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Cascade genetic testing and surveillance reduce morbidity and mortality in Lynch syndrome. However, barriers to conveying information about genetic disorders within families result in low uptake of genetic testing. Provider-mediated interventions may increase uptake but raise legal and ethical concerns. We describe 30 years of national experience with cascade genetic testing combining family- and provider-mediated contact in Lynch syndrome families in the Danish Hereditary Non-Polyposis Colorectal Cancer (HNPCC) Register. We aimed to estimate the added value of information letters to family members in Lynch syndrome families (provider-mediated contact) compared to family members not receiving such letters and thus relying on family-mediated contact. National clinical practice for cascade genetic testing, encompassing infrastructure, legislation, acceptance, and management of the information letters, is also discussed. Cascade genetic testing resulted in 7.3 additional tests per family. Uptake of genetic testing was 54.4% after family-mediated and 64.9% after provider-mediated contact, corresponding to an odds ratio of 1.8 (p < 0.001). The uptake of genetic testing was highest in the first year after diagnosis of Lynch syndrome in the family, with 72.5% tested after provider-mediated contact. In conclusion, the Danish model combining family- and provider-mediated contact can increase the effect of cascade genetic testing.

Immune checkpoint inhibitors (ICI) targeting programmed death 1 (PD-1), its ligand (PD-L1), or cytotoxic T-lymphocyte antigen 4 (CTLA-4) have shown promising results against multiple cancers, where they reactivate exhausted T cells primed to eliminate tumor cells. ICI therapies have been particularly successful in hypermutated cancers infiltrated with lymphocytes. However, resistance may appear in tumors evading the immune system through alternative mechanisms than the PD-1/PD-L1 or CTLA-4 pathways. A systematic pan-cancer literature search was conducted to examine the association between alternative immune evasion mechanisms via the antigen presentation machinery (APM) and resistance towards ICI treatments targeting PD-1 (pembrolizumab and nivolumab), PD-L1 (durvalumab, avelumab, and atezolizumab), and CTLA-4 (ipilimumab). The APM proteins included the human leucocyte antigen (HLA) class I, its subunit beta-2 microglobulin (B2M), the transporter associated with antigen processing (TAP) 1, TAP2, and the NOD-like receptor family CARD domain containing 5 (NLRC5). In total, 18 cohort studies (including 21 original study cohorts) containing 966 eligible patients and 9 case studies including 12 patients were reviewed. Defects in the APM significantly predicted poor clinical benefit with an odds ratio (OR) of 0.39 (95% CI 0.24–0.63, p < 0.001). The effect was non-significant, when considering complete and partial responses only (OR = 0.52, 95% CI 0.18–1.47, p = 0.216). In summary, the APM contains important targets for tumorigenic alterations which may explain insensitivity towards ICI therapy.

Cultured meat is an emerging alternative food technology which aims to deliver a more ethical, sustainable, and healthy muscle-tissue-derived food item compared to conventional meat. As start-up companies are rapidly forming and accelerating this technology, many aspects of this multi-faceted science have still not been investigated in academia. In this study, we investigated if bovine satellite cells with the ability to proliferate and undergo myogenic differentiation could be isolated after extended tissue storage, for the purpose of increasing the practicality for cultured meat production. Proliferation of bovine satellite cells isolated on the day of arrival or after 2 and 5 days of tissue storage were analyzed by metabolic and DNA-based assays, while their myogenic characteristics were investigated using RT-qPCR and immunofluorescence. Extended tissue storage up to 5 days did not negatively affect proliferation nor the ability to undergo fusion and create myosin heavy chain-positive myotubes. The expression patterns of myogenic and muscle-specific genes were also not affected after tissue storage. In fact, the data indicated a positive trend in terms of myogenic potential after tissue storage, although it was non-significant. These results suggest that the timeframe of which viable myogenic satellite cells can be isolated and used for cultured meat production can be greatly extended by proper tissue storage.

Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.

Previously, bite force, occlusal contact and pain were investigated in orthodontic patients with moderate-to-severe malocclusion, but not in patients with minor malocclusion. The purpose of this study was to investigate changes in bite force, teeth in occlusal contact and pain in orthodontic patients with minor crowding before orthodontic treatment (T0), after bonding (T1), during treatment (T2), post-treatment (T3) and during retention (T4). In total, 27 patients (21 females, 6 males, median age 15.3 years) with neutral occlusion and normal craniofacial morphology were treated with non-extractions and fixed appliances. Differences in the registered data were analysed by a mixed linear model with repeated measures. Bite force and teeth in occlusal contact significantly decreased between T0 and T1 (p < 0.0001, respectively) and between T0 and T2 (p < 0.01, respectively). Bite force and teeth in occlusal contact significantly increased between T1 and T4 (p < 0.05, p < 0.0001, p < 0.001, respectively) and between T2 and T4 (p < 0.05, p < 0.0001, p < 0.01, respectively). No significant difference in pain was found. The results indicate that bite force and teeth in occlusal contact significantly decreased during treatment and reached baseline level at retention. The findings may prove valuable for informing orthodontic patients with minor malocclusion.

Mechanical weeding is an important tool in organic farming. However, the use of mechanical weeding in conventional agriculture is increasing, due to public demands to lower the use of pesticides and an increased number of pesticide-resistant weeds. Ground nesting birds are highly susceptible to farming operations, like mechanical weeding, which may destroy the nests and reduce the survival of chicks and incubating females. This problem has limited focus within agricultural engineering. However, when the number of machines increases, destruction of nests will have an impact on various species. It is therefore necessary to explore and develop new technology in order to avoid these negative ethical consequences. This paper presents a vision-based approach to automated ground nest detection. The algorithm is based on the fusion of visual saliency, which mimics human attention, and incremental background modeling, which enables foreground detection with moving cameras. The algorithm achieves a good detection rate, as it detects 28 of 30 nests at an average distance of 3.8 m, with a true positive rate of 0.75.

During the last decades, high-efficiency farming equipment has been developed in the agricultural sector. This has also included efficiency improvement of moving techniques, which include increased working speeds and widths. Therefore, the risk of wild animals being accidentally injured or killed during routine farming operations has increased dramatically over the years. In particular, the nests of ground nesting bird species like grey partridge (Perdix perdix) or pheasant (Phasianus colchicus) are vulnerable to farming operations in their breeding habitat, whereas in mammals, the natural instinct of e.g., leverets of brown hare (Lepus europaeus) and fawns of roe deer (Capreolus capreolus) to lay low and still in the vegetation to avoid predators increase their risk of being killed or injured in farming operations. Various methods and approaches have been used to reduce wildlife mortality resulting from farming operations. However, since wildlife-friendly farming often results in lower efficiency, attempts have been made to develop automatic systems capable of detecting wild animals in the crop. Here we assessed the suitability of thermal imaging in combination with digital image processing to automatically detect a chicken (Gallus domesticus) and a rabbit (Oryctolagus cuniculus) in a grassland habitat. Throughout the different test scenarios, our study animals were detected with a high precision, although the most dense grass cover reduced the detection rate. We conclude that thermal imaging and digital imaging processing may be an important tool for the improvement of wildlife-friendly farming practices in the future.

Since human-wildlife conflicts are increasing, the development of cost-effective methods for reducing damage or conflict levels is important in wildlife management. A wide range of devices to detect and deter animals causing conflict are used for this purpose, although their effectiveness is often highly variable, due to habituation to disruptive or disturbing stimuli. Automated recognition of behaviours could form a critical component of a system capable of altering the disruptive stimuli to avoid this. In this paper we present a novel method to automatically recognise goose behaviour based on vocalisations from flocks of free-living barnacle geese (Branta leucopsis). The geese were observed and recorded in a natural environment, using a shielded shotgun microphone. The classification used Support Vector Machines (SVMs), which had been trained with labeled data. Greenwood Function Cepstral Coefficients (GFCC) were used as features for the pattern recognition algorithm, as they can be adjusted to the hearing capabilities of different species. Three behaviours are classified based in this approach, and the method achieves a good recognition of foraging behaviour (86–97% sensitivity, 89–98% precision) and a reasonable recognition of flushing (79–86%, 66–80%) and landing behaviour(73–91%, 79–92%). The Support Vector Machine has proven to be a robust classifier for this kind of classification, as generality and non-linearcapabilities are important. We conclude that vocalisations can be used to automatically detect behaviour of conflict wildlife species, and as such, may be used as an integrated part of awildlife management system.