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Background: We aimed to assess perioperative changes in fibrinogen in the cerebrospinal fluid (CSF), their association with markers of blood–brain barrier breakdown and neuroinflammation, and their association with postoperative delirium severity. Methods: We conducted a secondary analysis of the Interventions for Postoperative Delirium-Biomarker 2 (IPOD-B2, NCT02926417) study, a prospective observational cohort study. We included 24 patients aged >21 yr undergoing aortic aneurysm repair. CSF samples were obtained before (n=24) and after surgery (n=13), with some participants having multiple postoperative samples. Our primary outcome was the perioperative change in CSF fibrinogen. Delirium was assessed using the Delirium Rating Scale-Revised-98. Results: CSF fibrinogen increased after surgery (P

Summary: In an era of ‘big data’, we propose that a collaborative network approach will drive a better understanding of the mechanisms of delirium, and more rapid development of therapies. We have formed the International Delirium Pathophysiology & Electrophysiology Network for Data sharing (iDEPEND) group with a key aim to ‘facilitate the study of delirium pathogenesis with electrophysiology, imaging, and biomarkers including data acquisition, analysis, and interpretation’. Our initial focus is on studies of electrophysiology as we anticipate this methodology has great potential to enhance our understanding of delirium. Our article describes this principle and is used to highlight the endeavour to the wider community as we establish key stakeholders and partnerships.

Abstract The human brain displays a rich repertoire of states that emerge from the microscopic interactions of cortical and subcortical neurons. Difficulties inherent within large-scale simultaneous neuronal recording limit our ability to link biophysical processes at the microscale to emergent macroscopic brain states. Here we introduce a microscale biophysical network model of layer-5 pyramidal neurons that display graded coarse-sampled dynamics matching those observed in macroscale electrophysiological recordings from macaques and humans. We invert our model to identify the neuronal spike and burst dynamics that differentiate unconscious, dreaming, and awake arousal states and provide insights into their functional signatures. We further show that neuromodulatory arousal can mediate different modes of neuronal dynamics around a low-dimensional energy landscape, which in turn changes the response of the model to external stimuli. Our results highlight the promise of multiscale modelling to bridge theories of consciousness across spatiotemporal scales.

BackgroundDisconnected consciousness describes a state in which subjective experience (i.e., consciousness) becomes isolated from the external world. It appears frequently during sleep or sedation, when subjective experiences remain vivid but are unaffected by external stimuli. Traditional methods of differentiating connected and disconnected consciousness, such as relying on behavioral responsiveness or on post-anesthesia reports, have demonstrated limited accuracy: unresponsiveness has been shown to not necessarily equate to unconsciousness and amnesic effects of anesthesia and sleep can impair explicit recollection of events occurred during sleep/sedation. Due to these methodological challenges, our understanding of the neural mechanisms underlying sensory disconnection remains limited.MethodsTo overcome these methodological challenges, we employ a distinctive strategy by combining a serial awakening paradigm with auditory stimulation during mild propofol sedation. While under sedation, participants are systematically exposed to auditory stimuli and questioned about their subjective experience (to assess consciousness) and their awareness of the sounds (to evaluate connectedness/disconnectedness from the environment). The data collected through interviews are used to categorize participants into connected and disconnected consciousness states. This method circumvents the requirement for responsiveness in assessing consciousness and mitigates amnesic effects of anesthesia as participants are questioned while still under sedation. Functional MRI data are concurrently collected to investigate cerebral activity patterns during connected and disconnected states, to elucidate sensory disconnection neural gating mechanisms. We examine whether this gating mechanism resides at the thalamic level or results from disruptions in information propagation to higher cortices. Furthermore, we explore the potential role of slow-wave activity (SWA) in inducing disconnected consciousness by quantifying high-frequency BOLD oscillations, a known correlate of slow-wave activity.DiscussionThis study represents a notable advancement in the investigation of sensory disconnection. The serial awakening paradigm effectively mitigates amnesic effects by collecting reports immediately after regaining responsiveness, while still under sedation. Ultimately, this research holds the potential to understand how sensory gating is achieved at the neural level. These biomarkers might be relevant for the development of sensitive anesthesia monitoring to avoid intraoperative connected consciousness and for the assessment of patients suffering from pathologically reduced consciousness.Clinical trial registrationEuropean Union Drug Regulating Authorities Clinical Trials Database (EudraCT), identifier 2020-003524-17.

Abstract Background The prevalence and clinical importance of cardiac abnormalities in dogs with acute pancreatitis (AP) is unknown. Animals Twelve dogs with AP and 60 archived serum samples from dogs with suspected AP. Methods Two‐phase study. Phase I: Analysis of archived serum samples from dogs with clinical signs of AP and high Spec cPL concentrations. High sensitivity troponin I (TnIH) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) concentrations were measured in achieved serum samples. Phase II: Prospective observational study. Dogs with AP underwent echocardiography and Holter monitoring. Serum cardiac troponin I (cTnI) and plasma NT‐proBNP concentrations were measured. Previously described disease severity indices were calculated for each dog. Results Phase I: 41 of 60 dogs suspected of having AP had abnormally high TnIH concentrations and 13 of 60 had abnormally high serum NT‐proBNP concentrations. Higher TnIH concentrations were observed in dogs with Spec cPL concentration >2000 μg/L as compared to those with concentrations of 1000‐2000 μg/L. Phase II: 11 of 12 dogs diagnosed with pancreatitis had abnormal cTnI concentrations (median: 0.384 ng/mL, range: 0.041‐2.966 ng/mL, RI: ≤0.06 ng/mL) and 7 of 12 dogs had plasma NT‐proBNP concentrations above the reference interval (median: 971 pmol/L, range: 250‐2215 pmol/L, RI: ≤900 pmol/L). Supraventricular and ventricular ectopic beats occurred in 3 dogs. Echocardiographic abnormalities were detected in 5 dogs. Cardiovascular variables were not associated with indices of disease severity. Conclusions and Clinical Importance Myocardial injury is common in dogs with AP, but clinical consequences appeared to be uncommon in our small cohort. Cardiac biomarkers should be interpreted with caution in dogs with AP.

The neural mechanisms through which individuals lose sensory awareness of their environment during anesthesia remains poorly understood despite being of vital importance to the field. Prior research has not distinguished between sensory awareness of the environment (connectedness) and consciousness itself. In the current study, we investigated the neural correlates of sensory awareness by contrasting neural responses to an auditory roving oddball paradigm during consciousness with sensory awareness (connected consciousness) and consciousness without sensory awareness (disconnected consciousness). These states were captured using a serial awakening paradigm with the sedative alpha2 adrenergic agonist dexmedetomidine, chosen based on our published hypothesis that suppression of noradrenaline signaling is key to induce a state of sensory disconnection. High-density electroencephalography was recorded from 18 human subjects before and after administration of dexmedetomidine. By investigating event-related potentials and taking advantage of advances in Dynamic Causal Modeling (DCM), we assessed alterations in effective connectivity between nodes of a previously established auditory processing network. We found that during disconnected consciousness, the scalp-level response to standard tones produced a P3 response that was absent during connected consciousness. This P3 response resembled the response to oddball tones seen in connected consciousness. DCM showed that disconnection produced increases in standard tone feedback signaling throughout the auditory network. Simulation analyses showed that these changes in connectivity, most notably the increase in feedback from right superior temporal gyrus to right A1, can explain the new P3 response. Together these findings show that during disconnected consciousness there is a disruption of normal predictive coding processes, so that all incoming auditory stimuli become similarly surprising.

Background: Micro-electrode recordings are often necessary during electrode implantation for deep brain stimulation of the subthalamic nucleus. Dexmedetomidine may be a useful sedative for these procedures, but there is limited information regarding its effect on neural activity in the subthalamic nucleus and on micro-electrode recording quality. Methods: We recorded neural activity in five patients undergoing deep brain stimulation implantation to the subthalamic nucleus. Activity was recorded after subthalamic nucleus identification while patients received dexmedetomidine sedation (loading – 1 μg kg−1 over 10–15 min, maintenance – 0.7 μg kg−1 h−1). We compared the root-mean square (RMS) and beta band (13–30 Hz) oscillation power of multi-unit activity recorded by microelectrode before, during and after recovery from dexmedetomidine sedation. RMS was normalised to values recorded in the white matter. Results: Multi-unit activity decreased during sedation in all five patients. Mean normalised RMS decreased from 2.8 (1.5) to 1.6 (1.1) during sedation (43% drop, p = 0.056). Beta band power dropped by 48.4%, but this was not significant (p = 0.15). Normalised RMS values failed to return to baseline levels during the time allocated for the study (30 min). Conclusions: In this small sample, we demonstrate that dexmedetomidine decreases neuronal firing in the subthalamic nucleus as expressed in the RMS of the multi-unit activity. As multi-unit activity is a factor in determining the subthalamic nucleus borders during micro-electrode recordings, dexmedetomidine should be used with caution for sedation during these procedures. Clinical trial number: NCT01721460.

Summary: Background: Delirium predicts poor outcomes, however identifying patients with the worst outcomes is challenging. Plasma neurofilament light protein (NfL) is a sensitive indicator of neuronal damage. We undertook an exploratory observational study to determine the association between plasma NfL and delirium in the critically ill. Methods: MoDUS was a randomised placebo-controlled delirium trial of simvastatin done in an UK adult general ICU. We measured NfL levels in plasma samples using a Single molecule array (Simoa) platform. We explored associations between patient's plasma NfL levels and number of delirium days, and clinical outcomes. The control group for baseline NfL were preoperative patients undergoing major surgery. Findings: The majority of critically ill patients already had a high NfL level on admission. Patients with higher plasma NfL levels at days one and three spent more days in delirium or deep sedation. Patients with zero or one day in delirium or deep sedation had day one mean concentrations of 37.8 pg/ml (SD 32.6) compared with 96.5 pg/ml (SD 106.1)) for patients with two days or more, p-value 0.002 linear mixed effects model.Survivors discharged before 14 days had lower mean plasma NfL concentrations compared to those with longer hospital stays and/or who died within six months. The area under ROC curve for predicting death within six months using day one NfL was 0.81 (0.7,0.9). Interpretation: Measurement of plasma NfL within three days of admission may be useful to identify those patients with worse clinical outcomes, and as an enrichment strategy for future delirium interventional trials in the critically ill. Funding: Alzheimer's Society UK, UK Dementia Research Institute.

Background: Perioperative inflammation is associated with perioperative complications, including delirium, that are associated with a reduced number of postoperative days alive and at home at 90 days (DAH90). We tested whether inflammation was associated with DAH90 even when adjusting for perioperative factors, and whether inflammation independently was associated with DAH90 when adjusting for delirium. Methods: We conducted a prospective cohort study of major, non-intracranial surgical patients who were older than 65 yr (n=134). We measured postoperative delirium incidence and severity, and changes in interleukin (IL)-8 and IL-10 in blood plasma. Our primary outcome, DAH90, was analysed using quantile regression. Results: Before adjusting for delirium, a postoperative day 1 increased IL-8 was associated with fewer DAH90 at the 0.75 quantile (β=–0.082; 95% confidence interval [CI], –0.19 to –0.006) after adjusting for demographic (age and sex) and perioperative factors (cardiovascular surgery, National Surgical Quality Improvement Program risk of death, and operative time). IL-10 was similarly associated with DAH90 at the 0.5 (β=–0.026; 95% CI, –0.19 to –0.001) and 0.75 (β= –0.035; 95% CI, –0.07 to –0.006) quantiles. Neither cytokine was significantly associated with DAH90 once delirium and baseline Trail Making Test B were added to the models. Conclusions: Perioperative inflammation predicts DAH90, but when delirium is added to the model inflammation loses significance as a predictor, whereas delirium is significant. Targeting perioperative inflammation may reduce delirium and moderate hospital readmission and mortality. Clinical trial registration: NCT03124303.

During a cruise from October to November 2019, along the West Antarctic Peninsula, between 64.32 and 68.37°S, we assessed the diversity and composition of the active microbial eukaryotic community within three size fractions: micro- (> 20 μm), nano- (20–5 μm), and pico-size fractions (5–0.2 μm). The communities and the environmental parameters displayed latitudinal gradients, and we observed a strong similarity in the microbial eukaryotic communities as well as the environmental parameters between the sub-surface and the deep chlorophyll maximum (DCM) depths. Chlorophyll concentrations were low, and the mixed layer was shallow for most of the 17 stations sampled. The richness of the microplankton was higher in Marguerite Bay (our southernmost stations), compared to more northern stations, while the diversity for the nano- and pico-plankton was relatively stable across latitude. The microplankton communities were dominated by autotrophs, mostly diatoms, while mixotrophs (phototrophs-consuming bacteria and kleptoplastidic ciliates, mostly alveolates, and cryptophytes) were the most abundant and active members of the nano- and picoplankton communities. While phototrophy was the dominant trophic mode, heterotrophy (mixotrophy, phagotrophy, and parasitism) tended to increase southward. The samples from Marguerite Bay showed a distinct community with a high diversity of nanoplankton predators, including spirotrich ciliates, and dinoflagellates, while cryptophytes were observed elsewhere. Some lineages were significantly related—either positively or negatively—to ice coverage (e.g., positive for Pelagophyceae, negative for Spirotrichea) and temperature (e.g., positive for Cryptophyceae, negative for Spirotrichea). This suggests that climate changes will have a strong impact on the microbial eukaryotic community.

Hot compression experiments were performed on alloy 5182 with small additions of Sc and Zr. The 5182 alloy containing Sc and Zr is critical for expanding the 5182 alloy’s range of applications, and a thorough understanding of its thermal processing behavior is of great importance to avoid processing defects. Alloy microstructure, including grain structures and Al3(ScxZr1−x) dispersoids were analyzed by EBSD and TEM. Stable flow stresses were observed below a strain rate of 1 s−1 for the Sc-Zr containing alloy. The results of constitutive models, with and without strain−compensation, and artificial neural network (ANN) were used to compare to the experimental results. The Al3(ScxZr1−x) dispersoid data was introduced into the ANN model as a nonlinear influence factor. Addition of the Al3(ScxZr1−x) dispersoid information as input data improved the accuracy and practicality of the artificial neural network in predicting the deformation behavior of the alloy. The squared correlation coefficients of ANN prediction data reached 0.99.

The Ehlers-Danlos syndromes (EDS) represent a group of genetically diverse disorders characterized by the variable combination of joint hypermobility, hyperextensibility of the skin, and connective tissue fragility affecting the skin and other organs. Based on clinical features, 13 different types of EDS have been delineated, 12 of which represent monogenic conditions caused by pathogenic variants in 21 confirmed genes. Pathogenesis is related to disturbances of collagen formation and/or stability. No monogenic cause has been identified for hypermobile EDS (hEDS), a more common EDS type, which is unlikely to represent a single gene disorder in the majority of affected individuals and at present cannot be diagnosed by genetic investigations. Here we summarize the clinical features and the molecular bases of the monogenic EDS types, highlight diagnostic challenges, and provide guidance for the molecular work-up of affected individuals. In general, genetic tests are indicated if clinical features suggest a monogenic EDS type but are usually unrewarding for other cases of hypermobility. [ABSTRACT FROM AUTHOR]

Background: Dominant mutations in COL3A1 are known to cause vascular Ehlers–Danlos syndrome (vEDS) by impairing extracellular matrix (ECM) homeostasis. This disruption leads to the fragility of soft connective tissues and a significantly increased risk of life-threatening arterial and organ ruptures. Currently, treatments for vEDS are primarily symptomatic, largely due to a limited understanding of its underlying pathobiology and molecular mechanisms. Methods: In this study, we conducted a comprehensive analysis of the intracellular proteome of vEDS fibroblasts, integrating these findings with our previous transcriptome results to identify key molecular pathways that drive the disease. Additionally, we explored the therapeutic potential of inhibiting miR-29b-3p as a proof of concept. Results: Our integrative multi-omics analysis revealed complex pathological networks, emphasizing the critical role of miRNAs, particularly miR-29b-3p, in impairing ECM organization, autophagy, and cellular stress responses, all of which contribute to the pathogenesis of vEDS. Notably, the inhibition of miR-29b-3p in vEDS fibroblasts resulted in the upregulation of several differentially expressed target genes involved in these critical processes, as well as increased protein expression of essential ECM components, such as collagen types V and I. These changes suggest potential therapeutic benefits aimed at improving ECM integrity and restoring intracellular homeostasis. Conclusions: Overall, our findings advance our understanding of the complex biological mechanisms driving vEDS and lay a solid foundation for future research focused on developing targeted and effective treatment strategies for this life-threatening disorder. [ABSTRACT FROM AUTHOR]

Hereditary aortopathies are a group of rare genetic diseases affecting the aorta and its major branches, and they represent a cause of sudden cardiac death. These pathologies are classified into syndromic hereditary aortopathies and non-syndromic hereditary aortopathies. The epidemiology of hereditary aortopathies varies according to the specific genetic condition involved; however, these disorders are believed to account for a significant proportion of sudden cardiac death in young individuals with a family history of inherited cardiovascular conditions. The causes of hereditary aortopathies are primarily genetic, with pathogenic variants in various genes encoding structural proteins of the vascular wall, leading to dissection, aneurysms, rupture, and ultimately sudden cardiac death. When the cause of death remains unknown after an autopsy, it is referred to as sudden unexplained death, and post-mortem genetic testing, known as a molecular autopsy, is crucial to confirm hereditary aortopathies and assess the genetic risk in the patient's relatives. This helps to facilitate diagnostic and therapeutic pathways and/or implement monitoring strategies to prevent sudden cardiac death. In this state-of-the-art review, we focus on syndromic and non-syndromic hereditary aortopathies causing sudden cardiac death in the young and explore preventive strategies for affected family members. [ABSTRACT FROM AUTHOR]

The current study looked at the influence of different L1s, different proficiency levels, and other factors on the think-alouds in connection with oppositional speech acts by eighty tertiary-level Korean and Chinese learners of L2 English at two proficiency levels. The research instruments consisted of think-aloud protocols elicited during the learners' production of written oppositional speech acts in the form of responses to the other learners' essays, questionnaires, and focus group interviews. In particular, in the think-aloud protocols the number and content of pragmatic-related episodes (PREs) were identified. The results indicated that proficiency level, but not L1, significantly impacted the learners' think-alouds. Other factors were revealed to include intensification of claims, focus on face issues, pragmatic transfer, and insufficient syntactic/semantic knowledge. These factors related to the sub-categories of the PREs involving 'lexical upgrading' and 'external downgrading'. [ABSTRACT FROM AUTHOR]

Research on translanguaging practices in multilingual contexts has explored how translanguaging highlights the multilingual and multicultural nature of social interactions and its transformative nature in transgressing established norms and boundaries. This article aims to provide an alternative view of interactional competence by connecting it to the notion of translanguaging and its emphasis on the active deployment of multiple linguistic, semiotic, and sociocultural resources in a dynamic and integrated way. We argue for extending the notion of interactional competence as we suggest that translanguaging is the practice of drawing on a speaker's interactional competence for constructing new configurations of language practices for communicative purposes. Such a conceptualization reinforces the meaning-making process as a locally emergent phenomenon and a jointly accomplished social action. It also conceptualizes the undertaking of co-constructing social interactions as a process of translanguaging whereby interactants need to seek out available multilingual and multimodal resources and make strategic choices among these resources in order to achieve their social actions on a moment-by-moment basis. This article utilizes Sequential-Categorial Analysis, which combines Multimodal Conversation Analysis and Membership Categorisation Analysis, in its analysis of classroom video recordings of vocabulary instruction in a beginner-level adult English-for-Speakers-of-Other-Languages classroom in order to demonstrate our argument. [ABSTRACT FROM AUTHOR]

I utilized a discourse analytic approach to examine how young adult couples pursue closeness by negotiating entitled requests in their everyday interactions. Although freely expressing entitled requests may at times be treated as relationally off-putting, I suggest that they may be a method that romantic partners use to enact closeness or intimacy, albeit counterintuitively, by pursuing controversy. I draw on data to reveal how entitled requests are often formulated to do a lot more than simply ask for things. They are used to engage in relational coaching, offer object lessons, and reciprocal tit-for-tats, but are typically created in light-hearted ways that involve humor, exaggeration, and sarcasm. I show that the interactive contexts for making and receiving entitled requests can be a valuable space for observing how relational expectations are negotiated to index accountability, relational identities, and the cultural communicative norms which govern romantic relationships among young adults. [ABSTRACT FROM AUTHOR]

The 1838 congressional race between John T. Stuart and Stephen A. Douglas in Illinois was marked by allegations of fraud and corruption, with Stuart ultimately emerging as the victor. Despite the contentious nature of the race, Stuart and Douglas maintained a sense of mutual courtesy and amity. The election had a lasting impact on Illinois politics, leading to changes in the state constitution regarding voting rights and ballot procedures. [Extracted from the article]

Background: Ehlers–Danlos syndrome (EDS), Marfan syndrome (MFS), and Loeys–Dietz syndrome (LDS) are connective tissue disorders frequently associated with vascular aneurysm formation, dissections, and subsequent major complications. Regular imaging surveillance is recommended for these conditions. However, no guidelines currently exist regarding imaging modality or surveillance intervals. Methods: This retrospective single-center observational study analyzed clinical and imaging data of patients attending an outpatient clinic for vascular connective tissue disorders between August 2008 and January 2024. Imaging (1424 data points in total) and clinical data were extracted from electronic health records. Analysis primarily included a comparison of vessel diameter progression across imaging modalities, with an additional review of the clinical history of vascular events. Results: In total, 19 patients with vascular connective tissue disorders (vCTDs) underwent consultations at our outpatient clinic. Nine (47.4%) patients experienced vascular events, while two (10.5%) passed away during the study period. Multimodal imaging surveillance revealed a tendency towards arterial diameter increase. Consistent ultrasound monitoring provided more reliable diameter progression data for the same arterial segment than a combination of imaging modalities. Temporal analysis indicated a tendency for the continuous growth of the abdominal aorta, the common and internal carotid artery, and the common femoral and popliteal artery. Conclusion: The study highlights the importance of standardized, modality-specific imaging protocols in monitoring patients with vCTDs. The variability in disease progression among these patients further complicates surveillance strategies, contemplating the need for individualized approaches. Further research and prospective multicenter studies are required to refine and improve monitoring protocols. [ABSTRACT FROM AUTHOR]

Vascular Ehlers–Danlos syndrome (vEDS) is a rare autosomal dominant connective tissue disease resulting from pathogenic variants in the collagen type III alpha 1 chain (COL3A1) gene, encoding type III procollagen. Patients with vEDS present with severe tissue fragility that can result in arterial aneurysm, dissection, or rupture, especially of medium-caliber vessels. Although early reports have indicated a very high mortality rate in affected patients, with an estimated median survival of around 50 years, recent times have seen a remarkable improvement in outcomes in this population. This shift could be related to greater awareness of the disease among patients and physicians, with improved management both in terms of follow-up and treatment of complications. Increasing use of drugs acting on the cardiovascular system may also have contributed to this improvement. In particular, celiprolol, a β1 cardio-selective blocker with a β2-agonist vasodilator effect, has been shown to reduce rates of vascular events in patients with vEDS. However, the evidence on the true benefits and possible mechanisms responsible for the protective effect of celiprolol in this specific setting remains limited. Drugs targeting the extracellular matrix organization and autophagy–lysosome pathways are currently under investigation and could play a role in the future. This narrative review aims to summarize current evidence and future perspectives on vEDS medical treatment, with a specific focus on vascular prevention. [ABSTRACT FROM AUTHOR]

Background and Objectives: Spontaneous colonic perforations (SCPs) in teenagers and young adults are extremely rare. Common underlying conditions, such as colonic tumors and diverticulitis, are absent at that age. The vascular type of Ehlers–Danlos Syndrome (vEDS) is one cause of SCP. Methods: A 23-year-old male presented with an acute abdomen. The abdominal CT showed pneumoperitoneum with a large amount of fluid in the pelvis and abdomen, indicating hollow viscus rupture. At the level of the sigmoid colon, a defect in the intestinal wall and gas bubbles were seen. Results: Exploratory laparotomy confirmed sigmoid colon perforation without underlying pathology. Loop sigmoid colostomy was performed. Revisional surgery was undertaken due to clinical deterioration and intra-abdominal free fluid with small-bowel distension and air-liquid levels on abdominal CT 6 days later. Ileal subserosal hematomas were found, and many had ruptured, leaving a "zebra" pattern with lines of residual hematomas on the borders of subserosal hematomas. Genetic analysis confirmed vEDS. Conclusions: SCP in young adults or teenagers, in the absence of colonic disease, with clinical manifestations of connective tissue disorders should trigger genetic investigations for vEDS. SCP with a known vEDS could be treated with total colectomy to prevent further SCPs in the remaining colon. If segmental resections are performed, further SCP should be immediately excluded with any significant abdominal pain. [ABSTRACT FROM AUTHOR]

Marfan syndrome (MFS) is a rare congenital disorder of the connective tissue, leading to thoracic aortic aneurysms (TAA) and dissection, among other complications. Currently, the most efficient strategy to prevent life-threatening dissection is preventive surgery. Periodic imaging applying complex techniques is required to monitor TAA progression and to guide the timing of surgical intervention. Thus, there is an acute demand for non-invasive biomarkers for diagnosis and prognosis, as well as for innovative therapeutic targets of MFS. Unraveling the intricate pathomolecular mechanisms underlying the syndrome is vital to address these needs. High-throughput platforms are particularly well-suited for this purpose, as they enable the integration of different datasets, such as transcriptomic and epigenetic profiles. In this narrative review, we summarize relevant studies investigating changes in both the coding and non-coding transcriptome and epigenome in MFS-induced TAA. The collective findings highlight the implicated pathways, such as TGF-β signaling, extracellular matrix structure, inflammation, and mitochondrial dysfunction. Potential candidates as biomarkers, such as miR-200c, as well as therapeutic targets emerged, like Tfam, associated with mitochondrial respiration, or miR-632, stimulating endothelial-to-mesenchymal transition. While these discoveries are promising, rigorous and extensive validation in large patient cohorts is indispensable to confirm their clinical relevance and therapeutic potential. [ABSTRACT FROM AUTHOR]

Unicellular eukaryotic plankton communities (protists) are the major basis of the marine food web. The spring bloom is especially important, because of its high biomass. However, it is poorly described how the protist community composition in Arctic surface waters develops from winter to spring. We show that mixotrophic and parasitic organisms are prominent in the dark winter period. The transition period toward the spring bloom event was characterized by a high relative abundance of mixotrophic dinoflagellates, while centric diatoms and the haptophyte Phaeocystis pouchetii dominated the successive phototrophic spring bloom event during the study. The data shows a continuous community shift from winter to spring, and not just a dormant spring community waiting for the right environmental conditions. The spring bloom initiation commenced while sea ice was still scattering and absorbing the sunlight, inhibiting its penetration into the water column. The initial increase in fluorescence was detected relatively deep in the water column at ~55 m depth at the halocline, at which the photosynthetic cells accumulated, while a thick layer of snow and sea ice was still obstructing sunlight penetration of the surface water. This suggests that water column stratification and a complex interplay of abiotic factors eventually promote the spring bloom initiation. [ABSTRACT FROM AUTHOR]

The article focuses on technology company, Amazon's private label (PL) products and the scrutiny they face from competition authorities in the U.S. and Europe due to concerns over potential self-preferencing practices and data advantages. It emphasizes that Amazon's approach to managing PLs aligns with standard practices used by many traditional retailers, which have long utilized consumer transaction data and engaged in self-preferencing.

The number of known alien ant species throughout Europe has been steadily increasing during the last few decades and Italy has been no exception, with four new taxa reported in the last five years. Here, we document new data on the Asian needle ant Brachyponera chinensis (Emery, 1895), an invasive alien species whose first establishment in Europe was detected in the southern Italian city of Naples in 2022 and which has now been found near Lake Como in northern Italy, representing the second European record, about 730 km distant from the first. Furthermore, we report for the first time the presence of Nylanderia vividula (Nylander, 1846) in the country, based on specimens collected both in Rome and near Lake Como. This is at least the second Nylanderia species established in the country after N. jaegerskioeldi, first reported in 2018. Unlike B. chinensis, N. vividula is not considered an ecological and health threat in the invaded range and is already known to occur in several other European countries. While only a few introduced ants in Europe are considered serious ecological, economic or health threats, the increasing circulation of several alien species and the poor ability to swiftly track their movements and detect their establishment can render management very difficult. [ABSTRACT FROM AUTHOR]

The article introduces a Dual-Branch Learning Model with Gradient-Balanced Loss (DBGB) to tackle the long-tailed problem in multi-label text classification. It is reported that DBGB employs a dual-branch structure, shared text representation, and a gradient-balanced loss to enhance tail-label prediction accuracy without compromising overall precision.

Background: Disconnected consciousness describes a state in which subjective experience (i.e., consciousness) becomes isolated from the external world. It appears frequently during sleep or sedation, when subjective experiences remain vivid but are unaffected by external stimuli. Traditional methods of differentiating connected and disconnected consciousness, such as relying on behavioral responsiveness or on post-anesthesia reports, have demonstrated limited accuracy: unresponsiveness has been shown to not necessarily equate to unconsciousness and amnesic effects of anesthesia and sleep can impair explicit recollection of events occurred during sleep/sedation. Due to these methodological challenges, our understanding of the neural mechanisms underlying sensory disconnection remains limited. Methods: To overcome these methodological challenges, we employ a distinctive strategy by combining a serial awakening paradigm with auditory stimulation during mild propofol sedation. While under sedation, participants are systematically exposed to auditory stimuli and questioned about their subjective experience (to assess consciousness) and their awareness of the sounds (to evaluate connectedness/disconnectedness from the environment). The data collected through interviews are used to categorize participants into connected and disconnected consciousness states. This method circumvents the requirement for responsiveness in assessing consciousness and mitigates amnesic effects of anesthesia as participants are questioned while still under sedation. Functional MRI data are concurrently collected to investigate cerebral activity patterns during connected and disconnected states, to elucidate sensory disconnection neural gating mechanisms. We examine whether this gating mechanism resides at the thalamic level or results from disruptions in information propagation to higher cortices. Furthermore, we explore the potential role of slow-wave activity (SWA) in inducing disconnected consciousness by quantifying high-frequency BOLD oscillations, a known correlate of slow-wave activity. Discussion: This study represents a notable advancement in the investigation of sensory disconnection. The serial awakening paradigm effectively mitigates amnesic effects by collecting reports immediately after regaining responsiveness, while still under sedation. Ultimately, this research holds the potential to understand how sensory gating is achieved at the neural level. These biomarkers might be relevant for the development of sensitive anesthesia monitoring to avoid intraoperative connected consciousness and for the assessment of patients suffering from pathologically reduced consciousness. [ABSTRACT FROM AUTHOR]

The paper offers a preliminary overview of studies on lesser-described languages carried out in recent decades within the theoretical and methodological framework of Conversation Analyis, an ethnomethodologically inspired approach to the investigation of language use and social interaction. Reported results of large-scale comparative investigations on fundamental conversational mechanisms like turn-taking, sequential organization and repair thereby show the universal character of such practices, while highlighting peculiarities of languages like ╪Ākhoe Hai||om, Cha’palaa, Murrinh-Phata, Yélî-Dnye and Tzeltal, in comparison with widespread Western European languages. It is thus discussed how Conversation Analysis – with its data-driven, emic, situated, and multimodal perspective on spoken interaction – can fruitfully complement language documentation work on lesser-described languages and speech communities. [ABSTRACT FROM AUTHOR]

This report describes a unique case of vascular Ehlers-Danlos syndrome (vEDS) characterized by multiple spontaneous direct carotid-cavernous sinus fistulas (CCF). The patient initially presented with ocular symptoms and was effectively treated with transarterial coil embolization. Five years later, the patient developed recurrent contralateral CCF that required complex endovascular techniques. Genetic testing identified a novel mutation in the COL3A1 gene, confirming the diagnosis of vEDS. This case report provides a near-term perspective on the identification of structural abnormalities in the COL3A1 protein to ensure the safety of endovascular therapy for patients with vEDS. [ABSTRACT FROM AUTHOR]

Adolescents, particularly those in multiethnic, multilingual communities, have become central to sociolinguistic research in the variationist tradition (Cheshire, Nortier & Adger 2015). In several studies of adolescent speech in European urban centres, the same set of Arabic-derived epistemic phrases, namely wallah , wallahi and related phrases meaning 'swear', appear to be in use (see, e.g., Quist 2005; Opsahl 2009; Lehtonen 2015). In this article, we document how these phrases are used in the speech of adolescents from a borough of West London and demonstrate the functional similarities between the current data and studies of adolescents in other West European contexts. Using a distributional analysis, we also draw several comparisons between our data and data collected in previous studies of adolescent speech in London. We find functional and distributional similarities and contrasts in both cases. We then discuss the consequences of these findings for the study of epistemic markers and their relevance in adolescent speech. [ABSTRACT FROM AUTHOR]

Thoracic aortic aneurysms (TAAs) are commonly seen in cardiovascular practice. Acquired and genetic conditions contribute to TAA formation. The natural history of genetically mediated TAA underscores the importance of early detection, regular monitoring, and prompt treatment to prevent complications, including dissection or rupture. The prognosis is poor in the event of acute dissection, with high rates of in-hospital mortality. Healthcare providers need to remain vigilant in their efforts to identify and surveil TAA to reduce the risk of complications. In this manuscript, we review the natural history of TAA, discuss the most common causes leading to the development of TAA, assess the value and limitations of diagnostic modalities, and review the management and long-term surveillance of patients with aortic disease. [ABSTRACT FROM AUTHOR]

This article discusses the 2023 Annual Meeting of the American Society for Bone and Mineral Research (ASBMR). The article presents a list of award recipients as well as all abstracts of all research presented at the meeting. Research topics include bone mineral density, osteoporosis and osteoclasts. [Extracted from the article]

The aim of this study is to surface pragmatic forces and the semiotically constructed self-governed persona in the self-tracking context. In so doing, the article adopts a pragma-semiotic approach to investigate the self-tracking app "Habiticia" as an example of the construction of new regimes of algorithmic self-governance. The adopted approach benefits from intersecting pragmatics and Greimassian semiotics as proposed by Sbisá, Sbisá and Fabbri and Cooren. The article deploys Foucault's notion of "self-governance" to frame Habiticia self-tracking activities through the motifs of the optimization of the self, self-regulation and subjectivation. It concludes that a semio-pragmatic model can make a significant contribution to the notions of the quantified self and digital surveillance. The study contributes to the research on the quantified self-movement, self-tracking apps and governance through developing a dialog with linguistic pragmatics. [ABSTRACT FROM AUTHOR]

Pragmatic markers are linguistic resources, many of them highly ubiquitous, that provide speakers with a means to display their stance toward a given proposition and, at the same time, toward their fellow interlocutors and others. Using naturally-occurring spoken data from the Sejong Spoken Corpus, we examine the role of Korean pragmatic marker com as an interactional resource for stance management in conversation. We integrate a 'stance triangle' framework and a dialogicality model that involves both 'internal' and 'external' dialogic processes, and analyze how Korean com is recruited as a face-threat mitigator to attenuate the assertive force of a speaker's utterance in a variety of conversational contexts. Our findings indicate that the use of com is frequently motivated by sociocultural values, reframed as politeness norms, which prompt speakers to modulate their position in ways that mitigate face-loss for both themselves and others. We thus propose an expanded version of the 'stance triangle' for situations involving mitigation acts whereby, in potentially dis-aligning contexts, the speaker's external positioning toward the stance object often does not directly nor fully reflect their internal evaluation, indicating a frequent desire among fellow interlocutors to preserve solidarity with each other. [ABSTRACT FROM AUTHOR]

In agreement to the analyses of Dr. Kim and colleagues, higher delirium severity was associated with lower LZC in theta and higher LZC in alpha (Figure 1A). Similarly, patients with a delirium diagnosis had lower LZC in the theta band and higher LZC in alpha band (Figure 1B). Although it would have been interesting to see a broadband calculation of Lempel-Ziv complexity (LZC) as we had originally published, the findings of divergent changes in alpha and theta band LZC with delirium are intriguing. [Extracted from the article]

Introduction: Ehlers–Danlos syndromes (EDS) comprise a rare variety of genetic disorders, affecting all types of collagen. Herein, we describe a case of the vascular type of EDS, with coexisting segmental absence of intestinal musculature, while simultaneously performing a narrative review of the existing literature. Case Presentation: A 23-year-old male patient with a history of multiple abdominal operations due to recurrent bowel perforations and the presence of a high-output enterocutaneous fistula was admitted to our surgical department for further evaluation and treatment. After detailed diagnostic testing, the diagnosis of vascular-type EDS (vEDS) was made and a conservative therapeutic approach was adopted. In addition, a comprehensive review of the international literature was carried out by applying the appropriate search terms. Results: The diagnosis of vEDS was molecularly confirmed by means of genetic testing. The patient was treated conservatively, with parenteral nutrition and supportive methods. Thirty-four cases of bowel perforation in vEDS have been reported so far. Interestingly, this case is the second one ever to report co-existence of vEDS with Segmental Absence of Intestinal Musculature. Conclusions: Establishing the diagnosis of vEDS promptly is of vital significance in order to ensure that patients receive appropriate treatment. Due to initial non-specific clinical presentation, EDS should always be included in the differential diagnoses of young patients with unexplained perforations of the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Studies show that processes like teacher–child interactions are a key dimension of childcare quality and that global and domain-specific interactions seem to have different effects on child development. A variety of instruments have been used to assess quality in the field of early childhood research. The aim of this study was to identify and discuss instruments that assess global and/or math-specific interaction quality in childcare settings (birth to school-entry). In the systematic literature review, we found 4211 publications using instruments that assess global and/or math-specific interaction quality, of which 148 remained after a screening of titles, abstracts, and full-texts. In all, 55 instruments assessing interaction quality were identified and analyzed regarding their (sub)scales, items, method, procedure, children's age, reliability, and validity. We identified more instruments measuring global aspects of teacher–child interactions than measuring math-specific aspects. In general, some instruments might be over- or underrepresented, due to linguistic and publication bias. [ABSTRACT FROM AUTHOR]

The present study examined the effects of study schedule (interleaving vs. blocking) and feature descriptions on category learning and metacognitive predictions of learning. Across three experiments, participants studied exemplars from different rock categories and later had to classify novel exemplars. Rule-based and information-based categorization was also manipulated by selecting rock sub-categories for which the optimal strategy was the one that aligned with the extraction of a simple rule, or the one that required integration of information that may be difficult to describe verbally. We observed consistent benefits of interleaving over blocking on rock classification, which generalized to both rule-based (Experiment 1) and information-integration learning (Experiments 1–3). However, providing feature descriptions enhanced classification accuracy only when the stated features were diagnostic of category membership, indicating that their benefits were limited to rule-based learning (Experiment 1) and did not generalize to information-integration learning (Experiments 1–3). Furthermore, our examination of participants' metacognitive predictions demonstrated that participants were not aware of the benefits of interleaving on category learning. Additionally, providing feature descriptions led to higher predictions of categorization even when no significant benefits on actual performance were exhibited. [ABSTRACT FROM AUTHOR]

Many phytoplankton taxa function on multiple trophic levels by combining photosynthesis and ingestion of bacteria, termed mixotrophy. Despite the recognition of mixotrophy as a universal functional trait, we have yet to fully resolve how environmental conditions influence community grazing rates in situ. A microcosm study was used to assess bacterivory by mixotrophic nanoflagellates following nutrient enrichment and light attenuation in a temperate lake. We found contrasting results based on assessment of mixotroph abundance or bacterivory. Despite an interactive effect of nutrient enrichment and light attenuation on mixotroph abundance, significant differences within light treatments were observed only after enrichment with P or N + P. The greatest abundance of mixotrophs across treatments occurred under co‐nutrient enrichment with full exposure to irradiance. However, bacterivory by mixotrophic nanoflagellates was greatest under shaded conditions after either N or P enrichment. We suggest that PAR availability dampened the stimulatory effect of nutrient limitation, and bacterivory supplemented a suboptimal photosynthetic environment. In a saturating light regime, the mixotrophic community was less driven to ingest bacteria because photosynthesis was able to satisfy energetic demands. These findings quantify community bacterivory in response to environmental drivers that may characterize future ecosystem conditions and highlight the importance of considering grazing rates in conjunction with abundance of mixotrophic protists. [ABSTRACT FROM AUTHOR]