Combined Frequency Research Articles

Role Of Clinical Pharmacist In Identifying And Managing Drug-Drug Interactions In Critical Care Unit- An Interventional Study

The risk that one medication may change the effects of another when taken at the same time is known as a drug-drug interaction (DDI). Finding out how often and how serious pDDIs are among intensive care unit (ICU) patients is the primary goal of this research.Finding and controlling possible DDIs is the goal of the research. Additionally, assess how well the clinical pharmacist has handled any drug-drug interactions (DDIs) in the intensive care unit.Research Approach: The intensive care unit at Basaweshwar Teaching and General Hospital was the site of a prospective interventional trial that lasted for six months. Patients hospitalized to the intensive care unit were included in the study at random after the study requirements were considered. The results showed that out of 102 cases tested, 61 (or 59.80%) were male and 41 (or 40.29%) were female. Out of the total number of patients, 22 (or 21.57%) were between the ages of 61 and 70, and 21 (or 20.59%) were 75 and older. Of the 102 instances that were examined, 76 had DDIs. Of these, 124 (31.58%) had 1 DDI and 15 (19.74%) had 2 DDIs. Out of the 76 DDIs that were noticed, 143 (or 65.60%) were classified as major, 64 (or 29.36%) as moderate, and 5 (or 2.29%) as small. Out of the 52 DDIs that were accepted, 24 (or 31.58%) were not. For 52 of these DDIs, the advised actions were monitoring for 25 (or 48.08%) and changing the administration time for 17 (or 32.69%). The two most often interfering drugs are ondansetron and tramadol. Ondansetron and tramadol is the most frequent medicine combination, occurring 13 times, while atorvastatin and clopidogrel is the second most common, occurring 11 times. In addition, medication interactions were more common when the dosage of each medicine was raised.Our research leads us to believe that clinical pharmacists may help stop these DDIs in the ED. Adequate understanding of the most prevalent pDDIs to permit the health care.

DOP009 Effectiveness and Safety of Advanced Combination Treatment (ACT) in patients with refractory inflammatory bowel disease or concomitant immune mediated disease or extra-intestinal manifestations: A Multi-Center Canadian Study

Abstract Background Some patients with inflammatory bowel disease (IBD) do not respond to multiple advanced therapies, resulting in off-label use of two advanced therapeutic agents, known as advanced combination treatment (ACT) (1). Methods This multi-center study in 9 Canadian centers included adult IBD patients treated with either two biological therapies, a biological plus an oral small molecule, or two small molecules. The indication for ACT was characterized as: 1) refractory IBD; 2) concomitant uncontrolled IMID; 3) concomitant uncontrolled EIMs. Primary outcomes were cumulative rates of clinical and endoscopic response and remission at 12 months. Clinical activity was assessed using physician global assessments for both IBD and the concomitant IMID/EIMs. Secondary outcomes included serious adverse events and infections. Cox-proportional hazard analyses identified independent predictors of treatment effectiveness. Multivariate Imputation by Chained Equations accounted for missing data. Results We included 105 IBD patients (76 CD, 29 UC), median age 35 years (IQR 35.4-40.8). At baseline, 39% had perianal involvement, and 58% had failed at least 3 advanced therapies. Most patients (61%) had moderate to severe disease activity, and 40% had prior surgery. The cohort was categorized into three groups based on the rationale for ACT: 63.8% (67/105) received ACT for refractory IBD, 28.8% (30/105) for concomitant IMID, and 7.6% (8/105) for concomitant EIMs. The primary reason for ACT was refractory IBD (63.8%), with the add-on approach used in 97.1% combinations. The most frequent combination was anti-TNF + anti-integrin, followed by the combination of anti-IL-(12)/23 agent + anti-integrin. At 12 months, the cumulative rates of clinical and endoscopic response were 60% and 32.4%, respectively. Cumulative clinical and endoscopic remission rates were 29.5% and 28.6%, respectively (Table 1). Multivariate analysis showed perianal disease was associated with reduced chances of both clinical remission (HR = 0.33, p=0.001), and endoscopic remission (HR = 0.42, p=0.0001) (Table 2). Longer disease duration (HR = 0.96, p = 0.035), baseline moderate-severe disease (HR = 0.41, p = 0.026), and baseline steroid use (HR = 0.39, p = 0.006) were associated with a reduced likelihood of clinical remission. Serious adverse events and infections were reported in 12.4% and 7.6% of patients, respectively. Among serious infections, 5 (62.5%) required hospitalization, 3 (37.5%) were reported as important medical events, and none was life-threatening. Conclusion In this large real-world cohort, ACT was effective in achieving clinical and endoscopic outcomes in patients with refractory IBD or concomitant IMID/EIMs. ACT was well-tolerated, with a favorable safety profile.

P0601 Is advanced combination therapy effective in patients with refractory Inflammatory Bowel Disease?

Abstract Background Advanced combination therapy (ACT) involves combining two biological therapies or a biological drug with a small molecule, in order to complement their mechanisms of action inhibiting multiple inflammatory cascades. The primary aim of our study was to evaluate the effectiveness of combination therapies in Inflammatory Bowel Disease (IBD) Methods A prospective, single-centre observational study was conducted, including all patients diagnosed with ulcerative colitis (UC) or Crohn´s disease (CD) starting treatment with ACT from March to August 2024. Clinical and biological response and remission were assessed at week 16 and the last available visit. Clinical response was defined as a decrease ≥3 points from baseline Harvey-Bradshaw Index (HBI) in CD or baseline Partial Mayo Score (pMS) in UC. Clinical remission was considered as a HBI score ≤4 or pMs of 0-1. Biological response was determined as a ≥50% decrease from baseline C-reactive protein (CRP) and faecal calprotectin (FC) and remission as a CRP<5 and FC<250 Results A total of 20 patients were included, 70% (14/20) diagnosed with UC (Figure 1A). The most frequent combination was vedolizumab (VEDO) with upadactitinib (UPA) (Figure 1B) The median baseline HBI was 10.5 [IQR 6-15] decreasing to 6.5 at week 16 [IQR 3-11] and to 5.5 [IQR 2-10] at the last follow-up (p<0.001)(Figure 2A). The median baseline pMS was 7 [IQR 5-8] decreasing to 4 [IQR 2-4] at week 16 and to 2 [IQR 1-3] at the last visit (p<0.005) (Figure 2B) The median baseline FC was 1994 [IQR 805-3238], decreasing to 635 [IQR 183-222] at week 16 and to 387 [IQR 93-1115] at the last follow-up (p=0.047) (Figure 2C). Regarding CRP, the median baseline was 5.3 [IQR 1-31], decreasing to 2.4 [IQR 1-5] at week 16 and to 1.2 [IQR 1-4] at the end of follow-up (p=0.014) (Figure 2D) 65% of patients achieved clinical response and 20% reached clinical remission at week 16. At the end of follow-up, 80% achieved clinical response and 65% clinical remission (Figure 2E) At week 16, 45% and 20% of patients achieved biological response and remission, respectively. At the end of follow-up, 65% were in biological response and 45% in biological remission (Figure 2F) Treatment was discontinued in 3 patients, in 2 of them due to improvement and in the reimaining one due to lack of response. Treatment intensification was required in 7 patients. A total of 8 mild adverse effects were recorded, none of which led to discontinuation of the ACT Conclusion These results demonstrate adequate clinical and biological response in patients treated with ACT. Clinical and biological remission was achieved in 65% and 45% of patients at the end of follow-up, with good safety profile. Nevertheless, to confirm this results futher large prospective studies are needed

P1085 Early and sustained improvement in patient-reported outcomes and biomarker concentrations with tulisokibart induction in patients with moderately to severely active ulcerative colitis: A post-hoc analysis from ARTEMIS-UC

Abstract Background In the phase 2, double-blind, placebo-controlled, multicenter ARTEMIS-UC trial, 12 weeks of induction treatment with the anti-tumor necrosis factor-like cytokine 1A (TL1A) monoclonal antibody tulisokibart led to significant rates of clinical remission, endoscopic improvement and mucosal healing, and improvement in patient-reported outcome (PRO) measures and disease surrogate biomarkers in patients with moderately to severely active ulcerative colitis (UC).1 This post-hoc analysis from ARTEMIS-UC examined the time course of improvement from baseline in patient-reported symptoms (PRO-2 score [combined Mayo stool frequency and rectal bleeding subscores]) and biomarkers (fecal calprotectin and high-sensitivity C-reactive protein [hs-CRP]) with tulisokibart. Methods Adults with moderately to severely active UC were randomized 1:1 to receive i.v. placebo or tulisokibart (1000 mg on Day 1 and 500 mg at Weeks 2, 6, and 10). The study population consisted of 2 cohorts based on a genetic diagnostic test (Dx) assessing likelihood for responding to anti-TL1A treatment. Cohort 1 included participants stratified by Dx results while Cohort 2 included only Dx positive participants. Cohort 1 is the population used in this post-hoc analysis. Participants recorded stool frequency and rectal bleeding scores daily using an e-diary. Fecal calprotectin was assessed at baseline and Weeks 6 and 12, and hs-CRP was assessed at baseline and Weeks 2, 6, 10, and 12. Symptomatic response was defined as a reduction from baseline in PRO-2 score ≥ 1 point. A mixed model repeated measures approach was used to compare tulikisobart to placebo for the difference in PRO-2 score for the first 14 days of treatment and the fold change from baseline in fecal calprotectin and hs-CRP at each timepoint. Results Among 135 randomized participants in Cohort 1, 60/67 (89.6%) receiving placebo and 68/68 (100%) receiving tulisokibart completed the 12-week induction period. The numerical difference in improvement of PRO-2 started as early as Day 2 and achieved significant improvement with tulisokibart compared to placebo at Day 9, with a sustained improvement persisting from the latter part of Week 2 through Week 12 (Figure 1, Table 1). Significant improvements with tulikisobart compared to placebo in fecal calprotectin and hs-CRP were observed by Weeks 6 and 2 (the first time point when these biomarkers were measured), respectively, which were maintained through Week 12 (Table 1). Conclusion In patients with moderately to severely active UC, induction with tulisokibart led to early and sustained improvement in patient-reported outcomes. Induction with tulisokibart also led to early and persistent improvement in biomarkers.

Acupoint selection patterns for epilepsy in ancient texts based on visual network analysis

To analyze the disease patterns and acupoint selection characteristics of acupuncture for epilepsy in ancient acupuncture texts, providing references and ideas for clinical acupuncture treatment of epilepsy. Texts from the Chinese Medical Classics (5th edition) regarding acupuncture for epilepsy are reviewed. The frequency of acupoints, meridian association, distribution, specific points, corresponding epilepsy subtypes, and needling techniques are statistically analyzed. The Apriori algorithm is used for association rule analysis, and a complex network analysis is conducted for high-frequency acupoints and their corresponding subtypes and treatments. A total of 205 acupuncture prescriptions are identified. Ancient texts favored differentiation-based treatments for epilepsy, primarily classified into epilepsy, wind epilepsy, and five epilepsy. Commonly used acupoints include Baihui (GV20), Jiuwei (CV15), Shenmen (HT7), Shenting (GV24), and Xinshu (BL15), with a focus on the acupoints of the governor vessel, the bladder meridian, and the conception vessel. The acupoints on the head, face are combined with the acupoints on the limbs, with skillful use of the five-shu points and intersection acupoints. The most frequent combinations are Shenmen (HT7)-Baihui (GV20), Shenting (GV24)-Baihui (GV20), and Xinshu (BL15)-Shenmen (HT7). Visual network analysis revealed that Baihui (GV20)-Shenting (GV24), Baihui (GV20)-Shenmen (HT7), and Baihui (GV20)-Zhaohai (KI6) are core acupoint combinations. Treatment mainly involved moxibustion or combined acupuncture and moxibustion. The acupoint selection for epilepsy treatment in ancient texts is precise, frequently using Baihui (GV20), Jiuwei (CV15), Shenmen (HT7), Shenting (GV24), and Xinshu (BL15), etc., with emphasis on calming epilepsy, awakening the spirit, relaxing tendons, and nourishing the heart.

Psychotropic medication usage in sporadic versus genetic behavioral-variant frontotemporal dementia.

Psychotropic medication (PM) use in behavioral-variant frontotemporal dementia (bvFTD) is higher than in other dementias. However, no information exists on whether PM use differs between sporadic and genetic bvFTD. We analyzed data from sporadic and genetic bvFTD participants with PM prescriptions in the Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects study. We estimated ordinal odds ratio (OOR) of having more PM comparing sporadic and genetic bvFTD. Finally, we explored the neuropsychiatric symptom (NPS) combinations using classification and regression trees (CART). We included 263 with sporadic and 193 with genetic bvFTD. The OOR for sporadic bvFTD to be on PM was 1.75 (95% confidence interval: 1.21 to 2.53) for the fully adjusted model. CART revealed the most common NPS combination was apathy + personality changes in 18% of participants. Participants with sporadic bvFTD were twice as likely to be on PM compared to genetic bvFTD. The reason for increased PM usage in sporadic bvFTD participants should be further investigated. We report on patients with behavioral variant frontotemporal dementia (bvFTD). We evaluated the psychotropic medication (PM) prescription at baseline in the cohort. Patients with sporadic bvFTD had more prescriptions for PM than genetic patients. The frequency of symptoms combination was different in sporadic and genetic bvFTD.

Towards Real-Time Detection of Wakes for Various Sea States with Lightweight Deep Learning Model in Synthetic Aperture Radar Images

Synthetic aperture radar (SAR) is an essential tool for monitoring and managing maritime traffic and ensuring safety. It is particularly valuable because it can provide surveillance in all weather conditions. Ship wake detection has attracted considerable attention in offshore management as it has potential for widespread use in ship positioning and motion parameter inversion, surpassing conventional ship detection methods. Traditional wake detection methods depend on linear feature extraction through image transformation processing techniques, which are often ineffective and time-consuming when applied to large-scale SAR data. Conversely, deep learning (DL) algorithms have been infrequently utilized in wake detection and encounter significant challenges due to the complex ocean background and the effect of the sea state. In this study, we propose a lightweight rotating target detection network designed for detecting ship wakes under various sea states. For this purpose, we initially analyzed the features of wake samples across various frequency domains. In the framework, a YOLO structure-based deep learning is implemented to achieve wake detection. Our network design enhances the YOLOv8’s structure by incorporating advanced techniques such as deep separation convolution and combined frequency domain–spatial feature extraction modules. These modules are used to replace the usual convolutional layer. Furthermore, it integrates an attention technique to extract diverse features. By conducting experiments on the OpenSARWake dataset, our network exhibited outstanding performance, achieving a wake detection accuracy of 66.3% while maintaining a compact model size of 51.5 MB and time of 14 ms. This model size is notably less than the existing techniques employed for rotating target detection and wake detection. Additionally, the algorithm exhibits excellent generalization ability across different sea states, addressing to a certain extent the challenge of wake detection being easily influenced by varying sea states.

Mixed pancreatic ductal adenocarcinoma and well-differentiated neuroendocrine tumor: A case report

BACKGROUND Pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare malignancies affecting the pancreas. The World Health Organization defines MiNENs as neoplasms composed of morphologically recognizable neuroendocrine and non-neuroendocrine components, each constituting 30% or more of the tumor volume. Adenocarcinoma-neuroendocrine carcinoma is the most frequent MiNEN combination. A well-differentiated neuroendocrine tumor (NET) component is rarely reported in MiNENs. CASE SUMMARY Here we report a rare case with intermingled components of ductal adenocarcinoma and grade 1 well-differentiated NET in the pancreas. The two tumors show distinct histology and significant differentiation discrepancy (poorly differentiated high grade adenocarcinoma and well-differentiated low grade NET), and also present as metastases in separate lymph nodes. Next generation sequencing of the two components demonstrates KRAS and TP53 mutations in the ductal adenocarcinoma, but no genetic alterations in the NET, suggesting divergent origins for these two components. Although tumors like this meet the diagnostic criteria for MiNEN, clinicians often find the diagnosis and staging confusing and impractical for clinical management. CONCLUSION Mixed NET/non-NET tumors with distinct histology and molecular profiles might be better classified as collision tumors rather than MiNENs.

Efficient Composite Infrared Spectroscopy: Combining the Double-Harmonic Approximation with Machine Learning Potentials.

Vibrational spectroscopy is a cornerstone technique for molecular characterization and offers an ideal target for the computational investigation of molecular materials. Building on previous comprehensive assessments of efficient methods for infrared (IR) spectroscopy, this study investigates the predictive accuracy and computational efficiency of gas-phase IR spectra calculations, accessible through a combination of modern semiempirical quantum mechanical and transferable machine learning potentials. A composite approach for IR spectra prediction based on the double-harmonic approximation, utilizing harmonic vibrational frequencies in combination squared derivatives of the molecular dipole moment, is employed. This approach allows for methodical flexibility in the calculation of IR intensities from molecular dipoles and the corresponding vibrational modes. Various methods are systematically tested to suggest a suitable protocol with an emphasis on computational efficiency. Among these methods, semiempirical extended tight-binding (xTB) models, classical charge equilibrium models, and machine learning potentials trained for dipole moment prediction are assessed across a diverse data set of organic molecules. We particularly focus on the recently reported foundational machine learning potential MACE-OFF23 to address the accuracy limitations of conventional low-cost quantum mechanical and force-field methods. This study aims to establish a standard for the efficient computational prediction of IR spectra, facilitating the rapid and reliable identification of unknown compounds and advancing automated high-throughput analytical workflows in chemistry.

Results of various somatic mutations detection in patients with chronic myeloid leukemia

Background. Somatic mutations in chronic myeloid leukemia (CML) patients are considered as possible factors for the failure of tyrosine kinase inhibitor (TKI) therapy, and the study of their characteristics is of interest.Aim. To evaluate the genetic profile of blood cells in CML patients using nextgeneration sequencing.Materials and methods. Retrospective study was conducted in two groups of patients: group 1 with TKI therapy failure (n = 29) and group 2 with optimal response to TKI therapy (n = 29). The target panel for nextgeneration sequencing included 19 genes: ASXL1, DNMT3A, FLT3, IDH1, IDH2, NPM1, RUNX1, SF3B1, SRSF2, TET2, TP53, U2AF2, KIT, WT1, CEBPA, ZRSR2, JAK2, GATA2, ABL1. In order to assess clonal evolution, additional samples were examined at a retrospective point in time closest to the primary CML diagnosis.Results. In group 1, mutations in 8 genes (including ABL1) were identified in 19/29 (66 %) patients. Excluding ABL1, mutations were identified in 15 (52 %) patients. In 9 (31 %) patients, >1 mutation (2 to 4) was detected. Frequency of genes mutations in group 1: ABL1 in 11 (38 %) patients, ASXL1 in 9 (31 %) patients, DNMT3A in 3 (10 %) patients, RUNX1, CEBPA in 2 patients (7 %), WT1, NPM1, TET2 in 1 patient (3.5 %). In 7 (24 %) patients there was a combination of mutations in ABL1 gene and in another gene; the most frequent combination of mutations in genes: ABL1 + ASXL1 – in 4 patients (14 %). The dynamics of mutant clones in group 1 was evaluated in 21/29 (72 %) patients. In 10/21 (48 %) patients somatic mutations in genes appeared during CML treatment, in 14/21 (67 %) patients previously detected mutations persisted, in 1 (5 %) the mutation disappeared. In group 2, somatic mutations were detected in 2/29 (7 %) patients: in DNMT3A (ariant Allele Frequency (AF) 5 %) and TP53 (AF 9 %) genes – these mutations were not detected at the diagnosis of CML. In one patient ASXL1 mutation (AF 5 %) was detected only at diagnosis, and was not detected subsequently with optimal response to therapy.Conclusion. The presence of somatic gene mutations is associated with a resistant CML course: somatic mutations in genes other than ABL1 were more common in CML patients with TKI therapy failure than in those with optimal response: 52 % vs. 7 % (p ≤0.05). Mutations in ASXL1 (31 %) and DNMT3A (10 %) were the most frequently detected. The frequency of ABL1 and ASXL1 mutations combination amounted to 14 %. uring followup, somatic mutations predominantly persisted or appeared over time in CML patients with TKI therapy resistance.

Catheter ablation of atrial fibrillation in patients with systolic left ventricular dysfunction

Atrial fibrillation (AF) is the most common arrhythmia among the adult population, affecting up to 2% of the population. Among patients with chronic heart failure (CHF), the prevalence of AF reaches 12.3%. The presence of common risk factors and pathophysiological mechanisms of AF and CHF development lead to the frequent combination of these two pathologies, which has a negative impact on the course of the underlying disease and further prognosis, increasing the chances of adverse outcomes such as stroke, myocardial infarction, and cardiovascular mortality. The results of most randomized studies indicate that interventional treatment of AF in patients with CHF and intermediate to low left ventricular ejection fraction (LV) contributes to reducing the functional class of CHF and improving quality of life, but at the same time, there is currently no consensus on the effectiveness, safety, and extent of catheter intervention. In this review, we attempted to summarize the literature data regarding the outcomes of interventional treatment of AF in patients with systolic LV dysfunction.

Analysis of Concussions with Persisting Symptoms Caused by Motor Vehicle Crashes in 136 Vehicle Occupants Shows that Females Are Vulnerable Road Users.

At the Canadian Concussion Centre, we treated 136 patients from 2000 to 2020 who sustained concussion plus persisting concussion symptoms (C+PCS) as motor vehicle occupants involved in motor vehicle crashes (MVCs). This center specializes in the treatment of patients with C+PCS. The objective of the present study was to identify strategies for preventing concussion among vehicle occupants involved in MVC. Indeed, this is the first study focused on C+PCS in MVC occupants, and our main purpose was to evaluate the effectiveness of onboard concussion prevention strategies. In this retrospective, consecutive cohort of 136 patients with C+PCS, we examined the patients' demographic and injury features in relation to the nature of the MVC including speed, direction of impact, and availability, deployment, and effectiveness of onboard occupant safety measures including seatbelts, head restraints, and airbags. The most frequent combination of factors was a belted female driver of an automobile struck from behind by another automobile. Surprisingly, the entire patient cohort comprised more females (69.1%) than males (30.9%), and rear-end collision was the most common type in females. Most injured occupants of both sexes were wearing seatbelts, but only a minority of the crashes caused airbag deployment. The seven most common symptoms were headache (84.6%), anxiety (72.8%), sensitivity to light (70.6%), memory problems (69.9%), sensitivity to noise (66.2%), irritability (56.6%), and depression (55.9%). Whiplash was a frequent associated injury in both sexes. Complete recovery from C+PCS was rare, and most patients with known follow-up continued to suffer from persisting symptoms for months to years. The median symptom duration for all 136 patients was 30.0 months (interquartile range: 16.8-56.0 months). Based on these findings, we conclude that females are indeed vulnerable road users with respect to C+PCS, and our literature search showed that there had been some previous evidence of increased injury risk of other injuries in female occupants. We recommend that additional prevention strategies are required to reduce the post-crash acceleration-deceleration "bobble-head" movement of the head on trunk causing both concussion and whiplash as has been accomplished in auto racing. Also, these prevention measures must be investigated in crash studies that include low-to-high speed rear-end collisions using anthropometrically appropriate models of male and female occupants reflecting the range of sizes of both sexes. There is a need for more concussion brain injury prevention research focusing on the vulnerability of female occupants, which has not been sufficiently addressed even though the deficiency was identified many years ago. The sex inequity of current onboard motor vehicle concussion brain injury prevention measures especially with respect to females should be addressed by governments and the automobile and insurance industries.

A newly developed method for assessing co-exposure to free dose combinations: a proof-of-concept study using antihypertensive medications in Danish registers

BackgroundElevated blood pressure is a major risk factor for severe medical conditions. Adherence to antihypertensive medication, especially in free-dose combinations, poses a significant challenge. This study aims to develop a novel method for assessing co-exposure to free-dose antihypertensive medications using secondary data sources.MethodsA register-based cohort study was conducted on individuals aged 65 years or older in Denmark who initiated antihypertensive therapy from 1996 to 2016 and followed for 730 days from the index date. A new method was developed to assess co-exposure to antihypertensive medications through redeemed prescriptions, treatment episodes, and overlapping medication events. The method's accuracy was evaluated using a random sample of 400 individuals.ResultsA total of 1,021,819 individuals were included in the study, with a mean age of 68.8 years, and 53.7% were women. The method achieved 100% accuracy in identifying co-exposure periods. During the early stage of the follow-up (0–180 days), 54.1% of individuals were co-exposed to at least two antihypertensive medications, while 37.5% were co-exposed during the late stage of the follow-up period (181–730 days). The most frequent antihypertensive combinations included bendroflumethiazide and potassium with either amlodipine or enalapril in the early (13.2% and 12.5% of patients, respectively) and late stages (16.9% and 15.0% of patients, respectively).ConclusionsThe newly developed method effectively assesses co-exposure to antihypertensive medications, overcoming previous limitations. The findings reveal common co-exposure combinations and evolving trends in antihypertensive medication use among older individuals, reflecting changes in clinical practice and guidelines over two decades.

Extraction of patterns from images using a model of combined frequency localization spaces

An algorithm for image decomposition and separation of superposed stationary contributions is proposed. It is based on the concept of sparse-to-sparse domain representation achieved through a relationship between block-based and full-size discrete cosine transform. The L-statistics is adapted to discard nonstationary components from the frequency domain vectors, leaving just a few coefficients associated with stationary pattern. These fewer stationary components are then used under the compressive sensing framework to reconstruct the stationary pattern. The original image is observed as a nonstationary component, acting as a non-desired part at this stage of the procedure, while the stationary pattern is observed as a “desired part” that should be extracted through the reconstruction process. The problem of interest is formulated as underdetermined system of equations resulting from a relationship between the two considered transformation spaces. Once the stationary pattern is reconstructed, it can be removed entirely from the image. Furthermore, it will be shown that the efficiency of pattern extraction cannot be affected, even when image contains additional nonstationary disturbance (here, the noisy image is observed as nonstationary undesired part). The proposed approach is motivated by challenges in removing Moiré-like patterns from images, enabling some interesting applications, including extraction of hidden sinusoidal signatures.

Impact of Advanced Thyristor Controlled Series Capacitor on Load Frequency Control and Automatic Voltage Regulator Dual Area System with Interval Type-2 Fuzzy Sets-PID Usage

A major priority for practicing engineers in an electric power system is preserving the stability of frequency and voltage levels. Any change in these two factors will impact the efficiency and lifespan of the machines connected to the power supply. Therefore, this paper provides a control approach utilizing the Interval Type-2 Fuzzy Sets- Proportional Integral Derivative (IT2FSs-PID) controller and Advanced Thyristor Controlled Series Capacitor (ATCSC) with a combined Load Frequency Control-Automatic Voltage Regulator (LFC-AVR). Several inspections were implemented to demonstrate the controller’s strength, including various disturbances in the power system. The LFC-AVR was studied using two different dynamic models, referred to as open and closed loops on the Generation Rate Constraint (GRC) forms. A comparison was made using different techniques from the literature using the same model. Before using the approach, the frequency deviation of area-1 had a very large settling time value, which was caused by system instability. However, after implementing the approach, this value decreased to 4.9236 s. Finally, an additional ATCSC was added to the proposed model to observe its effect on the power system. The simulation was implemented using MATLAB/SIMULINK tools.

Intensified synthesis of olive oil-based structured lipids based on enzymatic acidolysis using multi-frequency ultrasound

Intensified synthesis of structured lipids based on olive oil and capric acid through enzymatic acidolysis was investigated utilizing a multifrequency hexagonal ultrasonic reactor. The ultrasound-assisted process achieved a 59 % conversion of olive oil into structured lipids in just 4 h, compared to a 52 % conversion in 6 h with the conventional approach. The optimized parameters for the ultrasound-assisted process were a 4:1 reactant molar ratio, 4 % enzyme loading, 60 °C temperature, 30 W ultrasonic power, a 60 % duty cycle, and a combined frequency as 22 + 33 kHz. Sn-2 positional analysis confirmed the enzyme’s specificity for the glycerol 1,3 positions in the acidolysis reaction. Only 20 % loss in enzyme activity was observed after the sixth cycle, indicating the enzyme’s reusability within the process. Overall, the study effectively highlights the use of ultrasound as a powerful approach to intensify the enzymatic synthesis of designer lipids, while also elucidating the optimal operating conditions.

Research on lateral–torsional coupled vibration induced by substantial imbalance in an overhung flexible rotor

Substantial imbalance is a real possibility in aero–engines and is usually caused by blade off, bird strikes, etc. A substantially unbalanced rotor system will exhibit extremely complicated nonlinear lateral–torsional behavior, and the related dynamics are critical to the safe design of a rotor system. In this paper, a comprehensive nonlinear model of an imbalanced flexible rotor system is proposed, in which translational–torsional coupling and angular–torsional coupling are introduced simultaneously. Based on the model, the lateral–torsional coupling features are discussed, and the lateral as well as the torsional vibration behaviors are further analyzed in detail. The results show that the lateral–torsional coupling factors only exist under the nonsynchronous whirl condition. Thus, if the imbalance is small, the lateral vibration exhibits the linear feature of a traditional unbalanced response, and the torsional vibration does not occur in steady state. However, under substantially unbalanced conditions, the vibration responses are significantly changed. In lateral vibration, many combined frequency components between rotation frequency (fu) and torsional natural frequency (ft1 and ft2) such as fu-ft1, fu-2ft1 and fu-ft2 can be induced, which can lead to combined resonance phenomena and many additional resonance peaks. The lateral–torsional coupling effect is strong at that time. Both the lateral translational–torsional coupling excitation and lateral angular–torsional coupling excitation exhibits the multiple harmonics whose frequencies are closely related to ft1 and ft2. Consequently, the torsional vibration in those combined resonance regions can be very high. The corresponding vibration exhibits the steady harmonic feature with vibration frequency being ft1 or ft2.

The Effect of Sampling Schedule on Assessment of Dietary Measures: Evidence From Blue Monkeys (Cercopithecus mitis stuhlmanni).

Accurately assessing primate diets is important in studies of behavioral ecology and evolution. While previous research has compared sampling methods (scan, focal), we examined how sampling schedule influences accuracy of dietary measures. We define sampling schedule as the combined distribution (random vs. consecutive) and frequency of sampling days within a given month. Under field conditions, time may be required to locate a study group, and we therefore also subtracted 1, 2, or 3 h from the beginning of all non-consecutive days in each sampling schedule to mimic observation time lost to search. From a dense (near daily) 5-year record of feeding behavior derived from focal animal follows of adult females in five wild blue monkey (Cercopithecus mitis) groups, we created data subsets matching various sampling schedules, and compared monthly dietary measures calculated from each subset to those based on the full data set. These measures included (1) the proportion of observation time feeding on fruit, (2) diet composition (three top-ranked food items), (3) species richness of plant diet, (4) Shannon-Wiener diversity index based on plant species, and (5) Holmes-Pitelka index expressing dietary overlap with the previous month. We used generalized linear mixed models to assess how frequency and sampling type (a combination of distribution and hours lost) relate to a subset's deviation from the full data set, where a smaller deviation (or higher chance of matching, for diet composition) implies greater accuracy. For all dietary measures, increasing observation frequency increased accuracy. The response to distribution varied among measures, but sampling types generally differed more at lower frequencies. Deviation varied widely within and between dietary measures, and some sampling schedules resulted in values with large percentage differences from the "full" data. Accordingly, when designing and comparing studies, researchers should consider how sampling schedules may influence the accuracy of the dietary measures of interest.

IDENTIFICATION OF PERIODONTAL PATHOGENS IN PATIENTS WITH CHRONIC GENERALIZED PERIODONTITIS DEPENDING ON THE SEVERITY OF INFLAMMATION

Introduction. The progression of chronic generalized periodontitis is associated with gram-negative anaerobic bacteria. Microbiological diagnostics of periodontal disease provides an opportunity for selecting the most effective therapeutic approach for both local and systemic conditions in patients. Aim of this study is to conduct a qualitative assessment of the presence of pathogenic microorganisms in the periodontal pockets of patients, based on the severity of inflammation. Materials and methods. The presence of five key pathogenic microorganisms in the periodontal pocket contents of 90 individuals aged 25-60 years (45 with grade I severity and 45 with grade II) was assessed using real-time polymerase chain reaction (PCR). The analysis was conducted with the CFX96™ Real-Time PCR Detection System (BIO-RAD) and the PeriodontScreen Real-TM reagent kit (Sacace Biotechnologies Srl, Italy). Non-parametric correlation statistical analysis was performed to calculate Kendall’s Tau and Gamma coefficients. In 27 patients (60%) with grade I severity, bacteria of a single species were identified. Two types of periodontal pathogens were detected in 13 patients (28.9%), with the most common combination being Tannerella forsythia and Aggregatibacter actinomycetemcomitans, found in 5 patients (11.1%); 5 patients (11.1%) showed the presence of three microbial species: Tannerella forsythia, Treponema denticola, and Porphyromonas gingivalis. Among the patients with grade II severity, 8 patients (17.8%) had bacteria of one species, specifically Prevotella intermedia. Two microbial species were identified in 9 patients (20%), while three species were present in 15 patients (33.3%). The most frequent combination included Prevotella intermedia, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans, found in 5 patients (11.1%). Four types of microbes were detected in 13 patients (28.9%), with the predominant combination being Tannerella forsythia, Porphyromonas gingivalis, Treponema denticola, and Aggregatibacter actinomycetemcomitans (17.8%). None of the patients with grade II severity had all five periodontopathogenic agents. The correlation analysis confirmed that chronic periodontitis is strongly associated with the presence of Tannerella forsythia within microbial associations. Conclusions. The spectrum of periodontal pathogens affects the severity of inflammation in the periodontium. In grade II inflammation, associations of periodontal pathogens were detected by 82.2% of cases, while in grade I by in 40%. Tannerella forsythia was detected in 42.2% of patients with grade I inflammation, 15.6% of them as a mono-infection; in patients with grade II inflammation in 71.1%, in associations with Treponema denticola in 48.9%. Determining the spectrum of periodontal pathogens, taking into account their characteristics and associated virulence factors, is necessary for choosing the effective differentiated treatment approach.

Previously defined variants of uncertain significance may play an important role in epilepsy and interactions between certain variants may become pathogenic.

Epilepsy is a chronic neurological disorder related to various etiologies, and the prevalence of active epilepsy is estimated to be between 4 and 10 per 1000 individuals having a significant role in genetic mutations. Next-Generation Sequencing (NGS) panels are utilized for genetic testing, but a substantial proportion of the results remain uncertain and are not considered directly causative of epilepsy. This study aimed to reevaluate pediatric patients diagnosed with epilepsy who underwent genetic investigation using NGS panels, focusing on inconclusive variant findings or multiple variants of uncertain significance (VUSs). A subgroup of pediatric patients aged 0-25 years, diagnosed with epilepsy, who underwent genetic investigation with an NGS epilepsy panel at the Child Neurology Unit, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, between 2018 and 2022 through Invitae, was reevaluated. Patients with inconclusive variant findings or multiple VUSs in their test results were included. Genetic data were analyzed to identify potentially pathogenic variants and frequent genetic combinations. Two unrelated potentially pathogenic variants were identified in the SCN9A and QARS1 genes. A frequent genetic combination, RANBP2&RYR3, was also observed among other combinations. The RANBP2 gene consistently co-occurred with RYR3 variants in uncertain results, suggesting potential pathogenicity. Analysis of unaffected parents' data revealed certain combinations inherited from different parents, suggesting specific gene combinations as possible risk factors for the disease. This study highlights the importance of reevaluating genetic data from pediatric epilepsy patients with inconclusive variant findings or multiple VUSs. Identification of potentially pathogenic variants and frequent genetic combinations, such as RANBP2&RYR3, could aid in understanding the genetic basis of epilepsy and identifying potential hotspots. We have performed a retrospective analysis on a subpopulation of pediatric patients diagnosed with epilepsy. We found that specific genetic variants were repeatable, indicating their potential pathogenicity to the disease.