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Abstract Background Lower respiratory tract infections (LRTIs) are among the most frequent infections and a significant contributor to inappropriate antibiotic prescription. Currently, no single diagnostic tool can reliably identify bacterial pneumonia. We thus evaluate a multimodal approach based on a clinical score, lung ultrasound (LUS), and the inflammatory biomarker, procalcitonin (PCT) to guide prescription of antibiotics. LUS outperforms chest X-ray in the identification of pneumonia, while PCT is known to be elevated in bacterial and/or severe infections. We propose a trial to test their synergistic potential in reducing antibiotic prescription while preserving patient safety in emergency departments (ED). Methods The PLUS-IS-LESS study is a pragmatic, stepped-wedge cluster-randomized, clinical trial conducted in 10 Swiss EDs. It assesses the PLUS algorithm, which combines a clinical prediction score, LUS, PCT, and a clinical severity score to guide antibiotics among adults with LRTIs, compared with usual care. The co-primary endpoints are the proportion of patients prescribed antibiotics and the proportion of patients with clinical failure by day 28. Secondary endpoints include measurement of change in quality of life, length of hospital stay, antibiotic-related side effects, barriers and facilitators to the implementation of the algorithm, cost-effectiveness of the intervention, and identification of patterns of pneumonia in LUS using machine learning. Discussion The PLUS algorithm aims to optimize prescription of antibiotics through improved diagnostic performance and maximization of physician adherence, while ensuring safety. It is based on previously validated tests and does therefore not expose participants to unforeseeable risks. Cluster randomization prevents cross-contamination between study groups, as physicians are not exposed to the intervention during or before the control period. The stepped-wedge implementation of the intervention allows effect calculation from both between- and within-cluster comparisons, which enhances statistical power and allows smaller sample size than a parallel cluster design. Moreover, it enables the training of all centers for the intervention, simplifying implementation if the results prove successful. The PLUS algorithm has the potential to improve the identification of LRTIs that would benefit from antibiotics. When scaled, the expected reduction in the proportion of antibiotics prescribed has the potential to not only decrease side effects and costs but also mitigate antibiotic resistance. Trial registration This study was registered on July 19, 2022, on the ClinicalTrials.gov registry using reference number: NCT05463406. Trial status Recruitment started on December 5, 2022, and will be completed on November 3, 2024. Current protocol version is version 3.0, dated April 3, 2023.

Abstract Glucose is a universally available inexpensive biomarker, which is increased as part of the physiological stress response to acute myocardial infarction (AMI) and may therefore help in its early diagnosis. To test this hypothesis, glucose, high-sensitivity cardiac troponin (hs-cTn) T, and hs-cTnI were measured in consecutive patients presenting with acute chest discomfort to the emergency department (ED) and enrolled in a large international diagnostic study (NCT00470587). Two independent cardiologists centrally adjudicated the final diagnosis using all clinical data, including serial hs-cTnT measurements, cardiac imaging and clinical follow-up. The primary diagnostic endpoint was index non-ST-segment elevation MI (NSTEMI). Prognostic endpoints were all-cause death, and cardiovascular (CV) death or future AMI, all within 730-days. Among 5639 eligible patients, NSTEMI was the adjudicated final diagnosis in 1051 (18.6%) patients. Diagnostic accuracy quantified using the area under the receiver-operating characteristics curve (AUC) for the combination of glucose with hs-cTnT and glucose with hs-cTnI was very high, but not higher versus that of hs-cTn alone (glucose/hs-cTnT 0.930 [95% CI 0.922–0.937] versus hs-cTnT 0.929 [95% CI 0.922–0.937]; glucose/hs-cTnI 0.944 [95% CI 0.937–0.951] versus hs-cTnI 0.944 [95% CI 0.937–0.951]). In early-presenters, a dual-marker strategy (glucose

Abstract Background Acute heart failure patients are often encountered in emergency departments (ED) from 11% to 57% using emergency medical services (EMS). Our aim was to evaluate the association of EMS use with acute heart failure patients’ ED management and short-term outcomes. Methods This was a sub-analysis of a European EURODEM study. Data on patients presenting with dyspnoea were collected prospectively from European EDs. Patients with ED diagnosis of acute heart failure were categorized into two groups: those using EMS and those self-presenting (non- EMS). The independent association between EMS use and 30-day mortality was evaluated with logistic regression. Results Of the 500 acute heart failure patients, with information about the arrival mode to the ED, 309 (61.8%) arrived by EMS. These patients were older (median age 80 vs. 75 years, p 30/min in 17.1% patients vs. 7.5%, p = 0.005). The only difference in ED management appeared in the use of ventilatory support: 78.3% of EMS patients vs. 67.5% of non- EMS patients received supplementary oxygen (p = 0.007), and non-invasive ventilation was administered to 12.5% of EMS patients vs. 4.2% non- EMS patients (p = 0.002). EMS patients were more often hospitalized (82.4% vs. 65.9%, p

Pseudoprogression of malignancy in patients treated with systemic immunotherapy is a well- recognised phenomenon and has also been seen in patients treated with combined chemoimmunotherapy. Neoadjuvant chemoimmunotherapy prior to surgery is a relatively new treatment strategy for the management of many malignancies. We report the case of a patient who was suspected to have primary lung squamous cell carcinoma progression following neoadjuvant chemoimmunotherapy. Tissue histopathology from biopsies demonstrated granulomatous sarcoid-like inflammation rather than progression or metastatic disease. The patient proceeded to have successful surgical clearance of residual tumour. Significantly, failure to suspect granulomatous reactions and pseudoprogression has profound influence on the trajectory of patient care, such as, the potential for patients to miss out on curative surgery. In this case report and review of the literature, we evaluate the role of pseudoprogression and the need for radiologists to be aware of this phenomenon so that they do not mistakenly report new metastases and derail the treatment paradigm for patients with curable malignant conditions.

Abstract Background Symptoms of autonomic neuropathy (AN) are common in patients with diabetes and advanced renal disease. As yet different domains of autonomic neuropathy cannot be detected by a singular laboratory or invasive test. COMPASS 31, a new self-assessment test, has shown reliable results not only in cardiac autonomic neuropathy but also in different sub-domains when judging manifestation of AN by scores. Methods One hundred eighty-three patients with or without diabetes were enrolled, one hundred nineteen of them were treated with permanent dialysis therapy (HD), sixty-four patients served as controls (eGFR > 60 ml/min.) Using COMPASS 31 different symptoms of AN were assessed (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, pupillomotor changes) and transferred into AN-scores. Results AN was more pronounced in dialysis patients compared with controls (AN-score 27,5 vs. 10,0; p

North-central Nigeria is facing a challenging dilemma as displaced farmers struggle to recover agricultural productivity due to land tenure insecurity. This study examines the effect of land rights violation on agricultural output among displaced returnees in the region using descriptive statistics and ordinary least square regression analysis from a sample of 854 respondents. Drawing from the data collected across the selected states affected by farmersherders conflict in North-central Nigeria, the study reveals that unclear ownership and lack of formal land titles affect returnees’ decision to invest in farm land. The results of this study show that when land rights are violated due to conflict or land intrusion, the income and overall productivity of returnees drop. The study also reveals that assistance given as interventions during the period of displacement is found not to significantly affect production and return to economic activities among displaced returnees. Based on these findings, this study suggests strengthening property rights policy on land and resources, especially in rural communities so as to promote agricultural recovery and food security conflict-affected areas like North-central Nigeria.

The construction industry tends to have a higher level of turnover intention compared to other industries. impact on workforce changes can disrupt productivity, increase training costs, and impact the quality of work. This can lead to project delays and budget overruns. This is primarily related to the influence of job insecurity and job satisfaction on turnover intention. The purpose of this research is to investigate the determinants of employee turnover intention of an Indonesian foreign construction company. The respondents in this study are permanent employees in foreign construction companies. A quantitative approach with 124 respondents is employed, using SEM-PLS and SmartPLS 4.0. Job insecurity and HRM practices influence turnover intention. This occurs because increased job insecurity, which makes employees feel more threatened of losing their jobs, leads to a higher desire to leave the company.

Abstract Background There are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic antidepressant, to be effective in reducing methamphetamine use. The proposed Tina Trial is the first phase 3 placebo-controlled randomised trial to examine the effectiveness and safety of mirtazapine as an outpatient pharmacotherapy for methamphetamine use disorder. Methods This is a multi-site phase 3 randomised, double-blind, placebo-controlled parallel trial. Participants are randomly allocated (1:1) to receive either mirtazapine (30 mg/day for 12 weeks) or matched placebo, delivered as a take-home medication. The target population is 340 people aged 18–65 years who have moderate to severe methamphetamine use disorder. The trial is being conducted through outpatient alcohol and other drug treatment clinics in Australia. The primary outcome is measured as self-reported days of methamphetamine use in the past 4 weeks at week 12. Secondary outcomes are methamphetamine-negative oral fluid samples, depressive symptoms, sleep quality, HIV risk behaviour and quality of life. Other outcomes include safety (adverse events), tolerability, and health service use. Medication adherence is being monitored using MEMS® Smart Caps fitted to medication bottles. Discussion This trial will provide information on the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder when delivered as an outpatient medication in routine clinical practice. If found to be safe and effective, this trial will support an application for methamphetamine use disorder to be included as a therapeutic indication for the prescription of mirtazapine. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022.

Purpose Despite numerous mentoring strategies to promote academic success and eligibility in medicine, Black students remain disproportionately underrepresented in medicine. Therefore, we conducted a scoping review to identify the mentoring practices available to Black pre-medical students, medical students and medical residents, specifically the mentoring strategies used, their application, and their evaluation. Method Between May 2023 and October 2023, the authors conducted a literature review. Studies that described a mentoring strategy applied among Black learners were eligible for inclusion, and all years of publication were included. Two reviewers screened each article using the Covidence tool, and conflicts were resolved by a third author. All reviewers extracted the data to summarize the various mentoring practices. Results After screening 6292 articles, 42 articles met the criteria for full review. Of these, 14 studies were included in the study. Mentoring practices for Black students included peer mentoring, dyad mentoring, and group mentoring. Mentoring was typically offered through discussion groups, educational internships, and didactic activities. Evaluation of mentoring programs took into account (1) pass rates on medical exams (eg, MCAT, Casper), (2) receipt of an invitation to a medical school admissions interview, (3) successful match to a competitive residency program, and (4) a mentee's report of the overall experience and effectiveness of the program. Conclusion This review is the first, to our knowledge, to focus on mentoring strategies implemented among Black learners in medicine. The results will inform mentoring strategies adapted for Black learners and will therefore address the underrepresentation of Black students in medicine.

Actio Pauliana in bankruptcy, as stipulated under Law Number 37 of 2004, empowers the Curator to seek the annulment of transactions undertaken by the bankrupt debtor, causing harm to the bankrupt estate. Actio Pauliana requires proof that a third party, the debtor's transaction partner is proven to not have acted in good faith, as outlined in the law. However, the legislation lacks clarity on the criteria safeguarding third parties in good faith against Actio Pauliana claims. This research employs a doctrinal research method involving a statute, conceptual, case, and comparative approach. The novelty of this research expounds upon and elucidates the need for amendments to Law Number 37 of 2004, particularly concerning the criteria protecting third parties in good faith. These criteria could be differentiated based on the third parties' position in bankruptcy and the nature of the objects constituting the bankrupt estate, including tangible and intangible movable objects, unregistered objects, immovable objects, and/or registered objects. Furthermore, proposed improvements to the law include refining provisions related to creditors' right to file Actio Pauliana lawsuits, affirming a one-year period rather than a deadline, and addressing timelines within Actio Pauliana lawsuits. Actio Pauliana claims should only be submitted after the debtor's bankruptcy declaration, excluding the Suspension of Debt Payment Obligations (PKPU) process. In conclusion, the research proposes possible solutions, such as the issuance of a Regulation (Perma) or a Circular Letter (SEMA) by the Supreme Court, containing the essential improvements to Law Number 37 of 2004.

Occurrences of introduced and invasive pollinators are increasing worldwide. To predict the potential impacts of exotic bees on native ecosystems we need to understand their ecological interactions. Life history traits are fundamental for understanding ecological interactions and often help to explain the spread of exotic species. We conducted home-and-away comparisons of life history traits of the first invasive bee in Europe, the sculptured resin bee Megachile sculpturalis Smith 1853. We compiled information on nest architecture, offspring, natural enemies, body size and phenology using published literature, museum specimen, data from citizen science initiatives, field observations and reared specimen. Megachile sculpturalis uses a broad variety of nesting materials for brood cell construction, including even plastic at the exotic range. Body size at warm temperate climate was similar in the native and exotic ranges, but phenology shifted forward by about one month (28.9 ± 3.3 SE days) in the exotic ranges. The abundance of natural enemies was similar between native and exotic ranges but specialist enemies were missing in the exotic ranges. These trait shifts may be explained by founder effects or ecological filtering. The comparison of life history traits in native and exotic ranges sheds light on the ecological-evolutionary process of this quickly spreading species and provides a better understanding of invasion processes in solitary bees.

Digitalization is the process of using technology in a company in its operational activities, and in the process, this digitalization involves management and employees in a company and can cause additional workload on the team that is the front line for the occurrence of digitalization. The purpose of this study is to see whether the workload on employees in a shipping company with digitalization crowned technostress (technostress creators and technostress inhibitors) during the digitization process and how it affected job satisfaction mediated by employee engagement.This study found that technostress creators and technostress inhibitors did not influence job satisfaction directly, but both variables would have a positive and significant influence if mediated by employee engagement. Hence, it can be concluded that employee engagement is fully mediating between technostress creators and technostress inhibitors on job satisfaction in the shipping company.

Abstract Background Glioblastoma is a malignant and aggressive type of central nevous system malignancy characterized by many distinct biological features including extensive hypoxia. Hypoxia in glioblatoma associates with complex signaling patterns including activation of several pathways such as MAPK, PI3K-AKT/mTOR and IL-6/JAK/STAT3 with the master regulator HIF-1, which in turn drive particular tumor behaviors determining, in the end, treatment outcomes and patients fate. Thus, the present study was designed to investigate the expression of selected hypoxia related factors including STAT3 in a small set of long-term surviving glioma patients. Methods The expression of selected hypoxia related factors including STAT3 was evaluated in a time series of formalin fixed paraffin embedded and cryopreserved glioma samples from repeatedly resected patients. In addition, comparative studies were also conducted on primary glioma cells derived from original patient samples, stabilized glioma cell lines and tumor-xenograft mice model. Obtained data were correlated with clinical findings too. Results Glioblastoma samples of the analyzed patients displayed heterogeneity in the expression of hypoxia- related and EMT markers with most interesting trend being observed in pSTAT3. This heterogeneity was subsequently confirmed in other employed models (primocultures derived from glioblastoma tissue resections, cryopreserved tumor specimens, stabilized glioblastoma cell line in vitro and in vivo) and concerned, in particular, STAT3 expression which remained stable. In addition, subsequent studies on the role of STAT3 in the context of glioblastoma hypoxia demonstrated opposing effects of its deletion on cell viability as well as the expression of hypoxia and EMT markers. Conclusions Our results suport the importance of STAT3 expression and activity in the context of hypoxia in malignant glioblastoma long-term surviving glioma patients while emphasizing heterogeneity of biological outcomes in varying employed tumor models.

Abstract Background Law enforcement officers (LEOs) are exposed to significant stressors that can impact their mental health, increasing risk of posttraumatic stress disorder, burnout, at-risk alcohol use, depression, and suicidality. Compromised LEO health can subsequently lead to aggression and excessive use of force. Mindfulness training is a promising approach for high-stress populations and has been shown to be effective in increasing resilience and improving mental health issues common among LEOs. Methods This multi-site, randomized, single-blind clinical feasibility trial was intended to establish optimal protocols and procedures for a future full-scale, multi-site trial assessing effects of mindfulness-based resilience training (MBRT) versus an attention control (stress management education [SME]) and a no-intervention control, on physiological, attentional, and psychological indices of stress and mental health. The current study was designed to enhance efficiency of recruitment, engagement and retention; optimize assessment, intervention training and outcome measures; and ensure fidelity to intervention protocols. Responsiveness to change over time was examined to identify the most responsive potential proximate and longer-term assessments of targeted outcomes. Results We observed high feasibility of recruitment and retention, acceptability of MBRT, fidelity to assessment and intervention protocols, and responsiveness to change for a variety of putative physiological and self-report mechanism and outcome measures. Conclusions Results of this multi-site feasibility trial set the stage for a full-scale, multi-site trial testing the efficacy of MBRT on increasing LEO health and resilience, and on decreasing more distal outcomes of aggression and excessive use of force that would have significant downstream benefits for communities they serve. Trial registration ClinicalTrials.gov, NCT03784846 . Registered on December 24th, 2018.

Payment systems have evolved quite quickly throughout the history of payment systems and the advent of digital technologies. In the digital age, economic expansion in Indonesia has resulted in an increase in the banking population and the growth of cashless payment channels. Surprisingly, despite the introduction of new non-cash payment channels, many consumers continue to use credit cards, particularly in major cities. Much previous research has indicated that the role of credit cards is directly tied to materialism and purchasing behavior. This is especially pertinent to impulsive and compulsive purchase behavior, which credit cards are extremely likely to facilitate. The purpose of this study was to investigate how materialism influences credit card use as well as impulsive and compulsive buying. This study also investigates whether materialism has mediation effects on compulsive buying. Adult credit card users in Jakarta were polled for the data. This quantitative approach, with 197 participants employs SEM-PLS and SMART PLS 3.0. Materialism influences credit card use and impulsive purchasing. In this instance, impulsive purchases become compulsive. Meanwhile, compulsive buying is caused by internal forces, and credit card use has no impact on it.

BackgroundRecent studies have shown that gut microbiota may be related to the occurrence of brain tumors, but direct evidence is lacking. This study used the Mendelian randomization study (MR) method to explore the potential causal link between gut microbiota and brain tumors.MethodWe analyzed the genome-wide association data between 211 gut microbiota taxa and brain tumors, using the largest existing gut microbiota Genome-Wide Association Studies meta-analysis data (n=13266) and combining it with brain tumor data in the IEU OpenGWAS database. We use inverse-variance weighted analysis, supplemented by methods such as Mendelian randomization-Egger regression, weighted median estimator, simple mode, and weighted mode, to assess causality. In addition, we also conducted the Mendelian randomization-Egger intercept test, Cochran’s Q test, and Mendelian randomization Steiger directionality test to ensure the accuracy of the analysis. Quality control includes sensitivity analysis, horizontal gene pleiotropy test, heterogeneity test, and MR Steiger directionality test.ResultOur study found that specific gut microbial taxa, such as order Lactobacillales and family Clostridiaceae1, were positively correlated with the occurrence of brain tumors, while genus Defluviitaleaceae UCG011 and genus Flavonifractor were negatively correlated with the occurrence of brain tumors. The Mendelian randomization-Egger intercept test showed that our analysis was not affected by pleiotropy (P>0.05).ConclusionThis study reveals for the first time the potential causal relationship between gut microbiota and brain tumors, providing a new perspective for the prevention and treatment of early brain tumors. These findings may help develop new clinical intervention strategies and point the way for future research.

This paper provides a first assessment of the fiscal and distributional consequences of the ongoing structural changes in the labour markets of EU member states, mostly driven by technological progress and ageing. The Cedefop 2020 Skills forecast (including the effects of COVID-19), population projections and the forecast on pension expenditures depict a scenario of an ageing population, an inverted U-shaped unemployment trend and potentially polarising labour markets in the EU till 2030, the latter mostly driven by a surge in high-skill occupations. We make use of the microsimulation model EUROMOD and reweighting techniques to analyse the fiscal and distributional impacts of these trends under a no-policy-change assumption. The results suggest that the macro trends will increase pressure on government budgets, however, we also show that the current tax-benefit systems have the capacity to counterbalance the increases in income inequality and poverty risks triggered by the expected future labour markets developments.

Background: The coronavirus disease 2019 (COVID-19) pandemic disrupted paediatric HIV services across South Africa. Shortly before COVID-19, updated national HIV guidelines were released. Objectives: This study describes COVID-19’s impact on paediatric HIV services in Tshwane District, South Africa. Method: A retrospective review of National Institute for Communicable Diseases and District Health Information System data for Tshwane District from April 2019 to March 2022. Data included: Early Infant Diagnosis (EID), HIV viral load (VL) and CD4 monitoring and HIV management among children ( 15 years) living with HIV (CLHIV). Pre-pandemic (2019/2020) and pandemic periods (2020/2021, 2021/2022) were compared. Results: Year-on-year, HIV testing improved at 10 weeks, 6 months, and 18 months, whereas birth testing decreased. HIV EID case rates were 485 (2019/2020), 410 (2020/2021) and 454 (2021/2022). HIV EID test positivity was 0.77% – 1.2%. Antiretroviral treatment initiation declined from 2019/2020 to 2020/2021, but improved in 2021/2022. Initial HIV VL and CD4 testing declined, with HIV VL testing increasing in 2021/2022, and CD4 testing further declining. HIV VL suppression rate among CLHIV ranged from 69% to 73%. Conclusion: Initially, COVID-19 resulted in reduced paediatric HIV services as children disengaged from care. Indicators eventually recovered to proximate pre-pandemic levels; however, compensatory increases did not occur. Thus, some children may not have returned to care.

Background: The impact of extreme heat on out-of-hospital cardiac arrest (OHCA) incidence and outcomes is under-studied. We investigated OHCA incidence and outcomes over increasing temperatures. Methods: We included non-traumatic EMS (Emergency Medical Services)-assessed OHCAs in British Columbia during the warm seasons of 2020–2021. We fit a time-series quasi-Poisson generalized linear model to estimate the association between temperature and incidence of both EMS-assessed, EMS-treated, and EMS-untreated OHCAs. Second, we employed a logistic regression model to estimate the association between “heatwave” periods (defined as a daily mean temperature > 99th percentile for ≥ 2 consecutive days, plus 3 lag days) with survival and favourable neurological outcomes (cerebral performance category ≤ 2) at hospital discharge. Results: Of 5478 EMS-assessed OHCAs, 2833 were EMS-treated. OHCA incidence increased with increasing temperatures, especially exceeding a daily mean temperature of 25 °C Compared to the median daily mean temperature (16.9 °C), the risk of EMS-assessed (relative risk [RR] 3.7; 95%CI 3.0–4.6), EMS-treated (RR 2.9; 95%CI 2.2–3.9), and EMS-untreated (RR 4.3; 95%CI 3.2–5.7) OHCA incidence were higher during days with a temperature over the 99th percentile. Of EMS-treated OHCAs, during the heatwave (n = 179) and non-heatwave (n = 2654) periods, 4 (2.2%) and 270 (10%) survived and 4 (2.2%) and 241 (9.2%) had favourable neurological outcomes, respectively. Heatwave period OHCAs had decreased odds of survival (adjusted OR 0.28; 95%CI 0.10–0.79) and favourable neurological outcome (adjusted OR 0.31; 95%CI 0.11–0.89) at hospital discharge, compared to other periods. Conclusion: Extreme heat was associated with a higher incidence of OHCA, and lower odds of survival and favourable neurological status at hospital discharge.

Abstract Background Congenital talipes equinovarus (clubfoot) is a common musculoskeletal anomaly, with a suspected multifactorial etiopathogenesis. Herein, we used publicly available data to ascertain liveborn infants with clubfoot delivered in Denmark during 1994–2021, and to classify co-occurring congenital anomalies, estimate annual prevalence, and compare clubfoot occurrence with maternal smoking rates, a commonly reported risk factor. Characterizing this nationwide, liveborn cohort provides a population-based resource for etiopathogenic investigations and life course surveillance. Methods This case-cohort study used data from the Danish National Patient Register and Danish Civil Registration System, accessed through the publicly available Danish Biobank Register, to identify 1,315,282 liveborn infants delivered during 1994–2021 in Denmark to Danish parents. Among these, 2,358 infants (65.1% male) were ascertained with clubfoot and classified as syndromic (co-occurring chromosomal, genetic, or teratogenic syndromes) and nonsyndromic (isolated or co-occurring multiple congenital anomalies [MCA]). Annual prevalence estimates and corresponding 95% confidence intervals (CIs) for children with nonsyndromic clubfoot were estimated using Poisson regression and compared with population-based, maternal annual smoking rates obtained from publicly available resources. Results Infants most often presented with nonsyndromic clubfoot (isolated = 88.6%; MCA = 11.4%); limb and heart anomalies were the most frequently identified MCAs. Prevalence (per 1,000 liveborn infants) was 1.52 (CI 1.45–1.58) for isolated and 0.19 (CI 0.17–0.22) for MCA clubfoot. Prevalence estimates for both isolated and MCA clubfoot remained relatively stable during the study period, despite marked decreases in population-based maternal smoking rates. Conclusions From 1994 to 2021, prevalence of nonsyndromic clubfoot in Denmark was relatively stable. Reduction in population-level maternal smoking rates did not seem to impact prevalence estimates, providing some support for the suspected multifactorial etiopathogenesis of this anomaly. This nationwide, liveborn cohort, ascertained and clinically characterized using publicly available data from the Danish Biobank Register, provides a population-based clinical and biological resource for future etiopathogenic investigations and life course surveillance.

Background: The ongoing COVID-19 pandemic affects several aspects of food safety and food delivery hygiene for online food delivery applications (OFDAs). Several previous studies conducted at various times during the COVID-19 pandemic have yielded interesting results. This study aimed to determine and analyze whether perceptions of food safety and food delivery hygiene are short-term and long-term predictors of behavioral intention to use OFDAs. Methods: A quantitative approach and structural modeling were used in this study. SmartPLS is used to analyze five direct and two mediating effects of the variables used in this study. The data sample consists of OFDA users in Greater Jakarta during the second year of the COVID-19 pandemic. Results: Perceived food safety has a significant effect on behavioral intention to use these applications but does not affect behavioral intention to continue using these applications. Perceived food delivery hygiene does not influence using these apps for either short-term or long-term behavioral purposes. Experience with these apps related to food safety and food delivery hygiene during a pandemic can be indicative of their long-term viability. The mediating effect of behavioral intention to use on behavioral intention to continue using these apps affects perceived food safety but not food delivery hygiene. Conclusion: By emphasizing vaccination and boosting against COVID-19, providing hand sanitizer, and preserving the cleanliness and integrity of food packaging, the findings of this study can be put into practice towards the sustainable usage of OFDAs.

Abstract Background Lung cancer screening in high-risk populations with low-dose computed tomography is supported by international associations and recommendations. Overdiagnosis is considered a risk of screening with associated harms. The aim of this paper is to determine the prevalence of subclinical lung cancer diagnosed post-mortem to better understand the reservoir of subclinical lung cancer. Methods We searched EMBASE, PubMed, and MEDLINE databases from inception until March 2022 with no language restrictions. We considered all studies with ≥100 autopsies in adults. Two reviewers independently assessed eligibility of studies, extracted data, and assessed risk of bias of included studies. We performed a meta-analysis using a random-effects model for prevalence of subclinical lung cancer diagnosed post-mortem with sensitivity and subgroup analyses. Results A total of 13 studies with 16 730 autopsies were included. Pooled prevalence was 0.4% (95% CI 0.20 to 0.82%, I2 = 84%, tau2 = 1.19, low certainty evidence,16 730 autopsies). We performed a sensitivity analysis excluding studies which did not specify exclusion of children in their cohort, with a pooled prevalence of subclinical lung cancer of 0.87% (95% CI 0.48 to 1.57%, I2 = 71%, tau2 = 0.38, 6998 autopsies, 8 studies). Conclusions This is the first published systematic review to evaluate the prevalence of post-mortem subclinical lung cancer. Compared to autopsy systematic reviews in breast, prostate and thyroid cancers, the pooled prevalence is lower in lung cancer for subclinical cancer. This result should be interpreted with caution due to the included studies risk of bias and heterogeneity, with further high-quality studies required in target screening populations.

Background Hemorrhage is the most common cause of potentially preventable death after injury. Early identification of patients with major hemorrhage (MH) is important as treatments are time-critical. However, diagnosis can be difficult, even for expert clinicians. This study aimed to determine how accurate clinicians are at identifying patients with MH in the prehospital setting. A second aim was to analyze factors associated with missed and overdiagnosis of MH, and the impact on mortality.Methods Retrospective evaluation of consecutive adult (≥16 years) patients injured in 2019–2020, assessed by expert trauma clinicians in a mature prehospital trauma system, and admitted to a major trauma center (MTC). Clinicians decided to activate the major hemorrhage protocol (MHPA) or not. This decision was compared with whether patients had MH in hospital, defined as the critical admission threshold (CAT+): administration of ≥3 U of red blood cells during any 60-minute period within 24 hours of injury. Multivariate logistical regression analyses were used to analyze factors associated with diagnostic accuracy and mortality.Results Of the 947 patients included in this study, 138 (14.6%) had MH. MH was correctly diagnosed in 97 of 138 patients (sensitivity 70%) and correctly excluded in 764 of 809 patients (specificity 94%). Factors associated with missed diagnosis were penetrating mechanism (OR 2.4, 95% CI 1.2 to 4.7) and major abdominal injury (OR 4.0; 95% CI 1.7 to 8.7). Factors associated with overdiagnosis were hypotension (OR 0.99; 95% CI 0.98 to 0.99), polytrauma (OR 1.3, 95% CI 1.1 to 1.6), and diagnostic uncertainty (OR 3.7, 95% CI 1.8 to 7.3). When MH was missed in the prehospital setting, the risk of mortality increased threefold, despite being admitted to an MTC.Conclusion Clinical assessment has only a moderate ability to identify MH in the prehospital setting. A missed diagnosis of MH increased the odds of mortality threefold. Understanding the limitations of clinical assessment and developing solutions to aid identification of MH are warranted.Level of evidence Level III—Retrospective study with up to two negative criteria.Study type Original research; diagnostic accuracy study.

The application of process mining in Information Technology (IT) incident management has been carried out. In the face of the increasing complexity of IT systems and a surge of incidents, traditional incident management is no longer effective. This study uses Kaggle's dataset on IT incident management to analyze event logs, identify process bottlenecks, and compare process flows seen in event logs with expected flows. Process mining techniques, such as process discovery and conformance, are applied using PM4PY and Celonis tools. The analysis results with process mining produce a new model process that can be applied in practice with a conformance rate of 81%.

Abstract The present multi-study article investigates the subjective experience of professional football (a.k.a. soccer) referees and players during the COVID-19 pandemic and the so-called ghost games (i.e., games without supporters). Referees from the Austrian Football Association completed questionnaires inquiring about self-efficacy, motivation, and general personal observations and perceptions (e.g., arousal or confidence). In addition, two players and one referee in the Austrian Football Bundesliga were interviewed retrospectively regarding their subjective experience during ghost games and the effects of emotions on behavior and performance using semi-structured, video-taped interviews. Results of the referee survey indicate that the most profound differences between regular games and ghost games lie in the domain of intrinsic motivation and multiple aspects of subjective experience. Specifically, the experience in ghost games compared with regular games was reported by referees as being significantly less motivating, less excited/tense, less emotional, less focused, and overall, more negative, despite being easier to referee and the players behaving more positively. Qualitative analyses of the video-taped interview footage indicated (i) substantial inter-individual variability regarding the extent of the effect of the empty stadiums on the subjective experience of emotions, (ii) consequently, different strategies to regulate emotions and arousal from suboptimal to optimal levels, both before and during competition, and (iii) interactions between reported emotions, arousal, motivation, self-confidence, behavior and performance on the pitch. In addition, non-verbal expressions of emotion were captured using fully automated AI-software that coded facial movements during interviews. The results of this exploratory facial expression analysis revealed varying degrees of arousal and valence in relation to the content of the statements during the interviews, demonstrating the convergent validity of our findings. Our findings contribute to the growing literature on the effects of football games without fans during the COVID-19 pandemic and provide insights into the subjective experience of professional football referees. Concerning referees and players alike, emotions are investigated as potential processes related to home-field advantage and performance in professional football by means of a multi-methods approach. Further, the combination of qualitative and quantitative measures—as well as verbal and non-verbal communication channels—can deepen our understanding of the emotional influence of (missing) spectators on the subjective experience and the behavior of sports professionals is discussed.

Abstract Background Timely and accurate identification of life- and limb-threatening injuries (LLTIs) is a fundamental objective of trauma care that directly informs triage and treatment decisions. However, the diagnostic accuracy of clinical examination to detect LLTIs is largely unknown, due to the risk of contamination from in-hospital diagnostics in existing studies. Our aim was to assess the diagnostic accuracy of initial clinical examination for detecting life- and limb-threatening injuries (LLTIs). Secondary aims were to identify factors associated with missed injury and overdiagnosis, and determine the impact of clinician uncertainty on diagnostic accuracy. Methods Retrospective diagnostic accuracy study of consecutive adult (≥ 16 years) patients examined at the scene of injury by experienced trauma clinicians, and admitted to a Major Trauma Center between 01/01/2019 and 31/12/2020. Diagnoses of LLTIs made on contemporaneous clinical records were compared to hospital coded diagnoses. Diagnostic performance measures were calculated overall, and based on clinician uncertainty. Multivariate logistic regression analyses identified factors affecting missed injury and overdiagnosis. Results Among 947 trauma patients, 821 were male (86.7%), median age was 31 years (range 16–89), 569 suffered blunt mechanisms (60.1%), and 522 (55.1%) sustained LLTIs. Overall, clinical examination had a moderate ability to detect LLTIs, which varied by body region: head (sensitivity 69.7%, positive predictive value (PPV) 59.1%), chest (sensitivity 58.7%, PPV 53.3%), abdomen (sensitivity 51.9%, PPV 30.7%), pelvis (sensitivity 23.5%, PPV 50.0%), and long bone fracture (sensitivity 69.9%, PPV 74.3%). Clinical examination poorly detected life-threatening thoracic (sensitivity 48.1%, PPV 13.0%) and abdominal (sensitivity 43.6%, PPV 20.0%) bleeding. Missed injury was more common in patients with polytrauma (OR 1.83, 95% CI 1.62–2.07) or shock (systolic blood pressure OR 0.993, 95% CI 0.988–0.998). Overdiagnosis was more common in shock (OR 0.991, 95% CI 0.986–0.995) or when clinicians were uncertain (OR 6.42, 95% CI 4.63–8.99). Uncertainty improved sensitivity but reduced PPV, impeding diagnostic precision. Conclusions Clinical examination performed by experienced trauma clinicians has only a moderate ability to detect LLTIs. Clinicians must appreciate the limitations of clinical examination, and the impact of uncertainty, when making clinical decisions in trauma. This study provides impetus for diagnostic adjuncts and decision support systems in trauma.

Abstract Background Systems science approaches like simulation modeling can offer an opportunity for community voice to shape policies. In the episteme of many communities there are elders, leaders, and researchers who are seen as bearers of historic knowledge and can contextualize and interpret contemporary research using knowledge systems of the community. There is a need for a systematic methodology to collaborate with community Knowledge Bearers and Knowledge Interpreters. In this paper we report the results of piloting a systematic methodology for collaborating with a community Knowledge-Bearer and Knowledge-Interpreter to develop a conceptual model revealing the local-level influences and architecture of systems shaping community realities. The use case for this pilot is ‘persistent poverty’ in the United States, specifically within the inner-city African American community in Baltimore City. Methods This pilot of a participatory modeling approach was conducted over a span of 7 sessions and included the following steps, each with an associated script: Step 1: Knowledge-Bearer and Knowledge-Interpreter recruitment Step 2: Relationship building Step 3: Session introduction, Vignette development & enrichment Step 4: Vignette analysis & constructing architecture of systems map Step 5: Augmenting architecture of systems map Results Each step of the participatory modeling approach resulted in artifacts that were valuable for both the communities and the research effort. Vignette construction resulted in narratives representing a spectrum of lived experiences, trajectories, and outcomes within a community. The collaborative analysis of vignettes yielded the Architecture of Systemic Factors map, that revealed how factors inter-relate to form a system in which lived experience of poverty occurs. A literature search provided an opportunity for the community to contextualize existing research about them using realities of lived experience. Conclusion This methodology showed that a community Knowledge Bearer can function as communicators and interpreters of their community’s knowledge base, can develop coherent narratives of lived experiences within which research and knowledge is contextualized, and can collaboratively construct conceptual mappings necessary for simulation modeling. This participatory modeling approach showed that even if there already exists a vast body of research about a community, collaborating with community gives context to that research and brings together disparate findings within narratives of lived experience.

Since the start of the COVID-19 pandemic, there has been a rapid transition to telehealth across the United States, primarily involving virtual clinic visits. Additionally, the proliferation of consumer technologies related to health reveals that for many people health and care in the contemporary world extends beyond the boundaries of a clinical interaction and includes sensors and devices that facilitate health in personal environments. The ideal connected environment is networked and intelligent, personalized to promote health and prevent disease. The combination of sensors, devices, and intelligence constitutes a connected health system around an individual that is optimized to improve and maintain health, deliver care, and predict and reduce risk of illness. Just as modern medicine uses the pathophysiology of disease as a framework for the basis of pharmacologic therapy, a similar clinically reasoned approach can be taken to organize and architect technological elements into therapeutic systems. In this work, we introduce a systematic methodology for the design of connected health systems grounded in the pathophysiologic basis of disease. As the digital landscape expands with the ubiquity of health devices, it is pivotal to enable technology-agnostic clinical reasoning to guide the integration of technological innovations into systems of health and care delivery that extend beyond the boundaries of a clinical interaction. Applying clinical reasoning in a repeatable and systematic way to organizing technology into therapeutic systems can yield potential benefits including expanding the study of digital therapeutics from individual devices to networked technologies as therapeutic interventions; empowering physicians who are not technological experts to still play a significant role in using clinical reasoning for architecting therapeutic networks of sensors and devices; and developing platforms to catalog and share combinations of technologies that can form therapeutic networks and connected health systems.

Background: Microwave ablation (MWA) has gained relevance in the treatment of hepatic malignancies and especially in hepatocellular carcinoma (HCC), and it is an important alternative to surgery. The purpose of the study was to evaluate whether the minimal ablative margin (MAM) or the initial tumor size has a greater effect on the success of stereotactic MWA of HCC regarding the time to local tumor progression (LTP) and overall survival (OS). Methods: 88 patients, who received stereotactic MWA of 127 tumor lesions with a curative intention were included in this single-center, retrospective study. The MAM was evaluated in a side-by-side comparison of pre- and post-ablative, contrast-enhanced slice imaging. A Cox proportional hazard model with a frailty term was computed to assess the influence of the MAM and the maximum tumor diameter on the time to LTP and the OS. Results: The maximum tumor diameter was identified as a significant positive predictor for LTP (hazard ratio 1.04, 95% CI 1.00–1.08, p = 0.03), but it was not a significant positive predictor for the OS (p = 0.20). The MAM did not have a significant influence on LTP-free survival (p = 0.23) and OS (p = 0.67). Conclusion: For the successful stereotactic MWA of HCC, the MAM and maximum tumor diameter might not have an influence on the OS, but the maximum tumor diameter seems to be an independent predictor of the time to LTP.

Over the past decade, the Beveridge curve in the Austrian labour market has shifted significantly outward. Using detailed administrative data on job vacancies and registered unemployed persons by region and skill level, we investigate which factors have caused this shift. We find that the Beveridge curve has shifted mainly because mismatch has increased significantly. Looking at the regional and skill level dimensions of mismatch unemployment, we find a significant increase in mismatch unemployment in manual routine jobs and in the Vienna region of Austria.

BackgroundSmartphones are often equipped with inertial sensors that measure individuals’ physical activity (PA). However, their role in remote monitoring of the patients’ PAs in telemedicine needs to be adequately explored. ObjectiveThis study aimed to explore the correlation between a participant’s actual daily step counts and the daily step counts reported by their smartphone. In addition, we inquired about the usability of smartphones for collecting PA data. MethodsThis prospective observational study was conducted among patients undergoing lower limb orthopedic surgery and a group of nonpatients as control. The data from the patients were collected from 2 weeks before surgery until 4 weeks after the surgery, whereas the data collection period for the nonpatients was 2 weeks. The participant’s daily step count was recorded by PA trackers worn 24/7. In addition, a smartphone app collected the number of daily steps registered by the participants’ smartphones. We compared the cross-correlation between the daily steps time series obtained from the smartphones and PA trackers in different groups of participants. We also used mixed modeling to estimate the total number of steps, using smartphone step counts and the characteristics of the patients as independent variables. The System Usability Scale was used to evaluate the participants’ experience with the smartphone app and the PA tracker. ResultsOverall, 1067 days of data were collected from 21 patients (n=11, 52% female patients) and 10 nonpatients (n=6, 60% female patients). The median cross-correlation coefficient on the same day was 0.70 (IQR 0.53-0.83). The correlation in the nonpatient group was slightly higher than that in the patient group (median 0.74, IQR 0.60-0.90 and median 0.69, IQR 0.52-0.81, respectively). The likelihood ratio tests on the models fitted by mixed effects methods demonstrated that the smartphone step count was positively correlated with the PA tracker’s total number of steps (χ21=34.7, P

IntroductionA significant number of Restitution Training (RT) paradigms claim to ameliorate visual field loss after stroke by re-activating neuronal connections in the residual visual cortex due to repeated bright light-stimulation at the border of the blind and intact fields. However, the effectiveness of RT has been considered controversial both in science and clinical practice for years. The main points of the controversy are (1) the reliability of perimetric results which may be affected by compensatory eye movements and (2) heterogeneous samples consisting of patients with visual field defects and/or visuospatial neglect.MethodsBy means of our newly developed and validated Virtual Reality goggles Salzburg Visual Field Trainer (SVFT) 16 stroke patients performed RT on a regular basis for 5 months. By means of our newly developed and validated Eye Tracking Based Visual Field Analysis (EFA), we conducted a first-time full eye-movement-controlled perimetric pre-post intervention study. Additionally, patients subjectively rated the size of their intact visual field.ResultsAnalysis showed that patients’ mean self-assessment of their subjective visual field size indicated statistically significant improvement while, in contrast, objective eye tracking controlled perimetric results revealed no statistically significant effect.DiscussionBright-light detection RT at the blind-field border solely induced a placebo effect and did not lead to training-induced neuroplasticity in the visual cortex of the type needed to ameliorate the visual field size of stroke patients.

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer death worldwide. Immunotherapy with immune checkpoint inhibitors (ICI) has significantly improved outcomes in some patients, however 80-85% of patients receiving immunotherapy develop primary resistance, manifesting as a lack of response to therapy. Of those that do have an initial response, disease progression may occur due to acquired resistance. The make-up of the tumour microenvironment (TME) and the interaction between tumour infiltrating immune cells and cancer cells can have a large impact on the response to immunotherapy. Robust assessment of the TME with accurate and reproducible methods is vital to understanding mechanisms of immunotherapy resistance. In this paper we will review the evidence of several methodologies to assess the TME, including multiplex immunohistochemistry, imaging mass cytometry, flow cytometry, mass cytometry and RNA sequencing.

Abstract Background Plasmodium vivax forms dormant liver stages that can reactivate weeks or months following an acute infection. Recurrent infections are often associated with a febrile illness and can cause a cumulative risk of severe anaemia, direct and indirect mortality, and onward transmission of the parasite. There is an increased risk of P. vivax parasitaemia following falciparum malaria suggesting a rationale for universal use of radically curative treatment in patients with P. falciparum malaria even in the absence of detectable P. vivax parasitaemia in areas that are co-endemic for both species. Methods This is a multicentre, health care facility-based, randomized, controlled, open-label trial in Bangladesh, Indonesia and Ethiopia. Patients with uncomplicated falciparum malaria, G6PD activity of ≥70% of the adjusted male median (AMM) and haemoglobin levels ≥8g/dl are recruited into the study and randomized to either receive standard schizonticidal treatment plus 7-day high dose primaquine (total dose 7mg/kg) or standard care in a 1:1 ratio. Patients are followed up weekly until day 63. The primary endpoint is the incidence risk of any P. vivax parasitemia on day 63. Secondary endpoints include incidence risk on day 63 of symptomatic P. vivax malaria and the risk of any P. falciparum parasitaemia. Secondary safety outcomes include the proportion of adverse events and serious adverse events, the incidence risk of severe anaemia (Hb

Abstract In this study the diagnostic capability and additional value of sequential CT arterioportography–arteriosplenography (CT AP–AS) in comparison to standard cross-sectional imaging and upper gastrointestinal endoscopy (UGE) in pediatric portal hypertension (PH) was analyzed. Patients with clinical signs of PH who underwent CT AP–AS in combination with additional contrast-enhanced magnetic resonance imaging (CE-MR) and/or contrast-enhanced computed tomography (CE-CT) were included. Two radiologists reviewed independently imaging regarding the capability to prove patency of (1) extrahepatic and intrahepatic main stem portal vein (PV), (2) intrahepatic PV system and (3) splenomesenteric venous axis. Imaging was reviewed for detection of abdominal varices and results were compared to UGE. Main venous supply of varices (PV and/or splenic vein system) and splenorenal shunting were evaluated. 47 imaging studies (20 CT AP-AS, 16 CE-MR, 11 CE-CT) and 12 UGE records of 20 patients were analyzed. CT AP–AS detected significantly more splenorenal shunts (p = 0.008) and allowed more confident characterization of the extra-/intrahepatic PV-system and splenomesenteric veins in comparison to CE-MR (p

Breast cancer is a heterogeneous disease that comprises multiple histological and molecular subtypes. To gain insight into mutations that drive breast tumorigenesis, we describe a pipeline for the identification and validation of tumor suppressor genes. Based on an in vivo genome‐wide CRISPR/Cas9 screen in Trp53+/– heterozygous mice, we identified tumor suppressor genes that included the scaffold protein Axin1, the protein kinase A regulatory subunit gene Prkar1a, as well as the proof‐of‐concept genes Pten, Nf1, and Trp53 itself. Ex vivo editing of primary mammary epithelial organoids was performed to further interrogate the roles of Axin1 and Prkar1a. Increased proliferation and profound changes in mammary organoid morphology were observed for Axin1/Trp53 and Prkar1a/Trp53 double mutants compared to Pten/Trp53 double mutants. Furthermore, direct in vivo genome editing via intraductal injection of lentiviruses engineered to express dual short‐guide RNAs revealed that mutagenesis of Trp53 and either Prkar1a, Axin1, or Pten markedly accelerated tumor development compared to Trp53‐only mutants. This proof‐of‐principle study highlights the application of in vivo CRISPR/Cas9 editing for uncovering cooperativity between defects in tumor suppressor genes that elicit mammary tumorigenesis.

Hyposidra talaca (Walker) merupakan hama penting tanaman teh. Larva H. talaca dapat menyebabkan kerugian antara 40–100% pada musim kemarau jika tidak dilakukan pengendalian yang tepat. Hama ini memiliki musuh alami berupa predator, parasitoid, dan patogen. Salah satu entomopatogen H. talaca adalah NPV. Penelitian ini bertujuan untuk menganalisis kekerabatan molekuler dari HytaNPV asal Bogor melalui sekuens gen DNA polimerase dan mengukur tingkat virulensi isolat NPV yang berasal dari H. talaca. Spesies yang sama dari lokasi yang berbeda dapat memiliki variabilitas genetik. Oleh karena itu, karakterisasi molekuler dengan polymerase chain reaction (PCR) pada sekuens DNA polimerase merupakan salah satu cara untuk mempelajari genetik HytaNPV. NPV diisolasi dari larva H. talaca terinfeksi yang dikumpulkan dari lapangan. Isolat DNA tersebut digunakan sebagai cetakan PCR untuk amplifikasi gen DNA polimerase dengan target amplikon ±1.000 pb. Proses sekuensing mengikuti hasil PCR untuk mendapatkan data sekuens nukleotida. Hasil sekuensing DNA polimerase HytaNPV diselaraskan dengan data BLAST GenBank untuk memberikan informasi tentang hubungan HytaNPV dengan NPV yang diisolasi dari wilayah lain. Berdasarkan analisis karakteristik molekuler dengan sekuens gen DNA polimerase, HytaNPV Bogor memiliki tingkat homologi sebesar 93,9% dengan HytaNPV yang diisolasi dari India. HytaNPV Bogor memiliki hubungan genetik dengan NPV yang menginfeksi Buzura suppressaria dari China dan Australia. Uji virulensi isolat HytaNPV terhadap H. talaca menunjukkan nilai LT50 tertinggi sebesar 1,92 hari ditemukan pada perlakuan konsentrasi 1,58 x 107 POBs/ml pada larva instar 2.