Miracle-dz/UniFAR-FTUs huggingface dataset:
Carbonic Anhydrase as a Biomarker of Global and Local Impacts: Insights from Calcifying Animals

The emission of greenhouse gases has grown in unprecedented levels since the beginning of the industrial era. As a result, global climate changes, such as heightened global temperature and ocean acidification, are expected to negatively impact populations. Similarly, industrial and urban unsustainable development are also expected to impose local impacts of their own, such as environmental pollution with organic and inorganic chemicals. As an answer, biomarkers can be used in environmental programs to assess these impacts. These tools are based in the quantification of biochemical and cellular responses of target species that are known to respond in a sensitive and specific way to such stresses. In this context, carbonic anhydrase has shown to be a promising biomarker candidate for the assessment of global and local impacts in biomonitoring programs, especially in marine zones, such as coral reefs, considering the pivotal role of this enzyme in the calcification process. Therefore, the aim of this review is to show the recent advances in the carbonic anhydrase research and the reasons why it can be considered as a promising biomarker to be used for calcifying organisms.
Risk of sudden sensorineural hearing loss in patients with dysrhythmia: A nationwide population-based cohort study

Objective Whether dysrhythmia is a risk factor of sudden sensorineural hearing loss (SSNHL) remains unclear. In this study, we aimed to investigate the risk of developing SSNHL among patients with dysrhythmia in different age and gender groups by using population-based data in Taiwan. Methods We conducted a matched cohort study by analyzing data between January 2000 and December 2013 obtained from the Taiwan National Health Insurance Research Database. 41,842 newly diagnosed dysrhythmia patients and 83,684 comparison subjects without dysrhythmia were selected from claims. The incidence of sudden sensorineural hearing loss at the end of 2013 was determined in both groups. Univariate and multivariate logistic regression analyses were used to investigate the risk of SSNHL among patients with dysrhythmia. Results The incidence of SSNHL was 1.30-fold higher in the dysrhythmia group compared with the control group (53.2 versus 40.9 per 100,000 person-years), and using Cox proportional hazard regressions, the adjusted hazard ratio (HR) was 1.40 (95% confidence interval [CI], 1.15–1.70). Gender-stratified analysis revealed a significantly higher risk of SSNHL in patients with dysrhythmia than in those without dysrhythmia for both men and women (HR = 1.34, 95% CI = 1.02–1.76, P = 0.039, HR = 1.35, 95% CI = 1.02–1.78, P = 0.035, respectively). Age-stratified analysis revealed remarkable associations between dysrhythmia and SSNHL among those aged less than 40 years and more than 65 years (HR = 2.18, 95% CI = 1.03–4.64, P = 0.043 and HR = 1.54, 95% CI = 1.14–2.09, P = 0.006, respectively). Conclusions Our findings support dysrhythmia as an independent risk factor for SSNHL. Based on the study results, clinicians managing patients with dysrhythmia should be aware of the increased risk of developing SSNHL, especially among patients aged <40 and >65 years, and counsel patients to seek medical advice immediately if they experience any acute change in their hearing ability.
Immunotherapy with HDC/IL-2 may be clinically efficacious in acute myeloid leukemia of normal karyotype

ABSTRACT Immunotherapy with histamine dihydrochloride and low-dose interleukin-2 (HDC/IL-2) reduces the risk of relapse in the post-chemotherapy phase of acute myeloid leukemia (AML). Here we report the results of exploratory analyses of the clinical efficacy of HDC/IL-2 in AML with focus on the impact of karyotype aberrations in leukemic cells. Post-hoc analyses of phase III trial data suggested that HDC/IL-2 is primarily beneficial for patients with AML of normal karyotype. These results may be helpful in the selection of patients who are suitable for therapy and in the design of future immunotherapy protocols aiming at further defining the mechanism of relapse prevention by HDC/IL-2.
[Work on a building site at high altitude: physiopathological features and entailments for the occupational medicine].

SUMMARY Introduction. From a physiological perspective the high altitude is defined by altitudes higher than 3000 meters above sea level: at this altitude the atmospheric pressure is reduced to 525 mmHg and the partial pressure of Oxygen drops to 110 mmHg in the ambient air follows and 60 mmHg in the alveolar air. To stay at altitudes above 3000 m s.l. m. therefore places the human organism in front of a notable reduction of the functional respiratory reserve already in conditions of rest, leading to inevitable repercussions on the ability to sustain physical effort. Materials and methods. A population of 39 workers employed in the construction sector at a high altitude construction site (2200-3480 m) was examined. Data relating to sex, age, body mass index, smoking, residence altitude, mountaineering history (maximum altitude reached over a lifetime, frequency of ascents, time spent at high altitude, both for pleasure and for work) and sport practice were collected. Among them, for 25 workers the data of the ergometric tests in normobaric hypoxia (pO2, desaturation and peak values of heart rate, respiratory frequency, ventilation) conducted with simplified mode were collected. Purpose. The study aims to analyze the health of a group of workers exposed to the risk related to staying at high altitude in light of the indications of the scientific literature on health surveillance. Results. The data relating to the group of workers studied with regard to anamnestic data and to the results of ergospirometric examinations in hypoxic conditions are described. Conclusions. In working conditions at high altitude it is necessary to consider both the effect of high altitude in itself, similar to a sort of substantially unchangeable "background risk", and the ways in which high altitude interacts with other risk factors characteristic of the work site activity (which are the same as for any construction site activity that takes place at sea level), considering also the pathophysiological or frankly pathological conditions of which the worker is a carrier. This evaluation can be articulated on two levels: a first level concerning the suitability of the individual for access and the simple prolonged stay in altitude where the work activity will be performed; a second level regarding the suitability of the worker to carry out the work tasks required by the specific task in the particular environmental conditions.
Correlated Locality Data Distribution Policy for Improving Performance in SSD

In this paper, we propose in this paper present a novel locality data allocation policy as COLD(Correlated Locality Data) allocation policy. COLD is defined as a set of data that will be updated together later. By distributing a COLD into a NAND block separately, it can preserve th locality. In addition, by handling multiple COLD simultaneously, it can obtain the parallelism among NAND chips. We perform two experiment to demonstrate the effectiveness of the COLD data allocation policy. First, we implement COLD detector, and then, analyze a well-known workload. And we confirm the amount of COLD found depending on the size of data constituting the COLD. Secondly, we compared the traditional page-level mapping policy and COLD for garbage collection overhead in actual development board Cosmos OpenSSD. Experimental results have shown that COLD data allocation policy is significantly reduces the garbage collection overhead. Also, we confirmed that garbage collection overhead vary depending on the COLD size.
Efficient delivery of antisense Oligonucleotides by an amphipathic cell penetrating peptide in Acinetobacter baumannii.

Carbapenem-resistant Acinetobacter baumannii (A. baumannii) was number one on a list of the most threatening bacteria published by the WHO in 2017. Antisense oligonucleotides (ASOs) based therapy is a promising strategy for combating multi-drug resistant (MDR) bacteria because of its high specificity, simple design and lower induction of resistance, but poor cellular uptake by bacteria has restricted the further utilization of this therapy. Here, we used CADY, a secondary amphipathic peptide of 20 residues that could successfully carry siRNA into mammalian cells, to prepare CADY/ASOs nanoparticles (CADY-NPs) targeting acpP (encoding acyl carrier protein), and evaluated the uptake features, the inhibitory effects of CADY-NPs on gene expression and the growth of MDR-A. baumannii. We found that CADY-NPs could be quickly internalized by drug-sensitive and MDR-A. baumannii in an energy independent manner, but which could be restrained by chlorpromazine (an inhibitor of clathrin mediated endocytosis) significantly. In addition, CADY-NPs targeting acpP concentration-dependently retarded the growth of MDR-A. baumannii, which was associated with the decreased expression of targeted genes in A. baumannii. In conclusion, our research is the first to demonstrate that CADY can deliver ASOs into bacteria and provide a novel strategy for the treatment of MDR-A. baumannii.
Strategies toward High‐Performance Solution‐Processed Lateral Photodetectors

Due to their low cost and ease of integration, solution‐processed lateral photodetectors (PDs) are becoming an important device type among the PD family. In recent years, enormous effort has been devoted to improving their performances, and great achievements have been made. A summary of the core progress, especially from the perspective of design principles and device physics, is necessary to further the development of the field, but is currently lacking. Here, to address this need, first, the working mechanism of PDs and the device figures‐of‐merit are introduced. Second, by classifying the active materials into four categories, including inorganic, organic, hybrid, and perovskite, the developed strategies toward high performance are discussed respectively. To close, the common physical rules behind all these strategies are generalized, and suggestions for future development are given accordingly.
Astrocyte lineage cells are essential for functional neuronal differentiation and synapse maturation in human iPSC‐derived neural networks

Human astrocytes differ dramatically in cell morphology and gene expression from murine astrocytes. The latter are well known to be of major importance in the formation of neuronal networks by promoting synapse maturation. However, whether human astrocyte lineage cells have a similar role in network formation has not been firmly established. Here, we investigated the impact of human astrocyte lineage cells on the functional maturation of neural networks that were derived from human induced pluripotent stem cells (hiPSCs). Initial in vitro differentiation of hiPSC‐derived neural progenitor cells and immature neurons (glia+ cultures) resulted in spontaneously active neural networks as indicated by synchronous neuronal Ca2+ transients. Depleting proliferating neural progenitors from these cultures by short‐term antimitotic treatment resulted in strongly astrocyte lineage cell‐depleted neuronal networks (glia− cultures). Strikingly, in contrast to glia+ cultures, glia− cultures did not exhibit spontaneous network activity. Detailed analysis of the morphological and electrophysiological properties of neurons by patch clamp recordings revealed reduced dendritic arborization in glia− cultures. In addition, a reduced action potential frequency upon current injection in pyramidal‐like neurons was observed, whereas the electrical excitability of multipolar neurons was unaltered. Furthermore, we found a reduced dendritic density of PSD95‐positive excitatory synapses, and more immature properties of AMPA (alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid) miniature excitatory postsynaptic currents (mEPSCs) in glia− cultures, suggesting that the maturation of glutamatergic synapses depends on the presence of hiPSC‐derived astrocyte lineage cells. Intriguingly, addition of the astrocyte‐derived synapse maturation inducer cholesterol increased the dendritic density of PSD95‐positive excitatory synapses in glia− cultures.
Evaluating the potential impact and cost-effectiveness of dapivirine vaginal ring pre-exposure prophylaxis for HIV prevention

Background Expanded HIV prevention options are needed to increase uptake of HIV prevention among women, especially in generalized epidemics. As the dapivirine vaginal ring moves forward through regulatory review and open-label extension studies, the potential public health impact and cost-effectiveness of this new prevention method are not fully known. We used mathematical modeling to explore the impact and cost-effectiveness of the ring in different implementation scenarios alongside scale-up of other HIV prevention interventions. Given the knowledge gaps about key factors influencing the ring’s implementation, including potential uptake and delivery costs, we engaged in a stakeholder consultation process to elicit plausible parameter ranges and explored scenarios to identify the possible range of impact, cost, and cost-effectiveness. Methods and findings We used the Goals model to simulate scenarios of oral and ring pre-exposure prophylaxis (PrEP) implementation among female sex workers and among other women ≤21 years or >21 years with multiple male partners, in Kenya, South Africa, Uganda, and Zimbabwe. In these scenarios, we varied antiretroviral therapy (ART) coverage, dapivirine ring coverage and ring effectiveness (encompassing efficacy and adherence) by risk group. Following discussions with stakeholders, the maximum level of PrEP coverage (oral and/or ring) considered in each country was equal to modern contraception use minus condom use in the two age groups. We assessed results for 18 years, from 2018 to 2035. In South Africa, for example, the HIV infections averted by PrEP (ring plus oral PrEP) ranged from 310,000 under the highest-impact scenario (including ART held constant at 2017 levels, high ring coverage, and 85% ring effectiveness) to 55,000 under the lowest-impact scenario (including ART reaching the UNAIDS 90-90-90 targets by 2020, low ring coverage, and 30% ring effectiveness). This represented a range of 6.4% to 2.2% of new HIV infections averted. Given our assumptions, the addition of the ring results in 11% to 132% more impact than oral PrEP alone. The cost per HIV infection averted for the ring ranged from US$13,000 to US$121,000. Conclusions This analysis offers a wide range of scenarios given the considerable uncertainty over ring uptake, consistency of use, and effectiveness, as well as HIV testing, prevention, and treatment use over the next two decades. This could help inform donors and implementers as they decide where to allocate resources in order to maximize the impact of the dapivirine ring in light of funding and implementation constraints. Better understanding of the cost and potential uptake of the intervention would improve our ability to estimate its cost-effectiveness and assess where it can have the most impact.
Phytoglobin overexpression promotes barley growth in the presence of enhanced level of atmospheric nitric oxide

Abstract To investigate the effect of high atmospheric NO concentrations on crop plants and the role of phytoglobins under these conditions, we performed a long-term study on barley ‘Golden Promise’ wild type (WT), class 1 phytoglobin knockdown (HvPgb1.1−) and class 1 phytoglobin overexpression (HvPgb1.1+) lines. Plants were cultivated with nitrogen-free nutrient solution during the entire growth period and were fumigated with different NO concentration (ambient, 800, 1500, and 3000 ppb). Analysis of fresh weight, stem number, chlorophyll content, and effective quantum yield of PSII showed that NO fumigation promoted plant growth and tillering significantly in the HvPgb1.1+ line. After 80 d of NO fumigation, dry matter weight, spikes number, kernel number, and plant kernel weight were significantly increased in HvPgb1.1+ plants with increasing NO concentration. In contrast, yield decreased in WT and HvPgb1.1− plants the higher the NO level. Application of atmospheric 15NO and 15NO2 demonstrated NO specificity of phytoglobins. 15N from 15NO could be detected in RNA, DNA, and proteins of barley leaves and the 15N levels were significantly higher in HvPgb1.1+ plants in comparison with HvPgb1.1− and WT plants. Our results demonstrate that overexpression of phytoglobins allows plants to more efficiently use atmospheric NO as N source.
Frequency of undocumented medication discrepancies in discharge letters after hospitalization of older patients: a clinical record review study

Transitions of care may result in medication errors, when information about a patient’s medications is not communicated sufficiently. In this clinical record review study, we aimed to evaluate the frequency of undocumented medication discrepancies at discharge from hospital and evaluate which patient characteristics could be associated with undocumented medication discrepancies. Preadmission medication lists were compared against the medication list in the discharge letters, taking into account medication changes documented in the patient record throughout the inpatient stay and in the discharge summary. Out of 200 patients, 174 (87%) were affected by at least one undocumented medication discrepancy, mostly for regular medication. Of the 1972 medications used, 744 (38%) medications were changed without documentation in the patient record, the majority being over-the-counter supplements and herbal medications. Polypharmacy at admission and discharge was associated with increased undocumented medication discrepancies. This study indicates a lack of medication reconciliation during inpatient stay. Correct and complete medication lists at admission and discharge may resolve many of these discrepancies, supporting patient safety at transitions of care.
Neutrophil Gelatinase-Associated Lipocalin Is Not Associated with Tacrolimus-Induced Acute Kidney Injury in Liver Transplant Patients Who Received Mycophenolate Mofetil with Delayed Introduction of Tacrolimus

Tacrolimus is widely used as an immunosuppressant in liver transplantation, and tacrolimus-induced acute kidney injury (AKI) is a serious complication. The urinary neutrophil gelatinase-associated lipocalin (NGAL) level has been linked to tacrolimus-induced AKI in patients starting tacrolimus treatment the morning after liver transplantation. Here we tested this association using a different immunosuppression protocol: Mycophenolate mofetil administration beginning on Postoperative Day 1 and tacrolimus administration beginning on Postoperative Day 2 or 3. Urine samples were collected from 26 living donor liver transplant recipients before (Postoperative Day 1) and after (Postoperative Day 7 or 14) tacrolimus administration. NGAL levels were measured via enzyme-linked immunosorbent assays, as were those of three additional urinary biomarkers for kidney diseases: Monocyte chemotactic protein-1 (MCP-1), liver-type fatty acid-binding protein (L-FABP), and human epididymis secretory protein 4 (HE4). HE4 levels after tacrolimus administration were significantly higher in patients who developed AKI (n = 6) than in those who did not (n = 20), whereas NGAL, MCP-1, and L-FABP levels did not differ significantly before or after tacrolimus administration. These findings indicate that NGAL may not be a universal biomarker of AKI in tacrolimus-treated liver transplant recipients. To reduce the likelihood of tacrolimus-induced AKI, our immunosuppression protocol is recommended.
Assessment of the Safety of Glucocorticoid Regimens in Combination With Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer

Key Points Question What are the physiological effects associated with abiraterone acetate plus various glucocorticoid regimens to treat metastatic castration-resistant prostate cancer? Findings In this open-label, phase 2 randomized clinical trial, the 164 men with metastatic castration-resistant prostate cancer treated with abiraterone acetate plus prednisone, 5 mg, twice or once daily, 2.5 mg twice daily, or dexamethasone, 0.5 mg, once daily showed no mineralocorticoid excess toxic effects (grade ≥1 hypokalemia or grade ≥2 hypertension) through cycle 6. Insulin resistance and loss of total body bone mineral density at the end of study were only significant with dexamethasone. Meaning Lowering glucocorticoid dose combined with abiraterone acetate requires careful monitoring for toxic effects related to mineralocorticoid excess.
Targeting Quorum Sensing: High-Throughput Screening to Identify Novel LsrK Inhibitors

Since quorum sensing (QS) is linked to the establishment of bacterial infection, its inactivation represents one of the newest strategies to fight bacterial pathogens. LsrK is a kinase playing a key role in the processing of autoinducer-2 (AI-2), a quorum-sensing mediator in gut enteric bacteria. Inhibition of LsrK might thus impair the quorum-sensing cascade and consequently reduce bacterial pathogenicity. Aiming for the development of a target-based assay for the discovery of LsrK inhibitors, we evaluated different assay set-ups based on ATP detection and optimized an automation-compatible method for the high-throughput screening of chemical libraries. The assay was then used to perform the screening of a 2000-compound library, which provided 12 active compounds with an IC50 ≤ 10 µM confirming the effectiveness and sensitivity of our assay. Follow-up studies on the positive hits led to the identification of two compounds, harpagoside and rosolic acid, active in a cell-based AI-2 QS interference assay, which are at the moment the most promising candidates for the development of a new class of antivirulence agents based on LsrK inhibition.
Regular physical activity modulates perceived visual speed when running in treadmill-mediated virtual environments

In virtual reality, visual speed is usually underestimated relative to locomotor speed. Here we investigated how physical activity and fitness affect perceived visual speed when running in a treadmill-mediated virtual environment. Thirty healthy participants (ten sedentary individuals, ten team sport players and ten expert runners) ran on a treadmill at two different speeds (8, 12km/h) in front of a moving virtual scene. Participants were asked to match the speed of the visual scene to their running speed (i.e. treadmill speed), indicating for each trial whether the scene was moving slower or faster than the treadmill. The speed of the visual scene was adjusted according to the participant’s response using a staircase until visual and running speeds were perceived as equivalent. More sedentary participants underestimated visual speed relative to their actual running speed. Specifically, visual speed had to exceed running speed to be perceived as equivalent. The underestimation of visual speed was speed-dependent, and it was significantly larger for sedentary participants than for team sports players and expert runners. The volume of physical activity per week was found to be the best predictor of visual speed perception for both running speeds, while the perceived effort constituted a good predictor only at 8km/h. Physical fitness, on the other hand turned out to be a poor predictor of visual speed perception. Therefore, in order to enhance users’ engagement and their adherence to physical activity programs, the development of “personalized” treadmill-mediated virtual environments should take into account users’ personal characteristics to provide the most natural and engaging feedback possible.