Miracle-dz/UniFAR-FTUs huggingface dataset:
EBV Latency III–Transformed B Cells Are Inducers of Conventional and Unconventional Regulatory T Cells in a PD-L1–Dependent Manner

Key Points EBV latency III B cells display an immunosuppressive profile similar to Bregs. They repress proliferation of T cells and promote expansion of cTregs and uTregs. Expansion of Tregs depends on PD-L1 whose expression depends on the EBV oncogene LMP1. EBV infects and immortalizes B cells in vitro and in vivo. It is the causative agent of most immune deficiency–related lymphoproliferative disorders and is associated with various lymphomas. EBV latency III–transformed B cells are known to express two immunosuppressive molecules, IL-10 and PD-L1, two characteristics of regulatory B cells (Bregs). In this study, we show that, in addition to secretion of the Breg immunosuppressive cytokines IL-10, IL-35, and TGF-β1, EBV latency III–transformed B cells were able to repress proliferation of their autologous T cells preactivated by CD2, CD3, and CD28. This inhibitory effect was likely caused by CD4+ T cells because EBV latency III–transformed B cells induced a strong proliferation of isolated autologous CD8 T cells. Indeed, EBV was able to promote expansion of autologous FOXP3+ CD39high CTLA4+, Helios+, GITR+, LAG3+ CD4 T cells (i.e., regulatory T cells [Tregs]). Two types of Tregs were induced: unconventional CD25neg and conventional CD25pos Tregs. These Tregs expressed both the latency-associated peptide (LAP) and the PD-1 receptor, two markers of functional Tregs. Expansion of both Treg subtypes depended on PD-L1, whose expression was under the control of LMP1, the main EBV oncogene. These results demonstrate that, like Bregs, EBV latency III–transformed B cells exhibit strong immunoregulatory properties. These data provide clues to the understanding of how after EBV primo-infection, EBV-proliferating B cells can survive in an aggressive immunological environment and later emerge to give rise to EBV-associated B cell lymphomas such as in elderly patients.
Application of Artificial Intelligence in the Detection and Differentiation of Colon Polyps: A Technical Review for Physicians

Research in computer-aided diagnosis (CAD) and the application of artificial intelligence (AI) in the endoscopic evaluation of the gastrointestinal tract is novel. Since colonoscopy and detection of polyps can decrease the risk of colon cancer, it is recommended by multiple national and international societies. However, the procedure of colonoscopy is performed by humans where there are significant interoperator and interpatient variations, and hence, the risk of missing detection of adenomatous polyps. Early studies involving CAD and AI for the detection and differentiation of polyps show great promise. In this appraisal, we review existing scientific aspects of AI in CAD of colon polyps and discuss the pitfalls and future directions for advancing the science. This review addresses the technical intricacies in a manner that physicians can comprehend to promote a better understanding of this novel application.
Perspectives of Nurse Managers on Virtual Communication and e-Leadership.

AIM We sought nurse managers' perspectives on challenges and opportunities with technology and how it may influence communication and leadership. BACKGROUND e-Leadership is a conceptual framework used to understand and teach organizational leaders about the application of technology to leadership. Technology is integral to leadership, yet little is understood about how nurse managers may use this technology and how they negotiate the complexity of the multiple communication systems currently in use. METHODS Sixteen nurse managers from individual hospitals within a large US healthcare system participated in qualitative open-ended interviews and focus groups. RESULTS Four themes emerged from the qualitative data regarding the nurse managers' perspectives of e-Leadership and their use of information and communication technologies: (1) Can't live without it, (2) Too much, too many, (3) Poor onboarding education; and (4) Difficulty maintaining virtual relationships. IMPLICATIONS FOR NURSING MANAGEMENT Effective and safe patient care is dependent on multiple technology applications that require significant knowledge and practice. Nursing leadership may consider the need for more supported mentorship, and engaging programs to educate nurse managers about the dozens of applications required to effectively manage and lead. For technology to be used to its full potential it should be designed with nursing involvement. This article is protected by copyright. All rights reserved.
Enhanced l-Lysine into 1,5-Diaminopentane Conversion via Statistical Optimization of Whole-Cell Decarboxylation System

The global lysine companies in the feed industry have steadily built their production facilities due to the high demand for l-lysine in animal farms, and in recent years there have been excessive supply problems and the world market price of l-lysine has fallen. In this study, the conversion of 1,5-diaminopentane (DAP) by decarboxylation of l-lysine was strategically chosen to enhance the value of lysine. The decarboxylation is enzymatically accessible, and Hafnia alvei, which is the producer of l-lysine decarboxylase, was applied as a whole-cell form. In the designed whole-cell biocatalytic system, the major four reaction factors were selected by fundamental investigation and then statistical optimization was performed to estimate the optimum condition. The predicted conversion was assessed at about 94.6% at the optimum conditions (125.1 mM l-lysine and 71.5 g/L acetone concentration at 35.2 °C for 8.4 h). Under the determined conditions, DAP conversions by using analytical, feed and industrial crude l-lysine were found to be 98.3%, 92.5% and 72.4%, respectively. These results could be suggested to solve the problem of excessive supplied lysine and also to provide guidance for improved enzymatic conversion by statistical optimization.
Clinical and Molecular Characteristics of Klebsiella pneumoniae Isolates Causing Bloodstream Infections in Japan: Occurrence of Hypervirulent Infections in Health Care

Although hypervirulent Klebsiella pneumoniae (hvKp) has been associated with severe community-acquired infections that occur among relatively healthy individuals, information about hvKp infections in health care settings remains limited. Here, we systematically analyzed the clinical and molecular characteristics of K. pneumoniae isolates causing bloodstream infections in a cross-sectional study. ABSTRACT Although hypervirulent Klebsiella pneumoniae (hvKp) has been associated with severe community-acquired infections that occur among relatively healthy individuals, information about hvKp infections in health care settings remains limited. Here, we systematically analyzed the clinical and molecular characteristics of K. pneumoniae isolates causing bloodstream infections in a cross-sectional study. Clinical characteristics of K. pneumoniae bloodstream infections from hospitals across Japan were analyzed by a review of the medical records. Whole-genome sequencing of the causative isolates was performed. Bacterial species were confirmed and hvKp were identified using whole-genome sequencing data. Clinical characteristics of hvKp infections were compared with those of non-hvKp infections by bivariate analyses. Of 140 cases of K. pneumoniae bloodstream infections, 26 cases (18.6%) were caused by various clones of hvKp defined by the carriage of cardinal virulence genes. Molecular identification revealed that 24 (17.1%) and 14 (10%) cases were caused by Klebsiella variicola and Klebsiella quasipneumoniae, respectively. Patients with hvKp infections had higher proportions of diabetes mellitus (risk ratio [RR], 1.75; 95% confidence interval [CI], 1.05 to 2.94), and their infections had significantly higher propensity to involve pneumonia (RR, 5.85; 95% CI, 1.39 to 24.6), liver abscess (RR, 5.85; 95% CI, 1.39 to 24.6), and disseminated infections (RR, 6.58; 95% CI, 1.16 to 37.4) than infections by other isolates. More than one-half of hvKp infections were health care associated or hospital acquired, and a probable event of health care-associated transmission of hvKp was documented. hvKp isolates, which are significantly associated with severe and disseminated infections, are frequently involved in health care-associated and hospital-acquired infections in Japan.
Major patterns of cancer cure: Clinical implications.

INTRODUCTION This review aimed to classify major patterns of cancer cure and discuss clinical implications. Patterns of cancer cure were identified, in terms of long-term survival and life expectancy, by means of two recently estimated indicators: cure fraction (CF) and time to cure (TTC). METHODS We considered population-based studies reporting results for some cancer types on CF, defined as the proportion of patients who will reach the same life expectancy of the general population, or/and TTC, the time span necessary to experience a negligible excess mortality. TTC is obtained using conditional relative survival, which indicates the probability of surviving an additional y number of years, given that patients already survived x number of years. RESULTS Four major patterns of cancer types emerged from published studies: (a) cancers with a CF > 60% and a TTC < 5 years (e.g., testicular, thyroid); (b) cancers with a CF between 20% and 50% and a TTC < 10 years (colon, rectum); (c) cancers showing a CF of approximately 50% and TTC > 10 years (breast, prostate and bladder); (d) cancers with a CF < 20% and uncertain TTC (lung or pancreas). CONCLUSION Clinical and social impact of "cancer cure" categorisation are discussed in details. Recognising a cancer patient as cured represents an opportunity to improve their quality of life.
Increased Chondrocytic Gene Expression Is Associated With Improved Repair Tissue Quality and Graft Survival in Patients After Autologous Chondrocyte Implantation

Background: Assays to quantitate the quality of autologous chondrocyte implants have recently become available. However, the correlation of the assay score with radiological and clinical outcomes has not been established. Purpose/Hypothesis: The purpose was to assess the influence of cell identity (chondrocyte/synoviocyte gene expression ratio) and viability on patient-reported outcome measures, graft survival, and repair tissue quality. It was hypothesized that greater cell product quality as assessed through an identity assay and cell viability is associated with superior outcomes after autologous chondrocyte implantation (ACI) for symptomatic cartilage defects. Study Design: Cohort study; Level of evidence, 3. Methods: Seventy-nine patients with a minimum follow-up of 2 years were included in this study. Of these, 67 patients were available for imaging assessment utilizing the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scoring system. Patients were assigned to groups either below or above the cohort’s mean based on their individual cell identity score and viability percentage. Results: Patients were predominantly female (57.7%) with a mean age of 30.0 ± 9.3 years. No differences were seen between Knee injury and Osteoarthritis Outcome Score, Lysholm, Tegner, or International Knee Documentation Committee Subjective Knee Evaluation Form within the viability and cell identity groups at a final follow-up of 3.8 ± 1.4 years after ACI (P > .05). In a subset of patients, the mean MOCART score was 68.3 ± 15.6 at an average magnetic resonance imaging follow-up of 17.7 ± 9.56 months. Low cell identity was significantly associated with the degree of defect filling (P = .025), integration of border zone (P = .01), effusion (P = .024), and ACI graft failure (P = .002). Patients with above-average cell identity scores had a significantly higher survival rate at 5-year follow-up compared with patients with below-average scores (95.8% vs 64.7%; P = .013). Cell viability did not influence MOCART subscales or graft failure (all P > .05). Cell viability and identity showed no significant correlation with each other (r = −0.045; P = .694). Conclusion: Cell identity was significantly correlated with structural repair quality and graft survival after second-generation ACI for symptomatic chondral lesions in the knee. While improved imaging outcome and higher graft survivorship were associated with a higher individual cell identity score indicating a higher chondrocyte/synoviocyte gene expression ratio in the final cell product, clinical outcome did not correlate with the identity score.
Cervical length should be measured for women with placenta previa: cohort study

Abstract Objectives To study the relevance between cervical length (CL) and different maternal/neonatal outcomes in pregnancies complicated with placenta previa/accreta. Methods Three hundred twenty-eight women, who had medically free singleton live pregnancies with the diagnosis of placenta previa and/or accreta, were included and divided regarding their CL into two groups. Threatened preterm labor, maternal tocolysis, multiple gestations, polyhydramnios, ruptured fetal membranes, fetal complications, history of cervical conization, and the presence of cervical cerclage were the exclusion criteria. Demographic data, obstetric history, as well as, the courses of the complicated pregnancies were collected and statistically analyzed. Results The short CL group had significantly less distance between the placenta and the internal cervical os (p-value < .001) Also, they showed more ultrasound parameters of complete placenta previa with anterior location (p-value < .001 and .003 respectively) and placental adherence (21.8 versus 41.1%). Women with short cervix had significantly higher rates of preterm birth, antepartum hemorrhage, emergency cesarean sections, intraoperative estimated blood loss, massive bleeding, prevalence of placental adherence and cesarean hysterectomy (p-value < .001 for the entire outcomes). Multivariable binary logistic regression showed that CL (<30 mm) was a significant independent risk factor in prediction of severe hemorrhage, PTB, emergency CS, placental adherence, cesarean hysterectomy (p-value < .001 for adverse maternal outcomes) and low cord Ph (p-value = .016). Conclusions Assessment of the cervical length could be a crucial step in the work-up and decision making for pregnancies complicated with abnormally situated and/or adherent placenta as it is strongly associated with a wide range of maternal and neonatal morbidities.
Facial presentations of migraine, TACs, and other paroxysmal facial pain syndromes

Objective To assess the prevalence of facial pain (V2 and/or V3) presentations among nearly 3,000 patients with headache treated in a university tertiary care center. Methods Between 2010 and 2018, we routinely assessed the prevalence of facial pain presentations of all patients with primary headaches. Results Of 2,912 patient datasets, 291 patients reported facial pain either as an independent or as an additional symptom. Among patients with migraine, 2.3% (44 of 1,935) reported a facial involvement, most commonly in V2. Of these, 18 patients (40.9%) experienced the pain predominantly in the face. In patients with cluster headache, 14.8% (42 of 283) reported a facial involvement, of which 31.0% perceived the pain predominantly in the face. A facial involvement was seen in 45.0% of patients with paroxysmal hemicrania (9 of 20), 21.4% of patients with hemicrania continua (9 of 42), and 20.0% of patients with short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing/short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (3 of 15). In addition, we present 6 patients who reported a constant side-locked facial pain with superseded well-defined facial pain attacks of 10- to 30-minute duration that appeared several times per day. Conclusion Our data suggest that a facial involvement in primary headaches is infrequent but not uncommon. A sole facial presentation of primary headache symptomatology seems to be exceptionally rare. We describe 3 different types of facial pain involvement and, in this context, distinguish patients with paroxysmal orofacial pain syndromes that have not been previously described. These patients may represent a new entity that could tentatively be called constant unilateral facial pain with added attacks.
Effectiveness of fluoride varnish four times a year in preventing caries in the primary dentition: A 2 year randomized controlled trial.

OBJECTIVES To test the effectiveness of fluoride varnish in preventing caries in early childhood in children at high risk of caries. BASIC RESEARCH DESIGN Randomized controlled trial. PARTICIPANTS 504 participants, with mean age of 21 months at baseline randomly allocated into a test and a control group. 427 children remained in the study after two years. INTERVENTION Fluoride varnish applied four times a year, every three months. The intervention lasted for two years. MAIN OUTCOME MEASURES Dental status was recorded based on the International Caries Detection and Assessment System (ICADS). RESULTS Mean dmfs was similar in the control and test groups at baseline (1.0 and 1.2 respectively) but was significantly different (10.1 and 5.2, p ⟨ 0.001, ANOVA) at endpoint. The proportion caries free in the two groups was 40% and 69.4% after two years. CONCLUSIONS The application of fluoride varnish four times a year prevented the incidence and reduced the severity of caries in pre-school children. TRIAL REGISTRATION NUMBER DRKS00013980.
Long noncoding RNA KCNQ1OT1 promotes apoptosis in neuroblastoma cells by regulating miR‐296‐5p/Bax axis

Long noncoding RNAs (lncRNAs) are emerging as important regulators of multiple cellular processes such as cell invasion, growth, apoptosis and differentiation. LncRNAs can function as competing endogenous RNAs (ceRNAs) which sponge and sequester microRNA (miRNA) to regulate specific targets. Previously, we found that the target genes of several miRNAs, including FADD, Fas, Casp and Bax, are related to neuronal apoptosis and form a regulatory network. Among several factors, microRNA‐296‐5p expression was found to be negatively correlated with caspase activity and apoptosis. Here, we aimed to investigate the role of miR‐296‐5p in neuroblastoma (NB) cells. By performing quantitative real‐time PCR (qRT‐PCR), western blot and flow cytometry assays we analysed the expression of apoptotic markers in NB cells transfected with miR‐296‐5p mimics or inhibitor. Pathway‐specific PCR array allowed us to identify the target genes of miR‐296‐5p. Using LncBase online tool, we predicted lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) as an upstream regulator of miR‐296‐5p. The binding of KCNQ1OT1 and miR‐296‐5p was validated via RNA immunoprecipitation and Biotin pull‐down assays. We also demonstrate that miR‐296‐5p suppresses apoptosis of NB cells in vitro and in vivo. Mechanistically, miR‐296‐5p directly bound the 3′UTR of Bax mRNA, thus repressing Bax at the mRNA and protein level. Moreover, through bioinformatic analysis and molecular experiments, we showed that KCNQ1OT1 sponged miR‐296‐5p and impaired its effect on NB cell apoptosis. In summary, KCNQ1OT1 is a potent promoting factor of cell apoptosis, which acts by sponging miR‐296‐5p and upregulating Bax. Our findings identify a regulatory axis of cell fate in NB cells.
Relationship Between Implementation Of The Primary Nursing Model And The Reduction Of Missed Nursing Care.

AIMS To evaluate and predict the relationship between the implementation of the primary nursing model and the reduction of missed nursing care. BACKGROUND Primary nursing can provide hospital leaders and nursing staff with guidance in implementing safe, patient-centred care, with responsibility and accountability during the nursing process. The implementation can be measured in terms of missed nursing care. METHODS A predictive-correlational study was used. The study was conducted in four inpatient units at the University Hospital, northeast, Brazil. Data was collected from 96 registered nurses, using the MISSCARE instrument at four and seven months after the implementation of the primary nursing model. RESULTS Missed nursing care was reduced by 78.5%. Job title and staff satisfaction showed significant associations with decreased missed care (p <0.05). CONCLUSION The predictive effect between efficacy in reducing missed nursing care and reasons and efficiency in the management of nursing care, using the primary nursing model, was verified. IMPLICATIONS FOR NURSING MANAGEMENT Nursing staff and managers should consider adopting a Primary Nursing Model of care to reduce missed nursing care. This article is protected by copyright. All rights reserved.
The autophagy-activating kinase ULK1 mediates clearance of free α-globin in β-thalassemia

Rapamycin alleviates β-thalassemia by stimulating ULK1-dependent clearance of toxic free α-globin. Unclogging red blood cells In β-thalassemia, a genetic disorder caused by mutations in the β-globin subunit of adult hemoglobin, the pathological consequences are caused by two problems. One is a shortage of adult hemoglobin that can function to transport oxygen, while the other is a buildup of excess α-globin subunits, which damages the red blood cells and thus further impairs oxygen transport in the body. Using mouse models of β-thalassemia as well as patient-derived cells, Lechauve et al. determined that autophagy-activating kinase ULK1 plays a key role in the clearance of accumulated α-globin. The authors also showed that the drug rapamycin stimulates ULK1-dependent autophagy and thus facilitates α-globin clearance. In β-thalassemia, accumulated free α-globin forms intracellular precipitates that impair erythroid cell maturation and viability. Protein quality control systems mitigate β-thalassemia pathophysiology by degrading toxic free α-globin, although the associated mechanisms are poorly understood. We show that loss of the autophagy-activating Unc-51–like kinase 1 (Ulk1) gene in β-thalassemic mice reduces autophagic clearance of α-globin in red blood cell precursors and exacerbates disease phenotypes, whereas inactivation of the canonical autophagy-related 5 (Atg5) gene has relatively minor effects. Systemic treatment with the mTORC1 inhibitor rapamycin reduces α-globin precipitates and lessens pathologies in β-thalassemic mice via an ULK1-dependent pathway. Similarly, rapamycin reduces free α-globin accumulation in erythroblasts derived from CD34+ cells of β-thalassemic individuals. Our findings define a drug-regulatable pathway for ameliorating β-thalassemia.
Medication safety incidents in paediatric oncology after electronic medication management system implementation

Abstract Objective To explore medication safety issues related to use of an electronic medication management system (EMM) in paediatric oncology practice, through the analysis of patient safety incident reports. Methods We analysed 827 voluntarily reported incidents relating to oncology patients that occurred over an 18‐month period immediately following implementation of an EMM in a paediatric hospital in Australia. We identified medication‐related and EMM‐related incidents and carried out a content analysis to identify patterns. Results We found ~79% (n = 651) of incidents were medication‐related and, of these, ~45% (n = 294) were EMM‐related. Medication‐related incidents included issues with: prescribing; dispensing; administration; patient transfers; missing chemotherapy protocols and information on current stage of patient treatment; coordination of chemotherapy administration; handling or storing medications; children or families handling medications. EMM‐related incidents were classified into four groups: technical issues, issues with the user experience, unanticipated problems in EMM workflow, and missing safety features. Conclusions Incidents reflected difficulties with managing therapies rich in interdependencies. EMM, and especially its ‘automaticity’, contributed to these incidents. As EMM impacts on safety in such high‐risk settings, it is essential that users are aware of and attend to EMM automatic behaviours and are equipped to troubleshoot them.