Miracle-dz/UniFAR-FTUs huggingface dataset:
Translesion DNA Synthesis Across Lesions Induced by Oxidative Products of Pyrimidines: An Insight into the Mechanism by Microscale Thermophoresis

Oxidative stress in cells can lead to the accumulation of reactive oxygen species and oxidation of DNA precursors. Oxidized nucleotides such as 2’-deoxyribo-5-hydroxyuridin (HdU) and 2’-deoxyribo-5-hydroxymethyluridin (HMdU) can be inserted into DNA during replication and repair. HdU and HMdU have attracted particular interest because they have different effects on damaged-DNA processing enzymes that control the downstream effects of the lesions. Herein, we studied the chemically simulated translesion DNA synthesis (TLS) across the lesions formed by HdU or HMdU using microscale thermophoresis (MST). The thermodynamic changes associated with replication across HdU or HMdU show that the HdU paired with the mismatched deoxyribonucleoside triphosphates disturbs DNA duplexes considerably less than thymidine (dT) or HMdU. Moreover, we also demonstrate that TLS by DNA polymerases across the lesion derived from HdU was markedly less extensive and potentially more mutagenic than that across the lesion formed by HMdU. Thus, DNA polymerization by DNA polymerase η (polη), the exonuclease-deficient Klenow fragment of DNA polymerase I (KF–), and reverse transcriptase from human immunodeficiency virus type 1 (HIV-1 RT) across these pyrimidine lesions correlated with the different stabilization effects of the HdU and HMdU in DNA duplexes revealed by MST. The equilibrium thermodynamic data obtained by MST can explain the influence of the thermodynamic alterations on the ability of DNA polymerases to bypass lesions induced by oxidative products of pyrimidines. The results also highlighted the usefulness of MST in evaluating the impact of oxidative products of pyrimidines on the processing of these lesions by damaged DNA processing enzymes.
EFFECTS OF A WILD GREEN OAT EXTRACT ON MENTAL PERFORMANCE: A HUMAN CLINICAL STUDY USING SOURCE DENSITY ANALYSIS OF THE HUMAN EEG

Preparations from green oat have traditionally been used to support mental health and cognitive function [1, 2]. The patented wild green oat extract NeuravenaÂ® has been shown to support learning, increase alertness, have stress coping and stimulating abilities and to influence brain activity in-vivo [3,4]. Underlying study is a randomized, double-blind, placebo-controlled cross-over clinical trial to confirm NeuravenaÂ®’s effects on mental fitness and performance under pressured situations, using source density analysis of the EEG [5] in human volunteers. Twenty healthy men and women ingested one single dose of 2500 mg NeuravenaÂ®, or placebo, at start of the trial. Brain activity signals were recorded during 4 hours under relaxed and pressured conditions, using a standardized set of electrodes. NeuravenaÂ® was found to change the basic brain activity through a significant decrease of frontal and temporal delta and theta waves as well as an increase in alpha2 wave activity. Changes in evoked short term brain activity during the performance of the concentration stress test showed that NeuravenaÂ® significantly increases delta and theta wave activity in the brain regions closely connected to mental performance. The abovementioned changes confirm the positive effects of NeuravenaÂ® on cognitive function and are in line with the extract mediating stimulating properties. The intake of NeuravenaÂ® helps increase overall mental fitness in an individual’s daily life. Moreover, it has been shown to help improve cognitive function (concentration, learning, alertness) under pressure.
Activity patterns related to depression symptoms in stressed dementia caregivers.

OBJECTIVES Self-reported activity restriction is an established correlate of depression in dementia caregivers (dCGs). It is plausible that the daily distribution of objectively measured activity is also altered in dCGs with depression symptoms; if so, such activity characteristics could provide a passively measurable marker of depression or specific times to target preventive interventions. We therefore investigated how levels of activity throughout the day differed in dCGs with and without depression symptoms, then tested whether any such differences predicted changes in symptoms 6 months later. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS We examined 56 dCGs (mean age = 71, standard deviation (SD) = 6.7; 68% female) and used clustering to identify subgroups which had distinct depression symptom levels, leveraging baseline Center for Epidemiologic Studies of Depression Scale-Revised Edition and Patient Health Questionnaire-9 (PHQ-9) measures, as well as a PHQ-9 score from 6 months later. Using wrist activity (mean recording length = 12.9 days, minimum = 6 days), we calculated average hourly activity levels and then assessed when activity levels relate to depression symptoms and changes in symptoms 6 months later. RESULTS Clustering identified subgroups characterized by: (1) no/minimal symptoms (36%) and (2) depression symptoms (64%). After multiple comparison correction, the group of dCGs with depression symptoms was less active from 8 to 10 AM (Cohen's d ≤ -0.9). These morning activity levels predicted the degree of symptom change on the PHQ-9 6 months later (per SD unit β = -0.8, 95% confidence interval: -1.6, -0.1, p = 0.03) independent of self-reported activity restriction and other key factors. CONCLUSIONS These novel findings suggest that morning activity may protect dCGs from depression symptoms. Future studies should test whether helping dCGs get active in the morning influences the other features of depression in this population (i.e. insomnia, intrusive thoughts, and perceived activity restriction).
Docetaxel/cabazitaxel and fatty acid binding protein 5 inhibitors produce synergistic inhibition of prostate cancer growth

Prostate cancer (PCa) remains the second leading cause of cancer‐related death among men. Taxanes, such as docetaxel and cabazitaxel are utilized in standard treatment regimens for chemotherapy naïve castration‐resistant PCa. However, tumors often develop resistance to taxane chemotherapeutics, highlighting a need to identify additional therapeutic targets. Fatty acid‐binding protein 5 (FABP5) is an intracellular lipid carrier whose expression is upregulated in metastatic PCa and increases cell growth, invasion, and tumor formation. Here, we assessed whether FABP5 inhibitors synergize with semi‐synthetic taxanes to induce cytotoxicity in vitro and attenuate tumor growth in vivo.
TMC1 is an essential component of a leak channel that modulates tonotopy and excitability of auditory hair cells in mice

Hearing sensation relies on the mechano-electrical transducer (MET) channel of cochlear hair cells, in which transmembrane channel-like 1 (TMC1) and transmembrane channel-like 2 (TMC2) have been proposed to be the pore-forming subunits in mammals. TMCs were also found to regulate biological processes other than MET in invertebrates, ranging from sensations to motor function. However, whether TMCs have a non-MET role remains elusive in mammals. Here, we report that in mouse hair cells, TMC1, but not TMC2, provides a background leak conductance, with properties distinct from those of the MET channels. By cysteine substitutions in TMC1, we characterized four amino acids that are required for the leak conductance. The leak conductance is graded in a frequency-dependent manner along the length of the cochlea and is indispensable for action potential firing. Taken together, our results show that TMC1 confers a background leak conductance in cochlear hair cells, which may be critical for the acquisition of sound-frequency and -intensity.
Quinclorac resistance in Echinochloa phyllopogon is associated with reduced ethylene synthesis rather than enhanced cyanide detoxification by β-cyanoalanine synthase.

BACKGROUND Multiple herbicide resistant Echinochloa phyllopogon exhibits resistance to the auxin herbicide quinclorac. Previous research observed enhanced activity of the cyanide-detoxifying enzyme β-cyanoalanine synthase (β-CAS) and reduced ethylene production in the resistant line, suggesting β-CAS-mediated cyanide detoxification and insensitivity to quinclorac stimulation as the resistance mechanisms. To investigate the molecular mechanisms of quinclorac resistance, we characterized the β-CAS genes alongside plant transformation studies. The association of β-CAS activity and ethylene production to quinclorac resistance was assayed in the F6 progeny of susceptible and resistant lines of E. phyllopogon. RESULTS A single nucleotide polymorphism in a β-CAS1 intron deleted aberrantly spliced mRNAs and enhanced β-CAS activity in the resistant line. The enhanced activity, however, was not associated with quinclorac resistance in F6 lines. The results were supported by lack of quinclorac resistance in Arabidopsis thaliana expressing E. phyllopogon β-CAS1 and no difference in quinclorac sensitivity between β-CAS knockout and wild type rice. Reduced ethylene production co-segregated with quinclorac resistance in F6 lines which were previously characterized to be resistant to other herbicides by enhanced metabolism. CONCLUSION β-CAS does not participate in quinclorac sensitivity in E. phyllopogon. Our results suggest that mechanism(s) leading to reduced ethylene production is behind the resistance. This article is protected by copyright. All rights reserved.
Associations of Social Determinants of Health and Self-Reported Visual Difficulty: Analysis of the 2016 National Health Interview Survey

ABSTRACT Purpose: To determine the association of selected social determinants of health (SDH) assessed by the National Health Interview Survey (NHIS) among adults with visual difficulty. Methods: Data from adults 18 years of age and older relevant to self-reported visual difficulty were extracted from the 2016 NHIS dataset. A multivariate logistic regression model was used to determine associations between self-reported visual difficulty and key social determinants of health identified by the Kaiser Family Foundation and American College of Physicians. Outcomes were reported as odds ratios (OR) with 95% confidence intervals (CI). Results: Self-reported visual difficulty was significantly associated with lower educational attainment (OR 1.54; 95% CI, 1.30–1.81), having healthcare coverage through Medicaid (OR 1.44; 95% CI, 1.23–1.67), food insecurity (OR 1.75; 95% CI, 1.54–1.99), problems with paying medical bills (OR 1.60; 95% CI, 1.40–1.83), trouble finding a doctor (OR 1.49; 95% CI, 1.19–1.86), cost-related medication underuse (OR 1.72; 95% CI, 1.54–1.93), and identification as a non-heterosexual male (OR 1.82; 95% CI, 1.21–2.73). Those who were employed were at lower risk of visual difficulty compared to those who were looking for work or not working (OR 0.79; 95% CI, 0.71–0.89). Conclusion: A subset of SDH as evaluated by the NHIS are positively associated with self-reported visual difficulty. If validated, these results could inform future public health interventions that may reduce the incidence and burden of visual difficulty.
Poor prognoses of open globe injuries with concomitant orbital fractures

ABSTRACT Purpose Orbital trauma, particularly with open globe injury, can have a wide range of visual outcomes, which can be difficult to predict at presentation. Clinical features on presentation may provide insight into visual prognosis. We hypothesized that patients with open globe injuries and concomitant orbital fractures have poorer visual outcomes than patients without orbital fractures. Methods We reviewed the charts of 77 patients with isolated open globe injuries (OG) and 76 patients with open globe injuries and concomitant orbital fractures (OGOF). Multivariate regression analysis was performed to assess the relative influence of individual presenting historical and clinical features on visual outcome. Results OGOF patients were more likely to have sustained blunt trauma than a sharp, penetrating injury compared to OG patients. Ocular wound locations were more posterior and likely to involve multiple zones in OGOF compared to OG patients. Among OGOF patients, orbital floor fractures were the most common and roof fractures were the least common, but the latter was associated with presenting NLP vision and multiple zone involvement. The presence of an orbital fracture independently increased the odds of subsequent evisceration/enucleation (OR: 4.6, 95% CI 1.3–20.1, p = .0246) and NLP vision (OR: 6.81, 95% CI 2.42–21.85, p = .0005) when controlling for zone, mechanism of injury, uveal prolapse and demographic variables. Conclusions The presence of an orbital fracture independently confers a worse visual and ocular prognosis in patients with open globe injuries. Patients with open globe injuries in this category should be appropriately counseled.
The Effect of Sleep Curtailment on Hedonic Responses to Liquid and Solid Food

It is currently unclear whether changes in sweet taste perception of model systems after sleep curtailment extend to complex food matrices. Therefore, the primary objective of this study was to use a novel solid oat-based food (crisps) and oat-based beverage stimulus sweetened with sucralose to assess changes in taste perception after sleep curtailment. Forty-one participants recorded a habitual and curtailed night of sleep using a single-channel electroencephalograph. The next morning, overall sweetness, flavor, and texture liking responses to energy- and nutrient-matched oat products across five concentrations of sweetness were measured. Overall (p = 0.047) and flavor (p = 0.017) liking slopes across measured concentrations were steeper after curtailment, suggesting that sweeter versions of the oat products were liked more after sleep curtailment. Additionally, a hierarchical cluster analysis was used to classify sweet likers and non-likers. While the effect of sleep curtailment on sweet liking did not differ between sweet liking classification categories, sleep curtailment resulted in decreased texture liking in the solid oat crisps for sweet non-likers (p < 0.001), but not in the oat beverage. These findings illustrate the varied effects of sleep on hedonic response in complex food matrices and possible mechanisms by which insufficient sleep can lead to sensory-moderated increases in energy intake.
Therapeutic Breast Reconstruction Using Gene Therapy–Delivered IFNγ Immunotherapy

After mastectomy, breast reconstruction is increasingly performed using autologous tissue with the aim of improving quality of life. During this procedure, autologous tissue is excised, relocated, and reattached using microvascular anastomoses at the site of the extirpated breast. The period during which the tissue is ex vivo may allow genetic modification without any systemic exposure to the vector. Could such access permit delivery of therapeutic agents using the tissue flap as a vehicle? Such delivery may be more targeted and oncologically efficient than systemic therapy, and avoid systemic complications. The cytokine IFNγ has antitumor effects, and systemic toxicity could be circumvented by localized delivery of the IFNγ gene via gene therapy to autologous tissue used for breast reconstruction, which then releases IFNγ and exerts antitumor effects. In a rat model of loco-regional recurrence (LRR) with MADB-106-Luc and MAD-MB-231-Luc breast cancer cells, autologous tissue was transduced ex vivo with an adeno-associated viral vector encoding IFNγ. The “Therapeutic Reconstruction” released IFNγ at the LRR site and eliminated cancer cells, significantly decreased tumor burden, and increased survival compared with sham reconstruction (P <0.05). Mechanistically, localized IFNγ immunotherapy stimulated M1 macrophages to target cancer cells within the regional confines of the modified tumor environment. This concept of “Therapeutic Breast Reconstruction” using ex vivo gene therapy of autologous tissue offers a new application for immunotherapy in breast cancer with a dual therapeutic effect of both reconstructing the ablative defect and delivering local adjuvant immunotherapy.
Understanding an Urban Park through Big Data

To meet the needs of park users, planners and designers must know what park users want to do and how they want the park to offer different activities. Big data may help planners and designers gain this knowledge. This study examines how big data collected in an urban park could be used to identify meaningful implications for planning and design. While big data have emerged as a new data source, big data have not become an accepted source of data due to a lack of understanding of big data analytics. By comparing a survey as a traditional data source with big data, this study identifies the strengths and weaknesses of using big data analytics in park planning and design. There are two research questions: (1) what activities do park users want; and (2) how satisfied are users with different activities. The Gyeongui Line Forest Park, which was built on an abandoned railway, was selected as the study site. A total of 177 responses were collected through the onsite survey, and 3703 tweets mentioning the park were collected from Twitter. Results from the survey show that ordinary activities such as walking and taking a rest in the park were the most common. These findings also support existing studies. The results from social media analytics found notable things such as positive tweets about how the railway was turned into a park, and negative tweets about diseases that may occur in the park. Therefore, a survey as traditional data and social media analytics as big data can be complementary methods for the design and planning process.
Mollison's Blood Transfusion in Clinical Medicine

Preface to twelfth edition v Preface to eleventh edition vii Preface to first edition ix In memoriam: Professor Mollison xi 1 Blood donors and the withdrawal of blood 1 2 Transfusion of blood, blood components and plasma alternatives in oligaemia 22 3 Immunology of red cells 53 4 ABO, H, LE, P1PK, GLOB, I and FORS blood group systems 118 5 The Rh blood group system (including LW and RHAG) 167 6 Other red cell antigens 214 7 Red cell antibodies against self-antigens, bound antigens and induced antigens 259 8 Blood grouping techniques 303 9 The transfusion of red cells 356 10 Red cell incompatibility in vivo 411 11 Haemolytic transfusion reactions 458 12 Haemolytic disease of the fetus and the newborn 499 13 Immunology of leucocytes, platelets and plasma components 549 14 The transfusion of platelets, leucocytes, haematopoietic progenitor cells and plasma components 611 15 Some unfavourable effects of transfusion 660 16 Infectious agents transmitted by transfusion 696 17 Exchange transfusion and haemapheresis 764 18 Alternatives to allogeneic transfusion 800 19 Plasma fractionation and fractionation products 846 Appendices 873 Index 892 Colour plate section facing p. 148
The Anterolateral Structure of the Knee Does Not Affect Anterior and Dynamic Rotatory Stability in Anterior Cruciate Ligament Injury: Quantitative Evaluation With the Electromagnetic Measurement System

Background: The biomechanical function of the anterolateral structure (ALS), which includes the anterolateral joint capsule and anterolateral ligament (ALL), remains a topic of debate. Hypothesis: The ALS contributes to knee joint stability during the Lachman test and the pivot-shift test in anterior cruciate ligament (ACL)–deficient knees. Study Design: Controlled laboratory study. Methods: Fourteen fresh-frozen hemipelvis lower limbs were used. For 7 specimens, the anterior one-third of the ALS and the residual ALS were cut intra-articularly with a radiofrequency device. Subsequently, the ACL was cut arthroscopically. For the other 7 specimens, the ACL was cut first, followed by the anterior one-third of the ALS and the residual ALS intra-articularly. During the procedures, the iliotibial band (ITB) was kept intact. At each condition, the anterior tibial translation (ATT) during the manual Lachman test and the acceleration of posterior tibial translation (APT) and the posterior tibial translation (PTT) during the manual pivot-shift test were measured quantitatively with an electromagnetic measurement system. The mean values of those parameters were compared among 6 groups (ACL intact, one-third ALS cut, all ALS cut, ACL cut, ACL/one-third ALS cut, and ACL/all ALS cut). Results: The mean ATTs during the Lachman test and the mean APTs and PTTs in the ACL-cut conditions (ACL cut, ACL/one-third ALS cut, and ACL/all ALS cut) were significantly larger than those under the ACL-intact conditions (ACL intact, one-third ALS cut, all ALS cut) (P < .01). However, no statistically significant differences were observed among the intact, one-third ALS–cut, and all ALS–cut conditions, within the ACL-intact or ACL-cut conditions. Conclusion: Intra-articular dissection of the ALS did not increase the ATT during the Lachman test or the APT and PTT during the pivot-shift test under the intact condition of the ITB, regardless of the integrity of the ACL. When the ITB is intact, the ALS does not have a significant role in either anterior or dynamic rotatory knee stability, while the ACL does. Clinical Relevance: Recent growing interest about ALL reconstruction or ALS augmentation may not have a large role in controlling either anterior or dynamic rotatory knee instability in isolated ACL-deficient knees.
Inflammatory markers of contrast-induced nephropathy in patients with acute coronary syndrome

Objective: Contrast-induced nephropathy (CIN) is among the serious complications of invasive cardiovascular procedures that are performed with the administration of contrast agents. We investigated the role of the inflammatory markers in predicting CIN in acute coronary syndrome patients. Methods: This study included 232 consecutive patients with acute coronary syndrome who underwent emergency angiography at our center. Results: There were 38 (19.1%) patients in the CIN group (mean age: 62.4 ± 10.2; 68.4% male), and 162 patients in the non-CIN group (mean age: 62.1 ± 11.5; 60.5% male). In the CIN positive group, serum gamma-glutamyl transferase (GGT) (P < 0.001), uric acid (P < 0.001), high sensitivity C-reactive protein (P < 0.001), the neutrophil-to-lymphocyte ratio (P = 0.02) were higher, whereas vitamin D (P < 0.001), hemoglobin (P < 0.001) and baseline glomerular filtration rate (P = 0.011) were lower compared with the CIN negative group. The receiver operating characteristic analysis showed that the cutoff point of GGT was 56 U/L for predicting CIN with a 84.2% sensitivity and a 72.2% specificity (area under the curve = 0.879, P < 0.001). The predictive value of GGT was the highest compared other inflammatory markers for CIN (area under the curve = 0.879). Conclusion: Our study showed that the levels of GGT, high sensitivity C-reactive protein, vitamin D, uric acid and neutrophil-to-lymphocyte ratio were the effective factors in development of CIN. The level of GGT was found as the most effective factor in prediction of the development of CIN.