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Purpose: Accurate detection of microcalcifications ( µ Calcs ) is crucial for the early detection of breast cancer. Some clinical studies have indicated that digital breast tomosynthesis (DBT) systems with a wide angular range have inferior µ Calc detectability compared with those with a narrow angular range. This study aims to (1) provide guidance for optimizing wide-angle (WA) DBT for improving µ Calcs detectability and (2) prioritize key optimization factors. Approach: An in-silico DBT pipeline was constructed to evaluate µ Calc detectability of a WA DBT system under various imaging conditions: focal spot motion (FSM), angular dose distribution (ADS), detector pixel pitch, and detector electronic noise (EN). Images were simulated using a digital anthropomorphic breast phantom inserted with 120 µ m µ Calc clusters. Evaluation metrics included the signal-to-noise ratio (SNR) of the filtered channel observer and the area under the receiver operator curve (AUC) of multiple-reader multiple-case analysis. Results: Results showed that FSM degraded µ Calcs sharpness and decreased the SNR and AUC by 5.2% and 1.8%, respectively. Non-uniform ADS increased the SNR by 62.8% and the AUC by 10.2% for filtered backprojection reconstruction with a typical clinical filter setting. When EN decreased from 2000 to 200 electrons, the SNR and AUC increased by 21.6% and 5.0%, respectively. Decreasing the detector pixel pitch from 85 to 50 µ m improved the SNR and AUC by 55.6% and 7.5%, respectively. The combined improvement of a 50 µ m pixel pitch and EN200 was 89.2% in the SNR and 12.8% in the AUC. Conclusions: Based on the magnitude of impact, the priority for enhancing µ Calc detectability in WA DBT is as follows: (1) utilizing detectors with a small pixel pitch and low EN level, (2) allocating a higher dose to central projections, and (3) reducing FSM. The results from this study can potentially provide guidance for DBT system optimization in the future.

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Objective: This study aimed to investigate the usefulness of endoscopic ultrasound-guided tissue acquisition (EUS-TA) for diagnosing focal liver lesions in patients with a history of multiple primary malignant neoplasms. Methods: Among patients who underwent EUS-TA for focal liver lesions between 2016 and 2022, those with a history of multiple malignant neoplasms were included. A histologically confirmed malignant tumor within the past 5 years before EUS-TA was defined as a history of malignant neoplasm. The primary outcomes were diagnostic ability and adverse events of EUS-TA. Results: This study included 16 patients (median age, 73 [33-90] years), the median tumor size was 32 (6-51) mm, 14 had a history of double malignant neoplasms, whereas two had triple malignant neoplasms. Malignant neoplasms were detected histologically or cytologically in all cases. Immunohistochemistry was performed in 75% (12/16), and the final diagnosis of EUS-TA was metastatic liver tumor in 12 patients, and primary malignant liver tumor in four patients. The primary site could be identified in 11 of 12 metastatic tumor cases. The diagnostic yield of EUS-TA was 100% (16/16) for differentiating benign and malignant tumors and 94% (15/16) for confirming the histological type including the primary site of metastatic lesions. No adverse events were associated with the procedure. Conclusion: EUS-TA is a useful diagnostic modality for focal liver lesions in patients with a history of multiple malignant neoplasms, allowing for the differential diagnosis of primary and metastatic tumors and identification of the primary site of metastatic lesions.

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This study sought to explore the perspective of medical faculty on the mental health of their students. This qualitative study based on a focus group is part of a longitudinal research that studied the mental health of Brazilian students. One group was conducted with faculty employed at a medical school. Topics discussed covered the concept of mental health and medical education. Six professors participated in one group. The mental health of medical students is a construct that encompasses emotional aspects, ability to solve problems and multiple facets of a human being, according to the participants. Artistic practices, moments of socialization and leisure were perceived as stimulating students' good mental health. Excessive demands generate competitiveness and the teacher's expectation of the student's good performance based on their own experience can harm the student's mental health. Participants also highlighted that a pedagogical reformulation that makes sense for the student's learning process is necessary to update traditional curricula. Medical students' mental health is influenced by experiences and exchanges during the medical school, mainly between professor and student, understood as necessary and inherent to the process of becoming physician. The findings of this study show the need for curriculum changes in the medical education process and updating teacher training for good practices that reinforce good mental health.

Este estudio buscó explorar la perspectiva de los profesores de medicina sobre la salud mental de sus estudiantes. Este estudio cualitativo basado en un grupo focal es parte de una investigación longitudinal que estudió la salud mental de estudiantes brasileños. Un grupo se llevó a cabo con profesores empleados en una escuela de medicina. Los temas tratados abarcaron el concepto de salud mental y educación médica. Seis docentes participaron en un grupo. La salud mental de los estudiantes de medicina es un constructo que abarca aspectos emocionales, capacidad de resolución de problemas y múltiples facetas del ser humano, según los participantes. Las prácticas artísticas, los momentos de socialización y el ocio fueron percibidos como estimulantes de la buena salud mental de los estudiantes. Las exigencias excesivas generan competitividad y la expectativa del docente sobre el buen desempeño del estudiante basándose en su propia experiencia puede perjudicar la salud mental del estudiante. Los participantes también resaltaron que es necesaria una reformulación pedagógica que tenga sentido para el proceso de aprendizaje del estudiante para actualizar los currículos tradicionales. La salud mental de los estudiantes de medicina está influenciada por las experiencias y los intercambios durante la carrera de medicina, principalmente entre profesor y estudiante, entendidos como necesarios e inherentes al proceso de convertirse en médico. Los hallazgos de este estudio muestran la necesidad de cambios curriculares en el proceso de formación médica y de actualización de la formación docente hacia buenas prácticas que refuercen la buena salud mental.

Este estudo buscou explorar a perspectiva dos docentes de medicina sobre a saúde mental de seus alunos. Este estudo qualitativo baseado em grupo focal faz parte de uma pesquisa longitudinal que estudou a saúde mental de estudantes brasileiros. Um grupo foi conduzido com professores empregados em uma faculdade de medicina. Os temas discutidos abrangeram o conceito de saúde mental e educação médica. Seis professores participaram de um grupo. A saúde mental dos estudantes de medicina é um construto que engloba aspectos emocionais, capacidade de resolução de problemas e múltiplas facetas do ser humano, segundo os participantes. As práticas artísticas, os momentos de socialização e de lazer foram percebidos como estimuladores da boa saúde mental dos estudantes. Exigências excessivas geram competitividade e a expectativa do professor pelo bom desempenho do aluno com base na própria experiência pode prejudicar a saúde mental do aluno. Os participantes destacaram também que é necessária uma reformulação pedagógica que faça sentido para o processo de aprendizagem do aluno para atualizar os currículos tradicionais. A saúde mental dos estudantes de medicina é influenciada pelas experiências e trocas durante o curso de medicina, principalmente entre professor e aluno, entendidas como necessárias e inerentes ao processo de tornar-se médico. Os achados deste estudo mostram a necessidade de mudanças curriculares no processo de formação médica e de atualização da formação docente para boas práticas que reforcem a boa saúde mental.

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Introduction: The potential toxic effects of wastewater discharges containing silver nanoparticles (AgNPs) and their release into aquatic ecosystems on aquatic organisms are becoming a major concern for environmental and human health. However, the potential risks of AgNPs to aquatic organisms, especially for cardiac development by Focal adhesion pathway, are still poorly understood. Methods: The cardiac development of various concentrations of AgNPs in zebrafish were examined using stereoscopic microscope. The expression levels of cardiac development-related genes were analyzed by qRT-PCR and Whole-mount in situ hybridization (WISH). In addition, Illumina high-throughput global transcriptome analysis was performed to explore the potential signaling pathway involved in the treatment of zebrafish embryos by AgNPs after 72 h. Results: We systematically investigated the cardiac developing toxicity of AgNPs on the embryos of zebrafish. The results demonstrated that 2 or 4 mg/L AgNPs exposure induces cardiac developmental malformations, such as the appearance of pericardial edema phenotype. In addition, after 72 h of exposure, the mRNA levels of cardiac development-related genes, such as myh7, myh6, tpm1, nppa, tbx5, tbx20, myl7 and cmlc1, were significantly lower in AgNPs-treated zebrafish embryos than in control zebrafish embryos. Moreover, RNA sequencing, KEGG (Kyoto Encyclopedia of Genes) and Genomes and GSEA (gene set enrichment analysis) of the DEGs (differentially expressed genes) between the AgNPs-exposed and control groups indicated that the downregulated DEGs were mainly enriched in focal adhesion pathways. Further investigations demonstrated that the mRNA levels of focal adhesion pathway-related genes, such as igf1ra, shc3, grb2b, ptk2aa, akt1, itga4, parvaa, akt3b and vcla, were significantly decreased after AgNPs treatment in zebrafish. Conclusion: Thus, our findings illustrated that AgNPs could impair cardiac development by regulating the focal adhesion pathway in zebrafish.

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Triple negative breast cancer (TNBC) is the most aggressive subtype in breast tumors. When re-analyzing TCGA breast cancer dataset, we found cell adhesion molecules are highly enriched in differentially expressed genes in TNBC samples, among which Focal Adhesion Kinase (FAK) is most significantly associated with poor survival of TNBC patients. FAK is precisely modulated in the focal adhesion dynamics. To investigate whether lncRNAs regulate FAK signaling, we performed RNA immunoprecipitation sequencing and found FAISL (FAK Interacting and Stabilizing LncRNA) abundantly enriched in FAK-interacting lncRNAs and frequently overexpressed in TCGA TNBC tissues. FAISL promotes TNBC cell adhesion, cytoskeleton spreading, proliferation, and anchor-independent survival. FAISL doesn't affect FAK mRNA but positively regulates FAK protein level by blocking Calpain 2-mediated proteolysis. FAISL interacts with the C-terminus domain of FAK, whereby masks the binding site of Calpain 2 and prevents FAK cleavage. High level of FAISL correlates with FAK expression in tumor tissues and poor prognosis of TNBC patients. A siRNA delivery system targeting FAISL using reduction-responsive nanoparticles effectively inhibits tumor growth and metastasis in TNBC mouse models. Together, these findings uncover a lncRNA-mediated mechanism of regulating FAK proteolysis in the TNBC progression, and highlight the potential of targeting lncRNA FAISL for TNBC treatment.

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Alpha-synuclein (aSyn) aggregates in the central nervous system are the main pathological hallmark of Parkinson's disease (PD). ASyn aggregates have also been detected in many peripheral tissues, including the skin, thus providing a novel and accessible target tissue for the detection of PD pathology. Still, a well-established validated quantitative biomarker for early diagnosis of PD that also allows for tracking of disease progression remains lacking. The main goal of this research was to characterize aSyn aggregates in skin biopsies as a comparative and quantitative measure for PD pathology. Using direct stochastic optical reconstruction microscopy (dSTORM) and computational tools, we imaged total and phosphorylated-aSyn at the single molecule level in sweat glands and nerve bundles of skin biopsies from healthy controls (HCs) and PD patients. We developed a user-friendly analysis platform that offers a comprehensive toolkit for researchers that combines analysis algorithms and applies a series of cluster analysis algorithms (i.e., DBSCAN and FOCAL) onto dSTORM images. Using this platform, we found a significant decrease in the ratio of the numbers of neuronal marker molecules to phosphorylated-aSyn molecules, suggesting the existence of damaged nerve cells in fibers highly enriched with phosphorylated-aSyn molecules. Furthermore, our analysis found a higher number of aSyn aggregates in PD subjects than in HC subjects, with differences in aggregate size, density, and number of molecules per aggregate. On average, aSyn aggregate radii ranged between 40 and 200 nm and presented an average density of 0.001-0.1 molecules/nm2. Our dSTORM analysis thus highlights the potential of our platform for identifying quantitative characteristics of aSyn distribution in skin biopsies not previously described for PD patients while offering valuable insight into PD pathology by elucidating patient aSyn aggregation status.

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Based on the joint analysis of multi-omic data and the biological experiments, we demonstrate that FOXF1 inhibits invasion and metastasis of lung adenocarcinoma cells and enhances anti-tumor immunity via regulating MFAP4/FAK signal axis in this study. The levels of FOXF1 and MFAP4 are significantly down-regulated in LUAD, and the increased levels of two genes can improve the clinical prognosis of LUAD patients. Fluorescein reporter gene determination, chromatin immunoprecipitation and gene co-expression analysis indicate that MFAP4 level is positively regulated by transcription factor FOXF1. The function enrichment analysis shows that the levels of FOXF1 and MFAP4 are closely associated with an enrichment of tumor metastasis signatures. FOXF1 can inhibit the migration and invasion of LAUD cells by transcriptionally activating MFAP4 expression. And the overexpression of FOXF1/MFAP4 can reduce focal adhesion kinase (FAK) phosphorylation, while their knockdown result in the opposite effects. The increased levels of FOXF1/MFAP4 enhance the antitumor immunity by increasing the infiltration of dendritic cells and CD4+ T cells, and the interactions between LUAD cells and immune cells, and activating multiple anti-tumor immunity-related pathways. In conclusion, our study reveals the potential function of FOXF1/MFAP4/FAK signal axis in inhibiting metastasis of LUAD cells and modulating anti-tumor immunity of LUAD patients.

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of advanced diagnostic methods shed the light on the variable course of age-related macular degeneration (AMD). Despite establishing AMD classifications used in clinical practice, there are still forms of AMD that do not fit into these systems. The case report presents a rare evolution of non-neovascular form of AMD presenting at baseline as large soft drusen. Within the 5 years of observation one eye with such form of AMD transformed to retinal pigment epithelial detachment and subsequently simultaneous separation of the neurosensory retina and the choroid from the RPE. As a result, on the spectral domain optical coherence tomography scan, the case presented with lone line of the RPE neighbored by subretinal fluid from the inner side and choroidal excavation from the outside. Macular neovascularization was excluded at each timepoint of the follow-up. During 2.5 years of observation post the onset of RPE separation, the case remained stable with maintained visual acuity at 0.25 Snellen and lack of progression to wet form of AMD. Further observation is needed to fully assess the eye's potential for visual preservation in the long term.

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BACKGROUND: Focal segmental glomerulosclerosis (FSGS), a histologic pattern of injury in the glomerulus, is one of the leading glomerular causes of end-stage renal disease (ESRD) worldwide. Despite extensive research, the underlying biological alterations causing FSGS remain poorly understood. Studying variations in gene expression profiles offers a promising approach to gaining a comprehensive understanding of FSGS molecular pathogenicity and identifying key elements as potential therapeutic targets. This work is a meta-analysis of gene expression profiles from glomerular samples of FSGS patients. The main aims of this study are to establish a consensus list of differentially expressed genes in FSGS, validate these findings, understand the disease's pathogenicity, and identify novel therapeutic targets. METHODS: After a thorough search in the GEO database and subsequent quality control assessments, seven gene expression datasets were selected for the meta-analysis: GSE47183 (GPL14663), GSE47183 (GPL11670), GSE99340, GSE108109, GSE121233, GSE129973, and GSE104948. The random effect size method was applied to identify differentially expressed genes (meta-DEGs), which were then used to construct a regulatory network (STRING, MiRTarBase, and TRRUST) and perform various pathway enrichment analyses. The expression levels of several meta-DEGs, specifically ADAMTS1, PF4, EGR1, and EGF, known as angiogenesis regulators, were analyzed using quantitative reverse transcription polymerase chain reaction (RT-qPCR). RESULTS: The identified 2,898 meta-DEGs, including 665 downregulated and 669 upregulated genes, were subjected to various analyses. A co-regulatory network comprising 2,859 DEGs, 2,688 microRNAs (miRNAs), and 374 transcription factors (TFs) was constructed, and the top molecules in the network were identified based on degree centrality. Part of the pathway enrichment analysis revealed significant disruption in the angiogenesis regulatory pathways in the FSGS kidney. The RT-qPCR results confirmed an imbalance in angiogenesis pathways by demonstrating the differential expression levels of ADAMTS1 and EGR1, two key angiogenesis regulators, in the FSGS condition. CONCLUSION: In addition to presenting a consensus list of differentially expressed genes in FSGS, this meta-analysis identified significant distortions in angiogenesis-related pathways and factors in the FSGS kidney. Targeting these factors may offer a viable strategy to impede the progression of FSGS.

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Dipeptidyl peptidase 4 (DPP4; CD26) is involved in the regulation of various metabolic, immunological, and neurobiological processes in healthy individuals. Observations based on epidemiological data indicate that DPP4 inhibition by gliptins, typically used in patients with diabetes, may reduce the risk for cerebral ischemia and may also improve related outcomes. However, as DPP4 inhibitor application is neither complete nor specific for suppression of DPP4 enzymatic activity and DPP4 has non-enzymatic functions as well, the variety of consequences is a matter of debate. Therefore, we here used DPP4 knock-out (KO) mice to analyze the specific contribution of DPP4 to cellular, immunological, and functional consequences of experimental focal cerebral ischemia. We observed a significantly higher survival rate of DPP4 KO mice after ischemia, which was accompanied by a lower abundance of the pro-inflammatory chemokine CCL2 and reduced activation of Iba1-positive microglia cells in brain tissue of DPP4 KO mice. In addition, after ischemia for 24 h to 72 h, decreased concentrations of CCL5 and CCL12 in plasma and of CCL17 in brain tissue of DPP4 KO mice were observed when compared to wild type mice. Other aspects analyzed, such as the functional Menzies score, astrocyte activation and chemokine levels in plasma and brain tissue were affected by ischemia but appeared to be unaffected by the DPP4 KO genotype. Taken together, experimental ablation of DPP4 functions in mice improved survival and ameliorates aspects of cellular and molecular inflammation after focal cerebral ischemia.

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BACKGROUND: Focal therapy, a minimally invasive procedure, offers targeted treatment for kidney and prostate cancer using image guidance. However, the current institutional landscape of its adoption in localized prostate and kidney cancer remains less understood. This analysis compares its usage between the 2 cancers to discern health system determinants affecting the adoption of these treatments. METHODS: The study used data from adult patients with localized prostate and kidney cancer from the National Cancer Database. We calculated adjusted probabilities of focal therapy usage per facility via multivariable mixed-effects logistic regression model with hospital-level random effects. We analyzed interhospital variability through ranked caterpillar plots and Spearman correlation coefficient. RESULTS: Among 1,559,334 prostate and 425,753 kidney cancer patients, 1.6% and 6.3% received focal therapy, respectively. The interhospital variation ranged from 0.13% to 32.17% for prostate cancer and 1.16% to 30.48% for kidney cancer. The hospital-level odds of focal therapy for prostate and kidney cancer were weakly correlated (Spearman's ρ = 0.21; P < .001). CONCLUSIONS: Our analysis revealed a substantial hospital-level discrepancy in the utilization of focal therapy. Despite this, there was a limited correlation between the use of focal therapy for these two types of cancer within the same hospital. Our findings emphasize the presence of multifaceted factors influencing the adoption of focal therapy, both at facility and healthcare system levels.

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Small extracellular vesicles (sEVs) obtained from mesenchymal stromal cells (MSCs) have shown considerable promise as restorative stroke treatment. In a head-to-head comparison in mice exposed to transient proximal middle cerebral artery occlusion (MCAO), sEVs obtained from MSCs cultured under hypoxic conditions particularly potently enhanced long-term brain tissue survival, microvascular integrity, and angiogenesis. These observations suggest that hypoxic preconditioning might represent the strategy of choice for harvesting MSC-sEVs for clinical stroke trials. To test the efficacy of hypoxic MSCs in a second stroke model in an additional species, we now exposed 6-8-month-old Sprague-Dawley rats to permanent distal MCAO and intravenously administered vehicle, platelet sEVs, or sEVs obtained from hypoxic MSCs (1% O2; 2 × 106 or 2 × 107 cell equivalents/kg) at 24 h, 3, 7, and 14 days post-MCAO. Over 28 days, motor-coordination recovery was evaluated by rotating pole and cylinder tests. Ischemic injury, brain inflammatory responses, and peri-infarct angiogenesis were assessed by infarct volumetry and immunohistochemistry. sEVs obtained from hypoxic MSCs did not influence infarct volume in this permanent MCAO model, but promoted motor-coordination recovery over 28 days at both sEV doses. Ischemic injury was associated with brain ED1+ macrophage infiltrates and Iba1+ microglia accumulation in the peri-infarct cortex of vehicle-treated rats. Hypoxic MSC-sEVs reduced brain macrophage infiltrates and microglia accumulation in the peri-infarct cortex. In vehicle-treated rats, CD31+/BrdU+ proliferating endothelial cells were found in the peri-infarct cortex. Hypoxic MSC-sEVs increased the number of CD31+/BrdU+ proliferating endothelial cells. Our results provide evidence that hypoxic MSC-derived sEVs potently enhance neurological recovery, reduce neuroinflammation. and increase angiogenesis in rat permanent distal MCAO.

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Human periodontal ligament cells (hPDLCs) contain multipotent postnatal stem cells that can differentiate into PDL fibroblasts, osteoblasts, and cementoblasts. Interaction between the extracellular environment and stem cells is an important factor for differentiation into other progenitor cells. To identify cell surface molecules that induce PDL fibroblastic differentiation, we developed a series of monoclonal antibodies against membrane/ECM molecules. One of these antibodies, an anti-PDL25 antibody, recognizes approximately a 100 kDa protein, and this antigenic molecule accumulates in the periodontal ligament region of tooth roots. By mass spectrometric analysis, we found that the antigenic molecule recognized by the anti-PDL25 antibody is fibroblast activation protein α (FAPα). The expression level of FAPα/PDL25 increased in TGF-ß1-induced PDL fibroblasts, and this protein was localized in the cell boundaries and elongated processes of the fibroblastic cells. Ectopic expression of FAPα induced fibroblastic differentiation. In contrast, expression of representative markers for PDL differentiation was decreased by knock down and antibody blocking of FAPα/PDL25. Inhibition of dipeptidyl peptidase activity by a potent FAPα inhibitor dramatically inhibited PDL fibroblastic marker expression but did not affect in cell proliferation and migration.

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Task-specific focal dystonia (TSFD), characterized by the loss of fine motor control and coordination, affects drummers' lower-limb movements. This study explores lower-limb dystonia's impact on drumming performance and underlying muscle activity in a professional rock drummer. The drummer executed an eight-beat pattern on a drum kit. The participant reported the occurrence of symptoms when he felt the abnormality such as the loss of control related to involuntary aspects of movement. We measured the peak amplitude of the bass drumhead vibration, synchronization errors as the time elapsed between the metronome onset and the bass drum onset, and amplitude of electromyographic (EMG) recordings centered on metronome beat. Dystonia symptoms primarily manifested in the initial beat, with fewer symptoms on syncopation of the third beat. Analysis revealed decreased bass-drum peak amplitude and earlier synchronization error during the initial beat. EMG measurements of 10 muscles in the affected right lower limb showed significant changes in the Biceps Femoris (BF), Tibialis Anterior (TA), Extensor Digitorum Longus (EDL), and Extensor Digitorum Brevis (EDB) muscles during symptom onset. We observed (1) earlier overactivation of the TA and EDL muscles during the leg lift-up motion or preparatory phase of pedaling, (2) reduced activation of the EDB muscle, and (3) increased activation of the BF muscle during the final pedaling movement when symptoms occurred. These findings suggest that lower-limb dystonia symptoms are characterized by a reduction in amplitude of the bass drumhead vibration and an increase in synchronization error, potentially due to premature overactivation of the ankle dorsiflexor muscles.

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BACKGROUND: Awareness is a state of consciousness that enables a subject to interact with the environment. Transient alteration of awareness (AA) is a disabling sign of many types of epileptic seizures. The brain mechanisms of awareness and its alteration are not well known. OBJECTIVE/HYPOTHESIS: Transient and isolated AA induced by electrical brain stimulation during a stereoelectroencephalography (SEEG) recording represents an ideal model for studying the associated modifications of functional connectivity and locating the hubs of awareness networks. METHODS: We investigated the SEEG signals-based brain functional connectivity (FC) changes vs background occurring during AA triggered by three thalamic and two insular stimulations in three patients explored by SEEG in the frame of presurgical evaluation for focal drug-resistant epilepsy. The results were compared to the stimulations of the same sites that did not induce clinical changes (negative stimulations). RESULTS: We observed decreased node strength in the pulvinar, insula, and parietal associative cortices during the thalamic and insular stimulations that induced AA. The link strengths characterizing functional coupling between the thalamus and the insular, prefrontal, temporal, or parietal associative cortices were also decreased. In contrast, there was an increased synchronization between the precuneus and the temporal lateral cortex. These FC changes were absent during the negative stimulations. CONCLUSION: Our study highlights the role of the pulvinar, insular, and parietal hubs in maintaining the awareness networks and paves the way for invasive or non-invasive neuromodulation protocols to reduce AA manifestations during epileptic seizures.

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We study game-theoretic models of human evolution to analyze fundamentals of human nature. Rival-claimants games represent common situations in which animals can avoid conflict over valuable resources by mutually recognizing asymmetric claiming rights. Unlike social-dilemma games, rival-claimants games have multiple equilibria which create a rational role for communication, and so they may be good models for the role of language in human evolution. Many social animals avoid conflict by dominance rankings, but intelligence and language allow mutual recognition of more complex norms for determining political rank or economic ownership. Sophisticated forms of economic ownership could become more advantageous when bipedalism allowed adaptation of hands for manufacturing useful objects. Cultural norms for claiming rights could develop and persist across generations in communities where the young have an innate interest in learning from their elders about when one can appropriately claim desirable objects. Then competition across communities would favor cultures where claiming rights are earned by prosocial behavior, such as contributions to public goods. With the development of larger societies in which many local communities share a common culture, individuals would prefer to interact with strangers who identifiably share this culture, because shared cultural principles reduce risks of conflict in rival-claimants games.

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Background: Visuo-perceptual and visuo-attentional disorders, such as global processing deficit and simultanagnosia, are not routinely investigated in prodromal forms of typical Alzheimer's disease, as amnestic mild cognitive impairment (MCI). Objective: This study evaluated global processing abilities through Navon's classical paradigm in individuals with amnestic MCI and investigated the related visuo-perceptual and attentional components involved in simultanagnosia. Methods: Sixteen consecutive patients with amnestic MCI (6 single-domain, 10 multiple-domain) and 16 matched controls were requested to identify global and local elements of hierarchical Navon letters, and to name large and small solid letters. Results: While correctly identifying solid letters, patients with multiple-domain amnestic MCI were less accurate in processing the global level of hierarchical stimuli compared to controls. Single-case analyses suggested that global processing may also be impaired in single-domain amnestic MCI. In addition, patients with pathological performance in the Navon task showed perceptual and/or visual focal attention deficits. Conclusions: Early dysfunction of holistic processing can be detected in amnestic MCI. Visuo-perceptual and/or visual focal attention mechanisms, which have been shown to be damaged in Posterior Cortical Atrophy patients with simultanagnosia, may be impaired in individuals with amnestic MCI. Investigation and identification of global processing deficits in MCI could contribute to early diagnosis and longitudinal monitoring of the disease.

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Accurate 6DoF (degrees of freedom) pose and focal length estimation are important in extended reality (XR) applications, enabling precise object alignment and projection scaling, thereby enhancing user experiences. This study focuses on improving 6DoF pose estimation using single RGB images of unknown camera metadata. Estimating the 6DoF pose and focal length from an uncontrolled RGB image, obtained from the internet, is challenging because it often lacks crucial metadata. Existing methods such as FocalPose and Focalpose++ have made progress in this domain but still face challenges due to the projection scale ambiguity between the translation of an object along the z-axis (tz) and the camera's focal length. To overcome this, we propose a two-stage strategy that decouples the projection scaling ambiguity in the estimation of z-axis translation and focal length. In the first stage, tz is set arbitrarily, and we predict all the other pose parameters and focal length relative to the fixed tz. In the second stage, we predict the true value of tz while scaling the focal length based on the tz update. The proposed two-stage method reduces projection scale ambiguity in RGB images and improves pose estimation accuracy. The iterative update rules constrained to the first stage and tailored loss functions including Huber loss in the second stage enhance the accuracy in both 6DoF pose and focal length estimation. Experimental results using benchmark datasets show significant improvements in terms of median rotation and translation errors, as well as better projection accuracy compared to the existing state-of-the-art methods. In an evaluation across the Pix3D datasets (chair, sofa, table, and bed), the proposed two-stage method improves projection accuracy by approximately 7.19%. Additionally, the incorporation of Huber loss resulted in a significant reduction in translation and focal length errors by 20.27% and 6.65%, respectively, in comparison to the Focalpose++ method.

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INTRODUCTION: The FLAME trial demonstrated that the dose to the gross tumor volume (GTV) is associated with tumour control in prostate cancer patients. This raises the question if dose de-escalation to the remaining prostate gland can be considered. Therefore, we investigated if intraprostatic recurrences occur at the location of the GTV and which dose was delivered at that location. MATERIALS AND METHODS: For FLAME trial patients with an intra-prostatic recurrence, we collected pre-treatment images, GTV delineations, dose distributions and post-recurrence images. Pre-treatment images were registered to the post-recurrence images (PSMA-PET CT). An overlap between GTV and PSMA-PET activity was considered an intra-prostatic recurrence at the location of the primary tumor. RESULTS: Twenty eight out of 535 patients in the FLAME trial had an intra-prostatic recurrence. Its location could be determined for 24 patients. One patient recurred in the prostate gland outside the GTV. The median D98% to the GTV was 76.5 Gy (range: 73.3-86.5 Gy). Only one patient with a recurrence in the GTV received a substantial focal boost of 86.5 Gy. The D98% of all remaining patients was < 81 Gy. CONCLUSION: Intra-prostatic recurrences of intermediate- and high-risk prostate cancer patients treated with radiotherapy appeared predominantly at the location of the primary tumor. All but one patient did not receive a high dose to the GTV. Intra-prostatic failure is likely a consequence of the undertreatment of the primary tumor rather than the undertreatment of the remaining prostate gland.