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Background: Advanced chronic liver disease (ACLD) patients are usually malnourished, and both conditions in combination increase the likelihood of unfavourable clinical outcomes. Handgrip strength (HGS) has been suggested as a relevant parameter for nutritional assessment and predictor of adverse clinical outcomes in ACLD. However, the HGS cut‐off values for ACLD patients have not yet been reliably established. The aims of this study were to preliminarily identify HGS reference values in a sample population of ACLD male patients and to assess their association with survival over a 12‐month follow‐up period. Methods: This was a prospective observational study with preliminary analysis of outpatients and inpatients. A total of 185 male patients with a medical diagnosis of ACLD met the inclusion criteria and were invited to participate in the study. The physiological variation in muscle strength related to the age of the individuals included in the study was considered to obtain cut‐off values. Results: After categorising HGS by age group (adults: 18–60 years; elderly: ≥60 years), the reference values obtained were 32.5 kg for the adults and 16.5 kg for the elderly. During the 12‐month follow‐up, 20.5% of the patients died, and 76.3% of those had been identified with reduced HGS. Conclusions: Patients with adequate HGS showed significantly higher 12‐month survival than those with reduced HGS within the same period. Our findings show that HGS is an important predictive parameter for clinical and nutritional follow‐up in ACLD male patients. Key points: Strength measurement is an indicator of nutritional status that is not compromised by the presence of oedema and ascites and, therefore, has an advantage over methods traditionally used in clinical practice for advanced chronic liver disease (ACLD) patients.However, to date, very few studies have presented cut‐off values for ACLD patients. Furthermore, studies that have accounted for variables that directly influence muscle strength, including age group and various levels of severity of liver disease, are scarce.As dynamometry is a low‐cost method and easily reproducible in clinical practice, handgrip strength (HGS) can be effectively applied for inpatient and outpatient nutritional care. HGS cut‐off values may be used to plan a more tailored nutritional therapy and, most importantly, for the early detection of individuals at greater risk of negative outcomes in ACLD.The results of this study show that reduced HGS was associated with increased mortality and reduced survival in ACLD male patients.A multicentre study which presents HGS cut‐off accurate enough to predict mortality in larger populations of ACLD adult and elderly patients of both sexes will bring certainty as to the applicability of our results to larger settings. [ABSTRACT FROM AUTHOR]

This paper explores the multifaceted nature of digital entrepreneurship, tracing its evolution alongside the digital transformation of the broader economy. Entrepreneurship research has expanded to encompass a wide range of theoretical perspectives. It outlines the evolution of theoretical perspectives in entrepreneurship studies, shifting from a focus on individual characteristics to a broader emphasis on environmental, social, and institutional factors. The paper highlights the diversity of methodological approaches utilized in entrepreneurship research, ranging quantitative, qualitative, and computational techniques. The advent of the internet opened the door for e-commerce in the 1990s, followed by the rise of Web 2.0 social platforms in the 2000s, further empowering entrepreneurs through user-generated content and the power of networks. The current phase of digital entrepreneurship is characterized by data-driven platforms, sophisticated algorithms, and the blurring of physical and digital boundaries. Theoretical frameworks, including innovation theory, resource-based views, lean startup methodologies, and institutional perspectives, aid in understanding the opportunities and challenges within this dynamic field. Digital entrepreneurship is presented as a dynamic force reshaping the modern economy. The paper traces the evolution of digital entrepreneurship through three key phases: the emergence of e-commerce in the 1990s, the rise of Web 2.0 social platforms in the 2000s, and the current dominance of data-driven platforms. The ongoing digital revolution has profoundly altered the entrepreneurial landscape, demanding new skills, strategies, and models for success. The COVID-19 pandemic further accelerated digital adoption across businesses and society. The paper underscores the significance of digital entrepreneurship within the context of technological advancement, institutional shifts, and evolving market dynamics.

Background: This study describes the characteristics of men attending a primary health care screening initiative, determines the proportion of men who have elevated International Prostate Symptom Score (IPSS) scores and prostate-specific antigen (PSA) levels, and determines any correlation between these scores as indicators for benign prostatic hyperplasia (BPH) or prostate cancer. Methods: Data were collected from all patient records during men’s health screening initiatives that occurred in December 2018, January 2019, and March 2019 in Trinidad and Tobago. A total of 350 medical records were analyzed to record patient demographics, PSA levels, and IPSS scores. Analysis of the data was performed with the use of Statistical Package for the Social Sciences software (version 27). Results: Most men who attended the screening initiative belonged to the 61–65 age group (20.57%), with more than half of the men being married (57.71%) and employed (52.57%) and of patients with comorbidities (17%), the most prevalent included hypertension (6%) and diabetes mellitus (3.7%). A mean PSA level of 2.94 ng/ml and a mean IPSS of 7.62 were recorded. Moreover, 11.5% of the males had elevated PSA levels (>4 ng/ml) and 32.9% had elevated IPSS levels (>8). There were correlations between PSA and IPSS values (r = 0.161 and P = 0.006). Age was a predictor of both IPSS and PSA values (r = 0.214, P = 0.000 and r = 0.192, P = 0.000, respectively). Among diabetic participants, a small but significant correlation between IPSS and diabetes was shown (r = 0.223, P = 0.028). As a predictor of elevated IPSS, diabetes had an odds ratio of 1.132 (95% confidence interval (CI): 1.021–1.255). Conclusion: Our findings are similar to those described in previous studies; however, further investigations are required to fully describe the relationship between PSA and IPSS. This may assist in advancing screening measures and improving health outcomes for men with BPH and prostate cancer. Primary care physicians should recognize the possible association between BPH and diabetes mellitus and offer appropriate screening where indicated.

Abstract Background Technology-based assessments using 2D virtual reality (VR) environments and goal-directed instrumented tasks can deliver digital health metrics describing upper limb sensorimotor function that are expected to provide sensitive endpoints for clinical studies. Open questions remain about the influence of the VR environment and task complexity on such metrics and their clinimetric properties. Methods We aim to investigate the influence of VR and task complexity on the clinimetric properties of digital health metrics describing upper limb function. We relied on the Virtual Peg Insertion Test (VPIT), a haptic VR-based assessment with a virtual manipulation task. To evaluate the influence of VR and task complexity, we designed two novel tasks derived from the VPIT, the VPIT-2H (VR environment with reduced task complexity) and the PPIT (physical task with reduced task complexity). These were administered in an observational longitudinal study with 27 able-bodied participants and 31 participants with multiple sclerosis (pwMS, VPIT and PPIT only) and the value of kinematic and kinetic metrics, their clinimetric properties, and the usability of the assessment tasks were compared. Results Intra-participant variability strongly increased with increasing task complexity (coefficient of variation + 56%) and was higher in the VR compared to the physical environment (+ 27%). Surprisingly, this did not translate into significant differences in the metrics’ measurement error and test–retest reliability across task conditions (p > 0.05). Responsiveness to longitudinal changes in pwMS was even significantly higher (effect size + 0.35, p

Abstract The concept of an innovative human–machine interface and interaction modes based on virtual and augmented reality technologies for airport control towers has been developed with the aim of increasing the human performances and situational awareness of air traffic control operators. By presenting digital information through see-through head-mounted displays superimposed over the out-of-the-tower view, the proposed interface should stimulate controllers to operate in a head-up position and, therefore, reduce the number of switches between a head-up and a head-down position even in low visibility conditions. This paper introduces the developed interface and describes the exercises conducted to validate the technical solutions developed, focusing on the simulation platform and exploited technologies, to demonstrate how virtual and augmented reality, along with additional features such as adaptive human–machine interface, multimodal interaction and attention guidance, enable a more natural and effective interaction in the control tower. The results of the human-in-the-loop real-time validation exercises show that the prototype concept is feasible from both an operational and technical perspective, the solution proves to support the air traffic controllers in working in a head-up position more than head-down even with low-visibility operational scenarios, and to lower the time to react in critical or alerting situations with a positive impact on the human performances of the user. While showcasing promising results, this study also identifies certain limitations and opportunities for refinement, aimed at further optimising the efficacy and usability of the proposed interface.

Background: Cotesting with the Papanicolaou (Pap) and human papillomavirus tests detects most precancerous and cancerous lesions and increases the sensitivity for detecting high-grade precancerous and invasive cervical cancers compared with human papillomavirus testing alone. Objective: To compare the use of the Papette brush (hereafter Papette) to the traditional spatula with endocervical brush (cytobrush) for cervical cancer screening. Design: Pragmatic observational study. Methods: Adult women aged 21–64 years who were eligible for a Papanicolaou test at a Midwest Community Internal Medicine practice underwent cervical cancer screening using the Papette or spatula with cytobrush from 18 August 2021 through 1 February 2022. Cluster sampling was used across the practice. Pathology reports were then analyzed to compare the number of satisfactory versus unsatisfactory results between the two collection techniques. Results: We collected results for 756 Pap tests. The test results were satisfactory with the Papette 93.8% of the time compared with 93.0% for the spatula with cytobrush. Conclusion: The Papette is not inferior to a spatula with cytobrush as a collection method for Pap tests. [ABSTRACT FROM AUTHOR]

IntroductionOn 24 February 2022, Russia launched a large-scale offensive in Ukraine, resulting in significant casualties to civilians, including children. As part of a seven-stream trauma education initiative, a novel pediatric trauma fundamentals course (PTF) was developed to provide standalone pediatric trauma education by our academic/NGO partnership. The objective of the program was to develop, implement, and evaluate a novel PTF educational course in the active armed conflict zone of Ukraine.MethodsA novel two-day PTF course was internally developed, translated into Ukrainian, and implemented across eight Oblasts (regions) in Ukraine from November 2022 to December 2023. Participants completed pre-and post-assessments in knowledge and self-confidence, and critical skills were assessed against objective skill checklists. Change in knowledge and self-confidence were analyzed, respectively, with the nonparametric Wilcoxon matched-pairs signed-rank test and McNemar’s test for paired data. Anonymous course evaluations were solicited after each course. Six to eight-week follow-up surveys were conducted to assess skill utilization and stewardship.ResultsFour hundred and forty-six Ukrainian health care providers were trained during 30 courses across 8 Oblasts in Ukraine during the intervention period. Aggregated knowledge and self-confidence significantly improved across all measures. Ukrainian instructors of courses received higher raw scores across all evaluation points on instructor feedback surveys as compared to international instructors. Six to eight-week follow-up surveys demonstrated participants had positive views of the training, have used the training on patients, and have taught the material to other health care providers.DiscussionOur novel PTF intervention demonstrates a successful partnership-based model for implementing pediatric trauma education in an active conflict zone in Ukraine. Challenges to implementing such programs can be mitigated through strategic partnership-based models between academic institutions and organizations with local knowledge and expertise. Ukrainian instructors provide course experiences similar or superior to international instructors, likely due to multiple factors related to language, culture, and context.

Non-communicable diseases are the leading cause of global deaths. The risk of their development and progression is increased by modifiable behavioral risk factors. Yet, despite the known benefits of primary and secondary prevention, people often do not follow recommendations for a healthier lifestyle. To this end, mobile health (mHealth) applications offer features for behavioral interventions. Yet, reported user engagement is often low. The objective of the work presented in this article is thus to evaluate the suitability of Design Thinking (DT) as a means to inform the development of an mHealth application that helps increase long-term engagement, and consequently supports individuals in sustainably changing their lifestyle. Applying the DT approach, key user needs and challenges were investigated and used to design a first low-fidelity mHealth application prototype. Think-Aloud analysis, task completion, and post-test interviews were then used to evaluate the prototype and generate early-stage insights. Subsequently, a structured, retrospective analysis of this process, evaluating the insight-generation potential of each step in the DT process cycle, was used to reflect on its suitability to inform mHealth application development. The respective results highlight (1) the distinct value of the DT method, particularly in the early stages of a development project; (2) the strong need for interdisciplinary collaboration in such projects, so as to capture realistic end-user requirements and improve the overall effectiveness of the application design; and (3) the significance of integrating behavioral change theories into the design of mHealth applications, in order to promote long-term engagement.

BackgroundExtracellular particles (EPs), particularly extracellular vesicles, play a crucial role in regulating various pathological mechanisms, including immune dysregulations post-trauma. Their distinctive expression of cell-specific markers and regulatory cargo such as cytokines or micro-ribonucleic acid suggests their potential as early biomarkers for organ-specific damage and for identifying patients at risk for complications and mortality. Given the critical need for reliable and easily assessable makers to identify at-risk patients and guide therapeutic decisions, we evaluated the early diagnostic value of circulating EPs regarding outcomes in severely injured multiple-trauma patients.MethodsPlasma samples were collected from 133 severely injured trauma patients (Injury Severity Score (ISS) ≥16) immediately upon arrival at the emergency department (ED). Patients were categorized into survivors and non-survivors. Injury characteristics and outcomes related to sepsis, pneumonia, or early (

IntroductionAutism spectrum disorder (ASD) is characterised by difficulty with social communication and restricted, repetitive patterns of behaviour. This study aimed to improve understanding of the ASD patient experience with the treatment (bumetanide) regarding the changes in core symptoms and to assess changes considered as meaningful. To achieve this, qualitative interviews were conducted with caregivers of patients in two phase 3 clinical trials (NCT03715153; NCT03715166) of a novel ASD treatment.MethodsCaregivers were invited to participate in one interview after completion of the pivotal phase 3 study; for those of them who continued treatment after study completion, a second interview was held 3 months after trial completion. The interviews were conducted by qualitative researchers and followed a semi-structured interview guide. The interviews focused on patients’ ASD symptoms and their impact on their daily life before enrolment, and on any symptom changes patients experienced during the trial.ResultsOut of the 13 eligible patients’ caregivers, 11 were interviewed up to two times at clinical sites in the UK, Spain, and Italy. The caregivers reported impairments in a wide range of skills: deficits in communication and social interaction; restricted, repetitive patterns of behaviour, interests, or activities; and cognitive, emotional, and motor impairments. Compared to before the trial initiation, caregivers also reported improvements in the following domains: communication, interaction with others, cognition, aggression, emotions, repetitive movements, eating, and sleeping.ConclusionThe exit interviews provided a rich source of qualitative data, allowing a deeper understanding of caregivers’ and patients’ experience of the disease and allowing us to understand what constitutes a meaningful change. These data also helped identify important experiences that may inform the patient-reported outcome measurement strategy for future trials in ASD.

Abstract The Russian invasion of Ukraine on February 24, 2022, has had devastating effects on the Ukrainian population and the global economy, environment, and political order. However, little is known about the psychological states surrounding the outbreak of war, particularly the mental well-being of individuals outside Ukraine. Here, we present a longitudinal experience-sampling study of a convenience sample from 17 European countries (total participants = 1,341, total assessments = 44,894, countries with >100 participants = 5) that allows us to track well-being levels across countries during the weeks surrounding the outbreak of war. Our data show a significant decline in well-being on the day of the Russian invasion. Recovery over the following weeks was associated with an individual’s personality but was not statistically significantly associated with their age, gender, subjective social status, and political orientation. In general, well-being was lower on days when the war was more salient on social media. Our results demonstrate the need to consider the psychological implications of the Russo-Ukrainian war next to its humanitarian, economic, and ecological consequences.

The purpose of this research is to examines how is the competition and pricing for audit services in the audit service market in Indonesia from the perspective of the auditors. This study uses a questionnaire with auditor respondents at manager level to audit partners. The data analysis technique used in this research is descriptive statistical analysis. By using a total of 414 respondents from audit firms Big 4 and non-Big 4, this research found that most of the respondents considered the audit service market competition in Indonesia to be high and agree that competition for audit services creates pressure that creates relatively low audit fee in Indonesia. The results of this study confirm and strengthen previous studies which using secondary data that the level of concentration of the audit services market is related to the level of competition for audit services and create pressure to reduce audit fee. The implication of this research is that further research needs to be carried out using more objective secondary data to examine the impact of the level of competition of audit services on audit fees and audit quality as well as evaluating whether regulations are needed to determine minimum audit fees.

Abstract Frequent complications arising from low anterior resections include urinary and fecal incontinence, as well as sexual disorders, which are commonly associated with damage to the pelvic autonomic nerves during surgery. To assist the surgeon in preserving pelvic autonomic nerves, a novel approach for intraoperative pelvic neuromonitoring was investigated that is based on impedance measurements of the innervated organs. The objective of this work was to develop an algorithm called AMINA to classify the bioimpedance signals, with the goal of facilitating signal interpretation for the surgeon. Thirty patients included in a clinical investigation underwent nerve-preserving robotic rectal surgery using intraoperative pelvic neuromonitoring. Contraction of the urinary bladder and/or rectum, triggered by direct stimulation of the innervating nerves, resulted in a change in tissue impedance signal, allowing the nerves to be identified and preserved. Impedance signal characteristics in the time domain and the time–frequency domain were calculated and classified to develop the AMINA. Stimulation-induced positive impedance changes were statistically significantly different from negative stimulation responses by the percent amplitude of impedance change Amax in the time domain. Positive impedance changes and artifacts were distinguished by classifying wavelet scales resulting from peak detection in the continuous wavelet transform scalogram, which allowed implementation of a decision tree underlying the AMINA. The sensitivity of the software-based signal evaluation by the AMINA was 96.3%, whereas its specificity was 91.2%. This approach streamlines and automates the interpretation of impedance signals during intraoperative pelvic neuromonitoring.

Abstract Segmental instillation of lipopolysaccharide (LPS) by bronchoscopy safely induces transient airway inflammation in human lungs. This model enables investigation of pulmonary inflammatory mechanisms as well as pharmacodynamic analysis of investigational drugs. The aim of this work was to describe the transcriptomic profile of human segmental LPS challenge with contextualization to major respiratory diseases. Pre-challenge bronchoalveolar lavage (BAL) fluid and biopsies were sampled from 28 smoking, healthy participants, followed by segmental instillation of LPS and saline as control. Twenty-four hours post instillation, BAL and biopsies were collected from challenged lung segments. Total RNA of cells from BAL and biopsy samples were sequenced and analysed for differentially expressed genes (DEGs). After challenge with LPS compared with saline, 6316 DEGs were upregulated and 241 were downregulated in BAL, but only one DEG was downregulated in biopsy samples. Upregulated DEGs in BAL were related to molecular functions such as “Inflammatory response” or “chemokine receptor activity”, and upregulated pro-inflammatory pathways such as “Wnt-"/“Ras-"/“JAK-STAT” “-signaling pathway”. Furthermore, the segmental LPS challenge model resembled aspects of the five most prevalent respiratory diseases chronic obstructive pulmonary disease (COPD), asthma, pneumonia, tuberculosis and lung cancer and featured similarities with acute exacerbations in COPD (AECOPD) and community-acquired pneumonia. Overall, our study provides extensive information about the transcriptomic profile from BAL cells and mucosal biopsies following LPS challenge in healthy smokers. It expands the knowledge about the LPS challenge model providing potential overlap with respiratory diseases in general and infection-triggered respiratory insults such as AECOPD in particular.

Abstract Background Generating rigorous evidence to inform care for rare diseases requires reliable, sustainable, and longitudinal measurement of priority outcomes. Having developed a core outcome set for pediatric medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, we aimed to assess the feasibility of prospective measurement of these core outcomes during routine metabolic clinic visits. Methods We used existing cohort data abstracted from charts of 124 children diagnosed with MCAD deficiency who participated in a Canadian study which collected data from birth to a maximum of 11 years of age to investigate the frequency of clinic visits and quality of metabolic chart data for selected outcomes. We recorded all opportunities to collect outcomes from the medical chart as a function of visit rate to the metabolic clinic, by treatment centre and by child age. We applied a data quality framework to evaluate data based on completeness, conformance, and plausibility for four core MCAD outcomes: emergency department use, fasting time, metabolic decompensation, and death. Results The frequency of metabolic clinic visits decreased with increasing age, from a rate of 2.8 visits per child per year (95% confidence interval, 2.3–3.3) among infants 2 to 6 months, to 1.0 visit per child per year (95% confidence interval, 0.9–1.2) among those ≥ 5 years of age. Rates of emergency department visits followed anticipated trends by child age. Supplemental findings suggested that some emergency visits occur outside of the metabolic care treatment centre but are not captured. Recommended fasting times were updated relatively infrequently in patients’ metabolic charts. Episodes of metabolic decompensation were identifiable but required an operational definition based on acute manifestations most commonly recorded in the metabolic chart. Deaths occurred rarely in these patients and quality of mortality data was not evaluated. Conclusions Opportunities to record core outcomes at the metabolic clinic occur at least annually for children with MCAD deficiency. Methods to comprehensively capture emergency care received at outside institutions are needed. To reduce substantial heterogeneous recording of core outcome across treatment centres, improved documentation standards are required for recording of recommended fasting times and a consensus definition for metabolic decompensations needs to be developed and implemented.

Dysfunctionality in socialisation is undoubtedly the most crucial characteristic of autism. For a long time, social functioning and its improvement have been considered among the most important interventions in the literature. Individuals with autism are responsive to therapist-mediated and/or peer-mediated interventions that increase their social engagement. The present study examines the impact of outdoor integrated activities, such as music therapy, equine-assisted therapy, and art therapy, in autistic individuals (n=14). The analysis was carried out on the application of a questionnaire assessing three social skill domains: Joint Attention (JA), Imitation (IMI), and Turn-Taking (T-T) mediated by the therapists and by peers. The development and acquisition of these social behaviours were examined in a structured outdoor context (ASO). Data were collected by two independent observers by White's Scale questionnaire. The results revealed that the proposed interventions facilitated and led to an increase in social-behavioural experience.

Introduction: The Basic Emergency Care (BEC) course is an open-access training designed for frontline providers in low resource settings which focuses on recognizing and managing emergent conditions. This study describes the implementation of the BEC course for nurses at Bugando Medical Center (BMC) in Mwanza, Tanzania in March 2020 as part of an educational initiative to improve nurses’ knowledge and confidence in providing emergency care. Methods: This is a 2-week educational intervention with pre-post measurements. 12 nurses (cohort 1) received BEC training from in-country facilitators over the course of 4 days. A training-of-trainers (ToT) course followed immediately and the 5 newly trained facilitators then taught the BEC course to 12 additional nurses (cohort 2). Pre- and post-BEC knowledge was assessed with a standardized 25-question multiple choice (MCQ) exam; confidence levels were evaluated using a 4-point Likert scale survey; and qualitative feedback obtained was examined by thematic analysis. Results: 24 participants completed the BEC course, 5 of which completed a ToT to become BEC facilitators. For the combined group, knowledge assessment scores improved significantly from 63.8% to 85.2% with a mean difference of 21.5% (t(24)= 9.3, p

A study was conducted to examine patients' preferences for the collection of bodily fluids. Patients' preferences for the collection of saliva, blood, and urine were assessed. Findings indicate that patients regarded the donation of saliva as more comfortable and convenient than that of urine or blood at the doctor's office. It was reported that saliva and urine are the easiest to collect at home.