Prospective quantitative gene expression analysis of kallikrein-related peptidase KLK10 as a diagnostic biomarker for childhood acute lymphoblastic leukemia
Background The most common malignancy in children is acute lymphoblastic leukemia (ALL). This study aimed to explore KLK10 mRNA expression as a potential diagnostic biomarker for ALL in children and to examine the effect of chemotherapy on KLK10 mRNA expression following the induction and after three months of receiving chemotherapy. Methods In this prospective study, total RNA was extracted from blood samples of 23 pediatric ALL patients on diagnosis, after one month and three months of receiving chemotherapy. Healthy pediatric volunteers (n = 12) were selected as control individuals. After cDNA synthesis, KLK10 mRNA gene expression levels were quantified using quantitative real-time PCR (qRT-PCR). Results KLK10 mRNA expression levels were significantly decreased in leukemic cells compared to their levels in cells of normal blood samples (p = 0.0001). KLK10 expression levels in ALL patients after one month and three months of receiving chemotherapy decreased compared to normal blood samples (p < 0.0001 and p = 0.0175 respectively). The expression level of KLK10 mRNA in ALL patients after one month of chemotherapy was decreased compared to their level on diagnosis (p = 0.4413). KLK10 mRNA expression levels in ALL patients after three months of chemotherapy were increased compared to their level on diagnosis (p = 0.0602). The ROC curve illustrated that KLK10 mRNA expression could very efficiently discriminate ALL patients from normal counterparts (AUC=0.886, 95% CI [0.7720–1.000], SE = 0.0582, p = 0.0004). Conclusion KLK10 mRNA expression could serve as a potential diagnostic molecular biomarker for ALL in children.
Ahmad et al. (2022) Prospective quantitative gene expression analysis of kallikrein-related peptidase KLK10 as a diagnostic biomarker for childhood acute lymphoblastic leukemia. PeerJ 10:e13489 https://doi.org/10.7717/peerj.13489
Taxonomic and functional alterations in the salivary microbiota of children with and without severe early childhood caries (S-ECC) at the age of 3
Background Primary dental caries is the most prevalent oral disease among preschool children, which can cause severe damage to teeth and even affect the mental well-being of children. Various studies have demonstrated that the oral microbiome plays a pivotal role in the onset and development of dental caries. However, it remains uncertain about the key microbial markers associated with caries, owing to the limited evidence. Methods Fifteen S-ECC children and fifteen healthy controls were selected from three-year-old children in this study. Their clinical data and oral saliva samples were collected. Shotgun sequencing was conducted to investigate the microbial differences and the relevant functions between the two groups. Results We observed no apparent difference in oral microbial community diversity between the two groups. Still, at the genus/species levels, several characteristic genera/species such as Propionibacterium, Propionibacterium acidifaciens, Prevotella denticola, Streptococcus mutans and Actinomyces sp. oral taxon 448/414 increased significantly in S-ECC children, compared with the oral health group. Furthermore, we found that functional pathways involving glycolysis and acid production, such as starch and sucrose metabolism, fructose and mannose metabolism, glycolysis/gluconeogenesis, were prominently up-regulated in the high-caries group. Conclusions Our study showed that dental caries in children were associated with the alterations in the oral microbiota at the composition and functional levels, which may potentially inspire the exploration of microbial diagnosis or therapeutic treatments.
Tang et al. (2022) Taxonomic and functional alterations in the salivary microbiota of children with and without severe early childhood caries (S-ECC) at the age of 3. PeerJ 10:e13529 https://doi.org/10.7717/peerj.13529
Goal adjustment and well-being after an acquired brain injury: the role of cognitive flexibility and personality traits
Objective The tendency to flexibly adjust goals that are hindered by chronic illness is related to indicators of wellbeing. However, cognitive flexibility is often impaired in persons with an acquired brain injury (ABI), possibly affecting the ability to flexibly adjust goals. In this study we examined whether cognitive flexibility is positively related with the ability to disengage from goals to reengage with goals in persons with ABI. Second, we explored whether goal adjustment abilities are predictive of a unique proportion of the variance inabilities are predictive of quality of life and life satisfaction after controlling for personality traits. Method Seventy-eight persons with an ABI completed a set of questionnaires. Goal disengagement and goal reengagement were assessed using the Wrosch Goal Adjustment Scale (GAS). Indicators of wellbeing were measured with the European Brain Injury Questionnaire (EBIQ) and the Satisfaction with Life Scale (SWLS). The percentage of perseverative errors on the Wisconsin Card Sorting Test (WCST) was used as an indicator of cognitive inflexibility. Big Five personality traits were assessed via the NEO Five Factor Inventory (NEO-FFI). Four hierarchical multiple regression analyses were then conducted. The first two analyses tested the effect of cognitive flexibility on goal adjustment tendencies. The second two analyses tested whether goal adjustment has a predictive value for life satisfaction and QOL beyond personality. Results Cognitive flexibility was positively related to goal reengagement, but not to goal disengagement. Goal reengagement was positively associated with both quality of life and life satisfaction after controlling for demographic, illness characteristics and personality factors. Goal disengagement was negatively related to life satisfaction. Conclusion Flexible goal adjustment abilities have a unique explanatory value for indicators of wellbeing, beyond personality traits. The findings indicate that in persons with lower cognitive flexibility, goal reengagement ability might be negatively affected, and should be taking into account during rehabilitation.
Van Bost et al. (2022) Goal adjustment and well-being after an acquired brain injury: the role of cognitive flexibility and personality traits. PeerJ 10:e13531 https://doi.org/10.7717/peerj.13531
Seamens’ Sign: a novel electrocardiogram prediction tool for left ventricular hypertrophy
Introduction Patients with left ventricular hypertrophy (LVH) diagnosed by electrocardiogram (ECG) have increased mortality and higher risk for life-threatening cardiovascular disease. ECGs offer an opportunity to identify patients with increased risk for potential risk-modifying therapy. We developed a novel, quick, easy to use ECG screening criterion (Seamens’ Sign) for LVH. This new criterion was defined as the presence of QRS complexes touching or overlapping in two contiguous precordial leads. Methods This study was a retrospective chart review of 2,184 patient records of patients who had an ECG performed in the emergency department and a transthoracic echocardiogram performed within 90 days. The primary outcome was whether Seamens’ Sign was noninferior in confirming LVH compared to other common diagnostic criteria. Test characteristics were calculated for each of the LVH criteria. Inter-rater agreement was assessed on a random sample using Cohen’s Kappa. Results Median age was 63, 52% of patients were male and there was a 35% prevalence of LVH by transthoracic echocardiogram (TTE). Nine percent were positive for LVH on ECG based on Seamens’ Sign. Seamens’ Sign had a specificity of 0.92. Tests assessing noninferiority indicated Seamens’ Sign was non-inferior to all criteria (p < 0.001) except for Cornell criterion for women (p = 0.98). Seamens’ Sign had 90% (0.81–1.00) inter-rater agreement, the highest of all criteria in this study. Conclusion When compared to both the Sokolow-Lyon criteria and the Cornell criterion for men, Seamens’ Sign is noninferior in ruling in LVH on ECG. Additionally, Seamens’ Sign has higher inter-rater agreement compared to both Sokolow-Lyon criteria as well as the Cornell criteria for men and women, perhaps related to its ease of use.
Walker et al. (2022) Seamens’ Sign: a novel electrocardiogram prediction tool for left ventricular hypertrophy. PeerJ 10:e13548 https://doi.org/10.7717/peerj.13548
Glomerular filtration rate correlation and agreement between common predictive equations and standard 24-hour urinary creatinine clearance in medical critically ill patients
Background Determining kidney function in critically ill patients is paramount for the dose adjustment of several medications. When assessing kidney function, the glomerular filtration rate (GFR) is generally estimated either by calculating urine creatinine clearance (UCrCl) or using a predictive equation. Unfortunately, all predictive equations have been derived for medical outpatients. Therefore, the validity of predictive equations is of concern when compared with that of the UCrCl method, particularly in medical critically ill patients. Therefore, we conducted this study to assess the agreement of the estimated GFR (eGFR) using common predictive equations and UCrCl in medical critical care setting. Methods This was the secondary analysis of a nutrition therapy study. Urine was collected from participating patients over 24 h for urine creatinine, urine nitrogen, urine volume, and serum creatinine measurements on days 1, 3, 5, and 14 of the study. Subsequently, we calculated UCrCl and eGFR using four predictive equations, the Cockcroft–Gault (CG) formula, the four and six-variable Modification of Diet in Renal Disease Study (MDRD-4 and MDRD-6) equations, and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The correlation and agreement between eGFR and UCrCl were determined using the Spearman rank correlation coefficient and Bland–Altman plot with multiple measurements per subject, respectively. The performance of each predictive equation for estimating GFR was reported as bias, precision, and absolute percentage error (APE). Results A total of 49 patients with 170 urine samples were included in the final analysis. Of 49 patients, the median age was 74 (21–92) years-old and 49% was male. All patients were hemodynamically stable with mean arterial blood pressure of 82 (65–108) mmHg. Baseline serum creatinine was 0.93 (0.3–4.84) mg/dL and baseline UCrCl was 46.69 (3.40–165.53) mL/min. The eGFR from all the predictive equations showed modest correlation with UCrCl (r: 0.692 to 0.759). However, the performance of all the predictive equations in estimating GFR compared to that of UCrCl was poor, demonstrating bias ranged from −8.36 to −31.95 mL/min, precision ranged from 92.02 to 166.43 mL/min, and an unacceptable APE (23.01% to 47.18%). Nevertheless, the CG formula showed the best performance in estimating GFR, with a small bias (−2.30 (−9.46 to 4.86) mL/min) and an acceptable APE (14.72% (10.87% to 23.80%)), especially in patients with normal UCrCl. Conclusion From our finding, CG formula was the best eGFR formula in the medical critically ill patients, which demonstrated the least bias and acceptable APE, especially in normal UCrCl patients. However, the predictive equation commonly used to estimate GFR in critically ill patients must be cautiously applied due to its large bias, wide precision, and unacceptable error, particularly in renal function impairment.
Wongpraphairot et al. (2022) Glomerular filtration rate correlation and agreement between common predictive equations and standard 24-hour urinary creatinine clearance in medical critically ill patients. PeerJ 10:e13556 https://doi.org/10.7717/peerj.13556
Quality assessment of a serum and xenofree medium for the expansion of human GMP-grade mesenchymal stromal cells
Background Cell-based therapies are emerging as a viable modality to treat challenging diseases, resulting in an increasing demand for their large-scale, high-quality production. Production facilities face the issue of batch-to-batch consistency while producing a safe and efficient cell-based product. Controlling culture conditions and particularly media composition is a key factor of success in this challenge. Serum and Xeno-Free Media (SXFM) represent an interesting option to achieve this goal. By reducing batch to batch variability, they increase Good Manufacturing Practices (GMP)-compliance and safety regarding xenogenic transmission, as compared to fetal bovine serum (FBS) supplemented-media or human platelet lysate supplemented medium. Methods In this study, the isolation, expansion and characteristics including the anti-inflammatory function of human mesenchymal stromal cells (MSC) are compared after culture in MEMα supplemented with human Concentrate Platelet Lysate (hCPL, reference medium) or in MSC-Brew GMP Medium. The latter is a GMP SXFM manufactured in bags under strictly controlled conditions in volumes suitable for expansion to a clinical scale and does not require neither pre-coating of the cell culture units nor the addition of blood derivatives at the isolation step. Results We showed that MSC derived from human bone-marrow and adipose tissue can be successfully isolated and expanded in this SXFM. Number and size of Colony-Forming Unit fibroblast (CFU-F) is increased compared to cells cultivated in hCPL medium. All cells retained a CD90+, CD73+, CD105+, HLADR−, CD34−, CD45− phenotype. Furthermore, the osteogenic and adipocyte potentials as well as the anti-inflammatory activity were comparable between culture conditions. All cells reached the release criteria established in our production facility to treat inflammatory pathologies. Conclusions The use of MSC-Brew GMP Medium can therefore be considered for clinical bioprocesses as a safe and efficient substitute for hCPL media.
Aussel et al. (2022) Quality assessment of a serum and xenofree medium for the expansion of human GMP-grade mesenchymal stromal cells. PeerJ 10:e13391 https://doi.org/10.7717/peerj.13391
IL-4/IL-13 axis as therapeutic targets in allergic rhinitis and asthma
Allergic rhinitis (AR) is a common disorder of the upper airway, while asthma is a disease affecting the lower airway and both diseases are usually comorbid. Interleukin (IL)-4 and IL-13 are critical cytokines in the induction of the pathogenic Th2 responses in AR and asthma. Targeting the IL-4/IL-13 axis at various levels of its signaling pathway has emerged as promising targeted therapy in both AR and asthma patient populations. In this review, we discuss the biological characteristics of IL-4 and IL-13, their signaling pathways, and therapeutic antibodies against each cytokine as well as their receptors. In particular, the pleiotropic roles of IL-4 and IL-13 in orchestrating Th2 responses in AR and asthma patients indicate that dual IL-4/IL-13 blockade is a promising therapeutic strategy for both diseases.
Nur Husna et al. (2022) IL-4/IL-13 axis as therapeutic targets in allergic rhinitis and asthma. PeerJ 10:e13444 https://doi.org/10.7717/peerj.13444
Too perfect to be good? An investigation of magicians’ Too Perfect Theory
The “Too Perfect Theory” states that if a trick is too perfect, it might paradoxically become less impressive, or give away its secret method. This theory suggests that an increased impossibility results in a less magical effect. The Too Perfect Theory is often applied to magic effects, but it conflicts with recent scientific investigations showing that participants’ level of enjoyment of a magic performance is positively related to their perceived impossibility of the trick. The current article investigated whether an imperfect magic performance is more impressive than a perfect one. Across two experiments, we studied whether participants enjoy a performance more if the effect is not perfect. We also examined the different types of explanations people give to these two types of performances. The results showed that participants enjoyed a perfect performance more than an imperfect one. However, consistently with the Too Perfect Theory, participants watching the perfect performance also discovered the correct method behind the magic trick more frequently and believed the performance was staged more often. Moreover, participants’ method explanation significantly impacted their reports about the performance.
Pailhès et al. (2022) Too perfect to be good? An investigation of magicians’ Too Perfect Theory. PeerJ 10:e13449 https://doi.org/10.7717/peerj.13449
UDP-glucose pyrophosphorylase: genome-wide identification, expression and functional analyses in Gossypium hirsutum
In this study, a total of 66 UDP-glucose pyrophosphorylase (UGP) (EC 2.7.7.9) genes were identified from the genomes of four cotton species, which are the members of Pfam glycosyltransferase family (PF01702) and catalyze the reaction between glucose-1-phosphate and UTP to produce UDPG. The analysis of evolutionary relationship, gene structure, and expression provides the basis for studies on function of UGP genes in cotton. The evolutionary tree and gene structure analysis revealed that the UGP gene family is evolutionarily conserved. Collinearity and Ka/Ks analysis indicated that amplification of UGP genes is due to repetitive crosstalk generating between new family genes, while being under strong selection pressure. The analysis of cis-acting elements exhibited that UGP genes play important role in cotton growth, development, abiotic and hormonal stresses. Six UGP genes that were highly expressed in cotton fiber at 15 DPA were screened by transcriptome data and qRT-PCR analysis. The addition of low concentrations of IAA and GA3 to ovule cultures revealed that energy efficiency promoted the development of ovules and fiber clusters, and qRT-PCR showed that expression of these six UGP genes was differentially increased. These results suggest that the UGP gene may play an important role in fiber development, and provides the opportunity to plant researchers to explore the mechanisms involve in fiber development in cotton.
Xu et al. (2022) UDP-glucose pyrophosphorylase: genome-wide identification, expression and functional analyses in Gossypium hirsutum. PeerJ 10:e13460 https://doi.org/10.7717/peerj.13460
Risk factors for falls in community-dwelling older people with mild cognitive impairment: a prospective one-year study
Objective Mild cognitive impairment (MCI) is considered an intermediate stage between normal cognitive function and dementia. Fall risk is increased in this group, but there is limited literature exploring specific fall risk factors that may be addressed in fall prevention strategies. The aim of this study was to examine risk factors for falls in older people with MCI, focusing on cognitive, psychological and physical factors. Methods Participants (n = 266, 45% women) were community-dwelling older people aged 70–90 years who met the criteria for MCI. Cognitive, psychological, sensorimotor and physical assessments, physical activity levels, medication use, general health and disability were ascertained at baseline. Falls were monitored prospectively for 12 months. Results During follow-up, 106 (40%) participants reported one or more falls. Poorer visual contrast sensitivity, increased postural sway, lower levels of weekly walking activity, higher levels of depressive symptoms and psychotropic medication use were significantly associated with faller status (≥1 falls) in univariable analyses. Of these factors, poor visual contrast sensitivity, increased postural sway and psychotropic medication use were found to be significant independent predictors of falls in multivariable analysis while controlling for age and sex. No measures of cognitive function were associated with falls. Conclusions Poor visual contrast sensitivity, impaired balance and psychotropic medication use predicted falls in community-dwelling people with MCI. These risk factors may be amenable to intervention, so these factors could be carefully considered in fall prevention programs for this population.
Chantanachai et al. (2022) Risk factors for falls in community-dwelling older people with mild cognitive impairment: a prospective one-year study. PeerJ 10:e13484 https://doi.org/10.7717/peerj.13484