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Abstract Soil is one of the most important reservoirs of antibiotic resistance, global threat that needs to be addressed with the One Health approach. Despite urban parks playing a fundamental role in urban ecosystems, the diffusion, maintenance, and human impact of antibiotic-resistance genes in this substrate are still poorly addressed. To fill in this gap, we adopted a molecular and culturomics approach to study antibiotic resistance in urban parks, accounting for the environmental matrix and the level of urbanization. A higher abundance of efflux-mediated mechanisms in undisturbed environments was observed, while antibiotic alteration or inactivation, and target replacement were more abundant in areas with a higher level of urbanization, also confirmed by significant correlations with anthropogenic features of the environmental matrix. Overall, this study highlights the crucial need to monitor antibiotic resistance in urban parks’ soil through a dual molecular and culturomics approach to fully understand and fight antibiotic resistance diffusion.

New data on the distribution of 11 Symphyta species phyllophagous on birch trees (Betula L.) are presented. Dineura virididorsata (Retzius, 1783), Heterarthrus nemoratus (Fallén, 1808), Nematinus caledonicus (Cameron, 1882), Pamphilius varius (Audinet-Serville, 1823), and Pristiphora alpestris (Konow, 1903) are reported from Slovakia for the first time. The little-known Allantus cingillum (Klug, 1814), Euura ampla (Konow, 1895), E. leionota (Benson, 1933), Profenusa thomsoni (Konow, 1886), Trichiosoma lucorum (Linnaeus, 1758), and T. vitellina (Linnaeus, 1761) were found in Slovakia, either after many decades or for the second time.

Abstract The proline-rich antimicrobial designer peptide Api137 inhibits protein expression in bacteria by binding simultaneously to the ribosomal polypeptide exit tunnel and the release factor (RF), depleting the cellular RF pool and leading to ribosomal arrest at stop codons. This study investigates the additional effect of Api137 on the assembly of ribosomes using an Escherichia coli reporter strain expressing one ribosomal protein per 30S and 50S subunit tagged with mCherry and EGFP, respectively. Separation of cellular extracts derived from cells exposed to Api137 in a sucrose gradient reveals elevated levels of partially assembled and not fully matured precursors of the 50S subunit (pre-50S). High-resolution structures obtained by cryogenic electron microscopy demonstrate that a large proportion of pre-50S states are missing up to five proteins (uL22, bL32, uL29, bL23, and uL16) and have misfolded helices in 23S rRNA domain IV. These data suggest a second mechanism for Api137, wherein it disrupts 50S subunit assembly by inducing the formation of misfolded precursor particles potentially incapable of evolving into active ribosomes, suggesting a bactericidal mechanism.

Section 195 (i) of South Africa’s Constitution mandates that public administration must reflect the nation's diversity, with recruitment and personnel management practices based on competence, fairness, and impartiality, while addressing historical inequalities to ensure broad representation. This creates a dual obligation for public administration: to foster inclusivity and equity while ensuring merit-based recruitment. Merit-based recruitment is crucial for meeting the public service's human resource needs and achieving employment equity by making opportunities accessible to all societal groups. While the practical application of merit-based recruitment presents opportunities, it still encounters considerable obstacles, such as political interference, and fragile institutional structures. This paper explored both the challenges and opportunities of merit-based recruitment in the South African public service through an analysis of government reports, academic literature, and policy reviews. The findings reveal that while the concept of merit-based recruitment is embedded in policy, its execution is hampered by political interference, nepotism, a lack of institutional capacity, skills shortages, and tensions between affirmative action and meritocracy. The paper recommends strengthening monitoring and evaluation measures employed by the Public Service Commission (PSC) to effectively promote and oversee the implementation of merit-based recruitment processes in the public service.

Inpatient care facilities globally are facing a critical shortage of staff, posing significant challenges to resident well-being and care quality. This issue is further compounded by demographic shifts and increasing care demands. While technological advancements offer promise in alleviating nursing staff burdens, their effective integration remains complex, with nursing staff acceptance playing a pivotal role. This paper describes a systematic approach designed to streamline the process of identifying, categorizing, and prioritizing suitable technologies in inpatient care settings. By taking into account the specific needs and requirements of nursing staff, this approach, validated through a comprehensive case study, aims to facilitate targeted technology adoption, thereby contributing to the successful digitization of this occupational domain.

The integration of Artificial Intelligence (AI) into healthcare represents a transformative shift, offering opportunities for enhancing patient care, diagnostic accuracy, process optimization and treatment pathways. This research sets out to forge a strategic management decision support framework for leveraging AI within the healthcare sector, aimed at systematically exploring and integrating AI innovations to bolster the patient health outcomes. By creating a comprehensive categorization system, we attempt to navigate the complex array of possible AI applications within the field of healthcare, hence enabling the identification, selection, and advancement of AIdriven initiatives. Through a blend of systematic literature review and expert insights, this study maps possible AI applications across dimensions like ‘medical disciplines’, ‘healthcare processes’, ‘AI research areas’, and ‘user groups’. By reflecting the diverse perspectives, this system transcends mere classification and stands as a cornerstone for identifying, selecting, and developing AI-driven medical use cases to guide strategic implementations of AI within clinical settings. This multidimensional system offers a blueprint for healthcare entities to strategically navigate the AI landscape, enabling them to make informed decisions about technology adoption and change management processes, ultimately leading to improved patient care and operational efficiency.

Abstract Background Paracetamol is the most consumed medicine globally. Its accessibility contributes to common overdose. Paracetamol overdose is responsible for > 50% of acute liver failure cases, making it the second most common reason for a liver transplant. Rapid quantitation of paracetamol is crucial to guide treatment of paracetamol overdose. Current tests require invasive sampling and relatively long turnaround times. Paper arrow-mass spectrometry (PA-MS) combines sample collection, extraction, separation, enrichment and ionisation onto a single paper strip, achieving rapid, accurate, cost-effective and eco-friendly analysis direct from raw human saliva. Methods To validate PA-MS against an established test, 17 healthy adults were recruited. Samples were collected before and at 15, 30, 60, 120 and 240 min after ingesting 1 g of paracetamol. Plasma measured with an established clinical test served as the reference standard to validate PA-MS with three biofluids—plasma, resting saliva (RS) and stimulated saliva (SS). Participants’ views of blood, RS and SS sampling procedures were assessed qualitatively. Cross-validation was assessed using Lin’s concordance correlation coefficients (CCC), Bland–Altman difference plots, and ratios of PA-MS to the reference standard test. Results PA-MS using stimulated saliva offers a reliable alternative to intravenous blood sampling. The CCC is 0.93, the mean difference with the reference test is − 0.14 mg/L, and the ratios compared to the reference test are 0.84–1.27 from correlated samples collected at 5 intervals over 4 h for each participant. Conclusions Paracetamol detection from SS with PA-MS provides a reliable result that can aid timely treatment decisions. Differences between paracetamol concentration in resting and stimulated saliva were also identified for the first time, highlighting the importance of standardising saliva collection methods in general. This study marks a major milestone towards rapid and convenient saliva analysis.

Abstract Introduction Combating the several public health threats on the African continent requires trained and equipped workforce. The establishment of the 6-month Africa CDC Public Health Emergency Management (PHEM) fellowship provides a pathway for developing a cadre of workforce that is capable of initiating and leading emergency management programs in Africa. Objective We present the process undertaken to draw up a competency-based curriculum for the first continental advanced training program in PHEM. Method A multi-step, mixed methodology was employed in this study. Systematic review process was triangulated with case reviews of similar training programs to provide the first draft of competencies. Through subsequent consultations with experts and technical iterations, the program’s competencies and curriculum were developed. Result Through four iterative revisions, the competencies framework evolved with input from each stage, resulting in a final structure of three competency domains and 10 sub-domains. These informed the development of an 11-course syllabus with corresponding learning objectives, outline and content. Conclusion A curriculum that reflects the foundational skills desirable of professionals engaged in the practice, education, and research in public health emergency management in Africa was developed utilizing mixed methods. Although this exercise was designed for the advanced PHEM Fellowship program at Africa CDC, the process, emerging competencies and curriculum could benchmark competency-based emergency management training across the African continent.

Abstract Antimicrobial susceptibility testing is a key weapon against antimicrobial resistance. Diagnostic microbiology laboratories use one-size-fits-all testing approaches that are often imprecise, inefficient, and inequitable. Here, we report a personalised approach that adapts laboratory testing for urinary tract infection to maximise the number of appropriate treatment options for each patient. We develop and assess susceptibility prediction models for 12 antibiotics on real-world healthcare data using an individual-level simulation study. When combined with decision thresholds that prioritise selection of World Health Organisation Access category antibiotics (those least likely to induce antimicrobial resistance), the personalised approach delivers more susceptible results (results that encourage prescription of that antibiotic) per specimen for Access category antibiotics than a standard testing approach, without compromising provision of susceptible results overall. Here, we show that personalised antimicrobial susceptibility testing could help tackle antimicrobial resistance by safely providing more Access category antibiotic treatment options to clinicians managing urinary tract infection.

Abstract Previous pattern electroretinogram studies indicate reduced retinal contrast gain in patients with a major depressive disorder (MDD) which may contribute to alterations in visual perception. In line, psychophysical investigations reported elevated contrast thresholds in MDD. This study aims to gain insights into higher-level processing of visual information in MDD by evaluating contrast suppression. We examined contrast suppression of 21 MDD patients and 23 healthy controls (HC) using four different stimulus conditions (spatial frequencies 6.3 and 12.6 cpd at 30% and 60% background contrast) in a psychophysical test. Participants were instructed to adjust perceived contrasts between two vertical target patches, embedded in a horizontally or vertically oriented grid background. With finer stimulus gratings, MDD patients exhibited less contrast suppression compared to HC, particularly when the stimulus contrast was high (p = 0.006; MDD vs. HC = − 45%). Contrast suppression in the HC group was significantly reduced for the coarse compared to the fine grating, while contrast suppression scores in MDD did not change with the spatial properties of the stimulus. The reduced contrast suppression in patients with MDD supports the hypothesis of altered dopaminergic neurotransmission and could be attributed to alterations in the retinal receptive fields or in dysfunctional adaptation mechanisms in depression.

Abstract Background Research to date suggests that frailty is higher in women and is associated with functional difficulty. This study builds on the evidence by examining the association between frailty and functional difficulty between low- and higher-income groups and between older men and women in these income groups. Methods This study adopted a cross-sectional design that complied with the STROBE checklist and included steps against confounding and common methods bias. The population was community-dwelling older adults aged 50 years or older in two urban neighbourhoods in Accra, Ghana. Participants were either in the low-income group in a low socioeconomic neighbourhood (n = 704) or the higher-income group in a high socioeconomic neighbourhood (n = 510). The minimum sample necessary was calculated, and the hierarchical linear regression analysis was utilised to analyse the data. Results Frailty was positively associated with functional difficulty in the low- and higher-income samples, but this association was stronger in the higher-income sample. Frailty was positively associated with frailty in men and women within the low- and higher-income samples. Conclusion The association of frailty with functional difficulty was consistent between low- and higher-income samples, although the strength of the relationship differed between these samples. In both income samples, the foregoing relationship was consistent between men and women, although the strength of the relationship differed between men and women.

To investigate epidemiology of and risk factors for laboratory-confirmed mpox during the 2022 outbreak in Nigeria, we enrolled 265 persons with suspected mpox. A total of 163 (61.5%) were confirmed to have mpox; 137 (84.0%) were adults, 112 (68.7%) male, 143 (87.7%) urban/semi-urban dwellers, 12 (7.4%) self-reported gay men, and 3 (1.8%) female sex workers. Significant risk factors for adults were sexual and nonsexual contact with persons who had mpox, as well as risky sexual behavior. For children, risk factors were close contact with an mpox-positive person and prior animal exposure. Odds of being mpox positive were higher for adults with HIV and lower for those co-infected with varicella zoster virus (VZV). No children were HIV-seropositive; odds of being mpox positive were higher for children with VZV infection. Our findings indicate mpox affects primarily adults in Nigeria, partially driven by sexual activity; childhood cases were driven by close contact, animal exposure, and VZV co-infection.

Abstract The correlation and physical interconnection between space weather indices and cosmic ray flux has been well‐established with extensive literature on the topic. Our investigation is centered on the relationships among the solar radio flux, geomagnetic field activity, and cosmic ray flux, as observed by the Neutron Monitor at the Lomnický štít Observatory in Slovakia. We processed the raw neutron monitor data, generating the first publicly accessible data set spanning 42 years. The curated continuous data are available in.csv format in hourly resolution from December 1981 to July 2023 and in minute resolution from January 2001 to July 2023 (Institute of Experimental Physics SAS, 2024, https://doi.org/10.5281/zenodo.10790915). Validation of this processed data was accomplished by identifying distinctive events within the data set. As part of the selection of events for case studies, we report the discovery of TGE‐s visible in the data. Applying the Pearson method for statistical analysis, we quantified the linear correlation of the data sets. Additionally, a prediction power score was computed to reveal potential non‐linear relationships. Our findings demonstrate a significant anti‐correlation between cosmic ray and solar radio flux with a correlation coefficient of −0.74, coupled with a positive correlation concerning geomagnetic field strength. We also found that the neutron monitor measurements correlate better with a delay of 7–21 hr applied to the geomagnetic field strength data. The correlation between these data sets is further improved when inspecting periods of extreme solar events only. Lastly, the computed prediction power score of 0.22 for neutron flux in the context of geomagnetic field strength presents exciting possibilities for developing real‐time geomagnetic storm prediction models based on cosmic ray measurements.

We investigate properties of closed approximate subgroups of locally compact groups, with a particular interest for approximate lattices (i.e., those approximate subgroups that are discrete and have finite co-volume).

BackgroundIndividuals with a minority sexual orientation have consistently been found to face a greater risk of mental health problems and problematic substance use than heterosexual individuals. The present study examined whether differences in alcohol use or alcohol use disorder (AUD) symptoms across the spectrum of sexual orientations could be explained by drinking motives (i.e., enhancement, social, coping and conformity motives).MethodA non-self-selective sample of non-abstinent, young Swiss men (N = 5,139; mean age = 25.4, SD = 1.25) completed a self-reporting questionnaire on sexual orientation (on a five-point attraction scale: heterosexual, mostly-heterosexual, bisexual, mostly-homosexual, homosexual), drinking motives, alcohol use indicators (e.g., heavy episodic drinking, Alcohol Use Disorders Identification Test-Consumption [AUDIT-C]), and AUD symptoms. Structural equation modeling was used to test whether drinking motives mediated the associations between dummy-coded sexual orientation (with heterosexual men as the reference) and alcohol use indicators or AUD symptoms.ResultsMostly-heterosexual men exhibited higher scores on alcohol use indicators than heterosexual men, with almost full mediation through their drinking motives, specifically higher enhancement motives. They also reported more AUD symptoms, partially mediated through drinking motives, with comparable contributions from enhancement and coping motives. Homosexual men, however, displayed similar or lower scores for alcohol use indicators and AUD symptoms than heterosexual men, but these differences were not mediated by drinking motives. Indeed, homosexual men exhibited greater coping motives than heterosexual men. No significant results or discernible patterns emerged for bisexual or mostly-homosexual men.DiscussionThese findings highlight the importance of considering the full spectrum of sexual orientations in healthcare and of broadening the focus on drinking motives beyond coping. Understanding the varied motives for alcohol use across the spectrum of sexual orientations facilitates tailored prevention strategies.

Summary: Background: Diabetic gastroenteropathy is associated with nausea, vomiting, bloating, pain, constipation, and diarrhoea. Current therapies are scarce. We tested faecal microbiota transplantation (FMT) for patients with type 1 diabetes and gastroenteropathy. Methods: In a randomised, double-blinded, placebo-controlled pilot trial, adults with type 1 diabetes and moderate-to-severe gastrointestinal symptoms were randomised (1:1) to encapsulated FMT or placebo. Each patient received around 25 capsules containing 50 g of faeces, administered in a single dose. The placebo capsules contained glycerol, saline and food colouring. All patients received FMT as a second intervention. The primary endpoint was number of adverse events of severity grade 2 or more assessed by the Common Terminology Criteria for Adverse Events during the week following the first intervention. Secondary endpoints included gastrointestinal symptoms and quality of life assessed four weeks after treatment. Public trial registration, ClinicalTrials.gov NCT04749030. Findings: We randomised 20 patients to FMT or placebo. Following this intervention, 26 adverse events of grade 2 or more occurred. Four patients in the FMT group reported seven adverse events, and five patients in the placebo group reported 19, with no differences between the groups. The most frequent adverse events were diarrhoea, bloating, and abdominal pain. No serious adverse events were related to the treatment. Patients who received FMT reduced their median Gastrointestinal Symptom Rating Scale—Irritable Bowel Syndrome score from 58 (IQR 54–65) to 35 (32–48), whereas patients receiving placebo reduced their score from 64 (55–70) to 56 (50–77) (p = 0.01). The Irritable Bowel Syndrome Impact Scale score improved from 108 (101–123) to 140 (124–161) with FMT and 77 (53–129) to 92 (54–142) with placebo (p = 0.02). The Patient Assessment of Gastrointestinal Symptom Severity Index declined from a median of 42 (28–47) to 25 (14–31) after FMT and 47 (31–69) to 41 (36–64) after placebo (p = 0.03). Interpretation: FMT was safe and improved clinical outcomes for patients with type 1 diabetes suffering from bowel symptoms. Funding: Steno Collaborative Grant.

Background and Aims: Chronic fatigue is common in patients with inflammatory bowel disease (IBD). The gut microbiota, specifically, microbial diversity and butyrate-producing bacteria have been linked to the fatigue pathogenesis. High-dose oral thiamine reduces fatigue, potentially through gut microbiota modification. In this study, we investigated how the gut microbiota influences the efficacy of high-dose thiamine in alleviating chronic fatigue in quiescent IBD (qIBD). Methods: We analyzed the microbiota and short-chain fatty acids concentrations in fecal samples from patients with qIBD, with (n = 40) or without (n = 20) chronic fatigue. The 40 patients with qIBD and fatigue were included in a randomized, placebo-controlled, crossover trial to assess a 4-week high-oral-dose thiamine regimen. Results: Butyrate and butyrate-producing bacteria were similar in patients with and without fatigue and did not change with high-dose thiamine treatment. Notably, Faecalibacterium prausnitzii was more abundant in thiamine responders compared with nonresponders both pretreatment (P = .019) and post-treatment (P = .038). The relative abundances of Faecalibacterium prausnitzii and Roseburia hominis, both pretreatment and post-treatment, inversely correlated with IBD fatigue score changes for patients with chronic fatigue (PRE; R = −0.48, P = .004, and R = −0.40, P = .018; POST; R = −0.42, P = .012, and R = −0.40, P = .017) respectively. Conclusion: Faecalibacterium prausnitzii and Roseburia hominis may serve as markers for response to high-dose thiamine in alleviating chronic fatigue in patients with qIBD. The mechanistic role of gut bacteria and butyrate in patients with chronic fatigue and qIBD should be further explored.

Antonio Fernández Alba (1927-2024) fue una figura crucial en la arquitectura española desde la segunda mitad del siglo XX, conocida por su enfoque interdisciplinario y su interés en la integración de las artes. Durante los años 50 y 60, Alba desarrolló un estilo sensible a las corrientes de vanguardia, inspirándose en la abstracción geométrica, el suprematismo y el arte no figurativo, explorando pintura y escultura en paralelo a su labor arquitectónica. Colaboró con figuras de renombre como Eduardo Chillida y Jorge Oteiza y formó parte del Grupo El Paso, que impulsaba una modernidad en ruptura con el pasado. Su obra y pensamiento reflejan una defensa de la “integración de las artes”, un ideal que buscaba enriquecer la arquitectura a través de la colaboración con otras disciplinas artísticas. Fernández Alba también se desempeñó como crítico y ensayista, denunciando el agotamiento de la arquitectura moderna en su deriva hacia el formalismo y la postmodernidad. Su idealismo ético y social se manifestó en su compromiso con la comunidad, así como en su labor como presidente del Museo Español de Arte Contemporáneo y en la creación del Museo Reina Sofía. Su legado destaca por una búsqueda constante de autenticidad y responsabilidad cultural, abordando la arquitectura no solo como una disciplina técnica, sino como un proyecto utópico y humanista, centrado en los valores de la modernidad y el progreso, los cuales reivindicó hasta sus últimos años.

This study investigates how expansion of soyabean production enhances smallholder livelihoods in rural Zambia. Using a mixed-methods research design that integrates questionnaire surveys, focus group discussions, and interviews. The results show that a clear policy orientation has driven the expansion of soyabean production, which has been underpinned by market dynamics and private actors. Soyabean adoption among smallholders is top-down, and emphasizes income benefits among rural producers. Soyabean adoption enhances food security and provides wider benefits, including increased community, regional, and cross-border trade exchanges. Quantitative analysis shows that climate change adaptation of soyabean cultivation increases the probability of improved rural livelihoods of small-scale farmers in Zambia by 1.554 which is statistically significant at 0.05 significance level. However, the top-down nature of soyabean promotion raises questions about sustainability beyond current state policy and market dynamics. The hype around soyabean expansion has not been followed by significant smallholder improvements; hence, there is a need for capacity building in value addition and processing, including those that emphasize the nutritional dimensions of soyabean expansion.

Background: This study aims to evaluate the progression of morphological and functional alterations over time in patients with hypertrophic cardiomyopathy (HCM) using Cardiac Magnetic Resonance (CMR). Methods: A retrospective analysis was conducted on patients with HCM who underwent serial CMR at 1.5 Tesla. Left ventricular (LV) mass was measured during diastole, including papillary muscles and trabeculae assessment. Appearance of Late Gadolinium Enhancement (LGE) was volumetrically quantified using a 5-standard-deviation (SD) threshold. Results: Thirty-two patients, with a mean age of 44 ± 16 years (range: 11–70 years), were evaluated after an average follow-up period of 5.2 ± 2.4 years (range: 0.8–9.1 years). Significant increases were observed in LV mass (from 194 ± 56 g to 217 ± 60 g; p = 0.0001), septal wall thickness (from 18 ± 4 mm to 19 ± 4 mm; p = 0.01), LGE mass (from 6 ± 17 g to 8 ± 18 g; p = 0.006), and left atrial volume (from 109 ± 41 ml to 129 ± 40 ml; p = 0.0001). Both left and right ventricular ejection fractions (LVEF and RVEF) significantly decreased over time (LVEF: from 70 ± 9 % to 66 ± 9 %; p = 0.04 and RVEF: from 70 ± 7 % to 67 ± 9 %; p = 0.02). Multivariate regression analysis revealed that HCM mass gain was independently associated with age (B = -0.43; p = 0.02) and LGE mass (B = -0.46; p = 0.02). The median LV mass gain rate in adults was 1.7 g per year/BSA (IQR, 0.6–2.7) compared to 6.0 g per year/BSA (IQR, 0.5–11.6) in adolescents (mean age: 16 years; range: 11–20 years). A positive correlation was found between LV mass and LGE mass (B = 0.55; p = 0.001), while an inverse relationship was observed between LV mass gain and LGE mass gain rates (−0.37; p = 0.03). Conclusion: The range of morphological changes in HCM seems to reflect an age-related equilibrium between hypertrophy and fibrosis. The extent of changes in LV mass, fibrosis, and functional decline in HCM may help identify patients at risk, emphasizing the importance of ongoing follow-up studies.

Abstract Breath analysis is an area of significant interest in medical research as it allows for non-invasive sampling with exceptional potential for disease monitoring and diagnosis. Volatile organic compounds (VOCs) found in breath can offer critical insight into a person’s lifestyle and/or disease/health state. To this end, the development of a rapid, sensitive, cost-effective and potentially portable method for the detection of key compounds in breath would mark a significant advancement. Herein, we have designed, built and tested a novel reagent-less atmospheric pressure photoionisation (APPI) source, coupled with mass spectrometry (MS), utilising a bespoke bias electrode within a custom 3D printed sampling chamber for direct analysis of VOCs. Optimal APPI-MS conditions were identified, including bias voltage, cone voltage and vaporisation temperature. Calibration curves were produced for ethanol, acetone, 2-butanone, ethyl acetate and eucalyptol, yielding R2 > 0.99 and limits of detection

Behavior change is the foundation for effective lifestyle prescriptions, yet such change is individualized, nonlinear and typically requires ongoing support. Health and wellness coaching (HWC) is a behavior change intervention with rapidly accruing evidence of positive impact on health behaviors such as exercise, nutrition and stress management. Furthermore, HWC enhances prevention and mitigates exacerbation of chronic lifestyle diseases, at least in the short-term (up to 6 months post intervention). Although the impact on long-term stability of behavior change remains unclear, it is evident that effective partnering with patients using key communication strategies, autonomy promotion, and flexible permissiveness can empower patients to develop healthy lifestyles. This partnership can be cultivated by clinicians as well as clinical team members including nationally board-certified coaches. Although much research is needed regarding the ongoing maintenance of lifestyle changes beyond 6 months, this article seeks to equip clinicians with current evidence, theoretical insights and practical strategies from a “coach approach” to foster more intrinsic forms of motivation which, in turn, empowers patients to adopt and maintain health-promoting behaviors.

Abstract Background To compare the diagnostic value of 120-kV with conventional 96-kV Cone-Beam CT (CBCT) of the temporal bone after cochlear implant (CI) surgery. Methods This retrospective study included CBCT scans after CI surgery between 06/17 and 01/18. CBCT allowed examinations with 96-kV or 120-kV; other parameters were the same. Two radiologists independently evaluated following criteria on 5-point Likert scales: osseous spiral lamina, inner and outer cochlear wall, semi-circular canals, mastoid trabecular structure, overall image quality, metal and motion artefacts, depiction of intracochlear electrode position and visualisation of single electrode contacts. Effective radiation dose was assessed. Results Seventy-five patients (females, n = 39 [52.0%], mean age, 55.8 ± 16.5 years) were scanned with 96-kV (n = 32, 42.7%) and 120-kV (n = 43, 57.3%) protocols including CI models from three vendors (vendor A n = 7; vendor B n = 43; vendor C n = 25). Overall image quality, depiction of anatomical structures, and electrode position were rated significantly better in 120-kV images compared to 96-kV (all p

Abstract Background At a global scale, the SARS-CoV-2 virus did not remain in its initial genotype for a long period of time, with the first global reports of variants of concern (VOCs) in late 2020. Subsequently, genome sequencing has become an indispensable tool for characterizing the ongoing pandemic, particularly for typing SARS-CoV-2 samples obtained from patients or environmental surveillance. For such SARS-CoV-2 typing, various in vitro and in silico workflows exist, yet to date, no systematic cross-platform validation has been reported. Results In this work, we present the first comprehensive cross-platform evaluation and validation of in silico SARS-CoV-2 typing workflows. The evaluation relies on a dataset of 54 patient-derived samples sequenced with several different in vitro approaches on all relevant state-of-the-art sequencing platforms. Moreover, we present UnCoVar, a robust, production-grade reproducible SARS-CoV-2 typing workflow that outperforms all other tested approaches in terms of precision and recall. Conclusions In many ways, the SARS-CoV-2 pandemic has accelerated the development of techniques and analytical approaches. We believe that this can serve as a blueprint for dealing with future pandemics. Accordingly, UnCoVar is easily generalizable towards other viral pathogens and future pandemics. The fully automated workflow assembles virus genomes from patient samples, identifies existing lineages, and provides high-resolution insights into individual mutations. UnCoVar includes extensive quality control and automatically generates interactive visual reports. UnCoVar is implemented as a Snakemake workflow. The open-source code is available under a BSD 2-clause license at github.com/IKIM-Essen/uncovar.

Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults, representing substantial morbidity and significant financial and resource burdens. Typically, patients with progressive DCM will eventually receive surgical treatment. Nonetheless, despite advancements in pharmacotherapeutics, evidence for pharmacological therapy remains limited. Health professionals from various fields would find interest in pharmacological agents that could benefit patients with mild DCM or enhance surgical outcomes. This review aims to consolidate all clinical and experimental evidence on the pharmacological treatment of DCM. We conducted a comprehensive narrative review that presents all pharmacological agents that have been investigated for DCM treatment in both humans and animal models. Riluzole exhibits effectiveness solely in rat models, but not in treating mild DCM in humans. Cerebrolysin emerges as a potential neuroprotective agent for myelopathy in animals but had contradictory results in clinical trials. Limaprost alfadex demonstrates motor function improvement in animal models and exhibits promising outcomes in a small clinical trial. Glucocorticoids not only fail to provide clinical benefits but may also lead to adverse events. Cilostazol, anti-Fas ligand antibody, and Jingshu Keli display promise in animal studies, while erythropoietin, granulocyte colony-stimulating factor and limaprost alfadex exhibit potential in both animal and human research. Existing evidence mainly rests on weak clinical data and animal experimentation. Current pharmacological efforts target ion channels, stem cell differentiation, inflammatory, vascular, and apoptotic pathways. The inherent nature and pathogenesis of DCM offer substantial prospects for developing neurodegenerative or neuroprotective therapies capable of altering disease progression, potentially delaying surgical intervention, and optimizing outcomes for those undergoing surgical decompression.

The paper focuses on providing basic characteristics of income inequality in a group of selected European countries in the period from 2000 to 2019. After presenting stylized facts and brief literature review, the paper proceeds to empirical analysis of income inequality in the observed countries by panel data techniques. Fixed and random effects models are estimated. After Hausman test approved the usage of fixed effects model, it was tested for serial correlation and robust standard errors were calculated. The empirical analysis of the determinants of income inequality shows that GDP growth, share of population in upper 10% of income percentile, Human Development Index and unemployment rate increase income inequality measured by Gini index, while share of workforce and share of population with tertiary education decrease income inequality. The results of the empirical analysis provide insight into determinants of income inequality, which may be useful for economic policy decision makers in their efforts to decrease the income inequality.

Climate change is considered as one of the greatest challenges to humanity, with Africa seen as one of the most affected continents due to low resilience and adaptive capacities. The complex interaction between multiple socio-ecological and economic stressors pose a great challenge to the application of the concept of social justice and its associated principles in managing climate change in Africa. Based on empirical research with 150 respondents and interactions in Libode, this paper highlights that water, food and settlement insecurities, floods, crop and animal losses and water-borne diseases remain some of the key negative impacts of climate change to rural residents in the Eastern Cape Province. Despite these adverse effects, the application of the core principles embedded in social justice as a tool for managing climate change impacts in the study area is elusive due to inadequate socio-economic and natural adjustments in response to actual and/or expected climate change adverse effects. The paper concludes that various forms of socio-economic and environmental inequalities can be reduced to the barest minimum and increase social transformation drastically in the Eastern Cape through the application of the principles of social justice to enhance adaptive capabilities.

The methanation of biogenic syngas for GreenLNG production is a promising alternative for fossil gas. The market price of renewable methane is currently still too high to compete with fossil LNG. One of the reasons for that is the extensive gas cleaning that is necessary for the methanation of syngas from the thermochemical gasification of biomass. A main cost factor is the removal of tar components. As part of the Horizon Europe project CarbonNeutralLNG, we propose a 3D-printed methanation reactor, which makes use of the freedom in design gained by the additive manufacturing process in order to adapt the reactor design for the in-situ co-reforming of tars. The reactor uses heat pipes and a conically widened reaction channel to effectively control local temperatures, suiting the needs of the methanation reaction. A temperature hot spot near the inlet provides the necessary conditions (high temperature, a suitable catalyst and sufficient residence time) for the reforming of tar species, that are present in the syngas. Two reactor concepts are proposed. ADDmeth3.1 uses a dedicated internal channel structure that serves as a counter-current heat exchanger for the feed gas, whereas ADDmeth3.2 is optimized to fill the triangular footprint of a scalable reactor module as best as possible. Both designs were subject to a preliminary feasibility study, to ensure sufficient heat removal and a finite element analysis regarding structural stability was performed. Minimum safety factors against yielding of 3.53 and higher were achieved even without the internal diamond lattice support structure. The triangular modular reactor cell can easily be scaled up by connecting multiple cells in parallel, since the triangular shape can be extended efficiently into a honeycomb pattern.

BackgroundElectroretinograms (ERG) are usually recorded with non-invasive corneal electrodes, requiring direct contact with the ocular surface. However, corneal electrode application is not tolerated by some individuals. The advent of handheld ERG devices has facilitated the use of skin electrodes for ERG measurements. Skin electrodes do not require corneal contact and thus enhance patient comfort, simplify the attachment process, and reduce preparation time, which is particularly beneficial for clinical psychiatric research. Nevertheless, due to the different attachment methods, ERG amplitudes recorded with skin compared to corneal electrodes are considerably smaller. However, comparative data on ERGs recorded with skin vs. corneal electrodes in psychiatric populations are currently lacking.Materials and methodsWe recorded flash electroretinograms of 57 healthy controls (HC) and 30 patients with a major depressive disorder (MDD) using both sensor strip skin and corneal electrodes with the handheld RETeval® device.ResultsThe significant reduction in both the amplitude and peak time of the a-wave in MDD when using sensor strip skin electrodes could not be replicated with corneal electrodes. Comparing both electrode types in HC revealed a fair correlation between sensor strip and corneal electrodes for a- and b-wave amplitudes and a moderate correlation for a- and b-wave peak times.ConclusionIn addition to being better tolerated, sensor strip skin electrodes appear to be more effective than corneal electrodes in detecting ERG alterations in patients with MDD when using the RETeval® device, making them a promising alternative to traditional corneal electrodes.

Summary: Background: Plasma phospho-tau 217 (pTau217) assays can accurately detect Alzheimer's disease (AD) pathology, but clinical application is limited by the need for specialised equipment. This study tests the performance of a plasma pTau217 assay performed on the Lumipulse-G® platform, that is in widespread clinical use, for selecting patients for therapy based on β-amyloid (Aβ) status and tau staging. Methods: Participants included 388 individuals with 18F-NAV4694 Aβ-PET and 18F-MK6240 tau-PET. Association of pTau217 with PET was examined using Spearman's correlation. Discriminative performance for Aβ and tau PET status as well as tau staging was assessed using Receiver Operating Characteristic analysis. Findings: Plasma pTau217 had a high correlation with both Aβ Centiloid (r = 0.76) and tau SUVRmeta-temporal (r = 0.78). Area under curve (AUC) was 0.93 for Aβ− vs Aβ+ and 0.94 for tau− vs tau+. Applying one threshold (Youden's index), pTau217 was 87% accurate in classification of participants to Aβ− vs Aβ+. Applying two thresholds to classify participants into Low, Indeterminate, and High zones, 17.8% had Indeterminate results and among Low/High zone participants, 92% were correctly classified as Aβ− or Aβ+. The assay accurately discriminated moderate/high neocortical tau from no tau or tau limited to mesial-temporal lobe (AUC 0.97) and high neocortical tau from all others (AUC 0.94). Interpretation: Plasma pTau217, measured by the widely-available, fully-automated Lumipulse®, was a strong predictor of both Aβ and tau PET status and demonstrated strong predictive power in identifying individuals likely to benefit the most from anti-Aβ treatments. Funding: NHMRC grants 1132604, 1140853, 1152623 and AbbVie.

Background: Faecal microbiota transplantation (FMT) is a highly effective treatment for Clostridioides difficile infection. Its use is backed by solid evidence, but application methods differ. Encapsulated FMT is a non-invasive, patient-friendly and scalable application method that may be preferred over colonoscopy or nasoduodenal tube application. Objectives: We describe a detailed protocol, the Glyprotect protocol, for producing glycerol-based capsules to increase FMT accessibility. Design: Using iterative quality improvement methods, we developed and validated the Glyprotect protocol as a reproducible protocol for cryopreserving minimally processed donor faeces in a standard hospital laboratory setting. Methods: We describe detailed standard operating procedures for producing glycerol-based capsules, including all necessary materials and troubleshooting guidelines. Capsule integrity was tested at various temperatures and pH levels. Flow cytometry was used to measure microbiota counts and dose accuracy. Results: The Glyprotect protocol has been used for more than 2500 capsule-based FMT treatments and complies with European tissue and cell standards. The protocol is optimised to preserve microbes and minimise modulation of the donated microbiota by removing debris and water, which also reduces the number of capsules needed per FMT treatment. The intestinal microbiota is preserved in glycerol for cryoprotection and to prevent capsule leakage. Each capsule contains 650 µL microbe–glycerol mass, estimated to contain an average of 2.5 × 10 8 non-specified bacteria. Conclusion: The Glyprotect protocol enables hospitals and tissue establishments to set up capsule production in a standard laboratory, improving patients’ access to FMT. The protocol facilitates the scalability of FMT services because capsule FMT is less time-consuming and less expensive than liquid-suspension FMT applied by colonoscopy or nasojejunal tube. Trial registration: Not applicable.

Alzheimer’s disease (AD) is a devastating neurodegenerative condition that affects memory and cognition, characterized by neuronal loss and currently lacking a cure. Mutations in PSEN1 (Presenilin 1) are among the most common causes of early-onset familial AD (fAD). While changes in neuronal excitability are believed to be early indicators of AD progression, the link between PSEN1 mutations and neuronal excitability remains to be fully elucidated. This study examined iPSC-derived neurons (iNs) from fAD patients with PSEN1 mutations S290C or A246E, alongside CRISPR-corrected isogenic cell lines, to investigate early changes in excitability. Electrophysiological profiling revealed reduced excitability in both PSEN1 mutant iNs compared to their isogenic controls. Neurons bearing S290C and A246E mutations exhibited divergent passive membrane properties compared to isogenic controls, suggesting distinct effects of PSEN1 mutations on neuronal excitability. Additionally, both PSEN1 backgrounds exhibited higher current density of voltage-gated potassium (Kv) channels relative to their isogenic iNs, while displaying comparable voltage-gated sodium (Nav) channel current density. This suggests that the Nav/Kv imbalance contributes to impaired neuronal firing in fAD iNs. Deciphering these early cellular and molecular changes in AD is crucial for understanding disease pathogenesis.

Background: Bolus administration of adrenaline during cardiopulmonary resuscitation (CPR) results in only short-term increases in systemic and cerebral perfusion pressure (CePP) with unclear effects on cerebral oxygenation. The aim of this study was to investigate the effects of bolus compared to continuous adrenaline administration on cerebral oxygenation in a porcine CPR model. Methods: After five minutes of cardiac arrest, mechanical CPR was performed for 15 min. Adrenaline (45 μg/kg) was administered either as a bolus every five minutes or continuously over the same period via an infusion pump. Main outcome parameter was brain tissue oxygen tension (PbtO2), secondary outcome parameters included mean arterial pressure (MAP), intracranial pressure (ICP), CePP and cerebral regional oxygen saturation (rSO2) as well as arterial and cerebral venous blood gases. Results: During CPR, mean MAP (45 ± 8 mmHg vs. 38 ± 8 mmHg; p = 0.0827), mean ICP (27 ± 7 mmHg vs. 20 ± 7 mmHg; p = 0.0653) and mean CePP (18 ± 8 mmHg vs. 18 ± 8 mmHg; p = 0.9008) were similar in the bolus and the continuous adrenaline group. Also, rSO2 (both 24 ± 6 mmHg; p = 0.9903) and cerebral venous oxygen saturation (18 ± 12% versus 27.5 ± 12%; p = 0.1596) did not differ. In contrast, relative PbtO2 reached higher values in the continuous group after five minutes of CPR and remained significantly higher than in the bolus group until the end of resuscitation. Conclusion: Continuous administration of adrenaline improved brain tissue oxygen tension compared with bolus administration during prolonged CPR.

En el presente trabajo nos proponemos indagar en las memorias de la última dictadura cívico-militar argentina que difunden los miembros de la coalición La Libertad Avanza con la finalidad de comprender su posicionamiento en torno al pasado, la importancia que adquiere ese pasado en la actualidad, y los modos en que articulan sus visiones con una disputa más amplia respecto al rol del Estado y de la democracia. Para ello, analizaremos el discurso de los principales referentes de la coalición tomando como fuente de información sus relatos en los medios de comunicación modernos y tradicionales, considerando las coyunturas políticas y los contextos de enunciación.

Abstract Quantum annealing (QA) holds promise for optimization problems in quantum computing, especially for combinatorial optimization. This analog framework attracts attention for its potential to address complex problems. Its gate-based homologous, QAOA with proven performance, has attracted a lot of attention to the NISQ era. Several numerical benchmarks try to compare these two metaheuristics, however, classical computational power highly limits the performance insights. In this work, we introduce a parametrized version of QA enabling a precise 1-local analysis of the algorithm. We develop a tight Lieb–Robinson bound for regular graphs, achieving the best-known numerical value to analyze QA locally. Studying MaxCut over cubic graph as a benchmark optimization problem, we show that a linear-schedule QA with a 1-local analysis achieves an approximation ratio over 0.7020, outperforming any known 1-local algorithms.

Abstract Elucidating the relationship between non-coding regulatory element sequences and gene expression is crucial for understanding gene regulation and genetic variation. We explored this link with the training of interpretable deep learning models predicting gene expression profiles from gene flanking regions of the plant species Arabidopsis thaliana, Solanum lycopersicum, Sorghum bicolor, and Zea mays. With over 80% accuracy, our models enabled predictive feature selection, highlighting e.g. the significant role of UTR regions in determining gene expression levels. The models demonstrated remarkable cross-species performance, effectively identifying both conserved and species-specific regulatory sequence features and their predictive power for gene expression. We illustrated the application of our approach by revealing causal links between genetic variation and gene expression changes across fourteen tomato genomes. Lastly, our models efficiently predicted genotype-specific expression of key functional gene groups, exemplified by underscoring known phenotypic and metabolic differences between Solanum lycopersicum and its wild, drought-resistant relative, Solanum pennellii.

Coffee leaf diseases are a significant challenge for coffee cultivation. They can reduce yields, impact bean quality, and necessitate costly disease management efforts. Manual monitoring is labor-intensive and time-consuming. This research introduces a pioneering mobile application equipped with global positioning system (GPS)-enabled reporting capabilities for on-site coffee leaf disease detection. The application integrates advanced deep learning (DL) techniques to empower farmers and agronomists with a rapid and accurate tool for identifying and managing coffee plant health. Leveraging the ubiquity of mobile devices, the app enables users to capture high-resolution images of coffee leaves directly in the field. These images are then processed in real-time using a pre-trained DL model optimized for efficient disease classification. Five models, Xception, ResNet50, Inception-v3, VGG16, and DenseNet, were experimented with on the dataset. All models showed promising performance; however, DenseNet proved to have high scores on all four-leaf classes with a training accuracy of 99.57%. The inclusion of GPS functionality allows precise geotagging of each captured image, providing valuable location-specific information. Through extensive experimentation and validation, the app demonstrates impressive accuracy rates in disease classification. The results indicate the potential of this technology to revolutionize coffee farming practices, leading to improved crop yield and overall plant health.

Background: Immunization plays a substantial role in reducing the under-five mortality rate. However, Tanzania still has a significant number of zero-dose and under-vaccinated children and was ranked among the top ten African countries with the highest numbers of zero-dose children in 2022. The human-centered design (HCD) approach is more ethical and effective at addressing public health challenges in complex sociocultural settings. This study aimed to use the HCD approach to aid in identifying, prioritizing, and implementing community-centric interventions in Tanzania, particularly in the Ilala District of Dar es Salaam, to increase vaccine demand and close the zero-dose gap by at least 50%. Methods: The study involved co-creation workshops with 483 participants to identify, design, and test solutions. The study followed the UNICEF Journey to Health and Immunization framework to identify barriers and enablers influencing stakeholders in adopting and sustaining health- and immunization-related actions. Results: The study identified the causes of under-five defaulting and the zero-dose gap, i.e., the inadequate support of local community leaders in under-five vaccination sensitization and surveillance; poor infrastructure to new settlement areas; hesitancy and unwillingness of parents/guardians; absence of house numbers; limited/time-constrained availability of resources to facilitate mobile immunization services, etc. The participants were able to come up with 309 ideas, which were refined through multiple iterations using the impact–-effort matrix and skimmed down to three (3) solutions: (i) having health facilities to notify and alert local leaders about vaccination dates; (ii) using parents, kids, and grownups who got vaccinated to influence others; (iii) using local government leaders and house representatives for vaccine advocacy. Of these, the solution involving local government leaders and house representatives for vaccine advocacy was implemented. An advocacy strategy was used to enhance the collaboration of the District Commissioner, Council leaders, and community leaders. A home-to-home interpersonal sensitization approach accompanied by the household delivery of vaccination services was employed. The findings reveal that the HCD framework was impactful in increasing collaborations/cooperation with local government leaders and community ownership of the under-five vaccination initiative. As a result, 67,145 houses, equal to 104%, were reached, surpassing the initial target of 64,800 houses, and 131,088 families, equal to 83% of the targeted 156,995 households, were sensitized through a home-to-home campaign approach. This study demonstrates the effectiveness of the approach. Researchers and practitioners are encouraged to adopt the HCD approach when addressing public health challenges, especially in complex sociocultural settings.

Bayesian approaches to decision trees (DTs) using Markov Chain Monte Carlo (MCMC) samplers have recently demonstrated state-of-the-art accuracy performance when it comes to training DTs to solve classification problems. Despite the competitive classification accuracy, MCMC requires a potentially long runtime to converge. A widely used approach to reducing an algorithm’s runtime is to employ modern multi-core computer architectures, either with shared memory (SM) or distributed memory (DM), and use parallel computing to accelerate the algorithm. However, the inherent sequential nature of MCMC makes it unsuitable for parallel implementation unless the accuracy is sacrificed. This issue is particularly evident in DM architectures, which normally provide access to larger numbers of cores than SM. Sequential Monte Carlo (SMC) samplers are a parallel alternative to MCMC, which do not trade off accuracy for parallelism. However, the performance of SMC samplers in the context of DTs is underexplored, and the parallelization is complicated by the challenges in parallelizing its bottleneck, namely redistribution, especially on variable-size data types such as DTs. In this work, we study the problem of parallelizing SMC in the context of DTs both on SM and DM. On both memory architectures, we show that the proposed parallelization strategies achieve asymptotically optimal O(log2N) time complexity. Numerical results are presented for a 32-core SM machine and a 256-core DM cluster. For both computer architectures, the experimental results show that our approach has comparable or better accuracy than MCMC but runs up to 51 times faster on SM and 640 times faster on DM. In this paper, we share the GitHub link to the source code.

We tackle the problem of Clifford isometry compilation, i.e, how to synthesize a Clifford isometry into an executable quantum circuit. We propose a simple framework for synthesis that only exploits the elementary properties of the Clifford group and one equation of the symplectic group. We highlight the versatility of our framework by showing that several normal forms of the literature are natural corollaries. We recover the state of the art two-qubit gate depth necessary for the execution of a Clifford circuit on an LNN architecture, concomitantly with another work. We also propose practical synthesis algorithms for Clifford isometries with a focus on Clifford operators, graph states and codiagonalization of Pauli rotations. Benchmarks show that in all three cases we improve the 2-qubit gate count and depth of random instances compared to the state-of-the-art methods. We also improve the execution of practical quantum chemistry experiments.

Traumatic brain injury (TBI) remains one of the leading causes of death. Because of the individual nature of the trauma (brain, circumstances and forces), humans experience individual TBIs. This makes it difficult to generalise therapies. Clinical management issues such as whether intracranial pressure (ICP), cerebral perfusion pressure (CPP) or decompressive craniectomy improve patient outcome remain partly unanswered. Experimental drug approaches for the treatment of secondary brain injury (SBI) have not found clinical application. The complex, cellular and molecular pathways of SBI remain incompletely understood, and there are insufficient experimental (animal) models that reflect the pathophysiology of human TBI to develop translational therapeutic approaches. Therefore, we investigated different injury patterns after acute subdural hematoma (ASDH) as TBI in a post-hoc approach to assess the impact on SBI in a long-term, human-sized porcine TBI animal model. Post-mortem brain tissue analysis, after ASDH, bilateral ICP, CPP, cerebral oxygenation and temperature monitoring, and biomarker analysis were performed. Extracerebral, intraparenchymal–extraventricular and intraventricular blood, combined with brainstem and basal ganglia injury, influenced the experiment and its outcome. Basal ganglia injury affects the duration of the experiment. Recognition of these different injury patterns is important for translational interpretation of results in this animal model of SBI after TBI.

Summary: Background: The most near-term clinical application of genome-wide association studies in lung cancer is a polygenic risk score (PRS). Methods: A case-control dataset was generated consisting of 4002 lung cancer cases from the LORD project and 20,010 ethnically matched controls from CARTaGENE. A genome-wide PRS including >1.1 million genetic variants was derived and validated in UK Biobank (n = 5419 lung cancer cases). The predictive ability and diagnostic discrimination performance of the PRS was tested in LORD/CARTaGENE and benchmarked against previous PRSs from the literature. Stratified analyses were performed by smoking status and genetic risk groups defined as low (80th percentile) PRS. Findings: The phenotypic variance explained and the effect size of the genome-wide PRS numerically outperformed previous PRSs. Individuals with high genetic risk had a 2-fold odds of lung cancer compared to low genetic risk. The PRS was an independent predictor of lung cancer beyond conventional clinical risk factors, but its diagnostic discrimination performance was incremental in an integrated risk model. Smoking increased the odds of lung cancer by 7.7-fold in low genetic risk and by 11.3-fold in high genetic risk. Smoking with high genetic risk was associated with a 17-fold increase in the odds of lung cancer compared to individuals who never smoked and with low genetic risk. Interpretation: Individuals at low genetic risk are not protected against the smoking-related risk of lung cancer. The joint multiplicative effect of PRS and smoking increases the odds of lung cancer by nearly 20-fold. Funding: This work was supported by the CQDM and the IUCPQ Foundation owing to a generous donation from Mr. Normand Lord.

HIV self-testing (HIVST) has the potential to reduce barriers associated with clinic-based preexposure prophylaxis (PrEP) delivery. We conducted a substudy nested in a prospective, pilot implementation study evaluating patient-centered differentiated care services. Clients chose either a blood-based or oral fluid HIVST kit at the first refill visit. Data were abstracted from program files and surveys were administered to clients. We purposively sampled a subset of PrEP clients and their providers to participate in in-depth interviews. We surveyed ( n = 285). A majority (269/285, 94%) reported HIV risk. Blood-based HIVST was perceived as easy to use (76/140, 54%), and (41/140, 29%) perceived it to be more accurate. Oral fluid-based HIVST was perceived to be easy to use (95/107, 89%), but almost all (106/107, 99%) perceived it as less accurate. HIVST improved privacy, reduced workload, and saved time. HIVST demonstrates the potential to streamline facility-based PrEP care in busy African public health facilities.

Objective: Romiplostim is used to treat chemotherapy-induced thrombocytopenia in a variety of tumor types; however, few studies have examined its use in breast and gynecologic cancers. We evaluated platelet response and durability of response to romiplostim in patients with gynecologic or breast cancer complicated by chemotherapy-induced thrombocytopenia. Methods: We retrospectively identified 33 patients with gynecologic or breast cancer who received romiplostim between 07/1/2021–07/31/2022 at an academic cancer center. Results: Thirty-three patients met inclusion criteria; 26 (79 %) had breast cancer, 4 (12 %) had ovarian cancer, and 3 (9 %) had endometrial cancer. Twenty patients (61 %) experienced treatment delays and 12 (36 %) required dose reductions prior to starting romiplostim for chemotherapy-induced thrombocytopenia, with some patients experiencing both. Eleven patients (33 %) did not undergo a dose reduction or delay prior to initiation of romiplostim. Median platelet count prior to romiplostim therapy was 53 k/mcL (range, 40.5–78.8). Median platelet count within 3 weeks following initiation of romiplostim was 147 k/mcL (range, 31–562). Twenty-one patients (64 %) achieved platelet correction within 3 weeks, of whom 10 (48 %) resumed anticancer therapy and maintained platelet levels above 100 k/mcL at 8 weeks. Twelve patients did not achieve platelet correction within 3 weeks of romiplostim initiation; 4 (33 %) required a treatment change secondary to persistent thrombocytopenia, 3 (25 %) required a treatment dose reduction, 3 (25 %) were deemed too ill to continue therapy, and 2 (17 %) required a treatment delay. Conclusions: Romiplostim facilitated the resumption of anticancer therapy in 64 % of patients with gynecologic or breast cancer complicated by chemotherapy-induced thrombocytopenia.

Background. Normothermic machine perfusion (NMP) of liver grafts has been shown to reduce intraoperative catecholamine consumption and the need for allogenic blood products after reperfusion compared with organs undergoing classical static cold storage (SCS). This study aimed to investigate the effects of an NMP phase after SCS (NMP after SCS) of liver grafts in terms of postreperfusion hemodynamics and transfusion requirements. Methods. Eighteen recipients of NMP after SCS grafts were matched according to recipient age, donor age, and model for end-stage liver disease score in a 1:2 ratio with recipients of an SCS graft. Postreperfusion hemodynamics and the need for catecholamines, blood products, and clotting factors were compared. Results. After reperfusion of the organ, patients in the NMP after SCS group showed significantly reduced transfusion requirements for packed red blood cells and platelet concentrates compared with patients of the SCS group (P

Repressor element-1 silencing transcription factor (REST) is a transcriptional repressor involved in neurodevelopment and neuroprotection. REST forms a complex with the REST corepressors, CoREST1, CoREST2, or CoREST3 (encoded by RCOR1, RCOR2, and RCOR3, respectively). Emerging evidence suggests that the CoREST family can target unique genes independently of REST, in various neural and glial cell types during different developmental stages. However, there is limited knowledge regarding the expression and function of the CoREST family in human neurodevelopment. To address this gap, we employed 2D and 3D human pluripotent stem cell (hPSC) models to investigate REST and RCOR gene expression levels. Our study revealed a significant increase in RCOR3 expression in glutamatergic cortical and GABAergic ventral forebrain neurons, as well as mature functional NGN2-induced neurons. Additionally, a simplified astrocyte transdifferentiation protocol resulted in a significant decrease in RCOR2 expression following differentiation. REST expression was notably reduced in mature neurons and cerebral organoids. In summary, our findings provide the first insights into the cell-type-specific expression patterns of RCOR genes in human neuronal and glial differentiation. Specifically, RCOR3 expression increases in neurons, while RCOR2 levels decrease in astrocytes. The dynamic expression patterns of REST and RCOR genes during hPSC neuronal and glial differentiation underscore the potential distinct roles played by REST and CoREST proteins in regulating the development of these cell types in humans.