Miracle-dz/UniFAR-FTUs huggingface dataset:
Translocation of Zymomonas mobilis pyruvate decarboxylase to periplasmic compartment for production of acetaldehyde outside the cytosol

Acetaldehyde, a valuable commodity chemical, is a volatile inhibitory byproduct of aerobic fermentation in Zymomonas mobilis and in several other microorganisms. Attempting to improve acetaldehyde production by minimizing its contact with the cell interior and facilitating its removal from the culture, we engineered a Z. mobilis strain with acetaldehyde synthesis reaction localized in periplasm. For that, the pyruvate decarboxylase (PDC) was transferred from the cell interior to the periplasmic compartment. This was achieved by the construction of a Z. mobilis Zm6 PDC‐deficient mutant, fusion of PDC with the periplasmic signal sequence of Z. mobilis gluconolactonase, and the following expression of this fusion protein in the PDC‐deficient mutant. The obtained recombinant strain PeriAc, with most of its PDC localized in periplasm, showed a twofold higher acetaldehyde yield, than the parent strain, and will be used for further improvement by directed evolution.
Clinical Predictors of Diabetic Retinopathy Progression; A Systematic Review.

OBJECTIVE The study aims to review the published clinical predictors of Diabetic Retinopathy Progression and discuss their level of clinical significance. METHODS The data for systematic review has been gathered from the studies that were searched through scholarly platforms and several libraries. These studies discussed the clinical predictors of Diabetic Retinopathy (DR) progression. The common keywords included in the review were diabetic retinopathy, anemia, systolic blood pressure, dyslipidemia, genetics and risk factors. RESULTS Diabetic Retinopathy is associated with visual impairments and blindness, which significantly affects the patients' quality of life. The factors leading to progression of diabetic retinopathy include hypertension, poor glycemic condition, duration of diabetes, dyslipidemia, and microalbuminuria are known as the major risk factors for the development of diabetic retinopathy. Considering the development of diabetic peripheral neuropathy, the increased aortic stiffness is considered as a significant prognostic marker. CONCLUSION Certain clinical predictors are of valuable importance to predict those diabetics whom are at higher risk to develop diabetic retinopathy and could help clinicians and public health planners to develop a risk-based screening strategy for such prevalent condition.
Cardiology patient page: device interventions for stroke prevention in atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained heart rhythm disorder, with an estimated prevalence of 0.4% to 1% in the general population. In addition, AF is responsible for approximately 15% to 20% of ischemic strokes. Device interventions to prevent strokes in patients with AF are nonsurgical procedures to block blood clots (thrombus) from forming and traveling out of the heart. The “quivering” rather than normal contractions of the upper chambers of the heart (atria) from disorganized electric activity (AF) leads to blood stasis and thrombus formation. A small cul-de-sac called the left atrial appendage (LAA) is especially prone to thrombus formation (Figure 1). In AF patients without valvular heart disease, almost all thrombus originates from the LAA. The thrombus travels to and block major vessels in the body. Blocking blood vessels to the brain leads to strokes and transient ischemic attacks (mini-strokes). Figure 1. Transesophageal echocardiogram image of a thrombus in the left atrial appendage (dotted line). Patients with the following risk factors have a higher stroke risk: heart failure, hypertension, age of 75 years or greater, diabetes mellitus, and prior history of strokes or mini-strokes. These are often combined to form the CHADS2 score. The more risk factors you have, the higher your CHADS2 score and risk of stroke are. Blood-thinning medications (anticoagulants) such as warfarin, dabigatran, rivaroxaban, and apixaban are effective stroke prevention therapies. The risks of bleeding associated with long-term anticoagulation led to the development of permanent treatment options like surgery. Closures by sutures (ligation) and removal (amputation) of the LAA …
Feasibility of reduced-dose CT of the head and neck with iterative reconstruction: a phantom and prospective clinical study

Background There is growing concern over computed tomography (CT)-related radiation exposure, particularly in patients requiring head and neck CT due to the proximity of radiosensitive organs. Purpose We aimed to evaluate the feasibility of reduced-dose CT of the head and neck with iterative reconstruction in a phantom and patient study. Material and Methods In the phantom study, low-contrast resolution test of the American Association of Physicists in Medicine CT performance phantom was scanned to determine the lowest acceptable tube current (mAs). In the patient study, three sets of CT images (standard-dose [200 mAs] and reduced-dose with iterative reconstruction or filtered back projection [FBP]) were prospectively obtained. The image noise, qualitative image quality, and radiation dose were compared. Results In the phantom study, 100 mAs was determined as the lowest acceptable value. In the patient study (n = 29), reduced-dose CT with FBP showed significantly higher image noise and lower qualitative image quality than reduced-dose CT with iterative reconstruction and standard-dose CT (P < 0.05). There was no significant difference in image noise and qualitative image quality between reduced-dose CT with iterative reconstruction and standard-dose CT (P > 0.05). The radiation dose of the reduced-dose CT was significantly lower than that of the standard-dose CT (volume CT dose index = 6.9 vs. 14.3, P < 0.001; dose-length product = 223.6 vs. 455.8, P < 0.001). Conclusions Reduced-dose CT with iterative reconstruction is a potential alternative to standard-dose CT of the head and neck, reducing radiation dose by approximately 50% while preserving image quality.
MicroRNA‐876‐5p inhibits cell proliferation, migration and invasion by targeting c‐Met in osteosarcoma

Recently, aberrant expression of miR‐876‐5p has been reported to participate in the progression of several human cancers. However, the expression and function of miR‐876‐5p in osteosarcoma (OS) are still unknown. Here, we found that the expression of miR‐876‐5p was significantly down‐regulated in OS tissues compared to para‐cancerous tissues. Clinical association analysis indicated that underexpression of miR‐876‐5p was positively correlated with advanced clinical stage and poor differentiation. More importantly, OS patients with low miR‐876‐5p level had a significant shorter overall survival compared to miR‐876‐5p high‐expressing patients. In addition, gain‐ and loss‐of‐function experiments demonstrated that miR‐876‐5p restoration suppressed whereas miR‐876‐5p knockdown promoted cell proliferation, migration and invasion in both U2OS and MG63 cells. In vivo studies revealed that miR‐876‐5p overexpression inhibited tumour growth of OS in mice. Mechanistically, miR‐876‐5p reduced c‐Met abundance in OS cells and inversely correlated c‐Met expression in OS tissues. Herein, c‐Met was recognized as a direct target of miR‐876‐5p using luciferase reporter assay. Notably, c‐Met restoration rescued miR‐876‐5p attenuated the proliferation, migration and invasion of OS cells. In conclusion, these findings indicate that miR‐876‐5p may be used as a potential therapeutic target and promising biomarker for the diagnosis and prognosis of OS.
Taste, olfactory and texture related genes and food choices: implications on health status.

OBJECTIVE The food choices are due to a mixture of sensory signals including gustatory, olfactory, and texture sensations. The aim of this quality review was to update data about studies concerning genetics of taste, olfactory and texture receptors and their influence on the health status in humans. MATERIALS AND METHODS An electronic search was conducted in MEDLINE, Pubmed database and Scopus, for articles published in English until December 2018. Two independent researches selected the studies and extracted the data. RESULTS The review confirms the importance of inter-individual variations in taste, olfactory and texture related genes on food choices and their implications in the susceptibility to nutrition-related conditions such as obesity, dental caries, diabetes, cardiovascular disease, hypertension, hyperlipidemia and cancer. CONCLUSIONS The knowledge of variants in taste, olfactory and texture related genes can contribute to the prevention of diseases related to unhealthy nutrition. Further studies would be useful to identify other variants in the genes involved in these systems.
Impact of a Novel Smartphone App (CureApp Smoking Cessation) on Nicotine Dependence: Prospective Single-Arm Interventional Pilot Study

Background Mobile apps have been considered to provide active and continuous support for smoking cessation. However, it is yet to be known whether a smoking cessation smartphone app improves long-term abstinence rates in nicotine-dependent patients. Objective This study aimed to evaluate the long-term abstinence effect of a novel smartphone app, CureApp Smoking Cessation (CASC), in patients with nicotine dependence. Methods In this prospective, interventional, multicenter, single-arm study, we provided the CASC app to all the participants, who used it daily for 24 weeks. The CASC app includes features to maximize the therapeutic effect of pharmacological therapies and counseling at outpatient clinics for smoking cessation. The primary endpoint was a continuous abstinence rate (CAR) from weeks 9 to 24, whereas secondary endpoints were CARs from weeks 9 to 12 and 9 to 52. Results Of the 56 adult smokers recruited, 1 did not download the app; therefore, 55 participants constituted the full analysis sample. The CAR from weeks 9 to 24 was 64% (35/55, 95% CI 51%-76%), whereas the CARs from weeks 9 to 12 and 9 to 52 were 76% (42/55, 95% CI 65%-88%) and 58% (32/55, 95% CI 46%-71%), respectively. These CARs were better than the results of the national survey on outpatient clinics with regard to smoking cessation under the National Health Insurance Program and that of the varenicline phase 3 trial in Japan and the United States. There was only 1 participant who dropped out during the 12 weeks of the treatment period. This treatment decreased the scores related to withdrawal and craving symptoms. Conclusions The addition of CASC to usual smoking cessation therapies resulted in high CARs, high patient retention rates, and improvement of cessation-related symptoms. The smartphone app CASC is a feasible and useful tool to help long-term continuous abstinence that can be combined with a standard smoking cessation treatment program.
Effects of Housing First approaches on health and well-being of adults who are homeless or at risk of homelessness: systematic review and meta-analysis of randomised controlled trials

Background Homelessness is associated with poor health. A policy approach aiming to end homelessness across Europe and North America, the ‘Housing First’ (HF) model, provides rapid housing, not conditional on abstinence from substance use. We aimed to systematically review the evidence from randomised controlled trials for the effects of HF on health and well-being. Methods We searched seven databases for randomised controlled trials of interventions providing rapid access to non-abstinence-contingent, permanent housing. We extracted data on the following outcomes: mental health; self-reported health and quality of life; substance use; non-routine use of healthcare services; housing stability. We assessed risk of bias and calculated standardised effect sizes. Results We included four studies, all with ‘high’ risk of bias. The impact of HF on most short-term health outcomes was imprecisely estimated, with varying effect directions. No clear difference in substance use was seen. Intervention groups experienced fewer emergency department visits (incidence rate ratio (IRR)=0.63; 95% CI 0.48 to 0.82), fewer hospitalisations (IRR=0.76; 95% CI 0.70 to 0.83) and less time spent hospitalised (standardised mean difference (SMD)=−0.14; 95% CI −0.41 to 0.14) than control groups. In all studies intervention participants spent more days housed (SMD=1.24; 95% CI 0.86 to 1.62) and were more likely to be housed at 18–24 months (risk ratio=2.46; 95% CI 1.58 to 3.84). Conclusion HF approaches successfully improve housing stability and may improve some aspects of health. Implementation of HF would likely reduce homelessness and non-routine health service use without an increase in problematic substance use. Impacts on long-term health outcomes require further investigation. Trial registration number CRD42017064457
In vitro injection of osteoporotic cadaveric femurs with a triphasic calcium‐based implant confers immediate biomechanical integrity

Current pharmaceutical therapies can reduce hip fractures by up to 50%, but compliance to treatment is low and therapies take up to 18 months to reduce risk. Thus, alternative or complementary approaches to reduce the risk of hip fracture are needed. The AGN1 local osteo‐enhancement procedure (LOEP) is one such alternative approach, as it is designed to locally replace bone lost due to osteoporosis and provide immediate biomechanical benefit. This in vitro study evaluated the initial biomechanical impact of this treatment on human cadaveric femurs. We obtained 45 pairs of cadaveric femurs from women aged 77.8 ± 8.8 years. One femur of each pair was treated, while the contralateral femur served as an untreated control. Treatment included debridement, irrigation/suction, and injection of a triphasic calcium‐based implant (AGN1). Mechanical testing of the femora was performed in a sideways fall configuration 24 h after treatment. Of the 45 pairs, 4 had normal, 16 osteopenic, and 25 osteoporotic BMD T‐scores. Altogether, treatment increased failure load on average by 20.5% (p < 0.0001). In the subset of osteoporotic femurs, treatment increased failure load by 26% and work to failure by 45% (p < 0.01 for both). Treatment did not significantly affect stiffness in any group. These findings provide evidence that local delivery of the triphasic calcium‐based implant in the proximal femur is technically feasible and provides immediate biomechanical benefit. Our results provide strong rationale for additional studies investigating the utility of this approach for reducing the risk of hip fracture. © 2019 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society.
Hypertension and lifestyle modification: how useful are the guidelines?

Hypertension is a significant risk factor for coronary artery disease and stroke, a leading cause of death and disability worldwide, and a major risk for dementia, chronic kidney disease, coronary heart disease, and heart failure. The prevalence of hypertension-related events is increasing, with the majority occurring among pre-hypertensives (120–139 mmHg systolic; 80–89 mmHg diastolic) and stage-1 hypertensives (140–159 mmHg systolic; 90–99 mmHg diastolic). In the UK it was estimated that there are 62 000 needless deaths per year due to uncontrolled blood pressure,1 with the condition presenting a particular problem among Asian immigrant communities. There has been some discussion in this Journal of the helpfulness of guidelines for a number of conditions. One editorial has highlighted the possible mismatch between guidelines and internationally-agreed quality criteria, the lack of a concise set of concrete recommendations, and a risk of bias in that, notwithstanding the availability of scientific evidence, the guidelines may in fact largely reflect local culture or personal viewpoints.2 It is with this in mind that we intend to examine the guidelines for control of hypertension with respect to diet/behavioural modification. The hypertension clinical guideline from the National Institute for Health and Clinical Excellence (NICE) usefully recommends regular aerobic exercise and reduction of salt, alcohol, and smoking, and advocates ‘healthy, low-calorie diets' for ‘overweight individuals with raised blood pressure’, but gives a rather negative comment about its ‘modest effect’ …
Effect of rapid influenza diagnostic tests on patient management in an emergency department

Objective We evaluated the effect of rapid influenza diagnostic tests (RIDTs) on patient management in an emergency department for 3 years after 2009, and also identified factors associated with the choice of treatment for patients with influenza-like illnesses. Methods The study period consisted of three influenza epidemic seasons. Patients older than 15 years who underwent RIDTs in the emergency department and were then discharged without admission were included. Results A total of 453 patients were enrolled, 114 of whom had positive RIDT results and 339 had negative results. Antiviral medication was prescribed to 103 patients (90.4%) who had positive RIDT results, while 1 patient (0.3%) who tested negative was treated with antivirals (P<0.001). Conservative care was administered to 11 RIDT-positive patients (9.6%) and 244 RIDT-negative patients (72.0%) (P<0.001). Symptom onset in less than 48 hours, being older than 65 years, and the presence of comorbidities were not associated with the administration of antiviral therapy. Conclusion RIDT results had a critical effect on physician decision-making regarding antiviral treatment for patients with influenza-like illnesses in the emergency department. However, symptom onset in less than 48 hours, old age, and comorbidities, which are all indications for antiviral therapy, were not found to influence the administration of antiviral treatment.
The Prognostic Significance of Puncture Timing to Survival of Arteriovenous Fistulas in Hemodialysis Patients: A Multicenter Retrospective Cohort Study

(1) Background: A functional shunt is critical to hemodialysis, but the ideal timing of shunt cannulation is still not established. In this study, we assessed the association between ideal puncture timing and shunt survival. (2) Methods: This retrospective cohort study using data from the Taiwan Health and Welfare database, which included 26885 hemodialysis patients with arteriovenous fistulas from 1 July 2008 to 30 June 2012. Fistulas were categorized by functional maturation time, defined as the time from the date of shunt construction to the first successful cannulation. Functional cumulative survival, measured as the duration from the first puncture to shunt abandonment, was mainly regarded. (3) Results: The fistulas created between 91 and 180 days prior to the first cannulation had significantly greater cumulative functional survival (HR 0.883; 95% CI 0.792–0.984), and there was no more benefit on their survival from waiting more than 180 days (HR 0.957; 95% CI 0.853–1.073) for shunt maturity. (4) Conclusions: Our results showed that to achieve better long-term shunt survivals, fistulas should be constructed at least 90 days before starting hemodialysis. Notably, there was no additional benefit on waiting more than 180 days prior to cannulation.
Genistein protects intervertebral discs from degeneration via Nrf2‐mediated antioxidant defense system: An in vitro and in vivo study

Oxidative stress has been reported to be closely associated with the development of intervertebral disc degeneration (IDD). IDD is one of the major causes of low back pain. Genistein (GES), one of the main isoflavones of soybean, has been shown to exert multiple biological functions on different diseases. Here, we tested the therapeutic potential of GES for IDD. In vitro experiments, we confirmed GES was nontoxic to rat nucleus pulposus cells (NPCs) within the concentration of 100 μM. Furthermore, GES was able to suppress apoptosis in tert‐butyl hydroperoxide (TBHP)‐treated NPCs. In the aspect of extracellular matrix (ECM), GES not only reduced metalloproteinase‐13 (MMP‐13) and a disintegrin‐like and MMP thrombospondin type 1 motif 5 expression, but also increased aggrecan and type II collagen levels. Also, we found GES might rescue TBHP‐induced NPCs degeneration by enhancing Nrf2‐mediated antioxidant defense system. Silencing Nrf2 partly abolished the protective effects of GES on apoptosis and ECM disruption in TBHP‐treated NPCs. Correspondingly, GES ameliorated IDD in a rat model by preserving morphology of degenerative intervertebral discs and promoting Nrf2 expression. To sum up, our study suggests that GES exerts protective effects in NPCs against degeneration and reveals the underlying mechanism of GES on Nrf2 activation in NPCs.
Origin, Behaviour, and Transmission of B Chromosome with Special Reference to Plantago lagopus

B chromosomes have been reported in many eukaryotic organisms. These chromosomes occur in addition to the standard complement of a species. Bs do not pair with any of the A chromosomes and they have generally been considered to be non-essential and genetically inert. However, due to tremendous advancements in the technologies, the molecular composition of B chromosomes has been determined. The sequencing data has revealed that B chromosomes have originated from A chromosomes and they are rich in repetitive elements. In our laboratory, a novel B chromosome was discovered in Plantago lagopus. Using molecular cytogenetic techniques, the B chromosome was found to be composed of ribosomal DNA sequences. However, further characterization of the chromosome using next generation sequencing (NGS) etc. revealed that the B chromosome is a mosaic of sequences derived from A chromosomes, 5S ribosomal DNA (rDNA), 45S rDNA, and various types of repetitive elements. The transmission of B chromosome through the female sex track did not follow the Mendelian principles. The chromosome was found to have drive due to which it was perpetuating in populations. The present paper attempts to summarize the information on nature, transmission, and origin of B chromosomes, particularly the current status of our knowledge in P. lagopus.
Increased mitochondrial DNA4977-bp deletion in catheterization laboratory workers with long-term low-dose exposure to ionizing radiation

Aims Ionizing radiation may lead to mitochondrial DNA (mtDNA) mutations and changes in mtDNA content in cells, major driving mechanisms for carcinogenesis, vascular aging and neurodegeneration. The aim of this study was to investigate the possible induction of common mitochondrial deletion (mtDNA4977) and mtDNA copy number (mtDNA-CN) changes in peripheral blood of personnel working in high-volume cardiac catheterization laboratories (Cath Labs). Methods A group of 147 Cath Lab workers (median individual effective dose = 16.8 mSv, for the 41 with lifetime dosimetric record) and 74 unexposed individuals were evaluated. The occupational radiological risk score was computed for each subject on the basis of the length of employment, individual caseload and proximity to the radiation source. mtDNA4977 deletion and mtDNA-CN were assessed by using quantitative real-time polymerase chain reaction. Results Increased levels of mtDNA4977 deletion were observed in high-exposure Cath Lab workers compared with unexposed individuals (p < 0.0001). Conversely, mtDNA-CN was significantly greater in the low-exposure workers (p = 0.003). Occupational radiological risk score was positively correlated with mtDNA4977 deletion (Spearman's r = 0.172, p = 0.03) and inversely correlated with mtDNA-CN (Spearman's r = –0.202, p = 0.01). In multiple regression model, occupational radiological risk score emerged as significant predictor of high levels of mtDNA4977 deletion (ß coefficient = 0.236, p = 0.04). Conclusion mtDNA4977 deletion is significantly high in Cath Lab personnel. Beyond the well-recognized nuclear DNA, mtDNA damage might deserve attention as a pathogenetic molecular pathway and a potential therapeutic target of ionizing radiation damage.