Explore the vast range of titles available.

During speech processing, neural activity in non-autistic adults and infants tracks the speech envelope. Recent research in adults indicates that this neural tracking relates to linguistic knowledge and may be reduced in autism. Such reduced tracking, if present already in infancy, could impede language development. In the current study, we focused on children with a family history of autism, who often show a delay in first language acquisition. We investigated whether differences in tracking of sung nursery rhymes during infancy relate to language development and autism symptoms in childhood. We assessed speech-brain coherence at either 10 or 14 months of age in a total of 22 infants with high likelihood of autism due to family history and 19 infants without family history of autism. We analyzed the relationship between speech-brain coherence in these infants and their vocabulary at 24 months as well as autism symptoms at 36 months. Our results showed significant speech-brain coherence in the 10- and 14-month-old infants. We found no evidence for a relationship between speech-brain coherence and later autism symptoms. Importantly, speech-brain coherence in the stressed syllable rate (1–3 Hz) predicted later vocabulary. Follow-up analyses showed evidence for a relationship between tracking and vocabulary only in 10-month-olds but not in 14-month-olds and indicated possible differences between the likelihood groups. Thus, early tracking of sung nursery rhymes is related to language development in childhood.

Individuals with autism spectrum disorder (ASD) show atypical processing of facial expressions. Research with autistic toddlers suggests that abnormalities in processing of spatial frequencies (SFs) contribute to such differences. The current event-related-potential (ERP) study investigated differences between 10-month-old infants with high- and low-likelihood for ASD in SF processing and in discrimination of fearful and neutral faces, filtered to contain specific SF. Results indicate no group differences in general processing of higher (HSF, detailed) and lower-SF (LSF, global) information. However, unlike low-likelihood infants, high-likelihood infants do not discriminate between facial expressions when either the LSF or HSF information is available. Combined with previous findings in toddlers, the current results indicate a developmental delay in efficient processing of facial expressions in ASD.

Over the past two decades, converging evidence from neuroscience and psychology has shown that predictions based on learnt statistical regularities exert a widespread influence on perception, action and cognition. Predictive processes in cognition and the brain are usually modelled as tracking objective event probabilities, deriving predictions and prediction errors from the statistical structure of the environment. However, our subjective models of our environments do not always align with these objective statistics. Currently we know little about how these subjective representations may determine the predictive functions. To separate subjective and objective contributions to prediction, we conducted three studies where cues (actions or tones) predicted visual outcomes (shapes or Gabors) with varying contingencies, and adult participants discriminated these outcomes. Uniquely to our paradigm, participants also reported their experiences of the statistical structure embedded in the task – the subjective probability (Experiment 1; N = 68), expectedness (Experiment 2; N = 35), or surprise (Experiment 3; N = 35) associated with the outcomes. When modelling subjective ratings alongside objective structure, the speed of perceptual decisions was best explained by independent, additive contributions of both. The decision itself was usually only explained by the subjective ratings, with little additional variance explained by objective statistical structure. These findings suggest that subjective experience may play a key, overlooked role in predictive processes, and open a host of interesting questions about the relative objective and subjective contributions to prediction, perception, and learning.

Macrophages are important drivers of pathogenesis and progression to AIDS in HIV infection. The virus in the later phases of the infection is often predominantly macrophage-tropic and this tropism contributes to a chronic inflammatory and immune activation state that is observed in HIV patients. Pattern recognition receptors of the innate immune system are the key molecules that recognise HIV and mount the inflammatory responses in macrophages. The innate immune response against HIV-1 is potent and elicits caspase-1-dependent pro-inflammatory cytokine production of IL-1β and IL-18. Although, NLRP3 has been reported as an inflammasome sensor dictating this response little is known about the pattern recognition receptors that trigger the “priming” signal for inflammasome activation, the NLRs involved or the HIV components that trigger the response. Using a combination of siRNA knockdowns in monocyte derived macrophages (MDMs) of different TLRs and NLRs as well as chemical inhibition, it was demonstrated that HIV Vpu could trigger inflammasome activation via TLR4/NLRP3 leading to IL-1β/IL-18 secretion. The priming signal is triggered via TLR4, whereas the activation signal is triggered by direct effects on Kv1.3 channels, causing K + efflux. In contrast, HIV gp41 could trigger IL-18 production via NAIP/NLRC4, independently of priming, as a one-step inflammasome activation. NAIP binds directly to the cytoplasmic tail of HIV envelope protein gp41 and represents the first non-bacterial ligand for the NAIP/NLRC4 inflammasome. These divergent pathways represent novel targets to resolve specific inflammatory pathologies associated with HIV-1 infection in macrophages.

There is considerable interest in developing novel psychological interventions for eating disorders targeting characteristics potentially serving as maintaining factors in eating disorder pathology. An estimated 94% of patients with an eating disorder report a dominant internal voice commenting on weight and self-worth, often referred to as the 'eating disorder voice'. The experience of a more dominating 'eating disorder voice' has been linked to longer illness duration. Within psychotic disorders, an intervention termed AVATAR therapy, using computerized avatars, has proven effective in reducing the severity of the psychotic voice and the associated distress. Building on this evidence and the proof-of-concept for AVATAR therapy adapted to eating disorders, this study investigates an immersive version targeting eating disorder symptoms. In this adaptation participants engage with an avatar representing their inner eating disorder voice in virtual reality. The study is designed as a randomized parallel-group superiority clinical trial. A total of 96 patients with an eating disorder will be allocated to either seven sessions of virtual reality-based avatar intervention plus treatment as usual (TAU) or TAU. All participants will be assessed at baseline, at treatment cessation (12 weeks), and at 24 weeks post baseline. A stratified block-randomization with concealed randomization sequence will be conducted. A case-series study has demonstrated that a non-immersive (2D) application of avatar-based therapy is feasible and acceptable for patients with an eating disorder. While this preliminary evidence is promising, further research is needed to evaluate the efficacy of an avatar-based intervention for eating disorders. This current study will be the first investigating this by testing a 3D immersive version of the intervention in a large-scale, methodologically rigorous trial. Should the efficacy of this intervention be confirmed, it could open new avenues for research into psychological treatments for eating disorders. ClinicalTrials.gov NCT06345040.

Aging is associated with remodeling of the immune system to enable the maintenance of life-long immunity. In the CD8 + T cell compartment, aging results in the expansion of highly differentiated cells that exhibit characteristics of cellular senescence. Here we found that CD27 − CD28 − CD8 + T cells lost the signaling activity of the T cell antigen receptor (TCR) and expressed a protein complex containing the agonistic natural killer (NK) receptor NKG2D and the NK adaptor molecule DAP12, which promoted cytotoxicity against cells that expressed NKG2D ligands. Immunoprecipitation and imaging cytometry indicated that the NKG2D–DAP12 complex was associated with sestrin 2. The genetic inhibition of sestrin 2 resulted in decreased expression of NKG2D and DAP12 and restored TCR signaling in senescent-like CD27 − CD28 − CD8 + T cells. Therefore, during aging, sestrins induce the reprogramming of non-proliferative senescent-like CD27 − CD28 − CD8 + T cells to acquire a broad-spectrum, innate-like killing activity. Akbar and colleagues show that sestrins induce the reprogramming of non-proliferative, senescent-like CD27 – CD28 – CD8 + T cells to acquire an innate-like killing activity modulated by the NK receptor NKG2D and the adaptor molecule DAP12.

RationaleHeterogeneity of the host response within sepsis, acute respiratory distress syndrome (ARDS) and more widely critical illness, limits discovery and targeting of immunomodulatory therapies. Clustering approaches using clinical and circulating biomarkers have defined hyper-inflammatory and hypo-inflammatory subphenotypes in ARDS associated with differential treatment response. It is unknown if similar subphenotypes exist in sepsis populations where leucocyte transcriptomic-defined subphenotypes have been reported.ObjectivesWe investigated whether inflammatory clusters based on cytokine protein abundance were seen in sepsis, and the relationships with previously described transcriptomic subphenotypes.MethodsHierarchical cluster and latent class analysis were applied to an observational study (UK Genomic Advances in Sepsis (GAinS)) (n=124 patients) and two clinical trial datasets (VANISH, n=155 and LeoPARDS, n=484) in which the plasma protein abundance of 65, 21, 11 circulating cytokines, cytokine receptors and regulators were quantified. Clinical features, outcomes, response to trial treatments and assignment to transcriptomic subphenotypes were compared between inflammatory clusters.Measurements and main resultsWe identified two (UK GAinS, VANISH) or three (LeoPARDS) inflammatory clusters. A group with high levels of pro-inflammatory and anti-inflammatory cytokines was seen that was associated with worse organ dysfunction and survival. No interaction between inflammatory clusters and trial treatment response was found. We found variable overlap of inflammatory clusters and leucocyte transcriptomic subphenotypes.ConclusionsThese findings demonstrate that differences in response at the level of cytokine biology show clustering related to severity, but not treatment response, and may provide complementary information to transcriptomic sepsis subphenotypes.Trial registration number ISRCTN20769191, ISRCTN12776039.

Background Prevalence rates of mental health disorders, non-suicidal self-injury and suicidality among Lesbian, Gay, Bisexual, Transgender, Queer and Asexual (LGBTQA+) higher education students are consistently higher than rates for heterosexual students. Nevertheless, in the United Kingdom, there remains limited prevalence data and evidence on the risk factors that confer increased risk of suicide among this population. The purpose of the present study was to investigate mental health disorders, childhood adversities, and recent stressors as risk factors for non-suicidal self-injury, and suicidality among LGBTQA + students. Methods The Student Psychological Interventional Trial (SPIT) was conducted as part of the World Mental Health International College Student Initiative (WMH-ICS). First year undergraduate students aged 18–24 years were recruited ( n  = 1525), including LGBTQA + students ( n  = 190). Chi-squared test of independence was used to identify significant differences in lifetime prevalence rates between heterosexual and LGBTQA + students. Bivariate and multivariate logistic regression analyses examined the associations between mental health disorders, childhood adversities, recent stressors, non-suicidal self-injury, and suicidality among LGBTQA + students. Results LGBTQA + students were significantly more likely to have experienced mental health difficulties, childhood adversities, recent stressors, non-suicidal self-injury, and suicidality than their heterosexual counterparts. One in four LGBTQA + students reported experiencing major depressive episode, and non-suicidal self-injury in their lifetime. LGBTQA + students also reported earlier onset of mental health disorders and suicidality, with much higher rates of interpersonal conflict, and probable post-traumatic stress disorder. Among LGBTQA + students, major depressive disorder, probable post-traumatic stress disorder, and non-suicidal self-injury were significantly associated with an increased likelihood of suicidal ideation and suicide plan. Childhood adversities, and recent stressors such as bullying were significantly associated with an increased likelihood of suicide attempt. Conclusions Our findings highlight the existing mental health disparities, childhood adversities, and recent stressors which may contribute to higher prevalence rates of non-suicidal self-injury, and suicidality among LGBTQA + students. The results emphasise the importance of early intervention, prevention, and treatment, focused on reducing the impact of childhood adversities and recent stressors such as bullying. In addressing these risk factors, educational settings may offer unique opportunities for the practice of inclusion, preventative care, and harm reduction for LGBTQA + students.

Circulating tumor DNA (ctDNA) detection can predict clinical risk in early-stage tumors. However, clinical applications are constrained by the sensitivity of clinically validated ctDNA detection approaches. NeXT Personal is a whole-genome-based, tumor-informed platform that has been analytically validated for ultrasensitive ctDNA detection at 1–3 ppm of ctDNA with 99.9% specificity. Through an analysis of 171 patients with early-stage lung cancer from the TRACERx study, we detected ctDNA pre-operatively within 81% of patients with lung adenocarcinoma (LUAD), including 53% of those with pathological TNM (pTNM) stage I disease. ctDNA predicted worse clinical outcome, and patients with LUAD with <80 ppm preoperative ctDNA levels (the 95% limit of detection of a ctDNA detection approach previously published in TRACERx) experienced reduced overall survival compared with ctDNA-negative patients with LUAD. Although prospective studies are needed to confirm the clinical utility of the assay, these data show that our approach has the potential to improve disease stratification in early-stage LUADs. In the TRACERx cohort of 171 patients with lung cancer, the ultrasensitive detection of ctDNA improves preoperative patient stratification, also in early-stage disease.

We conducted voluntary Covid-19 testing programmes for symptomatic and asymptomatic staff at a UK teaching hospital using naso-/oro-pharyngeal PCR testing and immunoassays for IgG antibodies. 1128/10,034 (11.2%) staff had evidence of Covid-19 at some time. Using questionnaire data provided on potential risk-factors, staff with a confirmed household contact were at greatest risk (adjusted odds ratio [aOR] 4.82 [95%CI 3.45–6.72]). Higher rates of Covid-19 were seen in staff working in Covid-19-facing areas (22.6% vs. 8.6% elsewhere) (aOR 2.47 [1.99–3.08]). Controlling for Covid-19-facing status, risks were heterogenous across the hospital, with higher rates in acute medicine (1.52 [1.07–2.16]) and sporadic outbreaks in areas with few or no Covid-19 patients. Covid-19 intensive care unit staff were relatively protected (0.44 [0.28–0.69]), likely by a bundle of PPE-related measures. Positive results were more likely in Black (1.66 [1.25–2.21]) and Asian (1.51 [1.28–1.77]) staff, independent of role or working location, and in porters and cleaners (2.06 [1.34–3.15]).