Coming dissertations at MedFak
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The leading and following brain
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-538396
Leading and following are daily activities for most individuals, as these behaviors are crucial for social interactions. When these interactions fail, they can negatively affect the individuals and the activity. The driving force behind this thesis was to understand more about the neural underpinnings of leading and following. The accomplishment of this aim required a fundamental examination of leadership and followership. A thorough and rigorous process was followed to develop a minimal model for study I to investigate neural reactivity during leading and following. This model aims to analyze leader and follower behavior in a standardized manner. The model used finger tapping of rhythms representing the core of the interactions during leading and following. Participants were invited to assume the roles of both leaders and followers, with no requirement for prior expertise. The model did not incorporate a status difference between leaders and followers.
Data collection occurred in Japan, but most analyses were conducted in Sweden. Study II translated the Swedish Universities Scales of Personality from Swedish to Japanese. Its three dimensions represent personality facets for emotional stability, extraversion, and agreeableness. Study II resulted in SSPJ-11 with 11 reliable personality scales of these three facets that are most probably relevant for leading and following. In study III and IV, participants were paired to engage in the minimal model for leading and following while their brain activity was recorded using hyperscanning EEG. For study III, a graph-based algorithm was introduced to analyze directed causal connections in time series data. It was combined with hyperscanning EEG prefrontal cortex activation of single and two interacting brains. The PCMCI algorithm effectively detected directed causal connections within and between participants. In study IV, PCMCI assessed whole brain-directed causal networks of leading and following within and between brains. The results of Study I and IV indicate a significant overlap in neural reactivation between the roles of leading and following, albeit with certain role-specific differences. Leadership activations indicate focus on decision-making, task performance, social cognition, and effective processing and followership activation stipulate social adaptivity and task focus. These results could be a first step towards elucidating the pivotal components of neural reactivations in the context of leading and following. Ultimately, these discoveries could provide a foundation for the creation of novel, sustainable, and effective cross-cultural training techniques designed to enhance both performance and well-being in leadership and followership, thereby presenting a promising vision for the future.
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Spatial characterization of proteins in reproductive tissues : Insights into health and disease states
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-536635
The molecular building blocks of human cells have been increasingly mapped in large-scale projects by emerging high-throughput antibody profiling and sequencing methods. These transformational efforts have shown remarkable progress in resolving the expression levels and spatial locations of proteins in many human cells. This thesis aimed to characterize the spatial protein expression at the single-cell level in human reproductive tissues, testis and fallopian tube (FT), and additionally study how aberrantly expressed testis-proteins repurposed in non-small cell lung cancer (NSCLC) affect the immune microenvironment.
In Paper I, more than 500 proteins with elevated RNA expression levels in the testis were profiled in eight different cell types with immunohistochemistry (IHC). Several poorly characterized proteins, so-called “missing proteins,” were localized at the cell-type level at various stages of spermatogenesis, providing novel insights into their possible function.
In Paper II, a spatiotemporal map of human spermatogenesis was created by combining single-cell transcriptomics and multiplex IHC. High-throughput image analysis determined the cell state-specific protein expression for almost 500 proteins. By examining RNA and protein correlation dynamics, we highlighted the complex spatiotemporal landscape of the human testis. These proteins serve as targets for functional studies.
In Paper III, protein-coding genes elevated in FT based on RNA levels were profiled by IHC, and most proteins were functionally related to cilia motility, a mechanism necessary for creating the tubal flow essential for fertilization. Of 133 proteins annotated at the cell-type level, most were exclusive to ciliated cells, including several proteins previously not described in motile cilia.
In Paper IV, cancer-testis antigens (CTA) were characterized by IHC on more than 300 immunophenotyped NSCLC patients. CTAs are typically expressed in the testis and harbor immunogenic properties that may be used as treatment targets due to aberrant expression in NSCLC. CTAs were associated with immune profiles, such as macrophage and plasma cell infiltration, possibly demonstrating an in situ immunogenic effect. These associations can be studied and exploited as potential immunotherapy targets.
This thesis defines the spatial proteome of reproductive tissues at the single-cell resolution and identifies many proteins with previously unknown functions in reproduction. The integrative approach to mapping tissue-specific cellular diversity at the molecular level shows the importance of combining RNA and protein detection methods. The thesis developed emerging methods like multiplexed staining and bioimage analysis, which hold promise for large-scale efforts. This work significantly contributes to the cellular atlas of reproductive tissues, which historically have not been well-studied.
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Evaluation of some MR and PET techniques in the differential diagnosis of intracranial lesions
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-538142
There are many different causes of intracranial lesions including infection, inflammation, stroke, tumors, and trauma. To investigate the nature of a lesion, various MR (magnetic resonance) and PET (positron emission tomography) techniques are used that can give information about the anatomical, physiological, and metabolic properties of the lesion and thereby aid in the differential diagnostic procedure. The treatment for brain tumors can include radiation therapy, which can induce brain changes that are difficult to differentiate from a recurring tumor. This thesis evaluates the investigation of intracranial lesions with several MR and PET techniques.
Paper I delt with an evaluation of how much additional information MRS (magnetic resonance spectroscopy) provides in clinical patients compared to MRI (magnetic resonance imaging). In this study that included 208 cases, it was found that the additional information gained from MRS was beneficial or very beneficial in 15% of the cases and misleading in 17% of the cases. In Paper II, a sub-population (n = 100) of the patients in Paper I was investigated. In this paper, use of a decision-support system, INTERPRET DSS 3.1, was compared with conventional analysis of MRS with regard to the correct evaluation of focal lesions. Comparing INTERPRET DSS with conventionally analyzed MRS and MRI, the diagnostic category was correct in 67/58/52 cases, indeterminate in 5/8/20 cases, and incorrect in 28/34/28 cases. In Papers III–IV, the differentiation of tumor recurrence from treatment-induced changes was evaluated. In Paper III, MR examinations were performed for calculation of the perfusion fraction (f) using the intravoxel incoherent motion imaging (IVIM) technique and for the relative cerebral blood volume (rCBV) using dynamic susceptibility contrast (DSC) perfusion in 60 patients. The accuracy of the IVIM parameter f was similar to that of rCBV in differentiating tumor recurrence from treatment-induced changes. In Paper IV, two PET techniques (11C-methionine and 18F-fluorothymidine) were compared in 48 patients. Both techniques had similar efficacy in differential diagnosis between recurrent intracranial tumor and treatment-induced changes.
In conclusion, conventionally analyzed MRS did not add to the diagnostic value of MRI in general. In focal lesions, the INTERPRET DSS system did not improve the categorization of the lesions significantly compared to conventional analysis of MRS but did so compared to MR imaging alone. IVIM can be used to differentiate tumor recurrence from treatment-induced changes. The PET tracers 11C-methionine and 18F-fluorothymidine have a similar diagnostic ability to separate tumor recurrence from treatment-induced changes.