Miracle-dz/UniFAR-FTUs huggingface dataset:
Prescribers’ approval rate of pharmacist-initiated interventions to optimise patients’ clinical status of hypertension in the ambulatory care setting

Abstract This perspective, pre- and post-intervention study with a one-year follow-up primarily aimed to ascertain prescribers’ approval rate of pharmacists’ interventions and clinical status of hypertension following comprehensive medication management (CMM) intervention in the ambulatory care clinic. Between January 2018 and January 2022 overall 100 patients with hypertension and other comorbidities were referred to the CMM services at the Health Centre Zagreb – Centar (HCZC). Out of 275 interventions directed to prescribers, 73.1 % of interventions were approved, 12.4 % were rejected and 14.5 % were not reviewed. The percentage of patients with a blood pressure goal increased from 45 % at the initial consultation to 82.5 % at the patients’ latest encounter (p < 0.001). The average number of drug therapy problems (DTPs) per patient totaled 3.53 ± 1.80, where 98 % of patients had one or more DTPs, 48 % had 4 or more DTPs, whereas 26 % had 5 or more DTPs. Sub-therapeutic dosage (32.6 %) and the need for additional drug therapy (30.9 %) were the two most commonly identified DTPs. These results reinforce the need to integrate pharmacy-led services in the primary care setting with the aim of improving patients’ health outcomes.
Beliefs about medicines’ association with endocrine therapy adherence in early breast cancer survivors in Croatia

Abstract This observational, cross-sectional study conducted at the University Hospital Centre Zagreb (UHC Zagreb) aimed to explore patients’ beliefs about adjuvant endocrine therapy (AET) as well as their association with non-adherence and sociodemographic and clinical factors. Out of 420 early breast cancer (BC) patients included in the study, 79.5 % perceived AET necessary and important for their health, as measured by the Belief About Medicines Questionnaire (BMQ), with the mean necessity score (20.4 ± 3.68) significantly higher than the mean concerns score (13 ± 4.81) (p < 0.001). Based on the Medication Adherence Report Scale (MARS-5), 44.4 % (n = 182) of the participants were non-adherers, out of which 63.2 % (n = 115) were unintentional and 36.8 % (n = 67) intentional non-adherers. Significantly higher concern beliefs were found among patients that were younger (p < 0.001), employed (p < 0.001), intentionally non-adherent to AET (p = 0.006), had a lower body-mass index (p = 0.005) and a higher level of education (p < 0.001), were premenopausal at the time of diagnosis (p < 0.001), taking tamoxifen treatment (p = 0.05) and receiving ovarian suppression (p < 0.001). Younger patients should be recognized as being at risk of non-adherence as they hold greater concern beliefs about medicines.
Effects of epidurally administered dexmedetomidine and dexamethasone on postoperative pain, analgesic requirements, inflammation, and oxidative stress in thoracic surgery

Abstract The aim of this study was to compare the effects of dexmedetomidine and dexamethasone as adjuvants to preoperative epidural administration of local anesthetic (ropivacaine) in thoracic surgery on the postoperative level of pain, use of analgesics, inflammation, and oxidative stress. The study enrolled 42 patients who underwent elective thoracic surgery in a one-year period at the University Hospital Dubrava (Zagreb, Croatia). Based on a computer-generated randomization list the patients were assigned to the dexmedetomidine (n = 18) or dexamethasone (n = 24) group. Postoperatively, patients of dexmedetomidine group reported lower pain (VAS value 1 h post surgery, 3.4 ± 2.7 vs. 5.4 ± 1.8, dexmedetomidine vs. dexamethasone, p < 0.01) and had lower anal-gesic requirements in comparison with dexamethasone group. Thus, dexmedetomidine in comparison with dexamethasone was more efficient in lowering pain and analgesia requirements 24 h after the surgery. On the contrary, dexamethasone had better anti-inflammatory properties (CRP level 24 h post surgery, 131.9 ± 90.7 vs. 26.0 ± 55.2 mg L−1, dexmedetomidine vs. dexamethasone, p < 0.01). Both dexmedetomidine and dexamethasone exhibited antioxidant effects, however, their antioxidant properties should be further explored. The results of this study improve current knowledge of pain control in thoracic surgery.
Students'Perceptions towards Duolingo App as a Microlearning Tool

Mobile-based micro-learning which combines features of mobile learning and micro-learning to deliver small learning units and short-term learning activities, has gained a lot of attention lately. This study aimed to investigate students’ perceptions of Duolingo app as a microlearning tool in English language learning. The context of this study was a vocational school where Duolingo is integrated in the first level of English as a mandatory requirement. The participants of this study were 150 students who have completed or are still taking English courses at this school. Qualitative data were collected from an online survey in which the participants had to provide answers to two open-ended questions regarding the strengths and weaknesses of employing Duolingo as a mocrolearning tool in level 1 English course. The data were then analyzed using manual coding technique. The results showed that the positive perceptions outweighted the negative ones.
Elevation correction of ERA‐Interim temperature data in the Tibetan Plateau

The near surface air temperature is the primary indicator for climate change. Reanalysis as the surrogates for large‐scale observations are widely used in the Tibetan Plateau because of the sparse meteorological network. However, an average bias of −3.54 °C and root‐mean‐square error (RMSE) of 4.31 °C were found between ERA‐Interim monthly 2‐m temperature and observation over the Tibetan Plateau, which indicated that a correction procedure for ERA‐Interim is necessary before local scale applications. To overcome this challenge, a robust elevation correction method is developed to downscale ERA‐Interim 2° × 2° monthly 2‐m temperature data based on ERA‐Interim internal vertical lapse rates. This method is validated against 80 meteorological stations from 1979 to 2013 located in 26 ERA‐Interim grid cells. It is also compared with other four correction methods, which are using different lapse rate schemes such as fixed monthly lapse rates, surface lapse rates calculated from the meteorological stations (within a single grid or with neighbouring sites), as well as a third‐order curvilinear function of ERA‐Interim pressure level data. The results indicate that the correction method using ERA‐Interim internal vertical lapse rates cannot only significantly reduce the bias (89%) and RMSE (62%) for the original ERA‐Interim data, but also capture the inter‐annual variations for the plateau‐wide climatology very well. The seasonal and annual temperature warming trends are also modelled encouragingly compared with other four methods. The strongest advantage of this method is that it is independent of local meteorological stations. Therefore, it is possible to extrapolate ERA‐Interim temperature data for any other high mountain areas where no measurements exist. This work will help the scientific community identify the most proper and easiest method to downscale reanalysis temperature data for climate impact assessments at the site or regional scale.
Coral Reef Carbonate Chemistry Reveals Interannual, Seasonal, and Spatial Impacts on Ocean Acidification Off Florida

Ocean acidification (OA) threatens coral reef persistence by decreasing calcification and accelerating the dissolution of reef frameworks. The carbonate chemistry of coastal areas where many reefs exist is strongly influenced by the metabolic activity of the underlying benthic community, contributing to high spatiotemporal variability. While characterizing this variability is difficult, it has important implications for the progression of OA and the persistence of the ecosystems. Here, we characterized the carbonate chemistry at 38 permanent stations located along 10 inshore‐offshore transects spanning 250 km of the Florida Coral Reef (FCR), which encompass four major biogeographic regions (Biscayne Bay, Upper Keys, Middle Keys, and Lower Keys) and four shelf zones (inshore, mid‐channel, offshore, and oceanic). Data have been collected since 2010, with approximately bi‐monthly periodicity starting in 2015. Increasing OA, driven by increasing DIC, was detected in the mid‐channel, offshore, and oceanic zones in every biogeographic region. In the inshore zone, however, increasing TA counteracted any measurable OA trend. Strong seasonal variability occurred at inshore sites and included periods of both exacerbated and mitigated OA. Seasonality was region‐dependent, with greater variability in the Lower and Middle Keys. Elevated pH and aragonite saturation states (ΩAr) were observed in the Upper and Middle Keys, which could favor reef habitat persistence in these regions. Offshore reefs in the FCR could be more susceptible to global OA by experiencing open‐ocean‐like water chemistry conditions. By contrast, higher seasonal variability at inshore reefs could offer a temporary OA refuge during periods of enhanced primary production.
Physics‐Informed Neural Networks for Elliptical‐Anisotropy Eikonal Tomography: Application to Data From the Northeastern Tibetan Plateau

We develop a novel approach for multi‐frequency, elliptical‐anisotropic eikonal tomography based on physics‐informed neural networks (pinnEAET). This approach simultaneously estimates the medium properties controlling anisotropic Rayleigh waves and reconstructs the traveltimes. The physics constraints built into pinnEAET's neural network enable high‐resolution results with limited inputs by inferring physically plausible models between data points. Even with a single source, pinnEAET can achieve stable convergence on key features where traditional methods lack resolution. We apply pinnEAET to ambient noise data from a dense seismic array (ChinArray‐Himalaya II) in the northeastern Tibetan Plateau with only 20 quasi‐randomly distributed stations as sources. Anisotropic phase velocity maps for Rayleigh waves in the period range from 10–40 s are obtained by training on observed traveltimes. Despite using only about 3% of the total stations as sources, our results show low uncertainties, good resolution and are consistent with results from conventional tomography.
Randomness and probability: exploring student teachers’ conceptions

ABSTRACT Understanding randomness is essential for modern life, as it underpins decisions under uncertainty. It is also an essential part of both the mathematics and science curricula in schools. Yet, research has shown that many people consider randomness difficult to perceive and argue about, with a number of different and contradictory views on the nature of randomness prevailing. This study explores beginning mathematics and science teachers’ understanding of randomness. A questionnaire was used with student teachers in an initial teacher-education course to explore their understanding of and reasoning about randomness and random events. Results suggest that mathematics and science student teachers conceptualize and argue about randomness in a variety of ways. Furthermore, these different conceptualizations affect how they respond to both common classroom tasks and everyday contexts involving randomness. This raises important implications for the education of teachers who will themselves be teaching probability and statistical inference.
Specific inhibition and disinhibition in the higher-order structure of a cortical connectome

Neuronal network activity is thought to be structured around the activation of assemblies, or low-dimensional manifolds describing states of activity. Both views describe neurons acting not independently, but in concert, likely facilitated by strong recurrent excitation between them. The role of inhibition in these frameworks – if considered at all – is often reduced to blanket inhibition with no specificity with respect to which excitatory neurons are targeted. We analyzed the structure of excitation and inhibition in the MICrONS 1mm3 dataset, an electron microscopic reconstruction of a piece of cortical tissue. We found that excitation was structured around a feed-forward flow in non-random motifs of seven or more neurons. This revealed a structure of information flow from a small number of sources to a larger number of potential targets that became only visible when larger motifs were considered instead of individual pairs. Inhibitory neurons targeted and were targeted by neurons in specific sequential positions of these motifs. Additionally, disynaptic inhibition was strongest between target motifs excited by the same group of source neurons, implying competition between them. The structure of this inhibition was also highly specific and symmetrical, contradicting the idea of non-specific blanket inhibition. None of these trends are detectable in only pairwise connectivity, demonstrating that inhibition is specifically structured by these large motifs. Further, we found that these motifs represent higher order connectivity patterns which are present, but to a lesser extent in a recently released, detailed computational model, and not at all in a distance-dependent control. These findings have important implications for how synaptic plasticity reorganizes neocortical connectivity to implement learning and for the specific role of inhibition in this process.
Task-Switch Related Reductions in Neural Distinctiveness in Children and Adults: Commonalities and Differences

Goal-directed behavior requires the ability to flexibly switch between task sets with changing environmental demands. Switching between tasks generally comes at the cost of slower and less accurate responses. Compared to adults, children show greater switch costs, presumably reflecting the protracted development of the ability to flexibly update task-set representations. To examine whether the distinctiveness of neural task-set representations is more strongly affected by a task switch in children compared to adults, we examined multi-voxel patterns of fMRI activation in 88 children (8–11 years, 49 girls) and 53 adults (20–30 years, 28 women) during a task-switching paradigm. Using multivariate pattern analysis (MVPA), we investigated whether task-set representations were less distinct on switch than on repeat trials across frontoparietal, cingulo-opercular, and temporo-occipital regions. Children and adults showed lower accuracy and longer response times on switch than on repeat trials, with higher accuracy costs in children. Decoding accuracy across regions was lower on switch than repeat trials, consistent with the notion that switching reduces the distinctiveness of task-set representations. Reliable age differences in switch-related representational distinctiveness reductions were absent, pointing to a remarkable degree of maturity of neural representations of task-relevant information in late childhood. However, we also observed that switch-related reductions in distinctiveness were more highly correlated across frontoparietal and cingulo-opercular regions in children than in adults, potentially reflecting the ongoing specialization of different control networks with respect to the representation of task features. Significance statement The ability to flexibly switch between tasks enables goal-directed behavior, but is particularly challenging for children, potentially due to protracted development in the ability to represent multiple and overlapping task rules that link stimuli to appropriate responses. We tested this hypothesis by using neuroimaging to measure brain activity during task switching in 8–11-year-olds and adults. Activation patterns in frontal, parietal, and temporal regions could tell us with above-chance accuracy which task a person was performing when the task remained the same, but not when it had switched. Adults showed greater differentiation across regions in terms of switch-related reductions in distinctiveness than children, suggesting that the relevant functional circuity is present but has not yet fully matured by late childhood.
Shieldin and CST co-orchestrate DNA polymerase-dependent tailed-end joining reactions independently of 53BP1-governed repair pathway choice

53BP1 regulates DNA end-joining in lymphocytes, diversifying immune antigen receptors. This involves nucleosome-bound 53BP1 at DNA double-stranded breaks (DSBs) recruiting RIF1 and shieldin, a poorly understood DNA-binding complex. The 53BP1-RIF1-shieldin axis is pathological in BRCA1-mutated cancers, blocking homologous recombination (HR) and driving illegitimate non-homologous end-joining (NHEJ). However, how this axis regulates DNA end-joining and HR suppression remains unresolved. We investigated shieldin and its interplay with CST, a complex recently implicated in 53BP1-dependent activities. Immunophenotypically, mice lacking shieldin or CST are equivalent, with class-switch recombination co-reliant on both complexes. ATM-dependent DNA damage signalling underpins this cooperation, inducing physical interactions between these complexes that reveal shieldin as a DSB-responsive CST adaptor. Furthermore, DNA polymerase ζ functions downstream of shieldin, establishing DNA fill-in synthesis as the physiological function of shieldin-CST. Lastly, 53BP1 suppresses HR and promotes NHEJ in BRCA1-deficient mice and cells independently of shieldin. These findings showcase the resilience of the 53BP1 pathway, achieved through the collaboration of chromatin-bound 53BP1 complexes and DNA end-processing effector proteins.
Prevalence study of cellular capsid-specific immune responses to AAV1, 2, 4, 5, 8, 9 and rh10 reveals particular features for AAV9

: Recombinant adeno-associated virus (rAAV) vectors appear, more than ever, to be efficient viral vectors for in vivo gene transfer as illustrated by the approvals of 7 drugs across Europe and the USA. Nevertheless, pre-existing immunity to AAV capsid in humans remains one of the major limits for a successful clinical translation. Whereas pre-existing humoral response to AAV capsid is well documented, the prevalence of pre-existing capsid-specific T cell responses still needs to be studied and characterized. Here, we investigated the prevalence of AAV-specific circulating T cells towards AAV2, 4, 5, 8, 9 and rh10 in a large cohort of healthy donors using the standard IFNγ ELISpot assay. We observed the highest prevalence of pre-existing cellular immunity to AAV9 serotype followed by AAV8, AAV4, AAV2, AAVrh10 and AAV5 independently of the donor’s serological status. An in-depth analysis of T cell responses towards the 2 most prevalent serotypes 8 and 9 shows that IFNγ secretion is mainly mediated by CD8 T cells for both serotypes. A polyfunctional analysis reveals different cytokine profiles between AAV8 and AAV9. Surprisingly, no IL-2 secretion was mediated by anti-AAV9 immune cells suggesting that these cells are rather exhausted than cytotoxic T cells. Altogether, these results suggest that pre-existing immunity to AAV may vary depending on the serotype and support the necessity of using multiparametric monitoring methods to better characterize anti-capsid cellular immunity and foresee its impact in rAAV-mediated clinical trials.
Krizový management. Případové bezpečnostní studie

Monograficka publikace obsahuje ucelený soubor studii, věnovaných přistupům krizoveho managementu k eliminaci krizi, vyvolaných zavažnými bezpecnostnimi hrozbami. Kniha je výsledkem spoluprace autorskeho kolektivu z Ekonomicko-spravni fakulty a Fakulty socialnich studii Masarykovy univerzity. Jejim zakladnim cilem je objasnit problematiku krizoveho managementu v bezpecnostni oblasti ve vztahu ke konkretnim problemům a oblastem. Na rozdil od řady dalsich publikaci na ceskem knižnim trhu neni zaměřena na obecný ramec terminologie, struktury a legislativy krizoveho managementu, ale věnuje se specifickým připadům využiti krizoveho managementu.
Artemisinin resistance mutations in Pfcoronin impede hemoglobin uptake

Artemisinin (ART) combination therapies have been critical in reducing malaria morbidity and mortality, but these important drugs are threatened by growing resistance associated with mutations in Pfcoronin and Pfkelch13. Here, we describe the mechanism of Pfcoronin-mediated ART resistance. PfCoronin interacts with PfActin and localizes to membranes of the parasite periphery, the digestive vacuole (DV), and a putative pre-DV compartment (PPDC)—all structures involved in the trafficking of hemoglobin from the RBC for degradation in the DV. Pfcoronin mutations alter PfActin homeostasis and impair the development and morphology of the PPDC. Ultimately, these changes are associated with decreased uptake of red blood cell cytosolic contents by ring-stage Plasmodium falciparum. Previous work has identified decreased hemoglobin uptake as the mechanism of Pfkelch13-mediated ART resistance. This work demonstrates that PfCoronin appears to act via a parallel pathway. For both Pfkelch13-mediated and Pfcoronin-mediated ART resistance, we hypothesize that the decreased hemoglobin uptake in ring stage parasites results in less heme-based activation of the artemisinin endoperoxide ring and reduced cytocidal activity. This study deepens our understanding of ART resistance, as well as hemoglobin uptake and development of the DV in early-stage parasites.
A new perspective on global mean sea level (GMSL) acceleration

The vast body of contemporary climate change science is largely underpinned by the premise of a measured acceleration from anthropogenic forcings evident in key climate change proxies—greenhouse gas emissions, temperature, and mean sea level. By virtue, over recent years, the issue of whether or not there is a measurable acceleration in global mean sea level has resulted in fierce, widespread professional, social, and political debate. Attempts to measure acceleration in global mean sea level (GMSL) have often used comparatively crude analysis techniques providing little temporal instruction on these key questions. This work proposes improved techniques to measure real‐time velocity and acceleration based on five GMSL reconstructions spanning the time frame from 1807 to 2014 with substantially improved temporal resolution. While this analysis highlights key differences between the respective reconstructions, there is now more robust, convincing evidence of recent acceleration in the trend of GMSL.
Prevalence of Peri-Implantitis in Implants with Turned and Rough Surfaces: a Systematic Review

ABSTRACT Objectives Moderately-rough implant surface may improve implant therapy in terms of bone integration, but the increased surface roughness might affect the initiation and development of peri-implantitis. The aim of the present review was to compare the prevalence of peri-implantitis in implants with rough and turned (machined) implant surfaces. Material and Methods An electronic literature search was conducted of the MEDLINE and EMBASE databases for articles published between 1 January 1990 and 1 March 2018. Clinical human studies in the English language that had reported on prevalence of peri-implantitis in tuned and rough surface implants were searched. The initial search resulted in 690 articles. Results Eight articles with 2992 implants were included in the systematic review. The incidence of peri-implantitis for two implant surfaces varied between studies. A meta-analysis was not feasible due to the heterogeneity among studies. Implant with rough surfaces were more favourable for plaque accumulation during short-term follow-up. On a long-term, turned implants surfaces were associated with more plaque and higher peri-implant bone loss. Peri-implant clinical parameters and survival rate for two implant surfaces was similar. Conclusions Within the limitations of the present study, rough implant surface does not seem to increase the incidence of peri-implantitis in comparison to turned implants surface.