Significant Reduction Research Articles

Progress in site-specific cancer mortality in Canada over the last 70 years

In Canada, the absolute number of cancer deaths has been steadily increasing, however, age-standardized cancer mortality rates peaked decades ago for most cancers. The objective of this study was to estimate the reduction in deaths for each cancer type under the scenario where peak mortality rates had remained stable in Canada. Data for this study were obtained the Global Cancer Observatory and Statistics Canada. We estimated age-standardized mortality rates (ASMR, per 100,000) from 1950 to 2022, standardized to the 2011 Canadian standard population. We identified peak mortality rates and applied the age-specific mortality rates from the peak year to the age-specific Canadian population estimates for subsequent years (up to 2022) to estimate the number of expected deaths. Avoided cancer deaths were the difference between the observed and expected number of cancer deaths. There have been major reductions in deaths among cancers related to tobacco consumption and other modifiable lifestyle habits (417,561 stomach; 218,244 colorectal; 186,553 lung; 66,281 cervix; 32,732 head and neck; 27,713 bladder; 22,464 leukemia; 20,428 pancreas; 8863 kidney; 3876 esophagus; 290 liver). There have been 201,979 deaths avoided for female-specific cancers (breast, cervix, ovary, uterus). Overall, there has been a 34% reduction in mortality for lung cancer among males and a 9% reduction among females. There has been a significant reduction in cancer mortality in Canada since site-specific cancer mortality rates peaked decades ago for many cancers. This shows the exceptional progress made in cancer control in Canada due to substantial improvements in prevention, screening, and treatment. This study highlights priority areas where more attention and investment are needed to achieve progress.

Clinical Evaluation of a 2-Minute Ultrafast Brain MR Protocol for Evaluation of Acute Pathology in the Emergency and Inpatient Settings.

The use of MR imaging in emergency settings has been limited by availability, long scan times, and sensitivity to motion. This study assessed the diagnostic performance of an ultrafast brain MR imaging protocol for evaluation of acute intracranial pathology in the emergency department and inpatient settings. Sixty-six adult patients who underwent brain MR imaging in the emergency department and inpatient settings were included in the study. All patients underwent both the reference and the ultrafast brain MR protocols. Both brain MR imaging protocols consisted of T1-weighted, T2/T2*-weighted, FLAIR, and DWI sequences. The ultrafast MR images were reconstructed by using a machine-learning assisted framework. All images were reviewed by 2 blinded neuroradiologists. The average acquisition time was 2.1 minutes for the ultrafast brain MR protocol and 10 minutes for the reference brain MR protocol. There was 98.5% agreement on the main clinical diagnosis between the 2 protocols. In head-to-head comparison, the reference protocol was preferred in terms of image noise and geometric distortion (P < .05 for both). The ultrafast ms-EPI protocol was preferred over the reference protocol in terms of reduced motion artifacts (P < .01). Overall diagnostic quality was not significantly different between the 2 protocols (P > .05). The ultrafast brain MR imaging protocol provides high accuracy for evaluating acute pathology while only requiring a fraction of the scan time. Although there was greater image noise and geometric distortion on the ultrafast brain MR protocol images, there was significant reduction in motion artifacts with similar overall diagnostic quality between the 2 protocols.

Assessing the Long-Term (48-Week) Effectiveness, Safety, and Tolerability of Fremanezumab in Migraine in Real Life: Insights from the Multicenter, Prospective, FRIEND3 Study.

Long-term (1-year) fremanezumab treatment proved to be effective, safe, and well tolerated in individuals with migraine and < 2 medication clusters in a randomized controlled trial (RCT). We aimed to assess real-world evidence (RWE), long-term effectiveness, tolerability, and safety of fremanezumab in people with high-frequency episodic migraine (HFEM) or chronic migraine (CM) with > 3 treatment failures and various comorbidities. A 48-week, prospective, multicenter (n = 26), cohort study assessed fremanezumab's effectiveness, safety, and tolerability in consecutive adults with HFEM or CM with > 3 treatment failures. Primary endpoint was variation from baseline in monthly migraine days (MMD) in HFEM and monthly headache days (MHD) in CM at weeks45-48. Secondary endpoints were changes in monthly analgesic medications, Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), and the Migraine Disability Assessment Scale (MIDAS) scores and ≥ 50%, ≥ 75%, and 100% responder rates. Of 533 participants who had received ≥ 1 fremanezumab dose, 130 were treated for ≥ 48weeks and considered for effectiveness analysis. No participant missed any treatment dosage every other consecutive month during the 12-month period. fremanezumab significantly (p < 0.001) reduced both MMD (- 6.4) in HFEM and MHD (- 14.5) in CM. Secondary endpoints: a significant reduction (p < 0.001) was observed in monthly analgesic medications (HFEM -6.0; CM -16.5), NRS (HFEM -3.4; CM -3.4), HIT-6 (HFEM -16.9; CM -17.9) and MIDAS score (HFEM -50.4; CM -76.6). The ≥ 50%, ≥ 75%, and 100% response rates to fremanezumab were 75.5%, 36.7%, and 2% in HFEM and 71.6%, 44.4%, and 3.7% in CM. Corresponding response rates were 60.5%, 37.2%, and 2.3% in individuals with psychiatric comorbidities, 74.2%, 50%, and 4.8% in CM with medication overuse, and 60.9%, 39.1%, and 4.3% in CM with medication overuse and psychiatric comorbidities. Mild and transient treatment-emergent adverse events occurred in 7.8% of the participants. No subject discontinued the treatment for any reason. This RWE study documents that long-term fremanezumab treatment is highly effective and remarkably well tolerated in subjects with HFEM or CM with multiple (> 3) therapeutic failures, even in the presence of concomitant medication overuse, psychiatric comorbidities, or both. The effectiveness-to-tolerability ratio appears to be better in RWE than in RCTs.

SOLUBILITY ENHANCEMENT OF ATAZANAVIR BY HYDROTROPIC SOLUBILIZATION TECHNIQUE

Objective: The present study aims to increase the solubility and dissolution of atazanavir sulfate (ATZ) by employing a hydrotropic solubilization technique. Methods: ATZ is a poorly soluble drug classified under the biopharmaceutical classification system (BCS)-II, which accounts for its poor oral bioavailability. Different hydrotropic agents, such as urea and sodium benzoate and their combinations at different ratios were prepared. The prepared hydrotropes were systematically investigated for compatibility between the drug and excipients using Fourier Transform Infra-Red Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) approaches. Further, in order to understand the conversion from crystalline to amorphous nature, X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM) studies were also performed. The formulation of a mixed hydrotropic mixture comprising urea (2.5% w/v) and sodium benzoate (5% w/v) exhibited a 100.35±1.7 % drug release at 0.25 h with higher dissolution efficiency as compared with other batches of individual hydrotrope, mixed hydrotropes as well as pure drug. Results: FTIR studies revealed that there is no incompatibility between the drug and the selected hydrotropes. DSC studies also confirmed the fact that there is no interaction between the drug and the hydrotropes by the disappearance of an endothermic peak. XRD studies revealed that there was a significant reduction in the intensity of peaks, indicating the conversion of crystalline to the amorphous form. The SEM studies indicated that the drug appears crystalline in the shape of an irregular tiny prismatic needle, indicating its crystallinity. At the same time, the hydrotrope mixtures appeared in agglomerated form with a porous nature, which may be accountable for its increase in solubility. The hydrotropes prepared using urea alone exhibited an increase in solubility of 4.42 folds, and the hydrotrope prepared using sodium benzoate alone exhibited an increase in solubility of 3.178 folds; the combination hydrotropes of urea and sodium benzoate exhibited an increase in solubility of 8.78 folds in water as compared to pure drug. The drug release from the mixed hydrotropes obeys zero-order kinetics with diffusion as the main mechanism. Conclusion: The present investigation concluded that the combination of hydrotropes enhanced the solubility of the aqueous soluble drug ATZ. However, in vivo studies are essential to establish its potential effect.

Neurocognitive correlates of metabolic dysregulation in individuals with mood disorders: a systematic review and meta-analysis.

Individuals with mood disorders are predisposed to metabolic dysfunction, while those with metabolic dysregulation such as diabetes and obesity experience more severe depressive symptoms. Both metabolic dysfunction and mood disorders are independently associated with cognitive deficits. Therefore, given their close association, this study aimed to explore the association between metabolic dysfunction in individuals with mood disorders in relation to cognitive outcomes. A comprehensive search comprised of these three domains was carried out; a random-effects meta-analysis pooling mean cognitive outcomes was conducted (PROSPERO ID: CRD42022295765). Sixty-three studies were included in this review; 26 were synthesized in a quantitative meta-analysis. Comorbid metabolic dysregulation was associated with significantly lower global cognition among individuals with mood disorders. These trends were significant within each mood disorder subgroup, including major depressive disorder, bipolar disorder, and self-report depression/depressive symptoms. Type 2 diabetes was associated with the lowest cognitive performance in individuals with mood disorders, followed by peripheral insulin resistance, body mass index ⩾25 kg/m2, and metabolic syndrome. Significant reduction in scores was also observed among individual cognitive domains (in descending order) of working memory, attention, executive function, processing speed, verbal memory, and visual memory. These findings demonstrate the detrimental effects of comorbid metabolic dysfunction in individuals with mood disorders. Further research is required to understand the underlying mechanisms connecting mood disorders, metabolism, and cognition.

Allelopathic Responses of Crop Species to Chromolaena odorata Root Exudate Extracts: A Comprehensive Study

This study investigates the allelopathic effects of root exudate extracts from Chromolaena odorata on the germination and growth of six crop species. The results reveal variable sensitivity among the species, with the control treatment consistently exhibiting superior germination percentages. Initially, some species, including Abelmoschus esculentus (okra), Solanum lycopersicum (tomato), and Cicer arietinum (chickpea), experienced a substantial decline in germination, indicating a potential inhibitory effect of the exudates, although partial recovery was observed in subsequent treatments. Phaseolus vulgaris (common bean) displayed a moderate decrease, while Zea mays (corn) exhibited the most significant drop in germination rates, albeit with slight recovery at higher concentrations of exudates. Conversely, Cucumis sativus (cucumber) appeared least affected by the exudates. Moreover, all species demonstrated reductions in shoot and root lengths with increasing concentrations of exudates. Chlorophyll content analysis revealed a significant reduction across most treatments, highlighting concerns regarding photosynthetic efficiency and overall plant health. The species-specific response to root exudates suggests varying metabolic or adaptive mechanisms among crops. Additionally, malondialdehyde (MDA) levels, indicative of oxidative stress, varied among species, with A. esculentus and P. vulgaris showing a dose-dependent increase, while S. lycopersicum displayed a peak at intermediate treatment levels. Z. mays exhibited marginal elevation in MDA content, potentially indicating the presence of protective compounds within the exudates. Conversely, C. arietinum and C. sativus showed a steady increase in MDA, suggesting limited mitigation of allelopathic effects. These findings feature the complexity of allelopathic interactions and highlight the need for further research into active compounds and their modes of action to develop sustainable weed management strategies while safeguarding crop health. Understanding these dynamics is crucial for maximizing the potential benefits of allelopathy in agriculture.

DYNAMICS OF MORTALITY FROM DISEASES OF THE CIRCULATORY ORGANS IN BULGARIA, SOUTH CENTRAL REGION AND PLOVDIV PROVINCE

In the European Union, Bulgaria ranks first in terms of mortality and last in terms of life expectancy. According to Eurostat data for 2018 in Bulgaria, from 2011 until this moment, the coefficients of both preventable mortality with good prevention and mortality preventable with good treatment are higher than the corresponding values for the EU as a whole. There are no prospects for their improvement. The rate of preventable mortality with good prophylaxis reached 226 per 100,000 population, which is significantly higher than the value of the rate in the whole EU (160 per 100,000). On the one hand, weak primary prevention and health promotion, and on the other hand, the need to improve protocols for diagnosis and treatment of the leading causes of death can be pointed out as reasons.The aim of the present study is to perform a comparative analysis of the dynamics of mortality from diseases of the circulatory organs for Bulgaria, its South Central Region and the Plovdiv province as part of this region.Materials and methods: documentary analysis - based on data from the National Statistical Institute; inductive and deductive methods; comparative analysis; structural analysis; economical analysis; statistical methods - analysis of the dynamics of phenomena, tabular and graphic analyzes - to visualize the obtained results.Results: Both for Bulgaria as a whole, as well as for its South Central region and the Plovdiv province, there is a trend of increasing mortality (per 100,000 people of the population) from diseases of the circulatory organs.Conclusion: From the data of our study, it is clear that, in general, for the observed 10-year period, and more specifically for the last of the years under consideration - 2022, for the entire country, the highest relative share in mortality (per 100,000 population) is occupied by other diseases of the heart. For the South Central region, the mortality rate from ischemic heart disease is the highest. The situation is similar for the Plovdiv province, as part of this region, where the relative share is also the highest - a noticeable 44.0% of the mortality from IHD.Recommendations: A comprehensive approach and addressing health inequities in all areas aimed at reducing the burden of cardiovascular disease as part of non-communicable chronic diseases is imperative. Of primary importance is the fact that health promotion and disease prevention can lead to a significant reduction in this burden.

Load Frequency Control Strategy for Islanded Microgrid Based on SCQ(λ) Algorithm

In the evolving landscape of power grids, where green transportation and intermittent clean energy play a crucial role, ensuring the security and reliability of the urban network is of utmost importance. However, the increasing volatility associated with these new energy sources poses a challenge to the traditional control methods. The large-scale integration of new energy in microgrids often leads to frequency instability and deviation in control performance standards. Addressing these issues, this paper introduces the SCQ(λ) algorithm, which accurately estimates the system's state to enhance controller capabilities. To evaluate the effectiveness of the proposed SCQ(λ) algorithm, the authors employ a load frequency control model in our simulation. In this model, they introduce various load change disturbances, including sine waves, square waves, and step disturbances to simulate realistic scenarios encountered in power systems. Throughout the simulation, they observe a significant reduction in frequency deviation in the case of step perturbation, with the deviation value decreasing by 0.0096.

On the fair scheduling of truck drivers in delivery companies: balancing fairness and profit

AbstractFairness is crucial in transportation systems to ensure that all drivers are treated equally and have the same opportunities. Fair payment policies, equal access to work opportunities, and fair scheduling are some of the policies delivery companies implement to ensure fairness between drivers. In this paper, we study a fair scheduling mixed-integer programming problem where we consider a bi-objective function that aims to maximize profit and improve fairness between drivers by minimizing the maximum deviation from the average driving time. To solve this problem, we employ the weighted comprehensive criterion method and propose an iterative population-based heuristic. The results show that the relative gap between the heuristic and exact approach is acceptable. We also report the fairness price which is the relative difference between total profit with and without incorporating fairness. We find out that improving fairness between drivers does not always lead to a significant reduction in total profit. When the reduction in total profit is important, we recommend formulating the scheduling problem differently where instead of minimizing the maximum deviation from the average driving time, drivers are rewarded when their driving times are longer than the average. We explore incorporating the cost of rewarding these drivers in the objective function.

Exploring the Nexus: Gaseous Micro-embolic Activity and Pressure Drop on ALONE ECMO Oxygenator

AbstractThe role of inlet and outlet oxygenator pressure know as pressure drop (ΔP) in the elimination of the gaseous micro-emboli activity (GMEA) remains obscured during Extracorporeal Membrane Oxygenation (ECMO) and Minimally Invasive Extracorporeal Circulation (MiECC). There is conflicting literature on the role of pressure drop in oxygenators as well as on oxygenating performance, fluid dynamics and in the role of gaseous micro-embolic activity elimination. We analyzed 14 procedures, 10 MiECC with polypropylene fibers ALONE AF oxygenator and 4 ECMO with polymethylpentene Alone ECMO Oxygenator (Eurosets, SRL, Medolla,Italy), in the central and peripheral cannulation configuration, respectively, through the use of GAMPT BCC300 for air gas micro-emboli (GME) in relation to the ΔP of Oxygenator and incidence of cavitation. The groups of MiECC, Central Cannulation VS Peripheral Cannulation reported: mean values for cavitation n° of bubbles was 330 ± 12 vs 80 ± 13; 1.5 vs 0% reported a diameter &gt; 500 μm; GME volume was 1.51 ± 0.2 vs 0.121 ± 0.2 (μL) in the arterial line, the mean ΔP of oxygenator reported was 89 ± 11 vs 130 ± 29 mmHg. The groups of ECMO, Central Cannulation VS Peripheral Cannulation reported: mean values for cavitation n° of bubbles was 470 ± 12 vs 140 ± 17; 2.1 vs 0% reported a diameter &gt; 500 μm; GME volume was 2.5 ± 0.5 vs 0.355 ± 0.7 (μL) in the arterial line, the mean ΔP of oxygenator reported was 88 ± 15vs 150 ± 23 mmHg. In this report, patients with low pressure drop in the oxygenator reported a statistically significant increase in GMEA in the arterial line of the circuit for each cavitation phenomenon, compared to the group with high pressure drop in the oxygenator who reported a reduced GMEA. In this report, oxygenators with higher pressure drops demonstrated a significant reduction of GMEA, however, further studies are needed to confirm these results.

Neuronal deletion of Gtf2i results in developmental microglial alterations in a mouse model related to Williams syndrome.

Williams syndrome (WS) is a genetic neurodevelopmental disorder caused by a heterozygous microdeletion, characterized by hypersociability and unique neurocognitive abnormalities. Of the deleted genes, GTF2I has been linked to hypersociability in WS. We have recently shown that Gtf2i deletion from forebrain excitatory neurons, referred to as Gtf2i conditional knockout (cKO) mice leads to multi-faceted myelination deficits associated with the social behaviors affected in WS. These deficits were potentially mediated also by microglia, as they present a close relationship with oligodendrocytes. To study the impact of altered myelination, we characterized these mice in terms of microglia over the course of development. In postnatal day 30 (P30) Gtf2i cKO mice, cortical microglia displayed a more ramified state, as compared with wild type (controls). However, postnatal day 4 (P4) microglia exhibited high proliferation rates and an elevated activation state, demonstrating altered properties related to activation and inflammation in Gtf2i cKO mice compared with control. Intriguingly, P4 Gtf2i cKO-derived microglial cells exhibited significantly elevated myelin phagocytosis invitro compared to control mice. Lastly, systemic injection of clemastine to P4 Gtf2i cKO and control mice until P30, led to a significant interaction between genotypes and treatments on the expression levels of the phagocytic marker CD68, and a significant reduction of the macrophage/microglial marker Iba1 transcript levels in the cortex of the Gtf2i cKO treated mice. Our data thus implicate microglia as important players in WS, and that early postnatal manipulation of microglia might be beneficial in treating inflammatory and myelin-related pathologies.

Variability of stock status walleye pollock fishery

The analysis of the variability of walleye pollock stocks assessment and fisheries showed that in most areas the degree of exploitation is at a low level (4,7–13,5%), with the exception of the Navarinsky region of the Bering Sea, the coast of eastern Kamchatka, the northern Kuril Islands and western Sakhalin (16,7–18,9%). Climate change has a significant impact on the of walleye pollock stocks assessment. Positive anomalies of the PDO climate index (Pacific Decadal Oscillation) create favorable conditions for northern populations, whereas for southern populations living on the southern border of the area, on the contrary, those periods when negative anomalies are noted are more comfortable. Subject to the implementation of the cooling scenario in the North Pacific Ocean, walleye pollock biomass centers may shift to the southern regions (the economic zone of the DPRK), which will lead to a significant reduction in catches in the economic zones of the Russian Federation and the United States, which are currently the main players in the walleye pollock market.

Magnetic Resonance Imaging in Breast Cancer Tissue In Vitro after PDT Therapy.

Photodynamic therapy (PDT) is increasingly used in modern medicine. It has found application in the treatment of breast cancer. The most common cancer among women is breast cancer. We collected cancer cells from the breast from the material received after surgery. We focused on tumors that were larger than 10 mm in size. Breast cancer tissues for this quantitative non-contrast magnetic resonance imaging (MRI) study could be seen macroscopically. The current study aimed to present findings on quantitative non-contrast MRI of breast cancer cells post-PDT through the evaluation of relaxation times. The aim of this work was to use and optimize a 1.5 T MRI system. MRI tests were performed using a clinical scanner, namely the OPTIMA MR360 manufactured by General Electric HealthCare. The work included analysis of T1 and T2 relaxation times. This analysis was performed using the MATLAB package (produced by MathWorks). The created application is based on medical MRI images saved in the DICOM3.0 standard. T1 and T2 measurements were subjected to the Shapiro-Wilk test, which showed that both samples belonged to a normal distribution, so a parametric t-test for dependent samples was used to test for between-sample variability. The study included 30 sections tested in 2 stages, with consistent technical parameters. For T1 measurements, 12 scans were performed with varying repetition times (TR) and a constant echo time (TE) of 3 ms. For T2 measurements, 12 scans were performed with a fixed repetition time of 10,000 ms and varying echo times. After treating samples with PpIX disodium salt and bubbling with pure oxygen, PDT irradiation was applied. The cell relaxation time after therapy was significantly shorter than the cell relaxation time before PDT. The cells were exposed to PpIX disodium salt as the administered pharmacological substance. The study showed that the therapy significantly affected tumor cells, which was confirmed by a significant reduction in tumor cell relaxation time on the MRI results.

Real-world experience of using stereotactic radiotherapy combined with anti-vascular endothelial growth factor to treat neovascular AMD.

Adjunctive treatment or longer-acting drugs are required to treat nAMD to help ease burdens for patients and hospital clinics alike. Stereotactic therapy is one such option, providing a reduction in the number of injections over time. To determine the clinical outcomes in a cohort of patients with nAMD receiving a combination therapy of stereotactic radiotherapy (SRT) with intravitreal anti-VEGF injections (IVI). A retrospective analysis of 74 patients with nAMD, who had received IVI and SRT (16 Gray maximum dose to the macula) at a large tertiary university eye hospital, between March 2018 and September 2019 was performed. The number of IVIs, visual acuity (VA), and central retinal thickness (CRT) were evaluated at 12, 24, and 36months after patients received SRT and compared to the same time interval prior to SRT. Follow-up data at 12, 24, and 36months following and prior to SRT was available for 74, 48, and 22 patients respectively. Overall there was a significant reduction in the number of injections post-SRT. Twelve months following SRT, the median number of IVI was reduced by 1 (p < 0.05). The reduction in the median number of IVI was significantly reduced by 3 and 6 injections at 24- and 36-month follow-up respectively (p < 0.05). The CRT was significantly reduced post-SRT compared to the baseline values at all time periods. There was no statistically significant difference in VA at 12-month follow-up compared to baseline. The VA, however, significantly decreased at 24- and 36-month follow-up (p < 0.05). A therapy combining SRT with IVI has shown an overall reduction in the number of injections required in nAMD patients at 12, 24, and 36months following SRT compared to IVI treatment alone. These real-world outcomes are comparable to other studies while also confirming the maintenance of the reduced frequency of required IVI for patients with nAMD.

Comparison of the therapeutic efficacy of magneto-LED therapy and magnetostimulation applied as the adjuvant treatment of venous leg ulcers – preliminary study

ABSTRACT Purpose Venous leg ulcers are chronic wounds that are difficult to cure. The aim of the study was to compare the therapeutic efficacy of two methods of physical medicine – magneto-LED therapy and magnetostimulation, applied as adjuvant treatment in the treatment of venous leg ulcers. Methods The study included 81 patients, 37 male (45.6%) and 44 female (54.3%) ones, age range between 45 and 90 years, with venous leg ulcers. The patients were assigned to two study groups: magneto-LED therapy (group 1) or magnetostimulation (group 2). In both groups, a total of 40 daily procedures were performed. Wound healing was evaluated using computerized planimetry and the pain intensity on numeric rating scale. Results After treatment, the decrease in healing rate in group 1 was statistically significantly higher in comparison to group 2 (p < 0.001), while a statistically significant reduction in the surface area of ulcers was obtained, amounting on the average from 6.34 ± 1.29 cm2 to 2.31 ± 1.25 cm2 in group 1 (p < 0.001), and from 6.52 ± 1.20 cm2 to 4.79 ± 1.17 cm2 in group 2 (p < 0.001). The percentage changes of ulcers area in group 1 (64.21 ± 17.94%) were statistically significantly greater as compared to group 2 (25.87 ± 14.07%) (p < 0.001). After treatment, the decrease in pain relief in group 1 was statistically significantly higher in comparison to group 2 (p = 0.006), while pain intensity after treatment decreased statistically significantly in both compared groups of patients (p < 0.001). Conclusions Magneto-LED therapy and magnetostimulation caused significant reduction of surface area of the treated venous leg ulcers and pain intensity, yet magneto-LED therapy was more efficient. Both evaluated methods also significantly reduced pain intensity.

Spatially Amplified and Rigid Junction in Diblock Copolymers: Reduced Microphase Separation Size via Interface Expansion.

We introduce an approach in diblock copolymer design, where modifying the junction point with rigid bulky monomer expands the cross-sectional area of the interface and leads to a decrease in the repeat period. Using living anionic polymerization, we synthesized a series of dialkynyl midfunctionalized poly(styrene-b-methyl methacrylate) (PSM-DA) and functionalized them using the thiol-alkyne click reaction with specifically selected rigid bulky monomers: PSS-(3-mercapto)propyl-heptaisobutyl substituted (PSS) and 1-adamantanethiol (ADA). This modification, though involving only a single monomer unit within the diblock copolymer structure, brought about a significant reduction in domain size, with PSS and ADA reducing it by 18% and 15%, respectively. The results indicate a method for reducing the domain sizes of block copolymers, which could lead to advancements in lithography and various nanotechnological applications.

Effects of positive end-expiratory pressure on regional cerebral oxygen saturation in elderly patients undergoing thoracic surgery during one-lung ventilation: a randomized crossover-controlled trial

BackgroundA significant reduction in regional cerebral oxygen saturation (rSO2) is commonly observed during one-lung ventilation (OLV), while positive end-expiratory pressure (PEEP) can improve oxygenation. We compared the effects of three different PEEP levels on rSO2, pulmonary oxygenation, and hemodynamics during OLV.MethodsForty-three elderly patients who underwent thoracoscopic lobectomy were randomly assigned to one of six PEEP combinations which used a crossover design of 3 levels of PEEP—0 cmH2O, 5 cmH2O, and 10 cmH2O. The primary endpoint was rSO2 in patients receiving OLV 20 min after adjusting the PEEP. The secondary outcomes included hemodynamic and respiratory variables.ResultsAfter exclusion, thirty-six patients (36.11% female; age range: 60–76 year) were assigned to six groups (n = 6 in each group). The rSO2 was highest at OLV(0) than at OLV(10) (difference, 2.889%; [95% CI, 0.573 to 5.204%]; p = 0.008). Arterial oxygen partial pressure (PaO2) was lowest at OLV(0) compared with OLV(5) (difference, -62.639 mmHg; [95% CI, -106.170 to -19.108 mmHg]; p = 0.005) or OLV(10) (difference, -73.389 mmHg; [95% CI, -117.852 to -28.925 mmHg]; p = 0.001), while peak airway pressure (Ppeak) was lower at OLV(0) (difference, -4.222 mmHg; [95% CI, -5.140 to -3.304 mmHg]; p < 0.001) and OLV(5) (difference, -3.139 mmHg; [95% CI, -4.110 to -2.167 mmHg]; p < 0.001) than at OLV(10).ConclusionsPEEP with 10 cmH2O makes rSO2 decrease compared with 0 cmH2O. Applying PEEP with 5 cmH2O during OLV in elderly patients can improve oxygenation and maintain high rSO2 levels, without significantly increasing peak airway pressure compared to not using PEEP.Trial registrationChinese Clinical Trial Registry ChiCTR2200060112 on 19 May 2022.

MITF regulates the subcellular location of HIF1α through SUMOylation to promote the invasion and metastasis of daughter cells derived from polyploid giant cancer cells.

High concentrations of cobalt chloride (CoCl2) can induce the formation of polyploid giant cancer cells (PGCCs) in various tumors, which can produce daughter cells with strong proliferative, migratory and invasive abilities via asymmetric division. To study the role of hypoxia‑inducible factor (HIF) 1α in the formation of PGCCs, colon cancer cell lines Hct116 and LoVo were used as experimental subjects. Western blotting, nuclear and cytoplasmic protein extraction and immunocytochemical experiments were used to compare the changes in the expression and subcellular localization of HIF1α, microphthalmia‑associated transcription factor (MITF), protein inhibitor of activated STAT protein4 (PIAS4) and von Hippel‑Lindau disease tumor suppressor (VHL) after treatment with CoCl2. The SUMOylation of HIFα was verified by co‑immunoprecipitation assay. After inhibiting HIF1α SUMOylation, the changes in proliferation, migration and invasion abilities of Hct116 and LoVo were compared by plate colony formation, wound healing and Transwell migration and invasion. In addition, lysine sites that led to SUMOylation of HIF1α were identified through site mutation experiments. The results showed that CoCl2 can induce the formation of PGCCs with the expression level of HIF1α higher in treated cells than in control cells. HIF1α was primarily located in the cytoplasm of control cell. Following CoCl2 treatment, the subcellular localization of HIF1α was primarily in the nuclei of PGCCs with daughter cells (PDCs). After treatment with SUMOylation inhibitors, the nuclear HIF1α expression in PDCs decreased. Furthermore, their proliferation, migration and invasion abilities also decreased. After inhibiting the expression of MITF, the expression of HIF1α decreased. MITF can regulate HIF1α SUMOylation. Expression and subcellular localization of VHL and HIF1α did not change following PIAS4 knockdown. SUMOylation of HIF1α occurs at the amino acid sites K391 and K477 in PDCs. After mutation of the two sites, nuclear expression of HIF1α in PDCs was reduced, along with a significant reduction in the proliferation, migration and invasion abilities. In conclusion, the post‑translation modification regulated the subcellular location of HIF1α and the nuclear expression of HIF1α promoted the proliferation, migration and invasion abilities of PDCs. MITF could regulate the transcription and protein levels of HIF1α and participate in the regulation of HIF1α SUMOylation.

MRAS Using Lyapunov Theory with Sliding Modes for a Fixed-Wing MAV

This work applies an adaptive PD controller based on MRAS (Model Reference Adaptive System) using Lyapunov theory with sliding mode theory to a Fixed-wing MAV (Mini Aerial Vehicle). The objective is to design different adjustment mechanisms to obtain a robust adaptive control law in the presence of unknown perturbation due to wind gusts. Four adjustment mechanisms applied to an adaptive PD controller are compared. The adjustment mechanisms are Lyapunov theory, Lyapunov theory with first-order sliding mode, Lyapunov theory with second-order sliding mode, and Lyapunov theory with high-order sliding mode. Finally, after several simulations, a significant reduction and almost elimination of the unknown perturbations are presented with the addition of the sliding mode theory in the design of the adjustment mechanism for the adaptive PD controller.

Effects of Thermosonication on the Antioxidant Capacity and Physicochemical, Bioactive, Microbiological, and Sensory Qualities of Blackcurrant Juice.

This study investigated the effects of thermosonication (TS) on the quality of blackcurrant juice, along with its physicochemical properties, bioactive compounds, antioxidant capacity, and microbiological and sensory qualities. The treatments included raw juice (RJ), pasteurized juice (90 °C, 1 min, PJ), and thermosonicated juice (480 W, 40 kHz at 40, 50, or 60 °C, for 10, 20, 30, or 40 min, TJ). The results indicated that the effects of pasteurization and thermosonication on the pH, total soluble solids, and titratable acidity of the juice were not significant (p > 0.05). However, the cloudiness, browning index, and viscosity were significantly increased (p < 0.05), and the color properties of the blackcurrant juice were improved. The total phenolic, flavonoid, and anthocyanin contents of TJ (treated at 50 °C for 30 min) were increased by 12.6%, 20.9%, and 40.4%, respectively, and there was a notable decline in ascorbic acid content after the pasteurization treatment, while the loss was minor in all TJ samples compared with RJ. The scavenging ability of 1,1-diphenyl-2-pyridyl and hydroxyl radicals increased to 52.77% and 50.52%, respectively, which were significantly (p < 0.05) higher than those in the RJ and PJ samples. In addition, both pasteurization and thermosonication resulted in a significant (p < 0.05) reduction in microbial counts, while there were no significant (p > 0.05) differences in the sensory parameters compared with the RJ samples. In conclusion, this study suggests that TS is an effective method that can be used as an alternative to pasteurization to improve the quality of blackcurrant juice.