Identification of Genomic Regions Associated with Phenotypic Variation between Dog Breeds using Selection Mapping

Peer reviewe

Evaluation of in-house, haptic assisted surgical planning for virtual reduction of complex mandibular fractures

The management of complex mandible fractures, i.e severely comminuted or fractures of edentulous/atrophic mandibles, can be challenging. This is due to the three-dimensional loss of bone, which limits the possibility for accurate anatomic reduction. Virtual surgery planning (VSP) can provide improved accuracy and shorter operating times, but is often not employed for trauma cases because of time constraints and complex user interfaces limited to two-dimensional interaction with three-dimensional data. In this study, we evaluate the accuracy, precision, and time efficiency of the Haptic Assisted Surgery Planning system (HASP), an in-house VSP system that supports stereo graphics, six degrees-of-freedom input and haptics, to improve the surgical planning. Three operators performed planning in HASP on Computed Tomography (CT) and Come Beam Computed Tomography (CBCT) images of a plastic skull model and on twelve retrospective cases with complex mandible fractures. The result shows an accuracy and reproducibility of less than 2mm when using HASP, with an average planning time of 15 minutes, including time for segmentation in the software BoneSplit. This study presents an in-house haptic assisted planning tool for cranio-maxillofacial surgery with high usability that can be used for preoperative planning and evaluation of complex mandible fractures.

Risk factors for severe COVID-19 in the young—before and after ICU admission

Abstract Background Factors associated with severe COVID-19 and death among young adults are not fully understood, including differences between the sexes. The aim of this study was to identify factors associated with severe COVID-19 requiring intensive care and 90-day mortality among women and men below 50 years of age. Methods A register-based study using data from mandatory national registers, where patients with severe COVID-19 admitted to the ICU with need for mechanical ventilation (cases) between March 2020 and June 2021 were matched regarding age, sex, and district of residence with 10 population-based controls. Both the study population and the controls were divided into groups based on age (< 50 years, 50–64, and ≥ 65 years) and sex. Multivariate logistic regression models including socioeconomic factors were used to calculate odds ratios (OR) with 95% confidence intervals (CIs) for associations between severe COVID-19 in the population to compare the magnitude of the risk associations for co-morbidities in the different age categories, and subsequently factors associated with 90-day mortality among patients admitted to ICU. Results In total, 4921 cases and 49,210 controls (median age 63 years, 71% men) were included. The co-morbidities with the strongest associations with severe COVID-19 for the young population compared to older patients were chronic kidney disease (OR 6.80 [3.61–12.83]), type 2 diabetes (OR 6.31 [4.48–8.88]), hypertension (OR 5.09 [3.79–6.84]), rheumatoid arthritis (OR 4.76 [2.29–9.89]), obesity (OR 3.76 [2.88–4.92]), heart failure (OR 3.06 [1.36–6.89]), and asthma (OR 3.04 [2.22–4.16]). When comparing women vs. men < 50 years of age, stronger associations were seen for women regarding type 2 diabetes (OR 11.25 [6.00–21.08] vs OR 4.97 [3.25–7.60]) and hypertension (OR 8.76 [5.10–15.01] vs OR 4.09 [2.86–5.86]). The factors associated with 90-day mortality in the young were previous venous thromboembolism (OR 5.50 [2.13–14.22]), chronic kidney disease (OR 4.40 [1.64–11.78]) and type 2 diabetes (OR 2.71 [1.39–5.29]). These associations with 90-day mortality were foremost driven by the female population. Conclusion Chronic kidney failure, type 2 diabetes, hypertension, rheumatoid arthritis, obesity, heart failure, and asthma were the strongest risk factors associated with severe COVID-19 requiring ICU-care in individuals < 50 years compared to the older population. However, after ICU admission, previous thromboembolism, chronic kidney failure, and type 2 diabetes were associated with increased 90-day mortality. The risk associations for co-morbidities were generally stronger among younger individuals compared to older and in women compared to men

Altered relationship between subjective perception and central representation of touch hedonics in adolescents with autism-spectrum disorder

An impairment of social communication is a core symptom of autism-spectrum disorder (ASD). Affective touch is an important means of social interaction, and C-Tactile (CT) afferents are thought to play a key role in the peripheral detection and encoding of these stimuli. Exploring the neural and behavioral mechanisms for processing CT-optimal touch (similar to 3 cm/s) may therefore provide useful insights into the pathophysiology of ASD. We examined the relationship between touch hedonics (i.e. the subjective pleasantness with which affective touch stimuli are perceived) and neural processing in the posterior superior temporal sulcus (pSTS). This region is less activated to affective touch in individuals with ASD, and, in typically developing individuals (TD), is correlated positively with touch pleasantness. TD and ASD participants received brushing stimuli at CT-optimal, and CT-non-optimal speeds during fMRI. Touch pleasantness and intensity ratings were collected, and affective touch awareness, a measure of general touch hedonics was calculated. As expected, slow touch was perceived as more pleasant and less intense than fast touch in both groups, whereas affective touch awareness was moderately higher in TD compared to ASD. There was a strong, positive correlation between right pSTS activation and affective touch awareness in TD, but not in ASD. Our findings suggest that altered neural coupling between right pSTS and touch hedonics in ASD may be associated with social touch avoidance in ASD.Funding Agencies|Swedish Research CouncilSwedish Research CouncilEuropean Commission [538-2013-7434]; ALF Grants, Region ostergotland [LIO-535931, LIO-520131]</p

Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease

BackgroundAutoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology. MethodsTo understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls. ResultsWe identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 x 10(-15), MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex. ConclusionWhilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment