What works? Lessons from a pretrial qualitative study to inform a multi-component intervention for refugees and asylum seekers: Learning Through Play and EMDR Group Traumatic Episode Protocol.

Almost half of the trials failed to recruit their targeted sample size of which 89% could be preventable. Successful implementation of mental health trials in a context of forcibly displaced individuals can be even more challenging. Mental health difficulties have the potential to impact parenting skills, which are linked to poor development in children, while parenting interventions can improve parents' mental health and parenting behaviors. However, the evidence on parenting interventions for refugees is limited. A parenting intervention, Learning Through Play Plus Eye Movement Desensitization and Reprocessing Group Treatment Protocol, has been designed to address parental mental health. This pretrial qualitative study, conducted with refugees, asylum seekers and professionals, aimed to explore their perceptions of the intervention and to identify barriers and recommendations for better engagement, recruitment, and delivery. Three themes were generated from thematic analysis: the content of the intervention, suggestions for improvement and implementation, and understanding the role of the facilitator. These themes provided insights into the issues that might predict the barriers for delivery of the intervention and offered several changes, including destigmatization strategies to improve engagement.

Does being infected with SARS-CoV-2 in the first-trimester increase the risk of miscarriage?

Aim of this study is to investigate whether the risk of miscarriage increases in pregnant women who had COVID-19 in first trimester. Our study included 52 patients with SARS-CoV-2 infection detected by RT-PCR and 53 patients with negative RT-PCR test in samples taken with nasopharyngeal swab in the first trimester between March 1 and December 31, 2020. Complete abortion, incomplete abortion, blighted ovum, intrauterine exitus, biochemical pregnancies were accepted as in the miscarriage group (MG). Pregnant women with COVID-19 and control group were compared in terms of demographic data, miscarriage rate and laboratory results. Patients were divided into MG and ongoing pregnancy groups (OPG) and compared in terms of the diagnosed weeks, clinical findings, laboratory results, treatments, and hospitalization. While miscarriage was observed in 15 (28.8%) of pregnant women infected with SARS-CoV-2 in the first trimester, this number was 7 (13.2%) in the control group. While the common symptoms in the MG were cough (60%), fever (53.3%), shortness of breath (53.3%), and fatigue (46.7%) (p<0.05); asymptomatic patients (51.4%) were higher in the OPG (p<0.001). Hospitalized patients were 33.3% in the MG and 8.1% in the OPG (p=0.02). According to the results of our study, the risk of miscarriage increases in pregnant women infected with SARS-CoV-2 (especially in severe infection) in the first trimester.

Next-Generation Grade and Survival Expression Biomarkers of Human Gliomas Based on Algorithmically Reconstructed Molecular Pathways.

In gliomas, expression of certain marker genes is strongly associated with survival and tumor type and often exceeds histological assessments. Using a human interactome model, we algorithmically reconstructed 7494 new-type molecular pathways that are centered each on an individual protein. Each single-gene expression and gene-centric pathway activation was tested as a survival and tumor grade biomarker in gliomas and their diagnostic subgroups (IDH mutant or wild type, IDH mutant with 1p/19q co-deletion, MGMT promoter methylated or unmethylated), including the three major molecular subtypes of glioblastoma (proneural, mesenchymal, classical). We used three datasets from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas, which in total include 527 glioblastoma and 1097 low grade glioma profiles. We identified 2724 such gene and 2418 pathway survival biomarkers out of total 17,717 genes and 7494 pathways analyzed. We then assessed tumor grade and molecular subtype biomarkers and with the threshold of AUC > 0.7 identified 1322/982 gene biomarkers and 472/537 pathway biomarkers. This suggests roughly two times greater efficacy of the reconstructed pathway approach compared to gene biomarkers. Thus, we conclude that activation levels of algorithmically reconstructed gene-centric pathways are a potent class of new-generation diagnostic and prognostic biomarkers for gliomas.

The Role of Extracellular Vesicles Secreted From Thermal Stress-Induced Adipose-Derived Stem Cells on Bone Regeneration.

PURPOSE: Extracellular vesicles (EVs) are responsible for intercellular communication. Mesenchymal stem cell-derived vesicles have been shown to have similar properties as functional mesenchymal stem cells. The aim of this study was to compare the therapeutic benefit of EVs obtained from adipose tissue-derived stem cells (ADSC) on bone repair whereas using ß-tricalcium phosphate (ß-TCP) biomaterial as a carrier. MATERIALS AND METHOD: A single critical size bone defect of 8 mm in diameter was created on the right side of rat calvarium using a custom-made punch needle. Animals were randomly divided into 5 groups: group 1 (no treatment), group 2 (bone graft), group 3 (ß-TCP + ADSC), group 4 (ß-TCP + EV), group 5 (ß-TCP). Eight weeks later, animals were sacrificed and histologic and radiologic evaluation was performed. RESULTS: Semiquantitative histologic scoring demonstrated significantly higher bone regeneration scores for groups 2, 3, and 4 compared to group 1. Radiologic imaging showed significantly higher bone mineral density for groups 2, 3, and 5 compared to group 1. There were no significant differences between treatment groups in either histologic or radiologic scoring. CONCLUSIONS: Our data showed that EVs provided from thermally induced ADSCs did not show any significant difference in bone regeneration when compared to ADSCs themselves. Future studies should focus on determining the optimum amount and content of EV application since these vary significantly depending on the microenvironment.

Propolis-Based Nanofiber Patches to Repair Corneal Microbial Keratitis.

In this research, polyvinyl-alcohol (PVA)/gelatin (GEL)/propolis (Ps) biocompatible nanofiber patches were fabricated via electrospinning technique. The controlled release of Propolis, surface wettability behaviors, antimicrobial activities against the S. aureus and P. aeruginosa, and biocompatibility properties with the mesenchymal stem cells (MSCs) were investigated in detail. By adding 0.5, 1, and 3 wt.% GEL into the 13 wt.% PVA, the morphological and mechanical results suggested that 13 wt.% PVA/0.5 wt.% GEL patch can be an ideal matrix for 3 and 5 wt.% propolis addition. Morphological results revealed that the diameters of the electrospun nanofiber patches were increased with GEL (from 290 nm to 400 nm) and Ps addition and crosslinking process cause the formation of thicker nanofibers. The tensile strength and elongation at break enhancement were also determined for 13 wt.% PVA/0.5 wt.% GEL/3 wt.% Ps patch. Propolis was released quickly in the first hour and arrived at a plateau. Cell culture and contact angle results confirmed that the 3 wt.% addition of propolis reinforced mesenchymal stem cell proliferation and wettability properties of the patches. The antimicrobial activity demonstrated that propolis loaded patches had antibacterial activity against the S. aureus, but for P. aeruginosa, more studies should be performed.

Serum concentrations of heavy metals in women with endometrial polyps.

Endometrial polyps are one of the common reasons of abnormal uterine bleeding in women. Industrialisation, urbanisation and increased air pollution cause increased heavy metal exposure. Heavy metals that have oestrogenic effects in human body are named as metalloestrogens. The aim of this study was to investigate the serum metalloestrogen levels such as copper (Cu), zinc (Zn), aluminium (Al), lead (Pb), nickel (Ni) and Cu/Zn ratio and their possible relationship with the occurrence of endometrial polyps. Eighty women with abnormal uterine bleeding were divided into two groups: 40 women diagnosed with endometrial polyp (study group) and 40 women without endometrial polyp (control group). Ages, body mass indices, smoking behaviours, drinking water choices, chronic diseases and intrauterine device histories were noted for all patients. Blood levels of Cu, Zn, Al, Pb, Ni and Cu/Zn ratio were analysed by inductively coupled plasma-mass spectrometry method for both groups. No statistically significant differences were observed in terms of serum median levels of Cu and Pb between the study and the control groups. The serum median levels of Zn, Ni and Al were found to be statistically lower in the study group when compared with the control group. The Cu/Zn ratio was statistically higher in the study group. High Cu/Zn ratio, as a biomarker of oxidative stress, suggests the role of oxidative stress in etiopathogenesis of endometrial polyps.IMPACT STATEMENTWhat is already known on this subject? Studies demonstrate that oestrogen and progesterone play an important role in pathogenesis of endometrial polyps. Inorganic heavy metal ions that bind and activate oestrogen receptors are referred to as 'metalloestrogens'. Apart from toxic effects, metalloestrogens have been linked to the aetiology of oestrogen-dependent diseases such as breast and endometrium cancer and endometriosis. However, serum levels of heavy metals were not investigated in a large group of endometrial polyp patients.What do the results of this study add? This is the first study investigating the serum levels of heavy metals in a large group of endometrial polyp patients. We did not observe any increased serum levels of heavy metals in endometrial polyp patients. Our results might suggest that oestrogenic heavy metal exposure has no role in the appearance of endometrial polyps. However, increased Cu/Zn ratio due to low serum levels zinc suggests oxidative stress might play a role in endometrial polyps.What are the implications of these findings for clinical practice and/or further research? Further research of heavy metals in endometrial polyps with simultaneous blood and tissue samples could show the precise effect of environmental exposure of metalloestrogens in aetiopathogenesis of endometrial polyps.

Food Additive Sodium Benzoate (NaB) Activates NFκB and Induces Apoptosis in HCT116 Cells.

NaB, the metabolite of cinnamon and sodium salt of benzoic acid is a commonly used food and beverage preservative. Various studies have investigated NaB for its effects on different cellular models. However, the effects of NaB on cancer cell viability signaling is substantially unknown. In this study, the effects of NaB on viability parameters and NFκB, one of the most important regulators in apoptosis, were examined in HCT116 colon cancer cells. Cell culture, light microscopy, spectrophotometry, flow cytometry, and western blot were used as methods to determine cell viability, caspase-3 activity, NFκB, Bcl-xl, Bim, and PARP proteins, respectively. NaB (6.25 mM-50 mM) treatment inhibited cell viability by inducing apoptosis, which was evident with increased Annexin V-PE staining and caspase-3 activity. NFκB activation accompanied the induction of apoptosis in NaB treated cells. Inhibition of NFκB with BAY 11-7082 did not show a pronounced effect on cell viability but induced a more apoptotic profile, which was confirmed by increased PARP fragmentation and caspase-3 activity. This effect was mostly evident at 50 mM concentration of NaB. Bcl-xl levels were not affected by NaB or BAY 11-7082/NaB treatment; whereas, total Bim increased with NaB treatment. Inhibition of NFκB activity further increased Bim levels. Overall, these results suggest that NaB induces apoptosis and activates NFκB in HCT116 colon cancer cells. Activation of NFκB emerges as target in an attempt to protect cells against apoptosis.

Electrocardiographic intervals in foetuses with CHD.

OBJECTIVES: To assess foetal electrocardiographic intervals across gestational age among foetuses with and without congenital heart disease, and to investigate differences between groups. DESIGN: A prospective observational cohort study. SETTING: Center for Prenatal Pediatrics, Morgan Stanley Children's Hospital of New York-Presbyterian. Population or sample A total of 92 participants with singleton pregnancies, 41 with normal anatomy and 51 with congenital heart disease were included in this study. METHODS: Using a maternal abdominal monitor, foetal electrocardiogram was obtained serially from foetuses with and without congenital heart disease at 20-24 weeks (F1), 28-32 weeks (F2), and 34-38 weeks (F3) of gestation. A signal-averaged waveform was calculated, and PR, QRS, and QT intervals were measured. Intervals from controls were compared with gestational age norms. Using Pearson's correlation coefficient, we analysed the relationship between gestational age and foetal electrocardiographic intervals. Intervals from control and congenital heart disease foetuses were compared by Student's t-test. RESULTS: PR (r=0.333, p=0.02) and QRS (r=0.248, p=0.05) intervals correlated with gestational age only among controls. QRS intervals in foetuses with congenital heart disease were significantly longer than controls at F1 (63 ± 6 versus 52 ± 5 ms, p<0.001), F2 (61 ± 8 versus 56 ± 7 ms, p=0.02), and F3 (64 ± 10 versus 56 ± 9 ms, p=0.007). CONCLUSIONS: PR and QRS intervals lengthen across gestational age among foetuses with normal cardiac anatomy but not in foetuses with congenital heart diseases. As early as 20 weeks of gestation, differences between foetuses with and without congenital heart disease are discernible, with congenital heart disease foetuses demonstrating longer QRS intervals compared with controls.

Unusual variant of tetralogy of Fallot with pulmonary atresia: a right pulmonary artery from the ascending aorta and a coronary-to-left pulmonary artery collateral.

We present the case of a newborn with tetralogy of Fallot and pulmonary atresia, with a right pulmonary artery from the ascending aorta, and a left pulmonary artery arising from the right coronary artery via an indirect aortopulmonary collateral. The embryogenesis of this unusual combination of pulmonary blood supply has significant implications when considering normal migration of the aortopulmonary septum.

Digital natives of the labor market: Generation Z as future leaders and their perspectives on leadership.

Introduction: Today's labor market is comprised of different generations and in the near future, the majority of it will consist of Generation Z. In this respect, it is of great importance to know the perspective of Generation Z, which will take its place in leadership positions in organizations, on leadership and what kind of leader they will be. The present study probes to investigate how Generation Z will become a leader and their perspective on leadership. In this regard, the study aims to offer suggestions and guidance to the literature and organizations by providing information on what kind of leaders they will be as well as knowing the characteristics of Generation Z leaders. Methods: In the study conducted Generation Z, employed in the IT sector, semi-structured interviews were held with 13 participants. While analyzing the data obtained from the interviews, the MAXQDA 2020 program was utilized and the thematic analysis method was applied. Results: In our findings about how Generation Z will be leaders in the future, two themes were identified, which include intra-organizational communication and working conditions. In the light of findings on the leadership of Generation Z, the sub-themes of being supportive, empathetic, egoless, managing people well and managing with love and respect were reached on the theme of intra-organizational communication. On the other hand, on the theme of working conditions, sub-themes such as providing training, offering payment according to output, preferring flexible working hours, being friendly, assigning appropriate work to the employee, being fun and not giving importance to gender were identified. Discussion: The results revealed that Generation Z prefers managing their team with a people-oriented approach when they take leadership positions. From their perspective, the leader should understand and value his employees. Leaders who know the expectations of Generation Z will contribute to their organizations. In addition, organizations should improve their leadership skills by providing leadership training for Generation Z, who will be leaders in the future. In this way, they will make investment both in their leaders and their organizations.

Is seborrheic dermatitis associated with early-stage osteoarthritis?

Seborrheic dermatitis (SD) and osteoarthritis involve similar factors in their pathogenesis. Both of these diseases are associated with an increased frequency of metabolic syndrome and underlying systemic inflammation. This study evaluated the thickness of the distal femoral cartilage using ultrasonography in patients with SD. The study enrolled 60 patients with SD (19 females and 41 males, mean age: 34.07 ±â€…12.56 years) and 60 controls matched for age and sex (20 females and 40 males, mean age: 35.08 ±â€…12.78 years). Ultrasonography was used to measure the distal femoral cartilage thickness (FCT) of the right medial condyle, right lateral condyle, right intercondylar area, left medial condyle, left lateral condyle, and left intercondylar area. FCT values at all points were significantly higher in patients with SD than in the controls (P < .05). Further, all FCT values were significantly higher in patients with moderate SD than in those with mild SD (P < .001). A strong positive correlation was observed between disease severity and FCT measured at right medial condyle (r = .7, P < .001), right lateral condyle (r = .749, P < .001), right intercondylar area (r = .79, P < .001), left medial condyle (r = .624, P < .001), and left intercondylar area (r = .703, P < .001). Further, a moderately positive correlation was observed between disease severity and FCT measured at left lateral condyle (r = .581, P < .001). Increased FCT in patients with SD might be an early indicator of osteoarthritis. However, further studies, especially those evaluating older patients with SD, are required to support our findings.

Lack of NAD(P)+ transhydrogenase activity in patients with primary adrenal insufficiency due to NNT variants.

BACKGROUND: Pathogenic variants in the nicotinamide nucleotide transhydrogenase gene (NNT) are a rare cause of primary adrenal insufficiency (PAI), as well as functional impairment of the gonads. OBJECTIVE: Despite the description of different homozygous and compound heterozygous NNT variants in PAI patients, the extent to which the function and expression of the mature protein are compromised remains to be clarified. DESIGN: The activity and expression of mitochondrial NAD(P)+ transhydrogenase (NNT) were analyzed in blood samples obtained from patients diagnosed with PAI due to genetically confirmed variants of the NNT gene (n = 5), heterozygous carriers as their parents (n = 8), and healthy controls (n = 26). METHODS: NNT activity was assessed by a reverse reaction assay standardized for digitonin-permeabilized peripheral blood mononuclear cells (PBMCs). The enzymatic assay was validated in PBMC samples from a mouse model of NNT absence. Additionally, the PBMC samples were evaluated for NNT expression by western blotting and reverse transcription quantitative polymerase chain reaction and for mitochondrial oxygen consumption. RESULTS: NNT activity was undetectable (<4% of that of healthy controls) in PBMC samples from patients, independent of the pathogenic genetic variant. In patients' parents, NNT activity was approximately half that of the healthy controls. Mature NNT protein expression was lower in patients than in the control groups, while mRNA levels varied widely among genotypes. Moreover, pathogenic NNT variants did not impair mitochondrial bioenergetic function in PBMCs. CONCLUSIONS: The manifestation of PAI in NNT-mutated patients is associated with a complete lack of NNT activity. Evaluation of NNT activity can be useful to characterize disease-causing NNT variants.

Prognostic utility of serum neopterin in obstructive jaundice secondary to malignant lesions treated by percutaneous transhepatic biliary drainage.

PURPOSE: To perform biochemical profiles before and after percutaneous transhepatic biliary drainage (PTBD) and investigate the potential utility of measuring C-reactive protein (CRP), circulating cytokines, and neopterin, a marker of cell-mediated immunity, to predict outcomes of patients with obstructive jaundice. MATERIALS AND METHODS: In a prospective study, 47 patients with obstructive jaundice secondary to malignant lesions were evaluated before, at the fifth hour after, and on the fifth day after PTBD for neopterin, nitrate, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, CRP levels, and liver function. RESULTS: Neopterin levels on day 5 after PTBD were significantly higher than the levels before treatment and at the fifth hour. However, nitrate, cytokine, white blood cell, albumin, and creatinine levels were not significantly different. On the fifth day after PTBD, CRP levels were significantly higher and total bilirubin, direct bilirubin, alkaline phosphatase, aspartate transaminase, and alanine transaminase values were lower than the before-treatment values. Seven patients (15%) died within 30 days after drainage. On the fifth day after PTBD, neopterin, IL-6, IL-10, and creatinine levels were significantly higher and albumin levels were lower in the early mortality group. The performance characteristics of neopterin and creatinine were statistically significant in predicting mortality. CONCLUSIONS: Neopterin levels increased after PTBD, indicating cellular immune activation. The nonsignificant change in cytokine levels may be related to low enduring release in malignancy. The extremely elevated levels of neopterin and creatinine after PTBD might serve as harbingers of early death in patients with cholestasis secondary to malignant lesions.

Left ventricular assist device to avoid heart-lung transplant in an adolescent with dilated cardiomyopathy and severely elevated pulmonary vascular resistance.

Orthotopic heart transplantation remains the definitive treatment of choice for patients with end-stage heart failure; however, elevated PVRI is a reported risk factor for mortality after heart transplant and, when severely elevated, is considered an absolute contraindication. Use of a ventricular assist device has been proposed as one treatment for reducing pulmonary vascular resistance index in potential heart transplant candidates refractory to medical vasodilator therapies. We report on a teenage patient with dilated cardiomyopathy and severely elevated PVRI, unresponsive to pulmonary vasodilator therapy, who underwent left ventricular assist device implantation to safely allow for aggressive pulmonary vasodilator therapy and to decrease PVRI. The resulting dramatic improvement in PVRI in a relatively short period of time allowed for successful heart transplantation, avoiding the need for heart-lung transplant.

Differential co-expression network analysis elucidated genes associated with sensitivity to farnesyltransferase inhibitor and prognosis of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease and the most common form of acute leukemia with a poor prognosis. Due to its complexity, the disease requires the identification of biomarkers for reliable prognosis. To identify potential disease genes that regulate patient prognosis, we used differential co-expression network analysis and transcriptomics data from relapsed, refractory, and previously untreated AML patients based on their response to treatment in the present study. In addition, we combined functional genomics and transcriptomics data to identify novel and therapeutically potential systems biomarkers for patients who do or do not respond to treatment. As a result, we constructed co-expression networks for response and non-response cases and identified a highly interconnected group of genes consisting of SECISBP2L, MAN1A2, PRPF31, VASP, and SNAPC1 in the response network and a group consisting of PHTF2, SLC11A2, PDLIM5, OTUB1, and KLRD1 in the non-response network, both of which showed high prognostic performance with hazard ratios of 4.12 and 3.66, respectively. Remarkably, ETS1, GATA2, AR, YBX1, and FOXP3 were found to be important transcription factors in both networks. The prognostic indicators reported here could be considered as a resource for identifying tumorigenesis and chemoresistance to farnesyltransferase inhibitor. They could help identify important research directions for the development of new prognostic and therapeutic techniques for AML.

Chemical compounds isolated from aerial parts of Bolanthus aziz-sancarii, a new species from Türkiye.

Bolanthus aziz-sancarii identified in 2019 for the first time is an endemic species of Bolanthus genus belonging to Caryophyllaceae family. Ten compounds were isolated from aerial parts of the plant. The potential antioxidant and anti-inflammatory effects of all four phases (hexane, chloroform, ethyl acetate, and water) from the methanol extract of the plant were investigated. After considering the findings regarding both antioxidant and anti-inflammatory capacities, it was decided to investigate the phytochemical profile of the EtOAc layer of B. aziz-sancarii. An abscisic acid-type sesquiterpene glucoside and nine flavonoid derivatives were isolated from the ethyl acetate fraction of the B. aziz-sancarii methanol extract through the use of column chromatography with silica gel.

Molecular Cardiotoxic Effects of Proteasome Inhibitors Carfilzomib and Ixazomib and Their Combination with Dexamethasone Involve Mitochondrial Dysregulation.

With the development and approval of new proteasome inhibitors, proteasome inhibition is increasingly recognized in cancer therapy. Besides successful anti-cancer effects in hematological cancers, side effects such as cardiotoxicity are limiting effective treatment. In this study, we used a cardiomyocyte model to investigate the molecular cardiotoxic mechanisms of carfilzomib (CFZ) and ixazomib (IXZ) alone or in combination with the immunomodulatory drug dexamethasone (DEX) which is frequently used in combination therapies in the clinic. According to our findings, CFZ showed a higher cytotoxic effect at lower concentrations than IXZ. DEX combination attenuated the cytotoxicity for both proteasome inhibitors. All drug treatments caused a marked increase in K48 ubiquitination. Both CFZ and IXZ caused an upregulation in cellular and endoplasmic reticulum stress protein (HSP90, HSP70, GRP94, and GRP78) levels and DEX combination attenuated the increased stress protein levels. Importantly, IXZ and IXZ-DEX treatments caused upregulation of mitochondria fission and fusion gene expression levels higher than caused by CFZ and CFZ-DEX combination. The IXZ-DEX combination reduced the levels of OXPHOS proteins (Complex II-V) more than the CFZ-DEX combination. Reduced mitochondrial membrane potential and ATP production were detected with all drug treatments in cardiomyocytes. Our findings suggest that the cardiotoxic effect of proteasome inhibitors may be due to their class effect and stress response and mitochondrial dysfunction may be involved in the cardiotoxicity process.

The angiogenic gene profile of pulmonary endarterectomy specimens: Initial study.

Objectives: The underlying mechanisms for the development of chronic thromboembolic pulmonary hypertension and prognostic biomarkers are not clear yet. Thus, our aim is to assess and identify new biomarkers for the expression of 84 key genes linked to angiogenesis. Methods: Patients who had levels more than 1000 dynes·sec·cm-5 were included in the test group, and the other patients were included in the control group. Twelve specimens were taken from the patients. RT2 Profiler PCR Array (Qiagen) was used to quantify the expression of the 84 key genes. Results: Eight patients (6 male, 2 female, median age 54.4 ± 13.1 years) who underwent pulmonary endarterectomy were included. Pulmonary vascular resistance improved significantly from 811 ± 390 dyn/s/cm-5 to 413.3 ± 144.9 dyn/s/cm-5 (P < .005). A difference was also detected in median mean pulmonary arterial pressure, which decreased from 49.8 ± 9 mm Hg to 32.62 ± 2.50 mm Hg (P > .005) after surgery. Median length of hospital stay was 11.62 ± 2.97 days. The test group had a distinct pattern of impaired angiogenic and antiangiogenic genes. The expression levels of TGFA, TGFB1, THBS2, THBS1, TGFBR1, SERPINE1, SERPINF1, TGFB2, TIMP2, VEGFC, IFNA1, TNF, CXCL10, NOS3, IGF1, and MMP14 were downregulated in the specimens from the patients who had higher pulmonary vascular resistance values, whereas some genes, including PDGFA, showed upregulation that was statistically nonsignificant in the same group. Conclusions: These results can lead to the development of new markers that could predict adverse outcomes of patients with CTEPH. Identification of new markers that are related to worse outcomes would enable screening patients for early diagnosis and treatment.

Uniformly shaped harmonization combines human transcriptomic data from different platforms while retaining their biological properties and differential gene expression patterns.

Introduction: Co-normalization of RNA profiles obtained using different experimental platforms and protocols opens avenue for comprehensive comparison of relevant features like differentially expressed genes associated with disease. Currently, most of bioinformatic tools enable normalization in a flexible format that depends on the individual datasets under analysis. Thus, the output data of such normalizations will be poorly compatible with each other. Recently we proposed a new approach to gene expression data normalization termed Shambhala which returns harmonized data in a uniform shape, where every expression profile is transformed into a pre-defined universal format. We previously showed that following shambhalization of human RNA profiles, overall tissue-specific clustering features are strongly retained while platform-specific clustering is dramatically reduced. Methods: Here, we tested Shambhala performance in retention of fold-change gene expression features and other functional characteristics of gene clusters such as pathway activation levels and predicted cancer drug activity scores. Results: Using 6,793 cancer and 11,135 normal tissue gene expression profiles from the literature and experimental datasets, we applied twelve performance criteria for different versions of Shambhala and other methods of transcriptomic harmonization with flexible output data format. Such criteria dealt with the biological type classifiers, hierarchical clustering, correlation/regression properties, stability of drug efficiency scores, and data quality for using machine learning classifiers. Discussion: Shambhala-2 harmonizer demonstrated the best results with the close to 1 correlation and linear regression coefficients for the comparison of training vs validation datasets and more than two times lesser instability for calculation of drug efficiency scores compared to other methods.