luci has been demonstrated; however, knowledge of the potential mode(s) of action of this compound is still scarce. In this study, the transcriptome profile of M. luci second-stage juveniles (J2), the infective stage, in response to 1,4-NTQ exposure was determined by RNA-seq to identify genes and pathways that might be involved in 1,4-NTQ’s mode(s) of action. Control treatments, consisting of nematodes exposed to Tween® 80 (1,4-NTQ solvent) and to water, were included in the analysis. A large set of differentially expressed genes (DEGs) was found among the three tested conditions, and a high number of downregulated genes were found between 1,4-NTQ treatment and water control, reflecting the inhibitory effect of this compound on M. luci, with a great impact on processes related to translation (ribosome pathway). Several other nematode gene networks and metabolic pathways affected by 1,4-NTQ were also identified, clarifying the possible mode of action of this promising bionematicide.
Novel protein biomarkers for pneumonia and acute exacerbations in COPD: a pilot study

Introduction Community-acquired pneumonia (CAP) and acute exacerbations of chronic obstructive pulmonary disease (AECOPD) result in high morbidity, mortality, and socio-economic burden. The usage of easily accessible biomarkers informing on disease entity, severity, prognosis, and pathophysiological endotypes is limited in clinical practice. Here, we have analyzed selected plasma markers for their value in differential diagnosis and severity grading in a clinical cohort. Methods A pilot cohort of hospitalized patients suffering from CAP (n = 27), AECOPD (n = 10), and healthy subjects (n = 22) were characterized clinically. Clinical scores (PSI, CURB, CRB65, GOLD I-IV, and GOLD ABCD) were obtained, and interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-2-receptor (IL-2R), lipopolysaccharide-binding protein (LBP), resistin, thrombospondin-1 (TSP-1), lactotransferrin (LTF), neutrophil gelatinase-associated lipocalin (NGAL), neutrophil-elastase-2 (ELA2), hepatocyte growth factor (HGF), soluble Fas (sFas), as well as TNF-related apoptosis-inducing ligand (TRAIL) were measured in plasma. Results In CAP patients and healthy volunteers, we found significantly different levels of ELA2, HGF, IL-2R, IL-6, IL-8, LBP, resistin, LTF, and TRAIL. The panel of LBP, sFas, and TRAIL could discriminate between uncomplicated and severe CAP. AECOPD patients showed significantly different levels of LTF and TRAIL compared to healthy subjects. Ensemble feature selection revealed that CAP and AECOPD can be discriminated by IL-6, resistin, together with IL-2R. These factors even allow the differentiation between COPD patients suffering from an exacerbation or pneumonia. Discussion Taken together, we identified immune mediators in patient plasma that provide information on differential diagnosis and disease severity and can therefore serve as biomarkers. Further studies are required for validation in bigger cohorts.
Current understanding of disease control and its application in patients with chronic rhinosinusitis

Background Disease control is a primary treatment goal for patients with chronic rhinosinusitis (CRS). This study aims to summarize the evaluation parameters of disease control and then identify predictors of poorly controlled CRS. Methods A systematic review of the literature was performed on PubMed, Google Scholar, Scopus, and Cochrane databases to identify studies relating to disease control in CRS. Results The concept of disease control in patients with CRS involved the longitudinal assessment of the disease state and was also an important goal of treatment. As a metric of the disease state, the disease control reflected the ability to keep disease manifestations within certain limits, the efficacy after treatment, and the impact on quality of life. Validated measurements, such as EPOS2012 criteria, EPOS2020 criteria, Sinus Control Test, and patient/physician-reported global level of CRS control, have been utilized in clinical practice. These existing disease control instruments incorporated various disease manifestations and categorized patients into two (well-controlled and poor-controlled), three (uncontrolled, partly controlled, and controlled), or five (not at all, a little, somewhat, very, and completely) control categories. Eosinophilia, high computerized tomography score, bilateral sinonasal disease, asthma, allergic rhinitis, female gender, aspirin intolerance, revision surgery, low serum amyloid A, and specific T cell subtype would predict poorly controlled CRS. Conclusion The concept of disease control and its application were gradually developed in patients with CRS. The existing disease control instruments demonstrated a lack of uniformity regarding the controlled criteria and included parameters.
Organizational health climate as a precondition for health-oriented leadership: expanding the link between leadership and employee well-being

The link between leadership and employee well-being is long established. In particular, health-oriented leadership is discussed as a leadership style specifically promoting employee well-being. However, the preconditions of health-oriented leadership remain largely unexplored. From the perspective of conservation of resources theory, leaders can only provide resources when receiving some themselves. We propose that organizational health climate (OHC) is an important organization-based resource for a health-oriented leadership style. More specifically, we hypothesize that the relationship between OHC and employee job satisfaction and emotional exhaustion is mediated by health-oriented leadership. We thereby differentiate two levels of analysis: a within-team level and a between-team level. We examined 74 teams with 423 employees of childcare centers at three time points, each 6 months apart. By means of multilevel structural equation modeling, we found OHC to be a significant antecedent of health-oriented leadership at the between-team level. The relationship between OHC and employee job satisfaction was mediated by health-oriented leadership at the between-team level, but not at the within-team level. The relationship between OHC and employee exhaustion showed another pattern of relationships at the different levels of analysis, while it was not significantly mediated by health-oriented leadership. This indicates the value of differentiating between levels of analysis. We discuss the implications for theory and practice that can be drawn from our findings.
Colorectal polyps increase the glycolytic activity

In colorectal cancer (CRC) energy metabolism research, the precancerous stage of polyp has remained rather unexplored. By now, it has been shown that CRC has not fully obtained the glycolytic phenotype proposed by O. Warburg and rather depends on mitochondrial respiration. However, the pattern of metabolic adaptations during tumorigenesis is still unknown. Understanding the interplay between genetic and metabolic changes that initiate tumor development could provide biomarkers for diagnosing cancer early and targets for new cancer therapeutics. We used human CRC and polyp tissue material and performed high-resolution respirometry and qRT-PCR to detect changes on molecular and functional level with the goal of generally describing metabolic reprogramming during CRC development. Colon polyps were found to have a more glycolytic bioenergetic phenotype than tumors and normal tissues. This was supported by a greater GLUT1, HK, LDHA, and MCT expression. Despite the increased glycolytic activity, cells in polyps were still able to maintain a highly functional OXPHOS system. The mechanisms of OXPHOS regulation and the preferred substrates are currently unclear and would require further investigation. During polyp formation, intracellular energy transfer pathways become rearranged mainly by increasing the expression of mitochondrial adenylate kinase (AK) and creatine kinase (CK) isoforms. Decreased glycolysis and maintenance of OXPHOS activity, together with the downregulation of the CK system and the most common AK isoforms (AK1 and AK2), seem to play a relevant role in CRC development.
Polystyrene nanoplastics mediated the toxicity of silver nanoparticles in zebrafish embryos

The widespread distribution of nanoplastics and nanomaterials in aquatic environments is of great concern. Nanoplastics have been found to modulate the toxicity of other environmental pollutants in organisms, while few studies have focused on their influences on nanomaterials. Thus, this study evaluated the influences of polystyrene (PS) nanoplastics on the toxicity of silver nanoparticles (AgNPs) to zebrafish (Danio rerio) embryos, including acute toxicity, oxidative stress, apoptosis, immunotoxicity, and metabolic capability. The results showed that the presence of PS nanoplastics could act as a carrier of the co-existing AgNPs in waters. The release ratio of Ag+ from AgNPs was up to 4.23%. The lethal effects of AgNPs on zebrafish embryos were not significantly changed by the co-added PS nanoplastics. Whereas, the alterations in gene expression related to antioxidant and metabolic capability in zebrafish (sod1, cat, mt2, mtf-1, and cox1) caused by AgNPs were significantly enhanced by the presence of PS nanoplastics, which simultaneously lowered the apoptosis and immunotoxicity (caspase9, nfkβ, cebp, and il-1β) induced by AgNPs. It suggests the presence of PS nanoplastics suppressed the AgNPs-induced genotoxicity in zebrafish. The released Ag+ from AgNPs may be responsible for the toxicity of AgNPs in zebrafish, while the subsequent absorption and agglomeration of AgNPs and the released Ag+ on PS nanoplastics may alleviate the toxicity.
Allele distribution and phenotypic resistance to ciprofloxacin and gentamicin among extended-spectrum β-lactamase-producing Escherichia coli isolated from the urine, stool, animals, and environments of patients with presumptive urinary tract infection in Tanzania

Background Additional antimicrobial resistance to extended-spectrum β-lactamase (ESBL)-producing E. coli exhausts treatment options. We investigated allele distribution and resistance to ciprofloxacin and gentamicin among ESBL-producing E. coli isolates from the urine, stool, animals, and environments of presumptive urinary tract infection (UTI) patients, in order to gain a crucial insight toward devising prevention and control measures and treatment guidelines. Methods Archived ESBL-producing E. coli isolates from the urine, stool, animals, and surrounding environments of presumptive UTI patients were retrieved. Antimicrobial susceptibility profiles for ciprofloxacin and gentamicin were done followed by multiplex Polymerase chain reaction (PCR) for blaCTX-M , blaTEM , and blaSHV , to determine ESBL allele distribution. Data were analyzed using STATA version 17. Results A total of 472 confirmed ESBL-producing E. coli isolates from Mwanza 243 (51.5%), Kilimanjaro 143 (30.3%), and Mbeya 86 (18.2%) were analyzed. Of these, 75 (15.9%) were from urine, 199 (42.2%) from stool, 58 (12.3%) from rectal/cloaca swabs of animals, and 140 (29.7%) from surrounding environments. Out of the 472 ESBL-producing E. coli, 98.9% (467) had at least one ESBL allele. The most frequent allele was blaCTX-M , which was detected in 88.1% (416/472) of isolates, followed by the blaTEM allele, which was detected in 51.5% (243/472) of isolates. A total of 40.7% (192/472) of isolates harbored dual blaCTX-M + blaTEM alleles and only 0.2% (1/472) of isolates had dual blaCTX-M + blaSHV alleles, whereas 2.3% (11/472) of isolates had a combination of all three alleles (blaCTX-M + blaTEM + blaSHV ). None of the isolates harbored a combination of blaTEM + blaSHV only. Resistance to ciprofloxacin and gentamicin was observed in 70.8% (334/472) and 46.0% (217/472) of isolates, respectively. There was a significant difference in the distribution of resistance to ciprofloxacin as well as gentamicin among ESBL-producing E. coli isolated from various sources (p-value < 0.001 and 0.002, respectively). Conclusion Almost all ESBL-producing E. coli isolates carry blaCTX-M , blaTEM , and blaSHV either alone or in combination, with the most common allele being blaCTX-M. The resistance to ciprofloxacin and gentamicin, which are frontline antibiotics for UTIs among ESBL-producing E. coli, is high. This implies the need to continually revise the local guidelines used for optimal empirical therapy for UTIs, and for continual research and surveillance using one health approach.
Harnessing the probiotic properties and immunomodulatory effects of fermented food-derived Limosilactobacillus fermentum strains: implications for environmental enteropathy

Introduction Environmental enteropathy (EE), a chronic small intestine disease characterized by gut inflammation, is widely prevalent in low-income countries and is hypothesized to be caused by continuous exposure to fecal contamination. Targeted nutritional interventions using potential probiotic strains from fermented foods can be an effective strategy to inhibit enteric pathogens and prevent chronic gut inflammation. Methods We isolated potential strains from fermented rice water and lemon pickle and investigated their cell surface properties, antagonistic properties, adhesion to HT-29 cells, and inhibition of pathogen adherence to HT-29 cells. Bacteriocin-like inhibitory substances (BLIS) were purified, and in vivo, survival studies in Caenorhabditis elegans infected with Salmonella enterica MW116733 were performed. We further checked the expression pattern of pro and anti-inflammatory cytokines (IL-6, IL8, and IL-10) in HT-29 cells supplemented with strains. Results The strains isolated from rice water (RS) and lemon pickle (T1) were identified as Limosilactobacillus fermentum MN410703 and MN410702, respectively. Strains showed probiotic properties like tolerance to low pH (pH 3.0), bile salts up to 0.5%, simulated gastric juice at low pH, and binding to extracellular matrix molecules. Auto-aggregation of T1 was in the range of 85% and significantly co-aggregated with Klebsiella pneumoniae, S. enterica, and Escherichia coli at 48, 79, and 65%, respectively. Both strains had a higher binding affinity to gelatin and heparin compared to Bacillus clausii. Susceptibility to most aminoglycoside, cephalosporin, and macrolide classes of antibiotics was also observed. RS showed BLIS activity against K. pneumoniae, S. aureus, and S. enterica at 60, 48, and 30%, respectively, and the protective effects of BLIS from RS in the C. elegans infection model demonstrated a 70% survival rate of the worms infected with S. enterica. RS and T1 demonstrated binding efficiency to HT-29 cell lines in the 38–46% range, and both strains inhibited the adhesion of E. coli MDR and S. enterica. Upregulation of IL-6 and IL-10 and the downregulation of IL-8 were observed when HT-29 cells were treated with RS, indicating the immunomodulatory effects of the strain. Discussion The potential strains identified could effectively inhibit enteric pathogens and prevent environmental enteropathy.
Commentary: Evaluating stock status of 16 commercial fish species in the coastal and offshore waters of Taiwan using the CMSY and BSM methods

COPYRIGHT © 2023 Kuo, Su, Cheng, Liu, Chen, Lu and Lee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE General Commentary PUBLISHED 05 June 2023 DOI 10.3389/fmars.2023. 1152982
The Entrepreneurial Career Path: A Systematic Literature Review

Maneuvering towards a framework of entrepreneurship as a career path, first I carried out a systematic review of the literature including both bibliometric and document review. There is a scholarly understanding of entrepreneurship as a career although a great deal of entrepreneurship career research focuses on the founding of a new venture and yet less is known about entrepreneurship as a career path. Emerging works on the entrepreneurship career are disconnected and explain the various dimensions of the entrepreneurship career from the stages of entry, success, and outcomes instead of seeing them as a connected career trajectory. The bibliometric review identified five themes signaling the ongoing semantic conversations with reference to entrepreneurship career. Moreover, through the systematic review of documents, I identified three themes that hint at activities and possible transitions occurring along the entrepreneurship career path. I propose a framework on entrepreneurship as a career path and suggest potential directions for future research.