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Multicenter study on tumor budding in lung squamous cell carcinoma: comparison between biopsy and resection with interobserver variability assessment.
No full textGrading lung squamous cell carcinoma (LUSC) is controversial and not universally accepted. The histomorphological feature of tumor budding (TB) is an established independent prognostic factor in colorectal cancer and its importance is growing in other solid cancers, making it a candidate for inclusion in tumor grading schemes. We aimed to compare TB between preoperative biopsies and resection specimens in pulmonary squamous cell carcinoma and assess interobserver variability. A retrospective cohort of 249 consecutive patients primarily resected with LUSC in Bern (2000-2013, N=136) and Lausanne (2005-2020 N=113) with available preoperative biopsies was analyzed for TB and additional histomorphological parameters such as spread through airspaces (STAS) and desmoplasia by two expert pathologists. Results were correlated with clinicopathological parameters and survival. In resection specimens, peritumoral budding (PTB) score was low (0-4 buds/0.785 mm2) in 47.6%, intermediate (5-9 buds/0.785 mm2) in 27.4 %, and high (≥10 buds/0.785 mm2) in 25 % of cases (median bud count = 5, IQR = 0 - 26). Both the absolute number of buds and TB score were similar when comparing tumor edge and intratumoral zone (p=0.192) but significantly different from the score obtained in the biopsy (p<0.001). Interobserver variability was moderate, regardless of score location (Cohen's kappa 0.59). The discrepant cases were reassessed, and consensus was reached in all cases with identification of causes of discordance. TB score was significantly associated with stage (p=0.002), presence of lymph node (p=0.033) and distant metastases (p=0.020), without significant correlation with overall survival, tumor size or pleural invasion. Desmoplasia was significantly associated with higher PTB (p<0.001). STAS was present in 34% and associated with lower PTB (p<0.001). To conclude, despite confirming TB as a reproductible factor in LUSC we disclose areas of scoring ambiguity. Preoperative biopsy evaluation was insufficient in establishing the final tumor budding score of the resected tumor
The hidden value of MRI: modifying treatment decisions in C-spine injuries.
Get PDFBACKGROUND DATA
Computed Tomography (CT) is the gold standard for cervical spine (c-spine) evaluation. Magnetic resonance imaging (MRI) emerges due to its increasing availability and the lack of radiation exposure. However, MRI is costly and time-consuming, questioning its role in the emergency department (ED). This study investigates the added the value of an additional MRI for patients presenting with a c-spine injury in the ED.
METHODS
We conducted a retrospective monocenter cohort study that included all patients with neck trauma presenting in the ED, who received imaging based on the NEXUS criteria. Spine surgeons performed a full-case review to classify each case into "c-spine injured" and "c-spine uninjured". Injuries were classified according to the AO Spine classification. We assessed patients with a c-spine injury detected by CT, who received a subsequent MRI. In this subset, injuries were classified separately in both imaging modalities. We monitored the treatment changes after the additional MRI to evaluate characteristics of this cohort and the impact of the AO Spine Neurology/Modifier modifiers.
RESULTS
We identified 4496 subjects, 2321 were eligible for inclusion and 186 were diagnosed with c-spine injuries in the retrospective case review. Fifty-six patients with a c-spine injury initially identified through CT received an additional MRI. The additional MRI significantly extended (geometric mean ratio 1.32, p < 0.001) the duration of the patients' stay in the ED. Of this cohort, 25% had a change in treatment strategy and among the patients with neurological symptoms (AON ≥ 1), 45.8% experienced a change in treatment. Patients that were N-positive, had a 12.4 (95% CI 2.7-90.7, p < 0.01) times higher odds of a treatment change after an additional MRI than neurologically intact patients.
CONCLUSION AND RELEVANCE
Our study suggests that patients with a c-spine injury and neurological symptoms benefit from an additional MRI. In neurologically intact patients, an additional MRI retains value only when carefully evaluated on a case-by-case basis
TemBERTure: advancing protein thermostability prediction with deep learning and attention mechanisms.
Get PDFMOTIVATION
Understanding protein thermostability is essential for numerous biotechnological applications, but traditional experimental methods are time-consuming, expensive, and error-prone. Recently, deep learning (DL) techniques from natural language processing (NLP) was extended to the field of biology, since the primary sequence of proteins can be viewed as a string of amino acids that follow a physicochemical grammar.
RESULTS
In this study, we developed TemBERTure, a DL framework that predicts thermostability class and melting temperature from protein sequences. Our findings emphasize the importance of data diversity for training robust models, especially by including sequences from a wider range of organisms. Additionally, we suggest using attention scores from Deep Learning models to gain deeper insights into protein thermostability. Analyzing these scores in conjunction with the 3D protein structure can enhance understanding of the complex interactions among amino acid properties, their positioning, and the surrounding microenvironment. By addressing the limitations of current prediction methods and introducing new exploration avenues, this research paves the way for more accurate and informative protein thermostability predictions, ultimately accelerating advancements in protein engineering.
AVAILABILITY AND IMPLEMENTATION
TemBERTure model and the data are available at: https://github.com/ibmm-unibe-ch/TemBERTure
Modest forest and welfare gains from initiatives for reduced emissions from deforestation and forest degradation
Get PDFReduced emissions from deforestation and forest degradation (REDD+) projects and programmes promise to deliver performance-based, cost-effective climate change mitigation. Fifteen years after its conception, we analysed the rigorous counterfactual-based evidence for environmental and welfare effects from such national and subnational initiatives, along with a Theory of Change. Using machine-learning tools for literature review, we compared 32 quantitative studies including 26 primary forest-related and 12 socioeconomic effect sizes. Average environmental impacts were positively significant yet moderately sized, comparable to impacts from other conservation tools, and mostly impermanent over time. Socioeconomic impacts were welfare-neutral to slightly positive. Moderator analysis showed that environmental additionality was likely restricted by project proponents’ adverse spatial targeting of low-threat areas. Scarce funding flows from carbon markets and ill-enforced conditionality probably also limited impacts. Hence, important policy and implementation lessons emerge for boosting effectiveness in the current global transition towards larger-scale, jurisdictional action
Evaluating the Effectiveness of the Nudge Theory in Improving the Oral Self-Care of Schoolchildren with Refugee and Immigrant Backgrounds in Mashhad, Iran.
Get PDFNudge theory proposes using subtle interventions to encourage individuals to make better decisions. The aim of this study was to evaluate the effectiveness of the Nudge theory in plaque control and assess caries experience among third-grade primary schoolchildren with refugee and immigrant backgrounds in Mashhad, Iran. Moreover, Afghan and Iranian schoolchildren were compared to assess differences in oral health outcomes. A quasi-experimental field trial was conducted in three public primary schools, comprising 309 participants approximately 9 years old. Interventions were randomly assigned to three schools: School I Messages based on Social Norms (MSN), School II Messages based on Fear of Negative Outcome (MFNO), and School III control group (C). MSN and MFNO received customized motivational video clips at baseline, while C only received Oral hygiene instruction (OHI). All participants received OHI, a brush, and toothpaste. Baseline plaque index (PI) and caries experience in primary and permanent dentition (dmft/DMFT) were recorded. PI was reassessed at two weeks, two months, and six months post-intervention. All data were subjected to statistical analysis. The mean PI decreased significantly in all three groups at the two-week follow-up (p < 0.01). The PI improvements declined over a six-month follow-up period in all groups, and the mean PI difference after six months compared to the pre-intervention was significant only in MSN and MFNO (p < 0.01), while C reverted almost to the pre-study level. Schoolchildren with at least one filled tooth or Iranian nationality showed a greater PI reduction (p < 0.01, p = 0.05). The overall mean ± SD dmft and DMFT were 4.24 ± 2.11 and 1.70 ± 1.24, respectively. Among all the examined participants, 32 (10.40%) individuals were caries-free. The mean dmft was statistically significantly higher in Afghan children than in Iranians (p = 0.01). MSN was more effective on PI reduction in the short term, while MFNO was more long-lasting. Using the Nudge theory via visual aids was more effective in motivating children to perform better oral self-care than solely traditional OHI
Global net climate effects of anthropogenic reactive nitrogen.
Get PDFAnthropogenic activities have substantially enhanced the loadings of reactive nitrogen (Nr) in the Earth system since pre-industrial times1,2, contributing to widespread eutrophication and air pollution3-6. Increased Nr can also influence global climate through a variety of effects on atmospheric and land processes but the cumulative net climate effect is yet to be unravelled. Here we show that anthropogenic Nr causes a net negative direct radiative forcing of -0.34 [-0.20, -0.50] W m-2 in the year 2019 relative to the year 1850. This net cooling effect is the result of increased aerosol loading, reduced methane lifetime and increased terrestrial carbon sequestration associated with increases in anthropogenic Nr, which are not offset by the warming effects of enhanced atmospheric nitrous oxide and ozone. Future predictions using three representative scenarios show that this cooling effect may be weakened primarily as a result of reduced aerosol loading and increased lifetime of methane, whereas in particular N2O-induced warming will probably continue to increase under all scenarios. Our results indicate that future reductions in anthropogenic Nr to achieve environmental protection goals need to be accompanied by enhanced efforts to reduce anthropogenic greenhouse gas emissions to achieve climate change mitigation in line with the Paris Agreement
Seroprevalence of Toxoplasma gondii and Neospora spp. in horse population of Tehran, Iran.
Get PDFNeospora spp. and Toxoplasma gondii are two closely related protozoan parasites that are widely distributed throughout the world. Horses can act as intermediate hosts for both parasites and can acquire disease. Blood samples were taken from 487 clinically healthy horses from 17 different mechanized stables in Tehran, the capital of Iran, during September and November of 2022. IFAT and ELISA were employed to detect antibodies directed against Neospora spp. and T. gondii. The anti-N. caninum antibodies were detected in 52 of the horses (10.67%) based on IFAT and in 86 of the 487 horses (17.65%) based on the ELISA test. Also, antibodies against T. gondii were detected in 41 horses (8.42%) based on IFAT and in 63 of 487 horses (12.94%) based on the ELISA test. Also, in 6 of the horses (1.23%) based on IFAT and in 13 of the 487 horses (2.67%) based on the ELISA test, double positivity suggested co-infection with both parasites. Gender, age groups, and the presence of dogs for neosporosis, and age groups and the presence of cats for toxoplasmosis, could be considered factors having an influence on the seroprevalences (P < 0.05). The results proved the importance of the urgent implementation of stringent regulatory measures to prevent and control the spread of these parasites
Mental health and justice beyond borders: Global crises, sociopolitical determinants, and contemporary practices in forensic psychiatry
Get PDFIn an era marked by escalating international crises, environmental shifts, and sociopolitical volatilities, global mental health is facing profound challenges. With its distinctive position at the intersection between clinical and judicial domains, forensic psychiatry can be predisposed to the consequences of adverse external determinants and events. At present, geopolitical conflicts, rising insecurities, climate change, forced and voluntary migration, and regressive sociopolitical ideologies are all compounding role responsibilities, care models, and ethical expectations across forensic-psychiatric practice; in short, complex distal factors are increasingly informing domestic considerations. These far-reaching concerns indicate a need for adaptive and proactive responses, underpinned by cultural sensitivity, social justice, and respect for human rights. Through illustrative examples from different regions, this perspective paper calls for a greater recognition of the transnational dynamics that are affecting local contexts of practice. Equally, it outlines the importance of advocacy, interdisciplinary collaborations, and potential evolutions in training and ethical frameworks to address contemporary issues. By adopting these approaches, forensic psychiatrists can promote more just systems and equitable mental healthcare for patients amidst the uncertainties of an interconnected and rapidly transforming world
Histologic subtypes of non-muscle invasive bladder cancer.
Get PDFThe majority of bladder cancers (BCs) are non-muscle invasive BCs (NMIBCs) and show the morphology of a conventional urothelial carcinoma (UC). Aberrant morphology is rare but can be observed. The classification and characterization of histologic subtypes (HS) in UC in BC have mainly been described in muscle invasive bladder cancer (MIBC). However, the currently used classification is applied for invasive urothelial neoplasm and therefore, also valid for a subset of NMIBC. The standard transurethral diagnostic work-up misses the presence of HS in NMIBC in a considerable percentage of patients and the real prevalence is not known. HS in NMIBC are associated with an aggressive phenotype. Consequently, clinical guidelines categorize HS of NMIBC as "(very) high-risk" tumors and recommend offering radical cystectomy to these patients. Alternative strategies for bladder preservation can only be offered to highly selected patients and ideally within clinical trials. Novel treatment strategies and biomarkers have been established MIBC and NMIBC but have not been comprehensively investigated in the context of HS in NMIBC. Further evaluation prior to implementation into clinical practice is needed
Investigating the footprint of post-domestication dispersal on the diversity of modern European, African and Asian goats.
Get PDFBACKGROUND
Goats were domesticated in the Fertile Crescent about 10,000 years before present (YBP) and subsequently spread across Eurasia and Africa. This dispersal is expected to generate a gradient of declining genetic diversity with increasing distance from the areas of early livestock management. Previous studies have reported the existence of such genetic cline in European goat populations, but they were based on a limited number of microsatellite markers. Here, we have analyzed data generated by the AdaptMap project and other studies. More specifically, we have used the geographic coordinates and estimates of the observed (Ho) and expected (He) heterozygosities of 1077 European, 1187 African and 617 Asian goats belonging to 38, 43 and 22 different breeds, respectively, to find out whether genetic diversity and distance to Ganj Dareh, a Neolithic settlement in western Iran for which evidence of an early management of domestic goats has been obtained, are significantly correlated.
RESULTS
Principal component and ADMIXTURE analyses revealed an incomplete regional differentiation of European breeds, but two genetic clusters representing Northern Europe and the British-Irish Isles were remarkably differentiated from the remaining European populations. In African breeds, we observed five main clusters: (1) North Africa, (2) West Africa, (3) East Africa, (4) South Africa, and (5) Madagascar. Regarding Asian breeds, three well differentiated West Asian, South Asian and East Asian groups were observed. For European and Asian goats, no strong evidence of significant correlations between Ho and He and distance to Ganj Dareh was found. In contrast, in African breeds we detected a significant gradient of diversity, which decreased with distance to Ganj Dareh.
CONCLUSIONS
The detection of a genetic cline associated with distance to the Ganj Dareh in African but not in European or Asian goat breeds might reflect differences in the post-domestication dispersal process and subsequent migratory movements associated with the management of caprine populations from these three continents
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