Miracle-dz/UniFAR-FTUs huggingface dataset:
Water Tariffs as a Determinant for Water Consumption - The Analysis Across Polish Cities

This paper presents an empirical verification of the demand price elasticity for piped water in major cities in Poland – it was the main goal of the research. The information concerning the demand reaction to price changes is substantial for sustainable urban water demand. Any prediction of possible adaptation to global climate change also requires detailed information about consumer behaviour related to water consumption. This study was conducted on panel data consisting of approx. 100 largest Polish cities over the period of 5 years: 2010-2014. It was the second analysis in Poland and the first conducted on individual data from Polish agglomerations, instead of aggregated data for the whole country. Such detailed level of disaggregation has also some disadvantages – due to the lack of income data for each city – the income elasticity was skipped in the model. Finally the results were in the same range as figures obtained in other EU countries.
Characterisation of Microparticle Waste from Dental Resin-Based Composites

Clinical applications of resin-based composite (RBC) generate environmental pollution in the form of microparticulate waste. Methods: SEM, particle size and specific surface area analysis, FT-IR and potentiometric titrations were used to characterise microparticles arising from grinding commercial and control RBCs as a function of time, at time of generation and after 12 months ageing in water. The RBCs were tested in two states: (i) direct-placement materials polymerised to simulate routine clinical use and (ii) pre-polymerised CAD/CAM ingots milled using CAD/CAM technology. Results: The maximum specific surface area of the direct-placement commercial RBC was seen after 360 s of agitation and was 1290 m2/kg compared with 1017 m2/kg for the control material. The median diameter of the direct-placement commercial RBC was 6.39 μm at 360 s agitation and 9.55 μm for the control material. FTIR analysis confirmed that microparticles were sufficiently unique to be identified after 12 months ageing and consistent alteration of the outermost surfaces of particles was observed. Protonation-deprotonation behaviour and the pH of zero proton charge (pHzpc) ≈ 5–6 indicated that the particles are negatively charged at neutral pH7. Conclusion: The large surface area of RBC microparticles allows elution of constituent monomers with potential environmental impacts. Characterisation of this waste is key to understanding potential mitigation strategies.
Questionnaire and Portable Sleep Test Screening of Sleep Disordered Breathing in Acute Stroke and TIA

Sleep disordered breathing (SDB) is highly prevalent, but frequently unrecognized among stroke patients. Polysomnography (PSG) is difficult to perform soon after a stroke. We evaluated the use of screening questionnaires and portable sleep testing (PST) for patients with acute stroke, subarachnoid hemorrhage, or transient ischemic attack to expedite SDB diagnosis and management. We performed a single-center retrospective analysis of a quality improvement study on SDB screening of consecutive daytime, weekday, adult admissions to a stroke unit. We excluded patients who were unable to communicate and lacked available family members. Patients were screened with the Epworth Sleepiness Scale, Berlin Questionnaire, and STOP-BANG Questionnaire and underwent overnight PST and/or outpatient PSG. The 4-item STOP Questionnaire was derived from STOP-BANG for a secondary analysis. We compared the sensitivity and specificity of the questionnaires for the diagnosis of at least mild SDB (apnea hypopnea index (AHI) ≥5) on PST and correlated AHI measurements between PST and PSG using the Spearman correlation. Out of sixty-eight patients included in the study, 54 (80%) were diagnosed with SDB. Only one (1.5%) had a previous SDB diagnosis. Thirty-three patients completed all questionnaires and a PST. The STOP-BANG questionnaire had the highest sensitivity for at least mild SDB (0.81, 95% CI (confidence interval): 0.65–0.92) but a low specificity (0.33, 95% CI 0.10, 0.65). The discrimination of all questionnaires was overall poor (C statistic range 0.502–0.640). There was a strong correlation (r = 0.71) between the AHI results estimated using PST and outpatient PSG among 28 patients. The 4-item STOP Questionnaire was the easiest to administer and had a comparable or better sensitivity than the other questionnaires. Inpatient PSTs were useful for screening in the acute setting to facilitate an early diagnosis of SDB and to establish further outpatient evaluations with sleep medicine.
Structural and Functional Insights into the Biofilm-Associated BceF Tyrosine Kinase Domain from Burkholderia cepacia

BceF is a bacterial tyrosine kinase (BY-kinase) from Burkholderia cepacia, a Gram-negative bacterium accountable for respiratory infections in immunocompromised and cystic fibrosis patients. BceF is involved in the production of exopolysaccharides secreted to the biofilm matrix and promotes resistant and aggressive infections. BY-kinases share no homology with mammalian kinases, and thereby offer a means to develop novel and specific antivirulence drugs. Here, we report the crystal structure of the BceF kinase domain at 1.85 Å resolution. The isolated BceF kinase domain is assembled as a dimer in solution and crystallized as a dimer in the asymmetric unit with endogenous adenosine-diphosphate bound at the active sites. The low enzymatic efficiency measured in solution may be explained by the partial obstruction of the active sites at the crystallographic dimer interface. This study provides insights into self-assembly and the specific activity of isolated catalytic domains. Several unique variations around the active site compared to other BY-kinases may allow for structure-based design of specific inhibitors to target Burkholderia cepacia virulence.
Highly Efficient Inverted Organic Light-Emitting Diodes Adopting a Self-Assembled Modification Layer.

Inverted organic light-emitting diodes (IOLEDs) can be integrated with low-cost n-channel thin-film transistors for use in active-matrix OLEDs (AMOLEDs). However, the electron injection from conventional indium tin oxide (ITO) cathode to the upper electron transport layer usually suffers from a large injection barrier. To improve the electron injection efficiency, the electron injection layers (EILs) of ZnO modified by a self-assembled monolayer arginine (Arg) were developed to construct efficient IOLEDs. ZnO/Arg EILs present an ultralow work function (WF) of 2.35 eV, which is lower than that of ZnO modified by poly(ethylenimine) (PEI) (2.77 eV). The mechanism of low WF is attributed to the generation of strong molecular dipoles and interface dipoles at the interface of ZnO/Arg. The green fluorescent IOLEDs with ZnO/Arg present a low turn-on voltage (Von) of 3.5 V and a maximum current efficiency (CEmax) of 4.5 cd/A. Especially, the device possesses a half-life of 3600 h at an initial luminance of 1700 cd/m2, which is 36 times as long as that of the IOLEDs with ZnO/PEI as EILs. Furthermore, the green phosphorescent IOLEDs show a Von of 3.5 V, a CEmax of 59.1 cd/A, and a maximum external quantum efficiency (EQEmax) of 16.8%. At a luminance of 10 000 cd/m2, the efficiency roll-off of the device is only 6.3%.
Dynamic Contrast-Enhanced and Intravoxel Incoherent Motion MRI Biomarkers Are Correlated to Survival Outcome in Advanced Hepatocellular Carcinoma

Objective: This study assessed dynamic contrast-enhanced (DCE)-MRI and intravoxel incoherent motion diffusion-weighted imaging (IVIM DWI) parameters to prospectively predict survival outcomes in participants with advanced hepatocellular carcinoma (HCC) who received lenalidomide, a dual antiangiogenic and immunomodulatory agent, as second-line therapy in a Phase II clinical trial. Materials and methods: Forty-four participants with advanced HCC who had progression after sorafenib as first-line treatment were prospectively enrolled. Pretreatment MRI parameters—obtained from DCE-MRI (peak, slope, AUC, Ktrans, Kep, and Ve), apparent diffusion coefficient (ADC), and IVIM DWI (pure diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f))—were derived from the largest hepatic tumor. The Cox model was used to investigate the associations of the parameters with progression-free survival (PFS) and overall survival (OS). Results: Median PFS and OS were 2.3 and 8.0 months, respectively. Univariate analysis showed that participants with a high slope (p = 0.024), Kep (p < 0.001), and ADC (p = 0.018) values had longer PFS than those with low values; participants with a small tumor size (p = 0.006), high slope (p = 0.01), ADC (p = 0.015), and f (p = 0.012) values had longer OS than those with low values did. Cox multivariable analysis revealed that Kep (p < 0.001) and ADC (p = 0.009) remained independent predictors of PFS; slope (p = 0.003) and ADC (p = 0.009) remained independent predictors of OS. Moreover, Kep and slope were still significant after Bonferroni correction was performed (p < 0.005). Conclusion: Both pretreatment DCE-MRI and IVIM DWI parameters, especially slope and ADC, may predict PFS and OS in participants with HCC receiving lenalidomide as second-line therapy.
Reproducibility and Scalability of Magnetic Nanoheater Synthesis

The application of magnetic nanoparticles requires large amounts of materials of reproducible quality. This work explores the scaled-up synthesis of multi-core iron oxide nanoparticles through the use of thermal decomposition in organic media and kilograms of reagents. To this end, we check the effect of extending the high temperature step from minutes to hours. To address the intrinsic variability of the colloidal crystallization nucleation process, the experiments were repeated and analyzed statistically. Due to the simultaneity of the nuclei growth and agglomeration steps, the nanostructure of the samples produced was a combination of single- and multi-core nanoparticles. The main characteristics of the materials obtained, as well as the reaction yields, were analyzed and compared. As a general rule, yield, particle size, and reproducibility increase when the time at high temperature is prolonged. The samples obtained were ranked in terms of the reproducibility of different structural, colloidal, and magnetic features. The capability of the obtained materials to act as nanoheaters in magnetic hyperthermia was assessed, showing a strong dependence on the crystallite size (calculated by X-ray diffraction), reflecting the nanoparticle volume with a coherent magnetization reversal.
Low KIBRA Expression Is Associated with Poor Prognosis in Patients with Triple-Negative Breast Cancer

Background and Objectives: Kidney and brain protein (KIBRA) is a protein encoded by the WW and C2 domain containing 1 (WWC1) gene and is involved in the Hippo signaling pathway. Recent studies have revealed the prognostic value of KIBRA expression; however, its role in breast cancer remains unclear. The aim of this study was to examine KIBRA expression in relation to the clinical and pathological characteristics of patients with breast cancer and to disease outcomes. Materials and Methods: We analyzed the expression of KIBRA and its correlation with event-free survival (EFS) outcomes in resected samples from 486 patients with breast cancer. Results: KIBRA expression was significantly different among the molecular subgroups (low KIBRA expression: luminal A, 46.7% versus 50.0%, p = 0.641; luminal B, 32.7% versus 71.7%, p < 0.001; human epidermal growth factor receptor 2 (HER2)-enriched, 64.9% versus 45.5%. p = 0.001; triple-negative, 73.6% versus 43.8%, p < 0.001). Low KIBRA expression was also associated with high nuclear grade (60.4% versus 37.8%, p < 0.001), high histologic grade (58.7% versus 37.0%, p < 0.001), and estrogen receptor (ER) negativity (54.2% versus 23.6%, p < 0.001). Low KIBRA expression was significantly associated with poor EFS (p = 0.041; hazard ratio (HR) 1.658; 95% confidence interval (CI), 1.015–2.709). Low KIBRA expression was an independent indicator of poor prognosis (p = 0.001; HR = 3.952; 95% CI = 1.542–10.133) in triple-negative breast cancer (TNBC). Conclusion: Low KIBRA expression was associated with higher histological grade, ER negativity and poor EFS of breast cancer. In particular, our data highlight KIBRA expression status as a potential prognostic marker for TNBC.
Different Responses of Microbiota across Intestinal Tract to Enterococcus faecium HDRsEf1 and Their Correlation with Inflammation in Weaned Piglets

Enterococcus faecium HDRsEf1 (HDRsEf1) was identified to reduce the incidence of diarrhea in weaned piglets, but the mechanism has not been elucidated yet. Based on the fact that gut microbiota plays a crucial role in regulating inflammatory responses, the effects of HDRsEf1 on microbiota across the intestinal tract in weaned piglets were investigated. Microbiota from the luminal contents and the mucosa of the ileum, cecum, and colon of HDRsEf1-treated piglets were explored by 16S rRNA sequencing and qPCR. It was demonstrated that microbiota in different gut niches responded specifically to HDRsEf1, with major alterations occurring in the ileum and cecum. The total bacterial load of microbiota in ileal luminal contents and the relative abundance of Escherichia-Shigella in the ileal mucosa was significantly down-regulated by HDRsEf1 administration, while the relative abundance of butyrate-producing bacteria (including Clostridiaceae-1, Rumencoccidae, and Erysipelotrichaceae) in cecal luminal contents was significantly up-regulated. Moreover, the utilization of HDRsEf1 improved intestinal morphological development and reduced the inflammatory response, which were negatively correlated with the relative abundance of Escherichia-Shigella in the ileal mucosa and butyrate-producing bacteria in cecal luminal contents, respectively. Collectively, this study suggests that the administration of HDRsEf1 alters gut microbiota, thereby alleviating inflammation and improving intestinal morphological development in weaned piglets.
Prevalence of metabolic syndrome and associated factors among psychiatric patients at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia

Background Psychiatric patients are at increased risk of being overweight or obese, and subsequently develop metabolic syndrome. Nevertheless, data regarding associated factors for weight gain are limited and inconsistent. Objective The present study aimed to determine the risk of metabolic syndrome and its associated factors among psychiatric patients. Method A cross-sectional quantitative study was conducted among all psychiatric patients at the Psychiatric Unit of the University of Gondar Comprehensive Specialized Hospital from March 1- April 1, 2018. All eligible psychiatric patients were interviewed about their socio-demographic status,and clinical characteristics and useful parameters for the study were recorded from the medical records of the patients and by measuring waist to height ratio. Descriptive statistics were used to summarize baseline information.Binary logistic regression was used to determine the associated factors and P-value <0.05 and confidence interval (CI) of 95% were used as cut off points for determining statistical significance. Result From 300 patients included in the study, 168(56%) patients were females,and around 50.3% of the study participants had low literacy levels. As per waist to a height ratio scale, 58% (174) of the patients had a risk of metabolic syndrome. The Binary logistic regression analysis indicated that sex (p-<0.0001), occupation (p -0.032), marital status (p-0.006), and distance from the hospital (p<0.0001) were statistically significant determinants of metabolic syndrome risk in the psychiatric patient in our setting. Conclusion The majority of the psychiatric patients in the study setting had a risk of metabolic syndrome. Sex, marital status, employment status, and distance to the hospital were significantly associated with metabolic syndrome. Routine physical and laboratory investigations to detect metabolic syndrome are indispensable in psychiatric patients to prevent cardiovascular complications.
Identification of Sources and Transformations of Nitrate in the Intense Human Activity Region of North China Using a Multi-Isotope and Bayesian Model

Nitrate (NO3−) contamination in water is an environmental problem of widespread concern. In this study, we combined the stable isotopes of NO3− (δ15N and δ18O) and water (δ2H and δ18O) with a Bayesian mixing model (SIAR) to identify the sources and transformation of NO3− in groundwater and rivers in the Ye River basin of North China. The results showed that the mean NO3− concentrations in groundwater were 133.5 and 111.7 mg/L in the dry and flood seasons, respectively, which exceeded the required Chinese drinking water standards for groundwater (88.6 mg/L) (GB14848-2017). This suggests that groundwater quality has been severely impacted by human activity. Land use significantly affected the concentration of NO3− in the Ye River basin (p < 0.05). However, the NO3− concentrations in groundwater and river water had no obvious temporal variation (p > 0.05). The principal mode of nitrogen transformation for both groundwater and river water was nitrification, whereas denitrification did not significantly affect the isotopic compositions of NO3−. The sources of NO3− mainly originated from sewage and manure, soil nitrogen, and NH4+ in fertilizer for groundwater and from sewage and manure for the river water. According to the SIAR model, the primary sources of nitrate found in groundwater and river were sewage and manure in the Ye River basin. The proportional contributions of sewage and manure to nitrate contamination of groundwater and river were 58% and 48% in the dry season and 49% and 54% in the flood season, respectively. Based on these results, we suggest that the local government should enhance the sewage treatment infrastructure, construct an effective waste storage system to collect manure, and pursue a scientific fertilization strategy (such as soil formula fertilization) to increase the utilization rate of nitrogen fertilizer and prevent nitrate levels from increasing further.
Ventilation of the Southern Ocean Pycnocline.

Ocean ventilation is the transfer of tracers and young water from the surface down into the ocean interior. The tracers that can be transported to depth include anthropogenic heat and carbon, both of which are critical to understanding future climate trajectories. Ventilation occurs in both high- and midlatitude regions, but it is the southern midlatitudes that are responsible for the largest fraction of anthropogenic heat and carbon uptake; such Southern Ocean ventilation is the focus of this review. Southern Ocean ventilation occurs through a chain of interconnected mechanisms, including the zonally averaged meridional overturning circulation, localized subduction, eddy-driven mixing along isopycnals, and lateral transport by subtropical gyres. To unravel the complex pathways of ventilation and reconcile conflicting results, here we assess the relative contribution of each of these mechanisms, emphasizing the three-dimensional and temporally varying nature of the ventilation of the Southern Ocean pycnocline. We conclude that Southern Ocean ventilation depends on multiple processes and that simplified frameworks that explain ventilation changes through a single process are insufficient. Expected final online publication date for the Annual Review of Marine Science, Volume 14 is January 2022. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Identification of Novel Cathepsin B Inhibitors with Implications in Alzheimer’s Disease: Computational Refining and Biochemical Evaluation

Amyloid precursor protein (APP), upon proteolytic degradation, forms aggregates of amyloid β (Aβ) and plaques in the brain, which are pathological hallmarks of Alzheimer’s disease (AD). Cathepsin B is a cysteine protease enzyme that catalyzes the proteolytic degradation of APP in the brain. Thus, cathepsin B inhibition is a crucial therapeutic aspect for the discovery of new anti-Alzheimer’s drugs. In this study, we have employed mixed-feature ligand-based virtual screening (LBVS) by integrating pharmacophore mapping, docking, and molecular dynamics to detect small, potent molecules that act as cathepsin B inhibitors. The LBVS model was generated by using hydrophobic (HY), hydrogen bond acceptor (HBA), and hydrogen bond donor (HBD) features, using a dataset of 24 known cathepsin B inhibitors of both natural and synthetic origins. A validated eight-feature pharmacophore hypothesis (Hypo III) was utilized to screen the Maybridge chemical database. The docking score, MM-PBSA, and MM-GBSA methodology was applied to prioritize the lead compounds as virtual screening hits. These compounds share a common amide scaffold, and showed important interactions with Gln23, Cys29, His110, His111, Glu122, His199, and Trp221. The identified inhibitors were further evaluated for cathepsin-B-inhibitory activity. Our study suggests that pyridine, acetamide, and benzohydrazide compounds could be used as a starting point for the development of novel therapeutics.
Formative and Validation Human Factors studies of a new disposable autoinjector for subcutaneous delivery of chronic disease therapies

ABSTRACT Background Use-related risks related to autoinjector devices have been previously identified. To minimize these problems, the identification of potential use errors is a critical task during device development. Methods This article presents iterative human factor studies, which aim to assess user interaction with the tested push-on-skin BD Intevia™ 1 mL Disposable Autoinjector, across a wide range of indications, and a broad user population. Results Through the different human factor studies, use errors were recorded when the participants completed the critical tasks, but their occurrence continuously decreased. First, the incidence of use errors was reduced when the participants read the IFU. In addition, the IFU updates and design change implemented contributed to improve the usability performance. During the validation study, some use errors were still observed, mainly during the first uses. Nevertheless, providing a training to the participants almost fully eliminated the remaining use errors. Conclusion Thus, these results demonstrated that this new autoinjector can be safely and efficiently used for its intended uses and under the expected use conditions by all tested user groups.
Carbon Dots as an Emergent Class of Antimicrobial Agents

Antimicrobial resistance is a recognized global challenge. Tools for bacterial detection can combat antimicrobial resistance by facilitating evidence-based antibiotic prescribing, thus avoiding their overprescription, which contributes to the spread of resistance. Unfortunately, traditional culture-based identification methods take at least a day, while emerging alternatives are limited by high cost and a requirement for skilled operators. Moreover, photodynamic inactivation of bacteria promoted by photosensitisers could be considered as one of the most promising strategies in the fight against multidrug resistance pathogens. In this context, carbon dots (CDs) have been identified as a promising class of photosensitiser nanomaterials for the specific detection and inactivation of different bacterial species. CDs possess exceptional and tuneable chemical and photoelectric properties that make them excellent candidates for antibacterial theranostic applications, such as great chemical stability, high water solubility, low toxicity and excellent biocompatibility. In this review, we will summarize the most recent advances on the use of CDs as antimicrobial agents, including the most commonly used methodologies for CD and CD/composites syntheses and their antibacterial properties in both in vitro and in vivo models developed in the last 3 years.