Miracle-dz/UniFAR-FTUs huggingface dataset:
Self-regenerative capacity of intra-oral bone defects.

OBJECTIVE To provide an overview on the self-regenerative capacity of various types of intra-oral bone defects. MATERIALS AND METHODS This paper has narratively reviewed the most important aspects of bone biology and the healing outcomes related to the self-regenerative capacity (i.e. without the placement of any biomaterial) of bone defects that occur following tooth extraction, autogenous graft harvesting, periapical lesions, cystic lesions of the jaws, third molar extraction and experimentally created ridge defects. RESULTS In animals (i.e. dogs and monkeys), the greatest changes in horizontal and vertical dimension occur during the first 6 months following tooth extraction. In humans, bone remodelling may take from several months to years and exhibits marked inter-individual variability. Following tooth extraction at compromised sites (e.g. presence of severe bone loss at the time-point of extraction), the healing may occur slower and a substantial volume reduction can be expected than following tooth extraction at non-compromised sites. In the mandibular symphysis and ramus, the bone defects resulting following bone block harvesting are gradually healing to a large extent, but complete healing appears not to occur due to poorer space provision and wound stability capacities. Defects after peri-apical surgery display a substantial self-regenerative capacity and heal at a great extent without the use of any adjunct measures. The vast majority of jawbone defects after cystectomy heal at a great extent and without apparent influence in the shape of the jaw, without the need of adjunct measures. After surgical removal of mandibular third molars, bone fill can be observed over a period of at least 12 months, with the most substantial change (e.g. the greatest bone fill) occurring during the first 3 months after surgery. However, complete fill of these residual bone defects does not always occur. CONCLUSIONS Intra-oral bone defects possess a high self-regenerative capacity. Factors such as extent of bone loss, presence of bony walls, closed healing environment, space provision and mechanical wound stability substantially influence healing/regeneration.
Incidence and risk factors associated with development of clinical cardiotoxicity in dogs receiving doxorubicin

Background Doxorubicin (DOX) can cause cumulative cardiotoxicity in dogs, but the incidence of clinical cardiotoxicity in dogs receiving DOX has not been determined. Hypothesis/Objectives To determine if the duration of DOX infusion influences the incidence of cardiotoxicity, to characterize the incidence of clinical cardiotoxicity in dogs during or after DOX chemotherapy, and to identify any risk factors associated with cardiotoxicity. Animals Four‐hundred ninety‐four dogs that received at least 1 dose of DOX for the treatment of cancer. Methods Retrospective study of dogs that received DOX from 2006 to 2015. Results Of 494 dogs, 20 (4.0%) developed clinical cardiotoxicity. The duration of DOX infusion was not significantly associated with clinical cardiotoxicity, whereas a higher cumulative dose of DOX, higher body weight, decreases in fractional shortening after 5 doses of DOX, and development of ventricular premature contractions were significantly associated with clinical cardiotoxicity. High‐risk breeds for developing dilated cardiomyopathy had an incidence of 15.4%, whereas low‐risk breeds had an incidence of 3.0%. Conclusions and Clinical Importance Although the duration of DOX infusion did not influence the incidence of cardiotoxicity, premature contractions and decreases in fractional shortening should raise concern for the development of clinical cardiotoxicity. Overall, the incidence of clinical DOX‐induced cardiotoxicity is low, but Boxers and other breeds at high risk for dilated cardiomyopathy may be at an increased risk.
The Genetic and Environmental Relationship Between Childhood Behavioral Inhibition and Preadolescent Anxiety

Abstract This study uses novel approaches to examine genetic and environmental influences shared between childhood behavioral inhibition (BI) and symptoms of preadolescent anxiety disorders. Three hundred and fifty-two twin pairs aged 9–13 and their mothers completed questionnaires about BI and anxiety symptoms. Biometrical twin modeling, including a direction-of-causation design, investigated genetic and environmental risk factors shared between BI and social, generalized, panic and separation anxiety. Social anxiety shared the greatest proportion of genetic (20%) and environmental (16%) variance with BI with tentative evidence for causality. Etiological factors underlying BI explained little of the risk associated with the other anxiety domains. Findings further clarify etiologic pathways between BI and anxiety disorder domains in children.
Insight into novel RNA-binding activities via large-scale analysis of lncRNA-bound proteome and IDH1-bound transcriptome

Abstract RNA-binding proteins (RBPs) play pivotal roles in directing RNA fate and function. Yet the current annotation of RBPs is largely limited to proteins carrying known RNA-binding domains. To systematically reveal dynamic RNA–protein interactions, we surveyed the human proteome by a protein array-based approach and identified 671 proteins with RNA-binding activity. Among these proteins, 525 lack annotated RNA-binding domains and are enriched in transcriptional and epigenetic regulators, metabolic enzymes, and small GTPases. Using an improved CLIP (crosslinking and immunoprecipitation) method, we performed genome-wide target profiling of isocitrate dehydrogenase 1 (IDH1), a novel RBP. IDH1 binds to thousands of RNA transcripts with enriched functions in transcription and chromatin regulation, cell cycle and RNA processing. Purified IDH1, but not an oncogenic mutant, binds directly to GA- or AU-rich RNA that are also enriched in IDH1 CLIP targets. Our study provides useful resources of unconventional RBPs and IDH1-bound transcriptome, and convincingly illustrates, for the first time, the in vivo and in vitro RNA targets and binding preferences of IDH1, revealing an unanticipated complexity of RNA regulation in diverse cellular processes.
Conditional degradation of SDE2 by the Arg/N-End rule pathway regulates stress response at replication forks

Abstract Multiple pathways counteract DNA replication stress to prevent genomic instability and tumorigenesis. The recently identified human SDE2 is a genome surveillance protein regulated by PCNA, a DNA clamp and processivity factor at replication forks. Here, we show that SDE2 cleavage after its ubiquitin-like domain generates Lys-SDE2Ct, the C-terminal SDE2 fragment bearing an N-terminal Lys residue. Lys-SDE2Ct constitutes a short-lived physiological substrate of the Arg/N-end rule proteolytic pathway, in which UBR1 and UBR2 ubiquitin ligases mediate the degradation. The Arg/N-end rule and VCP/p97UFD1-NPL4 segregase cooperate to promote phosphorylation-dependent, chromatin-associated Lys-SDE2Ct degradation upon UVC damage. Conversely, cells expressing the degradation-refractory K78V mutant, Val-SDE2Ct, fail to induce RPA phosphorylation and single-stranded DNA formation, leading to defects in PCNA-dependent DNA damage bypass and stalled fork recovery. Together, our study elucidates a previously unappreciated axis connecting the Arg/N-end rule and the p97-mediated proteolysis with the replication stress response, working together to preserve replication fork integrity.
Comparison of intravenous, topical or combined routes of tranexamic acid administration in patients undergoing total knee and hip arthroplasty: a meta-analysis of randomised controlled trials

Objective This study aimed to compare the effects of intravenous, topical and combined routes of tranexamic acid (TXA) administration on blood loss and transfusion requirements in patients undergoing total knee arthroplasty (TKA) and total hip arthroplasty (THA). Design This was a meta-analysis of randomised controlled trials (RCT) wherein the weighted mean difference (WMD) and relative risk (RR) were used for data synthesis applied in the random effects model. Stratified analyses based on the surgery type, region, intravenous and topical TXA dose and transfusion protocol were also conducted. The main outcomes included intraoperative and total blood loss volume, transfusion rate, low postoperative haemoglobin (Hb) level and postoperative Hb decline. However, the secondary outcomes included length of hospital stay (LOS) and/or occurrence of venous thromboembolism (VTE). Setting We searched the PubMed, Embase and Cochrane CENTRAL databases for RCTs that compared different routes of TXA administration. Participants Patients undergoing TKA or THA. Interventions Intravenous, topical or combined intravenous and topical TXA. Results Twenty-six RCTs were selected, and the intravenous route did not differ substantially from the topical route with respect to the total blood loss volume (WMD=30.92, p=0.31), drain blood loss (WMD=−34.53, p=0.50), postoperative Hb levels (WMD=−0.01, p=0.96), Hb decline (WMD=−0.39, p=0.08), LOS (WMD=0.15, p=0.38), transfusion rate (RR=1.08, p=0.75) and VTE occurrence (RR=1.89, p=0.15). Compared with the combined-delivery group, the single-route group had significantly increased total blood loss volume (WMD=198.07, p<0.05), greater Hb decline (WMD=0.56, p<0.05) and higher transfusion rates (RR=2.51, p<0.05). However, no significant difference was noted in the drain blood loss, postoperative Hb levels and VTE events between the two groups. The intravenous and topical routes had comparable efficacy and safety profiles. Conclusions The combination of intravenous and topical TXA was relatively more effective in controlling bleeding without increased risk of VTE.
Estimating the epidemiological impact and cost-effectiveness profile of a nonavalent HPV vaccine in Spain

ABSTRACT Human papillomavirus (HPV) is one of the main causes of infection-related cancer. The bivalent vaccine (2vHPV) (16/18) and quadrivalent (6/11/16/18) HPV vaccine (4vHPV) have been included in the Spanish vaccination calendar since 2007. The new nonavalent HPV vaccine (9vHPV), approved in Europe in 2015, includes nine HPV types 6/11/16/18/31/33/45/52/58 and has been available in Spain since May 2017. Our study aims to estimate the epidemiological impact and the cost-effectiveness of a girls-only and a gender-neutral vaccination program with 9vHPV compared to the current vaccination program in Spain. A dynamic transmission model simulating the natural history of HPV infections was calibrated to the Spanish setting and applied to estimate costs and quality-adjusted life years (QALYs) associated with vaccination strategies using a payer perspective and a 100-year time horizon. A girls-only vaccination strategy at age 12 years with 9vHPV was found to be a cost-effective strategy compared with 4vHPV (incremental cost-effectiveness ratio (ICER) of €7,718 per QALY). Compared with girls-only vaccination with 4vHPV, gender-neutral vaccination with 9vHPV was associated with further reductions of up to 28.5% in the incidence of cervical intraepithelial neoplasia (CIN) 2/3 and 17.1% in the incidence of cervical cancer, as well as with a 14.0% reduction in cervical cancer mortality. Furthermore, a gender-neutral vaccination program with 9vHPV could potentially be cost-effective considering some parameters as head and neck protection or discount rates, leading to a reduction in the burden of HPV-related diseases in both sexes in the Spanish population.
Association of Total and Trimester-Specific Gestational Weight Gain Rate with Early Infancy Weight Status: A Prospective Birth Cohort Study in China

Studies to examine the associations of gestational weight gain (GWG) with offspring weight status during infancy are needed, especially among Asian populations. We examined 801 mother–infant pairs from a prospective cohort study in China to assess the associations of total and trimester-specific GWG with early infant weight status. We used linear mixed effects models and linear regression models to examine the longitudinal and time-point associations of GWG rate (kg/week) with infant growth measures (z-scores of body-mass-index (BMIZ), weight-for-age (WFAZ) and length-for-age (LFAZ)) at birth, 1, 3, and 6 months. Greater total GWG rate was associated with higher BMIZ (β:1.34 SD units (95% CI: 0.84, 1.83) per 1 kg/week increase in GWG) and higher WFAZ (β:1.18 SD units (95% CI: 1.01, 2.28)) across the first 6 months of life. GWG rate in the first two trimesters but not in the third trimester was positively associated with infant BMIZ. The association between GWG rate and infant BMIZ was significant at all timepoints and more pronounced in normal weight women and among male infants. In conclusion, greater GWG rate is positively associated with offspring BMIZ in the first 6 months of life, the association is mostly driven by GWG in the first two trimesters.
Multicomponent non-pharmacological intervention to prevent delirium for hospitalised people with advanced cancer: study protocol for a phase II cluster randomised controlled trial

Introduction Delirium is a significant medical complication for hospitalised patients. Up to one-third of delirium episodes are preventable in older inpatients through non-pharmacological strategies that support essential human needs, such as physical and cognitive activity, sleep, hydration, vision and hearing. We hypothesised that a multicomponent intervention similarly may decrease delirium incidence, and/or its duration and severity, in inpatients with advanced cancer. Prior to a phase III trial, we aimed to determine if a multicomponent non-pharmacological delirium prevention intervention is feasible and acceptable for this specific inpatient group. Methods and analysis The study is a phase II cluster randomised wait-listed controlled trial involving inpatients with advanced cancer at four Australian palliative care inpatient units. Intervention sites will introduce delirium screening, diagnostic assessment and a multicomponent delirium prevention intervention with six domains of care: preserving natural sleep; maintaining optimal vision and hearing; optimising hydration; promoting communication, orientation and cognition; optimising mobility; and promoting family partnership. Interdisciplinary teams will tailor intervention delivery to each site and to patient need. Control sites will first introduce only delirium screening and diagnosis, later implementing the intervention, modified according to initial results. The primary outcome is adherence to the intervention during the first seven days of admission, measured for 40 consecutively admitted eligible patients. Secondary outcomes relate to fidelity and feasibility, acceptability and sustainability of the study intervention, processes and measures in this patient population, using quantitative and qualitative measures. Delirium incidence and severity will be measured to inform power calculations for a future phase III trial. Ethics and dissemination Ethical approval was obtained for all four sites. Trial results, qualitative substudy findings and implementation of the intervention will be submitted for publication in peer-reviewed journals, and reported at conferences, to study sites and key peak bodies. Trial registration number ACTRN12617001070325; Pre-results.
The effect of flow on blood oxygen level dependent (R*2) MRI of orthotopic lung tumors

Blood oxygen level dependent (BOLD) MRI based on R2* measurements can provide insights into tumor vascular oxygenation. However, measurements are susceptible to blood flow, which may vary accompanying a hyperoxic gas challenge. We investigated flow sensitivity by comparing R2* measurements with and without flow suppression (fs) in 2 orthotopic lung xenograft tumor models.
Interim estimates of 2018/19 vaccine effectiveness against influenza A(H1N1)pdm09, Canada, January 2019

Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network assessed interim 2018/19 vaccine effectiveness (VE) against predominant influenza A(H1N1)pdm09 viruses. Adjusted VE was 72% (95% confidence interval: 60 to 81) against medically attended, laboratory-confirmed influenza A(H1N1)pdm09 illness. This substantial vaccine protection was observed in all age groups, notably young children who appeared to be disproportionately affected. Sequence analysis identified heterogeneity in emerging clade 6B.1 viruses but no dominant drift variant.
End-of-life Health-Care Utilization Patterns Among Chronically Ill Older Adults

Patients with chronic illness are associated with high health-care utilization and this is exacerbated in the end of life, when health-care utilization and costs are highest. Complex Care Management (CCM) is a model of care developed to reduce health-care utilization, while improving patient outcomes. We aimed to examine the relationship between health-care utilization patterns and patient characteristics over time in a sample of older adults enrolled in CCM over the last 2 years of life. Generalized estimating equation models were used. The sample (n = 126) was 52% female with an average age of 85 years. Health-care utilization rose sharply in the last 3 months of life with at least one hospitalization for 67% of participants and an emergency department visit for 23% of participants. In the last 6 months of life, there was an average of 2.17 care transitions per participant. The odds of hospitalization increased by 27% with each time interval (P < .001). Participants demonstrated 11% greater odds of having a hospitalization for each additional comorbidity (P = .05). A primary diagnosis of heart failure or coronary artery disease was associated with 21% greater odds of hospitalization over time compared to other primary diagnoses (P = .017). Females had 70% greater odds of an emergency department visit compared to males (P = .046). For each additional year of life, the odds of an emergency department visit increased by about 7% (P < .001). Findings suggest the need for further interventions targeting chronically ill older adults nearing end of life within CCM models.
Coalition building to create an Age-Friendly University (AFU)

ABSTRACT There is no single path to becoming an Age-Friendly University (AFU). This paper shares the story of one regional, public university that became the first in its state to join the AFU global network. We discuss how early efforts at coalition building both within and outside the university facilitated the campus-wide endorsement of the AFU principles. We highlight several partnerships and programs that reflect the AFU principles and discuss how becoming an AFU helped to further strengthen university ties and is now providing a valuable framework for continued collaboration and coalition building. We share lessons from our efforts, including the challenges and benefits of being the first AFU in our state as we forge a path forward. We conclude with our plans for ensuring the growth of age-friendly practices and policies at our university, and we hope that this paper will encourage you to do the same on your campus.
Cervical Cancer Treatment Delays and Associated Factors in a Cohort of Women From a Developing Country

PURPOSE To estimate treatment delays and associated factors among women diagnosed with cervical cancer who were treated at the main cancer center in Rio de Janeiro, Brazil. MATERIALS AND METHODS A retrospective cohort study was performed comprising 865 women newly diagnosed with cervical cancer between 2012 and 2014. Times from diagnosis to treatment initiation (less than or equal to 60 days) and from diagnosis to treatment ending (less than or equal to 120 days) were analyzed according to the Brazilian law for the treatment of patients with cancer. Associations between treatment delays and sociodemographic, economic, lifestyle, clinical, and treatment variables were estimated using logistic regression models, with 95% CIs. RESULTS The average age was 48 (± 13.7) years, and the median age was 47 years; 36.2% of patients had stage IIIB to IVA disease. The median time from diagnosis to treatment initiation was 114 days, which was statistically higher among women with stage IIB to IVA (105.5 days) compared with those with earlier stages (119 days). The delay in treatment initiation occurred in 92.8% of participants; the median time from diagnosis to treatment ending was 274 days, with a delay (more than 120 days) for 92.6% of patients. The median time interval from diagnosis to the first visit to the cancer center was 28 days, with a delay of more than 30 days for 46.6% of patients. Age (odds ratio [OR], 1.05; 95% CI,1.02 to 1.08), stage IIIB to IVA (OR, 0.38; 95% CI, 0.16 to 0.90), time to first visit to the cancer center (OR, 11.52; 95% CI, 4.32 to 30.66), chemoradiation treatment (OR, 4.56; 95% CI, 1.81 to 11.47), and adequate treatment (OR, 2.57; 95% CI, 1.26 to -5.40) were independently associated with delay of treatment initiation. CONCLUSION Significant delays in treatment initiation and ending were observed in this studied population. The treatment initiation delay was positively associated with age, time interval more than 30 days from diagnosis to first specialist assessment at the cancer center, treatment with chemoradiation, and adequate treatment.
Dietary Energy Levels Affect Growth Performance through Growth Hormone and Insulin-Like Growth Factor 1 in Yak (Bos grunniens)

Simple Summary Yak is always in a malnutrition condition under pure grazing in the cold season. Many studies have suggested that provision of supplementary feed to yak cannot only be an effective approach to avoid weight loss, but also improve productivity. Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) could improve yak productivity. In current work, we evaluated the effects of different energy feedstuffs on the serum concentration of GH, IGF-1, and relative hepatic expression of their associated binding proteins and receptors, as well as growth performance of yak. The results indicated that average daily gain (ADG), body weight (BW), feed conversion ratio, serum IGF-1 concentration, and relative expression of IGF-1 and IGFBP-3 were increased with an increase in dietary energy level, while serum GH concentration and hepatic growth hormone (GHR) expression were decreased. Serum IGF-1 concentration, relative hepatic expression of IGF-1, and insulin-like growth factor binding protein 3 (IGFBP-3) showed positive correlation with ADG, but serum GH concentration and GHR expression were negatively correlated with ADG. Yak offered with medium energy diet (NEg: 6.2 MJ/kg) displayed better growth by gaining 0.883 kg/d and showing a superior feed conversion ratio during experiment. Abstract The objective of this study was to investigate the effects of different dietary energy levels on serum concentrations of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), as well as gene expression of their associated binding proteins and receptors in yak. Fifteen adult male yaks with BW of 276.1 ± 3.5 kg were allotted in three dietary groups and were fed with low (LE), medium (ME), and high energy (HE) level diet having different NEg of 5.5 MJ/kg, 6.2 MJ/kg, 6.9 MJ/kg, respectively. The effects of these treatments on ADG, BW, ADFI, and feed conversion ratio were significant (p < 0.05) throughout the experimental period. Serum GH concentration decreased (p < 0.05) with an increase in dietary energy level on d 30 and d 60. While IGF-1 concentration was higher (p < 0.05) in ME group, as compared to LE and HE groups on d 60. The expression level of growth hormone receptor (GHR) was decreased (p < 0.001) and IGF-1 was increased with the increase in the dietary energy level. The relative expression of insulin-like growth factor binding protein 3 (IGFBP-3) was higher (p < 0.001) in ME and HE groups, except the LE group. In conclusion, our findings provide a first insight into the combined effect of GH and IGF-1 in controlling the metabolism and productivity of yak. It also showed that medium energy level diet contributed to promote growth performance of yak during the cold season.