Miracle-dz/UniFAR-FTUs huggingface dataset:
Clickable Cisplatin Derivatives as Versatile Tools to Probe the DNA Damage Response to Chemotherapy

Cisplatin induces DNA crosslinks that are highly cytotoxic. Hence, platinum complexes are frequently used in the treatment of a broad range of cancers. Efficiency of cisplatin treatment is limited by the tumor-specific DNA damage response to the generated lesions. We reasoned that better tools to investigate the repair of DNA crosslinks induced by cisplatin would therefore be highly useful in addressing drug limitations. Here, we synthesized a series of cisplatin derivatives that are compatible with click chemistry, thus allowing visualization and isolation of DNA-platinum crosslinks from cells to study cellular responses. We prioritized one alkyne and one azide Pt(II) derivative, Pt-alkyne-53 and Pt-azide-64, for further biological characterization. We demonstrate that both compounds bind DNA and generate DNA lesions and that the viability of treated cells depends on the active DNA repair machinery. We also show that the compounds are clickable with both a fluorescent probe as well as biotin, thus they can be visualized in cells, and their ability to induce crosslinks in genomic DNA can be quantified. Finally, we show that Pt-alkyne-53 can be used to identify DNA repair proteins that bind within its proximity to facilitate its removal from DNA. The compounds we report here can be used as valuable experimental tools to investigate the DNA damage response to platinum complexes and hence might shed light on mechanisms of chemoresistance.
Hierarchical adaptive low‐rank format with applications to discretized partial differential equations

A novel framework for hierarchical low‐rank matrices is proposed that combines an adaptive hierarchical partitioning of the matrix with low‐rank approximation. One typical application is the approximation of discretized functions on rectangular domains; the flexibility of the format makes it possible to deal with functions that feature singularities in small, localized regions. To deal with time evolution and relocation of singularities, the partitioning can be dynamically adjusted based on features of the underlying data. Our format can be leveraged to efficiently solve linear systems with Kronecker product structure, as they arise from discretized partial differential equations (PDEs). For this purpose, these linear systems are rephrased as linear matrix equations and a recursive solver is derived from low‐rank updates of such equations. We demonstrate the effectiveness of our framework for stationary and time‐dependent, linear and nonlinear PDEs, including the Burgers' and Allen–Cahn equations.
Sharia insurance efficiency in Indonesia and Malaysia using the stochastic frontier approach analysis

Purpose: This study aims to analyze the efficiency level of Indonesian sharia insurance and Malaysian takaful with a parametric stochastic frontier approach where the input is total assets and expenses, and the output of this research is claims and premiums.Methodology: This study uses quantitative methods with secondary data in the form of shariah insurance Malaysia and Indonesia annual reports 2016-2020. The data analysis uses a regression test with the help of stochastic frontier approach (SFA)Findings: Based on the results of processing using stochastic frontier analysis (SFA), Indonesian Sharia insurance's overall production efficiency level is known to be 0.6306 or 63.06%, Malaysian takaful on average is known to be 0.6160 or 61.60 %. Partially, Indonesian sharia insurance total assets, insurance expenses, and claims positively and significantly affect the number of premiums. Takaful Malaysia's total assets of Malaysian takaful partially have an insignificant negative effect on the premium amount. Malaysia's takaful expenses and claims partially have an insignificant positive effect on the premium amount.Originality: This study analyzes the efficiency and looks at the effect of the variables of Indonesian sharia insurance and Malaysian takaful with a parametric stochastic frontier approach.Practical implications: This research shows that the management of Indonesian sharia insurance and Malaysia's takaful is still inefficient, so each government needs to regulate the operations in this industry.
Rub tree use and selection by American black bears and grizzly bears in northern Yellowstone National Park

Abstract: Several of the world's bear species exhibit tree-rubbing behavior, which is thought to be a form of scent-marking communication. Many aspects of this behavior remain unexplored, including differences in rub tree selection between sympatric bear species. We compiled rub tree data collected on Yellowstone National Park's Northern Range (USA) and compared rub tree selection of sympatric American black bears (Ursus americanus) and grizzly bears (U. arctos) at local and landscape scales. During 2017 and 2018, we identified 217 rub trees and detected black bears at 117 rub trees and grizzly bears at 18 rub trees, based on genetic analysis of collected hair samples. Rub trees generally were located in areas with gentle slopes and close to existing animal trails. Trees selected by black bears were typically in forested areas, whereas trees selected by grizzly bears were in forested and more open areas. Use of rub trees varied seasonally and between sexes for black bears, but seasonal data were inconclusive for grizzly bears. Black bears showed preferences for certain tree species for rubbing, but we did not find evidence that rub tree selection by grizzly bears differed among tree species. Both bear species selected trees that lacked branches on the lower portions of tree trunks and the maximum rub height was consistent with the body length of the bear species that used the tree. Although the sample size for grizzly bears was small, identifying the species and sex of bears based on genetic analysis enhanced interpretation of rub tree use and selection by bears. Scent-marking by black bears and grizzly bears on similar rub objects in well-traversed areas likely serves to enhance communication within and between the 2 species.
The unexpected high frequency of nocturnal surface ozone enhancement events over China: characteristics and mechanisms

Abstract. Surface ozone concentrations typically peak during the daytime, driven by active photochemical production, and decrease gradually after sunset, due to chemical destruction and dry deposition. Here, we report that nocturnal ozone enhancement (NOE, defined as an ozone increase of more than 5 ppbv h−1 in 1 of any 2 adjacent hours between 20:00 and 06:00 LT, local time) events are observed at multiple monitoring sites in China at a high frequency, which has not been recognized in previous studies. We present an overview of the general characteristics of NOE events in China and explore the possible mechanisms based on 6 years of observations from the national monitoring network. We find that the mean annual frequency of NOE events is 41±10 % (i.e., about 140 d would experience an NOE event per year) averaged over all 814 Chinese sites between 2014 and 2019, which is 46 % larger than that over Europe or the United States. The NOE event frequency is higher in industrialized city clusters (>50 %) than in regions with lighter ozone pollution, and it is higher in the warm season (46 %) than in the cold season (36 %), consistent with the spatiotemporal evolution of ozone levels. The mean ozone peak during NOE events reaches 37±6 ppbv in the warm season. The ozone enhancements are within 5–15 ppbv h−1 during 85 % of the NOE events; however, in about 10 % of cases, the ozone increases can exceed 20 ppbv h−1. We propose that high photochemistry-induced ozone during the daytime provides a rich ozone source in the nighttime residual layer, determining the overall high frequency of NOE events in China, and that enhanced atmospheric mixing then triggers NOE events by allowing the ozone-rich air in the residual layer to mix into the nighttime boundary layer. This is supported by our analyses which show that 70 % (65 %) of the NOE events are associated with increases in friction velocity (planetary boundary layer height), indicative of enhanced atmospheric mixing, and also supported by the observed sharp decreases in surface NO2 and CO concentrations with ozone increases in NOE events, a typical signal of mixing with air in the residual layer. Three case studies in Beijing and Guangzhou show that synoptic processes such as convective storms and low-level jets can lead to NOE events by aggravating vertical mixing. Horizontal transport of ozone-rich plumes may also be a supplementary driver of NOE events. Our results summarize, for the first time, the characteristics and mechanism of NOE events in China based on nationwide and long-term observations, and our findings emphasize the need for more direct measurements and modeling studies on the nighttime ozone evolution from the surface to the residual layer.
Seroprevalence and Risk Factors for Equine West Nile Virus Infections in Eastern Germany, 2020

West Nile virus (WNV) infections were first detected in Germany in 2018, but information about WNV seroprevalence in horses is limited. The study’s overall goal was to gather information that would help veterinarians, horse owners, and veterinary-, and public health- authorities understand the spread of WNV in Germany and direct protective measures. For this purpose, WNV seroprevalence was determined in counties with and without previously registered WNV infections in horses, and risk factors for seropositivity were estimated. The cohort consisted of privately owned horses from nine counties in Eastern Germany. A total of 940 serum samples was tested by competitive panflavivirus ELISA (cELISA), and reactive samples were further tested by WNV IgM capture ELISA and confirmed by virus neutralization test (VNT). Information about potential risk factors was recorded by questionnaire and analyzed by logistic regression. A total of 106 serum samples showed antibodies against flaviviruses by cELISA, of which six tested positive for WNV IgM. The VNT verified a WNV infection for 54 samples (50.9%), while 35 sera neutralized tick-borne encephalitis virus (33.0%), and eight sera neutralized Usutu virus (7.5%). Hence, seroprevalence for WNV infection was 5.8% on average and was significantly higher in counties with previously registered infections (p = 0.005). The risk factor analysis showed breed type (pony), housing in counties with previously registered infections, housing type (24 h turn-out), and presence of outdoor shelter as the main significant risk factors for seropositivity. In conclusion, we estimated the extent of WNV infection in the resident horse population in Eastern Germany and showed that seroprevalence was higher in counties with previously registered equine WNV infections.
Multitarget Molecular Imaging in Metastatic Castration Resistant Adenocarcinoma Prostate Cancer with Therapy Induced Neuroendocrine Differentiation

Neuroendocrine differentiation of prostate cancer (NEDPC) includes de novo presentation and secondary to epigenetic changes, referred as therapy-induced neuroendocrine prostate cancer (t-NEPC). Molecular imaging with prostate-specific membrane antigen (PSMA) and somatostatin analogues positron emission tomography (PET/CT) in NEDPC have not been validated. 18F-FDG (fluorodeoxyglucose) PET/CT has numerous limitations in prostate cancer (PCa) and the utility in NEDPC has only been reported in a few series of cases. The objective of this study is to compare the lesions detection rate of the three radiotracers in metastatic t-NEPC patients. (1) Material and Methods: Retrospective evaluation of patients with prostate adenocarcinoma treated with androgen deprivation therapy, chemotherapy, a novel androgen receptor pathway inhibitor or a combination of them and a second tumour biopsy confirming t-NEPC was made. All patients underwent 18F PSMA-1007, 18F AlF-NOTA-Octreotide, and 18F-FDG PET/CT. Evaluation of positive lesions was determined and SUVmax of each radiotracer was estimated and correlated with computer tomography (CT) findings. (2) Results: A total of eight patients were included. The mean time from diagnosis of prostate adenocarcinoma to t-NEPC was 28.2 months, with a mean serum specific prostate antigen (PSA) of 16.6 ng/dl at the time of NEPC diagnosis. All patients were treated with antiandrogen therapy and 87.5% with chemotherapy. A total of 273 lesions were identified by CT from which 182 were detected by 18F-FDG PET/CT, 174 lesions by 18F PSMA-1007, and 59 by 18F AlF-NOTA-Octreotide. An interpatient analysis of the lesions was performed and dual tracer 18F-FDG PET/CT and 18F PSMA-1007 PET/CT detected a total of 270/273 lesions (98.9%). (3) Conclusions: NEDPC patients demonstrated wide inter and intrapatient molecular imaging heterogeneity within the three radiotracers. 18F-FDG detected most lesions in t-NEPC among all radiotracers, especially in visceral sites; 18F PSMA-1007 detected more bone lesions. 18F AlF-NOTA-Octreotide showed no significant utility.
The distribution of rest periods affects performance and adaptations of energy metabolism induced by high-intensity training in human muscle

The effect of the distribution of rest periods on the efficacy of interval sprint training is analysed. Ten male subjects, divided at random into two groups, performed distinct incremental sprint training protocols, in which the muscle load was the same (14 sessions), but the distribution of rest periods was varied. The ‘short programme’ group (SP) trained every day for 2 weeks, while the ‘long programme’ group (LP) trained over a 6-week period with a 2-day rest period following each training session. The volunteers performed a 30-s supramaximal cycling test on a cycle ergometer before and after training. Muscle biopsies were obtained from the vastus lateralis before and after each test to examine metabolites and enzyme activities. Both training programmes led to a marked increase (all signiﬁcant, P < 0.05) in enzymatic activities related to glycolysis (phosphofructokinase – SP 107%, LP 68% and aldolase – SP 46%, LP 28%) and aerobic metabolism (citrate synthase – SP 38%, LP 28.4% and 3-hydroxyacyl-CoA dehydrogenase – SP 60%, LP 38.7%). However, the activity of creatine kinase (44%), pyruvate kinase (35%) and lactate dehydrogenase (45%) rose signiﬁcantly ( P < 0.05) only in SP. At the end of the training programme, SP had suffered a signiﬁcant decrease in anaerobic ATP consumption per gram muscle ( P < 0.05) and glycogen degradation ( P < 0.05) during the post-training test, and failed to improve performance. In contrast, LP showed a marked improvement in performance ( P < 0.05) although without a signiﬁcant increase in anaerobic ATP consumption, glycolysis or glycogenolysis rate. These results indicate that high-intensity cycling training in 14 sessions improves enzyme activities of anaerobic and aerobic metabolism. These changes are affected by the distribution of rest periods, hence shorter rest periods produce larger increase in pyruvate kinase, creatine kinase and lactate dehydrogenase. However, performance did not improve in a short training programme that did not include days for recovery, which suggests that muscle ﬁbres suffer fatigue or injury.
Attitude and Level of COVID-19 Vaccination among Women in Reproductive Age during the Fourth Pandemic Wave: A Cross-Sectional Study in Poland

COVID-19 vaccination, apart from the sanitary regime, is the most efficient strategy to limit the spread of the SARS-CoV-2 virus and significantly reduce the severity of the disease following infection. A cross-sectional survey was conducted during the fourth wave of the COVID-19 pandemic among pregnant Polish women and women who have already given birth to evaluate the level and attitude to vaccination. Briefly, 1196 women (256 pregnant and 940 mothers) participated in the study; 68.0% of pregnant women and 66.2% of mothers declared that they had received COVID-19 vaccination. The most frequently stated reasons not to get vaccinated were possible adverse effects on the mother, fetus or breastfed child, post-vaccination complications and limited scientific evidence on the safety of the COVID-19 vaccine. The identified predictors of avoiding COVID-19 vaccination are young age, residing in small cities or rural areas, cohabitation, low anxiety level regarding SARS-CoV-2 infection, and little knowledge concerning maternal vaccine-induced immune protection delivered to offspring. Despite the unlimited access to COVID-19 vaccination, the declared level of vaccination is worryingly low. The knowledge concerning the benefits of vaccination to mothers and their offspring is not satisfactory and requires urgent educational action, particularly among young women living outside big cities and single motherhood.
Occurrence and Phylogenetic Analysis of Avian Coronaviruses in Domestic Pigeons (Columba livia domestica) in Poland between 2016 and 2020

While disease control in racing pigeons and the potential role of pigeons as vectors transmitting viruses to poultry are of importance, there is still a paucity of data concerning the occurrence of coronaviruses in pigeons. In this study, 215 domestic pigeons were tested for the presence of coronaviral genetic material using the nested PCR method, which revealed 57 positive samples (26.51%). The difference in coronavirus prevalence between young and adult pigeons (34.34% and 19.83%, respectively) has been found statistically significant. In contrast, no statistically significant difference has been demonstrated between the prevalence in symptomatic and asymptomatic birds, leaving the influence of coronavirus presence on pigeon health uncertain. Phylogenetic analysis of the RdRp gene fragment allowed us to assign all the obtained strains to the Gammacoronavirus genus and Igacovirus subgenus. The phylogenetic tree plotted using the ML method revealed that those sequences formed a group most similar to pigeon coronavirus strains from China, Finland, and Poland, and to a single strain from a common starling from Poland, which suggests wide geographical distribution of the virus and its possible transmission between various species.
Explorer The Transcriptional Response of Drosophila melanogaster to Infection with the Sigma Virus (Rhabdoviridae)

Background: The precise molecular changes that occur when a neural stem (NS) cell switches from a programme of self- renewal to commit towards a specific lineage are not currently well understood. However it is clear that control of gene expression plays an important role in this process. DNA methylation, a mark of transcriptionally silent chromatin, has similarly been shown to play important roles in neural cell fate commitment in vivo. While DNA methylation is known to play important roles in neural specification during embryonic development, no such role has been shown for any of the methyl-CpG binding proteins (Mecps) in mice. Methodology/PrincipalFindings: To explore the role of DNA methylation in neural cell fate decisions, we have investigated the function of Mecps in mouse development and in neural stem cell derivation, maintenance, and differentiation. In order to test whether the absence of phenotype in singly-mutant animals could be due to functional redundancy between Mecps, we created mice and neural stem cells simultaneously lacking Mecp2 , Mbd2 and Zbtb33 . No evidence for functional redundancy between these genes in embryonic development or in the derivation or maintenance of neural stem cells in culture was detectable. However evidence for a defect in neuronal commitment of triple knockout NS cells was found. Conclusions/Significance: Although DNA methylation is indispensable for mammalian embryonic development, we show that simultaneous deficiency of three methyl-CpG binding proteins genes is compatible with apparently normal mouse embryogenesis. Nevertheless, we provide genetic evidence for redundancy of function between methyl-CpG binding proteins in postnatal mice.
Role and leadership of nurse manager in improving the quality of care in Burkina Faso: A qualitative study

Care quality is a major concern for healthcare settings. Because of its essential place in hospital management, Nurse Manager (NM) is a critical link in the care system. This study aimed to analyse the role and leadership of the NM in the care quality improvement at the Charles de Gaulle Pediatric Teaching Hospital (CHUP-CDG). This was a qualitative and descriptive study. Ten NMs from clinical services selected on a reasoned sampling basis participated in individual semi-structured interviews. Non-participant observations and a documentary review were carried out. Data collection was conducted from August 1 st to 31 st , 2017 at the CHUP-CDG. A thematic analysis based on the professional practice framework (PPF) of Oldland et al. performed. The NM’s role and leadership nurse covered three of the seven healthcare quality domains of the PPF, namely: (1) Promotion of safety; (2) Positive interpersonal behaviours; (3) Clinical leadership and governance. Four healthcare quality domains are not covered: Management of the environment, evidence-based practice, medical/technical competence, and person-centred care. The NMs of clinical services hold a special place at the CHUP-CDG. Consequently, the success of quality care improvement depends on their involvement and commitment in all the domains of healthcare quality.
Contribution of wood burning to exposures of PAHs and oxy-PAHs in Eastern Sweden

Abstract. A growing trend in developed countries is the use of wood as fuel for domestic heating due to measures taken to reduce the usage of fossil fuels. However, this imposed another issue with the environment and human health. That is, the emission from wood burning contributed to the increased level of atmospheric particulates and the wood smoke caused various respiratory diseases. The aim of this study was to investigate the impact of wood burning on the polycyclic aromatic hydrocarbons (PAHs) in air PM10 using known wood burning tracers, i.e. levoglucosan, mannosan and galactosan from the measurement at the urban background and residential areas in Sweden. A yearly measurement from three residential areas in Sweden showed a clear seasonal variation of PAHs during the cold season mainly from increased domestic heating and meteorology. Together, an increased sugar level assured the wood burning during the same period. The sugar ratio (levoglucosan/(mannosan+galactosan)) was a good marker for wood burning source such as the wood type used for domestic heating and garden waste burning. On the Walpurgis Night, the urban background measurement demonstrated a dramatic increase in levoglucosan, benzo[a]pyrene (B[a]P) and oxygenated PAHs (OPAHs) concentrations from the increased wood burning. A significant correlation between levoglucosan and OPAHs was observed suggesting OPAHs to be an indicator of wood burning together with levoglucosan. The levoglucosan tracer method and modelling used in predicting the B[a]P concentration could not fully explain the measured levels in the cold season. The model showed that the local wood source contributed to 98 % of B[a]P emissions in the Stockholm area and 2 % from the local traffic. However, non-local sources were dominating in the urban background (60 %). A further risk assessment estimated that the airborne particulate PAHs caused 13.4 cancer cases per 0.1 million inhabitants in Stockholm County.