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The study aims to develop and pilot a telehealth social emotional program, MindChip™ delivered with a computer based interventions (CBI) (Mind Reading © ) for autistic adults. MindChip™ combined four theoretical perspectives and community feedback underpinning the essential mechanisms for targeting the social emotional understanding of autistic adults. A randomised pragmatic pilot trial (N = 25) was conducted to explore the feasibility of MindChip™ (n = 11) and to understand the preliminary efficacy of combining it with CBI compared to CBI only (n = 14). The use of MindChip™ and CBI combined demonstrated partial feasibility, with preliminary efficacy findings revealing increased emotion recognition generalisation outcomes compared to CBI only. Further research is required to improve the engagement and personalisation of the intervention for autistic adults.

Recent years have seen an emergence of social emotional computer games for individuals with Autism Spectrum Disorder (ASD). These games are heterogeneous in design with few underpinned by theoretically informed approaches to computer-based interventions. Guided by the serious game framework outlined by Whyte et al. (Journal of Autism and Developmental Disorders 45(12):1–12, 2014 ), this study aimed to identify the key motivating and learning features for serious games targeting emotion recognition skills from the perspectives of 11 youth with ASD and 11 experienced professionals. Results demonstrated that youth emphasised the motivating aspects of game design, while the professionals stressed embedding elements facilitating the generalisation of acquired skills. Both complementary and differing views provide suggestions for the application of serious game principles in a potential serious game.

Understanding the underlying visual scanning patterns of individuals with autism spectrum disorder (ASD) during the processing of complex emotional scenes remains limited. This study compared the complex emotion recognition performance of adults with ASD (n = 23) and matched neurotypical participants (n = 25) using the Reading the Mind in Films Task. Behaviourally, both groups exhibited similar emotion recognition accuracy. Visual fixation time towards key social regions of each stimuli was examined via eye tracking. Individuals with ASD demonstrated significantly longer fixation time towards the non-social areas. No group differences were evident for the facial and body regions of all characters in the social scenes. The findings provide evidence of the heterogeneity associated with complex emotion processing in individuals with ASD.

Condensates formed by complex coacervation are hypothesized to have played a crucial part during the origin-of-life. In living cells, condensation organizes biomolecules into a wide range of membraneless compartments. Although RNA is a key component of biological condensates and the central component of the RNA world hypothesis, little is known about what determines RNA accumulation in condensates and to which extend single condensates differ in their RNA composition. To address this, we developed an approach to read the RNA content from single synthetic and protein-based condensates using high-throughput sequencing. We find that certain RNAs efficiently accumulate in condensates. These RNAs are strongly enriched in sequence motifs which show high sequence similarity to short interspersed elements (SINEs). We observe similar results for protein-derived condensates, demonstrating applicability across different in vitro reconstituted membraneless organelles. Thus, our results provide a new inroad to explore the RNA content of phase-separated droplets at single condensate resolution. Here, the authors demonstrate that single cell RNA sequencing technology can be leveraged to characterize RNA content of individual membrane-free condensates formed by liquid-liquid phase separation processes such as coacervation.

Thoracic radiography and abdominal ultrasonography are part of standard diagnostic investigations in cases of canine immune-mediated polyarthritis (IMPA). However, the clinical importance of thoracic and abdominal imaging towards the management of canine IMPA currently remains unknown. The primary aim of this study was to describe the findings documented on thoracic radiography and abdominal ultrasonography in dogs diagnosed with IMPA, and to evaluate the diagnostic utility of thoracic radiography and abdominal ultrasonography in the initial approach and management of these cases. Seventy-seven dogs diagnosed with IMPA who underwent thoracic radiography and abdominal ultrasonography at a single referral hospital between 2008 and 2022 were included. The diagnostic imaging studies of these 77 dogs were reviewed by one blinded board-certified diagnostic imaging specialist for quality assurance. The medical records, including the diagnostic imaging reports of these dogs, were then reviewed by three blinded board-certified internal medicine specialists. Using a modified version of a previous question and scoring system, the three internal medicine specialists then generated an answer for the overall diagnostic utility and a diagnostic utility score for thoracic radiography and abdominal ultrasonography for each case. The abnormal findings identified in radiography and ultrasonography were described. In the cases where the findings were considered significant enough to immediately affect the case management, the results of the further investigations that were subsequently performed were also described. No abnormalities were detected in thoracic radiography for 30 cases, and none were detected in abdominal ultrasound for 6. The majority of the internists considered thoracic radiography to be not useful in the overall case management at the time of IMPA diagnosis in 70 cases, and considered abdominal ultrasonography to be not useful in the overall case management in 57 cases. The majority of the internists agreed on the utility of thoracic radiography in 95% of the cases, and in 61% of the cases for abdominal ultrasonography. The most common finding in the thoracic radiography was a mild bronchial pulmonary pattern, and the most common in the abdominal ultrasonography was mild lymphadenomegaly. Therefore, although thoracic radiography and abdominal ultrasonography identified numerous abnormal findings in this population of dogs, in the majority of the cases, the findings were deemed not useful towards the overall case management at the time of the initial diagnosis of IMPA. Thus, the use of thoracic radiography and abdominal ultrasonography should be taken into careful consideration when considering initial diagnostic investigations for canine IMPA.

The most common bacterial isolates in dogs with pyothorax include mixed anaerobes, Enterobacteriaceae (especially Escherichia coli), Pasteurella spp., Streptococcus spp., and Staphylococcus spp. A fluoroquinolone with amoxicillin (±clavulanate) or a fluoroquinolone with clindamycin are the most commonly recommended empirical antimicrobials whilst pending bacterial culture of the pleural effusion. The aim of this study is to review and compare the pleural effusion culture and antimicrobial susceptibility results to the PROTECT ME poster and other published antimicrobial use guidelines. The medical records of 53 dogs diagnosed with pyothorax between 2014 and 2020 at two veterinary referral centres were reviewed. Information, including culture and susceptibility results, was assessed. Antimicrobial susceptibility panels varied; susceptibility to a particular antibiotic was calculated as a percentage of isolates tested against the same antibiotic. A total of 30 of 53 dogs (57.7%) had a positive pleural fluid culture. The most common isolates were Pasteurella species (23.3%), Escherichia coli (23.3%), and mixed anaerobes (20%). From the aerobic isolates, 73–83% were susceptible to a fluoroquinolone, 14/19 (74%) to amoxicillin, and 20/22 (91%) to potentiated amoxicillin. Resistance to clindamycin was documented in 9/13 (69%) aerobic isolates, with all Gram-negative bacteria (9/9) being resistant. The combination of potentiated amoxicillin with marbofloxacin would have been appropriate in most of the dogs (75–92.9%). This study shows a high rate of resistance to clindamycin, which is not a suitable option for monotherapy and may be less effective in combination therapy compared to potentiated amoxicillin.

Regulatory T (Treg) cells are one of the major immunosuppressive cell types in cancer and a potential target for immunotherapy, but targeting tumor-infiltrating (TI) Treg cells has been challenging. Here, using single-cell RNA sequencing of immune cells from renal clear cell carcinoma (ccRCC) patients, we identify two distinct transcriptional fates for TI Treg cells, Fate-1 and Fate-2. The Fate-1 signature is associated with a poorer prognosis in ccRCC and several other solid cancers. CD177, a cell surface protein normally expressed on neutrophil, is specifically expressed on Fate-1 TI Treg cells in several solid cancer types, but not on other TI or peripheral Treg cells. Mechanistically, blocking CD177 reduces the suppressive activity of Treg cells in vitro, while Treg-specific deletion of Cd177 leads to decreased tumor growth and reduced TI Treg frequency in mice. Our results thus uncover a functional CD177 + TI Treg population that may serve as a target for TI Treg-specific immunotherapy. Regulatory T (Treg) cells are important modulators of the tumor microenvironment. Here the authors perform transcriptome profiling of immune cells from patients with renal clear cell carcinoma to find a Treg signature that correlates with poorer prognosis, with CD177 being implicated as the main mediator for related alterations in Treg activity and tumor outcome.

Inhibition of Janus kinase (JAK) family enzymes is a popular strategy for treating inflammatory and autoimmune skin diseases. In the clinic, small molecule JAK inhibitors show distinct efficacy and safety profiles, likely reflecting variable selectivity for JAK subtypes. Absolute JAK subtype selectivity has not yet been achieved. Here, we rationally design small interfering RNAs (siRNAs) that offer sequence-specific gene silencing of JAK1, narrowing the spectrum of action on JAK-dependent cytokine signaling to maintain efficacy and improve safety. Our fully chemically modified siRNA supports efficient silencing of JAK1 expression in human skin explant and modulation of JAK1-dependent inflammatory signaling. A single injection into mouse skin enables five weeks of duration of effect. In a mouse model of vitiligo, local administration of the JAK1 siRNA significantly reduces skin infiltration of autoreactive CD8 + T cells and prevents epidermal depigmentation. This work establishes a path toward siRNA treatments as a new class of therapeutic modality for inflammatory and autoimmune skin diseases. Therapeutic modulation of Janus kinase family enzymes is an established approach for inflammatory and autoimmune skin diseases. Here the authors rationally design small interfering RNAs to enable single Janus kinase targeting and test this new therapeutic approach in a skin disease model for maintaining efficacy and improving selectivity.

Black applicants are 13% less likely than white applicants to receive research funding from the National Institutes of Health (NIH) [22]. [...]the benefits of our research are not distributed equally; since the large majority of research subjects and tissue donors are white (even for many diseases that disproportionately affect BIPOC), biomedical research often has reduced relevance for BIPOC [29,30]. When healthcare professionals are taught to identify medical conditions by the presence of rashes, skin becoming pale, or lips turning blue, BIPOC patients may be overlooked in initial screenings; their quality of care is lower even before treatment because their symptoms are less likely to be recognized [33]. Racial bias in medicine not only exacerbates distrust of biomedical research, but also entrenches systemic healthcare disparities between racial and ethnic groups [34,35].

Maximizing vaccine efficacy is critical, but previous research has failed to provide a one-size-fits-all solution. Although vitamin A and vitamin D supplementation studies have been designed to improve vaccine efficacy, experimental results have been inconclusive. Information is urgently needed to explain study discrepancies and to provide guidance for the future use of vitamin supplements at the time of vaccination. We conducted a randomized, blinded, placebo-controlled study of influenza virus vaccination and vitamin supplementation among 2 to 8 (inclusive) year old children over three seasons, including 2015–2016 (n = 9), 2016–2017 (n = 44), and 2017–2018 (n = 26). Baseline measurements of vitamins A and D were obtained from all participants. Measurements were of serum retinol, retinol-binding protein (RBP, a surrogate for retinol), and 25-hydroxyvitamin D (25(OH)D). Participants were stratified into two groups based on high and low incoming levels of RBP. Children received two doses of the seasonal influenza virus vaccine on days 0 and 28, either with an oral vitamin supplement (termed A 20,000 IU retinyl palmitate and 2000 IU cholecalciferol) or a matched placebo. Hemagglutination inhibition (HAI) antibody responses were evaluated toward all four components of the influenza virus vaccines on days 0, 28, and 56. Our primary data were from season 2016–2017, as enrollment was highest in this season and all children exhibited homogeneous and negative HAI responses toward the Phuket vaccine at study entry. Responses among children who entered the study with insufficient or deficient levels of RBP and 25(OH)D benefited from the A&D supplement (p < 0.001 for the day 28 Phuket response), whereas responses among children with replete levels of RBP and 25(OH)D at baseline were unaffected or weakened (p = 0.02 for the day 28 Phuket response). High baseline RBP levels associated with high HAI titers, particularly for children in the placebo group (baseline RBP correlated positively with Phuket HAI titers on day 28, r = 0.6, p = 0.003). In contrast, high baseline 25(OH)D levels associated with weak HAI titers, particularly for children in the A&D group (baseline 25(OH)D correlated negatively with Phuket HAI titers on day 28, r = −0.5, p = 0.02). Overall, our study demonstrates that vitamin A&D supplementation can improve immune responses to vaccines when children are vitamin A and D-insufficient at baseline. Results provide guidance for the appropriate use of vitamins A and D in future clinical vaccine studies.