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Adoption of high-content omic technologies in clinical studies, coupled with computational methods, has yielded an abundance of candidate biomarkers. However, translating such findings into bona fide clinical biomarkers remains challenging. To facilitate this process, we introduce Stabl, a general machine learning method that identifies a sparse, reliable set of biomarkers by integrating noise injection and a data-driven signal-to-noise threshold into multivariable predictive modeling. Evaluation of Stabl on synthetic datasets and five independent clinical studies demonstrates improved biomarker sparsity and reliability compared to commonly used sparsity-promoting regularization methods while maintaining predictive performance; it distills datasets containing 1,400-35,000 features down to 4-34 candidate biomarkers. Stabl extends to multi-omic integration tasks, enabling biological interpretation of complex predictive models, as it hones in on a shortlist of proteomic, metabolomic and cytometric events predicting labor onset, microbial biomarkers of pre-term birth and a pre-operative immune signature of post-surgical infections. Stabl is available at https://github.com/gregbellan/Stabl .

Oral mucosal pathologies comprise an array of diseases with worldwide prevalence and medical relevance. Affecting a confined space with crucial physiological and social functions, oral pathologies can be mutilating and drastically reduce quality of life. Despite their relevance, treatment for these diseases is often far from curative and remains vastly understudied. While multiple factors are involved in the pathogenesis of oral mucosal pathologies, the host's immune system plays a major role in the development, maintenance, and resolution of these diseases. Consequently, a precise understanding of immunological mechanisms implicated in oral mucosal pathologies is critical (1) to identify accurate, mechanistic biomarkers of clinical outcomes; (2) to develop targeted immunotherapeutic strategies; and (3) to individualize prevention and treatment approaches. Here, we review key elements of the immune system's role in oral mucosal pathologies that hold promise to overcome limitations in current diagnostic and therapeutic approaches. We emphasize recent and ongoing multiomic and single-cell approaches that enable an integrative view of these pathophysiological processes and thereby provide unifying and clinically relevant biological signatures.

Preeclampsia is a complex disease of pregnancy whose physiopathology remains unclear. We developed machine-learning models for early prediction of preeclampsia (first 16 weeks of pregnancy) and over gestation by analyzing six omics datasets from a longitudinal cohort of pregnant women. For early pregnancy, a prediction model using nine urine metabolites had the highest accuracy and was validated on an independent cohort (area under the receiver-operating characteristic curve [AUC] = 0.88, 95% confidence interval [CI] [0.76, 0.99] cross-validated; AUC = 0.83, 95% CI [0.62,1] validated). Univariate analysis demonstrated statistical significance of identified metabolites. An integrated multiomics model further improved accuracy (AUC = 0.94). Several biological pathways were identified including tryptophan, caffeine, and arachidonic acid metabolisms. Integration with immune cytometry data suggested novel associations between immune and proteomic dynamics. While further validation in a larger population is necessary, these encouraging results can serve as a basis for a simple, early diagnostic test for preeclampsia.

This study explores nature’s role in the spatial development of the local Roman Catholic Church in Kikwit, a mid-size city in the Democratic Republic of Congo. Founded as a mission station by Belgian Jesuits in 1912, the local Church has experienced a peculiar development over the last century. Roman Catholic communities seem grouped spatially according to their function. Communities with apostolic functions are located in the western part of the city, while contemplative and intellectual communities are concentrated in the eastern part. The dividing line appears to be the Kwilu River, which separates the lively commercial and residential center on the left bank from more rural municipalities on the right bank. This paper proposes that this spatial organization results from the interplay of multiple theologies of nature that led to different ways of engaging with the natural surroundings in the region. Moreover, the research suggests that the Catholic Church’s transformation from a missionary institution to a (more or less) independent Church in Kikwit relied heavily on nature because it allowed further development of both the apostolic and contemplative functions of the Church.

While the coronavirus disease 2019 (COVID-19) pandemic placed a heavy burden on healthcare systems worldwide, it also induced urgent mobilisation of research teams to develop treatments preventing or curing the disease and its consequences. It has, therefore, challenged critical care research to rapidly focus on specific fields while forcing critical care physicians to make difficult ethical decisions. This narrative review aims to summarise critical care research -from organisation to research fields- in this pandemic setting and to highlight opportunities to improve research efficiency in the future, based on what is learned from COVID-19. This pressure on research revealed, i.e., (i) the need to harmonise regulatory processes between countries, allowing simplified organisation of international research networks to improve their efficiency in answering large-scale questions; (ii) the importance of developing translational research from which therapeutic innovations can emerge; (iii) the need for improved triage and predictive scores to rationalise admission to the intensive care unit. In this context, key areas for future critical care research and better pandemic preparedness are artificial intelligence applied to healthcare, characterisation of long-term symptoms, and ethical considerations. Such collaborative research efforts should involve groups from both high and low-to-middle income countries to propose worldwide solutions. As a conclusion, stress tests on healthcare organisations should be viewed as opportunities to design new research frameworks and strategies. Worldwide availability of research networks ready to operate is essential to be prepared for next pandemics. Importantly, researchers and physicians should prioritise realistic and ethical goals for both clinical care and research.

While atypical sensory processes have become central to scientific explanatory models of autism, such models usually do not explicitly address first-person experiences of sensory processes by autistic individuals. Detailed phenomenological research of this subjective domain is nonetheless essential to ground explanatory accounts in the actual experiences and challenges faced by autistic individuals. Therefore, our study consisted of an interpretative phenomenological analysis of 18 semi-structured interviews with autistic individuals about their experiences of hypersensitivity. Overall, our analysis showed how hypersensitivity pertained to disturbances at a basic level of bodily self-experience and also affected other crucial phenomenological experiential dimensions such as the subjective perception of time and space, sense-making processes, intersubjectivity, and moods. Hypersensitivities were described by participants as intrusive experiences of being vulnerably exposed to overwhelming stimuli that invaded their bodies and were simultaneously related to an invasive, chaotic, unpredictable or threatening perception of the (social) environment. Our study highlights the impact of hypersensitivities on experiential domains outside the strict sensory register, thereby providing further evidence for altered sensory processing as a potential core mechanism involved in a variety of autistic symptoms. Our study also indicates the clinical importance of therapeutic interventions that act on a fragile sense of embodiment in autism.

Author(s): Ilona Papousek [sup.1], Christian Rominger [sup.1], Elisabeth M. Weiss [sup.1], Corinna M. Perchtold [sup.1], Andreas Fink [sup.1], Kurt Feyaerts [sup.2] Author Affiliations: (1) grid.5110.5, 0000000121539003, Institute of Psychology, University [...], This interdisciplinary study examined the structure of humor creation in the specific context of efforts to positively reappraise stressful situations for effective coping. In a sample of n = 101 participants, a performance test was used to assess the quantity (fluency, number of generated ideas that qualified as humor) and quality (rated funniness) of humor creation in cognitive reappraisal. Linguistic mechanisms were identified and quantified using cognitive-linguistic methods of corpus analysis, and their employment was correlated with humor production performance on the level of the individual. Almost all individuals were able to come up with reappraisal ideas that qualified as humorous. Depressive symptoms, a negative mood state, and high perceptions of threat did not compromise the participants' capability to create humor. Individuals who were more serious-minded as a trait produced ideas that were rated as less funny, but their basic ability to create humor was unaffected. Metonymy (a contiguity-based principle of meaning extension) emerged as by far the most prominent semantic mechanism in the creation of humorous re-interpretations. Furthermore, its use was related to good humor creation performance in terms of quantity and quality, which is in line with its assumed importance in the extension of meaning in general and the creation of humor in particular. Further effective linguistic mechanisms and conceptual phenomena were identified. The empirical data may be valuable for the development of interventions involving the creation of humorous ideas for cognitive reappraisal.

Natural killer (NK) cells, with a unique NK cell receptor phenotype, are abundantly present in the non-pregnant (endometrium) and pregnant (decidua) humanuterine mucosa. It is hypothesized that NK cells in the endometrium are precursors for decidual NK cells present during pregnancy. Microenvironmental changes can alter the phenotype of NK cells, but it is unclear whether decidual NK cell precursors in the endometrium alter their NK cell receptor repertoire under the influence of pregnancy. To examine whether decidual NK cell precursors reveal phenotypic modifications upon pregnancy, we immunophenotyped the NK cell receptor repertoire of both endometrial and early-pregnancy decidual NK cells using flow cytometry. We showed that NK cells in pre-pregnancy endometrium have a different phenotypic composition compared to NK cells in early-pregnancy decidua. The frequency of killer-immunoglobulin-like receptor (KIR expressing NK cells, especially KIR2DS1, KIR2DL2L3S2, and KIR2DL2S2 was significantly lower in decidua, while the frequency of NK cells expressing activating receptors NKG2D, NKp30, NKp46, and CD244 was significantly higher compared to endometrium. Furthermore, co-expression patterns showed a lower frequency of NK cells co-expressing KIR3DL1S1 and KIR2DL2L3S2 in decidua. Our results provide new insights into the adaptations in NK cell receptor repertoire composition that NK cells in the uterine mucosa undergo upon pregnancy.

Abstract Cellular organization and functions encompass multiple scales in vivo. Emerging high-plex imaging technologies are limited in resolving subcellular biomolecular features. Expansion Microscopy (ExM) and related techniques physically expand samples for enhanced spatial resolution, but are challenging to be combined with high-plex imaging technologies to enable integrative multiscaled tissue biology insights. Here, we introduce Expand and comPRESS hydrOgels (ExPRESSO), an ExM framework that allows high-plex protein staining, physical expansion, and removal of water, while retaining the lateral tissue expansion. We demonstrate ExPRESSO imaging of archival clinical tissue samples on Multiplexed Ion Beam Imaging and Imaging Mass Cytometry platforms, with detection capabilities of > 40 markers. Application of ExPRESSO on archival human lymphoid and brain tissues resolved tissue architecture at the subcellular level, particularly that of the blood-brain barrier. ExPRESSO hence provides a platform for extending the analysis compatibility of hydrogel-expanded biospecimens to mass spectrometry, with minimal modifications to protocols and instrumentation.

Estimating the time of delivery is of high clinical importance because pre- and postterm deviations are associated with complications for the mother and her offspring. However, current estimations are inaccurate. As pregnancy progresses toward labor, major transitions occur in fetomaternal immune, metabolic, and endocrine systems that culminate in birth. The comprehensive characterization of maternal biology that precedes labor is key to understanding these physiological transitions and identifying predictive biomarkers of delivery. Here, a longitudinal study was conducted in 63 women who went into labor spontaneously. More than 7000 plasma analytes and peripheral immune cell responses were analyzed using untargeted mass spectrometry, aptamer-based proteomic technology, and single-cell mass cytometry in serial blood samples collected during the last 100 days of pregnancy. The high-dimensional dataset was integrated into a multiomic model that predicted the time to spontaneous labor [R = 0.85, 95% confidence interval (CI) [0.79 to 0.89], P = 1.2 × 10-40, N = 53, training set; R = 0.81, 95% CI [0.61 to 0.91], P = 3.9 × 10-7, N = 10, independent test set]. Coordinated alterations in maternal metabolome, proteome, and immunome marked a molecular shift from pregnancy maintenance to prelabor biology 2 to 4 weeks before delivery. A surge in steroid hormone metabolites and interleukin-1 receptor type 4 that preceded labor coincided with a switch from immune activation to regulation of inflammatory responses. Our study lays the groundwork for developing blood-based methods for predicting the day of labor, anchored in mechanisms shared in preterm and term pregnancies.

Conclusion: Malignant priapism should be suspected, especially in patients with no evident risk factors for priapism (hematological diseases, drugs, alcohol, neurological diseases, or metabolic disorders).

IntroductionFew studies have evaluated the presence of Post COVID-19 conditions (PCC) in people from Latin America, a region that has been heavily afflicted by the COVID-19 pandemic. In this study, we describe the frequency, co-occurrence, predictors, and duration of 23 symptoms in a cohort of Mexican patients with PCC.MethodsWe prospectively enrolled and followed adult patients hospitalized for severe COVID-19 at a tertiary care centre in Mexico City. The incidence of PCC symptoms was determined using questionnaires. Unsupervised clustering of PCC symptom co-occurrence and Kaplan–Meier analyses of symptom persistence were performed. The effect of baseline clinical characteristics was evaluated using Cox regression models and reported with hazard ratios (HR).ResultsWe found that amongst 192 patients with PCC, respiratory problems were the most prevalent and commonly co-occurred with functional activity impairment. 56% had ≥5 persistent symptoms. Symptom persistence probability at 360 days 0.78. Prior SARS-CoV-2 vaccination and infection during the Delta variant wave were associated with a shorter duration of PCC. Male sex was associated with a shorter duration of functional activity impairment and respiratory symptoms. Hypertension and diabetes were associated with a longer duration of functional impairment. Previous vaccination accelerated PCC recovery.DiscussionIn our cohort, PCC symptoms were frequent (particularly respiratory and neurocognitive ones) and persistent. Importantly, prior SARS-CoV-2 vaccination resulted in a shorter duration of PCC.

Stance-taking, the public act of positioning oneself toward objects, people or states of affairs, has been studied in many fields of research. Recently, its multimodal realization in interaction has received increasing attention. The current contribution aims to take stock of research on multimodal stance-taking so far, and to present possible avenues for future research. We systematically gathered and appraised 76 articles that investigate the involvement of bodily-visual resources in stance-taking in interaction. The critical appraisal focused on two dimensions of the stance act: form-function relations constituting it, and its dynamic organization in interaction. Regarding form-function relations, we found systematic involvement of specific bodily-visual resources in different stance acts, as well as patterns of multimodal intensification and mitigation of stances. As for its dynamic organization, the review discusses how stance-taking is organized temporally throughout an interaction, with all participants involved carefully negotiating and adapting their stances to one another. Finally, attention is paid to the broader context of stance-taking, including its role in different social and societal contexts. Based on this review, we were able to identify several gaps in the literature, and avenues for future research. We argue that much potential for broadening the scope of research lies in increasing the methodological diversity in approaching multimodal stance-taking, as well as in cross-linguistic studies and varying settings and participant constellations. In conclusion, research into multimodal stance-taking is vibrant, with ample opportunities for future work. This review can be considered as a call to action to move beyond the premise that stance-taking is multimodal, and further investigate this intriguing and fundamental human capacity.

Understanding alterations of selfhood (termed self-disorders or self-disturbances) that are considered typical of the schizophrenia-spectrum is a central focus of phenomenological research. The currently most influential way of phenomenologically conceiving self-disorders in schizophrenia is as disorders of the so-called most basic or "minimal self". In this paper, we first highlight some challenges for the minimal self-view of self-disorders, focusing on (1) problems arising from the supposedly "essential" or "universal" nature of minimal self with respect to phenomenal awareness and (2) the critical implications of alterations of self-experience in schizophrenia that involve heightened or exaggerated sense of self. In the second part, we tentatively explore how a (non-egological) transparency-view of consciousness may offer an alternative way of understanding the experiential abnormalities involved in self-disorders in schizophrenia. We discuss how such a transparency-view (1) may account for loss-of-self experiences; (2) is compatible with the key notion of "hyper-reflexivity"; and (3) can help explain instances of self-disorder involving increased sense of self. In conclusion, we consider some possible advantages of this alternative view for research on self-disorders and clinical approaches. [ABSTRACT FROM AUTHOR]

This study explores nature's role in the spatial development of the local Roman Catholic Church in Kikwit, a mid-size city in the Democratic Republic of Congo. Founded as a mission station by Belgian Jesuits in 1912, the local Church has experienced a peculiar development over the last century. Roman Catholic communities seem grouped spatially according to their function. Communities with apostolic functions are located in the western part of the city, while contemplative and intellectual communities are concentrated in the eastern part. The dividing line appears to be the Kwilu River, which separates the lively commercial and residential center on the left bank from more rural municipalities on the right bank. This paper proposes that this spatial organization results from the interplay of multiple theologies of nature that led to different ways of engaging with the natural surroundings in the region. Moreover, the research suggests that the Catholic Church's transformation from a missionary institution to a (more or less) independent Church in Kikwit relied heavily on nature because it allowed further development of both the apostolic and contemplative functions of the Church. [ABSTRACT FROM AUTHOR]

Background: Newly developed quantitative chest computed tomography (CT) outcomes designed specifically to assess structural abnormalities related to cystic fibrosis (CF) lung disease are now available. CFTR modulators potentially can reduce some structural lung abnormalities. We aimed to investigate the effect of CFTR modulators on structural lung disease progression using different quantitative CT analysis methods specific for people with CF (PwCF).Methods: PwCF with a gating mutation (Ivacaftor) or two Phe508del alleles (lumacaftor-ivacaftor) provided clinical data and underwent chest CT scans. Chest CTs were performed before and after initiation of CFTR modulator treatment. Structural lung abnormalities on CT were assessed using the Perth Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF), airway-artery dimensions (AA), and CF-CT methods. Lung disease progression (0–3 years) in exposed and matched unexposed subjects was compared using analysis of covariance. To investigate the effect of treatment in early lung disease, subgroup analyses were performed on data of children and adolescents aged

Psychosocial and stress-related factors (PSFs), defined as internal or external stimuli that induce biological changes, are potentially modifiable factors and accessible targets for interventions that are associated with adverse pregnancy outcomes (APOs). Although individual APOs have been shown to be connected to PSFs, they are biologically interconnected, relatively infrequent, and therefore challenging to model. In this context, multi-task machine learning (MML) is an ideal tool for exploring the interconnectedness of APOs on the one hand and building on joint combinatorial outcomes to increase predictive power on the other hand. Additionally, by integrating single cell immunological profiling of underlying biological processes, the effects of stress-based therapeutics may be measurable, facilitating the development of precision medicine approaches.ObjectivesThe primary objectives were to jointly model multiple APOs and their connection to stress early in pregnancy, and to explore the underlying biology to guide development of accessible and measurable interventions.Materials and MethodsIn a prospective cohort study, PSFs were assessed during the first trimester with an extensive self-filled questionnaire for 200 women. We used MML to simultaneously model, and predict APOs (severe preeclampsia, superimposed preeclampsia, gestational diabetes and early gestational age) as well as several risk factors (BMI, diabetes, hypertension) for these patients based on PSFs. Strongly interrelated stressors were categorized to identify potential therapeutic targets. Furthermore, for a subset of 14 women, we modeled the connection of PSFs to the maternal immune system to APOs by building corresponding ML models based on an extensive single cell immune dataset generated by mass cytometry time of flight (CyTOF).ResultsJointly modeling APOs in a MML setting significantly increased modeling capabilities and yielded a highly predictive integrated model of APOs underscoring their interconnectedness. Most APOs were associated with mental health, life stress, and perceived health risks. Biologically, stressors were associated with specific immune characteristics revolving around CD4/CD8 T cells. Immune characteristics predicted based on stress were in turn found to be associated with APOs.ConclusionsElucidating connections among stress, multiple APOs simultaneously, and immune characteristics has the potential to facilitate the implementation of ML-based, individualized, integrative models of pregnancy in clinical decision making. The modifiable nature of stressors may enable the development of accessible interventions, with success tracked through immune characteristics.

In this contribution, we examine the way in which orchestra conductors use the space around them to convey aspects of musical dynamics. In music, dynamics refers to the intensity of volume of notes and sounds and its interpretation is highly context-bound. We approach dynamics as a phenomenon of emergent and construed meaning in interaction, induced by the music score and the interpretation in situ by musicians and the conductor. Conductors' movement-based instructions on dynamics result in highly complex usage events. This study aims at disentangling these instances by asking how conductors move and use the space around them to instruct on (un)desired aspects of musical dynamics, zooming in on movement direction as a central formal feature. We find ourselves at the crossroads of cognitive and interactional linguistics, aligning with existing studies on the interactional and contextually embedded nature of music interaction. From a cognitive linguistic perspective, this endeavor translates as the identification of the construal mechanisms (metaphor, specificity and viewpoint) that underlie and therefore motivate movement directions in the specific instances under examination. The analysis is based on 10h of video data from a corpus recorded during rehearsals of five conductors instructing their respective orchestras in Dutch. Our data reveal that conductors use different movement patterns, some of which appear to involve opposite movement directions for expressing a similar music dynamical aspect, e.g., depending on the usage event, a vertical upward movement can mean both a request for playing louder and softer. By taking into account different construal mechanisms, we are able to provide an encompassing multimodal analysis, in which these allegedly deviating oppositional movements appear as consistently motivated (metaphorical) expressions, which profile a similar target concept involving different viewpoints.

Background: The penis is a relatively uncommon organ for metastases. Secondary lesions often originate from the bladder, prostate, or rectosigmoid cancers. Only a few cases have described penile lesions secondary to lung cancers, mostly as a later complication. Case Description: We hereby report the case of an 86‐year‐old male patient who presented with a 3‐week‐long nonpainful priapism. A penile Doppler ultrasound and a chest and abdominal CT scan were performed, showing a left hilar lung mass as well as lesions in the liver, the adrenal glands, the pancreas, bone structures, and the penis. Penile metastasis is associated with a poor prognosis because of the frequent disseminated malignant lesions in other sites. Conclusion: Malignant priapism should be suspected, especially in patients with no evident risk factors for priapism (hematological diseases, drugs, alcohol, neurological diseases, or metabolic disorders). [ABSTRACT FROM AUTHOR]

Single-cell technologies are increasingly prominent in clinical applications, but predictive modelling with such data in large cohorts has remained computationally challenging. We developed a new algorithm, ‘VoPo’, for predictive modelling and visualization of single cell data for translational applications.