Strontium and Copper Co-Doped Multifunctional Calcium Phosphates: Biomimetic and Antibacterial Materials for Bone Implants.

ß-tricalcium phosphate (ß-TCP) is a promising material in regenerative traumatology for the creation of bone implants. Previously, it was established that doping the structure with certain cations can reduce the growth of bacterial activity. Recently, much attention has been paid to co-doped ß-TCP, that is explained by their ability, on the one hand, to reduce cytotoxicity for cells of the human organism, on the other hand, to achieve a successful antibacterial effect. Sr, Cu-co-doped solid solutions of the composition Ca9.5-xSrxCu(PO4)7 was obtained by the method of solid-phase reactions. The Rietveld method of structural refinement revealed the presence of Sr2+ ions in four crystal sites: M1, M2, M3, and M4. The M5 site is completely occupied by Cu2+. Isomorphic substitution of Ca2+ → (Sr2+and Cu2+) expands the concentration limits of the existence of the solid solution with the ß-TCP structure. No additional phases were formed up to x = 4.5 in Ca9.5-xSrxCu(PO4)7. Biocompatibility tests were performed on cell lines of human bone marrow mesenchymal stromal cells (hMSC), human fibroblasts (MRC-5) and osteoblasts (U-2OS). It was demonstrated that cytotoxicity exhibited a concentration dependence, along with an increase in osteogenesis and cell proliferation. Ca9.5-xSrxCu(PO4)7 powders showed significant inhibitory activity against pathogenic strains Escherichia coli and Staphylococcus aureus. Piezoelectric properties of Ca9.5-xSrxCu(PO4)7 were investigated. Possible ways to achieve high piezoelectric response are discussed. The combination of bioactive properties of Ca9.5-xSrxCu(PO4)7 renders them multifunctional materials suitable for bone substitutes.

A systematic review of high impact CpG sites and regions for MGMT methylation in glioblastoma [A systematic review of MGMT methylation in GBM].

BACKGROUND: MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT gene by promoter methylation is associated with greater overall and progression free survival with alkylating agent regimens. To date, there is marked heterogeneity in how MGMT promoter methylation is tested and which CpG sites are interrogated. METHODS: To further elucidate which MGMT promoter CpG sites are of greatest interest, we performed comprehensive searches in PubMed, Web of Science, and Embase and reviewed 2,925 article abstracts. We followed the GRADE scoring system to assess risk of bias and the quality of the studies we included. RESULTS: We included articles on adult glioblastoma that examined significant sites or regions within MGMT promoter for the outcomes: overall survival, progression free survival, and/or MGMT expression. We excluded systemic reviews and articles on lower grade glioma. fifteen articles met inclusion criteria with variable overlap in laboratory and statistical methods employed, as well as CpG sites interrogated. Pyrosequencing or BeadChip arrays were the most popular methods utilized, and CpG sites between CpG's 70-90 were most frequently investigated. Overall, there was moderate concordance between the CpG sites that the studies reported to be highly predictive of prognosis. Combinations or means of sites between CpG's 73-89 were associated with improved OS and PFS. Six studies identified CpG sites associated with prognosis that were closer to the transcription start site: CpG's 8, 19, 22, 25, 27, 32,38, and CpG sites 21-37, as well as low methylation level of the enhancer regions. CONCLUSION: The following systematic review details a comprehensive investigation of the current literature and highlights several potential key CpG sites that demonstrate significant association with OS, PFS, and MGMT expression. However, the relationship between extent of MGMT promoter methylation and survival may be non-linear and could be influenced by potential CpG hotspots, the extent of methylation at each CpG site, and MGMT enhancer methylation status. There were several limitations within the studies such as smaller sample sizes, variance between methylation testing methods, and differences in the various statistical methods to test for association to outcome. Further studies of high impact CpG sites in MGMT methylation is warranted.

LNK/SH2B3 as a novel driver in juvenile myelomonocytic leukemia.

Mutations in five canonical Ras pathway genes (NF1, NRAS, KRAS, PTPN11 and CBL) are detected in nearly 90% of patients with juvenile myelomonocytic leukemia (JMML), a frequently fatal malignant neoplasm of early childhood. In this report, we describe seven patients diagnosed with SH2B3-mutated JMML, including five patients who were found to have initiating, loss of function mutations in the gene. SH2B3 encodes the adaptor protein LNK, a negative regulator of normal hematopoiesis upstream of the Ras pathway. These mutations were identified to be germline, somatic or a combination of both. Loss of function of LNK, which has been observed in other myeloid malignancies, results in abnormal proliferation of hematopoietic cells due to cytokine hypersensitivity and activation of the JAK/STAT signaling pathway. In vitro studies of induced pluripotent stem cell-derived JMML-like hematopoietic progenitor cells (HPCs) also demonstrated sensitivity of SH2B3- mutated HPCs to JAK inhibition. Lastly, we describe two patients with JMML and SH2B3 mutations who were treated with the JAK1/2 inhibitor ruxolitinib. This report expands the spectrum of initiating mutations in JMML and raises the possibility of targeting the JAK/STAT pathway in patients with SH2B3 mutations.

Combination NIPS/TIPS Synthesis of α-Fe2O3 and α/γ-Fe2O3 Doped PVDF Composite for Efficient Piezocatalytic Degradation of Rhodamine B.

Highly porous membranes based on polyvinylidene fluoride (PVDF) with the addition of nanoscale particles of non-magnetic and magnetic iron oxides were synthesized using a combined method of non-solvent induced phase separation (NIPS) and thermo-induced phase separation (TIPS) based on the technique developed by Dr. Blade. The obtained membranes were characterized using SEM, EDS, XRD, IR, diffuse reflectance spectroscopy, and fluorescent microscopy. It was shown that the membranes possessed a high fraction of electroactive phase, which increased up to a maximum of 96% with the addition of 2 wt% of α-Fe2O3 and α/γ-Fe2O3 nanoparticles. It was demonstrated that doping PVDF with nanoparticles contributed to the reduction of pore size in the membrane. All membranes exhibited piezocatalytic activity in the degradation of Rhodamine B. The degree of degradation increased from 69% when using pure PVDF membrane to 90% when using the composite membrane. The nature of the additive did not affect the piezocatalytic activity. It was determined that the main reactive species responsible for the degradation of Rhodamine B were •OH and •O2-. It was also shown that under piezocatalytic conditions, composite membranes generated a piezopotential of approximately 2.5 V.

Defining cardiac functional recovery in end-stage heart failure at single-cell resolution.

Recovery of cardiac function is the holy grail of heart failure therapy yet is infrequently observed and remains poorly understood. In this study, we performed single-nucleus RNA sequencing from patients with heart failure who recovered left ventricular systolic function after left ventricular assist device implantation, patients who did not recover and non-diseased donors. We identified cell-specific transcriptional signatures of recovery, most prominently in macrophages and fibroblasts. Within these cell types, inflammatory signatures were negative predictors of recovery, and downregulation of RUNX1 was associated with recovery. In silico perturbation of RUNX1 in macrophages and fibroblasts recapitulated the transcriptional state of recovery. Cardiac recovery mediated by BET inhibition in mice led to decreased macrophage and fibroblast Runx1 expression and diminished chromatin accessibility within a Runx1 intronic peak and acquisition of human recovery signatures. These findings suggest that cardiac recovery is a unique biological state and identify RUNX1 as a possible therapeutic target to facilitate cardiac recovery.

Morphotropic Phase Boundary Enhanced Photocatalysis in Sm Doped BiFeO3.

This paper presents the results of the synthesis of samarium-doped bismuth ferrite (BFO) nanoparticles by the solution combustion method. The dependence of BFO properties on the amount of the samarium (Sm) in the composition was studied. The synthesized nanocomposites were characterized by scanning electron microscopy SEM), X-ray diffractometry (XRD), Raman, Electron Diffuse Reflectance Spectroscopy (EDRS) and Electron Magnetic Resonance (EMR). The photocatalytic (PC) measurements showed the absence of a strict correlation between the PC activity and the crystallite size and band gap. An increase in the PC activity of BFO samples with 10 and 15% doping was observed and it was concluded that in controlling the PC properties in doped BFO, the processes of interfacial polarization at the boundaries of the morphotropic phase transition are of decisive importance. It was supposed that the internal electric field formed at these boundaries contributes to the efficient separation of photogenerated charge carriers.

Were there losses in social support during the pandemic? Testing the impact of COVID-19 on psychological adjustment to trauma in United States adults.

Introduction: Social support is a key protective factor in the psychological adjustment of individuals to traumatic events. However, since March 2020, extant research has revealed evidence of increased loneliness, social isolation, and disconnection, likely due to COVID-19 pandemic-related recommendations that restricted day-to-day contact with others. Methods: In this investigation, we applied a case-control design to test the direct impacts of the pandemic on social support in United States adults recovering from a significant injury caused by PTSD-qualifying, traumatic events (e.g., motor vehicle crashes, violence, etc.). We compared individuals who experienced trauma during the pandemic, the "cases" recruited and evaluated between December 2020 to April 2022, to trauma-exposed "controls," recruited and evaluated pre-pandemic, from August 2018 through March 9, 2020 (prior to changes in public health recommendations in the region). Cohorts were matched on key demographics (age, sex, education, race/ethnicity, income) and injury severity variables. We tested to see if there were differences in reported social support over the first 5 months of adjustment, considering variable operationalizations of social support from social network size to social constraints in disclosure. Next, we tested to see if the protective role of social support in psychological adjustment to trauma was moderated by cohort status to determine if the impacts of the pandemic extended to changes in the process of adjustment. Results: The results of our analyses suggested that there were no significant cohort differences, meaning that whether prior to or during the pandemic, individuals reported similar levels of social support that were generally protective, and similar levels of psychological symptoms. However, there was some evidence of moderation by cohort status when examining the process of adjustment. Specifically, when examining symptoms of post-traumatic stress over time, individuals adjusting to traumatic events during COVID-19 received less benefit from social support. Discussion: Although negative mental health implications of the pandemic are increasingly evident, it has not been clear how the pandemic impacted normative psychological adjustment processes. These results are one of the first direct tests of the impact of COVID-19 on longitudinal adjustment to trauma and suggest some minimal impacts.

Home-based physiology labs in the time of COVID-19 prove popular with medical students.

The COVID-19 pandemic and the resulting "lockdown" have forced many medical schools to shift from traditional "face-to-face" teaching methodologies and embrace full online delivery. Although lectures and tutorials are readily communicated by this approach, the execution of laboratory exercises is much more difficult. To overcome these challenges, face-to-face laboratory sessions were replaced by a blended learning approach in which students were provided instructional material online and then required to conduct the laboratory exercises at home. These laboratory exercises made use of easily accessible household materials and mobile applications. A self-report survey was designed to assess students' perception of their learning experience and attitudes to the home-based laboratory exercises. The survey consisted of 16 questions that students had to respond to using a 5-point Likert scale. Students were also allowed to provide open responses to select questions. Overall, the 80% of students that completed the survey expressed strong satisfaction with their learning experience and were enthusiastic toward home-based laboratory exercises. However, concerns about not being able to complete particular face-to-face exercises that required specialized equipment were expressed. Several students proposed a combined approach going forward. Our results show that home-based laboratory exercises offer a multimodal option that enriches the learning curriculum by engaging students in "hands-on" bespoke practicals using inexpensive household materials.

A cross-sectional study of neuromyths among teachers in a Caribbean nation.

BACKGROUND: The current COVID-19 pandemic and proliferation of misinformation regarding science highlights the importance of improving general science literacy. The continued preponderance of neuromyths among educators is of concern, especially in lower- and middle-income countries. METHOD: Using an adapted questionnaire, a cross-sectional survey was conducted among teachers in a small island developing state in the Caribbean. RESULTS: Two-thirds of the sample were unable to recognise at least 50% of the myths. Regression analysis demonstrated that higher scores in brain knowledge and exposure to prior teacher-training increased belief in neuromyths. On the other hand, specific in-service training pertaining to educational neuroscience improved scores. CONCLUSION: Neuromyths are prevalent among teachers and appear to inform their teaching practice. Further research needs to be conducted to explore not just the prevalence of these myths but in what ways they may be impacting teaching and learning outcomes in the classroom.

The road to optimal acceleration of Dixon imaging and quantitative T2-mapping in the ankle using compressed sensing and parallel imaging.

OBJECTIVE: This study aimed to find the optimal acceleration factor achievable with CS-SENSE for a clinical ankle protocol while maintaining comparable image quality. METHODS: We explored the optimal acceleration achievable with factor CS-SENSE, for an ankle protocol with T2-weighted, PD-weighted TSE-Dixon (coronal, axial and sagittal) and T2-mapping (sagittal) sequences, on a 3 T MRI-scanner. This study contained three steps: (1) phantom test, (2) pilot test on healthy volunteers, (3) anatomical assessment on a cohort of healthy volunteers and a quantitative analysis. CS-SENSE images (acceleration factors between 2.0× and 12.0×) were compared to reference SENSE images (acceleration factor 2.0×). Three blinded radiologists evaluated the image quality and provided an anatomical assessment using a five-point Likert scale of 25 anatomical regions. RESULTS: The total acquisition time of the TSE-Dixon sequence was reduced by 45 % from 13'38″ to 7'37″ (acceleration factor between 3.6× and 4.0×), the T2-mapping scan time was reduced by 31 % from 5'28″ to 3'47″ (acceleration factor of 3.0×), while maintaining comparable image quality. The results from the anatomical assessment of SENSE 2.0× versus CS-SENSE 3.6× were comparable in 88.7 % as shown by the 5-point Likert scale measurements. The T2-relaxation measurements had a good correlation of ρ = 0.7 between SENSE and CS-SENSE. CONCLUSION: We found an optimum acceleration factor with CS-SENSE between 3.6× and 4.0× for TSE-Dixon and 3.0× for T2-mapping sequences in a clinical MR imaging protocol of the ankle. The total scan time was reduced by 41 % while maintaining adequate image quality.

FOXM1 drives proximal tubule proliferation during repair from acute ischemic kidney injury.

The proximal tubule has a remarkable capacity for repair after acute injury, but the cellular lineage and molecular mechanisms underlying this repair response are incompletely understood. Here, we developed a Kim1-GFPCreERt2 knockin mouse line (Kim1-GCE) in order to perform genetic lineage tracing of dedifferentiated cells while measuring the cellular transcriptome of proximal tubule during repair. Acutely injured genetically labeled clones coexpressed KIM1, VIMENTIN, SOX9, and KI67, indicating a dedifferentiated and proliferative state. Clonal analysis revealed clonal expansion of Kim1+ cells, indicating that acutely injured, dedifferentiated proximal tubule cells, rather than fixed tubular progenitor cells, account for repair. Translational profiling during injury and repair revealed signatures of both successful and unsuccessful maladaptive repair. The transcription factor Foxm1 was induced early in injury, was required for epithelial proliferation in vitro, and was dependent on epidermal growth factor receptor (EGFR) stimulation. In conclusion, dedifferentiated proximal tubule cells effect proximal tubule repair, and we reveal an EGFR/FOXM1-dependent signaling pathway that drives proliferative repair after injury.

Molecular assessment of pretransplant chemotherapy in the treatment of juvenile myelomonocytic leukemia.

BACKGROUND: Despite the intensity of hematopoietic stem cell transplantation (HCT), relapse remains the most common cause of death in juvenile myelomonocytic leukemia (JMML). In contrast to other leukemias where therapy is used to reduce leukemic burden prior to transplant, many patients with JMML proceed directly to HCT with active disease. The objective of this study was to elucidate whether pre-HCT therapy has an effect on the molecular burden of disease and how this affects outcome post-HCT. PROCEDURE: Twenty-one patients with JMML who received pre-HCT therapy and were transplanted at UCSF were analyzed in this study. The mutant allele frequency of the driver mutation was assessed before and after pre-HCT therapy, using custom amplicon next-generation sequencing. RESULTS: Of the 21 patients, seven patients (33%) responded to therapy with a significant reduction in their mutant allele frequency and were classified as molecular responders. Six of these patients received moderate-intensity chemotherapy, one patient received only azacitidine. The 5-year progression-free survival after HCT of molecular responders was 100% versus 61% for nonresponders (P = .12). Survival of molecular nonresponders was not improved by use of high-intensity conditioning, but patients were salvaged if they experienced severe graft versus host disease. There were no baseline clinical characteristics that were associated with response to pre-HCT therapy. CONCLUSIONS: Despite the myelodysplastic nature of JMML, patients treated with pre-HCT therapy can achieve molecular remissions. These patients experienced a trend toward improved outcomes post-HCT. Importantly, molecular testing can be helpful to distinguish between responders and nonresponders and should become an integral part of clinical care.

The Relationship Between Self-Esteem, Emotional Intelligence, and Empathy Among Students From Six Health Professional Programs.

Theory: Psychosocial skills such as communication, empathy, and emotional intelligence are now considered key attributes of health professionals. Self-esteem is another important construct that is less well studied. Self-esteem is important because low levels have been linked to depression, suicide, and eating disorders. Given that health professional students experience high levels of stress and are at increased risk for similar psychopathology, self-esteem may be an important variable in student well-being and performance after graduation. Hypotheses: This study sought to explore self-esteem during students' 1st year of training hypothesizing that several would demonstrate low self-esteem. It is also hypothesized that emotional intelligence and empathy would be associated with self-esteem. Method: A cross-sectional survey was conducted, and data were gathered from dental, medical, nursing, optometry, pharmacy and veterinary students. Self-report questionnaires assessing self-esteem, emotional intelligence, and empathy were completed and demographic information was collected. Scores were calculated and differences between groups analyzed with analysis of variance and chi-square testing. Pearson's correlation was used to assess associations between the constructs. Results: The mean self-esteem score was 26.2 ± 2.3 but 21% of the sample evidenced low self-esteem. There was no difference in the proportion of students demonstrating low self-esteem among programs. Gender did not have a significant effect on self-esteem scores, though ethnicity did. Emotional intelligence scores were higher among male individuals than among female. Emotional intelligence and empathy showed a small association with self-esteem. Conclusions: A significant proportion of health professional students suffer from low self-esteem during their 1st year of study. Such students may be more susceptible to the stresses associated with study and the development of psychopathology. More research needs to be conducted to explore the relationships between self-esteem, emotional intelligence, and empathy with a view to strengthening training in these areas and managing the challenges faced by health professional students.

Cafeteria-diet induced obesity results in impaired cognitive functioning in a rodent model.

OBJECTIVES: This study seeks to characterize the progressive course of physiological and behavioural outcomes in rodents following excessive caloric intake through the chronic consumption of a highly palatable diet, the cafeteria (CAF) diet. METHODS: Male Sprague Dawley rats were maintained on either CAF or chow (CON) diets for 20 weeks. Metabolic and physiological parameters were monitored throughout the feeding period. From week 18, rats were subjected to behavioural testing, which included the Morris water maze (MWM) and novel object recognition (NOR) tasks. RESULTS: CAF rats consistently showed higher food intakes and consumed six times the energy of chow-fed rats, being significantly heavier by week 5. CAF rats further exhibited greater abdominal widths, fat pads, and larger fatty livers, as well as compromised glucose tolerance. Hyperinsulinemia and dyslipidaemia with elevated serum cholesterol and triglyceride levels and reduced HDL cholesterol were also evident along with a pro-inflammatory profile in the CAF rats. Cognitive decline in CAF rats manifested as a decline in long-term retention memory in the MWM. Further, CAF rats exhibited deficits in recognition memory as they spent less time exploring the novel object than chow-fed rats in the NOR task. DISCUSSION: This model of obesity is a robust paradigm for producing an obese animal phenotype that closely mimics the evolution of human obesity, complete with metabolic dysfunctions that are indicative of pre-diabetes. Additionally, chronic CAF-diet induced obesity promotes cognitive impairments in hippocampal-dependent reference and working memory.

Attitudes toward mental illness among Caribbean medical students.

Background: There are limited empirical data on all matters pertaining to mental illness in the Caribbean but what little there is suggests significant levels of stigmatization exist. In this context, health professionals reveal at least equal to or only slightly improved attitudes to mental illness as compared to the general population. In addition, while there is evidence of improved attitudes among the population at large over the past decade this trend has not been observed among health professionals. This study, therefore, sought to assess medical students' knowledge about and attitudes toward mental illness as they traversed medical school. Methods: Preclinical medical students were surveyed and then retested in their final year of training. Students completed a knowledge scale, and the medical conditions regard scale comparing attitudes to four mental illness and three physical illness. Results: Knowledge about and attitudes toward mental illness showed significant improvement over the 5-year period. However, both preclinical and clinical students revealed significant levels of stigmatization toward mental illness despite improvements in knowledge. Students recognized the need to prioritize treatment for persons with mental illness but did not want to be personally involved in the treatment process. Discussion: Results highlight that significant negative attitudes still exist among medical students toward mental illness and these persist up until graduation. There is a need for further research into innovations and interventions to address this matter.

Sex differences in the effects of acute stress on behavior in the ultimatum game.

Acute stress affects human decision making. It has been argued that there are systematic sex differences in behavioral responses to acute stress, with males showing a 'fight or flight' and females showing a 'tend and befriend' response. A 'tend and befriend' response would suggest that women become more cooperative under acute stress, while men do not. We investigated the effects of acute stress on social behavior. We induced stress via the Trier Social Stress Test (TSST) and then immediately after measured how participants reacted to offers made in the ultimatum game by a male proposer. We found that female participants were less likely to reject offers under stress (n = 25) vs. no stress (n = 37), p = 0.009, independent of how fair these offers were, cooperative behavior consistent with the 'tend and befriend' hypothesis. Male participants when stressed (n = 30) did not show differences in rejections rates compared to the control condition (n = 26), p = 0.41. Our results provide support for a qualitatively different behavioral response to acute stress among men and women.

Upregulation of cholesterol 24-hydroxylase following hypoxia-ischemia in neonatal mouse brain.

BackgroundMaintenance of cholesterol homeostasis is crucial for brain development. Brain cholesterol relies on de novo synthesis and is cleared primarily by conversion to 24S-hydroxycholesterol (24S-HC) with brain-specific cholesterol 24-hydroxylase (CYP46A1). We aimed to investigate the impact of hypoxia-ischemia (HI) on brain cholesterol metabolism in the neonatal mice.MethodsPostnatal day 9 C57BL/6 pups were subjected to HI using the Vannucci model. CYP46A1 expression was assessed with western blotting and its cellular localization was determined using immunofluorescence staining. The amount of brain cholesterol, 24S-HC in the cortex and in the serum, was measured with enzyme-linked immunosorbent assay (ELISA).ResultsThere was a transient cholesterol loss at 6 h after HI. CYP46A1 was significantly upregulated at 6 and 24 h following HI with a concomitant increase of 24S-HC in the ipsilateral cortex and in the serum. The serum levels of 24S-HC correlated with those in the brain, as well as with necrotic and apoptotic cell death evaluated by the expression of spectrin breakdown products and cleaved caspase-3 at 6 and 24 h after HI.ConclusionEnhanced cholesterol turnover by activation of CYP46A1 represents disrupted brain cholesterol homeostasis early after neonatal HI. 24S-HC might be a novel blood biomarker for severity of hypoxic-ischemic encephalopathy with potential clinical application.

Meis1 is specifically upregulated in kidney myofibroblasts during aging and injury but is not required for kidney homeostasis or fibrotic response.

The homeobox transcription factor Meis1 is required for mammalian development, and its overexpression plays a role in tumorigenesis, especially leukemia. Meis1 is known to be expressed in kidney stroma, but its function in kidney is undefined. We hypothesized that Meis1 may regulate stromal cell proliferation in kidney development and disease and tested the hypothesis using cell lineage tracing and cell-specific Meis1 deletion in development, aging, and fibrotic disease. We observed strong expression of Meis1 in platelet-derived growth factor receptor-ß-positive pericytes and perivascular fibroblasts, both in adult mouse kidney and to a lesser degree in human kidney. Either bilateral ischemia-reperfusion injury or aging itself led to strong upregulation of Meis1 protein and mRNA in kidney myofibroblasts, and genetic lineage analysis confirmed that Meis1-positive cells proliferate as they differentiate into myofibroblasts after injury. Conditional deletion of Meis1 in all kidney stroma with two separate tamoxifen-inducible Cre recombinase drivers had no phenotype with the exception of consistent induction of the tubular injury marker kidney injury molecule-1 (Kim-1) only in Meis1 mutants. Further examination of Kim-1 expression revealed linkage disequilibrium of Kim-1 and Meis1, such that Meis1 mutants carried the longer BALB/c Kim-1 allele. Unexpectedly, we report that this Kim-1 allele is expressed at baseline in wild-type BALB/c mice, without any associated abnormalities, including long-term fibrosis, as predicted from the literature. We conclude that Meis1 is specifically expressed in stroma and myofibroblasts of mouse and human kidney, that it is not required for kidney development, disease, or aging, and that BALB/c mice unexpectedly express Kim-1 protein at baseline without other kidney abnormality.

Genome-wide DNA methylation is predictive of outcome in juvenile myelomonocytic leukemia.

Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative disorder of childhood caused by mutations in the Ras pathway. Outcomes in JMML vary markedly from spontaneous resolution to rapid relapse after hematopoietic stem cell transplantation. Here, we hypothesized that DNA methylation patterns would help predict disease outcome and therefore performed genome-wide DNA methylation profiling in a cohort of 39 patients. Unsupervised hierarchical clustering identifies three clusters of patients. Importantly, these clusters differ significantly in terms of 4-year event-free survival, with the lowest methylation cluster having the highest rates of survival. These findings were validated in an independent cohort of 40 patients. Notably, all but one of 14 patients experiencing spontaneous resolution cluster together and closer to 22 healthy controls than to other JMML cases. Thus, we show that DNA methylation patterns in JMML are predictive of outcome and can identify the patients most likely to experience spontaneous resolution.