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H. Pretzsch, A. Bravo‐Oviedo, T. Hilmers, R. Ruiz‐Peinado, L. Coll, M. Löf, Shamim Ahmed, J. Aldea et al.

Heterogeneity of structure can increase mechanical stability, stress resistance and resilience, biodiversity and many other functions and services of forest stands. That is why many silvicultural measures aim at enhancing structural diversity. However, the effectiveness and potential of structuring may depend on the site conditions. Here, we revealed how the stand structure is determined by site quality and results from site-dependent partitioning of growth and mortality among the trees. We based our study on 90 mature, even-aged, fully stocked monocultures of Scots pine ( Pinus sylvestris L.) sampled in 21 countries along a productivity gradient across Europe. A mini-simulation study further analyzed the site-dependency of the interplay between growth and mortality and the resulting stand structure. The overarching hypothesis was that the stand structure changes with site quality and results from the site-dependent asymmetry of competition and mortality. First, we show that Scots pine stands structure across Europe become more homogeneous with increasing site quality. The coefficient of variation and Gini coefficient of stem diameter and tree height continuously decreased, whereas Stand Density Index and stand basal area increased with site index. Second, we reveal a site-dependency of the growth distribution among the trees and the mortality. With increasing site index, the asymmetry of both competition and growth distribution increased and suggested, at first glance, an increase in stand heterogeneity. However, with increasing site index, mortality eliminates mainly small instead of all-sized trees, cancels the size variation and reduces the structural heterogeneity. Third, we modelled the site-dependent interplay between growth partitioning and mortality. By scenario runs for different site conditions, we can show how the site-dependent structure at the stand level emerges from the asymmetric competition and mortality at the tree level and how the interplay changes with increasing site quality across Europe. Our most interesting finding was that the growth partitioning became more asymmetric and structuring with increasing site quality, but that the mortality eliminated predominantly small trees, reduced their size variation and thus reversed the impact of site quality on the structure. Finally, the reverse effects of mode of growth partitioning and mortality on the stand structure resulted in the highest size variation on poor sites and decreased structural heterogeneity with increasing site quality. Since our results indicate where heterogeneous structures need silviculture interventions and where they emerge naturally, we conclude that these findings may improve system understanding and modelling and guide forest management aiming at structurally rich forests.

Background: Coronary New blood in the vascular bed after Coronary Artery Bypass Grafting (CABG) may represent a turning point between ischemia and normal tissue nutrition. Its quantification can help to better understand coronary artery hemodynamics after revascularization. Objective: Quantification of coronary sinus blood flow changes over time after Coronary Artery Bypass Grafting (CABG) using Transthoracic Echocardiography (TTE). Methods: Prospective basic research, with repeated measurements on hospital sample of 61 patients whom CABG was conducted. We performed TTE recordings to measure CS flow before and two times after CABG (1 and 6 postoperative day). We measure CS diameter, Velocity Time Integral (VTI) and systemic hemodynamic data. Data needed for LV mass calculation were recorded once. During statistical analysis we define: α = 0,01, β = 0,01 (power = 1-β β= 0,99), Sample size = 60, Effect size= 0,68. We used ANOVA for Repeated Measures as main statistical test in SPSS. Results: Preoperatively we found low overall CS flow of 181 ±72 ml/min (0,68 ±0,30 ml/gram-LV/min). After surgery there was constant increase of CS flow from 276 ±79 ml/min (1,13 ±0,35 ml/gram-LV/min) first postoperative day, to 355 (±99) ml/min (1,30 ±0,46 ml/gram-LV/min) sixth postoperative day. Discussion: Amount of new blood was statistically significant after CABG with P<0,001. Same result was found after classifying patients per number of graft received, with the highest amount of new blood after four bypasses. Amount of new blood was not different if patient gets two or three bypasses. Conclusion: There was significantly new amount of blood in coronary bed after CABG, with constant increase over first 6 days.

Yuting Gu, Yu Wang, B. Adebisi, Guan Gui, H. Gačanin, Hikmet Sari

Blind signal recognition (BSR) is a significant research topic in the field of intelligent signal processing. However, existing BSR of space-time block codes (STBC) mainly depends on conventional algorithms, which require priori information and can only identify a relatively limited amount of STBC. Although deep learning (DL) has been widely used in signal recognition, so far there are few studies on BSR of STBC in multiple-input multiple-output (MIMO) systems using DL. In this paper, a blind recognition approach for STBC based on multichannel convolutional neural network (MCNN) is proposed. By leveraging the structure of multiple input channel, the in-phase and quadrature (IQ) channel information of STBC signals can be comprehensively extracted. Simulation results demonstrate that the proposed algorithm extends the recognizable STBC codes to 6, and can also improve the recognition accuracy in comparison to traditional convolutional neural network (CNN). The model proposed in this paper has been validated with two datasets and experimentally proved to be well generalized.

Can Kızılkale, F. Mehrabadi, Erfan Sadeqi Azer, Eva Pérez-Guijarro, Kerrie L. Marie, M. Lee, Chi-Ping Day, G. Merlino et al.

Marta Počkaj, R. Cerc-Korošec, Z. Popović, Ivana Balić, M. Sućeska, M. Dobrilović, Tomislav Balić

Atrial fibrillation is the most commonly experienced type of cardiac arrhythmia and is the most associated with substantial clinical occurrences and expenses. This arrhythmia often occurs in its "silent" asymptomatic form, revealed only after complications such as a stroke or congestive heart failure have transpired. New smart devices confer effective advantages in the detection of this heart arrhythmia, of which photoplethysmography-based smart devices have shown great potential, according to previous research. However, the solution becomes a problem as widespread use and high availability of various applications and smart devices may lead to substantial amounts of false and misleading recordings and information, causing unnecessary anxiety regarding arrhythmic occurrences diagnosed by the devices but not professionally confirmed. Thus, with most of the devices being photoplethysmography based for detection of atrial fibrillation, it is important to research devices studied up to this point to find the best smart device to detect the aforementioned arrhythmias.

D. Vejzović, Paulina Piller, R. Cordfunke, J. Drijfhout, T. Eisenberg, K. Lohner, N. Malanović

The need for alternative treatment of multi-drug-resistant bacteria led to the increased design of antimicrobial peptides (AMPs). AMPs exhibit a broad antimicrobial spectrum without a distinct preference for a specific species. Thus, their mechanism, disruption of fundamental barrier function by permeabilization of the bacterial cytoplasmic membrane is considered to be rather general and less likely related to antimicrobial resistance. Of all physico-chemical properties of AMPs, their positive charge seems to be crucial for their interaction with negatively charged bacterial membranes. Therefore, we elucidate the role of electrostatic interaction on bacterial surface neutralization and on membrane disruption potential of two potent antimicrobial peptides, namely, OP-145 and SAAP-148. Experiments were performed on Escherichia coli, a Gram-negative bacterium, and Enterococcus hirae, a Gram-positive bacterium, as well as on their model membranes. Zeta potential measurements demonstrated that both peptides neutralized the surface charge of E. coli immediately after their exposure, but not of E. hirae. Second, peptides neutralized all model membranes, but failed to efficiently disrupt model membranes mimicking Gram-negative bacteria. This was further confirmed by flow cytometry showing reduced membrane permeability for SAAP-148 and the lack of OP-145 to permeabilize the E. coli membrane. As neutralization of E. coli surface charges was achieved before the cells were killed, we conclude that electrostatic forces are more important for actions on the surface of Gram-negative bacteria than on their cytoplasmic membranes.

M. Kowal, P. Sorokowski, K. Pisanski, J. Valentova, M. Varella, D. Frederick, Laith Al-Shawaf, Felipe E. García et al.

Background: In the academic world, the debate continues on the subject of how far a lack of vitamin D can affect the healing of various wounds. Objective: To determine if basal serum levels of vitamin D significantly influence clinical parameters linked to post-extraction wound healing after surgical removal of impacted/semi-impacted third molars. Methods: A total of 23 patients were included in this study. Clinical outcome parameters were: edema, trismus, pain, soft tissue healing, and dry socket signs. The research was divided into four stages. Results: Due to the high prevalence of hypovitaminosis D (91%), patients were classified into an insufficient (≥ 20 ng/ml) or a deficient group (<20 ng/ml). The results showed no statistically significant differences in pain, edema, trismus, or soft tissue healing between those two groups. A slight statistical interaction was observed in the clinical parameters related to edema and trismus assessment, but not statistically significant. We did not notice signs of “dry socket” on any of the patients. Conclusion: Within its limitations (low number of patients, high prevalence of vitamin D deficiency), this pilot study failed to find a significant influence of serum vitamin D concentrations in wound healing or post-surgery symptom (pain, edema, trismus) development after third molar extraction. Further clinical investigations are necessary to elaborate on this function of vitamin D more precisely.

A. Šukalo, Jasna Džananović Jaganjac, A. Avdić, U. Glamočlija, Zeljka Popovic, A. Boloban, M. Čampara, M. Mehić

Objective. The objective of this non-interventional post-marketing clinical trial was to analyze the antihypertensive effect and safety of a fixed combination of perindopril and indapamide in the treatment of unregulated essential hypertension. Patients and Methods. The prospective clinical trial included patients aged 20 to 75 years with essential hypertension and blood pressure values ≥140/90 mmHg at baseline. On the basis of the investigator’s decision, patients received 2 mg perindopril + 0.625 mg indapamide (group 2+0.625) or 4 mg perindopril + 1.25 mg indapamide (group 4+1.25). Results. The study included 1173 patients (426 patients in group 2+0.625 and 747 patients in group 4+1.25) at 27 investigational centers in Bosnia and Herzegovina. Mean blood pressure values at baseline and visits after nine months were significantly higher in the 4+1.25 group compared to the 2+0.625 group. There was a significant drop in systolic and diastolic blood pressure in both groups. The target values of systolic and diastolic blood pressure, according to the European Society of Cardiology (2018), were reached after nine months of therapy by more than 80% of patients in the 2+0.625 group, and this number was significantly higher compared to the 4+1.25 group where more than 60% of patients reached target values. Newly diagnosed patients had a better response to therapy. The percentage of patients receiving additional antihypertensive therapy decreased by the end of the study. Age, gender and the existence of diabetes mellitus were identified as negative predictors of target blood pressure achievement. The therapy showed a good safety profile. Conclusion. A fixed combination of perindopril and indapamide was effective and safe in the treatment of unregulated essential hypertension.

Objectives Oral health in children is additionally burdened with the presence of dental fear and anxiety (DFA). These clinical psychologic entities in their progressive stages inevitably lead to avoidance of dental appointments, which makes prevention and therapy of oral diseases more difficult. Upon the onset of DFA in general, as one of the emotional outcomes of stress in a dental office, most children patients could define the specific stressors that were most intense for them, which could predict the presence of DFA. Aim To examine the predictors of DFA presence in 9-12-year-old children, and investigate how they could explain the DFA occurrence in study participants. Material and Methods The sample consisted of 200 children aged from 9 to 12 years. The DFA presence was determined by the modified version of the CFSS-DS scale. The child's behavior in the dental office during the treatment was evaluated by the trained observer using Venham anxiety and behavior rating scales. Socioeconomic status, characteristics of dental office visits, and previous caries experience were also analyzed. Results The main DFA predictors were related to invasive dental treatments, where the behavior during dental treatment was the most accurate expression of the DFA appearance. Conclusions Invasive dental procedures are the main stressful factor for DFA occurrence. Predisposing factors could strengthen the DFA occurrence.

S. Vranić, G. Basu, D. Hall, Z. Gatalica

In the present review, we briefly discuss the breakthrough advances in precision medicine using a tumor-agnostic approach and focus on BRAF treatment modalities, the mechanisms of resistance and the diagnostic approach in cancers with BRAF mutations. Tumor-type agnostic drug therapies work across cancer types and present a significant novel shift in precision cancer medicine. They are the consequence of carefully designed clinical trials that showed the value of tumor biomarkers, not just in diagnosis but in therapy guidance. Six tumor-agnostic drugs (with seven indications) have been approved through October 2022 by FDA. The first tumor-agnostic treatment modality was pembrolizumab for MSI-H/dMMR solid tumors, approved in 2017. This was followed by approvals of larotrectinib and entrectinib for cancers with NTRK fusions without a known acquired resistance mutation. In 2020, pembrolizumab was approved for all TMB-high solid cancers, while a PD-L1 inhibitor dostarlimab-gxly was approved for dMMR solid cancers in 2021. A combination of BRAF/MEK inhibitors (dabrafenib/trametinib) was approved as a tumor-agnostic therapy in June 2022 for all histologic types of solid metastatic cancers harboring BRAFV600E mutations. In September 2022, RET inhibitor selpercatinib was approved for solid cancers with RET gene fusions. Conclusion. Precision cancer medicine has substantially improved cancer diagnostics and treatment. Tissue type-agnostic drug therapies present a novel shift in precision cancer medicine. This approach rapidly expands to provide treatments for patients with different cancers harboring the same molecular alteration.

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