Immune Pathway and Gene Database (IMPAGT) Revealed the Immune Dysregulation Dynamics and Overactivation of the PI3K/Akt Pathway in Tumor Buddings of Cervical Cancer.

Tumor budding (TB) is a small cluster of malignant cells at the invasive front of a tumor. Despite being an adverse prognosis marker, little research has been conducted on the tumor immune microenvironment of tumor buddings, especially in cervical cancer. Therefore, RNA sequencing was performed using 21 formalin-fixed, paraffin-embedded slides of cervical tissues, and differentially expressed genes (DEGs) were analyzed. Immune Pathway and Gene Database (IMPAGT) was generated for immune profiling. "Pathway in Cancer" was identified as the most enriched pathway for both up- and downregulated DEGs. Kyoto Encyclopedia of Genes and Genomes Mapper and Gene Ontology further revealed the activation of the PI3K/Akt signaling pathway. An IMPAGT analysis revealed immune dysregulation even at the tumor budding stage, especially in the PI3K/Akt/mTOR axis, with a high efficiency and integrity. These findings emphasized the clinical significance of tumor buddings and the necessity of blocking the overactivation of the PI3K/Akt/mTOR pathway to improve targeted therapy in cervical cancer.

The NERSH Questionnaire and Pool of Data from 12 Countries: Development and Description.

Modern healthcare research has only in recent years investigated the impact of health care workers' religious and other values on medical practice, interaction with patients, and ethically complex decision making. So far, only limited international data exist on the way such values vary across different countries. We therefore established the NERSH International Collaboration on Values in Medicine with datasets on physician religious characteristics and values based on the same questionnaire. The present article provides (a) an overview of the development of the original and optimized questionnaire, (b) an overview of the content of the NERSH data pool at this stage and (c) a brief review of insights gained from articles published with the questionnaire. The pool at this stage consists of data from 17 studies from research units in 12 different countries representing six continents with responses from more than 6000 health professionals. The joint data pool suggests that there are large differences in religious and other moral values across nations and cultures, and that these values contribute to the observed differences in health professionals' clinical practices-across nations and cultures!

Mortality and Prognostic Factors of Nontuberculous Mycobacterial Infection in Korea: A Population-based Comparative Study.

BACKGROUND: Population-based studies on the mortality burden of nontuberculous mycobacteria (NTM) infection are lacking. We compared the long-term mortality of NTM-infected patients with tuberculosis (TB)-patients and the general population, and investigated mortality-associated factors. METHODS: We analyzed nationwide-data from the Korean National Health Insurance and Korea-Statistical Office between 2002 and 2017. NTM infection was identified using the International Classification of Disease, Tenth Revision code, with one-to-one matching to TB patients and general population controls. RESULTS: A total of 530 401 individuals were analyzed, including 183 267 with NTM infections; 166 666 with TB; and 180 468 controls. The overall 6-, 10-, and 14-year cumulative survival probabilities in the NTM group were 86.3%, 80.8%, and 77.1%, respectively, which were significantly lower than those of the TB or control groups (log-rank P < .0001). In cases of NTM and TB coinfection, the overall 6-, 10-, and 14-year cumulative survival probabilities were 75.1%, 65.4%, and 57.0%, respectively. Multivariable analysis indicated that old age, male gender, province, and various respiratory or nonrespiratory comorbidities were significantly associated with mortality of NTM infection. The use of a macrolide (more than 1 year) negatively correlated with mortality of NTM infection (adjusted hazard ratio [aHR] 0.61, 95% confidence interval [CI] .53-.71), regardless of azithromycin (aHR 0.60, 95% CI .43-.85) or clarithromycin use (aHR 0.63, 95% CI .53-.75). CONCLUSIONS: NTM-infected patients had poor prognosis when compared to TB patients or the general population, especially for NTM and TB coinfection. NTM mortality was associated with certain demographic characteristics, but long-term use of macrolides may provide survival benefits.

Serum folate concentration and health-related quality of life among the elderly in South Korea.

BACKGROUND: The purpose of this study was to investigate the association between serum folate concentration and health-related quality of life (HRQOL) among the elderly in South Korea. MATERIALS AND METHODS: The data used in this study were drawn from 1,021 participants over 65 years old in the Korea National Health and Nutrition Examination Survey from 2016-2018. HRQOL was measured by the EQ-5D questionnaire. Participants were divided into tertiles of folate concentration (ranges 1.7-5.6, 5.7-9.4, and 9.5-31.9 ng/mL). We performed multivariable linear regression to examine the relationship between folate and HRQOL, and multivariable logistic regression to examine the relationship between folate and the dimensional problem of HRQOL. RESULTS: Higher folate concentrations were significantly associated with higher HRQOL in the elderly. The average HRQOL score of the elderly in the highest tertile of the folate level was 0.0289 higher than that of the lowest tertile (coefficient: 0.0289; 95% CI 0.0016, 0.0563). The HRQOL score increased by 0.0174 points when the folate concentration increased by 100%. When analyzing specific dimensions, a significant association with folate concentration was found only for the self-care dimension of HRQOL (odds ratio for self-care problems: 0.63; 95% CI 0.41, 0.99). CONCLUSIONS: The elderly with higher serum folate concentration tended to have higher HRQOL. Among HRQOL dimensions, self-care was only significantly associated with folate concentration.

How do the influencing factors of health-related quality of life of the injured patient differ according to activity limitations?

PURPOSE: This study aimed to ascertain the general characteristics of injured patients and use the Andersen Model to identify factors affecting health-related quality of life (QOL) in injured patients with or without activity limitations. METHODS: We used data of 1602 injured patients from 2014 to 2017 from the population-based Korea National Health and Nutrition Examination Survey, South Korea. QOL was measured using the EQ-5D-3L, and activity limitations were analyzed alongside predisposing factors (gender, age, education level, and marital status), enabling factors (basic living security, health insurance type, private insurance status, household income, and living with family), need factors (number of chronic diseases, subjective health status, and unmet medical needs), and health behaviors (smoking status, alcohol consumption, physical activity, and health screening). Data were analyzed using homogeneity testing, t tests, and logistic and multiple regression. RESULTS: The mean EQ-5D index was 0.8 with activity limitations and 0.9 without activity limitations. In mobility domain, patients without activity limitations showed significant effects of age, education level, number of chronic diseases, subjective health status, and unmet medical needs on mobility, whereas patients with activity limitations only showed a significant effect of age. In self-care domain, age, household income, and number of chronic diseases showed significant factors on patients without activity limitations, but there was no significant factor associated with activity limitations. Among the factors affecting usual activities, gender was found to have a significant effect only on patients with activity limitations, and subjective health status was found to have a significant effect regardless of activity limitations. Among the factors affecting pain/discomfort, living with family only affected pain/discomfort in patients with activity limitations. Among the factors affecting anxiety/depression, gender and alcohol consumption had significant effects only on patients with activity limitations. CONCLUSION: Factors affecting the QOL of injured patients differed depending on whether patients had activity limitations. Therefore, when assessing injured patients, it may be necessary to ascertain the extent of activity limitations, and medical institutions and local communities need when implementing education and interventions to improve their QOL.

Patients' and Families' Experiences Regarding Disclosure of Patient Safety Incidents.

In South Korea, disclosure of patients' safety incidents is not common in health care settings. Thus, this study identified patients' and families' experiences regarding disclosure of patient safety incidents. Data were collected through in-depth individual interviews from May 25, 2020, to June 23, 2020, and analyzed using Colaizzi's phenomenological method. The participants consisted of 15 patients and their families who had experienced patient safety incidents in hospitals. It is essential to form a base of mutual understanding to enable disclosure and promote follow-up management systems that can ethically and responsibly handle patient safety incidents. Concrete protocols and policies need to be developed to protect patients and their families from physical/psychological injury and the stress experienced due to patient safety incidents. The patients and their families desired changes to improve protocols for proper disclosure, help health care professionals adopt an ethical and mature attitude, and develop professional health care policies regarding patients' safety incidents.

The International NERSH Data Pool of Health Professionals' Attitudes Toward Religiosity and Spirituality in 12 Countries.

The amount of research concerned with the values of health professionals (HPs) is steadily growing. Around the world HPs face similar challenges when patients express their existential and spiritual views. How HPs engage these views, and the degree of embedment into consultations, differ across cultures. Today, more than ever before, researchers in this field need to share experiences and build new knowledge upon local findings. To meet this demand, we founded the international collaboration "Network for Research on Spirituality and Health" ( https://NERSH.org ). One of the central projects of our network has been to build a large international data pool of health professionals' attitudes toward religiosity and spirituality. Today the data pool hosts answers from more than 6,000 health professionals from 17 separate surveys derived from 12 countries. Data were gathered by either the questionnaire "Religion and Spirituality in Medicine, Perspectives of Physicians" (RSMPP) or its successor 'NERSH Questionnaire'. In this article we describe the methodology behind the construction of the data pool. We also present an overview of five available scales related to HP religiosity and spirituality, including a description of scale reliability and dimensionality.

Baseline, delta, and achieved low-density lipoprotein cholesterol levels and cardiovascular risk in patients on statin therapy: A post-hoc resampling mediation analysis of treating new targets [TNT] trial.

Clinical guidelines for monitoring low-density lipoprotein cholesterol (LDL-C) after statin therapy do not clearly define the clinical roles of baseline LDL-C, ΔLDL-C, and achieved LDL-C according to statin intensity. We performed post-hoc analysis of the Treating to New Target (TNT) study to evaluate individual LDL-C parameters after statin therapy. Primary outcome was the risk for total major adverse cardiovascular events (MACE). We use resampling multilevel mediation analysis to analyze complex relationships among LDL-C parameters based on similar statin intensities. Tertiles for resample A (matched baseline LDL-C; distinct achieved LDL), resample B (matched ΔLDL-C; distinct baseline LDL-C), and resample C (matched achieved LDL-C; distinct ΔLDL-C) were analyzed using Cox proportional hazard ratios. In original data analysis, the incidence of MACE was reduced in those with lower achieved LDL-C in total, low, and high intensity statin users (hazard ratios [HRs] = 0.990, 0.992, 0.992; respectively; all P-values < .001). In mediation analysis, resample A showed consistently high incidence for MACE in the middle tertile (HR = 1.237; 95% confidential interval [CI] = 1.008-1.517; P-value = .041) and highest tertile (HR = 1.275; 95% CI = 1.021-1.592; P-value = .032) compared to the lowest tertile. However, resamples B and C did not show consistent differences. Similarly, no consistent statistical difference in MACE according to statin intensity. Lower achieved LDL-C decreased MACE in participants with a similar baseline LDL-C after statin therapy. However, the change in absolute values of ΔLDL-C and achieved LDL-C should be interpreted in an individualized manner due to their complex collinearity, and statin intensity should also be taken into consideration.

Risk of insulin resistance with statin therapy in individuals without dyslipidemia: A propensity-matched analysis in a registry population.

Several studies suggest the higher vulnerability of individuals with lower low-density lipoprotein cholesterol (LDL-C) levels to diabetes mellitus. However, the discordance between high and low baseline LDL-C levels shown by statin-induced insulin resistance is not fully understood. This study aimed to explore the relationship between baseline LDL-C levels and the risk of statin-induced insulin resistance during statin therapy. In total, 2660 (451 with dyslipidemia and 2209 without dyslipidemia) consecutive patients were enrolled. Their baseline clinical data were adjusted using a propensity score matching analysis, using the logistic regression model. Insulin resistance index was based on the homeostatic model assessment-insulin resistance (HOMA-IR) and was monitored for a median of 2 years. Among the individuals who received statin therapy, those with and without dyslipidemia showed significantly decreased LDL-C levels (all P < .0001) and significantly increased fasting plasma insulin levels (Δ = +24.1%, P = .0230; Δ = +30.1%, P < .0001); however, their glycated haemoglobin A1c and fasting blood glucose levels did not change (all P > .05). Although HOMA-IR was positively associated with statin therapy in individuals with and without dyslipidemia, statistically significant difference during follow-ups was observed only in individuals without dyslipidemia (Δ = +15.6%, P = .1609; Δ = 24.0%; P = .0001). Insulin resistance was higher in statin users without baseline dyslipidemia than in those with dyslipidemia. Thus, statin therapy could increase the risk of statin-induced insulin resistance in individuals with normal baseline cholesterol levels.

The relationship between the perception of open disclosure of patient safety incidents, perception of patient safety culture, and ethical awareness in nurses.

BACKGROUND: Scientific advances have resulted in more complex medical systems, which in turn have led to an increase in the number of patient safety incidents (PSIs). In this environment, the importance of honest disclosure of PSIs is rising, which highlight the need to settle a reliable system. This study aimed to investigate the effects of patient safety culture and ethical awareness on open disclosure of PSIs. METHODS: Data were collected from 389 nurses using self-reported perceptions of open disclosure of PSIs, perceptions of patient safety culture, and ethical awareness. RESULTS: Perception of open disclosure of PSIs was significantly correlated with ethical awareness and perception of patient safety culture. Ethical awareness had the greatest impact on perception of PSIs, and two components of the perception of patient safety culture, namely overall knowledge about patient safety and staffing, were found to have significant effects. CONCLUSIONS: To enhance nurses' perception of open disclosure of PSIs, educational curriculum and programs that teach and practice fundamental ethical values are needed. Furthermore, it also calls for effort on the part of healthcare institutions and the government, as well as people's trust, to implement a legal safety net and foster patient safety culture to promote honest disclosure of PSIs to patients.

Characteristics of Eating Alone Affecting the Stress, Depression, and Suicidal Ideation.

This study aimed to identify the characteristics of eating alone that influence stress, depression, and suicidal ideation in Korean adults. This study was a cross-sectional survey using the raw data of the sixth Korea National Health and Nutrition Examination Survey (KNHANES VI) conducted in 2015. The survey sampled 7380 adults, of whom 3515 were included in this analysis. The odds of stress were 1.308 times higher in individuals who ate dinner alone than those who ate dinner with others. The odds of having depressive symptoms were 1.711 times and 1.531 times higher in individuals who ate lunch and dinner alone, respectively, than those who ate lunch or dinner with others. The association between eating alone and suicidal ideation was statistically significant only in the simple model. There is a need for interventional programs that can reduce negative relationships of eating alone behaviors for preventing mental health problems.

Religious Values in Clinical Practice are Here to Stay.

Research to date has shown that health professionals often practice according to personal values, including values based on faith, and that these values impact medicine in multiple ways. While some influence of personal values are inevitable, awareness of values is important so as to sustain beneficial practice without conflicting with the values of the patient. Detecting when own personal values, whether based on a theistic or atheistic worldview, are at work, is a daily challenge in clinical practice. Simultaneously ethical guidelines of tone-setting medical associations like American Medical Association, the British General Medical Council and Australian Medical Association have been updated to encompass physicians' right to practice medicine in accord with deeply held beliefs. Framed by this context, we discuss the concept of value-neutrality and value-based medical practice of physicians from both a cultural and ethical perspective, and reach the conclusion that the concept of a completely value-neutral physician, free from influence of personal values and filtering out value-laden information when talking to patients, is simply an unrealistic ideal in light of existing evidence. Still we have no reason to suspect that personal values, whether religious, spiritual, atheistic or agnostic, should hinder physicians from delivering professional and patient-centered care.

The association between elderly people's sedentary behaviors and their health-related quality of life: focusing on comparing the young-old and the old-old.

BACKGROUND: Research on the effects of sedentary behavior on the health-related quality of life (HRQoL) of the elderly is limited. The present study aimed to determine the association between sedentary behavior and the HRQoL of the young-old (aged 65-74 years) people and old-old (aged ≥75 years) people. METHODS: This study used the raw data of the 7th Korea National Health and Nutrition Examination Survey for 2016. The study subjects were 1,415 people aged over 65 years. The association between HRQoL and average daily sitting time was analyzed using the point biserial correlation coefficient. The effect of sedentary behavior on HRQoL was analyzed by logistic regression analysis. RESULTS: Overall, elderly people aged ≥65 years spent 7.9 h in sedentary pursuits: the young-old spent 7.7 h and the old-old spent 9.0 h. Longer sitting time was found to be associated with lower HROoL while shorter sitting time was associated with higher HROoL, with the relationship stronger among the old-old than among the young-old. This means that the effects of either having longer time sitting per day and low quality of life or shorter time sitting per day and high quality of life are more pronounced in the old-old in comparison to the young-old. CONCLUSIONS: Sedentary behavior is significantly associated with people's HRQoL. Interventions towards improving the HRQoL by reducing sedentary behavior based on the respective characteristics of young-old and old-old people are needed.

Improving Sensitivity on Identification and Delineation of Intracranial Hemorrhage Lesion Using Cascaded Deep Learning Models.

Highly accurate detection of the intracranial hemorrhage without delay is a critical clinical issue for the diagnostic decision and treatment in an emergency room. In the context of a study on diagnostic accuracy, there is a tradeoff between sensitivity and specificity. In order to improve sensitivity while preserving specificity, we propose a cascade deep learning model constructed using two convolutional neural networks (CNNs) and dual fully convolutional networks (FCNs). The cascade CNN model is built for identifying bleeding; hereafter the dual FCN is to detect five different subtypes of intracranial hemorrhage and to delineate their lesions. Using a total of 135,974 CT images including 33,391 images labeled as bleeding, each of CNN/FCN models was trained separately on image data preprocessed by two different settings of window level/width. One is a default window (50/100[level/width]) and the other is a stroke window setting (40/40). By combining them, we obtained a better outcome on both binary classification and segmentation of hemorrhagic lesions compared to a single CNN and FCN model. In determining whether it is bleeding or not, there was around 1% improvement in sensitivity (97.91% [± 0.47]) while retaining specificity (98.76% [± 0.10]). For delineation of bleeding lesions, we obtained overall segmentation performance at 80.19% in precision and 82.15% in recall which is 3.44% improvement compared to using a single FCN model.

Plasticity and Potency of Mammary Stem Cell Subsets During Mammary Gland Development.

It is now widely believed that mammary epithelial cell plasticity, an important physiological process during the stages of mammary gland development, is exploited by the malignant cells for their successful disease progression. Normal mammary epithelial cells are heterogeneous and organized in hierarchical fashion, in which the mammary stem cells (MaSC) lie at the apex with regenerative capacity as well as plasticity. Despite the fact that the majority of studies supported the existence of multipotent MaSCs giving rise to both basal and luminal lineages, others proposed lineage restricted unipotent MaSCs. Consistent with the notion, the latest research has suggested that although normal MaSC subsets mainly stay in a quiescent state, they differ in their reconstituting ability, spatial localization, and molecular and epigenetic signatures in response to physiological stimuli within the respective microenvironment during the stages of mammary gland development. In this review, we will focus on current research on the biology of normal mammary stem cells with an emphasis on properties of cellular plasticity, self-renewal and quiescence, as well as the role of the microenvironment in regulating these processes. This will include a discussion of normal breast stem cell heterogeneity, stem cell markers, and lineage tracing studies.

Mimetics of suppressor of cytokine signaling 3: Novel potential therapeutics in triple breast cancer.

Suppressor of cytokine signaling (SOCS) family of proteins plays critical role in the regulation of immune responses controlling JAK/STAT mediated inflammatory cytokines. Among the members, SOCS1 and SOCS3 contain a kinase inhibitory region (KIR) and SOCS3 binds to JAK/STAT/gp130 complex by inhibiting the downstream signaling and suppressing inflammatory cytokines. Loss or reduced levels of SOCS3 have been linked to cancer-associated inflammation and suppressive immunity leading to enhanced tumor growth and metastasis. In line with these reports, we previously demonstrated that proteolytic degradation of SOCS3 in triple negative breast cancer (TNBC) subtype drives the expression of inflammatory cytokines. Therefore, we postulated that SOCS3 mimetics might suppress the inflammatory cytokine production in TNBC subtype and inhibit tumor growth and metastasis. Here we designed and characterized five linear peptides derived from the N-terminal region of SOCS3 encompassing regions that interface with the JAK2/gp130 complex using the Circular Dichroism and Surface Plasmon Resonance spectroscopies. The KIRESS peptide resulted the sequence containing the most part of the hot-spots required for binding to JAK2 and was further investigated in vivo in mouse xenografts of MDA-MB-231-luci tumors as models of human TNBC subtype. Expectedly, this peptide showed a significant inhibition of primary tumor growth and pulmonary metastasis. Our studies suggest that SOCS3 peptidomimetics may possess a therapeutic potential in aggressive cancers, such as TNBC subtype, with activated inflammatory cytokines.

A study on stress, depression and suicidal ideation according to sexual behaviours among Korean adolescents.

OBJECTIVE: The purpose of this study was to examine stress, depression and suicidal ideation in Korean adolescents according to their sexual behaviours, such as experience of sexual intercourse, time of first sexual intercourse, and sexual intercourse after alcohol drinking. METHODS: This study was conducted as a secondary data analysis using the raw data of the 9th Korea Youth Risk Behaviour Web-based Survey (KYRBWS-IX) conducted in 2013. The survey sampled 75,149 secondary school students, and 72,435 of them were included in this analysis. RESULTS: Stress level, depression and suicidal ideation were significantly higher in adolescents with experience of sexual intercourse than in those without it. Adolescents with experience of sexual intercourse after drinking had a 1.415 times higher odds ratio depression than those without it. When the time of first sexual intercourse was delayed by one year, the odds of stress increased by 1.022 times and the odds of suicidal ideation increased by 1.014 times. CONCLUSIONS: Adolescents with experience of sexual intercourse showed significantly higher stress, depression and suicidal ideation, the latter of which was particularly higher among low-grade female students that had experienced first sexual intercourse at a young age. Suicidal ideation was more common when first sexual intercourse was early. Adolescents with experience of sexual intercourse after drinking showed higher stress, depression and suicidal ideation than those without drinking.

Therapeutic Effect of Losartan, an Angiotensin II Type 1 Receptor Antagonist, on CCl4-Induced Skeletal Muscle Injury.

TGF-ß1 is known to inhibit muscle regeneration after muscle injury. However, it is unknown if high systemic levels of TGF-ß can affect the muscle regeneration process. In the present study, we demonstrated the effect of a CCl4 intra-peritoneal injection and losartan (an angiotensin II type 1 receptor antagonist) on skeletal muscle (gastrocnemius muscle) injury and regeneration. Male C57BL/6 mice were grouped randomly as follows: control (n = 7), CCl4-treatment group (n = 7), and CCl4 + losartan treatment group (n = 7). After CCl4 treatment for a 16-week period, the animals were sacrificed and analyzed. The expression of dystrophin significantly decreased in the muscle tissues of the control group, as compared with that of the CCl4 + losartan group (p < 0.01). p(phospho)-Smad2/3 expression significantly increased in the muscles of the control group compared to that in the CCl4 + losartan group (p < 0.01). The expressions of Pax7, MyoD, and myogenin increased in skeletal muscles of the CCl4 + losartan group compared to the corresponding levels in the control group (p < 0.01). We hypothesize that systemically elevated TGF-ß1 as a result of CCl4-induced liver injury causes skeletal muscle injury, while losartan promotes muscle repair from injury via blockade of TGF-ß1 signaling.

Changes of the Cytoplasmic Proteome in Response to Alcoholic Hepatotoxicity in Rats.

Proteomic analyses have already been used in a number of hepatological studies and provide important information. However, few reports have focused on changes in the cytoplasmic proteome. The present study therefore aimed to evaluate changes in cytoplasmic proteome of rats in response to alcoholic hepatotoxicity. Rats were fed a Liber-DeCarli liquid diet containing ethanol for four weeks. Cytoplasmic proteins except mitochondrial proteins from the livers of these animals were investigated using two-dimensional gel electrophoresis and mass spectrometry. Alcohol induced a decrease in body weight gain and an increase in alanine transaminase (ALT), cholesterol, and phospholipid levels. Histopathological observations revealed hepatic damage characterized by necrosis and fatty change in alcohol-treated group at week 2, which continues until week 4. Our proteomic analysis revealed that 25 proteins were differentially expressed in the ethanol-fed group. Of these, 12 cytoplasmic proteins are being reported for the first time. Taken together, our results provide further insights into the disease mechanism and therapeutic information of alcoholic liver disease.

The RNA in reticulocytes is not just debris: it is necessary for the final stages of erythrocyte formation.

Reticulocytes contain both RNA and micro-organelles and represent the last stage of erythropoiesis before full maturation to red blood cells (RBCs). Even though there is continuing synthesis of hemoglobin and membrane-bound proteins in reticulocytes, the small amount of RNA that they contain has been regarded as non-functional residual material. Here we show that this residual RNA is both functional and essential for further reticulocyte maturation. Reticulocytes from which the remnant RNA had been removed by exposure to RNase did not survive or mature into RBCs in either humans or mice. Conversely, reticulocytes treated with an RNase Inhibitor were able to form normal biconcave cells. Similarly, poor survival was also seen in reticulocytes in which protein synthesis had been blocked. To identify the signaling pathways involved we isolated RNAs in reticulocytes versus those present in fully matured erythroblasts cultured from hematopoietic stem cells. RNAs found in erythroblasts were related to exocytosis, metabolism, and signal transduction all of which are critical for maturation through reticulocyte and into a fully mature, biconcave erythrocyte. Our results suggest that the mRNA in reticulocytes has to be translated into novel proteins that act to preserve mitochondria and maintain cell membrane integrity as reticulocytes mature. These results enhance our understanding of the final stage of erythropoiesis and may clarify why in vitro-generated reticulocytes for transfusion purposes survive poorly.