Cognitive scientists have paid very little attention to magic as a distinctly human activity capable of creating situations or events that are considered impossible because they violate expectations and conclude with the apparent transgression of well-established cognitive and natural laws. And even though magic techniques appeal to all known cognitive processes from sensing, attention and perception to memory and decision making, the relation between science and magic has so far been mostly unidirectional, with the primary goal of unraveling how magic works. Building up from the deconstruction of a classic magic trick, we provide here a cognitive foundation for the use of magic as a unique and largely untapped research tool to dissect cognitive processes in tasks arguably more natural than those usually exploited in artificial laboratory settings. Magicians can submerge every spectator into the precise experimental protocol they have previously designed, accounting with ease for both circumstantial and social contexts. Magicians do not base the success of their experiments in statistical measures that smear out the individual in favor of an average spectator that we know never exists in the real world. They target each and everyone in the audience and, often, with a complete accomplishment. Magicians deliver their cognitive manipulations in real-time, in tight closed-loop with the audience, and in a single trial (they cannot afford to repeat the trick if it fails). Magic has also an inherent and strong social component, merging the private cognitive processes of each spectator with the group dynamics. Finally, when combined with the wide range of precise measuring and wearable technologies available today, magic paves the way for a road not taken towards real-world cognitive science. We dare to speculate that some of the mysteries of how the brain works may be trapped in the split realities present in each magic effect.

Most traditional theories of intelligence have little to do with the question of whether people with high intelligence can successfully address real world problems. A high IQ is correlated with many important outcomes (e.g., academic prominence, reduced crime), but it does not protect against cognitive biases, partisan thinking, reactance, confirmation bias, and even falling for discredited beliefs such as alchemy, cold fusion, and astrology. There are several newer theories that directly address the question about solving real-world problems. Prominent among them is Sternberg’s adaptive intelligence with “adaptation to the environment” as the central premise, a construct that does not exist on standardized IQ tests (e.g., Sternberg, 2019). Similarly, Stanovich and West (2014) argue that standardized tests of intelligence are not measures of rational thought—the sort of skill/ability that would be needed to address complex real-world problems. Halpern and Butler (2020) advocate for critical thinking as a better model of intelligence for addressing real-world problems than those that are based on psychometric properties of general intelligence. Yes, intelligence (i.e., critical thinking) can be enhanced and used for solving a real-world problem like Covid-19, which we use as an example of contemporary problems that need a new approach. Critical thinking may be an antidote for the chaos of the modern world.

Real-world evidence (RWE) is increasingly involved in the early benefit assessment of medicinal drugs. It is expected that RWE will help to speed up approval processes comparable to RWE developments in vaccine research during the COVID-19 pandemic. Definitions of RWE are diverse marking the highly fluid status in this field. So far, RWE comprises information produced from data routinely collected on patient’s health status and/or delivery of health care from various sources other than traditional clinical trials. These sources can include electronic health records, claims, patient-generated data including in home-use settings, data from mobile devices as well as patient, product and disease registries. The aim of the present update was to review the current RWE developments and guidelines mainly in the U.S., the UK, Europe and Germany field during the last decade. RWE has already been included in various approval procedures of regulatory authorities reflecting its actual acceptance and growing importance in evaluating and accelerating new therapies. However, since the RWE research is still in a transition process and since a number of gaps in this field have been explored, more guidance and a consented definition are necessary to increase the implementation of real-world data.

Background: Ceftobiprole is a fifth-generation cephalosporin that has been approved in Europe solely for the treatment of community-acquired and nosocomial pneumonia. The objective was to analyze the use of ceftobiprole medocaril (Cefto-M) in Spanish clinical practice in patients with infection in hospital or outpatient parenteral antimicrobial therapy (OPAT). Methods: This retrospective, observational, multicenter study included patients treated from September 1, 2021 to December 31, 2022. Results: 249 individuals were enrolled, aged 66.6±15.4 years, 59.4% male, with Charlson index of 4 (IQR 2-6); 13.7% had COVID-19, and 4.8% were in intensive care unit (ICU). The most frequent type of infection was respiratory (55.8%), followed by skin and soft tissue infection (21.7%). Cefto-M was administered to 67.9% as empirical treatment, being in monotherapy for 7 days (5-10) in 53.8% of cases. The infection-related mortality was 11.2%.The highest mortality rates were for ventilator-associated pneumonia [40%], and infections due to methicillin-resistant S. aureus (20.8%) and Pseudomonas aeruginosa (16.1%). Mortality-related factors were age (OR: 1.1, 95%CI [1.04-1.16]), ICU admission (OR:42.02, 95%CI[4.49-393.4]), and sepsis/septic shock (OR:2.94, 95%CI [1.01-8.54]).Conclusions: In real life, Cefto-M is a safe antibiotic, with only half of prescriptions in respiratory infections, mainly administered as rescue therapy in pluripathological patients with severe infectious diseases.

Background: Objectives were to determine the real-life effectiveness and safety of DT with dolutegravir (50 mg/QD) plus lamivudine (300 mg/QD) in multiple-tablet regimen (MTR) in naïve PLHIV followed up for 48 weeks and to evaluate the compliance and satisfaction of patients. Material and methods: Open, single-arm, multicenter, non-randomized clinical trial from May 2019 through September 2020 with 48-week follow-up. Results: The study included 88 PLHIV (91% male) with mean age of 35.9 years; 76.1% were MSM. Mean baseline CD4 was 516.4 cells/uL, with viral load (VL) of 104,828 cop/mL, and 11.4% were in AIDS stage. DT started within 7 days of first specialist consultation in all patients and the same day in 84.1%; 3.4% had baseline resistance mutations (K103N, V106I+E138A, and V108I); 12.5% were lost to follow-up. At week 48, 86.3% had VL< 50 cop/uL by intention-to-treat analysis and 98.7% by per-protocol (PP) analysis. Virological failure (VF) was recorded in 1.1%, with no resistance mutation. One blip was detected in 5.2%, without VF. Three reported anxiety, dizziness, and cephalgia, respectively, at week 4 and one insomnia at week 24; none reported adverse events at week 48. Mean weight was 4 kg higher at 48 weeks (p=0.0001) and abdominal circumference 3 cm larger at 24 weeks (p=0.022). No forgetfulness occurred in 98.7% of patients. Patient satisfaction was 90/100 at 4, 24, and 48 weeks. Conclusion: Real-world data demonstrate that dolutegravir plus lamivudine in MTR is effective, safe, and satisfactory, moderately increasing weight and abdominal circumference and administrable on a test-and-treat strategy.

Conventional cancer clinical trials can be time-consuming and expensive, often yielding results with limited applicability to real-world scenarios and presenting challenges for patient participation. Real-world data (RWD) studies offer a promising solution to address evidence gaps and provide essential information about the effects of cancer treatments in real-world settings. Defining RWD based on its original intent, which is the collection of data at the point of care for clinical purposes, can distinguish it from conventional clinical trial data. RWD can be generated using experimental designs that resemble those used in conventional clinical trials, but with several advantages, such as improved efficiency and a better balance between internal and external validity. RWD can support pharmacovigilance, insights into disease progression, and the development of external control groups. Prospective RWD collection enables evidence generation based on pragmatic clinical trials (PCTs) that support randomized study designs and expand clinical research to the point of care. To ensure the quality of real-world studies, it is crucial to implement auditable data abstraction methods and develop new incentives to capture clinically relevant data electronically at the point of care. The treatment landscape is constantly evolving, with the integration of front-line immune checkpoint inhibitors (ICIs), either alone or in combination with chemotherapy, affecting subsequent treatment lines. Real-world effectiveness and safety in underrepresented populations, such as the elderly, patients with poor performance status (PS), hepatitis, or human immunodeficiency virus-infected patients, are still largely unexplored. Similarly, the cost-effectiveness and sustainability of these innovative agents are important considerations in the real world.

When dealing with complex models in real situations, many optimization problems require using more than one objective function to represent the relevant characteristics of the system under consideration adequately. This is why multiobjective optimization algorithms that can deal with several objective functions are required in order to obtain reasonable results in an adequate processing time. This paper presents the multiobjective version of a recent metaheuristic algorithm that optimizes a single objective function, known as the Majority-minority Cellular Automata Algorithm (MmCAA), inspired by cellular automata operation. The algorithm presented here will be known as the Multiobjective Majority-minority Cellular Automata Algorithm (MOMmCAA). The MOMmCAA adds repository management and multiobjective search space density control to complement the performance of the MmCAA and make it capable of optimizing multiobjective problems. To evaluate the performance of the MOMmCAA, benchmark test sets are taken (DTLZ, quadratic, and CEC-2020), along with real-world engineering design problems, compared against other multiobjective algorithms recognized for their performance (MOLAPO, GS, MOPSO, NSGA-II, and MNMA). The results obtained in this work show that MOMmCA produces comparable performance with the other metaheuristic methods, which shows it as a competitive algorithm to be used for multiobjective problems. MOMmCAA was implemented in MATLAB, and its source code can be consulted in GitHub. https://github.com/juanseck/MOMmCAA

Background: Gram-negative bacteremia, especially from Klebsiella spp., Escherichia coli, and Pseudomonas aeruginosa, poses a significant public health threat due to multidrug resistance and high mortality rates. Cost-effective treatments are essential in low-middle income countries as Colombia. Methods: This descriptive, phase IV study was conducted in a tertiary care hospital in Colombia. Adult patients with Gram-negative bacteremia treated with generic piperacillin/tazobactam (Penibactam®) were evaluated. Clinical and microbiological responses were assessed over 12 months. Results: The study included 30 critically ill patients with an average APACHE II score of 22.12. The clinical response at day 7 was 66% (n = 20), and the microbiological response was 56.7% (n = 17). By the end of follow-up, clinical improvement was observed in 63.3% (n = 19), with a mortality rate of 23% (n = 7). The cardiovascular system was the most common infection site. Conclusions: Generic piperacillin/tazobactam demonstrated effectiveness and safety comparable to existing literature in treating Gram-negative bacteremia, offering a viable, cost-effective alternative for critically ill patients in real-world settings.

Introduction: Myasthenia gravis (MG), an immune disorder affecting nerve-muscle transmission, often necessitates tailored therapies to alleviative longitudinal symptom fluctuations. Here, we aimed to examine and compare the treatment cycle intervals and efficacy of efgartigimod in four patients. This case series mainly offers insights into personalized treatment cycle intervals and efficacy of efgartigimod for patients with MG in our facility in Japan. Methods: We retrospectively analyzed four patients with MG (2 patients with early-onset, 1 with late-onset, and 1 with seronegative MG, mainly managed with oral immunosuppressants as prior treatments) who completed four or more cycles of efgartigimod treatment from January 2022 to September 2023. We focused on changes in serum immunoglobulin (IgG) level, acetylcholine receptor antibody (AChR-Ab) titer, and quantitative MG (QMG) score. Results: Efgartigimod, administered at a median of 5.0 [IQR 5.0, 7.5] weeks between cycles, led to decreased serum IgG level in all patients and reduced AChR-Ab titers in seropositive patients. All patients showed sustained MG symptom improvement, with considerably reduced QMG scores before efgartigimod treatment. None of the patients required rescue medications or developed treatment-related adverse events. Conclusion: Customized efgartigimod administration intervals effectively enhanced clinical outcomes in patients with MG without notable symptom fluctuations, demonstrating the benefits of individualized treatment approaches and validating the safety of efgartigimod during the study period.

(1) Background: Aim was to investigate real-world effectiveness (hypothesizing non-inferiority) and safety profile of risdiplam in paediatric and adult nusinersen-risdiplam spinal muscular atrophy (SMA) switch cohort. (2) Methods: A retrospective and anonymous collection of relevant demographic and clinical data for all Croatian SMA patients switched from nusinersen to risdiplam up to September 2023 (reimbursed by Croatian Health Insurance Fund – CHIF) was performed using CHIF database and associated reimbursement documentation. Patients were included in effectiveness and safety analysis if they met the following inclusion criteria: i) risdiplam reimbursed by CHIF; ii) patient received at least 6 doses of nusinersen before switch to risdiplam; iii) no relevant pause between the latter disease modifying drugs (DMDs); iv) availability of all prespecified studied data and parameters. (3) Results: 17 patients met inclusion criteria [58.9% female; median age 12.75 (3.0-44.5) yr.]. In our ‘switch’ cohort, we have demonstrated a non-inferiority of risdiplam to nusinersen, in SMA 1 (+1.0 in CHOP INTEND; p=0.067), SMA 3p (+0.7 in HFMSE; p=0.897) and SMA 3a (+0.8 in RHS; p=0.463) subpopulations, during a one-year follow-up period. There were no reports on respiratory function worsening, feeding worsening, and no lethal events. No new safety concerns were identified, except of the weight gain that arose as a new potential adverse drug reaction ‘signal’ in two patients. (4) Conclusions: We have reported a pivotal real-world findings on switching SMA patients from nusinersen to risdiplam and demonstrated its effectiveness (non-inferiority), safety and tolerability in a heterogenous paediatric and adult ‘switch’ cohort, which will further increase the quality and standards of care as well as safety of a notable portion of SMA patients; especially for those who demand switch from nusinersen to other DMDs from clinical or personal reasons.

Prevention and management of cytomegalovirus (CMV) reactivation is important to improve outcome of allogeneic hematopoietic cell transplantation (allo-HCT) recipients. The aim of this study was to analyze real-world data for incidence and characteristics of CMV infections until 1-year after allo-HCT under 100-day letermovir prophylaxis. A single-center retrospective study was conducted between November 2020 and October 2021. During the study period, 358 patients underwent allo-HCT, 306 of whom received letermovir prophylaxis. Cumulative incidence of clinically significant CMV infection (CS-CMVi) was 11.4%, 31.7%, and 36.9% at 14-weeks, 24-weeks, and 1-year post-HCT, respectively. In multivariate analysis, risk of CS-CMVi increased with graft-versus-host disease (GVHD) ≥ grade 2 (adjusted odds ratio 3.640 [2.036–6.510]; P &lt; 0.001). One-year non-relapse mortality was significantly higher in letermovir breakthrough CS-CMVi patients than those with subclinical CMV reactivation who continued letermovir (P = 0.002). There were 18 (15.9%) refractory CMV infection in this study population. In summary, letermovir prophylaxis is effective in preventing CS-CMVi until day 100, which increased after cessation of letermovir. GVHD is still a significant risk factor in letermovir prophylaxis era. Further research is needed to establish individualized management strategies especially in patients with significant GVHD or letermovir breakthrough CS-CMVi.

Background Enfortumab vedotin shows promise as a targeted therapy for advanced urothelial carcinoma, particularly in patients who previously received platinum-based chemotherapy and immune checkpoint inhibitors. The EV-301 phase III trial demonstrated a significantly improved overall survival and response rates compared with standard chemotherapy. However, more data, especially from larger real-world studies, are needed to assess its effectiveness in Japanese patients. Methods A total of 6,007 urothelial cancer patients treated with pembrolizumab as second-line treatment were analyzed. Among them, 619 patients received enfortumab vedotin after pembrolizumab, while 394 received docetaxel or paclitaxel after pembrolizumab. Results The enfortumab vedotin group showed a longer overall survival than the paclitaxel/docetaxel group (p=0.013, hazard ratio: 0.71). In the multivariate analysis, enfortumab vedotin induction was an independent risk factor for the overall survival (p=0.013, hazard ratio: 0.70). There were no significant differences in the cancer-specific survival. Conclusions Enfortumab vedotin prolonged the overall survival in Japanese patients with advanced or metastatic urothelial carcinoma compared with paclitaxel or docetaxel after pembrolizumab treatment.

Hemianopia poses significant challenges and requires effective rehabilitation strategies. Traditional visual restoration methods have focused on low-level vision therapies in controlled environments. This paper proposes the integration of natural and ecologically valid environments, e.g., virtual reality (VR), three-dimensional (3D) settings, and cognitive interactions for visual rehabilitation. We review various studies that employed common practices in laboratory or controlled settings. We also discuss the disadvantages of traditional techniques and advocate for a comprehensive and ecological framework in visual rehabilitation. Instead of correcting visual inputs, we emphasize training the visual system to adapt and restore functionality in real-world contexts. By combining real-world environments and higher-level vision approaches, we can enhance visual recovery, improve daily functioning, and restore the quality of life for individuals with visual field defects. Moreover, we stress the importance of incorporating natural environments, VR, 3D settings, and cognitive interactions to maximize the effectiveness of visual rehabilitation and empower patients to regain their visual abilities in real-world scenarios. Continued research and development in this field are crucial to refine and expand the application of these innovative techniques, ultimately enhancing the lives of individuals affected by visual field defects.

The therapeutic management of acquired thrombotic thrombocytopenic purpura (aTTP) has recently benefited from the introduction of caplacizumab, an agent directed to inhibition of platelet aggregation. This real-world analysis investigated the epidemiology, the demographic and clinical characteristics of aTTP patients in Italy before and after caplacizumab introduction in 2020. Hospitalized adults with aTTP were included using the administrative databases of healthcare entities covering 17 million residents. Epidemiological estimates of aTTP considered the 3-year period before and after caplacizumab introduction. After stratification by treatment or not with caplacizumab, aTTP patients were characterized for their demographic and clinical features. The annual incidence before and after 2020 was estimated in the range 4.3-5.8 cases/million and 3.6-4.6/million, respectively. From 2018 to 2022, 393 patients with aTTP were included, 42 of them treated with caplacizumab. Caplacizumab-treated patients were aged on average 46.8 years, 31% were males, and showed tendentially better clinical outcomes: no treated patients died at either 1 month or 3 months after caplacizumab treatment initiation, compared to 10.5% (1 month) and 11.1% (3 months) mortality among the untreated. Caplacizumab treatment was associated with a trend towards shorter hospital stays. These findings suggest that caplacizumab advent provided clinical and survival benefits for patients with aTTP.

The purpose of this study was to quantify characteristics of bimanual movement intensity during 30-hour Hand Arm Bimanual Intensive Therapy (HABIT) and bimanual performance (activities and participation) in real-world using accelerometers in children with unilateral cerebral palsy (UCP). Twenty-five children with UCP participated in a 30-hour HABIT program. Data was collected from bilateral wrist-worn accelerometers during 30-hours HABIT to quantify the movement intensity, and three days pre- and post-HABIT to assess real-world performance gains. Movement intensity and performance gains were measured using six standard accelerometer-derived variables. Bimanual capacity (body function and activities) was assessed using standardized hand function tests. We found that accelerometer variables increased significantly during HABIT, indicating increased bimanual symmetry and intensity. Post-HABIT, children demonstrated significant improvements in all accelerometer metrics, reflecting real-world performance gains. Children also achieved significant and clinically relevant changes in the hand capacity following HABIT. Therefore, our findings suggest that accelerometers can objectively quantify bimanual movement intensity during HABIT. Moreover, HABIT enhances hand function as well as activities and participation in real-world situation in children with UCP.

As the automotive industry undergoes a phase of rapid transformation driven by technological advancements, the integration of driving simulators stands out as an important tool for research and development. The usage of such simulators offers a controlled environment for studying driver behavior; the alignment of data, however, remains a complex aspect that warrants a thorough investigation. This research investigates driver state classification using a dataset obtained from real-road and simulated conditions, recorded through JINS MEME ES_R smart glasses. The data set encompasses electrooculography signals, with a focus on standardizing and processing data for subsequent analysis. For this purpose, we used a recurrent neural network model, which yielded a high accuracy on the testing dataset (86.5%). The findings of this study indicate that the proposed methodology could be used in real scenarios and that it could be used for the development of intelligent transportation systems and driver monitoring technology.

Acute myeloid leukemia (AML) is a hematological malignancy that predominantly affects the elderly. Prognosis declines with age. For those who cannot tolerate intensive chemotherapy, historically established treatment options have been hypomethylating agents (HMAs), low dose cytarabine (LDAC), and best supportive care (BSC). As the standard of care evolves for those unfit for intensive chemotherapy, there is a need to understand established treatment pathways, clinical outcomes and healthcare resource utilization in Canada. The CURRENT study was a retrospective chart review of AML patients not eligible for intensive chemotherapy who initiated first-line treatment between 1 January 2015 and 31 December 2018. Data were collected from 170 Canadian patients treated at six hematology centers, of whom 118 received systemic therapy and 52 received BSC as first-line treatment. Median overall survival was 8.58 months and varied from 2.96 months for BSC to 13.31 months for HMAs. Over 80% of patients had at least one outpatient visit, and 67% of patients receiving systemic therapy and 71% of those receiving BSC had at least one admission to hospital, during their first line of therapy. A total of 96 (81.4%) patients receiving first line systemic therapy and 39 (75.0%) of those receiving first line BSC had at least one red blood cell or platelet transfusion. These findings highlight the unmet need for novel therapies for patients ineligible for intensive chemotherapy.

Background: Observational health data has the potential to be a rich resource to inform clinical practice and regulatory decision making. However, the lack of standard data quality processes makes it difficult to know if these data are research ready. The EHDEN COVID-19 Rapid Col-laboration Call presented the opportunity to assess how the newly developed open-source tool Data Quality Dashboard (DQD) informs the quality of data in a federated network. Methods: 15 Data Partners (DPs) from 10 different countries worked with the EHDEN taskforce to map their data to the OMOP CDM. Throughout the process at least two DQD results were collected and compared for each DP. Results: All DPs showed an improvement in their data quality between the first and last run of the DQD. The DQD excelled at helping DPs identify and fix conformance is-sues but showed less of an impact on completeness and plausibility checks. Conclusions: This is the first study to apply the DQD on multiple, disparate databases across a network. While study-specific checks should still be run, we recommend that all data holders converting their data to the OMOP CDM use the DQD as it ensures conformance to the model specifications and that a database meets a baseline level of completeness and plausibility for use in research.

The aim is to evaluate a program for direct oral anticoagulants (DOACs) management in nonvalvular atrial fibrillation (NVAF) patients, according to patient profiles, appropriateness of dosing, patterns of crossover, effectiveness and safety. This is an observational and longitudinal retrospective study in a cohort of patients attended in daily clinical practice in a single regional hospital in Spain with a systematic follow-up plan for up to 3 years for patients initiating dabigatran, rivaroxaban or apixaban between JAN/2012-DEC/2016. We analyzed 490 episodes of treatment (apixaban 2.5 mg: 9.4%, apixaban 5 mg: 21.4%, dabigatran 75 mg: 0.6%, dabigatran 110 mg: 12,4%, dabigatran 150 mg: 19.8%, rivaroxaban 15 mg: 17.8% and rivaroxaban 20 mg: 18.6%) in 445 patients. 13.6% of patients on dabigatran, 9.7% on rivaroxaban, and 3.9% on apixaban, switched to other DOACs or changed dosing. Apixaban was the most frequent DOAC switched to. The most frequent reasons for switching were toxicity (23.8%), bleeding (21.4%) and renal deterioration (16.7%). Inappropriateness of dose was found in 23.8% of episodes. Patients taking apixaban 2.5 mg were older, had higher CHA2DS2VASc score and lower creatinine clearance. Patients taking dabigatran 150 mg and rivaroxaban 20 mg were younger, had lower CHA2DS2VASc and higher creatinine clearance. Rates of stroke/transient ischemic attack (TIA) were 1.64/0.54 events/100 patients-years, while rates of major, clinically relevant non-major (CRNM) bleeding and intracranial bleeding where 2.4, 5, and 0.5 events/100 patients-years. Gastrointestinal and genitourinary bleeding were the most common type of bleeding events (BE). On multivariable analysis, prior stroke (RR: 4.2; CI: 1.5-11.8; p=0.006) and age (RR: 1.2; CI: 1.1-1.4; p=0.006) were independent predictors of stroke/TIA. Concurrent platelet inhibitors (RR: 7.1; CI: 2.3-21.8; p=0.001), male gender (RR: 2.1; CI: 1.2-3.7; p=0.0012) and age (RR: 1.1; CI: 1.02-1.13; p=0.005) were independent predictors of BE. This study complements the scant data available on the use of DOACs in NVAF patients in Spain, confirming a good safety and effectiveness profile

The higher education sector in Africa has experienced remarkable growth over the past decades, enrolling and graduating millions of students annually. Despite this progress, high unemployment rates among graduates and pervasive underdevelopment have raised questions about the relevance of higher education in Africa. Critics have intensely scrutinized the quality of curricula, highlighting a significant mismatch between the skills offered and the demands of the job market. This disconnect is often due to curricula that are unresponsive to both job requirements and students' needs. Enhanced pedagogical approaches are essential to address this issue. Community engagement and service learning (CE&SL) offer promising solutions by bridging the gap between theoretical knowledge and practical application. Recognizing the potential benefits, higher education institutions across the continent are gradually integrating CE and SL into their teaching and research frameworks. However, the adoption of these approaches has been slow. This paper explores the opportunities and challenges hindering the effective and widespread implementation of CE and SL in African higher education institutions and proposes practical strategies to overcome these obstacles. By embracing these innovative approaches, African universities can better prepare graduates for the dynamic job market and contribute more effectively to the continent's development.

Results from the phase III Keynote-024 clinical trial have established Pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR and ALK wild-type. However, given the differences between patients treated in routine clinical practice and within a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-up, we designed a retrospective observational study of patients with NSCLC who were treated with Pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were to assess PFS and OS using the Kaplan-Meier method, treatment response and safety. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6-10.0) and 25.5 months (95% CI: 21.8-31.6), respectively. We also found that ECOG PS, PD-L1 expression and smoking habit were prognostic factors for PFS, while age, sex, ECOG PS, smoking habit and histology had an impact on OS. Multivariable analysis confirms prognostic role of PD-L1 for PFS and ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of Pembrolizumab in the first-line setting as well as a safety profile consistent with the results of Keynote-042. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution.

In cognitive radio systems, identifying spectrum opportunities is fundamental to efficiently use the spectrum. Spectrum occupancy prediction is a convenient way of revealing opportunities based on previous occupancies. Studies have demonstrated that usage of the spectrum has a high correlation over multidimensions which includes time, frequency, and space. Accordingly, recent literature uses tensor-based methods to exploit the multidimensional spectrum correlation. However, these methods share two main drawbacks. First, they are computationally complex. Second, they need to re-train the overall model when no information is received from any base station for any reason. Different than the existing works, this paper proposes a method for dividing the multidimensional correlation exploitation problem into a set of smaller sub-problems. This division is achieved through composite two-dimensional (2D)-long short-term memory (LSTM) models. Extensive experimental results reveal a high detection performance with more robustness and less complexity attained by the proposed method. The real-world measurements provided by one of the leading mobile network operators in Turkey validate these results.

Background: Potential calcium-related adverse events of vitamin D supplement use have not been addressed in large-scale, real-world data so far. Methods: Leveraging data from the UK Biobank, encompassing 445,493 individuals aged 40-69, we examined associations of high 25-hydroxyvitamin (25[OH]D) levels ≥100 nmol/L and vitamin D supplementation with hypercalcemia (plasma calcium >2.6 mmol/L), kidney stones, and atherosclerosis assessments (pulse wave arterial stiffness index and carotid intima-medial thickness). Regression models were comprehensively adjusted for 49 covariates. Results: Approximately 1.5% of the participants had high 25(OH)D levels, 4.3% regularly used vitamin D supplements, and 20.4% reported regular multivitamin use. At baseline, the hypercalcemia prevalence was 1.6%, and 1.1% were diagnosed with kidney stones during follow-up. High 25(OH)D levels were neither associated with calcium-related adverse events nor atherosclerosis assessments. Vitamin D and multivitamin supplementation were associated with an increased prevalence of hypercalcemia (odds ratios and 95% confidence intervals: 1.46[1.32-1.62] and 1.11[1.04-1.18], respectively) but were neither associated with atherosclerosis nor future kidney stones. Conclusion: High 25(OH)D levels observable in routine care were not associated with any adverse outcome. Vitamin D users have a slightly higher prevalence of hypercalcemia, possibly due to co-supplementation with calcium, but without higher atherosclerosis prevalence or risk of kidney stones.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections represent the fourth-leading cause of death attributable to antimicrobial resistance globally, but a standardized therapy is still lacking. In this narrative review we focused the antibiotic treatment of CRAB infections in view of newly β-lactam agents (NBLs) like sulbactam/durlobactam and cefiderocol, discussing the main hot points such as the superiority of combination treatment over monotherapy and the best antibiotic partner to use in combination. Sulbactam/durlobactam seems to be the best candi-date to replace current back-bone agents. Cefiderocol, could play a crucial role in combina-tion-regimen. Due to toxicity and the PK/PD limitations, colistin (or polymyxin B) should be used as an alternative agent (when no other options are available). Tigecycline (or minocycline) and fosfomycin could represent suitable partners for both NBLs. Randomized clinical trials (RCTs) are needed to better evaluate the role of NBLs in CRAB infection treatment and to compare the ef-ficacy of tigecycline and fosfomycin as partner antibiotics. Synergism should be tested between NBLs and “old” drugs (rifampicin and trimethoprim/sulfamethoxazole). Huge efforts should be made to accelerate pre-clinical and clinical studies on safer polymyxin candidates with lung im-proved activity, as well as on the i.v. rifabutin formulation.

Background: Dual disorders (DD) involve the coexistence of substance use disorder (SUD) with another mental illness, often from psychotic and affective categories. This study explores the ef-fectiveness of brexpiprazole, a third-generation antipsychotic, in individuals diagnosed with schizophrenia spectrum disorder (DSM-V) and comorbid AUD/SUD (DSM-V). Methods: Eighteen enrolled patients underwent psychometric assessments at baseline and one month into brexpiprazole treatment administered at a mean dosage of 2 mg/day. Results: Brexpiprazole demonstrated significant reductions in psychopathological burden (PANSS total score, p=0.004), improved CGI total score (p=0.042), and decreased MOAS total score (p=0.012). Quality of life improved in SF-36 subscales (p<0.05). Substance craving reduction, though observed, did not reach statistical significance. Conclusions: This study provides initial evidence supporting brexpiprazole's efficacy and safety with positive effects on psychopathology and quality of life, emphasizing the need for tailored, comprehensive treatment strategies in this complex patient population.

Investigating the network response to node removal and the efficacy of the node removal strategies are related and fundamental questions in network science. Research studies proposed many node centralities based on the network structure ranking node to remove. The random walk (RW) on networks describes a stochastic process in which a walker travels among nodes. RW can be a model of transport, diffusion, and search on networks, and an essential tool for studying the importance of network nodes. In this manuscript, we propose four new measures of node centrality based on RW. Then, we compare the efficacy of the new RW node removal strategies to network dismantle with effective node removal strategies from the literature, such as betweenness and closeness node removal over synthetic and real-world networks. We evaluate the network dismantle along node removal using the size of the largest connected component (LCC). We find that, hence the betweenness nodes attack is the best strategy overall, the new node removal strategies based on RW show the highest efficacy in peculiar network topology. Specifically, RW strategies based on covering times emerge as the most effective strategy on a synthetic lattice network and two real-world road networks. Our results may be useful in selecting the best node attack strategies in a specific class of networks and in building more robust network structures.

Background: In schizophrenia (SZ), social cognition mediates the relationship between neurocognition and social functioning. Although people with major depressive disorder (MDD) also exhibit cognitive impairments, which are often prolonged, little is known about the role of social cognition in MDD. Methods: Using data obtained through an internet survey, 210 patients with SZ or MDD were selected using propensity score matching based on their demographic information and illness duration. Social cognition, neurocognition, and social functioning were evaluated using the Self-Assessment of Social Cognition Impairments, Perceived Deficits Questionnaire, and Social Functioning Scale, respectively. The mediation effects of social cognition on the relationship between neurocognition and social functioning were examined in each disease group. Invariances of the mediation model across the two groups were then analyzed. Results: The SZ and MDD groups had mean ages of 44.49 and 45.35 years, contained 42.0% and 42.8% women, and had mean illness durations of 10.76 and 10.45 years, respectively. In both groups, social cognition had significant mediation effects. Configural, measurement, and structural invariances across the groups were established. Conclusion: The role of social cognition in patients with chronic depression was similar to that in schizophrenia. Social cognition could be a common endophenotype for various psychiatric disorders.

Objective: To perform a systematic review of real-world outcomes for anti-CGRP-mAbs. Methods: Following the PRISMA guidelines, we searched PubMed for real-world data of Erenumab, Galcanezumab, Fremanezumab, or Eptinezumab in patients with migraine. Results: We identified 104 publications (73 retrospective), comprising 8 pharmaco-epidemiologic and 63 clinic-based studies, 30 case reports and 3 other articles. None of the clinic-based studies provided follow-up data over more than one year in more than 200 patients. Findings suggest reductions in health insurance claims and days with sick-leave as well as better treatment adherence with anti-CGRP-mAbss. Effectiveness, reported in 59 clinic-based studies, was comparable to randomized controlled trials. A treatment pause was associated with an increase in migraine frequency and switching to another antibody resulted in a better response in some of the patients. Adverse events and safety issues were addressed in 70 papers including 22 single case reports. Conclusion: Real-world data on anti-CGRP-mAbs are limited by retrospective data collection, small patient numbers and short follow-up periods. The majority of papers seem to support good effectiveness and tolerability of anti-CGRP-mAbs in the real-world setting. There is an unmet need for large prospective real-world studies providing long-term follow-up of patients treated with anti-CGRP-mAbs.

Private vehicle travel is the most basic mode of transportation, and the effective control of the real-world fuel consumption rate of light-duty vehicles plays a vital role in promoting sustainable economic development as well as achieving a green low-carbon society. Therefore, the impact factors of individual carbon emission must be elucidated. This study builds five different models to estimate real-world fuel consumption rate of light-duty vehicles in China. The results reveal that the Light Gradient Boosting Machine (LightGBM) model performs better than the linear regression, Naïve Bayes regression, Neural Network regression, and Decision Tree regression models, with mean absolute error of 0.911 L/100 km, mean absolute percentage error of 10.4%, mean square error of 1.536, and R squared (R2) of 0.642. This study also assesses a large number of factors, from which three most important factors are extracted, namely, reference fuel consumption rate value, engine power and light-duty vehicle brand. Furthermore, a comparative analysis reveals that the vehicle factors with greater impact on real-world fuel consumption rate are vehicle brand, engine power, and engine displacement. Average air pressure, average temperature, and sunshine time are the three most important climate factors.

This study reports the likely real-world effects of fleet replacement with electric vehicles (EVs) and higher efficiency EURO6 vehicles on the exhaust emissions of NOx, PM, and CO2 in the seven boroughs of the West Midlands (WM) region, UK. National fleet composition data, local EURO distributions and traffic compositions were used to project vehicle fleet compositions for different roads in each borough. A large dataset of real-world emission factors including over 90,000 remote-sensing measurements, obtained from remote sensing campaigns in five UK cities, was used to parameterise the emission profiles of the studied scenarios. Results show that adoption of the fleet electrification approach would have the highest emission reduction potential on urban roads in WM boroughs. It would result in maximum reductions ranging from 35.0-37.9%, 44.3-48.3%, 46.9-50.3% for NOx, PM, and CO2, respectively. In comparison, the EURO6 replacement fleet scenario would lead to reductions ranging from 10.0-10.4%, 4.0-4.2%, and 6.0-6.4% for NOx, PM, and CO2, respectively. The studied mitigation scenarios have higher efficacies on motorways than on rural and urban roads because of the differences in traffic fleet composition. The findings presented will help policymakers choose climate and air quality mitigation strategies.

This study aims to evaluate the outcomes of neoadjuvant chemotherapy with immunotherapy in patients with non-small cell lung cancer (NSCLC) within a real-world context. We analyzed medical records from January 2022 to August 2023, focusing on individuals aged 18 and older diagnosed with resectable NSCLC who received neoadjuvant chemoimmunotherapy prior to surgical intervention. The cohort comprised 56 patients, predominantly smokers (95%) and male (74%), with 80% presenting at stage III. Of the participants, 44 underwent surgery, with 95% receiving lobar resection. Clinical assessments via PET-CT imaging revealed an 86% rate of response or disease stabilization, while pathological evaluations showed complete and major pathological responses in 61% of cases. This real-world data supports the safety and efficacy of incorporating immune checkpoint inhibitors in the neoadjuvant treatment of NSCLC, followed by surgical resection.

A multicenter retrospective analysis of 408 patients diagnosed with onychomycosis and attended at three tertiary care Spanish hospitals was conducted to assess the effectiveness and safety of a combined treatment with ciclopirox 8% hydroxypropyl chitosan (CPX 8% HPCH) nail lacquer and oral antifungal agents (terbinafine, itraconazole, and fluconazole). Data were extracted and analyzed using the EHRead® technology based on natural language processing and machine learning and using SNOMED CT terminology. The median age was 51 years with a ratio male: female close to 1. Repeated nail trauma was the most common risk factor (7.1%). More than half of patients (56.6%) underwent fungal culture. Terbinafine was used in 67.7% of patients, itraconazole in 20.8%, and fluconazole in 11.5%. Treatment synchronicity distribution revealed that 59.1% of patients started concomitant treatment with CPX 8% HPCH and oral antifungals, 27.9% had initial oral antifungals, and 13% had initial nail lacquer. The response to treatment (positive response 15.7%, presumed positive 59.8%) was unrelated to treatment synchronicity or type of antifungal agent. Erythema (5.6%), diarrhea (4.9%) and fever (4.2%) were the most frequently registered potential adverse events. The present findings provide valuable insights for physicians paving the way for better management of patients with onychomycosis.

Serum neurofilament light chain (sNfL) levels have been proposed as a biomarker of the clinical activity, disability progression, and response to treatment of people with multiple sclerosis (PwMS); however, questions remain about its implementation in clinical practice. Ocrelizumab (OCR) has proven effective to improve clinical and radiological outcomes and to reduce sNfL levels. This real-life study followed the sNfL levels of 30 PwMS treated for 12 months with OCR and evaluated the usefulness of this biomarker for the short-term prognosis, considering expanded disability status scale (EDSS), annualized relapse rate (ARR), radiological activity, and NEDA-3 values. OCR reduced the ARR in 83% of PwMS and the radiological activity in 80%. Their EDSS was maintained, while NEDA-3 was achieved in 70% at 12 months. OCR produced an early reduction in sNfL levels (at 3 months). At baseline, greater MRI-evaluated radiological activity was associated with higher sNfL levels. sNFL levels over the first 12 months of treatment did not predict a suboptimal response or sustained control of the disease. Longer-term studies are needed to explore the predictive usefulness of sNfL levels in PwMS treated with high-efficacy drugs

Analyzing BRCA1/2 tumor pathogenic variants (TPVs) in epithelial tubal/ovarian cancers (EOC) has become an essential part of the diagnostic workflow in many centers to guide treatment options and genetic cascade testing. However, there is no standardization of testing procedures, including techniques, gene assays, or sequencers used, and data on the execution of tumor tests remains scarce. Therefore, we evaluated characteristics of BRCA1/2 tumor testing in advanced-stage EOC with real-world national data. Pathology reports of patients diagnosed with EOC in 2019 in the Netherlands were obtained from the Dutch Pathology Registry (PALGA), and data regarding histological subtype and BRCA1/2 tumor tests were extracted. A total of 999 patients with advanced-stage EOC were included. Tumor tests were performed for 502 patients (50.2%) and BRCA1/2 TPVs were detected in 14.7%. Of all tests, 48.6% used hybrid capture techniques and 26.5% used PCR-based techniques. More than half of the tests (55.0%) analyzed other genes in addition to BRCA1/2. Overall, this study highlights the heterogeneity in the execution of BRCA1/2 tumor tests. Despite a lack of evidence of quality differences, we emphasize that adequate reporting and internal and external quality monitors are essential for high-quality implementation and execution of reliable BRCA1/2 tumor testing, which is crucial for identifying all patients with BRCA1/2 TPVs.

The connectivity level of last-generation vehicles is constantly on the rise. The combined use of Vehicle-To-Everything (V2X) connectivity and autonomous driving can provide remarkable benefits through the optimization of the route and speed trajectory. In this framework, this paper focuses on vehicle eco-driving optimization in a connected environment. The virtual test rig of a premium segment passenger car was used for generating the simulation scenarios. The benefits, in terms of energy and time savings, that the introduction of V2X communication, integrated with cloud computing, can have in a real-world scenario were assessed. The Reference Scenario is a pre-defined Real Driving Emissions (RDE) compliant route, while the simulation scenarios were generated by assuming two different penetration levels of V2X technologies. The associated energy minimization problem is formulated and solved by means of a global optimization algorithm, i.e., Dynamic Programming (DP). The optimization framework includes information coming from the surrounding environment, e.g., traffic lights state, speed limits, distance to travel, etc. The simulations show that introducing a smart infrastructure along with optimizing the vehicle speed in a real-world route can potentially reduce the required energy by 54% while shortening the travel time by 38%. Finally, a sensitivity analysis is performed on the bi-objective optimization cost function to find a set of Pareto optimal solutions, between energy and travel time minimization.

Purpose: To meet the challenges of the precision medicine era, quality assessment of shared sarcoma care becomes pivotal. The MDT approach is the most important parameter for succesfull outcome. Because of all MDTs disciplines surgery is the key step to render sarcoma patients disease free, defining the spectrum of a sarcoma surgeon is critical. To the best of the authors knowledge, a comprehensive interoperable digital platform to assess the scope of sarcoma surgery and the experience of a sarcoma surgeon in its full complexity is lacking. Methods: A web-based real-world data (RWD) registry on sarcoma surgery has been created to assess the clinical exposure, tumor characteristics, and surgical settings and techniques applied for both resections and reconstructions of sarcomas and thereby the surgical exposure of an individual surgeon over time. Results: During 10 years, there were 723 sarcoma board/MDT meetings discussing 3130 patients. A total of 1094 patients underwent 1250 surgical interventions on mesenchymal tumors by one single sarcoma surgeon. These included 615 deep soft tissue tumors (197 benign, 102 intermediate, 281 malignant, 27 simulator, 7 metastasis, 1 blood), 116 superficial soft tissue tumors (45 benign, 12 intermediate, 40 malignant, 18 simulator, 1 blood) and 519 bone tumors (129 benign, 112 intermediate, 182 malignant, 18 simulator, 46 metastasis, 14 blood and 18 sequelae of 1st treatment). Detailed types of resections and reconstructions were analyzed. Conclusion: A web-based RWD sarcoma surgeon registry with transparent real-time descriptive analytics is feasible and enables large scale definition of the surgical complexity and ultimately quality of sarcoma care.

More than 179,000 individuals have fallen ill of the Coronavirus disease (COVID-19) caused by the SARS-CoV-2 virus, which first emerged in China less than four months ago in December 2019. As of today, there exist no approved treatments against COVID-19. Vaccines are being developed, but they will take time, at least one year, to reach the population. Drug repositioning represents a fast track because already approved medicines have been broadly tested through multiple trials. We developed a repositioning strategy that mostly leads to candidates that are commonly used. The advantages are that they will facilitate proof of concept in humans through a “real-world evidence” approach and should be rapidly available to the population. We focus on the established research results that the unfolded protein response (UPR) and autophagy pathways of the host cells are essential to the life cycle of previously known coronaviruses. We performed the relevant bioinformatics analysis to understand and confirm if SARS-CoV-2 may interact with these druggable pathways. Based on these considerations, we prioritized two additional druggable pathways, which are important to the viral life cycle and tightly connected to UPR/autophagy signaling: the mitochondrial permeability transition pores (MPTP) and NLRP-3 inflammasome pathways. These four important pathways are perturbed in most major common diseases and have therefore been targeted by numerous broadly prescribed drugs. We have identified 97 approved drugs that are known to modulate these four identified pathways, and which represent, therefore, interesting repositioning candidates. Although it is indisputable that these drugs should never be used for immediate self-medication against COVID-19, we notice that some of them could also be prescribed to individuals who have COVID-19 comorbidities (e.g., hypertension). It is debated if these comorbidities are linked to the pathology itself (e.g., hypertension) or the drugs used to treat the pathology (e.g., sartans). Therefore, relevant preclinical tests and massive electronic health records (i.e., real-world evidence) must be used to pre-screen them and check the COVID-19 prognosis of individuals taking these drugs.

A new treatment option for cluster headache (CH) prevention is needed. Monoclonal antibodies (mABs) against calcitonin gene-related peptide (CGRP) ligands are used as a preventative treatment for migraine. Considering the CGRP’s role in the CH attack’s ignition and upkeep, fremanezumab and galcanezumab have been evaluated for CH preventative treatment. However, only high-dose (300 mg) galcanezumab was proven for episodic CH prevention. We herein report 3 cases of migraine and comorbid CH with previous failures of preventive treatments. The 2 cases were treated with fremanezumab and the one with non-high-dose galcanezumab. All 3 cases showed good results not only on migraine but also on CH attacks. Our report suggested the efficacy of CGRP-mABs for CH prevention. Our cases differed from the cases in the phase 3 trials of CGRP-mABs for CH prevention in the following 2 points. First, the patients had both migraine and comorbid CH. Second, the combined use of CGRP-mABs with preventative drugs for CH, such as verapamil and/or prednisolone, was performed. Future accumulation of real-world data may prove the efficacy of CGRP-mABs for CH prevention.

Increasingly large numbers of people are using digital weight-loss services (DWLSs) to treat overweight or obesity. Although it is widely agreed that digital modalities improve access to care in general, obesity stakeholders remain concerned that many DWLSs are not comprehensive or sustainable enough to deliver meaningful health outcomes. This study adopted a mixed-methods approach to assess why and after how long patients tend to discontinue Austral-ia’s largest DWLS, a program that combines behavioural and pharmacological therapy under the guidance of a multidisciplinary care team. We found that in a cohort of patients who commenced the Eucalyptus DWLS between January and June 2022 (n=5604), mean program adherence was 171.2 (±158.2). Inadequate supply of a patient’s desired Glucose-like peptide-1 receptor agonist medication was the most common reason for discontinuation (43.7%), followed by program cost (26.2%), result dissatisfaction (9.9%), and service dissatisfaction (7.2%). Statistical tests revealed that ethnicity and age both had a significant effect on patient adherence. These findings suggest that DWLSs have the potential to improve access to comprehensive, continuous obesity care, but that care models need to improve upon the one observed in the Eucalyptus Australia DWLS to maximise program adherence.

(1) Background: Most patients with mycosis fungoides (MF), a form of cutaneous T-cell lym-phoma (CTCL), develop relapsed/refractory (R/R) disease following front-line systemic therapy. This report describes treatment patterns and outcomes from the subpopulation with R/R MF. (2) Methods: This observational, retrospective, cohort study analysed patient records (1984–2016) from 27 clinical sites in Eurpe. Outcomes included treatments received, response to first-, second- and third-line treatment, overall survival (OS), and progression-free survival (PFS). (3) Results: Of 104 patients with MF, 100 received second-line and 61 received third-line therapy. Median (range) times from start of first-line therapy to first R/R MF and from first to second R/R MF were 11.2 (0.3–166.5) and 13.5 (0.0–174.6) months, respectively. Second-and third-line treatment options varied and comprised systemic therapies (85% and 79% of patients, respectively), radio-therapy (32% and 34%, respectively) and topical therapies (48% and 36%, respectively). Median (95% confidence interval [CI]) OS from the diagnosis of first R/R MF was 11.5 (6.5–not reached [NR]) years and was higher with non-chemotherapy (NR) versus chemotherapy (6.5 years); es-timated median PFS (95% CI) from the time of first R/R MF was 1.3 (1.0–2.1) years. (4) Conclu-sion: High rates of R/R disease were observed after second- and third-line treatments in this re-al-world cohort, with longer median OS in patients receiving non-chemotherapy versus chemo-therapy. Following the standard management of MF and using recently approved targeted therapies can help improve patient outcomes in advanced-stage MF.

At the beginning of our observations, humanity believed that the Earth was the center of the uni-verse and that the sun was spinning around the Earth. Claude Ptolémée (100-168) made a mistake by modelling the movements in the geocentric referential, the model of the sun and planet move-ments was an illusion and all Humanity was wrong. Nicolas Copernic (1473-1543) showed the illusion and simplified the system by moving from the geocentric referential to the heliocentric referential. In the present paper, I would like to discuss about the possibility of making mistakes with quantum theory. I postulate that we are living in a virtual classical world that we consider as real. In my interpretation, the decoherence problem and wave function collapse do not exist at all, because we are the illusion, we are living in illusion, in a mirage. It is impossible to observe the quantum world as it is, in our virtual classical referential, and we see the quantum world with a false vison of quantum reality because we are not yet in the universal real quantum referential whose I postulate the existence. As we are illusions when seen from this universal quantum ref-erential, Schrödinger’s cat paradox is an illusion as life and death are illusions. We must be very humble with quantum theory and we should not put ourselves in the center of the quantum world again particularly with our lives and deaths. I also develop a cosmological model based on bipolarity and schizophrenia which explains well the recent observations of the James Webb’s spatial tele-scope. We will be collectively able to reach the universal quantum referential by changing our vision of life and quantum world. I also explain how to go out of human suffering. This will be our Big Bang.

We conducted a retrospective evaluation of the clinical outcomes and prognostic factors in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice in Japan. Between 2012 and 2023, a total of 127 consecutive patients with nmCRPC received ARSI treatment. Overall survival (OS), metastatic-free survival (MFS), and prostate-specific antigen progression–free survival (PSA-PFS) from ARSI initiation were assessed using Kaplan–Meier methodology. Clinical factors associated with OS in nmCRPC were analyzed using the Cox proportional hazards model. Among the patients, 72, 26, 12, and 17 received enzalutamide (ENZ), abiraterone (ABI), apalutamide (APA), and darolutamide (DARO) as first-line therapy. The median OS and MFS for all patients were 79.0 and 42.0 months, respectively. Median PSA-PFS was 27.0, 20.0, 10.0, and 14.0 months for patients treated with ENZ, ABI, APA, and DARO, respectively (p = 0.33). Multivariate analysis revealed that a baseline PSA level ≥3.67 ng/ml at ARSI initiation was significantly associated with poorer OS (p = 0.002). ARSI demonstrated favorable efficacy in nmCRPC patients. There were no significant differences in clinical outcomes among different types of ARSI therapy for nmCRP. Elevated baseline PSA at ARSI initiation was significantly associated with poorer OS.

Falls, highly common in the constantly increasing global aging population, can have a variety of negative effects on their health, well-being, and quality of life, including restricting their capabilities to conduct Activities of Daily Living (ADLs), which are crucial for one’s sustenance. Timely assistance during falls is highly necessary, which involves tracking the indoor location of the elderly during their diverse navigational patterns associated with ADLs to detect the precise location of a fall. With the decreasing caregiver population on a global scale, it is important that the future of intelligent living environments can detect falls during ADL.s while being able to track the indoor location of the elderly in the real world. Prior works in these fields have several limitations, such as – the lack of functionalities to detect both falls and indoor locations, high cost of implementation, complicated design, the requirement of multiple hardware components for deployment, and the necessity to develop new hardware for implementation, which make the wide-scale deployment of such technologies challenging. To address these challenges, this work proposes a cost-effective and simplistic design paradigm for an Ambient Assisted Living system that can capture multimodal components of user behaviors during ADLs that are necessary for performing fall detection and indoor localization in a simultaneous manner in the real world. Proof of concept results from real-world experiments are presented to uphold the effective working of the system. The findings from two comparison studies with prior works in this field are also presented to uphold the novelty of this work. The first comparison study shows how the proposed system outperforms prior works in the areas of indoor localization and fall detection in terms of the effectiveness of its software design and hardware design. The second comparison study shows that the cost for the development of this system is the least as compared to prior works in these fields, which involved real-world development of the underlining systems, thereby upholding its cost-effective nature.

In article 16 of the United Nations Convention (UN), or the United Nations Convention on the Rights of the Child (UNCRC), which is usually called the Convention on the Rights of the Child, outlines the right of every child to privacy and protection against violations of privacy related to the home. , family, communication, and their good name. Children's privacy, especially when it comes to personal data, requires strict boundaries. Current digital developments influence children's parenting and thinking patterns with potential negative impacts. Children can be targets of abuse in the digital world. Children's personal data is often used until they become independent. This research, using normative legal methods, aims to analyze regulations related to the protection of children's personal data in the digital era. Therefore, updates are needed in the laws and regulations governing children's personal data to safeguard their privacy rights in accordance with the UNCRC.

This study evaluates the incidence and characteristics of adverse events (AEs) following the second COVID-19 booster dose, leveraging Taiwan's distinctive approach of extending booster vaccinations to all citizens, unlike the targeted high-risk group strategies in other countries. Utilizing data from Taipei Veterans General Hospital's Vaccine Adverse Event Reporting System (VAERS) from October 27, 2022, to January 19, 2023, the research examines AEs in 441 out of 1711 second booster recipients, considering factors like age, vaccine brands, and booster combinations. The findings reveal incidence rates (IR) of 25.6% (95% CI: 21.1-30.8) after the first booster and 24.9% (95% CI: 20.5-30.0) after the second, mostly non-serious, with those having AEs post-first booster 5 times more likely to report them again (Incidence rat rato, 5.02, P&lt;0.001). Significantly, switching from the mRNA1273 vaccine to another brand reduced AE risk by 18%. The study underscores that AEs are more repetitive than cumulative with additional booster doses, advocating for personalized vaccination strategies based on individual medical histories and previous vaccine reactions. These insights are valuable for healthcare providers in discussing potential AEs with patients, thereby improving vaccine compliance and public trust, and for policymakers in planning future booster vaccination strategies.

In the TANGO study, the long-term noninferior efficacy of switching to dolutegravir/lamivudine (DTG/3TC) compared to continuing tenofovir alafenamide–based regimens was demonstrated in treatment-experienced adults with HIV. However, there is limited real-world data comparing the effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) and DTG/3TC in Asia. This retrospective observational study, conducted at a designated HIV-care hospital from March 2019 to January 2023, aimed to address this gap. Demographic, clinical, and laboratory data, including HIV viral loads and lipid profiles, were collected and analyzed. The primary outcome was the proportion of patients with HIV RNA <50 copies/mL at week 48 in both groups, utilizing a snapshot, per-protocol–exposed population. A total of 1086 patients were included, with 511 in the DTG/3TC group and 575 in the BIC/FTC/TAF group. At week 48, 98% of patients in the DTG/3TC group and 94% in the BIC/FTC/TAF group achieved HIV RNA <50 copies/mL (p <0.01). Logistic regression analysis identified risk factors for detectable viral loads at week 48, including HIV RNA >100,000 copies/mL (AOR 5.13, 95% CI 1.42–18.53), low-level viremia (AOR 3.91, 95% CI 1.07–14.25), and record of virologic failure ≥2 times (AOR 4.21, 95% CI 1.64–10.85) before the switch. Furthermore, no significant difference was found between the DTG/3TC and BIC/FTC/TAF regimens (AOR: 1.51, 95% CI 0.70–3.24). In conclusion, the study demonstrates that the effectiveness and safety profiles of DTG/3TC and BIC/FTC/TAF were comparable in treatment-experienced adults with HIV, particularly among those with undetectable viral loads at baseline.

As the aging of the world accelerates, clarifying the relationship between cultural differences and ageism is an urgent issue. Therefore, in this study, we conducted a correlation analysis between the six cultural scales of Hofstede et al. [1] and the 10 ageism scales calculated from data on 35,232 people from 31 countries included in the World Values Survey Wave 6 by Inglehart et al. [2]. The results of a partial correlation analysis controlling for economic and demographic factors showed that the cultural scales were correlated with ageism. This is the first study to show that diverse cultural scales are related to multiple dimensions of ageism.

As urbanization continues to increase, key conservation areas like World Heritage sites are being altered. This transformation is a cause for concern as it threatens the Outstanding Universal Value of these sites. To address this issue, a research question was formulated: How urban is World Heritage? The research focused on identifying and monitoring urbanization in heritage core zones listed on the World Heritage by tracking changes in built-up areas from 1985 to 2015. The findings revealed that urban developments, including housing, transport infrastructure construction, visitor accommodation facilities, and land conversions, have significantly impacted heritage properties. More than a third (37\%, 426) of the cultural heritage properties reported urban development, with the highest occurrences in Europe, North America, Asia, and the Pacific. Furthermore, these regions also displayed the highest rate of change per year between 1985 and 2015. This indicates the urgent need to identify and monitor the urbanization of World Heritage to preserve their OUV amidst increasing urban development.

It is time that universities reexamine what is meant by globalization. Contemporary researchers in science and the humanities (Critchley, Chomsky, Mumford, Ostrom, Eisenstein, Ferry, Orr, Shiva, Klein, Margulis, Meadows, Capra and Tolba, just to name a few) have aptly redefined the concept of « world » as a biological and cultural ecosystem. This paper seeks ways to integrate the theory and practice of eco-citizenship into various cross-disciplinary aspects of higher education, with a focus on curricular adjustments that may be steered by World Languages and Cultures programs. While "global citizenship" is still often understood today as a form of supranational citizenship that may find its actualization through the valuable, yet often arrested efforts of the United Nations, or as the individualistic result of a neoliberal economic emancipation of markets and capital throughout the world, this notion must rather be embedded within a radically cultural, natural and ethical bedrock from which a more potent world citizenry will stem. Departments of World Languages and Cultures and cultures are ideally positioned in the academic landscape to foster the development of a greater eco-civic and biospheric awareness that can permeate new curricular orientations of universities in the US and abroad.

Abstract. The remarks by the Supreme Leader of the Islamic Revolution on the toll of the famines that afflicted occupied Iran in World War I and World War II indicate a desire to incorporate these calamities in Iran’s national narrative and collective memory. His criticism of famine historiography and stated toll numbers, and the unfolding catastrophic famine in Gaza, justify and necessitate a fresh look at each famine’s historiography and toll. This article re-estimates the toll of each famine by including many overlooked and neglected primary sources and in ways not previously done. It builds a trajectory of Iran’s demographic development from 1810 to 1944, and derives the toll of each famine. The World War II famine and typhus epidemics had claimed 5.5 million. World War I famine was also more deadly, though the 1869-73 famine was not far behind. At least 15.5 million Iranians died in the two world wars, a fact nowhere reflected in the history of the conflicts. Iran’s 1944 population of 12 million was unchanged from that of 1850 and a century of population growth obliterated

In this study, I will present some documentary evidence that Carlos Drummond de Andrade’s poem “A Máquina do Mundo” [The Machine of the World] (1949) was based on prior reflections contained in a forgotten newspaper article entitled “Poesia e Pesadelo” [Poetry and Nightmare] (1949). In that article, Drummond critically analyzed some of the theses of Stephen Spender's essay “What Is Modern in Modern Poetry” (1948), which had just been published in The Tiger's Eye magazine. As soon as he read Spender's text, Drummond wrote “Poetry and Nightmare” and began to elaborate a narrative poem whose protagonist would be a machine. All the documentary evidence indicates that Drummond took Spender's lessons as touchstones for the elaboration of the narrative and allegorical structure of “The Machine of the World.” According to the interpretation I am proposing here, Drummond, in writing the machine poem, put into practice at least six lessons drawn from Spender’s essay, namely: 1) the modern poet must represent the tension between the external machinelike landscape and the landscape of the inner world of the creative imagination; 2) he must also represent the machinelike, ugly, and urban world around him in a beautiful and poetic way; 3) he must avoid the misconceptions of excessive utopian visionarism, as well as creeping realism; 4) he must reject the imperative of political engagement, whose principle of action states that poetry has a transformative mission in society; 5) he must free himself from the obsession with free verse as the only form of modern poetry and start using the traditional fixed forms; 6) he must understand machines as poetic symbols of human passions, and not just as exotic objects foreign to human reality. My conclusion is that, after reading Spender’s essay, Drummond changed his aesthetic and philosophical understanding of what defines the essence of modern poetry, both in terms of form and content.

We tested the possibility of using “adverse events count” (AEC) as a drug-risk indicator and side-effect severity indicator. Data from 3938 adverse event (AE) reports for COVID-19 vaccines (Comirnaty, Moderna, Vaxzevria, and Janssen) and 6869 AE reports for other medicines were collected from the Bulgarian Drug Agency database (01.01.2018–31.03.2022). AEC was modeled with zero-adjusted negative binomial (ZANBI) and zero-adjusted Poisson inverse Gaussian (ZAPIG) regression models, which account for zero absence and overdispersion. The models’ fit was checked with residual diagnostic plots and parametric correspondence to normality. Explanatory variables were: age, sex, sequence number (order of submission), severity of AE, and vaccine type. Average AEC was higher in severe vs. non-severe AE, and in females vs. males; it decreased with age and was lower in Comirnaty than other vaccines. Variability of AEC for COVID-19 data decreased with sequence number in severe AE and increased in non-severe AE. Full ZANBI models had greater sensitivity than parametric ZANBI or ZAPIG models. Results showed correlation between AEC and AE severity, suggesting AEC as a simple and reliable measure of drug-risk and side-effect severity for clinicians and regulators, especially for COVID-19 vaccines.

Drafting is a common technique to reduce the drag experienced by elite runners on races, leading to better running efficiency and energy savings. The tactic has been successfully used in previous races where world records were set, especially by Eliud Kipchoge in the 2018 and 2022 editions of the Berlin marathon. In the 2023 edition of the Chicago Marathon, Kenyan runner Kelvin Kiptum broke the Marathon record after a 2:00:35 finish. This feat becomes even more impressive by the lack of use of drafting formations, despite the availability of two pacers for the majority of the race. In this study, the drag faced by Kiptum and his pacers during the race is calculated by means of computational fluid dynamics (CFD). The performance of each runner is evaluated from an energetic standpoint, and the analysis is extended to include more efficient drafting formations. Our results indicate that, by properly using the advantages of drafting, Kiptum could have finished the race at a staggering 1:57:34, a full three minutes better than his own record and 215 seconds better than the previous world record.

Advances in cosmology and astronomical observations over the last two decades have revealed significant tensions and many ambiguities within the standard model of cosmology of a spatially flat Universe, the lambda cold dark matter model. Moreover, the recent Planck Legacy 2018 (PL18) release has confirmed the presence of an enhanced lensing amplitude in the cosmic microwave background (CMB) power spectra, which prefers a positively curved early Universe with a confidence level higher than 99%. This paper addresses the study of a quantum mechanism that could replace the concept of dark matter and energy by considering a primordial curvature as preferred by the PL18 release while yielding the present-day spatial flatness. The implied primordial curvature is incorporated as the background curvature to extend the field equations in terms of the brane-world modified gravity. The Universe evolution is modelled by utilizing a new wavefunction of the Universe that propagates in the bulk with reference to the scale factor of the early Universe and its radius of curvature upon the emission of the CMB, which revealed both positive and negative solutions. This characteristic implies that a pair of entangled wavefunctions was created and evolved in opposite directions as a manifestation of distinct matter and antimatter sides of the Universe. The wavefunction indicates a nascent hyperbolic expansion away from early energy is followed by a first phase of decelerating expansion during the first 10 Gyr, and then, a second phase of accelerating expansion in reverse directions, whereby both sides free-fall towards each other under gravitational acceleration. The predicted background curvature evolution demonstrates the fast orbital speed of outer stars owing to external fields exerted on galaxies as they travelled through earlier conformally curved spacetime. Finally, the wavefunction predicts an eventual phase of rapid spatial contraction that culminates in a Big Crunch, signaling a cyclic Universe. These findings reveal that early plasma could be separated and evolved into distinct sides of the Universe that collectively and geometrically inducing its evolution, physically explaining the effects attributed to dark matter and energy.

George Satayana stated that “those who do not learn from history are doomed to repeat it”. As our UK “good outcome” death toll of 20,000 from coronavirus (SARS CoV -2/ COVID -19) in 2020 has sadly been surpassed; never has a phrase been more pertinent. The last major pandemic on a similar scale to COVID-19 is “Spanish Flu” from 1918. We aim to delineate the timeline of events in response to the 1918 Spanish flu pandemic and compare this to the timeline of COVID 19 response, given that the NHS and WHO have since both been long established. In the last 102 years many changes have occurred. Health services across the world have significantly improved, with the advent of mechanical ventilation and antimicrobial treatments. Vaccination programmes against common pathogens have prevented many large-scale disease threats, however novel illnesses have also emerged. Worldwide communication through the Internet and many agencies including the World Health Organisation has improved, and the awareness and surveillance of disease is more prominent. Despite advances in healthcare and communication, the national and international timeline for public health intervention in the current COVID pandemic in comparison to the Spanish flu pandemic of more than 100 years ago is virtually identical. The World Health Organisation operates to promote global health and prevent spread of disease, with this in mind; should the WHO have intervened earlier?​ We need to learn quickly from this pandemic and improve planning for the future.

Teclistamab (TEC) is the first B-cell maturation antigen-directed bispecific antibody approved by the European Medicines Agency and Food and Drug Administration for triple-class exposed relapsed/refractory multiple myeloma (RRMM). As TEC is increasingly being used in real-world (RW) settings, this study sought to gather existing RW evidence on effectiveness, safety, healthcare resource utilization, and clinical practices associated with TEC. A systematic literature review was performed to identify RW observational studies of adults with RRMM treated with TEC. Sixty-one records representing 41 unique studies were included; sample sizes ranged from 8 to 572 patients. Where reported, median follow-up ranged from 2.3 to 33.6 months and more than 65% of patients would have been ineligible for the pivotal trial of TEC (MajesTEC-1) in all but one study. Across populations with ≥50 patients, overall response rates ranged from 50 to 66% and cytokine release syndrome (CRS) rates ranged from 18 to 64%. Tocilizumab use for CRS management was reported in 14 studies, with two indicating lower CRS rates (13% and 26%) when used prophylactically. Survival and infection outcomes showed wide variability due to short follow-up in most studies. Overall, early RW effectiveness and safety outcomes of TEC were comparable to findings from MajesTEC-1.

This study explores the limitations of current AI systems, which predominantly function in the digital realm, and investigates the transformative potential of embodied AI. Embodied AI involves AI agents equipped with physical bodies, enabling them to interact directly with the physical world. This research focuses on how embodied AI can bridge the "embodiment gap" and enhance human-machine collaboration and learning in dynamic environments. The research examines the fundamental differences between traditional AI systems and embodied AI, emphasizing the importance of physical interaction for contextual understanding, adaptive learning, and intuitive human-machine collaboration. It explores various applications of embodied AI, including robotics, autonomous vehicles, and assistive technologies, demonstrating how physical embodiment can improve performance, safety, and user experience. Through experimental studies and real-world case analyses, the study highlights the advantages of embodied AI in tasks requiring situational awareness, dexterity, and real-time decision-making. It also addresses the challenges associated with developing and deploying embodied AI systems, such as sensor integration, real-time processing, and human-machine interface design. Findings indicate that embodied AI can significantly improve the efficacy of AI systems in dynamic and unpredictable environments. By leveraging physical embodiment, AI agents can better understand and respond to their surroundings, facilitating more natural and effective interactions with humans. The research concludes with recommendations for advancing embodied AI, including interdisciplinary collaboration, investment in sensor and actuator technologies, and the development of standardized frameworks for embodied intelligence.

The urgency to develop vaccines against Covid-19 is putting pressure on the long and expensive development timelines which are normally required for development of lifesaving vaccines. There is a unique opportunity to take advantage of new technologies, smart and flexible design of clinical trials, and evolving regulatory science to speed up vaccine development against Covid-19 and transform vaccine development altogether.

The genus Dirphys Howard is synonymized with Encarsia Förster syn. n. and treated as a species-group of Encarsia, referred to henceforth as the Encarsia mexicana species-group. The monophyly of Encarsia is discussed in relation to Dirphys. The new synonymy is based on phylogenetic analyses of the nuclear ribosomal 28S-D2 gene region (43 taxa, 510 bp). The Encarsia mexicana species-group is recovered as strongly monophyletic within Encarsia. All species of the Encarsia mexicana species-group are revised. The group includes six previously described species, and fourteen newly described species. All species are described (or redescribed) and illustrated. Detailed distributional data, and, where available, plant associate and host records are provided for all species. Encarsia myartsevae Kresslein &amp; Polaszek nom. nov. is here proposed as a replacement name for Encarsia mexicana Myartseva, now preoccupied by Encarsia mexicana (Howard). A dichotomous identification key, supplemented by an online multiple-entry key, is provided for all species.

The following guide is aimed at aiding in the curation of herbarium collections in Melastomataceae, with an emphasis on the New World species. It contains a summary of the taxonomic realignments at the tribal and generic level within Neotropical taxa of Melastomataceae, as well as some general comments for other groups. A table with a generic linear sequence is also provided, as well as tables with new and synonymized New World genera since 2005 and all currently accepted species. Lastly, a table with the synonyms of over 1000 accepted Neotropical species that have been impacted by these generic realignments is also provided.

Current cellular facts allow us to follow the link from chemical to biochemical metabolites, from the ancient to the modern world. In this context, the "RNA world" hypothesis proposes that early in the evolution of life, the ribozyme was responsible for the storage and transfer of genetic information and for the catalysis of biochemical reactions. Accordingly, the hammerhead ribozyme (HHR) and the hairpin ribozyme, belong to a family of endonucleolytic RNAs performing self-cleavage that might occur during replication. Furthermore, regarding the ultraconserved occurrence of HHR in several genomes of modern organisms (from mammals to small parasites and elsewhere), these small ribozymes have been regarded as living fossils of a primitive RNA world. They fold into 3D structures that generally require long-range intramolecular interactions to adopt the catalytically active conformation under specific physicochemical conditions. By studying viroids as plausible remains of ancient RNA, we recently demonstrated that they replicate in non-specific hosts, emphasizing their adaptability to different environments, which enhanced their survival probability over the ages. All these results exemplify ubiquitously features of life. Those are the versatility and efficiency of small RNAs, viroids and ribozymes, as well as their diversity and adaptability to various extreme conditions. All these traits must have originated in early life to generate novel RNA populations.

In the world city theory, most researchers focus on the service sector in the urban economy and less discuss the role of manufacturing. However, the path of only emphasizing financial and corporate service could not fit the sustainability concept. Compared to Anglo-American world city, Global South’s world cities have distinct pathway to be industrialization, tertiarization and globalization. This paper adopted dynamic historic perspective with first-hand materials including in-depth interviews with managers and government officers and second-hand data including yearbook statics and economic census to closely examine the emerging world city-- ‘World Factory’ in Global South, Guangzhou in China, from 1949 to 2015, to emphasize how manufacturing affects the urban globalization through three dimensions, economic, social and spatial dimensions. To make the confirmation of the role of manufacturing in Guangzhou as sustainable world city, we find manufacturing in Guangzhou builds up the basic foundation of export-oriented economy and makes positive effects on urban economic transformation. In addition, manufacturing remains important source of employment and foreign immigration. Along with urbanization and industrialization, urban spatial expansion and aggregation changes with different urban development concept. We provide new insights on multiple globalization on manufacturing for sustainable world city.

A new method for short circuit fault location is proposed based on instantaneous signal measurement and its derivatives, and is based on the retardation phenomena. The difference between the times in which a signal is registered in two detectors is used to locate the fault. Although a description of faults in terms of a lumped circuit is useful for elucidating the methods for detecting the fault. This description will not suffice to describe the fault signal propagation hence a distributed models is needed which is given in terms of the telegraph equations. Those equations are used to derive a transmission line transfer function, and an exact analytical description of the short circuit signal propagating in the transmission line is obtained. The analytical solution was verified both by numerical simulations and experimentally.

Sarcocystis sp. are coccidian protozoans belonging to the Apicomplexa phylum. As other members of this phylum, they are obligate intracellular parasites having a complex cellular machinery for the invasion of host cells. Sarcocystis spp. display dixenous life cycles, involving a predator and a prey as definitive and intermediate hosts, respectively. Specifically, these parasites develop sarcocysts in the tissues of their intermediate hosts, ranging in size from microscopic to visible to the naked eye, depending on the species. When definitive hosts consume sarcocysts, infective forms are produced in the digestive system and discharged into the environment via feces. Consumption of oocyst-contaminated water and pasture by the intermediate host completes the parasitic cycle. More than 200 Sarcocystis spp. have been described infecting wildlife, domestic animals, and humans, some of which are of economic or public health importance. Interestingly, Old World camelids (dromedary, domestic Bactrian camel, and wild Bactrian camel) and New World or South American camelids (llama, alpaca, guanaco, and vicuña) can each be infected by two different Sarcocystis species: Old World camelids by S. cameli (producing micro- and macroscopic cysts) and S. ippeni (microscopic cysts); and South American camelids by S. aucheniae (macroscopic cysts) and S. masoni (microscopic cysts). Large numbers of Old and New World camelids are bred for meat production, but the finding of macroscopic sarcocysts in carcasses significantly hampers meat commercialization. This review tries to compile the information that is currently accessible regarding the biology, epidemiology, phylogeny, and diagnosis of Sarcocystis spp. infecting Old and New World camelids. In addition, knowledge gaps will be identified to encourage research that will lead to the control of these parasites.

A method of measuring the absolute pose parameters of a moving rigid body using a monocular camera is proposed, aiming at addressing calibration difficulties and inconsistencies of repeated measurements of the rigid-body pose for a camera having a varying focal length. The proposed method does not require calibration beforehand. Using more than six non-coplanar control points symmetrically arranged in the rigid-body and world coordinate systems, the matrices of rotation and translation between the camera and two coordinate systems are obtained and the absolute pose of the rigid body measured. In this paper, formulas of the absolute pose measurement of a moving rigid body are deduced systematically and the complete implementation is presented. Position and attitude measurement experiments carried out on a three-axis precision turntable show that the average absolute error in the attitude angle of a moving rigid body measured by an uncalibrated camera at different positions changes by no more than 0.2 degrees. Analysis of the three-dimensional coordinate errors of the centroid of a moving rigid body shows little deviation in measurements made at three camera positions, with the maximum deviation of the average absolute error being 0.53 cm and the maximum deviation of the standard deviation being 0.66 cm. The proposed method can measure the absolute pose of a rigid body and is insensitive to the position of the camera in the measurement process. This work thus provides guidance for the repeated measurement of the absolute pose of a moving rigid body using a monocular camera.

Concerns have been made about how children's health and psychology could be hurt by the growing number of mobile apps they use. This abstract looks at intervention methods and best practices for getting kids to use mobile apps in a healthy way, find a balance with technology, and build up their resilience. Key points include promoting digital literacy and critical thinking, setting clear boundaries and rules, encouraging digital balance, modeling healthy tech habits, building resilience and coping skills, encouraging face-to-face communication, setting up tech-free times and spaces, monitoring app usage and content, promoting mindfulness and self-reflection, and getting professional help when needed. By using these tactics, parents, teachers, and other caretakers can help kids build a healthy relationship with technology, live a balanced life, and build the resilience they need to handle the challenges of the digital world. The goal of these interventions is to make sure that kids' app use is good for their general health, helps them learn and get along with others, and sets them up for long-term success in the digital age.

Poliomyelitis, commonly known as “polio” is a paralytic and perilous disease caused by the poliovirus. Due to its highly contagious nature, the virus was a challenge to the world in the late 1980s. . Since 1988 the collective work of the Global Polio Eradication Initiative (GPEI), Centre for Disease Control and Prevention (CDC), and World Health Organization (WHO) through immunizations, communication awareness, and monitoring have helped the world exonerate polio. The mission of polio-free Pakistan was herculean and had confronted enormous challenges in different ways but came out with positive results. In 2019, with only two remaining polio-endemic countries, Pakistan and Afghanistan, GPEI launched an “Endgame strategy 2019-2023” which aims to eradicate polio globally, with a targeted focus, especially on polio-endemic countries, the plan emphasizes the early detection of polio cases for complete eradication and to restrict the spread of polio. Pakistan has achieved a milestone in combating polio despite having a web of factors that have thwarted Pakistan’s polio eradication efforts, but this is not the end, the struggle continues until we really get an internationally verified certification of Polio free nation, for this WHO has designed a multidisciplinary strategy 2022-2026 to really end this polio for once and for all.

Considerable efforts have been devoted to modifying gravity, which aim to elucidate the possible existence or nature of dark matter and energy, describe observational data more effectively, and formulate quantum gravity. In addition, despite the immense success of the quantum field theory, the framework requires renormalization techniques and breaks down at high energies. Recently, the Planck legacy 2018 release has confirmed the existence of an enhanced lensing amplitude in the cosmic microwave background power spectra, which prefers a positively curved early Universe with a confidence level higher than 99%. This study considers the implied curvature of the early Universe as the curvature of “the background or 4D conformal bulk as a manifestation of vacuum energy” and distinguishes it from the localized curvature that is induced in the bulk by the presence of celestial objects that are regarded as ”4D relativistic cloud-worlds.” Analogously, because gravity appears to emerge owing to spacetime curvature and does not exhibit critical characteristics shared by other fields, it has been incorporated as the local curvature of the bulk affecting the embedded quantum fields that are regarded as propagating “4D relativistic quantum clouds.” To consider the effects of the bulk on embedded clouds, this paper presents interaction field equations in terms of brane-world modified gravity and the perspective of geometrization of the quantum mechanics wherein gravity is manifested by the curvature of 4D conformal bulk as an indicator of the field strength of vacuum energy on the embedded 4D relativistic clouds in addition to the boundary interactions, which could remove the singularities and satisfy a conformal invariance theory. A visualization of the evolution of the 4D relativistic cloud-worlds over the conformal spacetime of the 4D bulk is presented, whereas the standard said theories can be recovered from the interaction field equations.

The provenance of the aminoacyl-tRNA synthetases (aaRS) poses challenging questions because of their role in the emergence and evolution of genetic coding. We investigate evidence about their ancestry from curated structure-based multiple sequence alignments of a structurally invariant “scaffold” shared by all 10 canonical Class I aaRS. Three uncorrelated phylogenetic metrics—residue-by-residue conservation, its variance, and row-by-row cladistic congruence—imply that the Class I scaffold is a mosaic assembled from distinct, successive genetic sources. These data are especially significant in light of: (i) experimental fragmentations of the Class I scaffold into three partitions that retain catalytic activities in proportion to their length; and (ii) evidence that two of these partitions arose from an ancestral Class I aaRS gene encoding a Class II ancestor in frame on the opposite strand. Phylogenetic metrics of different modules vary in accordance with their presumed functionality. A 46-residue Class I “protozyme” roots the Class I molecular tree prior to the adaptive radiation of the Rossmann dinucleotide binding fold that refined substrate discrimination. Such rooting is consistent with near simultaneous emergence of genetic coding and the origin of the proteome, resolving a conundrum posed by previous inferences that Class I aaRS evolved long after the genetic code had been implemented in an RNA world. Further, pinpointing discontinuous enhancements of aaRS fidelity establishes a timeline for the growth of coding from a binary amino acid alphabet.

This paper analyzes the political and economic changes in the world after the drastic changes in eastern Europe, starting with Chinese President Xi Jinping's viewpoint "the biggest change in a century". Also, the new international situation and new development in the post-epidemic as well as the development path and direction of China in the post-epidemicera are expected.

The origin of life has not been solved as yet, in spit of the time passage more than thirty years from publication of RNA world hypothesis by W. Gilbert (1986), which is based on the “gene/replicator--first” theory. On the contrary, I have proposed [GADV]-protein world hypothesis (GADV hypothesis), assuming that life emerged from [GADV]-protein world, which is grounded on the “protein/metabolism-first” theory. However, two weak points of protein world hypothesis, (i) protein cannot be produced without gene, and (ii) protein cannot be self-replicated, have been frequently pointed out by supporters of RNA world hypothesis. Then, I examined whether the two weak points could be overcome by GADV hypothesis or not. From the results, it was confirmed that (i) [GADV]-protein could be pseudo-replicated in the absence of gene owing to protein 0^th-order structure or [GADV]-amino acids, and (ii) the replication ability is not always required from the beginning but it is sufficient to acquire it at some time point until the emergence of life. Thus, it was concluded that life emerged as [GADV]-protein world hypothesis, which is grounded on the “protein/metabolism-first” theory, expects.

The primary motivation for this work is to develop the concept of Marshall's quotient (\cite{ribeiro2016functorial}) applicable to non-commutative multirings endowed with involution, expanding the main ideas of the classical (= commutative, without involution) case presented in Marshall's seminal paper \cite{marshall2006real}. We define two multiplicative properties to deal with the involutive case and characterize their Marshall quotient. Besides, this article presents various cases showing that the ''multi'' version of rings with involution offers many examples, applications, and relatives in (multi) algebraic structures.

Nowadays, security is a top priority. In fact, biometrics uses cutting-edge technologies to identify terrorists and criminals. But the practice of distinguishing humans based on intrinsic physical or behavior traits goes back thousands of years. With the widespread use of computers in the late 20th century, new possibilities for digital biometrics emerged and new technologies were generously used. Among these, we remember high resolution security video cameras and drones. So, the aim of the present project is to study and explain the features of these technologies, especially the ones of the the Phantom 4 Pro+ aircraft and analyze its operating methods in order to identify human faces during live streaming of videos. For this purpose, it will be used Paul Viola and Michael Jones’ face detection algorithm, which includes Haar features and cascade classifiers to identify faces, eyes and ears of an individual.

We investigate wealth accumulation in forestry, assuming that revenues are re-invested. Three different optimization criteria are compared, two of which are based on cash flows, the third financially grounded. Direct optimization of wealth appreciation rate always yields best results. Procedures gained by maximizing internal rate of return are only slightly inferior. With external discounting interest rate, the maximization of net present value yields arbitrary results, with at worst devastating financial consequences.

Billions of euros are invested every year by professional football clubs for the recruitment of players. This article presents the latest advances in the statistical modelling of the factors that market actors take into consideration to determine the transfer prices of professional football players. It extends to a global scale the econometric approach previously developed by the authors to evaluate the transfer prices of players under contract with clubs from the five major European leagues. The statistical technique used to build the model is multiple linear regression (MLR), with fees paid by clubs as an independent variable. The sample comprises over 8000 transactions of players transferred for money from clubs worldwide during the period stretching from July 2014 to March 2024. This paper shows that a statistical model can explain almost 85% of the differences in the transfer fees paid for players. Despite the specific cases and other possible distortions mentioned in the discussion, the use of a statistical model to determine player transfer prices seems highly relevant.

In conclusion, this qualitative exploration has unveiled the profound and essential impact of music on psychological well-being, especially in the post-pandemic world. Through in-depth literature reviews, informal interviews, and observations with thirty CAS participants from SMC, the researcher uncovered ten salient themes that collectively illustrate music's multifaceted role as a potent remedy. These findings showcase how music serves as an emotional outlet, a cognitive enhancer, and a source of inspiration. The emotional depth and spiritual resonance participants associate with music underscore its capacity to address diverse human needs, making it an indispensable tool in navigating the complexities of our post-pandemic reality. Moreover, the cognitive benefits observed, such as improved concentration and focus, are particularly pertinent in the context of remote work and education, highlighting music's necessity in our daily lives. Additionally, this study emphasizes the vital role of virtual music communities in fostering social connections, even amidst physical isolation, further underscoring the enduring relevance of music in these challenging times. This research contributes to the expanding knowledge of music's impact on well-being, offering a holistic perspective encompassing spiritual, emotional, social, and cognitive dimensions. It enriches existing music psychology theories and invites further exploration into the mechanisms underpinning music's diverse effects. These insights have practical implications for fields such as mental health, education, and remote work, where music can be utilized as an essential tool for stress reduction and emotional regulation. This is highlighted further in the Suggested songs that can help sought the mind, body, spirit and soul. Looking ahead, future research could delve deeper into the long-term impact of music engagement on well-being and explore the universality of music's benefits through cross-cultural studies. Overall, music, as illuminated by this study, stands as a timeless and indispensable companion, offering solace, inspiration, vitality, and connection in the face of any contemporary challenges.

With its sights set on sustainable development, transport policy finds itself confronted with the challenge of convincing people to abandon the current path of growth and instead use small, slower vehicles with a reduced range in the future. The problem with this goal is that people's mental structures are shaped by the car ensconced in their heads. Thinking in other terms hardly seems possible; moreover, many of the products classified as vehicles, but smaller in scale than the "car" and that already exist, remain unknown, nor can they be tried out - they are quite literally nowhere to be seen. In light of this situation, the German Federal Environmental Foundation has commissioned a feasibility study to explore the establishment of a World of Experience (Erlebniswelt) of sustainable urban mobility - the EcoMobileum®. Here, the aim is to open up the horizons of a new culture of mobility in order to get people excited about the transformation of mobility.

In recent years, the role of non-coding RNAs (ncRNAs) in regulating cell physiology has begun to be better understood. Recent discoveries in viral molecular biology have revealed that such cellular functions are disturbed during viral infections mainly due to host cell ncRNAs, cellular factors, and virus-derived ncRNAs. Apart from the interplay between those molecules, other interactions derive from the specific folding of RNA virus genomes. These fulfill canonical regulation functions such as replication, translation, and viral packaging. In some cases, folds serve as precursors of small viral RNAs whose biogenesis is not yet clearly understood. Since ncRNAs and RNA viral genomes modulate complex molecular and cellular processes in viral infections, a new taxonomy is being proposed here overarching three main categories, considering the current information about ncRNA interactions in some well-known viral infections. The first category shows examples of host ncRNAs associated with the trigger of the immune response under viral infections. The second category describes interactions between the virus and host ncRNAs. The last category shows how the shape of the RNA viral genome is essential in processing RNAs derived from viruses. Finally, we introduce evidence of how these three categories can also work as a framework in order to organize known interactions of ncRNAs and cellular factors under DENV infection. This new taxonomy of interactions provides a comprehensive framework for organizing the ncRNA regulatory roles in the context of viral interactions and an RNA world.

Simian endogenous retrovirus, SERV, is a successful germ line invader restricted to Old World monkey (OWM) species. (1) Background: The availability of high quality primate genomes warrants a study of the characteristics, evolution and distribution of SERV proviruses; (2) Methods: Cercopithecinae OWM genomes from public databases were queried for the presence of full length SERV proviruses. A dataset of 81 Cer-SERV genomes was generated and analyzed; (3) Results: Full length Cer-SERV proviruses were mainly found in terrestrial OWM, and less so in arboreal, forest- dwelling monkeys. Phylogenetic analysis confirmed the existence of two genotypes, Cer-SERV-1 and Cer-SERV-2, with Cer-SERV-1 showing evidence of recent germ line expansions. Long Terminal Repeat (LTR) variation indicated that most proviruses were of a similar age, and were estimated to be between &lt;0.3 and 10 million years old. Integrations shared between species were relatively rare. Sequence analysis further showed extensive CpG methylation-associated mutation, variable Primer Binding Site (PBS) use with Cer-SERV-1 using PBSlys3 and Cer-SERV-2 using PBSlys1,2, and the recent gain of LTR motifs for transcription factors active during embryogenesis in Cer-SERV-1; (4) Conclusions: sequence analysis of 81 SERV proviruses from Cercopithecinae OWM genomes provides evidence for the adaptation of this retrovirus to germ line reproduction.

Fruits play an important role in human diet and to maintain better health. Globally, India ranks second in fruits production after China. Grapes, mangoes, bananas and oranges were the selected fruit crops for study purpose. The study period is from 1990 to 2018. The present study analyzed the growth rates, instability and elasticity of export quantity, prices of selected fruit crops from major producing countries in the world and also dealt with the major export destinations of Indian fruits. The results showed that an exporting countries should export grapes to Peru, Spain and Chile; bananas to the Panama, Philippines and Ecuador; mangoes to Italy, Egypt and Australia; and, oranges to Thailand, Philippines and Mexico for generating higher revenue because in global market those countries were associated with highest export price with the stability. Globally, the export price elasticity was inelastic in all countries of grapes, oranges and bananas except Italy in oranges and panama in bananas. The study found that export price elasticity of mangoes was marginally higher in the Spain and the Netherlands. The study showed that the major destinations for Indian fruits are; USA, Germany and Netherlands for grapes; USA, Belgium and Germany for bananas; USA, the Netherlands and Viet Nam for mangoes; and, Germany, France and Netherlands for oranges. Globally, the current study gave useful data to comprehend competition of prices for fruits to importing countries. This study may assist in preparing major price strategies and policies on fruits and also assisted in foreign earnings for all nations.

As Christopher Alexander conceived and defined through his life’s work – The Nature of Order – wholeness is a recursive structure that recurs in space and matter and is reflected in human minds and cognition. Based on the definition of wholeness, a mathematical model of wholeness, together with its topological representation, has been developed, and it is able to address not only why a structure is beautiful, but also how much beauty the structure has. Given the circumstance, this paper is attempted to argue for the wholeness as the scientific foundation of sustainable urban design and planning, with the help of the mathematical model and topological representation. We start by introducing the wholeness as a mathematical structure of physical space that pervasively exists in our surroundings, along with two fundamental laws – scaling law and Tobler’s law – that underlie the 15 properties for characterizing and making living structures. We argue that urban design and planning can be considered to be wholeness-extending processes, guided by two design principles of differentiation and adaptation, to transform a space – in a piecemeal fashion – into a living or more living structure. We further discuss several other urban design theories and how they can be justified by and placed within the theory of wholeness. With the wholeness as the scientific foundation, urban design can turn into a rigorous science with creation of living structures as the primary aim.

In this paper, we propose two novel methods for robot-world/hand-eye calibration and provide a comparative analysis against six state-of-the-art methods. We examine the calibration problem from two alternative geometrical interpretations, called hand-eye and robot-world-hand-eye, respectively. The study analyses the effects of specifying the objective function as pose error or reprojection error minimization problem. We provide three real and three simulated datasets with rendered images as part of the study. In addition, we propose a robotic arm error modeling approach to be used along with the simulated datasets for generating a realistic response. The tests on simulated data are performed in both ideal cases and with pseudo-realistic robotic arm pose and visual noise. Our methods show significant improvement and robustness on many metrics in various scenarios compared to state-of-the-art methods.

A dogma is normally considered as a principle or a belief accepted as an indisputable truth by some individuals and/or groups. Theoretically there can be no dogmas in science, but it has been demonstrated that scientific thought operates by conceptual changes. A dogma therefore can be understood as a concept present at the heart of some contemporary research programmes that need to be altered to overcome paradigms. Here we argue that two ideas relating to emergence of the biological system research need to be re-evaluated. First, is the idea that research programmes about the emergence of the biological system are the same as those of the origin of cells. Cells are strikingly important biological entities, hard core concepts for the entire field of biology. The emergence of the biological system happened much earlier than the origin of cells and thus the First Universal Common Ancestor (FUCA) should be viewed as a great-grandfather to the Last Universal Cellular Ancestor (LUCA); i.e. the latter is the first cellular life form. Second, RNA-world theories are the focus of mainstream research programmes for the origin of life stricto sensu. In the RNA-world view, self-replication of nucleic acids is seen as one of the most relevant events in the pre-biotic world. Without denying the relevance of self-replication, we argue here that the most germane event which occurred in the pre-biotic world was the crosstalk between nucleic acids and peptides. When these two macromolecules started to interact, the singularity that aggregated the complexity required to produce life emerged. Thus, comprehension of the early origins of the translation machinery and the assembly of the genetic code is key. Therefore, the relevance of cell theory and self-replication should be re-evaluated as well as the concept of life itself.

The recognition of a place as a World Heritage Site (WHS) by UNESCO is fundamental to preserve its historical and artistic inheritance and, at the same time, to encourage visits to that area. The purpose of this article is to contribute to the study of the relationship between WHS and cultural tourism, with a marked sustainable character, through the presentation of the results of research conducted in the city of Cordoba (Spain) and which analyses the sociodemographic profile of the tourists, the variables that influence their level of satisfaction and of their loyalty and the classification of the travelers through different variables. The principal results of the research show the significant educational level of the surveyed tourists, as well as the high level of satisfaction with the visit, the high number of countries of origin and the outstanding motivation for knowing the city’s heritage roots.

The rationale of this study is to explore underlying sustainability assessment constructs in the context of WCSM implementation as a key focus by manufacturing industries in the journey of achieving world-class status in their manufacturing operations. This study primarily intends to collect primary data from 143 plant managers and supervisors through the structured questionnaires at select manufacturing companies in south India on the basis of area-cum-purposive sampling technique. The survey questionnaire is designed exclusively to reflect the sustainability assessment dimensions in terms of social, economic and environmental issues to examine the impetus of WCSM implementation on the competitive advantage of manufacturing companies. The empirical findings of this study clearly revealed that sustainable manufacturing practices, sustainability programs, creation of sustainable products, safety for employee, community and product, operational efficiency and integration of sustainability goals in day-to-day manufacturing activities were considered to be the key indicators by the manufacturing firms in their never-ending journey towards becoming the world class. Moreover, the WCSM practices & techniques adopted by sample manufacturers have a substantial positive influence on the achievement of competitive advantage in their manufacturing and business operations.

This study assesses the dynamic relationship between macroeconomic factors and bank asset quality based on changes in the condition of stock market returns. A Generalized Method of Moments (GMM) model is employed, using panel data from 18 universal banks spanning the period 2007 to 2021. The analysis revealed that the real GDP growth rate, the average lending rate, and the real exchange rate represent a set of macroeconomic factors with a marked influence on banks' asset quality. In addition, a high inflation rate was found to exert an adverse effect on asset quality, as it affects borrowers' financial ability to meet loan repayment obligations. Furthermore, the study verified the existence of a positive relationship between market condition and asset quality, which implies that bank performance adapts to changes in market conditions as posited under the Adaptive Market Hypothesis (AMH). Bank managers should consolidate banks' asset bases during conditions of market stability to withstand periodic market fluctuations to boost trading momentum. Policy recommendations are suggested to foster a conducive business environment for bank stability.

Investors are currently obliged to take ESG (Environment, Social, Governance) issues into consideration as part of their fiduciary duty. As such, it becomes increasingly important to identify sustainable investments that hold financial value as well. A sector where this is especially underdeveloped is real estate. This has a lot to do with the obfuscated conceptualization of ESG. The article identifies key gaps in literature and practice, and provides a framework to further the understanding of how ESG factors can add societal and financial value in the real estate sector. A key premise of the article is that the user in the building is grossly overlooked. Drawing on insights from behavioral social science and environmental psychology, the paper explains the role of the user in improving buildings’ ESG, also taking into account the investment value. To conclude, the article makes the case that the transition to user-centered smart real estate is the solution to improving both the environmental (E) and social (S) sustainability of buildings, as well as their investment value. Therefore, practitioners and academics are encouraged to critically evaluate and contextualize the ESG framework they are using, as well as the extent to which users are considered and smart technology is employed.

Monkeypox (mpox) caused by the monkeypox virus (MPXV) is currently the most common orthopoxvirus (OPXV) zoonotic disease. Since 2022, a multi-country outbreak of mpox has been reported with atypically rapid human-to-human transmission. The present work aimed to investigate the frequency of MPXV and OPXV DNA detection in different clinical materials taken at acute and convalescent phases of the infection in Bulgarian patients. A total of 181 clinical samples from 42 Bulgarian patients with possible mpox infections were tested. Screening for MPXV DNA (F3L gene) and OPXV DNA (rpo18 gene) were performed by real-time PCR assays. Of all tested patients six (14%) were confirmed with mpox infection. MPXV DNA was detected in 23/181 (12,71%) and OPXV DNA in 20/181 (11,05%) clinical samples. All confirmed patients were men who have sex with men, aged 23 to 44 (at an average age of 35,17±7,91 years) and two of them were HIV positive. The commonest clinical features of patients were fever (5/6), vesicular-pustular rash: perianal (6/6), penile (4/6), and limbs (4/6). MPXV DNA was found with the greatest frequency in specimens of vesicle contents and nasal/oropharyngeal swabs in 6/6 and 5/6. OPXV DNA mainly was detected in vesicle contents (6/6), nasal/oropharyngeal swabs (4/6), and urine (4/6). In the collected follow-up samples, MPXV DNA was detected in the highest percentage in the specimen's vesicle contents (6/6) and urine (6/6) and not demonstrated in samples of feces and saliva. The laboratory surveillance of MPXV is critical to contain the outbreak and to elucidate the new fast transmission of the virus.

Abstract Despite the lightning-fast advances in the management of SARS-CoV after 2 years of pandemic, COVID-19 continues to pose a challenge for fragile patients, who could benefit from early administration of monoclonal antibodies (mAbs) to reduce the risk of severe disease progression. We conducted a prospective study to evaluate effectiveness of mAbs against SARS-CoV-2 among patients at risk for severe disease progression, namely elderly and those with comorbidities, before the omicron variant surge. Patients were treated with either casirivimab/imdevimab, sotrovimab, and bamlanivimab/etesevimab. The rates and risk factos for clinical worsening, hospitalization, ICU admission and death (unfavourable outcomes) were evaluated. A stratified analysis according to the presence of SARS-CoV-2 IgG was also performed. Among 185 included patients, we showed low rates of unfavorable outcomes (9.2%), which were more frequent in patients with chronic kidney disease (aOR: 10.44, 95CI: 1.73-63.03; p<0.05) and basal D-dimer serum concentrations >600 ng/ml (aOR 21.74, 95CI: 1.18-397.70; p<0.05). Patients with negative SARS-CoV-2 serology at baseline showed higher C-reactive protein values compared with patients with positive serology (p <0.05) and showed a trend toward a higher admission rate to SICU and ICU compared with patients with positive serology. Our results thus showed, in a real-life setting, the efficacy of mAbs against SARS-CoV-2 before Omicron surge when the available mabs become not effective.

This paper examines how housing prices are determined by macroeconomic factors in Saudi Arabia, namely, Gross Domestic Product Per capita (GDPP), Consumer Prices Index (CPI), and Unemployment Rate (UNEMP). Quarterly data for a period (2014q1 – 2019q4) were collected from publications of Saudi Arabian Monetary Authority (SAMA). Vector Autoregression Analysis (VAR) is employed to capture the dynamic effect of the variables on housing prices. Granger Causality, Variance Decomposition and Impulse response function are also used. The results show that housing prices are insignificantly and positively related to GDPP, whereas it is negatively related to both (CPI & UNEMP). Only CPI has a significant relationship. The three variables, jointly, have Granger causality on HPI. Variance decompositions show that CPI is the variable with the highest explanatory power over the variation of housing prices, followed by GDPP and the UNEMP respectively indicating that CPI is the most influential determinants for housing prices.

Many historical areas are exposed to many problems and ongoing changes that may negatively affect those areas. One of these historical areas is Historic Jeddah in Saudi Arabia, which was placed on the UNESCO World Heritage List in 2014. This site is located within the scope of the second largest city in the Kingdom, which is witnessing a continuous urban movement in which the image of the city is changing in response to (Kingdom’s Vision 2030) to modernize the image of its major cities. The study aims to review the urban preservation strategies for historic Jeddah and the vision set for it through the ongoing modernization process of the city, especially with the projects that have been undertaken in it since 2021. The study follows both theoretical and descriptive approaches with the aim of reviewing current conservation strategies. This is with the aim of reaching results related to the challenges facing the area, demonstrating the effectiveness of the conservation strategies used, and deducing what could contribute in the future to the process of developing, preserving, and optimally exploiting it, without losing its value as a result of the modernization processes taking place now, but rather as a compatible part of it.

Despite concepts of human flourishing, a term connected to empowerment that acts as an archi-tectural structure within the development and sustainability discourse, tensions remain between exponential economic growth, planetary health and community empowerment. Scholars argue that the development agenda is maldevelopment due to the unrequested interventions delivered to communities, mainly in the Global South (Shiva, 1999). A current state of disorientation grips the modern world, and despite sophisticated global frameworks like the Sustainable Development Goals (SDGs), internal approaches are side-lined. This research article repositions empowerment and compassion at the centre of the sustainable development discourse by drawing on the Inner Development Framework, particularly goal one – Being – ‘Relationship to Self’ and goal three – Relating – ‘Caring for others and the World’ as a guiding theoretical underpinning. Accordingly, this research article presents a qualitative interpretative study that examines the lived experience of women and their journeys to empowerment. The key findings indicate an intricate relationship between wellbeing and empowerment and the realisation of inner development as a tool to re-imagine alternative futures. The Machiavellian tendency to the sustainability agenda is deeply embedded in the profiteering of the misery of affected communities.

Anthropogenic activities are the main cause of climate change globally. The World Health Organization (WHO) recognized that heating and precipitation are the reason for climate change due to anthropogenic actions over the past 30 years and claim 150,000 lives annually. Climate change is also affecting the atmospheres of polar regions. Numerous diseases are linked with climate change like cardiovascular mortality and respiratory illnesses. Due to climate change, lack of long-term and high-quality data sets, variations in drug resistance and immunity, the amplification or the resurgence of diseases, as well as many socio-economic factors, are uncertain.Potentially susceptible regions consist of the temperate latitudes, the regions near the Indian and Pacific oceans are affected due to the heavy rainfall where the heat of the cities could increase life-threatening climatic proceedings. The association between climate and health poses a risk to health under future guesses. Over the current decades, warming has contributed to increased mortality and morbidity in various provinces of the globe. The current study reviews the potential effects of climate change on temperature, human health, air quality, food & nutrition, livelihoods, and livestock & fisheries in detail.

The central dogma of molecular biology dictates that, with only a few exceptions, information proceeds from DNA to protein through an RNA intermediate. Examining the enigmatic steps from prebiotic to biological chemistry, we take another road suggesting that primordial peptides acted as template for the self-assembly of the first nucleic acids polymers. Arguing in favour of a sort of archaic “reverse translation” from proteins to RNA, our basic premise is a Hadean Hearth where key biomolecules such as amino acids, polypeptides, purines, pyrimidines, nucleosides and nucleotides were available under different prebiotically plausible conditions, including meteorites delivery, shallow ponds and hydrothermal vents scenarios. Supporting a protein-first scenario alternative to the RNA world hypothesis, we propose the primeval occurrence of short peptides termed “selective amino acid- and nucleotide-matching oligopeptides” (henceforward SANMAOs) that noncovalently bind at the same time the polymerized amino acids and the single nucleotides dispersed in the prebiotic milieu. We describe the chemical features of this hypothetical oligopeptide, its biological plausibility and its virtues from an evolutionary perspective. We provide a theoretical example of SANMAO’s selective pairing between amino acids and nucleosides, simulating a poly-Glycine peptide that acts as a template to build a purinic chain corresponding to the glycine’s extant triplet codon GGG. Further, we discuss how SANMAO might have endorsed the formation of low-fidelity RNA’s polymerized strains, well before the appearance of the accurate genetic material’s transmission ensured by the current translation apparatus.

A reliable and affordable energy supply is a fundamental prerequisite for reducing poverty, promoting investment, and boosting economic growth in the developing world. Among the different challenges that developing countries face, chronic energy crises are harrowing. The crises result from the unsatisfactory state of the central grid, a misguided energy mix, and ill-informed policies, among other things. The possibility of solving energy crises through a variety of alternative solutions is worth exploring. This review discusses two paths of energy development side by side: a traditional “hard” path of energy development (i.e., central grid extension powered by fossil fuels and nuclear energy expansion) and a relatively recent “soft” path of energy development, which is based on energy conservation and the deployment of renewable energy resources. This paper focuses on one central axis of the discussion: centralization vs. decentralization. This discussion, in turn, has technological, economic/business, and political dimensions. Finally, the paper discusses the significance of the debate from meeting the developing world’s energy demands. The paper intends not to prefer one or another path of energy development, nor it gives recommendations on diffusing or adopting those development paths. Instead, it explores the literature’s central arguments that might help frame the questions for further research. While this debate could be used to ask interesting questions that might help solve the energy crisis in the developing world, the discussion informs countries to advance policies specific to their circumstances under the umbrella of a sound and thoughtful energy productivity policy framework.

In situations of uncertainty, scenarios serve as input for evidence-based decision making. However, past experience shows that not all scenarios are treated equally, and we hypothise that only those based ion a world view shared by decision makers are perceived as credible and receive full attention. While intuitively plausible, this hypothesis has not been analysed by quantitative correlation analyses, so instead of drawing on quantitative data the paper analyses the archetypical scenarios developed in the ALARM project to substantiate the plausibility by a comparative analysis of world views, value systems and policy orientations. Shock scenarios are identified as a means to explore the possibility space of future developments beyond the linear developments models and most scenario storylines suggest. The analysis shows that the typical scenarios are based on mutually exclusive assumptions. In conclusion, a comparison of storyline and empirical data can reveal misperceptions, policy failures and the need to rethink world views as a necessary step to open up to new challenges. Deeply held beliefs will make this a transition unlikely to happen without severs crises, if not dedicated efforts to reveal the role of world views for scenarios and policies are undertaken.

Currently there is little doubt left on the symbiogenetic nature of eukaryotes - genomes of archaeon and bacterium participated in shaping a genome of last eukaryotic common ancestor in equal albeit asymmetric manner, while a merger event itself indicated the advent of a new domain of life. The “symbiogenetic” framework of interaction of two partners is proposed, outlining similar steps essential for three major advents: the origin of life, the origin of complex life and the origin of humans. Given the immense importance of proper energy source for the evolution of life it seems plausible that for any principal increase in complexity, a partnership with a novel energy donor is required. Moreover, a “language” elaborated in the course of communication of partners might have been a prerequisite for a subsequent increase in complexity. Transitions, which led to RNA-protein world, eukaryotes and human brain, resulted in advent of complex languages via communication onsets between two entities in close partnership. Accordingly this further facilitated formation of first cells, multicellular organisms and human society.

All life on Earth uses three integrated molecular systems in which genetic information contained in DNA base sequences is transmitted to ribosomes by RNA and a genetic code, then translated into the amino acid sequences of structural and catalytic proteins. Therefore, the most important point for understanding the origin of life is to determine how such systems could emerge from random processes on the early Earth. In this review, two alternatives are compared: the RNA world hypothesis and the [GADV]-protein world hypothesis. [GADV] refers to four amino acids, Gly [G], Ala [A], Asp [D] and Val [V] that are conserved in the amino acid sequences of many common proteins. Here I will argue that the origins of the three primary processes required for life to begin can be better explained by the GADV hypothesis than the RNA world hypothesis. The GADV hypothesis also incorporates a conversion process by which random polymers can evolve into proteins with ordered sequences.

A correct system design can be systematically obtained from a specification model of a real-time system that integrates hybrid measurements in a realistic industrial environment, this has been carried out through complete Matlab / Simulink / Stateflow models. However, there is a widespread interest in carrying out that modeling by resorting to Machine Learning models, which can be understood as Automated Machine Learning for Real-time systems that present some degree of hybridization. An induction motor controller which must be able to maintain a constant air flow through a filter is one of these systems and it is discussed in the paper as a study case of closed-loop control system. The article discusses a practical application of ML methods that demonstrates how to replace such closed loop in industrial control systems with a Simulink block generated from neural networks to show how the proposed procedure can be applied to derive complete hybrid system designs with artificial neural networks (ANN). In the proposed ANN-based method to design a real-time hybrid system with continuous and discrete components, we use a typical design of a neural network, in which we define the usual phases: training, validation, and testing. The generated output of the model is made up of reference variables values of the cyber-physical system, which represent the functional and dynamic aspects of model. They are used to feed Simulink/Stateflow blocks in the real target system.

The utilization of artificial intelligence in education can contribute to sustainable development goals in various ways. AI in education can effectively convey sustainability issues to students. Through simulations and virtual environments, learners can experience sustainable practices firsthand. On the other hand artificial intelligence can assist administrators and educators in making data-informed decisions. This allows for more effective shaping of educational policies. This study explores how teachers and artificial intelligence (AI) address ethical dilemmas in edu-cation, comparing their decisions and examining the influence of variables such as gender, years of service, and education level. A total of 141 teachers from public schools in Turkey participated, and their responses were compared to AI-generated decisions using Yin's nested multiple-case de-sign. The scenarios were analyzed through five ethical frameworks: virtue ethics, deontological ethics, utilitarianism, social justice ethics, and situation ethics. Results showed that AI provided the same answer as the majority of teachers in six out of eight dilemmas but differed in two. AI favored a more analytical, result-oriented approach, while teachers emphasized empathy and rule adherence. Gender differences revealed that males leaned towards utilitarianism, while females favored social justice and situation ethics. Less experienced teachers preferred deontological and social justice ethics, while more experienced teachers leaned towards virtue ethics and utilitarian-ism. Elementary teachers emphasized virtue and social justice ethics, while middle and high school teachers favored deontological ethics and utilitarianism. The findings provide insights into ethical decision-making in education by highlighting the differences between solutions proposed by artificial intelligence and those offered by teachers. Additionally, they emphasize the im-portance of adapting artificial intelligence to everyday life to foster a sustainable world.