Background Interpersonal difficulties of patients with borderline personality disorder (BPD) are closely related to rejection sensitivity. The aim of the present study was to gain further insight into the experience and cerebral processing of social interactions in patients with BPD by using fMRI during experimentally induced experiences of social exclusion, inclusion, and overinclusion. Methods The study involved 30 participants diagnosed with BPD (29 female and 1 male; age: M = 24.22, SD = 5.22) and 30 healthy controls (29 female and 1 male; age: M = 24.66, SD = 5.28) with no current or lifetime psychiatric diagnoses. In the fMRI session, all participants were asked to complete a Cyberball task that consisted of an alternating sequence of inclusion, exclusion, and overinclusion conditions. Results Compared to healthy controls, participants with BPD reported higher levels of inner tension and more unpleasant emotions across all experimental conditions. At the neural level, the participants with BPD showed lower recruitment of the left hippocampus in response to social exclusion (relative to the inclusion condition) than the healthy controls did. Lower recruitment of the left hippocampus in this contrast was associated with childhood maltreatment in patients with BPD. However, this difference was no longer significant when we added the covariate of hippocampal volume to the analysis. During social overinclusion (relative to the inclusion condition), we observed no significant differences in a group comparison of neural activation. Conclusions The results of our study suggest that patients with BPD experience more discomfort than do healthy controls during social interactions. Compared to healthy participants, patients with BPD reported more inner tension and unpleasant emotions, irrespective of the extent to which others included them in social interactions. At a neural level, the participants with BPD showed a lower recruitment of the left hippocampus in response to social exclusion than the healthy controls did. The reduced activation of this neural structure could be related to a history of childhood maltreatment and smaller hippocampal volume in patients with BPD.
For millennia humans have interacted with a range of chemical substances that are an integral part of human history and culture. The chemical characteristics of the three similar-looking chemical species psilocybin, nicotine, and caffeine have remarkably different biological effects. The narratives of these chemical characters are compelling—their role traverses the unobservable submicroscopic world, influences our biological essence, and impacts societal values and scientific judgement. Visual storytelling through modern display technologies offers an educational method to communicate the nature and effect of these chemical actors. Biological information that transcends multi-directionally and constantly from submicroscopic through to macroscopic processes can be made accessible and meaningful to students and the public. In doing so, links are forged between scientific knowledge and the manner we view these chemical forms from a human and societal context. In attempting to capture these complexities, the aim of this chapter is to conceptualise and design a visual story to communicate the effect of psilocybin, nicotine, and caffeine on humans for public engagement. Whilst remarkably similar in chemical structure, these chemical species have dramatically different psychological and physiological effects on the human body. At the same time, human interaction with these substances is intertwined with historical associations, cultural norms, as well as perceived and enacted taboos.
This work introduces an advantageous approach using soluble copper phosphinate complexes as molecular precursors for highly dispersed Cu-phosphate/SiO2 catalysts in ethanol dehydrogenation. The resulting catalysts demonstrated an unusual initial increase in activity, attributed to the phosphate phase hindering Cu2+ reduction. Despite the gradual deactivation, the catalysts exhibited a notable performance with a max 73% ethanol conversion and over 98% acetaldehyde selectivity at 325 °C and WHSV = 2.37 h−1.
Tennis is a popular and complex sport influenced by various factors. Early training increases the risk of career dropout before peak performance. This study analyzed game statistics of World Junior Tennis Final participants (2012–2016), their career paths and it examined how game statistics impact rankings of top 300 female players, aiming to develop an accurate model using percentage-based variables. Descriptive and inferential statistics, including neural networks, were employed. Four machine learning models with categorical predictors and one response were created. Seven models with up to 18 variables and one ordinal (WTA rank) were also developed. Tournament rankings could be predicted using categorical data, but not subsequent professional rankings. Although effects on rankings among top 300 female players were identified, a reliable predictive model using only percentage-based data was not achieved. AI models provided insights into rankings and performance indicators, revealing a lower dropout rate than reported. Participation in elite junior tournaments is crucial for career development and designing training plans in tennis. Further research should explore game statistics, dropout rates, additional variables, and fine-tuning of AI models to improve predictions and understanding of the sport.
Psoriasis is a chronic, immune-mediated inflammatory skin disease. Despite the availability of several therapies, many patients affected by this disease remain untreated, do not have adequate response, or suffer from treatment-related toxic effects. It has been shown that the interleukin (IL)-17 pathway plays a key role in the immunopathogenesis of psoriasis. Brodalumab, the first human monoclonal IgG2 antibody that selectively binds to subunit A of the human IL-17 receptor, blocking interactions with a number of cytokines of the IL-17 family, has confirmed fast onset of action, high complete clearance rates, and sustained efficacy. Nevertheless, there is only a limited amount of published real-world evidence (RWE) data. This was an open-label, multicenter, real-world, prospective, non-interventional, non-controlled (single-arm) observational study (LIBERO-CZ) assessing the management of moderate to severe psoriasis with brodalumab in daily practice for up to 52 weeks of treatment. Fifty-four patients (70.4% male, mean age 46.9 ± 13.4 years, weight 95.6 ± 22.7 kg, disease duration 18.6 ± 12.7 years) were enrolled and included in the final analysis. Forty-nine of the patients completed the study and five discontinued prematurely; 51.8% of all the enrolled patients were biologic-naïve. At baseline, 28% patients were classified as severe (psoriasis area severity index (PASI) ≥ 20). Overall, the mean PASI decreased by 15.6 from 16.1 (± 5.0) at baseline to 0.5 (± 1.2) at the last visit. The primary endpoint of an absolute PASI ≤ 3 at week 12 (as observed analysis) was achieved by 95.9% of patients. The static Physician’s Global Assessment (sPGA) success (defined as clear = 0 and almost clear = 1) at week 52 was achieved by 92.1% of patients. PASI 75, PASI 90, and PASI 100 were achieved by 98.0%, 87.8%, and 75.5% of patients, respectively, after approximately 52 weeks of treatment. The study also recorded very positive results concerning patient-reported outcomes. LIBERO-CZ confirms the fast onset and high clearance rates of brodalumab in real life in both biologic-naïve and biologic-experienced patients.
Background Women are underrepresented in research focused on alcohol (e.g., Brighton, Moxham & Traynor, 2016; DOI 10.1097/JAN.0000000000000136 ) despite the changing patterns of alcohol consumption, which has been increasing in women in recent decades. The purpose of this study was to analyse the relationship between habitual alcohol consumption and centre of pressure (CoP) parameters during stance and gait while intoxicated by alcohol. Methods Thirty women (24.39 ± 2.93 years) participated in this study. All participants were asked to answer the AUDIT questionnaire. Stance and gait analysis were repeated under two conditions on a Zebris platform (FDM GmbH; Munich, Germany): when the participants were sober (0.00% breath alcohol concentration, BrAC) and when they were in an intoxicated state (0.11% BrAC). Participants were divided by their AUDIT score into a low-risk alcohol consumption group ( n = 15; AUDIT score: 3 to 6) and a hazardous alcohol consumption group ( n = 15; AUDIT score: 7 to 13). Results No statistical difference was observed in stance and gait parameters when comparing the low-risk and hazardous groups under 0.00% BrAC and 0.11% BrAC conditions. A statistically significant difference was observed when comparing 0.00% BrAC and 0.11% BrAC conditions within each group. This significant difference was found in CoP path length and CoP average velocity during quiet stance. However, no statistically significant differences were observed in CoP parameters during gait. An alcohol intoxication of 0.11% BrAC was not sufficient to cause statistically significant impairments in butterfly parameters of gait.
NanoLuc, a superior β-barrel fold luciferase, was engineered 10 years ago but the nature of its catalysis remains puzzling. Here experimental and computational techniques are combined, revealing that imidazopyrazinone luciferins bind to an intra-barrel catalytic site but also to an allosteric site shaped on the enzyme surface. Structurally, binding to the allosteric site prevents simultaneous binding to the catalytic site, and vice versa, through concerted conformational changes. We demonstrate that restructuration of the allosteric site can boost the luminescent reaction in the remote active site. Mechanistically, an intra-barrel arginine coordinates the imidazopyrazinone component of luciferin, which reacts with O2 via a radical charge-transfer mechanism, and then it also protonates the resulting excited amide product to form a light-emitting neutral species. Concomitantly, an aspartate, supported by two tyrosines, fine-tunes the blue color emitter to secure a high emission intensity. This information is critical to engineering the next-generation of ultrasensitive bioluminescent reporters.
Poales are one of the most species-rich, ecologically and economically important orders of plants and often characterise open habitats, enabled by unique suites of traits. We test six hypotheses regarding the evolution and assembly of Poales in open and closed habitats throughout the world and examine whether diversification patterns demonstrate parallel evolution. We sampled 42% of Poales species and obtained taxonomic and biogeographic data from the World Checklist of Vascular Plants database, which was combined with open/closed habitat data scored by taxonomic experts. A dated supertree of Poales was constructed. We integrated spatial phylogenetics with regionalisation analyses, historical biogeography and ancestral state estimations. Diversification in Poales and assembly of open and closed habitats result from dynamic evolutionary processes that vary across lineages, time and space, most prominently in tropical and southern latitudes. Our results reveal parallel and recurrent patterns of habitat and trait transitions in the species-rich families Poaceae and Cyperaceae. Smaller families display unique and often divergent evolutionary trajectories. The Poales have achieved global dominance via parallel evolution in open habitats, with notable, spatially and phylogenetically restricted divergences into strictly closed habitats.
Research handbook on public sociology Research handbook on public sociology , edited by Lavinia Bifulco and Vando Borghi. Cheltenham, UK and Northampton, MA, USA, Edgar Elgar Publishing, 2023, 404 pp., USD $275(hardback), ISBN: 9781800377370: edited by Lavinia Bifulco and Vando Borghi. Cheltenham, UK and Northampton, MA, USA, Edgar Elgar Publishing, 2023, 404 pp., USD $275 (hardback), ISBN: 9781800377370
The Strongyloides genus of parasitic nematodes have a fascinating life cycle and biology, but are also important pathogens of people and a World Health Organization-defined neglected tropical disease. Here, a community of Strongyloides researchers have posed thirteen major questions about Strongyloides biology and infection that sets a Strongyloides research agenda for the future. This article is part of the Theo Murphy meeting issue ‘Strongyloides: omics to worm-free populations’.
Primates are an important source of infectious disease in humans. Strongyloidiasis affects an estimated 600 million people worldwide, with a global distribution and hotspots of infection in tropical and subtropical regions. Recently added to the list of neglected tropical diseases, global attention has been demanded in the drive for its control. Through a literature review of Strongyloides in humans and non-human primates (NHP), we analysed the most common identification methods and gaps in knowledge about this nematode genus. The rise of molecular-based methods for Strongyloides detection is evident in both humans and NHP and provides an opportunity to analyse all data available from primates. Dogs were also included as an important host species of Strongyloides and a potential bridge host between humans and NHP. This review highlights the lack of molecular data across all hosts—humans, NHP and dogs—with the latter highly underrepresented in the database. Despite the cosmopolitan nature of Strongyloides, there are still large gaps in our knowledge for certain species when considering transmission and pathogenicity. We suggest that a unified approach to Strongyloides detection be taken, with an optimized, repeatable molecular-based method to improve our understanding of this parasitic infection. This article is part of the Theo Murphy meeting issue ‘Strongyloides: omics to worm-free populations’.
Monoclonal gammopathies are a group of blood diseases characterized by presence of abnormal immunoglobulins in peripheral blood and/or urine of patients. Multiple myeloma and plasma cell leukemia are monoclonal gammopathies with unclear etiology, caused by malignant transformation of bone marrow plasma cells. Mass spectrometry with matrix-assisted laser desorption/ ionization and time-of-flight detection is commonly used for investigation of the peptidome and small proteome of blood plasma with high accuracy, robustness, and cost-effectivity. In addition, mass spectrometry coupled with advanced statistics can be used for molecular profiling, classification, and diagnosis of liquid biopsies and tissue specimens in various malignancies. Despite the fact there have been fully optimized protocols for mass spectrometry of normal blood plasma available for decades, in monoclonal gammopathy patients, the massive alterations of biophysical and biochemical parameters of peripheral blood plasma often limit the mass spectrometry measurements. In this paper, we present a new two-step extraction protocol and demonstrated the enhanced resolution and intensity (>50×) of mass spectra obtained from extracts of peripheral blood plasma from monoclonal gammopathy patients. When coupled with advanced statistics and machine learning, the mass spectra profiles enabled the direct identification, classification, and discrimination of multiple myeloma and plasma cell leukemia patients with high accuracy and precision. A model based on PLS-DA achieved the best performance with 71.5% accuracy (95% confidence interval, CI = 57.1−83.3%) when the 10× repeated 5-fold CV was performed. In summary, the two-step extraction protocol improved the analysis of monoclonal gammopathy peripheral blood plasma samples by mass spectrometry and provided a tool for addressing the complex molecular etiology of monoclonal gammopathies.
Svalbard has experienced a dramatic increase in air temperature and glacier retreat since the end of the Little Ice Age. In many cases, this retreat has resulted in glaciers transitioning from being marine-terminating to land-terminating. Nordenskiöldbreen is an excellent contemporary example of this transition. A set of historical observations of glacier front positions was used to assess Nordenskiöldbreen's retreat rate and we found that the southern portion of the glacier front retreated by ∼3500 m, since records began in 1896. The general retreat rate corresponds well with the air temperature trend during most of the 20th century. However, the average retreat rate has slowed since the 1990s despite increasing air temperatures. We show that this discrepancy between air temperature and retreat rate marks the transition from marine-terminating towards a land-terminating glacier, as the glacier's bedrock topography started to play an essential role in the glacier margin geometry, ice flow and retreat dynamics.
Measurable residual disease (MRD) monitoring in childhood acute myeloid leukemia (AML) is used to assess response to treatment and for early detection of imminent relapse. In childhood AML, MRD is typically evaluated using flow cytometry, or by quantitative detection of leukemia-specific aberrations at the mRNA level. Both methods, however, have significant limitations. Recently, we demonstrated the feasibility of MRD monitoring in selected subgroups of AML at the genomic DNA (gDNA) level. To evaluate the potential of gDNA-based MRD monitoring across all AML subtypes, we conducted a comprehensive analysis involving 133 consecutively diagnosed children. Integrating next-generation sequencing into the diagnostic process, we identified (presumed) primary genetic aberrations suitable as MRD targets in 97% of patients. We developed patient-specific quantification assays and monitored MRD in 122 children. The gDNA-based MRD monitoring via quantification of primary aberrations with a sensitivity of at least 10⁻⁴ was possible in 86% of patients; via quantification with sensitivity of 5 × 10⁻⁴, of secondary aberrations, or at the mRNA level in an additional 8%. Importantly, gDNA-based MRD exhibited independent prognostic value at early time-points in patients stratified to intermediate-/high-risk treatment arms. Our study demonstrates the broad applicability, feasibility, and clinical significance of gDNA-based MRD monitoring in childhood AML.
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