Miracle-dz/UniFAR-FTUs huggingface dataset:
Etoposide‐mediated deregulation of the G2M checkpoint in myeloid leukaemic cell lines results in loss of cell survival

Summary. The K562 leukaemic cell line expresses an inherent survival signal due to the antiapoptotic properties of Bcr‐abl, which is, in part, mediated by prolonging the G2M checkpoint and allowing DNA repair mechanisms to operate post genotoxic insult. Arrest of the cell cycle is mediated by retaining an inactivating state of phosphorylation of cyclin‐dependent kinase 1 (Cdk1) on tyrosine 15. Our data confirmed that cell survival in K562 was promoted by cell cycle arrest at G2M in response to the genotoxin etoposide. There was no predicted cell cycle arrest in Bcr‐abl‐positive derivative cell lines of K562 that did not survive the same genotoxic insult but, paradoxically, Cdk1 tyrosine phosphorylation was enhanced to a higher extent compared with the parental cell line where arrest of the cell cycle was observed. To ascertain that this was not an anomaly of the derivative lines, HL60 cells were treated with concentrations of etoposide that induced arrest of the cell cycle or apoptosis. Only HL60 cells that subsequently underwent apoptosis elicited the same effect of increased Cdk1 tyrosine phosphorylation. It is proposed that the augmented tyrosine phosphorylation status of Cdk1 is associated with the abolition of cell survival, in addition to the previously reported induction of cell cycle arrest in myeloid cell lines.
Suppression of Integrin Expression and Tumorigenicity by Sulfation of Lactosylceramide in 3LL Lewis Lung Carcinoma Cells*

To investigate the cellular functions of sulfated glycosphingolipids, we introduced the cerebroside sulfotransferase (CST) gene into J5 cells, a subclone of 3LL Lewis lung carcinoma cells. The J5 cells lack acidic glycosphingolipids but accumulate their common biosynthetic precursor, lactosylceramide. We established the stable CST transfectants, J5/CST-1 and J5/CST-2 clones, highly expressing sulfated lactosylceramide (SM3). Both clones exhibited more spherical morphology in comparison to mock transfectant, and their adhesiveness to fibronectin and laminin was significantly lower. The loss of cell-substratum interactions in these SM3-expressing cells could be attributed to decreased expression of integrins (α5, α6, and β1) on the cell surface and their whole cellular levels. However, the levels of H-2Kb and H-2Db antigens remained unchanged. Reverse transcriptase-polymerase chain reaction and Northern blot analyses for these integrins exhibited significant decrease of β1 gene expression in J5/CST-1 and 2, but there was no change in the levels of α5 and α6transcripts. Deglycosylation by endoglycosidase H treatment clearly demonstrated that the precursor form of β1 integrin, possessing high mannose oligosaccharide chains, was preferentially decreased in the CST transfectants. These results demonstrate that endogenous SM3 negatively regulates β1 integrin expression at the transcriptional level, and the decrease of α integrin proteins in the CST transfectants was due to the post-transcriptional modification. We suggest the putative importance of the intracellular pre-β1 integrin pool for normal integrin maturation and subsequent function. Although the rates of cell proliferation in vitro for mock and CST transfectants were similar, tumorigenicity of J5/CST-1 and -2 cells inoculated into syngeneic C57/BL6 mice was greatly decreased or even absent. This was probably due to global loss of the efficient cell-matrix interactions, which are essential for the development of malignant tumors in vivo. Thus, we showed the evidence that cellular SM3 negatively regulates the cell-substratum interaction, resulting in the loss of tumorigenicity.
Experiences of caregivers of infants who have been on bubble continuous positive airway pressure at Queen Elizabeth Central Hospital, Malawi: A descriptive qualitative study.

BACKGROUND An innovative, low-cost bubble continuous positive airway pressure (bCPAP) device has recently been introduced in Malawi for the treatment of respiratory distress in infants. While this novel bCPAP system has been shown to be safe and effective in reducing infant mortality, caregivers' experiences have not been investigated. The purpose of this study was to explore experiences of parents and guardians of infants who had been on bCPAP at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi. METHODS This was a descriptive phenomenological study that was carried out at the Chatinkha nursery unit and the paediatric nursery ward at QECH, from January to February 2015. Purposive sampling was used to select participants for in-depth interviews. Data saturation was reached with 12 caregivers. Data were analysed using Colaizzi's framework. RESULTS Caregivers received inadequate, inconsistent, and sporadic information about bCPAP. Student nurses and doctors were best able to answer caregivers' questions and concerns. When their infants were on bCPAP, caregivers felt anxious and fearful. However, upon implementation of bCPAP treatment for their children, the caregivers were satisfied with it. The main sources of psychological stress were limited parent-child interaction and the constraints of prescribed visiting hours. Family, friends, and caregiver involvement in the care of infants provided some psychological comfort. CONCLUSIONS The results show gaps in the information and psychological support that mothers of infants on bCPAP receive in hospital. We recommend that psychological support be given to the mothers of infants on bCPAP at QECH.
Effect of surfactant on morbidity, mortality, and resource use in newborn infants weighing 500 to 1500 g.

BACKGROUND The administration of surfactant decreased mortality, morbidity, and costs of care for very-low-birth-weight infants in clinical trials. The extent to which these benefits can be achieved in the usual clinical settings is not known. METHODS We analyzed clinical and financial data obtained from 1985 to 1990 at 14 perinatal centers in the United States on 5629 neonates weighing 500 to 1500 g. The infants were divided into groups according to whether they were born before or after surfactant was introduced into clinical practice. Regression models controlling for race, sex, and birth weight were used to assess mortality, morbidity, and use of resources. Mortality rates specific for these variables were projected to the nation as a whole with reference to the 1985 U.S. birth cohort. RESULTS The odds of death in the hospital for very-low-birth-weight infants were reduced by 30 percent after surfactant was introduced. Among infants with bronchopulmonary dysplasia, mortality declined 40 percent. Projections of mortality nationwide declined 5 percent. Eighty percent of the decline in the U.S. infant mortality rate between 1989 and 1990 could be attributed solely to the use of surfactant. Among the survivors, the overall odds of morbidity did not change, whether or not we adjusted for changes in race, sex, and birth weight. The odds of respiratory distress syndrome and pulmonary interstitial emphysema among the survivors declined by 20 percent and 40 percent, respectively, with surfactant. Inflation-adjusted charges per survivor declined by 10 percent, or $5,800, whereas the cost of care for each infant who died declined by 31 percent, or $4,400. CONCLUSIONS The introduction of surfactant has led to decreased mortality and morbidity in very-low-birth-weight infants and to decreased use of resources both for infants who survive and for those who die.
Mechanisms of Protein Kinase PKR-Mediated Amplification of Beta Interferon Induction by C Protein-Deficient Measles Virus

ABSTRACT The measles virus P gene products V and C antagonize the host interferon (IFN) response, blocking both IFN signaling and production. Using Moraten vaccine strain-derived measles virus and isogenic mutants deficient for either V or C protein production (Vko and Cko, respectively), we observed that the Cko virus was a potent inducer of IFN-β, while induction by Vko virus was an order of magnitude lower than that by the Cko virus. The parental recombinant Moraten virus did not significantly induce IFN-β. The enhanced IFN-inducing capacity of the Cko virus correlated with an enhanced activation of IFN regulatory factor 3 (IRF-3), NF-κB, and ATF-2 in Cko-infected compared to Vko or parental virus-infected cells. Furthermore, protein kinase PKR and mitochondrial adapter IPS-1 were required for maximal Cko-mediated IFN-β induction, which correlated with the PKR-mediated enhancement of mitogen-activated protein kinase and NF-κB activation. Our results reveal multiple consequences of C protein expression and document an important function for PKR as an enhancer of IFN-β induction during measles virus infection.
Economic impact of workplace productivity losses due to allergic rhinitis compared with select medical conditions in the United States from an employer perspective

ABSTRACT Objective: To evaluate the cost of lost productivity in the workplace due to allergic rhinitis compared to other selected medical conditions from an employer perspective. Setting and participants: A total of 8267 US employees at 47 employer locations who volunteered to participate in health/wellness screenings. Measurements: The Work Productivity Short Inventory was used to assess the impact of a predefined group of health conditions on workplace productivity for the previous 12 months. Both absenteeism and presenteeism (lost productivity while at work) were recorded. Costs were calculated using a standard hourly wage. Results: Allergic rhinitis was the most prevalent of the selected conditions; 55% of employees reported experiencing allergic rhinitis symptoms for an average of 52.5 days, were absent 3.6 days per year due to the condition, and were unproductive 2.3 h per workday when experiencing symptoms. The mean total productivity (absenteeism + presenteeism) losses per employee per year were US $593 for allergic rhinitis, $518 for high stress, $277 for migraine, $273 for depression, $269 for arthritis/rheumatism, $248 for anxiety disorder, $181 for respiratory infections, $105 for hypertension or high blood pressure, $95 for diabetes, $85 for asthma, and $40 for coronary heart disease. The mean total productivity loss per employee per year due to caregiving was $102 for pediatric respiratory infections, $85 for pediatric allergies, $49 for Alzheimer's disease, and $42 for otitis media/earache. Conclusions: Allergies are major contributors to the total cost of health-related absenteeism and presenteeism. Payers and employers need to consider this when determining health benefits for employees.
Clientelism and the Democratic Deficit

This article examines the usefulness of the theory of clientelism for understanding the politics of Andhra Pradesh (AP), where pressures to secure election funds as populations became more mobile led political leaders to seek centralized control over state resources and access to private funds. Innovative chief ministers sought new ways of relating to voters that undercut local leaders, leading to populist politics and a shift towards programmatic politics that provided individual benefits rather than collective benefits as under the prior system of patronage politics. These changes created a system that was more amenable to individual leadership but also more vulnerable when the leadership collapsed. The theory of clientelism provides a useful guide to the political and economic costs of this system, including the democratic deficit, but does not provide for voters’ innovative responses. The theory’s emphasis on transactional politics does not adequately address the continuing role of social groupings such as caste nor does it acknowledge the critical role of leadership in building and sustaining the system.
Cognitive Behavioural Group Treatment for Chinese Parents with Children with Developmental Disabilities in Melbourne, Australia: An Efficacy Study

Objectives: This study attempted to test the efficacy of a culturally attuned cognitive behavioural therapy (CBT) group for Chinese parents with children with developmental disabilities at risk of developing mental health problems in Melbourne, Australia. It was hypothesized that the participants in the experimental group would have less parenting stress and fewer dysfunctional attitudes, rules, and values, and better mental health and quality of life than the participants in the control group post-test. Method: A total of 58 participants were randomly assigned into CBT and waiting list control groups. While ANCOVAs were used to compare the differences in General Health Questionnaires-12 (GHQ-12), Parenting Stress Index- Parent Domain (PSI-PD), Quality of Life Enjoyment and Satisfaction Questionnnaire-18 (Q-LES-Q-18) and Dysfunctional Attitude Scale (DAS) between participants of the experiemental and control groups, effect size statistics were performed to measure the magnitude of changes in the above instruments at post treatment. Results: After ten weeks of treatment, the participants in the CBT group showed significant improvement in GHQ-12, Parenting Stress Index (PSI)-Parent Domain and Q-LES-Q-18 scores, but not in DAS scores. The effect size statistics revealed large differences in GHQ-12, PSI-Parent Domain and Q-LES-Q-18 scores between the participants in the experimental and control groups at post-treatment. When a GHQ score of 4 or greater was used as the recommended cut-off score, about 89% and 10% of the participants in the experimental and control groups, respectively, were classified as not at-risk cases at post-treatment. Conclusion: The initial findings suggest that a culturally attuned CBT group may help Chinese parents with children with developmental disabilities to reduce their parenting stress and improve their general mental health and quality of life.
Anticoccidial effect of supplemental dietary Galla Rhois against infection with Eimeria tenella in chickens

The anticoccidial effects of Galla Rhois (GR) powder, which contains a major tannin-derived component of 52.7%, were evaluated in chickens following oral infection with Eimeria tenella. One-day-old chickens were assigned to five groups (control, unsupplemented, GR 0.5% supplemented [GRS 0.5%], GRS 1.0% [GRS 1.0%] and salinomycin supplemented [SS]). The chickens were fed a standard diet supplemented or not supplemented with GR or salinomycin for 10 days prior to infection. The birds received the supplemented diets continuously until 10 days post infection. The effects of GR on a E. tenella infection were evaluated by several parameters, including body weight gain, feed intake, oocyst excretion, bloody diarrhoea, and lesion scores. Infected chickens on the GRS and SS diets had a relatively moderate body weight loss (reduction ratio < 15%) and improved feed conversion. GRS and SS chickens produced significantly fewer faecal oocysts (P<0.05) and showed milder bloody diarrhoea compared with the E. tenella-infected control group. Furthermore, the lesion scores of both the GRS 0.5% and GRS 1.0% groups were significantly lower than the scores of the unsupplemented group on day 5 post infection. The lesion scores for the GR groups were similar to the scores for the SS group. In conclusion, this study suggests that GR appears to be as efficacious as salinomycin against E. tenella infection. GR supplementation leads to a reduction in infected chickens, although infected chickens are still affected compared with the uninfected control group. GR-based diets may be beneficial in preventing or treating coccidial infections in poultry.
Nucleotide-dependent conformational states of actin

The influence of the state of the bound nucleotide (ATP, ADP-Pi, or ADP) on the conformational free-energy landscape of actin is investigated. Nucleotide-dependent folding of the DNase-I binding (DB) loop in monomeric actin and the actin trimer is carried out using all-atom molecular dynamics (MD) calculations accelerated with a multiscale implementation of the metadynamics algorithm. Additionally, an investigation of the opening and closing of the actin nucleotide binding cleft is performed. Nucleotide-dependent free-energy profiles for all of these conformational changes are calculated within the framework of metadynamics. We find that in ADP-bound monomer, the folded and unfolded states of the DB loop have similar relative free-energy. This result helps explain the experimental difficulty in obtaining an ordered crystal structure for this region of monomeric actin. However, we find that in the ADP-bound actin trimer, the folded DB loop is stable and in a free-energy minimum. It is also demonstrated that the nucleotide binding cleft favors a closed conformation for the bound nucleotide in the ATP and ADP-Pi states, whereas the ADP state favors an open confirmation, both in the monomer and trimer. These results suggest a mechanism of allosteric interactions between the nucleotide binding cleft and the DB loop. This behavior is confirmed by an additional simulation that shows the folding free-energy as a function of the nucleotide cleft width, which demonstrates that the barrier for folding changes significantly depending on the value of the cleft width.
A First Step Towards Behavioral Coaching for Managing Stress: A Case Study on Optimal Policy Estimation with Multi-stage Threshold Q-learning

Psychological stress is a major contributor to the adoption of unhealthy behaviors, which in turn accounts for 41% of global cardiovascular disease burden. While the proliferation of mobile health apps has offered promise to stress management, these apps do not provide micro-level feedback with regard to how to adjust one's behaviors to achieve a desired health outcome. In this paper, we formulate the task of multi-stage stress management as a sequential decision-making problem and explore the application of reinforcement learning to provide micro-level feedback for stress reduction. Specifically, we incorporate a multi-stage threshold selection into Q-learning to derive an interpretable form of a recommendation policy for behavioral coaching. We apply this method on an observational dataset that contains Fitbit ActiGraph measurements and self-reported stress levels. The estimated policy is then used to understand how exercise patterns may affect users' psychological stress levels and to perform coaching more effectively.
Improvement of normothermic rat liver ischemia/reperfusion by muramyl dipeptide.

Normothermic ischemia and reperfusion (I/R) of the liver remains a major problem after liver surgery and transplantation. Activation of Kupffer cells (KCs) after normothermic I/R is responsible for a massive release of various monokines such as tumor necrosis factor alpha (TNF-alpha) and a decrease in phagocytic activity. Muramyl dipeptide (MDP) is an immunostimulant that increases phagocytic activity of KCs. The aim of this study was to demonstrate that MDP pretreatment might protect the liver against I/R injury by a modification of KC functions. Rats were divided into three groups: group 1, control, Ringer's lactate administration; group 2, MDP (N-acetyl-muramyl-d-alanyl-d-isoglutamine) treatment; group 3, sham-operated control animals. MDP (500 microg/250 g) was injected intravenously 5 min before the induction of 90 min ischemia. Survival rates were compared and serum activities of TNF-alpha, aspartate aminotransferase, and alanine aminotransferase were assessed in the blood collected from the suprahepatic vena cava. Histology of the liver and KC activity were assessed 6 and 9 h after the end of ischemia, respectively. MDP treatment significantly increased 7-day survival (86.6%) compared with nontreated rats (40%, P < 0.001). Serum activities of TNF-alpha and aminotransferases were significantly decreased after MDP treatment, whereas phagocytic capacity of KCs was partially restored. The extent of liver necrosis was decreased after MDP administration. A significant difference was observed for other histological parameters studied, except for steatosis. Our findings have demonstrated that MDP is able to protect the liver from ischemic insult by modulation of KC activity (TNF-alpha release and phagocytic capacity). Control of macrophage activity may offer a new strategy to reduce ischemic injury of the liver.
Genome-wide survey of codons under diversifying selection in a highly recombining bacterial species, Helicobacter pylori

Selection has been a central issue in biology in eukaryotes as well as prokaryotes. Inference of selection in recombining bacterial species, compared with clonal ones, has been a challenge. It is not known how codons under diversifying selection are distributed along the chromosome or among functional categories or how frequently such codons are subject to mutual homologous recombination. Here, we explored these questions by analysing genes present in >90% among 29 genomes of Helicobacter pylori, one of the bacterial species with the highest mutation and recombination rates. By a method for recombining sequences, we identified codons under diversifying selection (dN/dS > 1), which were widely distributed and accounted for ∼0.2% of all the codons of the genome. The codons were enriched in genes of host interaction/cell surface and genome maintenance (DNA replication, recombination, repair, and restriction modification system). The encoded amino acid residues were sometimes found adjacent to critical catalytic/binding residues in protein structures. Furthermore, by estimating the intensity of homologous recombination at a single nucleotide level, we found that these codons appear to be more frequently subject to recombination. We expect that the present study provides a new approach to population genomics of selection in recombining prokaryotes.
Colonic propulsive and postprandial motor activity in patients with ulcerative colitis in remission

Background Although it is known that colon motility is abnormal in ulcerative colitis, data are still scarce with regard to the underlying mechanisms. Recent evidence suggests that the propulsive activity is highly increased during the active phase of the disease, probably contributing to the diarrhoea. However, data are even scarcer in the quiescent phase of the disease. Aims To assess the colonic high-amplitude and low-amplitude propulsive activity and the colonic motor response to eating in patients with ulcerative colitis in remission. Patients and methods Fourteen patients were recruited, all with the disease in remission as documented by clinical and endoscopic criteria. Twenty-four hour manometric recordings were obtained in these patients, and compared to those of 16 healthy controls. Results The high-amplitude propagated contractions were similar in both groups (5.8±2.6 events in ulcerative colitis patients and 5.5±0.8 in controls (P=0.13)), whereas patients tended to display a higher number of low-amplitude propagated events (134.4±34 vs. 60.9±16 in controls (P=0.058)). No differences were found in the colonic motor response to eating between patients and controls. Conclusions Colonic propulsive activity in ulcerative colitis in remission is almost normal, even though the low-amplitude propagated activity tends to be similar to that observed in patients with the irritable bowel syndrome, thus possibly contributing to the persistence of abdominal symptoms in a subgroup of patients.
Cerebral glucose metabolism in survivors of childhood acute lymphoblastic leukemia

Cranial radiation therapy (CRT) has been suggested to be a principal factor responsible for long term neurocognitive deficits in survivors of acute lymphoblastic leukemia (ALL). However, neither reduction of the irradiation dose nor the elimination of irradiation entirely appear to have abolished neurocognitive impairment in long term ALL survivors. Positron emission tomography (PET) and [18F]‐fluorodeoxyglucose (FDG) can be used to quantitate cerebral glucose metabolism, a potential indicator of treatment‐induced adverse central nervous system (CNS) effects. The purpose of this study was to assess whether CRT is associated with defects in cerebral glucose metabolism in long term ALL survivors. The authors also studied whether chemotherapy and/or the severity of disease have deleterious effects on glucose metabolism.