Background The full range of cardiovascular complications related to the use of Immune checkpoint inhibitors (ICI) is not fully understood. We aim to describe the spectrum of cardiovascular adverse events (cvAEs) by presenting our real-world experience of the diagnosis and management of these complications. Methods Two thousand six hundred and forty-seven (2647) patients were started on ICI treatment between 2014 and 2020. Data from 110 patients referred to the cardio-oncology service with a suspected cvAE was collected prospectively and analysed. Results Eighty-nine patients (3.4%) were confirmed to have cvAEs while on ICI therapy. Myocarditis was the most frequent event (33/89), followed by tachyarrhythmia (27/89), non-inflammatory left ventricular dysfunction (NILVD) (15/89) and pericarditis (7/89). Results from myocarditis and non-inflammatory left ventricular dysfunction cohorts were compared. Myocarditis and NILVD showed significant differences in respect toof troponin elevation, cardiac magnetic resonance abnormalities and ventricular function. Dual ICI therapy and other immune related adverse events were more frequently associated with myocarditis than NILVD. There was a significant difference in the median time from starting ICI treatment to presentation with myocarditis versus NILVD (12 vs 26 weeks p = 0.049). Through early recognition of myocarditis, prompt treatment with steroids and interruption of ICI, there were no cardiovascular in-hospital deaths. NILVD did not require steroid treatment and ICI could be restarted safely. Conclusions The full spectrum of cardiovascular complications in patients with immune checkpoint inhibitors is much broader than initially described. Myocarditis remains the most frequent cvAE related to ICI treatment. A novel type of myocardial injury was observed and defined as Atrial tachyarrhythmias and NILVD were also frequent in this cohort. NILVD has a This differs fromdifferent presentation from ICI-related myocarditis, mainly usually presenting afterby the lack of inflammatory features on CMR and biomarkers and a later presentation in time.

Dysphagia occurs secondary to a variety of underlying etiologies and can contribute to increased risk of adverse events such as aspiration pneumonia and premature mortality. Dysphagia is primarily diagnosed and characterized by instrumental swallowing exams such as videofluoroscopic swallowing studies. videofluoroscopic swallowing studies involve the inspection of a series of radiographic images for signs of swallowing dysfunction. Though effective, videofluoroscopic swallowing studies are only available in certain clinical settings and are not always desirable or feasible for certain patients. Because of the limitations of current instrumental swallow exams, research studies have explored the use of acceleration signals collected from neck sensors and demonstrated their potential in providing comparable radiation-free diagnostic value as videofluoroscopic swallowing studies. In this study, we used a hybrid deep convolutional recurrent neural network that can perform multi-level feature extraction (localized and across time) to annotate swallow segments automatically via multi-channel swallowing acceleration signals. In total, we used signals and videofluoroscopic swallowing study images of 3144 swallows from 248 patients with suspected dysphagia. Compared to other deep network variants, our network was superior at detecting swallow segments with an average area under the receiver operating characteristic curve value of 0.82 (95% confidence interval: 0.807-0.841), and was in agreement with up to 90% of the gold standard-labeled segments.

Abstract Using HPLC-DAD the presence of catechin, epicatechin, quercetin, kaempferol and protocatehuic acid was analysed in herb extracts of eight Ephedra species (Ephedra sinica, Ephedra major, Ephedra chilensis, Ephedra ciliata, Ephedra foeminea, Ephedra equisetina, Ephedra gerardiana and Ephedra distachya). For comparison purposes, the same phenolics were determined in Camellia sinensis herb, which is a common source of catechins and a medicinal plant with valuable antioxidant properties. The catechin content in Ephedra spp. ranged between 0.83 mg/g d.w.– 8.77 mg/g d.w., while the epicatechin content was between 0.11 mg/g d.w.– 3.38 mg/g d.w. In comparison to black tea, Ephedra major, Ephedra distachya and Ephedra equisetina had a higher catechin content. The selected Ephedra spp. are rich in catechins and the obtained results serve as the chemical rationale for the anti-inflammatory, antioxidant and anti-proliferative activities of Ephedra that are currently being investigated. Graphical Abstract

Various 4-alkylphenols can be easily obtained through reductive catalytic fractionation of lignocellulosic biomass. Selective dehydrogenation of 4-n-propylguaiacol results in the formation of isoeugenol, a valuable flavor and fragrance molecule and versatile precursor compound. Here we present the engineering of a bacterial eugenol oxidase to catalyze this reaction. Five mutations, identified from computational predictions, are first introduced to render the enzyme more thermostable. Other mutations are then added and analyzed to enhance chemoselectivity and activity. Structural insight demonstrates that the slow catalytic activity of an otherwise promising enzyme variant is due the formation of a slowly-decaying covalent substrate-flavin cofactor adduct that can be remedied by targeted residue changes. The final engineered variant comprises eight mutations, is thermostable, displays good activity and acts as a highly chemoselective 4-n-propylguaiacol oxidase. We lastly use our engineered biocatalyst in an illustrative preparative reaction at gram-scale. Our findings show that a natural enzyme can be redesigned into a tailored biocatalyst capable of valorizing lignin-based monophenols. Lignin can be depolymerized into 4-alkylphenols by chemical means. Here the authors show a three-step computational-assisted enzyme engineering process to generate a biocatalyst for the conversion of lignin-derived 4-n-propylguaiacol into isoeugenol, a valuable compound.

Carbon tetrachloride (CCl4) is known to have hepatotoxic and nephrotoxic effects. During the two‐month CCl4 exposure of Wistar rats, propolis extract (PE) and royal jelly (RJ) were added in order to test the potential protective effect against hepato‐renal injury. Ketonuria, proteinuria, high creatinine and urea levels are the result of CCl4‐induced nephrotoxicity. Severe disorders of hematological indicators indicate anemia; high values of leukocytes indicate inflammatory condition. Cytogenetic impairments in hepatocytes, aggregation of platelets, and hypoproteinemia indicate severe liver impairment. Results suggest a more significant protective role of RJ compared to PE. Both extracts regulated proteinuria, ketonuria, hypoproteinemia and reduced platelet aggregation in the hepatic circulation. The increase in the number of erythrocytes (RBC) suggest protective effects against anemia; the decrease in the number of leukocytes can be linked to anti‐inflammatory effects. PE and RJ have a beneficial effect against hepato‐renal injury, anemia and anti‐inflammatory conditions caused by CCl4.

Drone-aided ubiquitous applications play important roles in our daily lives. Accurate recognition of drones is required in aviation management due to their potential risks and disasters. Radiofrequency (RF) fingerprinting-based recognition technology based on deep learning (DL) is considered an effective approach to extracting hidden abstract features from the RF data of drones. Existing deep learning-based methods are either high computational burdens or have low accuracy. In this paper, we propose a deep complex-valued convolutional neural network (DC-CNN) method based on RF fingerprinting for recognizing different drones. Compared with existing recognition methods, the DC-CNN method has a high recognition accuracy, fast running time, and small network complexity. Nine algorithm models and two datasets are used to represent the superior performance of our system. Experimental results show that our proposed DC-CNN can achieve recognition accuracies of 99.5% and 74.1%, respectively, on four and eight classes of RF drone datasets.

Secretory leucoprotease inhibitor (SLPI) has multifaceted functions, including inhibition of protease activity, antimicrobial functions, and anti-inflammatory properties. In this study, we show that SLPI plays a role in controlling pulmonary Pseudomonas aeruginosa infection. Mice lacking SLPI were highly susceptible to P. aeruginosa infection, however there was no difference in bacterial burden. Utilising a model of P. aeruginosa LPS-induced lung inflammation, human recombinant SLPI (hrSLPI) administered intraperitoneally suppressed the recruitment of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and resulted in reduced BALF and serum levels of inflammatory cytokines and chemokines. This anti-inflammatory effect of hrSLPI was similarly demonstrated in a systemic inflammation model induced by intraperitoneal injection of LPS from various bacteria or lipoteichoic acid, highlighting the broad anti-inflammatory properties of hrSLPI. Moreover, in bone-marrow-derived macrophages, hrSLPI reduced LPS-induced phosphorylation of p-IkB-α, p-IKK-α/β, p-P38, demonstrating that the anti-inflammatory effect of hrSLPI was due to the inhibition of the NFκB and MAPK pathways. In conclusion, administration of hrSLPI attenuates excessive inflammatory responses and is therefore, a promising strategy to target inflammatory diseases such as acute respiratory distress syndrome or sepsis and could potentially be used to augment antibiotic treatment.

The aim of the present study was to describe the morphological and performance characteristics of elite handball players using data collected over the last two decades within the talent evaluation program of the Slovenian Handball Federation. A total of 1066 elite male handball players selected for one of the Slovenian national teams (U17, U19, U21 or senior) were recruited. The data were collected from 2007/8 to the 2021/22 season. The main effects were observed for: body height, body weight, and body mass index (BMI). The muscle mass percentage differed only between different age categories (p = 0.003; η2 = 0.015), while the fat mass percentage (FM%) differed between playing positions (p < 0.001; η2 = 0.107). Post-hoc comparisons showed that, within senior handball players, pivot players were 6.46 cm (p = 0.009) taller than wing players and heavier than goalkeepers (12.43 kg, p = 0.004), backcourts (13.30 kg, p < 0.001) and wings (17.83 kg, p < 0.001). Moreover, pivots had a greater BMI than goalkeepers (2.3 kg/m2, p = 0.003), backcourts (2.62 kg/m2, p < 0.001), and wings (3.07 kg/m2, p < 0.001), while FM% was significantly higher in pivots compared to wings (4.32%, p = 0.010). Taking into consideration playing positions and age, the main effects were also observed for squat jump height, countermovement jump height, end-running speed, and VO2max (all p < 0.001; η2 = 0.017 to 0.091). Both morphological and performance characteristics clearly differ across playing positions and age categories, which should be a valuable guide for coaches to develop position-specific talent identification programs and training plans.

Apstrakt: Ovim radom obuhvaćen je historijski okvir, tehničko i foto snimanje stećaka na lokalitetu Mramorje/Bektića brdo u naselju Bektići, općina Srebrenica. Analiza nadgrobnika na terenu omogućila je prikupljanje osnovnih podataka o spomenicima. Oblik nadgrobnika i zastupljenost ukrasa najčešće ovise od vremena u kojem su nastali. Tako se na osnovi zastupljenih formi stećaka i nišana te evidentiranih ukrasa na njima, stećci mogu datirati u razvijeni srednji vijek (XIV i XV stoljeće). Ključne riječi: stećci, Mramorje, Bektića brdo, Bektići, Srebrenica

This study analyzes the possibilities of preserving the form and renovating the historic mosque with a wooden porch and minaret, based on the Osman Cehaja Mosque in Tuzla as an example. The research is based on direct observation of property over several decades and a comparison of formal qualities with other relevant structures of a similar type and period. Except for its foundation, no information is available on its past or potential interventions. It is only reasonable to assert that it was originally covered with a wood shake. It is assumed that its appearance has not changed since the early twentieth century, based on a common memory. The mosque was renovated four years ago. Analysis of the previous and current appearances showed that the complete renovation did not compromise its form. In this respect, it is feasible to renovate the mahalle mosque with a wooden porch and minaret while preserving its historical character. More challenging cases may necessitate more extensive investigation, planning, and experience.

The ATLAS detector at the Large Hadron Collider has been used to measure jet substructure modification and suppression in Pb+Pb collisions at a nucleon-nucleon center-of-mass energy $\sqrt{s_{_\mathrm{NN}}}=5.02~\mathrm{TeV}$ in comparison with $pp$ collisions at $\sqrt{s}=5.02~\mathrm{TeV}$. The Pb+Pb data, collected in 2018, have an integrated luminosity of $1.72~\mathrm{nb^{-1}}$, while the $pp$ data, collected in 2017, have an integrated luminosity of $260~\mathrm{pb}^{-1}$. Jets used in this analysis are clustered using the anti-$k_{t}$ algorithm with a radius parameter $R=0.4$. The jet constituents, defined by both tracking and calorimeter information, are used to determine the angular scale $r_\mathrm{g}$ of the first hard splitting inside the jet by reclustering them using the Cambridge-Aachen algorithm and employing the soft-drop grooming technique. The nuclear modification factor, $R_\mathrm{AA}$, used to characterize jet suppression in Pb+Pb collisions, is presented differentially in $r_\mathrm{g}$, jet transverse momentum, and in intervals of collision centrality. The $R_\mathrm{AA}$ value is observed to depend significantly on jet $r_\mathrm{g}$. Jets produced with the largest measured $r_\mathrm{g}$ are found to be twice as suppressed as those with the smallest $r_\mathrm{g}$ in central Pb+Pb collisions. The $R_\mathrm{AA}$ values do not exhibit a strong variation with jet $p_\mathrm{T}$ in any of the $r_\mathrm{g}$ intervals. The $r_\mathrm{g}$ and $p_\mathrm{T}$ dependence of jet $R_\mathrm{AA}$ is qualitatively consistent with a picture of jet quenching arising from coherence and provides the most direct evidence in support of this approach.