Optimization Program Research Articles

Accurate image reconstruction within and beyond the field-of-view of CT system from data with truncation

Objective. Accurate image reconstruction from data with truncation in x-ray computed tomography (CT) remains a topic of research interest; and the works reported previously in the literature focus largely on reconstructing an image only within the scanning field-of-view (FOV). We develop algorithms to invert the truncated data model for numerically accurate image reconstruction within the subject support or a region slightly smaller than the subject support.Methods. We formulate image reconstruction from data with truncation as an optimization program, which includes hybrid constraints on region-based image total-variation (TV) and imageℓ1-norm (L1) for effectively suppressing truncation artifacts. An algorithm, referred to as the TV-L1 algorithm, is developed for image reconstruction (i.e. inversion of the data model) from data with truncation through solving the optimization program.Results. We perform numerical studies to evaluate accuracy and stability of the TV-L1 algorithm by using simulated and real CT data. Accurate images can be obtained stably by use of the TV-L1 algorithm within the subject support, or a region substantially larger than the FOV, from data with truncation of varying degrees.Conclusions. The TV-L1 algorithm can invert the truncated data model to accurately and stably reconstruct images within the subject support, or a region slightly smaller than the subject support but substantially larger than the FOV.Significance. Accurate image reconstruction within the subject support, or a region substantially larger than the FOV, from data with truncation can be of theoretical and practical implication. The insights and TV-L1 algorithm may also be generalized to accurate image reconstruction from data with truncation in other tomographic imaging modalities.

Operation Optimization Model of Regional Power Grid Considering Congestion Management and Security Check in Complex Market Operation Environment

Security checks are essential for ensuring the safe operation of the regional power grid (RPG) and the smooth functioning of the electricity spot market (ESM). Currently, China’s RPG operating environment encompasses a complex mix of centralized ESM, decentralized ESM, and planned power generation. This complexity has led to increasingly severe RPG congestion issues. To address this, this paper introduces a security check mechanism design and operational optimization approach tailored for RPGs in complex markets, with a focus on congestion management. Firstly, the paper elaborates on the practical foundations, unique constraints, and requirements for security checks and congestion management during the RPG’s operational mode transitions. Secondly, it outlines the principles underlying the security check mechanism and presents a framework for RPG security checks and congestion management. Through a comparative analysis of three different programs, including their advantages, disadvantages, and applicable scenarios, the paper provides an optimal program recommendation. Building on this, the paper develops an operational optimization method that incorporates congestion management for each of the three security check and congestion management programs. Lastly, an IEEE-39 node test system is simulated to validate the effectiveness of the proposed programs. The mechanism and simulation analysis results show that Program 3, based on market mechanisms, has theoretical and practical advantages over Program 1 (based on multiple adjustments) and Program 2 (based on dispatch plans) for congestion management. Under the same line congestion situation, Program 1 requires two adjustments to relieve the line congestion, while Program 2 and Program 3 can solve the problem with just one optimization adjustment, and the congestion management effect of Program 3 is more obvious and superior.

Cognitive Outcomes and Delirium After Cardiac Neurodevelopmental Program Implementation for Children With Congenital Heart Disease

A recent advisory from the American Heart Association delineated the potential benefits of developmental care for hospitalized children with congenital heart disease (CHD) and a critical gap in research evaluating the association of such inpatient programs with neurodevelopmental outcomes. To investigate associations between the Cardiac Inpatient Neurodevelopmental Care Optimization (CINCO) program interventions, delirium, and neurodevelopment in young children (newborn through age 2 years) hospitalized with CHD. This cohort study used quality improvement data from inpatient cardiac units at a tertiary care children's hospital in the US. Participants were children aged 0 to 2 years who were admitted for at least 7 days from September 1, 2018, to September 1, 2023. The CINCO program was implemented on September 1, 2020, in 6-month plan-do-study-act phases. The 5 CINCO interventions were medical and/or nursing order panels, developmental kits, bedside developmental plans, caregiver mental health support handouts, and developmental care rounds. Number of days with delirium per patient, which was measured using the Cornell Assessment of Pediatric Delirium (a score higher than 9 indicated delirium). Neurodevelopment was measured using the Bayley Scales of Infant and Toddler Development, Fourth Edition (BSID-4). The full sample included 1331 qualifying admissions for 1019 unique pediatric patients (median [range] age at admission, 3.65 [0-34.62] months; 771 males [57.9%]), with a subcohort of 121 unique patients (median [range] age at admission, 0.00 [0-9.85] months; 77 males [63.6%]) whose initial hospitalization occurred before age 10 months and who underwent BSID-4 evaluation at age 12 months or older. The mean (SD) number of days with delirium per patient was stable for 2 years prior to CINCO implementation, decreased by 54.0% between phases 1 and 2 of the CINCO program (from 3.05 [0.60] to 1.38 [0.21]), and then remained stable over time. Each of the 5 CINCO interventions was associated with lower delirium after false discovery rate (FDR) correction (eg, medical and/or nursing order panel: B = -1.376 [95% CI, -1.767 to -0.986]; F2,1273 = 47.767; partial η2 = 0.036; P < .001). Mean (SD) BSID-4 cognitive index scores were stable for 2 years prior to implementation, higher between phases 1 and 2 of the program (from 81.67 [14.14] to 93.92 [19.43]), and then remained stable over time. Four of the 5 interventions were associated with higher BSID-4 cognitive scores after FDR correction (eg, bedside developmental plans: B = 8.585 [95% CI, 2.247-14.923]; F5, 101 = 7.221; partial η2 = 0.067; P = .008). Delirium was associated with lower BSID-4 cognitive scores. There were no associations between delirium and BSID-4 language or motor scores. This cohort study found that among hospitalized children with CHD, the implementation of an inpatient developmental care program was associated with reduced incidence of delirium and higher cognitive scores. Pediatric cardiac centers may consider adopting these low-cost, low-risk, generalizable program interventions.

Identifying Preferred Features of Influenza Vaccination Programs Among Chinese Clinicians Practicing Traditional Chinese Medicine and Western Medicine: Discrete Choice Experiment.

Achieving high vaccine coverage among clinicians is crucial to curb the spread of influenza. Traditional Chinese medicine (TCM), rooted in cultural symbols and concepts without direct parallels in modern Western medicine, may influence perspectives on vaccination. Therefore, understanding the preferences of TCM clinicians towards influenza vaccines is of great importance. To understand preferences for features of influenza vaccination programs and identify the optimal influenza vaccination program among clinicians practicing TCM and Western medicine. We conducted a discrete choice experiment with a national sample of 3085 Chinese clinicians from various hospital levels (n=1013 practicing TCM) from January to May 2022. Simulations from choice models using the experimental data generated the coefficients of preference and predicted the uptake rate of different influenza vaccination programs. Clinicians were grouped by vaccine preference classification through a latent class analysis. All included attributes significantly influenced clinicians' preferences for choosing an influenza vaccination program. An approximate hypothetical 60% increase of vaccine uptake could be obtained when the attitude of the workplace changed from "no notice" to "encouraging of vaccination"; there was an approximate hypothetical 35% increase of vaccine uptake when vaccination campaign strategies changed from "individual appointment" to "vaccination in a workplace setting." In the entire sample, about 30% (946/3085) of clinicians preferred free vaccinations, while 26.5% (819/3085) comprehensively considered all attributes, except vaccination campaign strategies, when making a decision about choosing an influenza vaccination program. Clinicians who practiced TCM, worked in tertiary hospital, or had at least a postgraduate degree exhibited a lower preference for free vaccinations. Clinicians who practiced Western medicine, worked in primary hospital, or had at most a bachelor's degree had a higher preference for vaccinations in workplace settings. Offering a range of influenza vaccination programs targeting the preferred attributes of different clinician groups could potentially encourage more clinicians, including those practicing TCM, to participate in influenza vaccination programs.

Network-Based Drug Optimization toward the Treatment of Parkinson's Disease: NRF2, MAO-B, Oxidative Stress, and Chronic Neuroinflammation.

Parkinson's disease (PD), the second most common neurodegenerative disorder, affects around 10 million people worldwide. It is a multifactorial disease marked by dopaminergic neuron loss with oxidative stress (OS) and neuroinflammation as key pathological drivers. Current treatments focus on dopamine replacement and are symptomatic, underscoring the urgent need for disease-modifying therapies. Here, we present a novel class of dual MAO-B inhibitors and NRF2 inducers with neuroprotective properties in in vitro PD models. Through an optimization program, we enhanced their MAO-B inhibitory potency, selectivity, and NRF2 induction capacity while achieving favorable pharmacokinetic profiles. Virtual library screening identified two core derivatives, leading to the development of compound 11, which exhibited potent anti-inflammatory and neuroprotective activity in OS-related in vitro models. Compound 11 also demonstrated high liver microsomal stability and favorable pharmacokinetics in mice, making it a promising candidate for further investigation as a potential PD therapy.

Evidence-based exercise recommendations to improve functional mobility in older adults - A study protocol for living systematic review and meta-analysis.

This is a protocol for a living systematic review and meta-analysis.This review will assess the effects of state-of-the-art exercise interventions designed to promote functional mobility. Therefore, after identifying all potential interventions, we will use the F.I.T.T. principles (frequency, intensity, time, type) as well as the physical and health status of the participants as moderators to analyse the mechanisms for the positive benefits of exercise interventions.The main research questions are:Which exercise types are most beneficial for improving functional mobility in various populations of older adults?Which physical exercise characteristics in terms of frequency, intensity, time and duration will achieve the greatest benefit in terms of the defined outcomes, i.e, the functional mobility of older adults? The systematic literature research according to PRISMA guidelines will search databases like MEDLINE, APA Psych-Info and Web of Science.Inclusion criteria are: healthy older people ≥ 50 years, randomized-controlled trials including exercise intervention and a walking or mobility assessments (eg., TUG, SPPB) as an outcome measure. A preliminary search revealed more than 33,000 hits that will be screened by pairs of independent reviewers. The results will be summarized according to the effects regarding functional mobility and potential dose-response relations via respective meta-analysis. The systematic review will comprise the knowledge of the existing literature with regards to the effects of the physical activity interventions compared to an active or inactive control group.We will summarize the effects with respect to the F.I.T.T.. They provide a foundation for structuring an optimal exercise training program. If possible, we will also compare interventions from the different categories (eg. cardiovascular, resistance, motor-coordinative, multicomponent or mind-body exercise) as a network analysis and report the influence of moderator variables. Based on the results evidence-based guidelines following GRADE for physical exercise interventions to improve functional mobility in older adults will be provided.

Implementation of a Cost and Variation Reduction Program for Hemostasis Products at a Large Academic Medical Center: A Multi-Stakeholder Perspective.

Cost-saving initiatives targeting surgical supplies management have become increasingly common to address rising healthcare costs. However, few studies provide details on hospital stakeholder experiences or learnings from implementing such initiatives. Thus, we sought to evaluate hospital stakeholder satisfaction with conversion to a sole supplier for hemostasis products, in addition to economic and clinical impacts, to help develop best practices for implementation. This cross-sectional study assessed satisfaction with converting to a sole supplier for hemostasis products at a large US academic medical center using qualitative interviews and quantitative surveys with clinical and non-clinical stakeholders, on the decision-making process, conversion, and vendor-supported hemostasis optimization program (HOP) post-implementation (February 2022-May 2022). Perioperative hemorrhage events, adjunctive hemostat utilization, and total annual hospital expenditure on hemostatic products were also evaluated pre- and post-conversion (2020-2022) to identify impacts on clinical and economic outcomes. Ten hospital stakeholders completed qualitative interviews (n = 7 surgeons, n = 2 surgical technicians, n = 1 administrator) and 22 completed quantitative surveys (n = 6 surgeons, n = 5 surgical technicians, n = 11 nurses). Survey respondents noted overall satisfaction with conversion, including the level of input they provided in the decision-making process (75% were somewhat to extremely satisfied), availability of hemostatic agents during the conversion process (87%), and the vendor-supported HOP (100%). The outcomes analyses revealed a nearly 25% decrease in supply expenditure without changes to the number of postoperative hemorrhage events following implementation. Converting to a sole vendor for hemostasis products was achieved with high satisfaction among hospital stakeholders and cost savings to the institution without impacting the quality of patient care. This study provides a roadmap of best practices for other institutions interested in implementing similar initiatives and presents an example of a successful transition to a sole vendor for hemostasis products driven by effective supplier, institution, and hospital stakeholder coordination.

THE MODEL OF CHOOSING A CRM SYSTEM IN THE MANAGEMENT OF BUSINESS ROCESSES OF SMALL BUSINESSES

The article presents a model for choosing a CRM system for small and medium-sized enterprises (SMEs), which allows for effective business processes of interaction with clients. The authors came to the conclusion that in modern conditions, digitalization of SME activities is becoming one of the pressing issues.Active digitalization of business accelerates the process of transition of the economy to digital. The digital economy is based on information and communication technologies (ICT). Information technologies in the modern economy are used for the purpose of fast, high-quality and effective computer processing of information resources, their transmission over any distance in the shortest possible time. The authors argue that government support for business digitalization cannot and should not be the only stimulating factor for SMEs. In addition to external conditions, there are also internal motivating factors - these are the capabilities of the business environment. The authors of the article substantiate the idea that CRM systems allow optimizing the process of financial and economic interaction between a company and a buyer. Using the hierarchy analysis method, the key parameters for choosing a CRM system were determined. The final indicator of the CRM system selection allows choosing the optimal CRM system for the enterprise from alternative ones. The indicator is calculated based on the second-level indicators: the functionality of the CRM system, the program interface, the tariff scale.Each of these indicators is disclosed through the indicators of the 3rd level. The weights of the indicators of all levels were determined by experts through a pairwise comparison of the elements of each level on a nine-point scale. The criteria and their weight values proposed by the authors will allow SME sector entities to choose the optimal program depending on the requests and capabilities of the enterprise.

Architectural Computational Optimisation in Designing Acoustics and Seating Arrangements

In architectural practice, it is challenging for designers to predict future spatial performance based on limited information in the early stages of design. To address this design problem, architectural design optimisation can assist the designer by projecting building performance utilising single or multiple criteria over different architectural geometric analyses in the design process. The primary purpose of this paper is to describe how to design a computational optimisation program that can automatically generate concept design solutions, and determine its impact on the design outcome. In order to investigate the application of computational optimisation in architecture, this study involved analysis of a small-scale community performance facility as the proposed building type in the design exploration. Through this study, a deeper understanding of optimisation processes is intended to contribute to advancing architectural practice through computational generative design.

Pemberdayaan Masyarakat Desa Pasir Tanjung Melalui Optimalisasi Edu-Tani untuk Mencapai Pembangunan Desa Berkelanjutan

The Thematic Community Service Lecture (KKNT) activity held in Pasir Tanjung Village, Tanjungsari District, Bogor Regency aims to empower the Pasir Tanjung Village community to support sustainable village development through the edu-tani optimization program. This activity was carried out using a method involving socialization, demonstration, mentoring, and cooperative learning in several programs: making liquid organic fertilizer (Green Craft), natural pesticides (Integrated Pest Management), agricultural technology applications (IPB Digitani and Agricount), and character development of school-age children using the cooperative based learning method. As a result, this activity succeeded in achieving its target with a positive response from the community, where more than 60% of participants felt very satisfied. The programs implemented provided direct benefits in the form of increasing soil fertility, pest control, access to agricultural technology information, and strengthening children's character. This activity shows that the programs implemented are effective in supporting community empowerment and contributing to village sustainability. Recommendations include further training, program integration into the curriculum, and strengthening cooperation with partners are needed for program sustainability.

A New Tensor Summary Statistic for Real-Time Detection of Stealthy Anomaly in Avatar Interaction

Avatar is one of the most intuitive central components in Metaverse and faces serious security problems, particularly during the interaction with each other. In this article, we consider the problem of timely detecting the stealthy anomaly in the avatar interaction, which is crucial for security and privacy in Metaverse. With this goal, a new tensor summary statistic is proposed first to well depict the statistical discrepancy between normal and anomalous interaction volume samples, even when anomalies are stealthy. The proposed tensor summary statistic is established from the tensor linear representation residual, which naturally implies the statistical probability that an interaction volume sample lies within or deviates from the tensor lateral space. Moreover, a convex optimization programme is introduced to robustly recover the tensor lateral space in the presence of anomalous samples, thereby enhancing the robustness of our tensor summary statistic. On the basis of the tensor summary statistic, a non-parametric statistic framework is developed for the real-time detection of the stealthy interaction volume anomaly. We also provide theoretical analysis concerning its detection performance and parameter selection. Extensive experiments using synthetic and real-world datasets verify our effectiveness and superiority. Compared with benchmark methods, the proposed detection scheme achieves significantly lower detection delay and higher false alarm period, particularly in the detection of stealthy anomalies with a low change rate.

The possibilities of assessing regional risk factors for lung cancer

Introduction. Lung cancer remains one of the main causes of death for a long period of time. The existing screening methods are ambiguous. The presence of patients with metastatic stage of lung cancer justifies the creation of an optimal program for more accurate formation of risk groups. It is of interest to determine the intensity of the impact on the incidence rate from the point of view of both clarifying the parameters of urban pollution, but also a detailed analysis of other factors at the regional level.Aim. To identify the main potential risk factors in Saratov patients diagnosed with lung cancer, taking into account the ecological and geographical features of their place of residence in order to further create a model of active disease search by risk groups.Materials and methods. The complex of factors influencing the development of lung cancer among the population of Saratov has been studied. A group of 1049 patients was analyzed. The distribution of patients across urban landscape areas of the city has been determined depending on the impact of certain adverse environmental factors. To detail the remaining factors, the main group included 200 patients with the specified diagnosis who underwent outpatient and inpatient treatment in oncological institutions. All data was collected using official statistical documents and a medical information system.Results. When conducting a subgroup analysis by parameters (gender, age, localization and clinical form of the cancer process, stage of the disease, the patient’s attitude to smoking, body mass index, occupational hazards, the presence of oncopathology in the history of the patient and his relatives, the presence of chronic lung disease), the main patterns and features were identified depending on the histological variant. Given the complexity of the interaction of risk factors in the development of lung cancer, it becomes necessary to conduct further research to form a model questionnaire for lung cancer risk based on multifactorial analysis.Conclusion. The formation of a more precise risk group will increase the percentage of detection of early stages of lung cancer.

Individualized Physical Activity Prescriptions for Children and Adolescents With Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

For improved health outcomes, children and adolescents with cancer must maintain physical activity. Individualized physical activity prescription is an effective way to promote physical activity in this group. We reviewed and meta-analyzed evidence on the effectiveness of individualized physical activity prescriptions for improving physical activity and other health outcomes among children and adolescents with cancer. Seven databases were searched from inception up to January 2024 for randomized controlled trials. Two researchers independently extracted data and assessed the quality of studies using the Risk-of-Bias tool. Data were pooled into Review Manager 5.3 for data synthesis and subgroup analyses. Seventeen randomized controlled trials were included. The systematic review summarized the characteristics of recent interventions. Meta-analyses showed that although individualized physical activity prescriptions had no overall effect on physical activity (n = 8 studies), anthropometry and body composition (n = 5), functional capacity (n = 3), quality of life (n = 8), fatigue (n = 3), and self-efficacy (n = 5), they improved cardiovascular fitness (n = 8, P = .02) and muscle strength (n = 8, P = .04). Subgroup analyses showed that studies providing 6-month interventions (P = .003) or such interventions combined with motivational interviewing (P = .002) reported significantly increased physical activity in patients. Individualized physical activity prescriptions appear to improve cardiovascular fitness and muscle strength in children and adolescents with cancer. High-quality studies providing long-duration interventions and motivational interviewing are needed for optimal physical activity programs for children and adolescents with cancer. The application of electronic devices should increase the types of physical activities for this group to further improve health outcomes.

Beyond Just “Free Time”—Designing Effective and Lasting Slack Time Programs in Organizations

OVERVIEW Employee slack time programs aim to provide workers with pockets of unscheduled time to pursue innovative ideas, yet their efficacy varies greatly across organizations. This qualitative study explores optimal slack time program conditions. Rather than the traditional view of slack time as unstructured “free time,” the study findings reveal slack time outcomes depend on aligning (1) willing and able individuals through self-selection; (2) a supportive organization that provides management buy-in, psychological safety, mentorship, and appropriate evaluation mechanisms; and (3) a process that serves as a guide and includes a workflow, simple forms, and required interactions with peers and management. We propose a framework that integrates these individual, organizational, and process components. PRACTITIONER TAKEAWAYS A successful slack time program requires alignment on the individual, organizational, and process level. To maximize the benefits of slack time in your organization, (1) encourage voluntary participation to attract motivated individuals; (2) foster a culture of psychological safety and managerial support; (3) provide mentorship opportunities for participants; (4) implement evaluation criteria that emphasize behavior and action over unpredictable results; and (5) balance autonomy with flexibility through process. Slack time processes should serve as a guide for both scientists and management. A good slack time process harmonizes freedom and creativity with accountability for both scientists and managers through requiring simple documentation and regular interactions between participants, peers, and management.

Detailed Transfer Line Beam Characteristics at an Operational Proton Therapy Center

The McLaren Proton Therapy Center functions as a multi-room, clinically active cancer treatment center. Beam position, size, and current measurements along the transfer lines have been utilized together with simulations to validate computer models for the Center’s transfer lines and associated beam parameters. Beam profile monitor (BPM) data collected along the beamlines provided detailed beam measurements. A computer tool, utilizing nonlinear constrained optimization programs that are integrated with a beam envelope code, was used to find detailed beam phase space parameters (centroids, sigma matrices) that reproduced the measured data. Quadrupole scan and steerer scan experiments have been used to validate the calibration and alignment of these devices, as well as to independently confirm beam parameters at selected locations. Beam current measurements along the beamlines were used to infer transmission efficiencies and then compared to multi-particle simulations in order to identify beam loss locations. The work resulted in an improved understanding of the beams and beam transfer lines to support further beamline optimization and design activities. The experimental and simulation methodologies, tools, and results and their interpretations should be applicable to many types of operating accelerator facilities.

Pharmacist Medication Titration Program for Patients With Cardiac Sarcoidosis and Systolic Heart Failure: A Retrospective Cohort Study.

A multidisciplinary approach improves guideline-directed medical therapy in systolic heart failure (HF), but its efficacy in patients with HF due to cardiac sarcoidosis is unreported. In a retrospective cohort study, we reviewed 848 patients from our institutional cardiac sarcoidosis clinics, identifying those with a cardiac sarcoidosis diagnosis, HF (left ventricular ejection fraction <50%) at index evaluation, and echocardiograms within 90 days and 11 to 36 months. Patients were stratified by participation in a pharmacist-led medication therapy management (MTM) program for guideline-directed medical therapy optimization (MTM versus non-MTM [NMTM]) without randomization. Demographics, left ventricular ejection fraction, guideline-directed medical therapy (quantified by Kansas City Medical Optimization score), and immunosuppressive therapy were assessed. Primary outcomes included changes in Kansas City Medical Optimization score, left ventricular ejection fraction, and cardiovascular event-free survival (unplanned HF hospitalization, left ventricular assist device /heart transplant, or death). The final cohort included 111 patients (median age, 57 years; 34% women; 64% New York Heart Association class I-II); 43 (39%) were MTM and 68 (61%) were NMTM. Mean Kansas City Medical Optimization score was similar at index evaluation (MTM, 23.2; NMTM, 29.6; P=0.83). At follow-up (median, 16 months), the Kansas City Medical Optimization score increased significantly in both groups (MTM, 23.2 to 74.8; P<0.001; NMTM, 29.6 to 58.7; P<0.001) but was higher in MTM (P=0.001). Mean left ventricular ejection fraction trended toward higher values in MTM (44.4% versus 40.0%, P=0.05). The primary clinical outcome occurred in 1 MTM (2.3%) and 16 NMTM (23.5%) patients, with higher risk in NMTM (hazard ratio, 11.97 [95% CI, 1.58-90.54]; P=0.002). In this retrospective cohort study, a pharmacist-led MTM program was associated with favorable guideline-directed medical therapy optimization and lower risk of adverse cardiovascular outcomes in patients with cardiac sarcoidosis with HF.

Choosing the optimal programming language for the generation of mathematical problems

This paper compares mathematical libraries of web programming languages JavaScript, PHP, Python to create generators in the field of some topics of mathematical analysis and computational mathematics. The main objective of the study is to conduct an experiment with a given set of tasks, using the libraries Math.js, Algebrite, Nerdamer, MathPHP, NumPy, SymPy, SciPy to determine the optimal functionality and performance for performing character and numerical computing. The experimental study was carried out with the help of the libraries listed, where the corresponding tasks were computed with the measurement of their speed. A comparative analysis of the obtained results of the study is given. The main problems that arose during the experiment in different libraries are shown. The obtained results can be used by developers and researchers who are involved in the design and implementation of generators of mathematical problems. In the process of work it is identified that JavaScript and PHP libraries do not fully support all functions for creating generators of mathematical problems. Python was much more efficient in both symbolic and numerical calculations.

The progress of mother-to-child transmission of Human Immunodeficiency Virus (HIV) after Dolutegravir (DTG) optimization program: evidence from a multicenter cohort study in Ethiopia

BackgroundEthiopia aims to eliminate mother-to-child transmission (MTCT) of HIV by 2030. In 2020, Dolutegravir-based antiretroviral treatment (ART) regimen optimization was done for the Prevention of Mother-to-Child Transmission (PMTCT). However, data tracking progress, particularly post-rollout of the Dolutegravir (DTG)-based regimen, and the real-world effectiveness of the new regimen are unavailable.MethodsA multicenter retrospective cohort study was conducted among HIV-infected mothers and their HIV-exposed infants visiting the selected hospitals for routine care. Eligible participants were HIV-exposed infants enrolled in the PMTCT care from 2017 to 2022. However, only the 2021 and 2022 birth cohorts were considered post-DTG optimization considering 2020 a year of optimization. The cumulative incidence of perinatal MTCT tested at 6–8 weeks of infant age, and end of care MTCT tested at 18 months of age was assessed. The exposures of the study were the infant birth cohort years and the different ART regimens used for PMTCT of HIV.ResultsAmong a total of 2,643 routine care enrolled participants, 2521 (95.4%) HIV-exposed infants were included in the analysis. Of these, 210 were on follow-up and excluded from the breastfeeding MTCT analysis. A total of 30/2521(1.2%) [95% confidence interval (CI): 0.8-1.7%] were positive for HIV at 6–8 weeks. Additionally, 11 /2281 (0.50%) (95% CI: 0.3-0.9%) were positive during breastfeeding. At the end of the care, 41/2311 (1.8%) (95% CI: 1.3-2.4%) infants were HIV-positive. The highest end-of-care MTCT was reported in 2019 and 2022 birth cohorts while the lowest was in 2018 (P-value > 0.3). However, after adjusting for baseline characteristics, the trend showed a decrease in transmission rates following the rollout of DTG-based regimen, although statistical significance was not reached. The adjusted odds ratios (AORs) for perinatal, breastfeeding, and end-of-care transmission rates were 0.34 (95%CI: 0.08–1.39), 0.29(95%CI: 0.03–3.05), and 0.38(95%CI: 0.11–1.26) respectively. Compared with the Efavirenz (EFV)-based regimen, the DTG-based regimen was associated with a lower risk of MTCT in both the perinatal (AOR 0.23, 95% CI: 0.06–0.85) and at the end of care (AOR 0.27, 95% CI: 0.09–0.82). Pregnant women who started ART at late gestation had the highest transmission rate regardless of ART regimens (P-value < 0.001).ConclusionsIn the studied cohort population, we observed less than 3% MTCT rate at the end of PMTCT care. The findings might suggest the achievement of MTCT elimination at the hospital level. Although the DTG-based regimen demonstrated a lower risk of transmission, other contributing factors, such as late ART initiation, should be urgently addressed. Future research should focus on prospective designs, interventions targeting late ART initiation, and understanding regional disparities to further advance efforts to eliminate MTCT by 2030.

Exercise Interventions in the Management of Postural Orthostatic Tachycardia Syndrome: A Scoping Review.

This review aims to identify the exercise rehabilitation approaches used for patients with POTS (Postural Orthostatic Tachycardia Syndrome). An electronic literature search was conducted using the PubMed database, covering January 2005 to October 2023. Studies were included if they reported an exercise rehabilitation intervention for POTS patients and resulting clinical outcomes. Eligible study designs included randomized and non-randomized clinical trials and case reports. Initially, 34 publications were identified, but only 14 met the criteria for inclusion. After a thorough analysis, 7 studies were included in this scoping review. The majority of the studies stated aerobic exercise training significantly improves symptoms in most of the patients with orthostatic intolerance, reduces the frequency of syncope, enhances patient quality of life, and improves autonomic balance as assessed by heart rate variability analysis and cardiorespiratory endurance. Short-term exercise training was found to boost physical fitness and cardiorespiratory responses in patients with POTS. Therefore, exercise training can serve as an effective non-pharmacological therapy for managing POTS. This scoping review identified different approaches used for exercise rehabilitation in POTS patients. However, more research is needed to identify the optimal exercise rehabilitation program for this patient population.

Deciphering the Therapeutic Potential of Novel Pentyloxyamide-Based Class I, IIb HDAC Inhibitors against Therapy-Resistant Leukemia.

Histone deacetylase inhibitors (HDACi) are established anticancer drugs, especially in hematological cancers. This study aimed to design, synthesize, and evaluate a set of HDACi featuring a pentyloxyamide connecting unit linker region and substituted phenylthiazole cap groups. A structural optimization program yielded HDACi with nanomolar inhibitory activity against histone deacetylase class I/IIb enzymes. The novel inhibitors (4d and 4m) showed superior antileukemic activity compared to several approved HDACi. Furthermore, 4d and 4m displayed synergistic activity when combined with chemotherapeutics, decitabine, and clofarabine. In vitro pharmacokinetic studies showed the most promising profile for 4d with intermediate microsomal stability, excellent plasma stability, and concentration-independent plasma protein binding. Additionally, 4d demonstrated comparable in vivo pharmacokinetics to vorinostat. When administered in vivo, 4d effectively inhibited the proliferation of leukemia cells without causing toxicity. Furthermore, the binding modes of 4d and 4m to the catalytic domain 2 of HDAC6 from Danio rerio were determined by X-ray crystallography.