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Abstract Time-domain diffuse correlation spectroscopy (TD-DCS) has been introduced as an advancement of the “classical” continuous wave DCS (CW-DCS) allowing one to not only to measure depth-resolved blood flow index (BFI) but also to extract optical properties of the measured medium without using any additional diffuse optics technique. However, this method is a photon-starved technique, specially when considering only the late photons that are of primary interest which has limited its in vivo application. In this work, we present a TD-DCS system based on a superconducting nanowire single-photon detector (SNSPD) with a high quantum efficiency, a narrow timing response, and a negligibly low dark count noise. We compared it to the typically used single-photon avalanche diode (SPAD) detector. In addition, this system allowed us to conduct fast in vivo measurements and obtain gated pulsatile BFI on the adult human forehead.

In clinical scenarios, the use of biomedical sensors, devices and multi-parameter assessments is fundamental to provide a comprehensive portrait of patients’ state, in order to adapt and personalize rehabilitation interventions and support clinical decision-making. However, there is a huge gap between the potential of the multidomain techniques available and the limited practical use that is made in the clinical scenario. This paper reviews the current state-of-the-art and provides insights into future directions of multi-domain instrumental approaches in the clinical assessment of patients involved in neuromotor rehabilitation. We also summarize the main achievements and challenges of using multi-domain approaches in the assessment of rehabilitation for various neurological disorders affecting motor functions. Our results showed that multi-domain approaches combine information and measurements from different tools and biological signals, such as kinematics, electromyography (EMG), electroencephalography (EEG), near-infrared spectroscopy (NIRS), and clinical scales, to provide a comprehensive and objective evaluation of patients’ state and recovery. This multi-domain approach permits the progress of research in clinical and rehabilitative practice and the understanding of the pathophysiological changes occurring during and after rehabilitation. We discuss the potential benefits and limitations of multi-domain approaches for clinical decision-making, personalized therapy, and prognosis. We conclude by highlighting the need for more standardized methods, validation studies, and the integration of multi-domain approaches in clinical practice and research.

Measuring muscle fatigue and resistance to fatigue is a topical theme in many clinical research studies. Multi-domain approaches, including electromyography (EMG), are employed to measure fatigue in rehabilitation contexts. In particular, spectral features, such as the reduction in the median frequency, are accepted biomarkers to detect muscle fatigue conditions. However, applications of fatigue detection in clinical scenarios are still limited and with margin for improvement. One of the potential applications of such methodology in clinics concerns the evaluation of the rehabilitation after hip fracture. In this work, 20 inpatients, in the acute phase after hip fracture surgery and with lower limb weakness, performed isometric contractions with their healthy lower limb (quadriceps muscle) and their resistance to fatigue before and after 2 weeks of rehabilitation program was measured. Multi-channel EMG and Maximum Voluntary Contractions (MVC, force) were recorded on five muscle heads. We found that, after performing the same number of repetitions (repetitions pre-treatment: 19.7 ± 1.34; repetitions post-treatment: 19.9 ± 0.36; p = 0.223), MVC improved (MVC pre-treatment: 278 ± 112 N; MVC post-treatment: 322 ± 88 N; p = 0.015) after rehabilitation for most of the patients and fatigue did not change. These results suggest that higher force exertion was performed after rehabilitation, with the same level of fatigue (fatigued muscles pre-treatment: 1.40 ± 1.70; fatigued muscles post-treatment: 1.15 ± 1.59; p = 0.175) after. Results are discussed addressing the potential of multifactorial instrumental assessments for describing patients’ status and provide data for clinical decision making.

A high power setup for multichannel time-domain (TD) functional near infrared spectroscopy (fNIRS) measurements with high efficiency detection system was developed. It was fully characterized based on international performance assessment protocols for diffuse optics instruments, showing an improvement of the signal-to-noise ratio (SNR) with respect to previous analogue devices, and allowing acquisition of signals with sampling rate up to 20 Hz and source-detector distance up to 5 cm. A resting-state measurement on the motor cortex of a healthy volunteer was performed with an acquisition rate of 20 Hz at a 4 cm source-detector distance. The power spectrum for the cortical oxy- and deoxyhemoglobin is also provided.

The interest for Fused Deposition Modelling (FDM) in the field of Diffuse Optics (DO) is rapidly increasing. The most widespread FDM materials are polylactic acid (PLA) and acrylonitrile butadiene styrene (ABS), thanks to their low cost and easiness-to-print. This is why, in this study, 3D printed samples of PLA and ABS materials were optically characterized in the range from the UV up to the IR wavelengths, in order to test their possible employment for probe construction in DO applications. To this purpose, measurements with Near Infrared Spectroscopy and Diffuse Correlation Spectroscopy techniques were considered. The results obtained show how the material employed for probe construction can negatively affect the quality of DO measurements.

Biomarkers of microcirculation dysfunction may help in the study of cerebral small vessel disease (CSVD). Time-Domain Near-Infrared spectroscopy (TD-NIRS), estimating the oxygenation of microcirculation of cerebral outer layers, might indirectly correlate with CSVD. We retrospectively evaluated TD-NIRS data from healthy subjects with age ≥ 55 years; no history of brain disease; normal neurological examination; absence of stenosis > 50% of extra/intra-cranial arteries; incidental finding of asymptomatic CSVD at brain magnetic resonance imaging (MRI). According to Fazekas scale, subjects were classified by presence of white matter hyperintensities in periventricular region (pvWMHs), deep white matter region (dWMHs), or both (d+pvWMHs). We compared the concentration of hemoglobin species and tissue oxygen saturation (StO2) among these groups. The study included 20 subjects, median age 67.5 (IQR 61–78) years old (6 without WMHs, 5 with pvWMHs, 9 with d+pvWMHs). Subjects with d+pvWMHs had significantly lower StO2 compared to subjects without WMHs (p = 0.022) or with pvWMHs (p = 0.004). StO2 < 56.7% indicated the presence of d+pvWMHs with 91% sensitivity and 67% specificity [AUC 91% (CI 95% 78–100%)]. In this preliminary study, cerebral TD-NIRS detected significantly lower StO2 in subjects with radiological signs of asymptomatic CSVD. Further studies are needed to evaluate if StO2 might represent a marker of asymptomatic CSVD.

This work reviews physical concepts, technologies and applications of time-domain diffuse optics based on time-gated single-photon detection. This particular photon detection strategy is of the utmost importance in the diffuse optics field as it unleashes the full power of the time-domain approach by maximizing performances in terms of contrast produced by a localized perturbation inside the scattering medium, signal-to-noise ratio, measurement time and dynamic range, penetration depth and spatial resolution. The review covers 15 years of theoretical studies, technological progresses, proof of concepts and design of laboratory systems based on time-gated single-photon detection with also few hints on other fields where the time-gated detection strategy produced and will produce further impact.

In this review, we present an overview of the applications and computed parameters of electromyography (EMG) and near-infrared spectroscopy (NIRS) methods on patients in clinical practice. The eligible studies were those where both techniques were combined in order to assess muscle characteristics from the electrical and hemodynamic points of view. With this aim, a comprehensive screening of the literature based on related keywords in the most-used scientific data bases allowed us to identify 17 papers which met the research criteria. We also present a brief overview of the devices designed specifically for muscular applications with EMG and NIRS sensors (a total of eight papers). A critical analysis of the results of the review suggests that the combined use of EMG and NIRS on muscle has been only partially exploited for assessment and evaluation in clinical practice and, thus, this field shows promises for future developments.

In this paper, a time-domain fast gated near-infrared spectroscopy system is presented. The system is composed of a fiber-based laser providing two pulsed sources and two fast gated detectors. The system is characterized on phantoms and was tested in vivo, showing how the gating approach can improve the contrast and contrast-to-noise-ratio for detection of absorption perturbation inside a diffusive medium, regardless of source-detector separation.

Measurement of muscle oxidative metabolism is of interest for monitoring the training status in athletes and the rehabilitation process in patients. Time domain near infrared spectroscopy (TD NIRS) is an optical technique that allows the non-invasive measurement of the hemodynamic parameters in muscular tissue: concentrations of oxy- and deoxy-hemoglobin, total hemoglobin content, and tissue oxygen saturation. In this paper, we present a novel TD NIRS medical device for muscle oxidative metabolism. A custom-printed 3D probe, able to host optical elements for signal acquisition from muscle, was develop for TD NIRS in vivo measurements. The system was widely characterized on solid phantoms and during in vivo protocols on healthy subjects. In particular, we tested the in vivo repeatability of the measurements to quantify the error that we can have by repositioning the probe. Furthermore, we considered a series of acquisitions on different muscles that were not yet previously performed with this custom probe: a venous-arterial cuff occlusion of the arm muscle, a cycling exercise, and an isometric contraction of the vastus lateralis.

Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions.

Abstract Darknet forums dedicated to child sexual abuse material (CSAM) attract thousands of users interacting with each other through online communications. Given finite resources, law enforcement agencies seek ways to effectively prioritise their investigative efforts by identifying key-players that are central to the forum community. For the identification of such users, law enforcement agencies typically rely on the communication network that can be derived from messages posted on the public part of the forum. Many forums, however, also allow for private communications between members, raising the question to what extent relying on only a single mode of communication biases key-player identification. Using data on both public and private communications on two large-scale darknet CSAM forums, two communication networks are derived and their structures analysed. Measures of centrality robustness are applied to ascertain the level of bias introduced when determining key-players on only one of the available networks. Findings show only a minority of members to participate in forum communication, and limited overlap between participants active in public and private communications. Key-players emerging from combining the public and private communications resemble those from the public network only, suggesting that police prioritisation based on public postings only is still ‘on mark’. Members who are central to the private communications network may nevertheless be of special law enforcement interest.

To explore associations between histoplasmosis and race and ethnicity, socioeconomic status, and rurality, we conducted an in-depth analysis of social determinants of health and histoplasmosis in 8 US states. Using the Minority Health Social Vulnerability Index (MH SVI), we analyzed county-level histoplasmosis incidence (cases/100,000 population) from the 8 states by applying generalized linear mixed hurdle models. We found that histoplasmosis incidence was higher in counties with limited healthcare infrastructure and access as measured by the MH SVI and in more rural counties. Other social determinants of health measured by the MH SVI tool either were not significantly or were inconsistently associated with histoplasmosis incidence. Increased awareness of histoplasmosis, more accessible diagnostic tests, and investment in rural health services could address histoplasmosis-related health disparities.

Abstract Background Utilization by low acuity patients contributes to emergency department (ED) crowding. Both knowledge deficits about adequate care levels and access barriers in primary care are important promoters of such presentations. Concurrently, not having a general practitioner (GP) increases the likelihood of low-acuity ED utilization. This pilot study thus investigated feasibility, acceptance, and potential effects of an ED-delivered intervention for low-acuity patients with no regular primary care provider, consisting of an educational leaflet on acute care options and an optional GP appointment scheduling service. Methods Low-acuity ED consulters not attached to a GP were given an information leaflet about alternative care offers for acute health problems and offered optional personal appointment scheduling at a local GP practice. Patients were surveyed on demographics, medical characteristics, health care utilization, valuation of the intervention, and reasons for not being attached to a GP and visiting the ED. A follow-up survey was conducted after twelve months. Trends in health and health care utilization were evaluated. Results Between December 2020 and April 2022, n = 160 patients were enrolled, n = 114 were followed up. The study population was characterized by young age (mean 30.6 years) and predominantly good general health. Besides good health, personal mobility was a central reason for not being attached to a GP, but general preference for specialists and bad experiences with primary care were also mentioned. Most frequently stated motives for the ED consultation were subjective distress and anxiety, a belief in the superiority of the hospital, and access problems in primary care. The interventional offers were favorably valued, 52.5% (n = 84) accepted the GP appointment scheduling service offer. At follow-up, GP utilization had significantly increased, while there were no significant changes regarding utilization of other providers, including ED. An additional practice survey showed a 63.0% take-up rate for the appointment service. Conclusions With this pilot study, we were able to show that a personalized appointment scheduling service seems to be a promising approach to promote GP attachment and increase primary care utilization in patients without a regular GP in a highly urbanized setting. Further larger-scale studies are needed to investigate potential quantitative effects on ED visits. Trial Registration German Clinical Trials Register (DRKS00023480); date 2020/11/27.

Abstract The emergence of single nucleus RNA sequencing (snRNA-seq) offers to revolutionize the study of Alzheimer’s disease (AD). Integration with complementary multiomics data such as genetics, proteomics and clinical data provides powerful opportunities to link cell subpopulations and molecular networks with a broader disease-relevant context. We report snRNA-seq profiles from superior frontal gyrus samples from 101 well characterized subjects from the Banner Brain and Body Donation Program in combination with whole genome sequences. We report findings that link common AD risk variants with CR1 expression in oligodendrocytes as well as alterations in hematological parameters. We observed an AD-associated CD83(+) microglial subtype with unique molecular networks and which is associated with immunoglobulin IgG4 production in the transverse colon. Our major observations were replicated in two additional, independent snRNA-seq data sets. These findings illustrate the power of multi-tissue molecular profiling to contextualize snRNA-seq brain transcriptomics and reveal disease biology.

Social motivation, the human desire to engage with others, is likely to underlie higher levels of social cognition and the formation of interpersonal relationships. Yet, this topic has been understudied in adolescents despite the critical developmental and maturational changes that occur during this period and the relevance of social motivation to clinical and neurodevelopmental disorders. Using electroencephalography (EEG) and an implicit-association paradigm (Choose-A-Movie Task; Dubey et al., 2015), we examined how brain responses underlying socially motivated decisions informed future decisions in 54 youth (aged 10–14 years) and 50 young adults (aged 18–33 years). As the first study to use this task during EEG recording, we implemented time-frequency analyses and a trial-by-trial dynamic statistical approach. Results suggested that both age groups preferred low-effort choices and increasingly preferred nonsocial choices over time. P3 amplitude also increased over time and was sensitive to effortful decisions, particularly for adults, but not social content. Both groups showed larger leftward frontal alpha asymmetry (FAA) during nonsocial feedback, and FAA predicted future decisions differently for adults than youth. The current study highlights FAA and trial-by-trial analyses as useful tools in understanding the neural mechanisms underlying socially motivated decisions, which differ across development, time, and individuals.

Introduction Birth cohorts are valuable resources for studying early life, the determinants of health, disease, and development. They are essential for studying life course. Dynamic longitudinal electronic cohorts use routinely collected data, are live, and can reduce selection bias specifically associated with direct recruitment in traditional birth cohorts. However, they are limited to health and administrative data and may lack contextual information. The MIREDA (Mother and Infant Research Electronic Data Analysis) partnership creates a UK-wide birth cohort by aligning existing electronic birth cohorts to have the same structure, content, and vocabularies, enabling UK-wide federated analyses. Objectives 1) Create a core dynamic, live UK-wide electronic birth cohort with approximately 500,000 new births per year using a common data model (CDM). 2) Provide data linkage and automation for long-term follow up of births from the Clinical Practice Research Datalink (CPRD), MuM-PreDiCT and the `Born in' initiatives of Bradford, Wales, Scotland, and South London for comparable analyses. Methods We will establish core data content and collate linkable data. A suite of extraction, transformation, and load (ETL) tools will be used to transform data for each birth cohort into the CDM. Transformed datasets will remain within each cohort's trusted research environment (TRE). Metadata will be uploaded for the public to the Health Data Research (HDRUK) Innovation Gateway. We will develop a single online data access request for researchers. A cohort profile will be developed for researchers to reference the resource. Ethics Each cohort has approval from their TRE through compliance with their project application processes and information governance. Dissemination We will engage with researchers in the field to promote our resource through partnership networking, publication, research collaborations, conferences, social media, and marketing communications strategies.

Background Physician-assisted suicide (PAS) is typically associated with serious physical illnesses that are prevalent in palliative care. However, individuals with mental illnesses may also experience such severity that life becomes intolerable. In February 2020, the previous German law prohibiting PAS was repealed. Patients with severe mental illnesses are increasingly likely to approach physicians with requests for PAS. Aims To explore the ethical and moral perspectives of medical students and physicians when making individual decisions regarding PAS. Method An anonymised digital survey was conducted among medical students and physicians in Germany. Participants were presented with a case vignette of a chronically depressed patient requesting PAS. Participants decided on PAS provision and assessed theoretical arguments. We employed generalised ordinal regression and qualitative analysis for data interpretation. Results A total of N = 1478 participants completed the survey. Of these, n = 470 (32%) stated that they would refuse the request, whereas n = 582 (39%) would probably refuse, n = 375 (25%) would probably agree and n = 57 (4%) would definitely agree. Patient-centred arguments such as the right to self-determination increased the likelihood of consent. Concerns that PAS for chronically depressed patients might erode trust in the medical profession resulted in a decreased willingness to provide PAS. Conclusions Participants displayed relatively low willingness to consider PAS in the case of a chronically depressed patient. This study highlights the substantial influence of theoretical medical-ethical arguments and the broader public discourse, underscoring the necessity of an ethical discussion on PAS for mental illnesses.

Abstract Chronic imbalance is a frequent and limiting symptom of patients with chronic unilateral and bilateral vestibulopathy. A full-body kinematic analysis of the movement of patients with vestibulopathy would provide a better understanding of the impact of the pathology on dynamic tasks such as walking. Therefore, this study aimed to investigate the global body movement during walking, its variability (assessed with the GaitSD), and the strategies to stabilise the head (assessed with the head Anchoring Index). The full-body motion capture data of 10 patients with bilateral vestibulopathy (BV), 10 patients with unilateral vestibulopathy (UV), and 10 healthy subjects (HS) walking at several speeds (slow, comfortable, and fast) were analysed in this prospective cohort study. We observed only a few significant differences between groups in parts of the gait cycle (shoulder abduction–adduction, pelvis rotation, and hip flexion–extension) during the analysis of kinematic curves. Only BV patients had significantly higher gait variability (GaitSD) for all three walking speeds. Head stabilisation strategies depended on the plan of motion and walking speed condition, but BV and UV patients tended to stabilise their head in relation to the trunk and HS tended to stabilise their head in space. These results suggest that GaitSD could be a relevant biomarker of chronic instability in BV and that the head Anchoring Index tends to confirm clinical observations of abnormal head-trunk dynamics in patients with vestibulopathy while walking.

Abstract Background Emergency departments (ED) worldwide have to cope with rising patient numbers. Low-acuity consulters who could receive a more suitable treatment in primary care (PC) increase caseloads, and lack of PC attachment has been discussed as a determinant. This qualitative study explores factors that contribute to non-utilization of general practitioner (GP) care among patients with no current attachment to a GP. Method Qualitative semi-structured telephone interviews were conducted with 32 low-acuity ED consulters with no self-reported attachment to a GP. Participants were recruited from three EDs in the city center of Berlin, Germany. Data were analyzed by qualitative content analysis. Results Interviewed patients reported heterogeneous factors contributing to their PC utilization behavior and underlying views and experiences. Participants most prominently voiced a rare need for medical services, a distinct mobility behavior, and a lack of knowledge about the role of a GP and health care options. Views about and experiences with GP care that contribute to non-utilization were predominantly related to little confidence in GP care, preference for directly consulting medical specialists, and negative experiences with GP care in the past. Contrasting their reported utilization behavior, many interviewees still recognized the advantages of GP care continuity. Conclusion Understanding reasons of low-acuity ED patients for GP non-utilization can play an important role in the design and implementation of patient-centered care interventions for PC integration. Increasing GP utilization, continuity of care and health literacy might have positive effects on patient decision-making in acute situations and in turn decrease ED burden. Trial registration German Clinical Trials Register: DRKS00023480; date: 2020/11/27.

Background Psoriasis is a chronic immune-mediated systemic disease whose treatment has been revolutionized due to the induction of monoclonal antibody-based biologics. However, access to these drugs has been limited due to their high cost. Biosimilars utilize reverse engineering to create a highly similar product to an originator drug following patent expiration and provide an avenue to reduce costs of biologic treatment. This review seeks to synthesize current knowledge about the development, efficacy, and established benefits of biosimilars, including cost savings and increased access to biologic medicines.Results In 2023, the Veterans Health Administration (VA) generated a cost avoidance of over 67 million dollars through use of 6 currently adopted biosimilars across all indications. There is an opportunity for further cost avoidance, with the pre-set percent discount of statutory contract prices necessary for the adoption of future biosimilars, including adalimumab and etanercept, set at over 50%.Conclusions Biosimilars appear to offer an overall effective, safe, and well-tolerated treatment method for patients with psoriasis and are already providing substantial cost savings within the VA. Additional education is needed to address sources of ambivalence for both patients and providers to assist in further uptake of biosimilars for the treatment of psoriasis.

The prevalence of poor mental health among younger and older generations is rising. Urban greenspaces (UGS) can provide well-being benefits and are used by all ages, so it is important that these spaces provide benefits across the life course. So far, studies tend to focus on one age group and lack focus on properties of these spaces which shape well-being across generations. Our aim was to explore what properties of UGS can shape well-being across age groups and to what extent are UGS for social interactions across age groups. Qualitative semi-structured interviews were conducted online with 20 participants in four age groups: adolescents, young adults, adults, and older adults. Interviewees were asked about visits to UGS, preferences for multi-sensory components, and how spaces shape their well-being. Using thematic analysis, four themes were identified which were common across all age groups: UGS can provide a sense of escape; there are practical needs surrounding access and contact with UGS; being a space to share with other users; and the importance of seasonal multi-sensory components. Whilst findings showed that there are properties of UGS which are valued across multiple ages, differences were also revealed regarding interactions across ages. By researching qualitatively across ages, the complex similarities and differences between ages can be understood. Future research should also explore interactions between age groups as well as the views of non-users of UGS and their reasons for not visiting UGS.

Aims Neurodevelopmental disorders (NDDs), such as dyslexia, dyspraxia, and dyscalculia affect cognitive function and therefore share symptomology with neurodegenerative disorders, such as Alzheimer's disease, vascular dementia, and frontotemporal lobe dementia. The primary aim of this narrative systematic review is to ascertain if there is an association between NDDs and neurodegenerative disorders. Secondary aims are what the prevalence of NDDs within a dementia population is and what effect these early life learning disorders have on patients as they get older. It was hypothesised that NDDs would overestimate the severity of cognitive impairment, thereby increasing the severity of dementia staging, and impacting patient care. Methods Using a Population, Exposure, Comparator, Outcome, Setting, and Study design (PECOS) framework, keywords of “dementia”, “dyslexia”, “Dyspraxia/clumsy child syndrome/developmental apraxia/motor learning difficulty/disorder of attention and motor perception” and “dyscalculia/mathematical learning disability” were searched for on 4 databases (SCOPUS, OVID, Cochrane Central Register of Controlled Trials and Web of Science) from January 1, 1960 – June 10, 2022. Studies were included if they discussed both neurodegenerative and neurodevelopmental disorders or compared an intervention typically used in one disorder on the other (e.g., dementia intervention being used on neurodevelopmental disorder). Studies were excluded from grey literature articles, or if they only discussed a neurodevelopmental or neurodegenerative disorder without reference to the other, or if it included acquired, rather than neurodevelopmental dyslexia, dyscalculia, or dyspraxia. Results A total of 8 studies were included for narrative synthesis. The main finding was an association between dyslexia and both Alzheimer's disease and frontotemporal dementia. Many studies suggested this was due to a genetic phenotype that caused a vulnerability in the language regions of patients’ cortices. There was also evidence of structural changes associated with NDDs and increased levels of grey and white matter atrophy in dementia subtypes, particularly in the language areas of the brain. Conclusion Due to screening and consequently formal diagnosis of neurodevelopmental disorders only recently coming into education systems, many adults currently attending memory clinics did not have a formal diagnosis. As there was limited research on dyspraxia and dementia, partly due to limited research into dyspraxia itself and without a standardized diagnostic tool for adolescents and adults, further research is needed in this area. The hypothesis of NDDs increasing the severity of dementia staging was also not supported by the literature results, and on the contrary, some studies suggested greater global preservation of cognitive function in patients with NDDs and dementia.

Background: While previous literature has shown that resident involvement increases operative time, the influence of resident involvement on operative time is generally not considered in current methods of case time predictions or operating room planning. Furthermore, evidence of prolonged case times based on the level of the assisting resident is yet scarce. We hypothesized that operative time would increase with the post-graduate year of assisting residents as they gain more autonomy in the operating room. Study design: This was an observational cohort study in which we retrospectively analyzed 802 laparoscopic cholecystectomy cases performed in a single academic institution between May 2014 and December 2020. Only cases in which a Post Graduate Year 1 to 5 (PGY) resident was assisting were included. Results: PGY1–4 residents had statistically significant positive time coefficient results in all linear regression models, except PGY2s in urgent cases. PGY-2 residents had the longest overall average case time of 98 min. Emergent cases were more likely to have prolonged case times. Conclusions: The increased average case time associated with PGY-2 residents is likely due to a new level of increased autonomy in the operating room (OR) during this year of training. The linear regression results indicated PGY1–4 residents were more likely to have longer laparoscopic cholecystectomy operative times than the PGY5 residents, except PGY2s in urgent cases. This may reflect the accumulation of surgical skills at the PGY5 level. Resident involvement should be considered in the prediction of operative time in an academic setting.

Abstract The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has provided unprecedented insight into mutations enabling immune escape. Understanding how these mutations affect the dynamics of antibody-antigen interactions is crucial to the development of broadly protective antibodies and vaccines. Here we report the characterization of a potent neutralizing antibody (N3-1) identified from a COVID-19 patient during the first disease wave. Cryogenic electron microscopy revealed a quaternary binding mode that enables direct interactions with all three receptor-binding domains of the spike protein trimer, resulting in extraordinary avidity and potent neutralization of all major variants of concern until the emergence of Omicron. Structure-based rational design of N3-1 mutants improved binding to all Omicron variants but only partially restored neutralization of the conformationally distinct Omicron BA.1. This study provides new insights into immune evasion through changes in spike protein dynamics and highlights considerations for future conformationally biased multivalent vaccine designs.

Synaptic adhesion molecules (SAMs) are evolutionarily conserved proteins that play an important role in the form and function of neuronal synapses. Teneurins (Tenms) and latrophilins (Lphns) are well-known cell adhesion molecules that form a transsynaptic complex. Recent studies suggest that Tenm3 and Lphn2 (gene symbol Adgrl2) are involved in hippocampal circuit assembly via their topographical expression. However, it is not known whether other teneurins and latrophilins display similar topographically restricted expression patterns during embryonic and postnatal development. Here, we reveal the cartography of all teneurin (Tenm1-4) and latrophilin (Lphn1-3 [Adgrl1-3]) paralog expression in the mouse hippocampus across prenatal and postnatal development as monitored by large-scale single-molecule RNA in situ hybridization mapping. Our results identify a striking heterogeneity in teneurin and latrophilin expression along the spatiotemporal axis of the hippocampus. Tenm2 and Tenm4 expression levels peak at the neonatal stage when compared to Tenm1 and Tenm3, while Tenm1 expression is restricted to the postnatal pyramidal cell layer. Tenm4 expression in the dentate gyrus (DG) exhibits an opposing topographical expression pattern in the embryonic and neonatal hippocampus. Our findings were validated by analyses of multiple RNA-seq datasets at bulk, single-cell, and spatial levels. Thus, our study presents a comprehensive spatiotemporal map of Tenm and Lphn expression in the hippocampus, showcasing their diverse expression patterns across developmental stages in distinct spatial axes.