Ventricular Tachycardia in Patients With Takotsubo Cardiomyopathy: Prevalence, Predictors, and Associated In-Hospital Adverse Events.

Introduction  The purpose of this study was to determine the prevalence of ventricular tachycardia (VT) among patients admitted with takotsubo cardiomyopathy (TCM) as well as to analyze the predictors of VT and the predictors of mortality among patients admitted with TCM. Methods Data were obtained from the National Inpatient Sample (NIS) database from January 2016 to December 2019. Patients with a primary diagnosis of TCM were selected using ICD-10 code I51.81. Subsequently, the study population was divided into patients who developed VT vs. patients who did not develop this complication. We then used multivariate logistic regression to assess the predictors of VT in our patient cohort as well as the predictors of mortality among patients admitted with TCM. Results  Of 40114 patients with TCM, 1923 developed VT (4.8%) during their hospital stay. Predictors of VT include atrial fibrillation (AF) (adjusted odds ratio (aOR): 1.592; 95% confidence interval (CI): 0.00-1.424; p=0.001), congestive heart failure (aOR: 1.451; 95% CI: 1.307-1.610; p=0.001), coagulopathy (aOR: 1.436; 95% CI: 1.150-1.793; p=0.001), and patients who self-identify in the race category as Other (aOR: 1.427; 95% CI: 1.086-1.875; p=0.011). Female sex was found to be protective against VT (aOR: 0.587; 95% CI: 0.526-0.656; p=0.001). Predictors of mortality among patients admitted with TCM include, among other factors, age (aOR: 1.014; 95% CI: 1.011-1.018; p=0.001), Asian or Pacific Islander race (aOR: 1.533; 95% CI: 1.197-1.964; p=0.001), Black race (aOR: 1.242; 95% CI: 1.062-1.452; p=0.007), VT (aOR: 1.754; 95% CI: 1.505-2.045; p=0.001), and AF (aOR: 1.441; 95% CI: 1.301-1.597; p=0.001). Some comorbidities that were protective against mortality in TCM include tobacco use disorder (aOR: 0.558; 95% CI: 0.255-0.925; p=0.028) and obstructive sleep apnea (aOR: 0.803; 95% CI: 0.651-0.990; p=0.028). The female sex was found to be protective against mortality (aOR: 0.532; 95% CI: 0.480-0.590; p=0.001).  Conclusion  In a large cohort of women admitted with TCM, we found the prevalence of VT to be 4.8%. Predictors of VT included conditions such as AF and congestive heart failure. The female sex was found to be protective against VT and protective against mortality among patients admitted with TCM.

Oral mucosa and cutaneous manifestations of psoriasis in an older patient: A case report.

BACKGROUND: Psoriasis is a common cutaneous disease; however, information about psoriasis-related oral mucosal lesions is scarce in the literature. CASE DESCRIPTION: We report a case of a 73-year-old male patient with cutaneous and oral palatal alterations. An incisional biopsy of these lesions revealed psoriasis. CONCLUSION: The current case highlights the importance of a systematic examination of the oral cavity in psoriasis patients for the appropriate diagnosis and management on the control of these lesions.

Evaluating the Utility of Portal Vein Pulsatility Index for Detecting Fluid Unresponsiveness in the Intensive Care Unit.

OBJECTIVE: The primary aim of the authors' study was to evaluate the capacity of the portal vein pulsatility index (PVP) to detect fluid unresponsiveness in patients admitted to intensive care. DESIGN: This was a retrospective, diagnostic accuracy study SETTING: At a tertiary medical-surgical intensive care unit in Buenos Aires, Argentina. PARTICIPANTS: Patients were included during usual care in the intensive care unit, who were evaluated by ultrasonography for the flow of the portal vein, calculating their PVP prior to fluid expansion. INTERVENTIONS: Patients who exhibited an increase of <15% in left ventricle outflow tract velocity-time integral after receiving 500 mL of Ringer Lactate were considered non-responders to fluids. MEASUREMENTS AND MAIN RESULTS: The authors included a total of 63 patients between January 2022 and October 2022. The area under the receiver operating characteristic curve for PVP to predict fluid unresponsiveness was 0.708 (95% CI 0.580 to 0.816). A value of the PVP >32% predicted fluid unresponsiveness with a sensitivity of 30.8% (95% CI 17% to 47.6%) and specificity of 100% (95% CI 85.8 to 100). The positive predictive value was 100%, and the negative predictive value was 47.1% (95% CI 41.9% to 52.3%). CONCLUSIONS: Although PVP has limited value as the sole indicator for fluid management decisions, it can be used as a stopping rule or combined with other diagnostic tests to improve the accuracy of fluid responsiveness assessment.

Catechin potentiates the antifungal effect of miconazole in Candida glabrata.

The rising number of invasive fungal infections caused by drug-resistant Candida strains is one of the greatest challenges for the development of novel antifungal strategies. The scarcity of available antifungals has drawn attention to the potential of natural products as antifungals and in combinational therapies. One of these is catechins-polyphenolic compounds-flavanols, found in a variety of plants. In this work, we evaluated the changes in the susceptibility of Candida glabrata strain characterized at the laboratory level and clinical isolates using the combination of catechin and antifungal azoles. Catechin alone had no antifungal activity within the concentration range tested. Its use in combination with miconazole resulted in complete inhibition of growth in the sensitive C. glabrata isolate and a significant growth reduction in the azole resistant C. glabrata clinical isolate. Simultaneous use of catechin and miconazole leads to increased intracellular ROS generation. The enhanced susceptibility of C. glabrata clinical isolates to miconazole by catechin was accompanied with the intracellular accumulation of ROS and changes in the plasma membrane permeability, as measured using fluorescence anisotropy, affecting the function of plasma membrane proteins.

Essential Role of CgErg6p in Maintaining Oxidative Stress Tolerance and Iron Homeostasis in Candida glabrata.

The human pathogenic fungus Candida glabrata is the second leading cause of candidemia, a life-threatening invasive mycosis. Clinical outcomes are complicated by reduced susceptibility of C. glabrata to azoles together with its ability to evolve stable resistance to both azoles and echinocandins following drug exposure. Compared to other Candida spp., C. glabrata displays robust oxidative stress resistance. In this study, we investigated the impact of CgERG6 gene deletion on the oxidative stress response in C. glabrata. CgERG6 gene encodes sterol-24-C-methyltransferase, which is involved in the final steps of ergosterol biosynthesis. Our previous results showed that the Cgerg6Δ mutant has a lower ergosterol content in its membranes. Here, we show that the Cgerg6Δ mutant displays increased susceptibility to oxidative stress inducing agents, such as menadione, hydrogen peroxide and diamide, accompanied with increased intracellular ROS production. The Cgerg6Δ mutant is not able to tolerate higher concentrations of iron in the growth media. We observed increased expression of transcription factors, CgYap1p, CgMsn4p and CgYap5p, together with increased expression of catalase encoding the CgCTA1 gene and vacuolar iron transporter CgCCC1 in the Cgerg6Δ mutant cells. However, it seems that the CgERG6 gene deletion does not influence the function of mitochondria.

Health Maintenance and Preventative Care in Inflammatory Bowel Disease: A Systematic Review of the Overall Quality of Societal Recommendations.

BACKGROUND AIMS: Preventative care plays an important role in maintaining health in patients with inflammatory bowel disease (IBD). We aimed to assess the overall quality, strength, and transparency of conflicts among guidelines on preventative care in IBD. METHODS: A systematic literature search was performed in multiple databases to identify all guidelines pertaining to preventative care in IBD in April 2021. All guidelines were reviewed for the transparency of conflicts of interest and funding, recommendation quality and strength, external guideline review, patient voice inclusion, and plan for update-as per Institute of Medicine standards. In addition, recommendations and their quality were compared between societies. RESULTS: Fifteen distinct societies and a total of 89 recommendations were included. Not all guidelines provided recommendations on the key aspects of preventative care in IBD-such as vaccinations, cancer prevention, stress reduction, and diet/exercise. Sixty-seven percent of guidelines reported on conflicts of interest, 20% underwent external review, and 27% included patient representation. In all, 6.7%, 21.3%, and 71.9% of recommendations were based on high, moderate, and low-quality evidence, respectively. Twenty-seven percent, 23.6%, and 49.4% of recommendations were strong, weak/conditional, and did not provide a strength, respectively. The proportion of high-quality evidence ( P =0.28) and strong recommendations ( P =0.41) did not significantly differ across societies. CONCLUSIONS: Many guidelines do not provide recommendations on key aspects of preventative care in IBD. As over 70% of recommendations are based on low-quality evidence, further studies on preventative care in IBD are warranted to improve the overall quality of evidence.

WITHDRAWN: Non-Anti-TNF Biologics as Salvage Therapy for Refractory Acute Severe Ulcerative Colitis, A Systematic Review

Since the authors are not responding to the editor's requests to fulfill the editorial requirement, therefore, the article has been withdrawn.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Perfil clínico dos pacientes internados por Covid-19 na unidade de terapia intensiva / Clinical profile of patients hospitalized for Covid-19 in the intensive care unit

Objetivo: identificar o perfil clínico dos pacientes internados por COVID-19 na Unidade de Terapia Intensiva (UTI) de um hospital privado. Métodos: trata-se deum estudo de caráter descritivo, documental, retrospectivo, de corte transversal e análise quantitativa, conduzido em um hospital, no município de Montes Claros, MG, por meio da análise de prontuários de 142 pacientes da UTI com diagnóstico de COVID-19 no período de janeiro de 2020 a abril de 2021. Resultados: dos 142 indivíduos, a média de idadefoi de 64,1 anos, com 58,5% do sexo masculino. Das comorbidades prévias, as que tiveram maior prevalência foram a hipertensão arterial sistêmica com 26,8% e diabetes mellitus com 9,2%. Destes, 133 indivíduos utilizaram ventilação mecânica, com a prevalência de 47,9% no modo ventilação com volume controlado. O tempo médio de internação foi de 6 dias, sendo que 93,7% dos indivíduos foram a óbito, 4,9% receberam alta e 1,4% transferidos para outro hospital. Conclusão: evidenciou-se predominância do sexo masculino, com média de idade de 64,1 anos, o modo ventilatório mais utilizado foi o controlado o volume, com tempo de uso médio de uso 7,9 dias, ou seja, pouco tempo, fato que pode ser justificado pelo alto índice de óbitos na amostra estudada.

Objective: to identify the clinical profile of patients hospitalized for COVID-19 in the Intensive Care Unit (ICU) of a private hospital. Methods: this is a descriptive, documentary, retrospective, cross-sectional study with quantitative analysis conducted in a hospital in the city of Montes Claros, MG, through the analysis of medical records of 142 ICU patients diagnosed with COVID-19 from January 2020 to April 2021. Results: of the 142 individuals, the mean age was 64.1 years, with 58.5% male. Of the previous comorbidities, those with the highest prevalence were systemic arterial hypertension at 26.8% and diabetes mellitus at 9.2%. Of these, 133 individuals used mechanical ventilation, with a prevalence of 47.9% using volume-controlled ventilation. The average length of stay was 6 days, with 93.7% of the individuals dying, 4.9% being discharged, and 1.4% being transferred to another hospital. Conclusion: there was a predominance of males, with an average age of 64.1 years, the most used ventilatory mode was volume-controlled, with an average use time of 7.9 days, that is, a short time, a fact that can be justified by the high rate of deaths in the studied sample.

Erg6p is essential for antifungal drug resistance, plasma membrane properties and cell wall integrity in Candida glabrata.

ERG6 gene encodes C-24 methyltransferase, one of the specific enzymes that differ in mammalian and yeast sterol biosynthesis. To explore the function of CgErg6p in the yeast pathogen Candida glabrata, we have constructed the Cgerg6Δ deletion mutant. We found that C. glabrata cells lacking CgErg6p exhibit reduced susceptibility to both antifungal azoles and polyenes. The reduced content of ergosterol in the Cgerg6 deletion mutant was accompanied by increased expression of genes encoding the last steps of the ergosterol biosynthetic pathway. The absence of CgErg6p leads to plasma membrane hyperpolarization and decrease in its fluidity compared to the parental C. glabrata strain. The absence of sterols containing C-24 alkyls influenced the susceptibility of Cgerg6Δ mutant cells to alkali metal cations and several other metabolic inhibitors. Our results thus show that sterols lacking C-24 alkyls are not sufficient substitutes for maintaining yeast plasma membrane function. The absence of CgErg6p influences also the cell wall integrity and calcineurin signaling in C. glabrata.

Co-targeting CDK2 and CDK4/6 overcomes resistance to aromatase and CDK4/6 inhibitors in ER+ breast cancer.

Resistance to aromatase inhibitor (AI) treatment and combined CDK4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) are crucial clinical challenges in treating estrogen receptor-positive (ER+) breast cancer. Understanding the resistance mechanisms and identifying reliable predictive biomarkers and novel treatment combinations to overcome resistance are urgently needed. Herein, we show that upregulation of CDK6, p-CDK2, and/or cyclin E1 is associated with adaptation and resistance to AI-monotherapy and combined CDK4/6i and ET in ER+ advanced breast cancer. Importantly, co-targeting CDK2 and CDK4/6 with ET synergistically impairs cellular growth, induces cell cycle arrest and apoptosis, and delays progression in AI-resistant and combined CDK4/6i and fulvestrant-resistant cell models and in an AI-resistant autocrine breast tumor in a postmenopausal xenograft model. Analysis of CDK6, p-CDK2, and/or cyclin E1 expression as a combined biomarker in metastatic lesions of ER+ advanced breast cancer patients treated with AI-monotherapy or combined CDK4/6i and ET revealed a correlation between high biomarker expression and shorter progression-free survival (PFS), and the biomarker combination was an independent prognostic factor in both patients cohorts. Our study supports the clinical development of therapeutic strategies co-targeting ER, CDK4/6 and CDK2 following progression on AI-monotherapy or combined CDK4/6i and ET to improve survival of patients exhibiting high tumor levels of CDK6, p-CDK2, and/or cyclin E1.

Case Report: Cannabidiol-Induced Skin Rash: A Case Series and Key Recommendations.

Cannabidiol (CBD) is a non-psychotomimetic constituent of the Cannabis plant, with potential therapeutic properties for many physical and neuropsychiatric conditions. Isolated CBD has been suggested to have favorable safety and tolerability. Although CBD-related rash is described, few case reports are well documented in the literature, and usually, CBD was used concomitantly with other medications. Thus, we report four women who presented a skin rash after ongoing CBD use. Other causes of these skin rashes were ruled out after conducting an extensive viral and serological detection panel, and three patients had their lesions biopsied. Two patients were re-exposed to the vehicle (MCT) without developing a new skin rash. Therefore, clinicians must be aware of this potential adverse effect of CBD use.

The UPC2 gene in Kluyveromyces lactis stress adaptation.

KlUpc2p, a transcription factor belonging to the fungal binuclear cluster family, is an important regulator of ergosterol biosynthesis and azole drug resistance in Kluyveromyces lactis. In this work, we show that the absence of KlUpc2p generates Rag- phenotype and modulates the K. lactis susceptibility to oxidants and calcofuor white. The KlUPC2 deletion leads to increased expression of KlMGA2 gene, encoding an important regulator of hypoxic and lipid biosynthetic genes in K. lactis and also KlHOG1 gene. The absence of KlUpc2p does not lead to statistically significant changes in glycerol, corroborating the expression of KlGPD1 gene, encoding NAD+-dependent glycerol-3-phosphate dehydrogenase, that is similar in both the deletion mutant and the parental wild-type strain. Increased sensitivity of Klupc2 mutant cells to brefeldin A accompanied with significant increase in KlARF2 gene expression point to the involvement of KlUpc2p in intracellular signaling. Our observations highlight the connections between ergosterol and fatty acid metabolism to modulate membrane properties and point to the possible involvement of KlUpc2p in K. lactis oxidative stress response.

Generalized verrucosis in GATA2 deficiency successfully treated with systemic acitretin and trichloroacetic acid.

Generalized verrucosis is a clinical manifestation of human papillomavirus infection. Patients with generalized verrucosis present with over 20 verrucae distributed over various anatomical sites. The disorder occurs in association with several genetic syndromes with immunodeficiency, including GATA2 deficiency. We report a 12-year-old boy with GATA2 deficiency and generalized verrucosis that worsened after cyclosporine use following bone marrow transplant. Systemic treatment with acitretin and topical application of trichloroacetic acid, likely along with immune reconstitution, led to complete remission.

MCM3 upregulation confers endocrine resistance in breast cancer and is a predictive marker of diminished tamoxifen benefit.

Resistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer is a major clinical problem with poorly understood mechanisms. There is an unmet need for prognostic and predictive biomarkers to allow appropriate therapeutic targeting. We evaluated the mechanism by which minichromosome maintenance protein 3 (MCM3) influences endocrine resistance and its predictive/prognostic potential in ER+ breast cancer. We discovered that ER+ breast cancer cells survive tamoxifen and letrozole treatments through upregulation of minichromosome maintenance proteins (MCMs), including MCM3, which are key molecules in the cell cycle and DNA replication. Lowering MCM3 expression in endocrine-resistant cells restored drug sensitivity and altered phosphorylation of cell cycle regulators, including p53(Ser315,33), CHK1(Ser317), and cdc25b(Ser323), suggesting that the interaction of MCM3 with cell cycle proteins is an important mechanism of overcoming replicative stress and anti-proliferative effects of endocrine treatments. Interestingly, the MCM3 levels did not affect the efficacy of growth inhibitory by CDK4/6 inhibitors. Evaluation of MCM3 levels in primary tumors from four independent cohorts of breast cancer patients receiving adjuvant tamoxifen mono-therapy or no adjuvant treatment, including the Stockholm tamoxifen (STO-3) trial, showed MCM3 to be an independent prognostic marker adding information beyond Ki67. In addition, MCM3 was shown to be a predictive marker of response to endocrine treatment. Our study reveals a coordinated signaling network centered around MCM3 that limits response to endocrine therapy in ER+ breast cancer and identifies MCM3 as a clinically useful prognostic and predictive biomarker that allows personalized treatment of ER+ breast cancer patients.

MicroRNA-155-5p Plays a Critical Role in Transient Leukemia of Down Syndrome by Targeting Tumor Necrosis Factor Receptor Superfamily Members.

BACKGROUND/AIMS: Down syndrome associated disorders are caused by a complex genetic context where trisomy 21 is a central component in relation to other changes involving epigenetic regulators and signaling molecules. This unique genetic context is responsible for the predisposition of people with Down syndrome to acute leukemia. Although, the research in this field has discovered some important pathogenic keys, the exact mechanism of this predisposition is not known. METHODS: In this study we applied functional enrichment analysis to evaluate the interactions between genes localized on chromosome 21, genes already identify as having a key role in acute leukemia of Down syndrome, miRNAs and signaling pathways implicated in cancer and cell development and found that miR-155 has a high impact in genes present on chromosome 21. Forward, we performed next generation sequencing on DNA samples from a cohort of patients diagnosed with acute leukemia of Down syndrome and in vitro functional assay using a CMK-86 cell line, transfected with either mimic or inhibitor of the microRNA-155-5p. RESULTS: Our results show that the epigenetic alteration of the TNF superfamily receptors in Down syndrome, which can be correlated to microRNA-155-5p aberrant activity, may play an important role in cell signaling and thus be linked to acute myeloid leukemia. CONCLUSION: Some genes, already shown to be mutated in AML-DS, are potential targets for miR-155. Our results show that the epigenetic alteration of the TNF superfamily receptors in Down syndrome may play an important role in cell signaling and thus be linked to acute myeloid leukemia.

Koh group influence on titanium surfaces and pure sol-gel silica for enhanced osteogenic activity.

Although, the excellent level of success of titanium surfaces is based on the literature, there are some biological challenges such as unfavorable metabolic conditions or regions of poor bone quality where greater surface bioactivity is desired. Seeking better performance, we hypothesized that silica-based coating via sol-gel route with immersion in potassium hydroxide basic solution induces acceleration of bone mineralization. This in vitro experimental study coated titanium surfaces with bioactive glass synthesized by route sol-gel via hydrolysis and condensation of chemical alkoxide precursor, tetraethylorthosilicate (TEOS) and/or deposition of chemical compound potassium hydroxide (KOH) to accelerate bone apposition. The generated surfaces titanium(T), titanium with potassium hydroxide deposition (T + KOH), titanium with bioactive glass deposition synthesized by sol-gel route via tetraethylorthosilicate hydrolysis (TEOS), titanium with bioactive glass deposition synthesized by sol-gel route via tetraethylorthosilicate hydrolysis with potassium hydroxide deposition (TEOS + KOH) were characterized by 3D optical profilometry, scanning electron microscopy (SEM), transmission electron microscopy (TEM), contact angle by the sessile drop method, x-ray excited photoelectron spectroscopy (XPS) and energy dispersive x-ray spectrometer (EDX). The addition of the KOH group on the pure titanium (T) or bioactive glass (TEOS) surfaces generated a tendency for better results for mineralization. Groups covered with bioactive glass (TEOS, TEOS + KOH) tended to outperform even groups with titanium substrate (T, T + KOH). The addition of both, bioactive glass and KOH, in a single pure titanium substrate yielded the best results for the mineralization process.

Effect of surface treatments on staining and roughness of bleached enamel.

BACKGROUND: The objectives were to evaluate the effect of surface treatments and waiting time before contact with dye on bleached enamel staining and surface treatments on roughness. METHODS: One hundred bleached teeth were randomly assigned to G1 artificial saliva, G2 2% sodium fluoride (Flugel, Nova DFL), G3 casein phosphopeptide-amorphous calcium phosphate fluoride paste (MI Paste Plus, GC America), G4 rinse for bleached color maintenance (Keep White Rinse, DMC), and G5 polishing with impregnated disks (SuperBuff Disk, Shofu). Fifty specimens were immersed in coffee immediately after treatment; the others 1 h after. Color difference (ΔE) was evaluated with a spectrophotometer (Vita EasyShade) and roughness (Ra, Rq) with an optical profilometer (NewView 7300). Effects were analyzed with two-way ANOVA, Friedman, and Kruskal-Wallis test (P < 0.05). RESULTS: Surface treatments (P = 0.878), waiting time (P = 0.105), and interaction (P = 0.145) were not significant to bleached color maintenance. Roughness was different among the evaluation time points (2nd evaluation >1st evaluation >3rd evaluation) (P < 0.001); not among surface treatments (G1, G2, G3, G4, G5) (P > 0.05). CONCLUSIONS: Surface treatments were similar to saliva for bleached enamel color maintenance. Immediate or 1-h postponed contact with coffee did not affect bleached enamel color. Bleaching increased enamel roughness; surface treatments and artificial saliva decreased it.

Tumor Initiation Capacity and Therapy Resistance Are Differential Features of EMT-Related Subpopulations in the NSCLC Cell Line A549.

Cell lines are essential tools to standardize and compare experimental findings in basic and translational cancer research. The current dogma states that cancer stem cells feature an increased tumor initiation capacity and are also chemoresistant. Here, we identified and comprehensively characterized three morphologically distinct cellular subtypes in the non-small cell lung cancer cell line A549 and challenge the current cancer stem cell dogma. Subtype-specific cellular morphology is maintained during short-term culturing, resulting in the formation of holoclonal, meroclonal, and paraclonal colonies. A549 holoclone cells were characterized by an epithelial and stem-like phenotype, paraclone cells featured a mesenchymal phenotype, whereas meroclone cells were phenotypically intermediate. Cell-surface marker expression of subpopulations changed over time, indicating an active epithelial-to-mesenchymal transition (EMT), in vitro and in vivo. EMT has been associated with the overexpression of the immunomodulators PD-L1 and PD-L2, which were 37- and 235-fold overexpressed in para- versus holoclone cells, respectively. We found that DNA methylation is involved in epigenetic regulation of marker expression. Holoclone cells were extremely sensitive to cisplatin and radiotherapy in vitro, whereas paraclone cells were highly resistant. However, inhibition of the receptor tyrosine kinase AXL, whose expression is associated with an EMT, specifically targeted the otherwise highly resistant paraclone cells. Xenograft tumor formation capacity was 24- and 269-fold higher in holo- than mero- and paraclone cells, respectively. Our results show that A549 subpopulations might serve as a unique system to explore the network of stemness, cellular plasticity, tumor initiation capacity, invasive and metastatic potential, and chemo/radiotherapy resistance.