Programmed Death-1 Ligand 2-Mediated Regulation of the PD-L1 to PD-1 Axis Is Essential for Establishing CD4(+) T Cell Immunity.

Many pathogens, including Plasmodium spp., exploit the interaction of programmed death-1 (PD-1) with PD-1-ligand-1 (PD-L1) to "deactivate" T cell functions, but the role of PD-L2 remains unclear. We studied malarial infections to understand the contribution of PD-L2 to immunity. Here we have shown that higher PD-L2 expression on blood dendritic cells, from Plasmodium falciparum-infected individuals, correlated with lower parasitemia. Mechanistic studies in mice showed that PD-L2 was indispensable for establishing effective CD4(+) T cell immunity against malaria, because it not only inhibited PD-L1 to PD-1 activity but also increased CD3 and inducible co-stimulator (ICOS) expression on T cells. Importantly, administration of soluble multimeric PD-L2 to mice with lethal malaria was sufficient to dramatically improve immunity and survival. These studies show immuno-regulation by PD-L2, which has the potential to be translated into an effective treatment for malaria and other diseases where T cell immunity is ineffective or short-lived due to PD-1-mediated signaling.

Comparative Analysis of Chemical Descriptors by Machine Learning Reveals Atomistic Insights into Solute-Lipid Interactions.

This study explores the research area of drug solubility in lipid excipients, an area persistently complex despite recent advancements in understanding and predicting solubility based on molecular structure. To this end, this research investigated novel descriptor sets, employing machine learning techniques to understand the determinants governing interactions between solutes and medium-chain triglycerides (MCTs). Quantitative structure-property relationships (QSPR) were constructed on an extended solubility data set comprising 182 experimental values of structurally diverse drug molecules, including both development and marketed drugs to extract meaningful property relationships. Four classes of molecular descriptors, ranging from traditional representations to complex geometrical descriptions, were assessed and compared in terms of their predictive accuracy and interpretability. These include two-dimensional (2D) and three-dimensional (3D) descriptors, Abraham solvation parameters, extended connectivity fingerprints (ECFPs), and the smooth overlap of atomic position (SOAP) descriptor. Through testing three distinct regularized regression algorithms alongside various preprocessing schemes, the SOAP descriptor enabled the construction of a superior performing model in terms of interpretability and accuracy. Its atom-centered characteristics allowed contributions to be estimated at the atomic level, thereby enabling the ranking of prevalent molecular motifs and their influence on drug solubility in MCTs. The performance on a separate test set demonstrated high predictive accuracy (RMSE = 0.50) for 2D and 3D, SOAP, and Abraham Solvation descriptors. The model trained on ECFP4 descriptors resulted in inferior predictive accuracy. Lastly, uncertainty estimations for each model were introduced to assess their applicability domains and provide information on where the models may extrapolate in chemical space and, thus, where more data may be necessary to refine a data-driven approach to predict solubility in MCTs. Overall, the presented approaches further enable computationally informed formulation development by introducing a novel in silico approach for rational drug development and prediction of dose loading in lipids.

Consideration and Disclosure of Group Risks in Genomics and Other Data-Centric Research: Does the Common Rule Need Revision?

Harms and risks to groups and third-parties can be significant in the context of research, particularly in data-centric studies involving genomic, artificial intelligence, and/or machine learning technologies. This article explores whether and how United States federal regulations should be adapted to better align with current ethical thinking and protect group interests. Three aspects of the Common Rule deserve attention and reconsideration with respect to group interests: institutional review board (IRB) assessment of the risks/benefits of research; disclosure requirements in the informed consent process; and criteria for waivers of informed consent. In accordance with respect for persons and communities, investigators and IRBs should systematically consider potential group harm when designing and reviewing protocols, respectively. Research participants should be informed about any potential group harm in the consent process. We call for additional public discussion, empirical research, and normative analysis on these issues to determine the right regulatory and policy path forward.

Testing meshes in a computer model of a laparoscopic ventral hernia repair.

BACKGROUND: The ideal mesh for hernia repair has yet to be found, in addition our knowledge of the biomechanics of the abdominal wall is poor. The aim of this study was to develop a computer model of a laparoscopic ventral hernia repair and to test different meshes in that model at various intra-abdominal pressures. METHODS: Four meshes were tested in a computer model of a ventral hernia. Mechanical failure testing of each mesh was performed in both the longitudinal and transverse directions. A CT scan of a patient with a 5 cm umbilical hernia was used to generate a 3 dimensional model. Meshes were then applied to the model in an intraperitoneal onlay position with a 5 cm overlap. The model was then tested with intraabdominal pressures for standing, coughing and jumping with and without meshes. RESULTS: Meshes varied significantly (p < 0.001) in both rupture force 14.8 (5.6) to 78 (5) n/cm and force in which they changed from elastic to plastic 1.6 (0.1) to 14.2 (0.2) n/cm. When applied to the computer model all significantly reduced the strain on the abdominal wall from 17.5% without mesh to less than 1% with mesh. All meshes prevented the hernia from bulging in the model. CONCLUSIONS: We have developed a computer model of laparoscopic ventral hernia repair based on engineering principles. This model demonstrated that meshes tested significantly reduced the strain on the abdominal wall. Further studies are required to refine this model in order to best simulate the biomechanics of the abdominal wall.

Using Clustering to Examine Inter-individual Variability in Topography of Auditory Event-Related Potentials in Autism and Typical Development.

Although prior studies have compared sensory event-related potential (ERP) responses between groups of autistic and typically-developing participants, it is unclear how heterogeneity contributes to the results of these studies. The present study used examined individual differences in these responses. 130 autistic children and 81 typically-developing children, aged between 2 and 5 years, listened to tones at four identity levels while 61-channel electroencephalography was recorded. Hierarchical clustering was used to group participants based on rescaled ERP topographies between 51 and 350 ms. The hierarchical clustering analysis revealed substantial heterogeneity. Some of the seven clusters defined in this analysis were characterized by prolonged fronto-central positivities and/or weak or absent N2 negativities. However, many other participants fell into clusters in which N2 responses were present at varying latencies. Atypical response morphologies such as absent N2 responses and/or prolonged positive-going responses found in some autistic participants may account for prior research findings of attenuated N2 amplitudes in autism. However, there was also considerable overlap between groups, with participants of both groups appearing in all clusters. These results emphasize the utility of using clustering to explore individual differences in brain responses, which can expand on and clarify the results of analyses of group mean differences.

Novel Biphasic Lipolysis Method To Predict in Vivo Performance of Lipid-Based Formulations.

The absence of an intestinal absorption sink is a significant weakness of standard in vitro lipolysis methods, potentially leading to poor prediction of in vivo performance and an overestimation of drug precipitation. In addition, the majority of the described lipolysis methods only attempt to simulate intestinal conditions, thus overlooking any supersaturation or precipitation of ionizable drugs as they transition from the acidic gastric environment to the more neutral conditions of the intestine. The aim of this study was to develop a novel lipolysis method incorporating a two-stage gastric-to-intestinal transition and an absorptive compartment to reliably predict in vivo performance of lipid-based formulations (LBFs). Drug absorption was mimicked by in situ quantification of drug partitioning into a decanol layer. The method was used to characterize LBFs from four studies described in the literature, involving three model drugs (i.e., nilotinib, fenofibrate, and danazol) where in vivo bioavailability data have previously been reported. The results from the novel biphasic lipolysis method were compared to those of the standard pH-stat method in terms of reliability for predicting the in vivo performance. For three of the studies, the novel biphasic lipolysis method more reliably predicted the in vivo bioavailability compared to the standard pH-stat method. In contrast, the standard pH-stat method was found to produce more predictive results for one study involving a series of LBFs composed of the soybean oil, glyceryl monolinoleate (Maisine CC), Kolliphor EL, and ethanol. This result was surprising and could reflect that increasing concentrations of ethanol (as a cosolvent) in the formulations may have resulted in greater partitioning of the drug into the decanol absorptive compartment. In addition to the improved predictivity for most of the investigated systems, this biphasic lipolysis method also uses in situ analysis and avoids time- and resource-intensive sample analysis steps, thereby facilitating a higher throughput capacity and biorelevant approach for characterization of LBFs.

Relationship between ventral hernia defect area and intra-abdominal pressure: dynamic in vivo measurement.

BACKGROUND: It is an acceptable concept that the ventral hernia defect area will increase with a rise in intra-abdominal pressure (IAP). The literature lacks the evidence about how much this increase is in vivo. The aim of this study was to objectively measure the change in the ventral hernia defect area with increasing intra-abdominal pressure. METHODS: In a prospective study of laparoscopic ventral hernia repair, the area of hernia defect was measured from inside the abdomen using a sterile paper ruler. The horizontal (width) and vertical (length) measurements of the defect were taken at two pressure points: (IAP = 8 mmHg) and (IAP = 15 mmHg). The hernia defect area was calculated as an oval shape using a standard formula. RESULTS: Eighteen consecutive patients with a ventral hernia were included in this study (8 males: 10 females). Median age was 60 years (30-81), body mass index (BMI) was 29.9 (22.6-37.6). Changing the IAP significantly, (P < 0.001) changed the values of horizontal and vertical measurements, and the calculated area of the ventral hernia defect. The median calculated defect area, as an oval shape, was 5.6 cm(2) (Q1-Q3 = 3.5-15.5) and 6.9 cm(2) (Q1-Q3 = 4.5-18.7) at 8 and 15 mmHg IAP, respectively. The calculated area of mesh required to cover the defect with a 5 cm overlap increased by a median of 5% (Q1-Q3 = 3-6%). The change in defect area did not differ significantly between obese and non-obese patients (P = 0.5). CONCLUSIONS: Dynamic, rather than static, measurements of ventral hernia area during laparoscopy provide a simple way of in vivo objective measurement that helps the surgeon choose the appropriate area of mesh. When choosing mesh area, we support the trend toward a larger overlap of at least 5 cm if less precise methods of measuring defect area are been used.

All-atom CHARMM force field and bulk properties of perfluorozinc phthalocyanines.

Classical force fields within the CHARMM parametrized model are developed for zinc phthalocyanines including the parent per-hydro molecule and per-fluoro-alkyl substituted derivatives. Partial atomic charges, 2-body bond lengths, and 3-body angle parameters were obtained from B3LYP-level density functional calculations. Force constants for 2-, 3-, and 4-body interactions were derived from existing fluoroalkane models and incorporated assuming transferability. The force fields were validated by comparing equilibrium molecular geometries from molecular dynamics simulations with density functional theory (DFT) calculations and, where available, published experimental XRD refinements. The models produce molecular geometries for the target materials within 1-2% of expected values. Intermolecular interaction geometries were also investigated using molecular dynamics simulations. The results provide new insight and predictions of the equilibrium stacking and orientational intermolecular interactions of this novel class of modified phthalocyanines.

The Neurodiversity Attitudes Questionnaire: Development and Initial Validation.

LAY ABSTRACT: Neurodiversity refers to the idea that brain differences (including disabilities) are valuable and should be accepted. Attitudes toward neurodiversity can have real-life impacts on the lives of neurodivergent people (those whose brains do not fit society's "standard"). These impacts can include effects on daily interactions, as well as how professionals such as teachers and doctors deliver services to neurodivergent people. In order to identify negative attitudes toward neurodiversity and potentially improve them, we first need to measure these attitudes. This article describes the development of the Neurodiversity Attitudes Questionnaire (NDAQ). NDAQ development included revision of questionnaire items based on feedback from experts and neurodivergent people, systematically evaluating the way participants responded to questionnaire items, and analysis of how the NDAQ items are grouped into different factors. A preliminary analysis with 351 individuals mostly living in the United States who were currently working or planning to work in a helping profession (e.g. doctors, teachers, therapists, and so on) indicates that the NDAQ measures attitudes toward neurodiversity, is well understood by participants, and fits a five-factor structure. While the NDAQ represents the first instrument designed to specifically assess attitudes toward the broad idea of neurodiversity, further work is still needed.

The Social Validity of Behavioral Interventions: Seeking Input from Autistic Adults.

Many in the autistic community have expressed concerns regarding the use of behavioral interventions with autistic children, suggesting that these interventions may not be socially valid. Though behavioral interventions have evolved to be more naturalistic and child-centered, little structured research has been done to explicitly seek autistic perspectives on the acceptability of specific components of behavioral interventions. Autistic adults (N = 235) were recruited online to take the Autism Intervention Attitudes Scale (AIAS), a questionnaire designed to gather feedback on common intervention goals and practices. Results indicate that participants find goals and practices that highlight quality of life, safety, and autistic interactions acceptable, while those that focus on normalization based on neurotypical standards are not. An exploratory graph analysis revealed three communities of goals ("uncontroversial goals", "controversial goals", and "social goals"). Comparison between naturalistic and structured intervention components additionally showed that autistic participants favored naturalistic strategies. These findings are in line with known criticisms of behavioral intervention from autistic adults, but also provide more information on the specific ways in which behavioral interventions can be reformed. This information can guide professionals in the development of appropriate goals and decisions around intervention planning.

Hyper-focus, sticky attention, and springy attention in young autistic children: Associations with sensory behaviors and cognitive ability.

The autistic-developed monotropism account suggests that atypical, domain-general attentional hyper-focus on interests is a central aspect of autism, but domain-general attention differences in autism can manifest differently. Prior research suggests autistic children are often slow to disengage attention from stimuli-a pattern often called "sticky attention"-and that they can show reduced novelty preference. These attentional patterns could influence sensory experiences and learning. We used eye-tracking to investigate novelty preference and "sticky attention" in young autistic children; we also examined whether attentional patterns were related to cognitive abilities and caregiver-reported sensory responsiveness. A total of 46 autistic and 28 nonautistic participants, aged between 2 and 4 years, provided usable data. We found no evidence that autistic children exhibited greater "sticky attention" than nonautistics, but "sticky attention" in autism was associated with more caregiver-reported sensory hyper-responsiveness, seeking/interests, and enhanced perception. Autistic children also nonsignificantly trended toward exhibiting reduced novelty preference. Unexpectedly, the time-course of this trending novelty preference difference implied it was not driven by reduced orienting to novelty, but increased returning to already-familiarized stimuli: what we call "springy attention." Exploratory analyses of data from the attentional disengagement task suggest autistic participants may have exhibited greater "springy attention," though further research with paradigms optimized for measuring this construct should confirm this. Importantly, "springy attention" was robustly related to reduced cognitive abilities and greater caregiver-reported hypo-responsiveness. Thus, this study illuminates two distinct domain-general attentional patterns, each with distinct correlates in young autistic children, which could have important implications for understanding autistic children's learning, development, and experiences.

Enhancing multi-site autism research through the development of a collaborative data platform.

Data repositories, particularly those storing data on vulnerable populations, increasingly need to carefully consider not only what data is being collected, but how it will be used. As such, the Autism Intervention Research Network on Physical Health (AIR-P) has created the Infrastructure for Collaborative Research (ICR) to establish standards on data collection practices in Autism repositories. The ICR will strive to encourage inter-site collaboration, amplify autistic voices, and widen accessibility to data. The ICR is staged as a three-tiered framework consisting of (1) a request for proposals system, (2) a REDCap-based data repository, and (3) public data dashboards to display aggregate de-identified data. Coupled with a review process including autistic and non-autistic researchers, this framework aims to propel the implementation of equitable autism research, enhance standardization within and between studies, and boost transparency and dissemination of findings. In addition, the inclusion of a contact registry that study participants can opt into creates the base for a robust participant pool. As such, researchers can leverage the platform to identify, reach, and distribute electronic materials to a greater proportion of potential participants who likely fall within their eligibility criteria. By incorporating practices that promote effective communication between researchers and participants, the ICR can facilitate research that is both considerate of and a benefit to autistic people.

Mal-positioned nasogastric feeding tubes: are medical students safe to identify them?

OBJECTIVES: Nasogastric tube (NGT) placement is listed against Clinical Imaging in the upcoming Medical Licensing Assessment-compulsory for every graduating UK medical student from 2025. This study aims to establish the ability of medical students to correctly identify the position of an NGT on Chest X-ray (CXR) and to evaluate a learning tool to improve student outcome in this area. METHODS: Fourth-year (MB4) and fifth-year (MB5) medical students were invited to view 20 CXRs with 14 correctly sited and 6 mal-positioned NGT. MB5 students (Intervention) were exposed to an online interactive learning tool, with MB4 students kept as control. One week later, both groups of students were invited to view 20 more CXRs for NGT placement. RESULTS: Only 12 (4.8%) of 249 MB5 students and 5 (3.1%) of 161 MB4 students correctly identified all the NGTs on CXRs. The number of students misidentifying 1 or more mal-positioned NGT as "safe to feed" was 129 (51.8%) for MB5 and 76 (47.2%) for MB4 students. This improved significantly (P < .001) following exposure to the learning tool with 58% scoring all CXRs correctly, while 28% scored 1 or more mal-positioned NGT incorrectly. Students struggled to determine if the NGT tip had adequately passed into the stomach. However, they failed to identify an NG tube in the lung ("never event") in just one out of 1,108 opportunities. CONCLUSION: Medical students' ability to determine if the NGT was in the stomach remains suboptimal despite exposure to over 60 CXRs. Feeding NGT should be formally reported before use. ADVANCES IN KNOWLEDGE: This is the first attempt at quantifying graduating medical students', and by inference junior doctors', competence in safely identifying misplaced nasogastric feeding tubes. An online, experiential learning resource significantly improved their ability.

Predictive computational models for assessing the impact of co-milling on drug dissolution.

Co-milling is an effective technique for improving dissolution rate limited absorption characteristics of poorly water-soluble drugs. However, there is a scarcity of models available to forecast the magnitude of dissolution rate improvement caused by co-milling. Therefore, this study endeavoured to quantitatively predict the increase in dissolution by co-milling based on drug properties. Using a biorelevant dissolution setup, a series of 29 structurally diverse and crystalline drugs were screened in co-milled and physically blended mixtures with Polyvinylpyrrolidone K25. Co-Milling Dissolution Ratios after 15 min (COMDR15 min) and 60 min (COMDR60 min) drug release were predicted by variable selection in the framework of a partial least squares (PLS) regression. The model forecasts the COMDR15 min (R2 = 0.82 and Q2 = 0.77) and COMDR60 min (R2 = 0.87 and Q2 = 0.84) with small differences in root mean square errors of training and test sets by selecting four drug properties. Based on three of these selected variables, applicable multiple linear regression equations were developed with a high predictive power of R2 = 0.83 (COMDR15 min) and R2 = 0.84 (COMDR60 min). The most influential predictor variable was the median drug particle size before milling, followed by the calculated drug logD6.5 value, the calculated molecular descriptor Kappa 3 and the apparent solubility of drugs after 24 h dissolution. The study demonstrates the feasibility of forecasting the dissolution rate improvements of poorly water-solube drugs through co-milling. These models can be applied as computational tools to guide formulation in early stage development.

Predictions of biorelevant solubility change during dispersion and digestion of lipid-based formulations.

Computational approaches are increasingly explored in development of drug products, including the development of lipid-based formulations (LBFs), to assess their feasibility for achieving adequate oral absorption at an early stage. This study investigated the use of computational pharmaceutics approaches to predict solubility changes of poorly soluble drugs during dispersion and digestion in biorelevant media. Concentrations of 30 poorly water-soluble drugs were determined pre- and post-digestion with in-line UV probes using the MicroDISS Profiler™. Generally, cationic drugs displayed higher drug concentrations post-digestion, whereas for non-ionized drugs there was no discernible trend between drug concentration in dispersed and digested phase. In the case of anionic drugs there tended to be a decrease or no change in the drug concentration post-digestion. Partial least squares modelling was used to identify the molecular descriptors and drug properties which predict changes in solubility ratio in long-chain LBF pre-digestion (R2 of calibration = 0.80, Q2 of validation = 0.64) and post-digestion (R2 of calibration = 0.76, Q2 of validation = 0.72). Furthermore, multiple linear regression equations were developed to facilitate prediction of the solubility ratio pre- and post-digestion. Applying three molecular descriptors (melting point, LogD, and number of aromatic rings) these equations showed good predictivity (pre-digestion R2 = 0.70, and post-digestion R2 = 0.68). The model developed will support a computationally guided LBF strategy for emerging poorly water-soluble drugs by predicting biorelevant solubility changes during dispersion and digestion. This facilitates a more data-informed developability decision making and subsequently facilitates a more efficient use of formulation screening resources.

Associations between patient-level health literacy and diagnostic time intervals for head and neck cancer: A prospective cohort study.

BACKGROUND: Health literacy (HL) comprises skills and knowledge required to understand, access, and make decisions about healthcare. Our aim was to examine associations between patient HL and time intervals (defined in the Aarhus statement) along the pathway to treatment of head and neck cancer (HNC). METHODS: A prospective cohort study was conducted from October 2018 to March 2020. Participants completed the Health Literacy Questionnaire (HLQ®) and described key events and dates along the pathway to treatment using validated questionnaires. Correlations between six diagnostic time intervals and domains of HL were explored, and factors predicting exceeding maximum acceptable timeframes were assessed using logistic regression. RESULTS: One hundred patients with a diagnosis of HNC within the preceding 6 months were recruited. HLQ® Domain 2 (sufficient information to manage health) was significantly negatively associated with four intervals: the patient interval (first symptom to first presentation), primary care interval (first presentation to referral to secondary care), diagnostic interval (first presentation to diagnosis), and total interval (first symptom to treatment onset); correlation coefficients -0.25 to -0.27 (P < 0.05). Domain 8 (ability to find good information) was significantly negatively associated with three intervals (primary care interval, diagnostic interval, and total interval; correlation coefficients -0.23 to -0.34; P < 0.05). Higher education, age, and comorbidity levels were associated with shorter patient and diagnostic intervals. CONCLUSIONS: HL may be a potential target to improve timeliness of HNC diagnosis and reduce disparities in outcomes.

Developing an in vitro lipolysis model for real-time analysis of drug concentrations during digestion of lipid-based formulations.

Understanding the effect of digestion on oral lipid-based drug formulations is a critical step in assessing the impact of the digestive process in the intestine on intraluminal drug concentrations. The classical pH-stat in vitro lipolysis technique has traditionally been applied, however, there is a need to explore the establishment of higher throughput small-scale methods. This study explores the use of alternative lipases with the aim of selecting digestion conditions that permit in-line UV detection for the determination of real-time drug concentrations. A range of immobilised and pre-dissolved lipases were assessed for digestion of lipid-based formulations and compared to digestion with the classical source of lipase, porcine pancreatin. Palatase® 20000 L, a purified liquid lipase, displayed comparable digestion kinetics to porcine pancreatin and drug concentration determined during digestion of a fenofibrate lipid-based formulation were similar between methods. In-line UV analysis using the MicroDISS ProfilerTM demonstrated that drug concentration could be monitored during one hour of dispersion and three hours of digestion for both a medium- and long-chain lipid-based formulations with corresponding results to that obtained from the classical lipolysis method. This method offers opportunities exploring the real-time dynamic drug concentration during dispersion and digestion of lipid-based formulations in a small-scale setup avoiding artifacts as a result of extensive sample preparation.

Laparoscopic resection of paraaortic or paracaval lesions: feasibility and outcome.

BACKGROUND: Laparoscopic retroperitoneal lymph node dissection of paraaortic and paracaval lymph nodes is used to stage nonseminomatous germ cell tumors. Primary tumors can arise from the retroperitoneum, and tumors from nonurologic malignancy also may metastasize to retroperitoneal lymph nodes. This study aimed to describe the authors' experience with laparoscopic resection of these lesions. METHODS: A consecutive series of patients between January 2007 and June 2011 with paraaortic, aortocaval, or paracaval tumors with a maximum diameter smaller than 10 cm and confined to the abdomen were considered for laparoscopic resection. Data were collected on size and pathology of the lesions, anesthesia time, postoperative stay, and postoperative morbidity and mortality. RESULTS: In this study, 25 patients with a median age of 49 years were assessed for laparoscopic resection. Eight patients were considered unsuitable for a laparoscopic approach because of tumor location (n = 5), previous retroperitoneal surgery (n = 1), stoma (n = 1), or lesion not clearly visible on computed tomography (n = 1). Of the 17 patients undergoing laparoscopic resection, 1 was found to have diffuse peritoneal disease at laparoscopy, whereas another was converted to an open procedure due to bleeding. All the laparoscopic patients had an R0 resection. The median hospital stay was significantly shorter in the laparoscopic group (2 days) than in the open group (6 days) (P = 0.009). One patient in the laparoscopic group with a functioning paraganglioma and advanced cardiac disease died on postoperative day 7. CONCLUSION: Laparoscopic paraaortic and paracaval surgery for primary and recurrent tumors of the retroperitoneum is feasible, with clear resection margin rates similar to that observed for open surgery.

The INSAR Community Collaborator Request: Using community-academic partnerships to enhance outcomes of participatory autism research.

Participatory approaches, in which researchers work together with members of the autism community (e.g., autistic people, family members, caregivers, or other stakeholders) to design, conduct, and disseminate research, have become increasingly prominent within the field of autism research over the past decade. Despite growing academic and community interest in conducting participatory studies, stakeholder collaboration remains infrequent in autism research, at least partially due to systemic barriers. To help reduce barriers to engaging in participatory autism research, the International Society for Autism Research (INSAR) Autistic Researchers Committee has launched the INSAR Community Collaborator Request (ICCR; https://www.autism-insar.org/page/iccr), a platform on the INSAR website that allows autism researchers conducting participatory research to seek out stakeholder collaborators from the autism community (including both autistic people and their family members/caregivers, as relevant to a given research project). Interested stakeholders also have the opportunity to subscribe to ICCR posts, allowing them to be alerted of new opportunities for collaboration and potentially increasing their involvement in autism research. Overall, the ICCR provides a venue to connect autism researchers with potential community collaborators, reducing barriers to participatory autism research and increasing the frequency of successful community-academic partnerships within the field. We are hopeful that in the long term, such changes will lead to greater alignment between research outputs and the goals of the greater autism community, and consequently an increase in the overall quality and relevance of autism research.

Habituation of auditory responses in young autistic and neurotypical children.

Prior studies suggest that habituation of sensory responses is reduced in autism and that diminished habituation could be related to atypical autistic sensory experiences, for example, by causing brain responses to aversive stimuli to remain strong over time instead of being suppressed. While many prior studies exploring habituation in autism have repeatedly presented identical stimuli, other studies suggest group differences can still be observed in habituation to intermittent stimuli. The present study explored habituation of electrophysiological responses to auditory complex tones of varying intensities (50-80 dB SPL), presented passively in an interleaved manner, in a well-characterized sample of 127 autistic (MDQ = 65.41, SD = 20.54) and 79 typically developing (MDQ = 106.02, SD = 11.50) children between 2 and 5 years old. Habituation was quantified as changes in the amplitudes of single-trial responses to tones of each intensity over the course of the experiment. Habituation of the auditory N2 response was substantially reduced in autistic participants as compared to typically developing controls, although diagnostic groups did not clearly differ in habituation of the P1 response. Interestingly, the P1 habituated less to loud 80 dB sounds than softer sounds, whereas the N2 habituated less to soft 50 dB sounds than louder sounds. No associations were found between electrophysiological habituation and cognitive ability or participants' caregiver-reported sound tolerance (Sensory Profile Hyperacusis Index). The results present study results extend prior research suggesting habituation of certain sensory responses is reduced in autism; however, they also suggest that habituation differences observed using this study's paradigm might not be a primary driver of autistic participants' real-world sound intolerance.