Background: Cancer research autopsy genomic studies offer insight into the metastatic cancer landscape but come with complexities that relate to the sampling and processing of post-mortem tissue. Clarifying the effect of autopsy variables on pre- and post-sequencing quality control (QC) is an unmet need that may inform tissue collection strategies. Methods: The effect of age, sex, post-mortem interval (PMI), and sample type (primary, metastatic, or normal) on pre-sequencing QC (nucleic acid concentration and integrity) was examined in 2678 samples (88.6% metastatic, 8.0% primary, 3.4% normal) from 83 patients with melanoma, lung, renal, or prostate cancer in the PEACE study. In the lung cohort, 160 surgical samples were also included through the TRACERx study, allowing surgery-autopsy tissue comparisons. Post-sequencing QC metrics were evaluated for lung samples that underwent DNA (n=522) or RNA (n=366) sequencing. Results: RNA concentration and RIN were greater in surgical samples than those collected at autopsy. Across cohorts, metastatic autopsy samples had greater nucleic acid concentrations than primary or normal autopsy samples, but not integrity. DNA and RNA concentration and integrity differed significantly between primary tumor types. When comparing samples of different metastatic sites from the whole cohort, concentration was lowest in bone (DNA) or the digestive tract (RNA), while integrity was greatest in the brain and lowest in the digestive tract (DIN, RIN). Although autopsy variables like age, sex and PMI correlated with pre-sequencing QC metrics in univariate analysis, they were not found to significantly correlate with these metrics in multivariate analysis, which identified that only primary cancer type and metastatic site were independent determinants of concentration and integrity. Similarly, for post-DNA (whole exome) sequencing QC, only the metastatic site was found to independently influence sequencing QC metrics like total number of sequences, average sequence length, and FastQC score. For RNA sequencing, only the metastatic site was found to influence sequencing QC metrics like total number of sequences, percentage of non-duplicated sequences, one hit-one genome percentage, and the alignment percentage on the human genome. Discussion: The lack of influence of PMI on QC in the largest QC-focused autopsy cancer study to date suggests that quality tissue can be obtained from non-rapid autopsy programs, which are more feasible and less resource-intensive than rapid programs. Citation Format: Petros Fessas, Sonya Hessey, Corentin Richard, Cristina Naceur-Lombardelli, Sophia Ward, David A. Moore, Karolina Nowakowska, Blanca Trujillo, Irene Lobon, Scott T. Shepherd, Fiona Byrne, Samra Turajlic, Gerhardt Attard, Charles Swanton, Mariam Jamal-Hanjani. The effect of cancer research autopsy parameters on DNA and RNA sequencing quality [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2926.

Background: Genetic evolution of clear cell renal cell carcinoma (ccRCC) follows distinct trajectories, with varying levels of intratumor heterogeneity (ITH) and chromosomal complexity (WGII). While these patterns associate with clinical outcomes, it remains unknown whether they fully reconcile tumor behavior and how genetic and transcriptional features co-evolve in relation to the tumor microenvironment (TME). Methods: To analyze the patterns of transcriptional and TME heterogeneity, we performed bulk whole-transcriptome sequencing on 244 samples, including 22 metastatic and 12 tumor-adjacent normal samples, from 79 ccRCC patients recruited to the TRACERx Renal study. We integrated transcriptional data with previously published genetic, phylogenetic, spatial and clinical information. Results: Transcriptional distances between paired samples from the same primary tumor mirrored but were not fully determined by genetic distance (p-value < 0.001); and increased from primary-primary to primary-metastasis and primary-normal pairs. Within primary-metastasis pairs, metastasis-seeding primary tumor regions were transcriptionally closest to their matched metastasis (p-value < 0.001), suggesting that an important fraction of metastatic transcriptional traits were acquired in the primary tumor. Regarding the tumor clonal structure, transcriptional evolution followed a conserved path through increasing cell proliferation and oxidative phosphorylation and downregulating DNA repair from earlier to later clones. Further, within tumors with increasing WGII we observed upregulation and downregulation of repressors and downstream effectors, respectively, of the canonical cGAS-STING pathway. Combining the presence of this transcriptional pattern with WGII predicted shorter PFS in TRACERx Renal (p-value < 0.001) and in TCGA-KIRC (p-value < 0.001). Clonal evolution was also linked to changes in TME, with each of the previously defined genetic evolutionary trajectories associated to a specific TME (p-value < 0.001). For example, ccRCCs on a PBRM1-SETD2 trajectory demonstrated increased infiltration of cytotoxic immune cells. TME ITH was pervasive and associated with shorter PFS (p-value = 0.03). A recurrent trend from earlier to later clones was progressive T cell depletion (p-value < 0.001). The evolution of the TCR repertoire mirrored the tumor clonal structure (p-value = 0.002), suggesting the thus far elusive antigenic source in ccRCC is heritable. Accordingly, the TCR repertoire in metastasis-seeding primary tumor regions resembled the closest the TCR repertoire of matched metastasis (p-value = 0.06). Conclusion: Integrated analysis of genetic and transcriptional data in TRACERx Renal showed i) transcriptional and TME ITH not fully recapitulated by genetic ITH, ii) conserved paths of transcriptional and TME evolution and iii) a heritable nature of part of the ccRCC antigen source. Citation Format: Ángel Fernández Sanromán, Lewis Au, Benjy Jek Yang Tan, Charlotte Spencer, Anne-Laure Catin, Irene Lobon, Husayn Pallikonda, Kevin Litchfield, Fiona Byrne, James Larkin, Annika Fendler, Samra Turajlic. Integrated analysis of genetic, transcriptional and TME evolution of ccRCC: TRACERx Renal [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1621.

Microbiome engineering – the targeted manipulation of microbial communities – is considered a promising strategy to restore ecosystems, but experimental support and mechanistic understanding are required. Here, we show that bacterial inoculants for soil microbiome engineering may fail to establish because they inadvertently facilitate growth of native resident microbiomes. By generating soil microcosms in presence or absence of standardized soil resident communities, we show how different nutrient availabilities limit outgrowth of focal bacterial inoculants (three Pseudomonads), and how this might be improved by adding an artificial, inoculant-selective nutrient niche. Through random paired interaction assays in agarose micro-beads, we demonstrate that, in addition to direct competition, inoculants lose competitiveness by facilitating growth of resident soil bacteria. Metatranscriptomics experiments with toluene as selective nutrient niche for the inoculant Pseudomonas veronii indicate that this facilitation is due to loss and uptake of excreted metabolites by resident taxa. Generation of selective nutrient niches for inoculants may help to favor their proliferation for the duration of their intended action while limiting their competitive loss. Bioremediation via microbial inoculation often performs poorly in real-world conditions. Here, the authors show that bacterial inoculants may fail to establish in complex soil microbiomes because they open new niches that facilitate growth of resident microbes.

Introduction: Classification of genetic variants has significant implications for clinical management. Artificial Intelligence (AI) has the potential to transform classification of genetic variants, such as AlphaMissense, which incorporates structure-function relationships and allele frequencies across large datasets of genetic variants. While this represents a promising new tool, the performance of AlphaMissense has only been compared to known pathogenic and benign variants. Therefore, the discriminatory power for variants of unknown significance (VUS) has yet to be determined. We have performed a comparison of these predictions with variants associated with inherited myeloid neoplasms: 1) to assess the accuracy of these models against VUS; 2) to enhance classification of unpublished VUS by leveraging published information about other variants; and 3) to map the predicted classification onto protein structures to examine spatial patterns. Methods: For 83 genes associated with inherited myeloid diseases, a systematic literature review for missense variants was performed using the Mastermind Genomic Intelligence Platform and ClinVar. We used Alphamissense to characterize VUS missense variants according to predicted pathogenicity scores as pathogenic, ambiguous, or benign. Known pathogenic (n=1594) and benign (n=501) variants served as controls to evaluate the accuracy of the system. AlphaFold2 structures were visualized for structure-function rendering of reclassified VUS and known pathogenic variants to compare and identify discernible patterns of spatial distribution. Results: This variant dataset comprised 1594 pathogenic, 501 benign, and 46676 VUS missense variants. Among VUS, AlphaMissense reclassified a majority of VUS missense mutations and established that the system was 88% accurate in predicting pathogenicity. A higher percentage of variants was classified as pathogenic among tumor suppressor genes e.g. DDX41 and RUNX1 (57.1% and 40.5%) compared to the oncogenes, GATA1 and GATA2 (25.7% and 34.9%). Furthermore, 3D models revealed a majority of variants reclassified to pathogenic were located in regions with defined tertiary structure clustered with known pathogenic variants, while benign variants were located at peripheral positions lacking definite structure. Conclusions: These results demonstrate the discriminatory power of AlphaMissense for VUS pathogenicity prediction for both loss-of-function and gain-of-function disease mechanisms. This work may also have implications for rare or challenging somatic cancer variants and variants in rare diseases. Finally, incorporating information available from empirical and clinical studies for disease-causing variants offers the possibility of significantly enhancing the predictive power of these models. Citation Format: Amina Kurtovic-Kozaric, Asja Campara, Melissa Jahibasic, Amar Mujkic, Adnan Fojnica, Mark J. Kiel. Assessment of AlphaMissense and structure-function predictions demonstrates efficient reclassification of genetic variants of unknown pathogenicity in inherited myeloid neoplasms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2267.

Students in Bosnia and Herzegovina (B&H) score very low on international assessments (TIMSS & PISA), lower than the countries in the region with which it shares similar background. In this paper the characteristics of teachers’ professional development (TPD) in the region of Western Balkan countries (Albania, B&H, Kosovo, Montenegro, North Macedonia, and Serbia) and Croatia are brought into correlation with average results in mathematics and science on TIMSS 2019. Research questions analyze teachers’ attitudes towards their profession and investigate the impact of professional development (PD) of mathematics and science teachers in the last two years, with a specific focus on the situation in B&H, on students’ achievement in mathematics and science. The findings indicate a lack of TPD as a contributing factor to lower results in B&H. The research suggests that B&H should consider reforms in the education system and enhance teachers’ attitudes towards their profession through intensified PD programs to advance education and learning.

The targeted use of social robots for the family demands a better understanding of multiple stakeholders’ privacy concerns, including those of parents and children. Through a co-learning workshop which introduced families to the functions and hypothetical use of social robots in the home, we present preliminary evidence from 6 families that exhibits how parents and children have different comfort levels with robots collecting and sharing information across different use contexts. Conversations and booklet answers reveal that parents adopted their child’s decision in scenarios where they expect children to have more agency, such as in cases of homework completion or cleaning up toys, and when children proposed what their parents found to be acceptable reasoning for their decisions. Families expressed relief when they shared the same reasoning when coming to conclusive decisions, signifying an agreement of boundary management between the robot and the family. In cases where parents and children did not agree, they rejected a binary, either-or decision and opted for a third type of response, reflecting skepticism, uncertainty and/or compromise. Our work highlights the benefits of involving parents and children in child- and family-centered research, including parental abilities to provide cognitive scaffolding and personalize hypothetical scenarios for their children.

Unlike classical artificial neural networks, which require retraining for each new set of parametric inputs, the Deep Operator Network (DeepONet), a lately introduced deep learning framework, approximates linear and nonlinear solution operators by taking parametric functions (infinite-dimensional objects) as inputs and mapping them to complete solution fields. In this paper, two newly devised DeepONet formulations with sequential learning and Residual U-Net (ResUNet) architectures are trained for the first time to simultaneously predict complete thermal and mechanical solution fields under variable loading, loading histories, process parameters, and even variable geometries. Two real-world applications are demonstrated: 1- coupled thermo-mechanical analysis of steel continuous casting with multiple visco-plastic constitutive laws and 2- sequentially coupled direct energy deposition for additive manufacturing. Despite highly challenging spatially variable target stress distributions, DeepONets can infer reasonably accurate full-field temperature and stress solutions several orders of magnitude faster than traditional and highly optimized finite-element analysis (FEA), even when FEA simulations are run on the latest high-performance computing platforms. The proposed DeepONet model's ability to provide field predictions almost instantly for unseen input parameters opens the door for future preliminary evaluation and design optimization of these vital industrial processes.

This paper explores the legal regulations on the termination of pregnancy in comparative law, a sensitive topic that, although it does represent the exclusive domain of state regulation, encroaches into human rights as well. The basic research question is how selected modern democratic states legally regulate the issue of the termination of pregnancy. Hence, the research goal is to prove that the trend of modern democratic states is to allow the termination of pregnancy even on request, but also to determine the existence of recent retrograde trends in this area. In this paper and research, except for the comparative method, the analytic, dogmatic, normative, and axiological methods are utilized. Although the core of the research is comparative legal, the historic and international legal segments are presented in short in this paper. In researching the following selected states, BiH, Serbia, Croatia, Germany, USA and Ireland, it is determined that the termination of pregnancy is currently largely allowed even on the request of a pregnant woman, especially for justified reasons, with regards to a specific legal regime (Germany), a sudden shift in complete liberalization (Ireland), and even for retrograde changes towards absolute prohibition (USA). In the argument section, the right of the state to ban a medical procedure out of arbitrary reasons (at least in modern discourse) is considered (even disputed). The conclusion is, considering the practice and development of democratic states, the trend of allowing the termination of pregnancy in early stages on demand of a pregnant woman without a reason, and in later stages with a reason, is evident. Concerning the region, the situation is relative satisfactory, although in greater parts of Bosnia and Herzegovina as well as Croatia the outdated legislation needs innovations, as well as certain improvements, which at this point is inevitable.

La cría de caracoles, también conocida como helicicultura, es un tipo de ganadería que implica la reproducción y cultivo de caracoles para consumo humano. Aunque la cría de caracoles sigue siendo relativamente rara en muchas partes del mundo, es una industria en crecimiento que ofrece una serie de beneficios, incluido el impacto ambiental pequeño, alto potencial de beneficios y ventajas nutricionales únicas. Entre varias especies comestibles, los caracoles como Cornu aspersum y Helix pomatia han demostrado un tremendo potencial como fuentes alternativas de proteínas en las dietas animales. Tienen un perfil nutricional favorable, que contiene aminoácidos esenciales, minerales y vitaminas, lo que los convierte en valiosos suplementos o sustitutos de fuentes de proteínas tradicionales. Las técnicas y prácticas de cría de caracoles han avanzado significativamente en los últimos años, lo que ha resultado en un aumento de la productividad y mejoras en los rasgos genéticos en las poblaciones de caracoles. Además, los esfuerzos de investigación en curso están explorando el desarrollo de protocolos de cría de caracoles adaptados a requisitos veterinarios específicos. La optimización de los métodos de cría, incluida la selección artificial, el apareamiento controlado y la mejora genética, tiene un enorme potencial para mejorar los rasgos deseables en las poblaciones de caracoles. Este progreso puede contribuir al desarrollo de razas de caracoles superiores con perfiles nutricionales mejorados, resistencia a enfermedades y propiedades terapéuticas. Además, la cría de caracoles presenta una oportunidad para abordar problemas ecológicos asociados con la producción tradicional de ganado. El uso eficiente de recursos, los requisitos mínimos de espacio y el bajo impacto ambiental hacen que la cría de caracoles sea una alternativa ecológica. Los caracoles también son menos susceptibles a ciertas enfermedades infecciosas que comúnmente afectan a los animales criados tradicionalmente, lo que reduce la necesidad de antimicrobianos y promueve prácticas sostenibles. La educación continua y la investigación sobre técnicas de cría de caracoles, perfiles nutricionales y aplicaciones terapéuticas allanan el camino para prácticas veterinarias innovadoras que priorizan la sostenibilidad, el bienestar animal y mejores resultados de salud. Una mayor investigación en este campo representa una nueva oportunidad para que veterinarios y agricultores contribuyan a la salud y el bienestar de los animales al tiempo que promueven prácticas sostenibles en la industria ganadera. Este artículo de revisión tiene como objetivo proporcionar una visión general de la literatura científica sobre la cría adecuada de caracoles comestibles y los posibles desafíos de los impactos antropogénicos y climáticos negativos como un desafío potencial para los criadores.

Tekst predstavlja prilagođeno izlaganje sa naučne konferencije ZAVNOBiH u retrospektivi: evaluacija historijske važnosti i savremene relevantnosti za društvo i državu koja je organizirana povodom 80. godišnjice od Prvog zasjedanja ZAVNOBiH-a. Konferencija je održana 20. novembra 2023. godine na Univerzitetu u Sarajevu - Fakultetu političkih nauka. The text represents an adapted presentation delivered at the scientific conference ZAVNOBiH in Retrospect – Evaluating Its Historical Importance and Contemporary Relevance for Society and the State, organized on the occasion of marking the 80th Anniversary of the First Session of ZAVNOBiH. The conference was held at the University of Sarajevo - Faculty of Political Sciences, on 20 November 2023.

This study aims to analyze the opinions of Bosnia and Herzegovina (BiH) citizens regarding mandatory pension insurance and the possibility of incorporating private insurance in future reforms. The research involves evaluating the satisfaction of BiH residents with the current pension system, understanding their perception of the pension fund’s risks, and identifying their attitudes towards possible pension system reforms, including the potential involvement of private insurance. The study also seeks to highlight any differences in attitudes towards socio-demographic characteristics, such as gender, employment, length of service, professional qualification, and monthly income. A survey of 812 BiH adults (representative but potentially not fully capturing the entire population) explored these aspects. While acknowledging limitations, the study reveals significant differences in attitudes based on demographics. For example, men are more optimistic about future pensions, while employed individuals are more inclined towards reform. The findings suggest general public support for pension system reform and openness to private insurance. However, the study highlights the need to consider these varying attitudes across different population groups when designing future reforms. This research provides the first quantitative data on BiH residents’ views on private insurance reform, contributing to public discourse and informing future policy changes.

Professional football players often need legal help in managing disputes with football clubs. The Professional Football Players Syndicate of Bosnia and Herzegovina is an organization founded with this purpose. Due to an increasing need for legal help and a large number of cases, their legal associates need systematic management of data. This work presents the first information system entirely intended for the usage by sports law professionals. It contains a desktop application where legal disputes are shown in the form of an organized dispute table. Real-time information about football players is acquired by using the TransferMarkt web API. The system was successfully used for two years, resulting in 103 documented cases involving 87 players and 31 clubs. As a result, 69.90% of disputes were archived and 43.69% of disputes resulted in agreements, indicating that the productivity of legal associates and the mediator role of the Syndicate were improved.