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Abstract Radioactive particles often contain very high radioactivity concentrations and are widespread. They pose a potential risk to human health and the environment. Their detection, quantification, and characterization are crucial if we are to understand their impact. Here, we present the use of a real-time autoradiography gaseous detector (using parallel ionization multiplier) to expedite and improve the accuracy of radioactive particle screening in complex environmental samples. First, standard particles were used to assess the detector capabilities (spatial resolution, spectrometry, and artefact contributions), then, we applied the technique to more complex and environmentally relevant samples. The real-time autoradiography technique provides data with a spatial resolution (≲100 µm) suitable for particle analysis in complex samples. Further, it can differentiate between particles predominantly emitting alpha and beta radiation. Here, the technique is applied to radioactive cesium-rich microparticles collected from the Fukushima Daiichi nuclear exclusion zone, showing their accurate detection, and demonstrating the viability of real-time autoradiography in environmental scenarios. Indeed, for more complex samples (radioactive particles in a less radioactive heterogeneous background mix of minerals), the technique permits relatively high selectivity for radioactive particle screening (up to 61.2% success rate) with low false positive percentages (~ 1%).

Abstract Background There is a rapid increase in the incidence of inflammatory bowel diseases (IBD) in newly industrialized countries, yet epidemiological data is incomplete. We herein report the methodology adopted to study the incidence of IBD in newly industrialized countries and to evaluate the effect of environmental factors including diet on IBD development. Methods Global IBD Visualization of Epidemiology Studies in the 21st Century (GIVES-21) is a population-based cohort of newly diagnosed persons with Crohn’s disease and ulcerative colitis in Asia, Africa, and Latin America to be followed prospectively for 12 months. New cases were ascertained from multiple sources and were entered into a secured online system. Cases were confirmed using standard diagnostic criteria. In addition, endoscopy, pathology and pharmacy records from each local site were searched to ensure completeness of case capture. Validated environmental and dietary questionnaires were used to determine exposure in incident cases prior to diagnosis. Results Through November 2022, 106 hospitals from 24 regions (16 Asia; 6 Latin America; 2 Africa) have joined the GIVES-21 Consortium. To date, over 290 incident cases have been reported. All patients have demographic data, clinical disease characteristics, and disease course data including healthcare utilization, medication history and environmental and dietary exposures data collected. We have established a comprehensive platform and infrastructure required to examine disease incidence, risk factors and disease course of IBD in the real-world setting. Conclusions The GIVES-21 consortium offers a unique opportunity to investigate the epidemiology of IBD and explores new clinical research questions on the association between environmental and dietary factors and IBD development in newly industrialized countries.

Purpose: Longitudinal patient-partnered experiences may promote medical student empathy, but evaluation of such programs is limited. The aim of this study was to compare areas of learning among first-year medical students randomized to a patient-centered track (PCT) or traditional track (TT) longitudinal clinical experience. Methods: PCT students (n = 24) were paired with 2 patients and a physician to participate in their patients’ care across multiple settings. TT students (n = 56) were paired with a physician preceptor and participated in caring for a variety of patients in a single setting. This qualitative study used a phenomenological approach to template analysis, examining and comparing student reflective essays for areas of learning. Results: Three domains of learning emerged: 1) Focus of learning (biomedical, patient-centered); 2) Roles and relationships (clinical skills, relationship-building, teaching from preceptor and patients); and 3) Context of care (health systems science, interprofessional care). PCT students described patient-centered learning, relationship-building, and patients’ role as teachers. In contrast, TT students emphasized biomedical learning, clinical skills development, and teaching from physician preceptors. Conclusions: Longitudinal patient-partnered clinical experiences provide rich opportunities for preclinical students to cultivate empathy and develop patient-centered values.

To successfully teach in a technologically advanced environment, an online instructor needs a wide abilities and competencies. This descriptive correlational study aimed to establish the extent to which faculty integrated technology in content development for effective online teaching in private universities in Kenya, with a focus on the United States International University -Africa. One hundred faculty from four schools responded to the questionnaire. Descriptive statistics, correlation, and linear regression analyses were used for data analysis. The results indicated that the faculty integrated different technologies in content development for online classes. For example, 85 % of the respondents integrated online course orientation (M = 4.3, SD= 0.855), and 86 % integrated eBooks/textbooks (M=4.2, SD=0.92). Only 42% of the respondents integrated personal generated videos (M=3.4, SD=1.42). A statistically significant linear relationship was found between integration of technology and effective online teaching . Integration of technology in content development accounted for approximately 17% of the variability in effective online teaching and had a statistically significant positive effect on effective online teaching (R2 = .165, β = .232, t(98) = 4.408, p < 0.05).

Usutu virus (USUV) is a mosquito-borne flavivirus of African origin. Over the past decades, USUV has spread through Europe causing mass die-offs among multiple bird species. The natural transmission cycle of USUV involves Culex spp. mosquitoes as vectors and birds as amplifying hosts. Next to birds and mosquitoes, USUV has also been isolated from multiple mammalian species, including humans, which are considered dead-end hosts. USUV isolates are phylogenetically classified into an African and European branch, subdivided into eight genetic lineages (Africa 1, 2, and 3 and Europe 1, 2, 3, 4, and 5 lineages). Currently, multiple African and European lineages are co-circulating in Europe. Despite increased knowledge of the epidemiology and pathogenicity of the different lineages, the effects of co-infection and transmission efficacy of the co-circulating USUV strains remain unclear. In this study, we report a comparative study between two USUV isolates as follows: a Dutch isolate (USUV-NL, Africa lineage 3) and an Italian isolate (USUV-IT, Europe lineage 2). Upon co-infection, USUV-NL was consistently outcompeted by USUV-IT in mosquito, mammalian, and avian cell lines. In mosquito cells, the fitness advantage of USUV-IT was most prominently observed in comparison to the mammalian or avian cell lines. When Culex pipiens mosquitoes were orally infected with the different isolates, no overall differences in vector competence for USUV-IT and USUV-NL were observed. However, during the in vivo co-infection assay, it was observed that USUV-NL infectivity and transmission were negatively affected by USUV-IT but not vice versa.

Abstract Background and Aim Environmental factors play a key role in development of Crohn's disease (CD), thought to be mediated by changes in the gut microbiota. We aimed to delineate the potential contribution of antibiotic exposure to subsequent development of CD, across diverse geographical populations. Methods This case–control study in Australia and three cities in China (Hong Kong, Guangzhou, and Kunming) included four groups: patients with CD, at‐risk individuals including non‐affected first‐degree relatives (FDRs) and household members of CD patients (HM), and unrelated healthy controls (HCs). Environmental risk factors, including childhood antibiotic use and 13 other categories, were assessed using a self‐developed questionnaire. Logistic regression and conditional logistic regression were used to determine environmental factors associated with CD development. Results From 2017 to 2019, a total of 254 patients with CD (mean age: 37.98 ± 13.76 years; 58.3% male), 73 FDR (mean age: 49.35 ± 13.28 years; 46.6% male), 122 HMs (including FDR) (mean age: 45.50 ± 13.25 years; 47.5% male), and 78 HC (mean age: 45.57 ± 11.24; 47.4% male) were included. Comparing CD patients with their FDR and HMs, antibiotic use before 18 years old was a risk factor for CD development (adjusted odds ratio [OR] 3.46, 95% confidence interval [CI] 1.38–8.69; P = 0.008). There were no significant differences in other childhood environmental risk factors between CD and their FDR or HMs. Subgroup analysis showed that antibiotic use

Abstract Background The importance of patient-centered measurement in cancer care has led to recognition of the potential for caregiver-reported outcomes to improve caregiver, patient and healthcare system outcomes. Yet, there is limited evidence to inform caregiver-reported outcome implementation. Our purpose was to generate evidence to inform the meaningful and constructive integration of caregiver-reported outcomes into cancer care to benefit caregivers, including exploration of the question of the extent to which these assessments should be shared with patients. We focused on caregivers of patients with colorectal cancer (CRC) because CRC is common, and associated caregiving can be complex. Results From our Interpretive Description analysis of qualitative interview data from 78 participants (25 caregivers, 37 patients, and 16 healthcare providers [HCPs]), we identified contrasting perspectives about the sharing of caregiver-reported outcome assessments with patients with CRC. Those who preferred open communication with both the patient and caregiver present considered this essential for supporting the caregiver. The participants who preferred private communication without the patient, cited concern about caregiver- and patient-burden and guilt. Recognizing these perspectives, HCPs described strategies used to navigate sensitivities inherent in preferences for open versus private communication. Conclusions The integration of caregiver-reported outcomes into cancer care will require careful consideration of caregiver and patient preferences regarding the communication of caregiver assessments to prevent additional burden.

BackgroundPatients’ perspectives and social contexts are critical for prevention of hospital readmissions; however, neither is routinely assessed using the traditional history and physical (H&P) examination nor commonly documented in the electronic health record (EHR). The H&P 360 is a revised H&P template that integrates routine assessment of patient perspectives and goals, mental health, and an expanded social history (behavioral health, social support, living environment and resources, function). Although the H&P 360 has shown promise in increasing psychosocial documentation in focused teaching contexts, its uptake and impact in routine clinical settings are unknown. ObjectiveThe aim of this study was to assess the feasibility, acceptability, and impact on care planning of implementing an inpatient H&P 360 template in the EHR for use by fourth-year medical students. MethodsA mixed methods study design was used. Fourth-year medical students on internal medicine subinternship (subI) services were given a brief training on the H&P 360 and access to EHR-based H&P 360 templates. Students not working in the intensive care unit (ICU) were asked to use the templates at least once per call cycle, whereas use by ICU students was elective. An EHR query was used to identify all H&P 360 and traditional H&P admission notes authored by non-ICU students at University of Chicago (UC) Medicine. Of these notes, all H&P 360 notes and a sample of traditional H&P notes were reviewed by two researchers for the presence of H&P 360 domains and impact on patient care. A postcourse survey was administered to query all students for their perspectives on the H&P 360. ResultsOf the 13 non-ICU subIs at UC Medicine, 6 (46%) used the H&P 360 templates at least once, which accounted for 14%-92% of their authored admission notes (median 56%). Content analysis was performed with 45 H&P 360 notes and 54 traditional H&P notes. Psychosocial documentation across all H&P 360 domains (patient perspectives and goals, mental health, expanded social history elements) was more common in H&P 360 compared with traditional notes. Related to impact on patient care, H&P 360 notes more commonly identified needs (20% H&P 360; 9% H&P) and described interdisciplinary coordination (78% H&P 360; 41% H&P). Of the 11 subIs completing surveys, the vast majority (n=10, 91%) felt the H&P 360 helped them understand patient goals and improved the patient-provider relationship. Most students (n=8, 73%) felt the H&P 360 took an appropriate amount of time. ConclusionsStudents who applied the H&P 360 using templated notes in the EHR found it feasible and helpful. These students wrote notes reflecting enhanced assessment of goals and perspectives for patient-engaged care and contextual factors important to preventing rehospitalization. Reasons some students did not use the templated H&P 360 should be examined in future studies. Uptake may be enhanced through earlier and repeated exposure and greater engagement by residents and attendings. Larger-scale implementation studies can help further elucidate the complexities of implementing nonbiomedical information within EHRs.

Advances in Next Generation Sequencing (NGS) technologies have enabled the accurate detection and quantification of circulating tumor-derived (ct)DNA in most gastrointestinal (GI) cancers. The prognostic and predictive utility of ctDNA in patiets with different stages of colorectal (CRC), gastro-esophageal (GEC) and pancreaticobiliary cancers (PBC) are currently under active investigation. The most mature clinical data to date are derived from studies in the prognostic utility of personalized ctDNA-based NGS assays in the detection of minimal residual disease (MRD) and early recurrence after surgery in CRC and other GI cancers. These findings are being validated in several prospective studies which are designed to test if ctDNA could outperform conventional approaches in guiding adjuvant chemotherapy, and in post-operative surveillance in some GI cancers. Several adaptive studies using ctDNA as a screening platform are also being used to identify patients with actionable genomic alterations for clinical trials of targeted therapies. In the palliative setting, ctDNA monitoring during treatment has shown promise in the detection and tracking of clonal variants associated with acquired resistance to targeted therapies and immune-checkpoint inhibitors (ICI). Moreover, ctDNA may help to guide the therapeutic re-challenge of targeted therapies in patients who have prior exposure to such treatment. This review will examine the most updated research findings on ctDNA as a biomarker in CRC, GEC and PBCs. It aims to provide insights into how the unique strengths of this biomarker could be optimally leveraged in improving the management of these GI cancers.

Electromagnetic navigation bronchoscopy (ENB)-guided indocyanine green (ICG) fluorescence dye marking of subsolid, small and deep lung lesions facilitates subsequent minimally invasive lung resection surgeries. The novel robotic-assisted bronchoscopy (RAB) platform can improve the accuracy and yield of ENB biopsy, and the use of RAB has been extended to ICG dye marking. However, performing this procedure in the hybrid operating room guided by cone-beam CT (CBCT) with immediate proceed to lung surgery has not been well reported. We studied the safety, feasibility and clinical outcomes of 5 consecutive cases performed between December 2021 and March 2022. Navigation success was 100% while localization success using ICG was 80%. The benefits and pitfalls of robotic bronchoscopy procedures, and challenges of combining with hybrid operating room CBCT were discussed in detail. In conclusion, robotic-assisted bronchoscopy is a promising and useful tool for ICG fluorescence dye-marking, providing accurate navigation, superior maneuverability and improved ergonomics compared to conventional bronchoscopy-guided ENB procedures. Learning curve is reasonable, but meticulous system set up to incorporate the robotic system into existing CBCT platform may be required to ensure a smooth procedure.

Purpose – tо study sought to delve into social capital and commercial banks' internationalization in Kenya drawing on the internationalization concept. Design/Method/Approach. The research adopted a positivist philosophical approach and used a descriptive cross-sectional research design targeting top and middle-level managers in Kenya's commercial banks. Data was collected using a structured questionnaire and analyzed using SPSS version 22.0 for both descriptive and inferential statistics. Structural Equation Modelling was used to establish the influence of social capital on commercial banks' internationalization in Kenya. Findings. The findings established a significant and positive relationship between the components of social capital: inter-cultural empathy, inter- personal impact and diplomacy, and commercial banks' internationalization. Practical implications. The results have significant consequences: Firstly, social capital has a positive and statistically significant relationship with commercial banks' internationalization. Secondly, all dimensions of social capital affect the acquisition of foreign market knowledge and financial resources. Thirdly, the use of individuals' social capital often changes during internationalization. Originality/Value. The study's novelty demonstrates the interaction of commercial banks' managers in Kenya on the application of social capital as an internationalization orientation process. Research Limitations/Future Research. The research contributes to the advancement of location theory. It opens avenues for future research to establish what extent social capital is beneficial to banks that have ventured into international markets. Paper type – empirical.

Lung cancer is a complex milieu of genomically altered cancer cells, a diverse collection of differentiated cells and nonneoplastic stroma. Lung cancer organoids is a three-dimensional structure grown from patient cancer tissue that could mimic in vivo complex behavior and cellular architecture of the cancer. Furthermore, the genomic alterations of the primary lung tumor is captured ex vivo. Lung cancer organoids have become an important preclinical model for oncology studies in recent years. It could be used to model the development of lung cancer, investigate the process of tumorigenesis, and also study the signaling pathways. The organoids could also be a platform to perform drug screening and biomarker validation of lung cancer, providing a promising prediction of patient-specific drug response. In this review, we described how lung cancer organoids have opened new avenues for translating basic cancer research into clinical therapy and discussed the latest and future developments in organoid technology, which could be further applied in lung cancer organoids research.

Objective To explore frequently hospitalised patients’ experiences and preferences related to primary care physician (PCP) involvement during hospitalisation across two care models.Design Qualitative study embedded within a randomised controlled trial. Semistructured interviews were conducted with patients. Transcripts were analysed using qualitative template analysis.Setting In the Comprehensive Care Programme (CCP) Study, in Illinois, USA, Medicare patients at increased risk of hospitalisation are randomly assigned to: (1) care by a CCP physician who serves as a PCP across both inpatient and outpatient settings or (2) care by a PCP as outpatient and by hospitalists as inpatients (standard care).Participants Twelve standard care and 12 CCP patients were interviewed.Results Themes included: (1) Positive attitude towards PCP; (2) Longitudinal continuity with PCP valued; (3) Patient preference for PCP involvement in hospital care; (4) Potential for in-depth involvement of PCP during hospitalisation often unrealised (involvement rare in standard care; in CCP, frequent interaction with PCP fostered patient involvement in decision making); and (5) PCP collaboration with hospital-based providers frequently absent (no interaction for standard care patients; CCP patients emphasising PCP’s role in interdisciplinary coordination).Conclusion Frequently hospitalised patients value PCP involvement in the hospital setting. CCP patients highlighted how an established relationship with their PCP improved interdisciplinary coordination and engagement with decision making. Inpatient–outpatient relational continuity may be an important component of programmes for frequently hospitalised patients. Opportunities for enhancing PCP involvement during hospitalisation should be considered.

Hookworm infections cause a neglected tropical disease (NTD) affecting ~740 million people worldwide, principally those living in disadvantaged communities. Infections can cause high morbidity due to their impact on nutrient uptake and their need to feed on host blood, resulting in a loss of iron and protein, which can lead to severe anaemia and impaired cognitive development in children. Currently, only one drug, albendazole is efficient to treat hookworm infection and the scientific community fears the rise of resistant strains. As part of on-going efforts to control hookworm infections and its associated morbidities, new drugs are urgently needed. We focused on targeting the blood-feeding pathway, which is essential to the parasite survival and reproduction, using the laboratory hookworm model Nippostrongylus brasiliensis (a nematode of rodents with a similar life cycle to hookworms). We established an in vitro-drug screening assay based on a fluorescent-based measurement of parasite viability during blood-feeding to identify novel therapeutic targets. A first screen of a library of 2654 natural compounds identified four that caused decreased worm viability in a blood-feeding-dependent manner. This new screening assay has significant potential to accelerate the discovery of new drugs against hookworms.

The novel coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus has spread rapidly across the globe, culminating in major global morbidity and mortality. As such, there has been a rapid escalation in scientific and clinical activity aimed at increasing our comprehension of this virus. This volume of work has led to early insights into risk factors associated with severity of disease, and mechanisms that underpin the virulence and dynamics involved in viral transmission. These insights ultimately may help guide potential therapeutics to reduce the human, economic and social impact of this pandemic. Importantly, the gastrointestinal (GI) tract has emerged as an important organ influencing propensity to, and potentially severity of, COVID-19 infection. Furthermore, the gut microbiome has been linked to a variety of risk factors for COVID-19 infection, and manipulation of the gut microbiome is an attractive potential therapeutic target for a number of diseases. While data profiling the gut microbiome in COVID-19 infection to date are limited, they support the possibility of several routes of interaction between COVID-19, the gut microbiome, angiotensin converting enzyme 2 (ACE-2) expression in the small bowel and colon and gut inflammation. This article will explore the evidence that implicates the gut microbiome as a contributing factor to the pathogenesis, severity and disease course of COVID-19, and speculate about the gut microbiome’s capability as a therapeutic avenue against COVID-19. Lay summary It has been noted that certain baseline gut profiles of COVID-19 patients are associated with a more severe disease course, and the gut microbiome impacts the disease course of several contributory risk factors to the severity of COVID-19. A protein called ACE-2, which is found in the small intestine among other sites, is a key receptor for COVID-19 virus entry; there is evidence that the gut microbiome influences ACE-2 receptor expression, and hence may play a role in influencing COVID-19 infectivity and disease severity. Furthermore, the gut microbiome plays a significant role in immune regulation, and hence may be pivotal in influencing the immune response to COVID-19. In terms of understanding COVID-19 treatments, the gut microbiome is known to interact with several drug classes being used to target COVID-19 and should be factored into our understanding of how patients respond to treatment. Importantly, our understanding of the role of the gut microbiome in COVID-19 infection remains in its infancy, but future research may potentially aid our mechanistic understanding of viral infection, and new ways in which we might approach treating it.

Diagnostics: Dual selection improves circulating tumor cell assay Using two selection markers, instead of one, can improve the sensitivity of a blood test for circulating tumor cells (CTCs). Steven A. Soper from the University of Kansas in Lawrence, USA, and colleagues analyzed blood samples from patients with cancers of the pancreas, colon, breast, ovaries and prostate, as well blood from healthy donors and those with benign disease. They ran each patient’s blood through two microfluidic devices, one chip targeting the established marker epithelial cell adhesion molecule (EpCAM) and another targeting a new marker, fibroblast activation protein alpha (FAPα). Doing so detected CTCs in nearly all the cancer patients—a substantial improvement over testing for EpCAM CTCs alone. Molecular and genetic analyses of the CTCs showed that those expressing EpCAM and FAPα are distinct subpopulations, and testing for both could prove valuable for clinical management.

Abstract The identification of mRNAs in distal projections of model organisms has led to the discovery of multiple proteins that are locally synthesized for functional roles such as axon guidance, injury signaling and regeneration. The extent to which local protein synthesis is conserved in human neurons is unknown. Here we used compartmentalized microfluidic chambers to characterize the transcriptome of distal projections of human embryonic stem cells differentiated using a protocol which enriched for glutamatergic neurons (hESC-neurons). Using gene expression analysis, we identified mRNAs proportionally enriched in these projections, representing a functionally unique local transcriptome as compared to the human neuronal transcriptome inclusive of somata. Further, we found that the most abundant mRNAs within these hESC-neuron projections were functionally similar to the axonal transcriptome of rat cortical neurons. We confirmed the presence of two well characterized axonal mRNAs in model organisms, β-actin and GAP43, within hESC-neuron projections using multiplexed single molecule RNA-FISH. Additionally, we report the novel finding that oxytocin mRNA localized to these human projections and confirmed its localization using RNA-FISH. This new evaluation of mRNA within human projections provides an important resource for studying local mRNA translation and has the potential to reveal both conserved and unique translation dependent mechanisms.

Multi-compartment microfluidic devices have become valuable tools for experimental neuroscientists, improving the organization of neurons and access to their distinct subcellular microenvironments for measurements and manipulations. While murine neurons are extensively used within these devices, there is a growing need to culture and maintain human neurons differentiated from stem cells within multi-compartment devices. Human neuron cultures have different metabolic demands and require longer culture times to achieve synaptic maturation. We tested different channel heights (100 μm, 400 μm, and open) to determine whether greater exposure to media for nutrient exchange might improve long-term growth of NIH-approved H9 embryonic stem cells differentiated into glutamatergic neurons. Our data showed an opposite result with both closed channel configurations having greater synaptic maturation compared to the open compartment configuration. These data suggest that restricted microenvironments surrounding neurons improve growth and maturation of neurons. We next tested whether covalently bound poly-D-lysine (PDL) might improve growth and maturation of these neurons as somata tend to cluster together on PDL adsorbed surfaces after long culture periods (>30 days). We found that covalently bound PDL greatly improved the differentiation and maturation of stem cell-derived neurons within the devices. Lastly, experimental paradigms using the multi-compartment platform show that axons of human stem cell derived neurons intrinsically regenerate in the absence of inhibitory cues and that isolated axons form presynaptic terminals when presented with synaptic targets.

Purpose: Despite advances in screening and awareness, Black and multiracial families continue to experience challenges when seeking an autism diagnosis for their children. Methods: We surveyed 400 Black and multiracial families of young children with autism from an existing research database in the United States about their retrospective diagnostic experiences. We gathered quantitative and qualitative data and engaged in iterative coding to understand timing and content of first concerns, families' experiences of care providers and systems, and the impact of race and culture on accessing care. Results: Families provided examples of early developmental concern and described provider, systemic, and cultural barriers and facilitators to care. Families also provided insight into the influence of culture and made recommendations on how the medical system could better care for Black and multiracial families of children with autism. Conclusions: Results add to a growing body of literature supporting the need for culturally sensitive and accessible care related to developmental monitoring, diagnosis, and follow-up care for Black and multiracial children.