Skin exhibits remarkable regional specificity. However, the epigenetic mechanism underlying this process remains elusive. In this study, we used the avian scalp skin as a model and leveraged the finding that a tandem 195-bp duplication in the intron of HoxC10 causes the chicken Crest phenotype. Crested chickens (e.g., Polish chickens) exhibit elongated feathers in the scalp region and the comb is minute. Along the anterior-posterior midline dermis of the control White Leghorn chicken, we showed a co-linear expression of HoxC members (using RNA seq,in situ hybridization), which correlated with region-specific chromatin accessibility (using ATAC seq). Configurations of topologically associating domains (TADs) over the HoxC gene cluster in the scalp, dorsal and tail dermis show reduced HoxC gene interactions with outside regulatory elements particularly in the scalp region (using Micro-C). In contrast, crested Polish scalp dermis exhibits a TAD configuration that is similar to the configuration found in dorsal dermis. HoxC8 over-expression in the scalp led to new feather bud formation at the expense of the comb domain, representing a homeotic transformation. Further analyses revealed six transcription factors as major potential upstream modulators of the HoxC cluster in the chicken scalp region, and the tandemly duplicated 195 bp in Polish chickens may facilitate the generation of ectopic chromatin loops to interact with distant putative enhancers. Our results provide a new clue to dissect how the HoxC gene cluster is regulated in different skin regions, setting up a platform to study the epigenetic control of skin regional specificity, and how the scalp region can exhibit so many diverse skin appendage phenotypes in birds as well as in mammals.

Incidence of perioperative AKI ranging from 7.5% in patients with normal kidney function to 40% in high-risk patients. Understanding of burden and aetiology of AKI in perioperative patients and developing a robust preventative framework should remain a top priority to prevent adverse outcomes.

Heart failure is a major cause of morbidity and mortality, in part owing to the inability of the human heart to replenish lost cardiomyocytes following cardiac injury. Recent studies have demonstrated that neonatal human and mouse heart can fully regenerate in response to injury. This regenerative capacity, however, is transient and age-dependent. The regenerative capacity of neonatal mouse heart, for example, declines sharply by 7 days of age. It has been demonstrated that tissue-resident macrophages in neonatal hearts are required for cardiac repair and recovery from injuries by promoting angiogenesis and cardiomyocyte proliferation. The cellular and molecular determinants underlying the reparative/pro-regenerative properties of neonatal cardiac macrophages, however, remain elusive. To reciprocally characterize macrophage heterogeneity and functionality that are critical for myocardial repair and regeneration following myocardial infarction (MI) injury in neonatal (regenerative) and adult (non-regenerative) mouse hearts. Cardiac tissue-sorted macrophages (CD45+CD11b+CD64+) from neonatal (P1–3) and adult (8 weeks) mouse heart 10 days following MI (by permanent coronary artery ligation) were subjected to bulk and single-cell RNA sequencing (scRNA-Seq) analyses. In response to MI injury, CCR2+ monocyte-derived macrophages predominate in adult, whereas CCR2- resident macrophages expand markedly in neonatal mouse hearts. Comparing to sham-operated controls, bulk RNA-Seq revealed that the expression levels of a total of 482 and 614 mRNAs were significantly (absolute fold change >2, P<0.05) altered in adult and neonatal cardiac macrophages following MI, respectively. Pathway analyses showed that genes involved in olfactory function and Wnt-signaling were dysregulated in adult, whereas transcripts involved in oxidative phosphorylation and interferon-g (IFN-g) pathway were upregulated in neonatal cardiac macrophages after MI. scRNA-Seq analysis identified 11 distinct cardiac macrophage clusters in adult mouse heart following MI, several of which showed strong upregulation in inflammatory mediators (Ly6c2, Clec4b1, Cxcl3 and Lilra5) and extracellular matrix protein genes (Fn1, and Dcn), suggesting macrophage polarization towards a pro-inflammatory and fibrogenic phenotype in post-injury adult heart. As distinct macrophage populations mentioned in current study, our results revealed divergent transcriptionl signatures of cardiac macrophages in post-MI neonatal and adult mouse hearts. While Wnt signaling, inflammation and fibrogenic activities are increased in adult cardiac macrophages, oxidative phosphorylation and IFN-g signaling are markedly activated in neonatal cardiac macrophages in response to injury. Phenotypic switching toward enhanced oxidative phosphorylation and IFN-g signaling in cardiac macrophages, therefore, could be the key to develop novel therapeutics to promote cardiac regeneration. Type of funding source: None

To investigate the economic burden of medical treatment of children with asthma in China. The China Medical Insurance Research Association (CHIRA) database was searched for patients with asthma from 0 to 14 years old who were diagnosed based on the criteria of “J45” and “J46” coded in ICD-10. A cross-sectional study with cost analysis was conducted. The annual per capita direct medical cost was RMB $525 (US$75) related to asthma. The percentages of medical cost covered by insurance for asthma in China was 58%. The cost of medication accounted for the majority of direct medical costs. The cost of asthma medication accounted for the greatest percentage of all medication costs, followed by the cost of antibiotics. The rate of using antibiotics during asthma attack was 50.3%. In subgroup analysis, the highest rates of using antibiotics were central China (100.0%), children aged 3 years and under (63.6%), as well as fourth-tier and fifth-tier cities (77.1%). Patients underwent the pulmonary function test (12.2%), and allergen test (5.8%) during treatment. Outpatient clinics(98.58% vs 1.42%, P <0.01), tertiary hospitals (62.08% vs 37.92%, P <0.01), and general hospitals (72.27% vs 27.73%, P <0.01) were more often visited than the inpatient clinics, mid-level and primary as well as the specialized clinics, respectively. The economic burden of childhood asthma in China is relatively high, but the national medical insurance reduces their economic burden to a large extent. Based on our findings, there remain opportunities to strengthen the hierarchical medical system, and the Global Initiative for Asthma (GINA) program and Chinese guidelines still need to be further popularized in order to achieve complete control of asthma, thereby reducing hospitalization and emergency visits, shortening the length of hospital stay, and ultimately reducing the economic burden of children with asthma.

Definitive treatment for LA-HNSCC varies by anatomic subsite and may include surgery, chemotherapy, and/or radiation therapy (RT). LA-HNSCC patients treated with RT are typically at risk for PEG placement due to symptomatic dehydration or malnutrition as a direct result of therapy. However, it is unclear whether therapies preceding or concurrent with RT are associated with PEG tube placement. Therefore our objective was to assess treatment-related risk factors leading to reactive PEG tube placement in patients undergoing RT.

Mackay region has one of the highest rates of overweight and obesity in Queensland, Australia, comprising 83.4 per cent of its adult population. In this retrospective clinical audit, we studied the results of renal biopsies, risk factors of renal impairment, and biopsy-related complications at the Mackay Base Hospital (MBH), Queensland, Australia. Based on this epidemiology data, we aim to have earlier identification of the modifiable risk factors of renal diseases, targeted and effective public health promotion, earlier renal surveillance and intervention for at risk population before developing chronic renal failure.

Herpes zoster is viewed as indicator of immunosuppression. Sometimes is also a maker for HIV, malignancy. Young adult suffered from herpes zoster is less common than old patient. There are some studies found that ocular involvement in young adult may suspect HIV infection. However, there are no answers whether early onset herpes zoster (20-49 year old) association malignancy or not. The study used non-sample claims data of the National Health Insurance of Taiwan in 2000-2010. 121104 patients newly diagnosed early onset HZ is included and randomly selected non-HZO cohort (N=484416) frequency matched by sex, age and diagnosis year control patients. We performed Cox regressions to compare the hazard ratio (HR) of herpes zoster in the early onset zoster cohort and comparison cohort. After adjustment for potential confounding factors, patients with early onset HZ were more likely to have incidents of hematology malignancy (adjusted HR 1.69, 95% confidence interval [CI] 1.40–2.03). In conclusion, early onset HZ patients are at a high risk to develop hematologic malignancy, including Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma and leukemia. Follow-up for hematologic conditions is suggested for early onset HZ patients who had suspected symptoms.

Clival Chordoma is a rare malignancy for which optimal surgery is typically followed by radiation therapy (RT). Proton RT has allowed for dose escalation, with improved local control compared to conventional photon RT. In this study, we utilize the National Cancer Database (NCDB) to assess utilization of radiation in these patients. We searched the NCDB for all patients with clival chordoma with chondroid, dedifferentiated or not otherwise specified histology diagnosed 2004 to 2014. Patients with unknown radiation information were excluded. All retrievable demographic, tumor specific, and treatment factors were recorded. The overall survival (OS) was estimated using the Kaplan-Meier method for patients with outcome data. A total of 118 patients with clival chordoma were identified, 8 patients were excluded due to lack of radiation information. There 16 patients with chondroid histology and 102 patients with histology not otherwise specified. Sixty-two patients underwent surgery alone, 29 were treated with resection followed by RT, 12 patients received no radiation or resection, and 7 patients were treated with radiation alone. Thirty six patients (32.7%) were treated with radiation. Patients who were treated with radiation were significantly more likely to be age 65 or greater (p=0.004) and treated at an academic institution (p= 0.003). Positive margins (macroscopic/microscopic) were present in 28% of patients treated with RT vs. 16% in patients without RT, p = 0.45. There was no significant difference in sex, year of diagnosis, Charlson-Deyo comorbidity score, education, income, or distance from treatment facility. Of patients treated with RT, 66% were treated with conventional photons, 11% with PRT, and 22% with stereotactic radiosurgery. Median dose for fractionated radiation was 70 Gy (range 50.4-79.2 Gy). Overall survival was available for 101 patients with a median follow up of 48.5 months (IQR 13.6 – 134). Median survival for patients treated with radiation is 51.5 months (95% confidence interval (CI) 30.2-72.8 months) vs 62.2 months (95% CI 51.8- 73.6 months) for patients treated without RT, with no significant difference in survival (p=0.86). Despite multiple studies showing a local control benefit of radiation in the management of clival chordoma, this national hospital based analysis shows that radiation is broadly underutilized. Older age and treatment at an academic center were associated with treatment with radiation.