Miracle-dz/UniFAR-FTUs huggingface dataset:
Telomerase Reverse Transcriptase and p53 Regulate Mammalian Peripheral Nervous System and CNS Axon Regeneration Downstream of c-Myc

Although several genes have been identified to promote axon regeneration in the CNS, our understanding of the molecular mechanisms by which mammalian axon regeneration is regulated is still limited and fragmented. Here by using female mouse sensory axon and optic nerve regeneration as model systems, we reveal an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. We also provide evidence that TERT and p53 act downstream of c-Myc to control sensory axon regeneration. More importantly, overexpression of p53 in sensory neurons and retinal ganglion cells is sufficient to promote sensory axon and optic never regeneration, respectively. The study reveals a novel c-Myc-TERT-p53 signaling pathway, expanding horizons for novel approaches promoting CNS axon regeneration. SIGNIFICANCE STATEMENT Despite significant progress during the past decade, our understanding of the molecular mechanisms by which mammalian CNS axon regeneration is regulated is still fragmented. By using sensory axon and optic nerve regeneration as model systems, the study revealed an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. The results also delineated a c-Myc-TERT-p53 pathway in controlling axon growth. Last, our results demonstrated that p53 alone was sufficient to promote sensory axon and optic nerve regeneration in vivo. Collectively, the study not only revealed a new mechanisms underlying mammalian axon regeneration, but also expanded the pool of potential targets that can be manipulated to enhance CNS axon regeneration.
Randomized Phase 0/I Trial of the Mitochondrial Inhibitor ME-344 or Placebo Added to Bevacizumab in Early HER2-Negative Breast Cancer

Purpose: We previously demonstrated that mitochondrial inhibitors' efficacy was restricted to a metabolic context in which mitochondrial respiration was the predominant energy source, a situation achievable by inducing vascular normalization/hypoxia correction with antiangiogenics. Vascular normalization can be tracked with 2[18F]fluoro-2-deoxy-d-glucose (FDG)-PET. We tested the efficacy of the mitochondrial inhibitor ME-344 or placebo added to bevacizumab in early breast cancer. Patients and Methods: Treatment-naïve HER2-negative patients with T > 1 cm (any N) underwent a breast-centered 18F-fluorodeoxyglucose (FDG)-PET (day 1) and received a single dose of bevacizumab (15 mg/kg), followed by a second FDG-PET (day 8). Patients were then randomized (1:1) to Arm A (ME-344 10 mg/kg intravenous on days 8, 15, and 21) or Arm B (placebo). Tumors were biopsied on days 0 and 29. Succinate dehydrogenase enzyme histochemistry (SDH-EHC), confocal microscopy of vessel architecture, and HIF1α staining were performed in pre- and posttreatment biopsies to assess the pharmacodynamics, vessel normalization, and tissue re-oxygenation by bevacizumab, respectively. Results: ME-344 displayed significant biological activity versus placebo: compared with a 186% increase in Arm B, Ki67 decreased by 23.4% from days 0 to 28 in Arm A (P < 0.001) (N = 42 patients). FDG-PET predicted vascular normalization in about one-third of the patients in each arm, which was confirmed using confocal microscopy and HIF1α staining. In the subgroup with vascular normalization, ME-344 induced a Ki67 decrease of 33.4% (placebo: 11.8 increase). SDH-EHC suggested on-target effects of ME-344. Conclusions: ME-344 has significant biological antitumor activity in HER2-negative breast cancer, particularly after induction of vascular normalization and tissue reoxygenation with bevacizumab.
A novel telehealth platform for alcohol use disorder treatment: preliminary evidence of reductions in drinking

ABSTRACT Background Alcohol use disorder (AUD) treatment remains greatly underutilized. Innovative strategies are needed to improve AUD treatment access and patient engagement. The Ria Treatment Platform (RTP) is a patient-centered telemedicine AUD treatment program accessed through a smartphone application (app) that includes a package of physician visits (with AUD prescriptions as appropriate), text- and phone-based support from a recovery coach, video monitoring of medication adherence, and Bluetooth-linked breathalyzer tracking of alcohol intake. Objectives The purpose of the current study is to examine changes in alcohol use among patients utilizing the RTP. Methods This study examines daily breathalyzer blood alcohol content (BAC) readings collected from 77 adult patients (50.7% male) over the first 90 days in treatment with the RTP. Data were analyzed using dynamic structural equation modeling. Results The treatment retention rate at 90 days was 55%. The best fit for the BAC data was given by a cubic curve, which showed that among patients who remained engaged for 90 days average BAC levels declined approximately 50% (from .091 to .045) from baseline to day 90. Conclusion This study provides preliminary evidence of substantial alcohol use reductions among patients utilizing the RTP, an innovative telemedicine program accessed via smartphone. Although other alcohol-reduction apps have shown promise from scientific evaluations, the RTP appears to be the only app that incorporates physician-prescribed medication and a recovery coach. Research incorporating random assignment and meaningful comparison groups is needed to further evaluate this promising strategy.
Highly Sensitive and Selective Colorimetric Detection of Creatinine Based on Synergistic Effect of PEG/Hg2+–AuNPs

A colorimetric sensor, based on the synergistic coordination effect on a gold nanoparticle (AuNP) platform has been developed for the determination of creatinine. The sensor selects citrate stabilized AuNPs as a platform, polyethylene glycol (PEG) as a decorator, and Hg2+ as a linkage to form a colorimetric probe system (PEG/Hg2−–AuNPs). By forming hydrogen bond between the oxygen-containing functional groups of PEG and citrate ions on the surface of AuNPs, this probe shows good stability. PEG coordinated with Hg2+ synergistically and specifically on the surface of dispersed AuNPs, and the existence of creatinine could induce the aggregation of AuNPs with a corresponding color change and an obvious absorption peak shift within 5 min. This PEG/Hg2+–AuNPs probe towards creatinine shows high sensitivity, and a good linear relationship (R2 = 0.9948) was obtained between A620–522 nm and creatinine concentration, which can achieve the quantitative calculations of creatinine. The limit of detection (LOD) of this PEG/Hg2+–AuNPs probe was estimated to be 9.68 nM, lower than that of many other reported methods. Importantly, the sensitive probe can be successfully applied in a urine simulating fluid sample and a bovine serum sample. The unique synergistic coordination sensing mechanism applied in the designation of this probe further improves its high selectivity and specificity for the detection of creatinine. Thus, the proposed probe may give new inspirations for colorimetric detection of creatinine and other biomolecules.
Promoting Community Awareness of Lung Cancer Screening Among Disparate Populations: Results of the cancer-Community Awareness Access Research and Education Project.

BACKGROUND Lung cancer is the no. 1 cause of cancer death in the United States. Racial/ethnic minority and medically underserved populations suffer higher mortality than whites. Early detection through uptake of low-dose computed tomography (LDCT) among screening-eligible adults may mitigate high mortality. However, nearly 5 years since the publication of the US Preventive Services Task Force lung cancer screening guideline, population awareness of LDCT is low, and only 4% of screening-eligible adults have undergone screening. OBJECTIVE This project used an education intervention to change participants' knowledge, attitudes, and beliefs about cancer risk factors and lung cancer and to connect eligible individuals to LDCT screening and tobacco cessation services. INTERVENTIONS/METHODS Community-engaged strategies were used to deliver a 4-week educational program in 13 community sites. Trained community health workers delivered the intervention. The intervention was guided by the Health Belief Model. Data were collected by survey to 481 participants; 93% were African American, the majority was female (73.1%), mean age was 58.3 (SD, 10.9) years. RESULTS There were knowledge increase regarding lung cancer screening (P = .001), a significant decrease in Perceived Severity and Perceived Barriers subscales (P = .001), and an overall increase in response to Perceived Benefits of lung cancer screening and Self-efficacy (P = .001). Fifty-four percent of tobacco users engaged in cessation; 38% of screening-eligible participants underwent LDCT screening. CONCLUSIONS Community health workers are effective in increasing awareness of lung cancer screening and affecting behavior change among disparate populations. IMPLICATIONS FOR PRACTICE Community health workers may have a clinical role in LDCT shared decision making.
Prediction of Motor Failure Time Using An Artificial Neural Network

Industry is constantly seeking ways to avoid corrective maintenance so as to reduce costs. Performing regular scheduled maintenance can help to mitigate this problem, but not necessarily in the most efficient way. In the context of condition-based maintenance, the main contributions of this work were to propose a methodology to treat and transform the collected data from a vibration system that simulated a motor and to build a dataset to train and test an Artificial Neural Network capable of predicting the future condition of the equipment, pointing out when a failure can happen. To achieve this goal, a device model was built to simulate typical motor vibrations, consisting of a computer cooler fan and several magnets. Measurements were made using an accelerometer, and the data were collected and processed to produce a structured dataset. The neural network training with this dataset converged quickly and stably, while the tests performed, k-fold cross-validation and model generalization, presented excellent performance. The same tests were performed with other machine learning techniques, to demonstrate the effectiveness of neural networks mainly in their generalizability. The results of the work confirm that it is possible to use neural networks to perform predictive tasks in relation to the conditions of industrial equipment. This is an important area of study that helps to support the growth of smart industries.
Molecular signatures of selection associated with host-plant differences in Pieris butterflies

Adaptive traits that enable organisms to conquer novel niches and experience subsequent diversification are ecologically and evolutionarily important. The larvae of Pieris butterflies express nitrile-specifier proteins (NSPs), a key innovation for overcoming the glucosinolate (GLS)-myrosinase-based defense system of their Brassicales host-plants. NSPs are a member of the NSP-like gene family, which includes the major allergen (MA) protein, a paralog of NSP with a GLS-disarming function, and a single domain major allergen (SDMA) protein, whose function is unknown. The arms-race between a highly variable host-plant defense system and members of the NSP-like gene family is suggested to mediate diversification in both Pierid butterflies and Brassicales plants. Here, we combined feeding experiments using 25 Brassicaceae plants and five Pieris species with larval transcriptome data to investigate the evolutionary forces acting on NSP-like gene family members associated with patterns of host-plant usage. Although we observed significantly elevated nonsynonymous to synonymous substitution ratios in NSPs, no such pattern was observed in MAs or SDMAs. Furthermore, we found a signature of positive selection of NSP at a phylogenetic branch which reflects different host-plant preferences. Our data indicate that NSPs have evolved in response to shifting preferences for host plants among five Pieris butterflies, whereas MAs and SDMAs appear to have more conserved functions. Our results show that the evolution and functional differentiation of key genes used in host-plant adaptation play a crucial role in the chemical arms-race between Pieris butterflies and their Brassicales host-plants.
Factors Predicting Voluntary and Involuntary Workforce Transitions at Mature Ages: Evidence from HILDA in Australia

The fast population ageing has generated and will continue to generate large social, economic and health challenges in the 21th century in Australia, and many other developed and developing countries. Population ageing is projected to lead to workforce shortages, welfare dependency, fiscal unsustainability, and a higher burden of chronic diseases on health care system. Promoting health and sustainable work capacity among mature age and older workers hence becomes the most important and critical way to address all these challenges. This paper used the pooled data from the longitudinal Household, Incomes and Labour Dynamics in Australia (HILDA) survey 2002–2011 data to investigate common and different factors predicting voluntary or involuntary workforce transitions among workers aged 45 to 64. Long term health conditions and preference to work less hours increased while having a working partner and proportion of paid years decreased both voluntary and involuntary work force transitions. Besides these four common factors, the voluntary and involuntary workforce transitions had very different underlying mechanisms. Our findings suggest that government policies aimed at promoting workforce participation at later life should be directed specifically to life-long health promotion and continuous employment as well as different factors driving voluntary and involuntary workforce transitions, such as life-long training, healthy lifestyles, work flexibility, ageing friendly workplace, and job security.
Opportunities to reduce antibiotic prescribing for patients with COPD in primary care: a cohort study using electronic health records from the Clinical Practice Research Datalink (CPRD)

Abstract Background In primary care there is uncertainty about which patients with acute exacerbations of COPD (AECOPD) benefit from antibiotics. Objectives To identify which types of COPD patients get the most antibiotics in primary care to support targeted antibiotic stewardship. Methods Observational study of COPD patients using a large English primary care database with 12 month follow-up. We estimated the incidence of and risk factors for antibiotic prescribing relative to the number of AECOPD during follow-up, considering COPD severity, smoking, obesity and comorbidity. Results From 157 practices, 19594 patients were diagnosed with COPD, representing 2.6% of patients and 11.5% of all prescribed antibiotics. Eight hundred and thirty-three (4.5%) patients with severe COPD and frequent AECOPD were prescribed six to nine prescriptions per year and accounted for 13.0% of antibiotics. Individuals with mild to moderate COPD and zero or one AECOPD received one to three prescriptions per year but accounted for 42.5% of all prescriptions. In addition to COPD severity, asthma, chronic heart disease, diabetes, heart failure and influenza vaccination were independently associated with increased antibiotic use. Conclusions Patients with severe COPD have the highest rates of antibiotic prescribing but most antibiotics are prescribed for patients with mild to moderate COPD. Antibiotic stewardship should focus on the dual goals of safely reducing the volume of prescribing in patients with mild to moderate COPD, and optimizing prescribing in patients with severe disease who are at significant risk of drug resistance.
Autologous haematopoietic stem cell therapy for multiple sclerosis: a review for supportive care clinicians on behalf of the Autoimmune Diseases Working Party of the European Society for Blood and Marrow Transplantation

Purpose of review In this review, we summarize the recently published literature that demonstrates the efficacy and safety of autologous haematopoietic stem cell therapy (AHSCT) in multiple sclerosis (MS) and highlight the importance of supportive care required for the safe and well-tolerated delivery of AHSCT. Recent findings MS is an autoimmune inflammatory and degenerative disorder of the central nervous system (CNS). In the majority of patients, the illness runs a relapsing remitting course (RRMS), culminating in a secondary progressive phase with gradual accumulation of fixed disabilities. Currently available disease-modifying therapies suppress CNS inflammation but have a limited effect on preventing disease progression for which there remains no effective therapy. Over the last two decades, there has been increasing evidence that AHSCT is a highly effective therapeutic strategy for treatment-resistant inflammatory types of MS, especially RRMS. Concerns about the safety of AHSCT in MS, usually a nonlife-threatening disease, have previously limited its use. However, AHSCT can now be delivered safely with major long-term benefits because of increasing transplant centre experience, judicious patient selection and good supportive care. Summary MS is currently the fastest growing indication for AHSCT in Europe. Supportive care before, during and after the transplant period is key to the successful delivery of AHSCT.
Perioperative Risks of Sleeve Gastrectomy Versus Roux-en-Y Gastric Bypass Among Patients With Chronic Kidney Disease

Objective: To determine whether patients with CKD experience higher rates of perioperative complications after RYGB compared to sleeve gastrectomy. Summary of Background Data: For obese CKD patients who qualify for bariatric surgery, sleeve gastrectomy is often preferred to RYGB based on perceptions of prohibitively-high perioperative risks surrounding RYGB. However, some patients with CKD are not candidates for sleeve gastrectomy and the incremental increased-risk from RYGB has never been rigorously tested in this population. Methods: CKD patients who underwent RYGB or sleeve gastrectomy between 2015 and 2017 were identified from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program Participant Use File. RYGB patients were 1:1 propensity-score matched with sleeve gastrectomy patients based on preoperative factors that influence operative choice. Primary outcomes included 30-day readmissions, surgical complications, medical complications, and death. Secondary outcomes included the individual complications used to create the composite surgical/medical complications. Univariate logistic regression was used to compare outcomes. E-value statistic was used to test the strength of outcome point estimates against possible unmeasured confounding. Results: Demographics were similar between RYGB (n = 673) and sleeve gastrectomy (n = 673) cohorts. There were no statistically significant differences in primary outcomes. Among secondary outcomes, only acute kidney injury was statistically-significantly higher among RYGB patients (4.9% vs 2.7%, P = 0.035, E-value 1.27). Conclusions: Among well-matched cohorts of RYGB and sleeve gastrectomy patients, incidence of primary outcomes were similar. Among secondary outcomes, only acute kidney injury was statistically-significantly higher among RYGB patients; however, the E-value for this difference was small and relatively weak confounder(s) could abrogate the statistical difference. The perception that RYGB has prohibitively-high perioperative risks among CKD patients is disputable and operative selection should be weighed on patient candidacy and anticipated long-term benefit.
Cost‐effectiveness of e‐cigarettes compared with nicotine replacement therapy in stop smoking services in England (TEC study): a randomized controlled trial

Abstract Aim To evaluate the cost‐effectiveness of e‐cigarettes as a smoking cessation aid used in routine stop smoking services in England. Design Cost‐effectiveness analysis was performed from the National Health Service (NHS) and Personal Social Services (PSS) perspective for 12‐month periods and life‐time. Costs, including that of both treatments, other smoking cessation help and health‐care services, and health benefits, estimated from EQ‐5D‐5L and measured in quality‐adjusted life‐years (QALYs), for the 12‐month analysis, came from a randomized controlled trial. Life‐time analysis was model‐based with input from both trial data and published secondary data sources. Cost‐effectiveness was measured by an incremental cost‐effectiveness ratio (ICER). Setting Three stop‐smoking service sites in England. Participants Adult smokers (n = 886) who sought help to quit in the participating sites. Intervention and comparator An e‐cigarette (EC) starter kit versus provision of nicotine replacement therapy (NRT) for up to 3 months, both with standard behavioural support. A total of 886 participants were randomized (439 in the EC arm, 447 in the NRT arm). Excluding one death in each arm, the 1‐year quit rate was 18.0 and 9.9%, respectively. Measurements Cost of treatments was estimated from the treatment log. Costs of other smoking cessation help and health‐care services and EQ‐5D‐5 L were collected at baseline, 6‐ and 12‐month follow‐ups. Incremental costs and incremental QALYs were estimated using regression adjusting for baseline covariates and their respective baseline values. Findings The ICER was £1100 per QALY gained at the 12 months after quit date (87% probability below £20 000/QALY). Markov model estimated the life‐time ICER of EC to be £65 per QALY (85% probability below £20 000/QALY). Conclusion Using e‐cigarettes as a smoking cessation aid with standard behavioural support in stop‐smoking services in England is likely to be more cost‐effective than using nicotine replacement therapy in the same setting.
Stem Cell Surgery and Growth Factors in Retinitis Pigmentosa Patients: Pilot Study after Literature Review

To evaluate whether grafting of autologous mesenchymal cells, adipose-derived stem cells, and platelet-rich plasma into the supracoroideal space by surgical treatment with the Limoli retinal restoration technique (LRRT) can exert a beneficial effect in retinitis pigmentosa (RP) patients. Twenty-one eyes underwent surgery and were divided based on retinal foveal thickness (FT) ≤ 190 or > 190 µm into group A-FT and group B-FT, respectively. The specific LRRT triad was grafted in a deep scleral pocket above the choroid of each eye. At 6-month follow-up, group B showed a non-significant improvement in residual close-up visus and sensitivity at microperimetry compared to group A. After an in-depth review of molecular biology studies concerning degenerative phenomena underlying the etiopathogenesis of retinitis pigmentosa (RP), it was concluded that further research is needed on tapeto-retinal degenerations, both from a clinical and molecular point of view, to obtain better functional results. In particular, it is necessary to increase the number of patients, extend observation timeframes, and treat subjects in the presence of still trophic retinal tissue to allow adequate biochemical and functional catering.