Mitochondrial polymorphism m.3017C>T of SHLP6 relates to heterothermy

Heterothermic thermoregulation requires intricate regulation of metabolic rate and activation of pro-survival factors. Eliciting these responses and coordinating the necessary energy shifts likely involves retrograde signalling by mitochondrial-derived peptides (MDPs). Members of the group were suggested before to play a role in heterothermic physiology, a key component of hibernation and daily torpor. Here we studied the mitochondrial single-nucleotide polymorphism (SNP) m.3017C>T that resides in the evolutionarily conserved gene MT-SHLP6. The substitution occurring in several mammalian orders causes truncation of SHLP6 peptide size from twenty to nine amino acids. Public mass spectrometric (MS) data of human SHLP6 indicated a canonical size of 20 amino acids, but not the use of alternative translation initiation codons that would expand the peptide. The shorter isoform of SHLP6 was found in heterothermic rodents at higher frequency compared to homeothermic rodents (p < 0.001). In heterothermic mammals it was associated with lower minimal body temperature (Tb, p < 0.001). In the thirteen-lined ground squirrel, brown adipose tissue—a key organ required for hibernation, showed dynamic changes of the steady-state transcript level of mt-Shlp6. The level was significantly higher before hibernation and during interbout arousal and lower during torpor and after hibernation. Our finding argues to further explore the mode of action of SHLP6 size isoforms with respect to mammalian thermoregulation and possibly mitochondrial retrograde signalling

Personalizing Medicine Through Hybrid Imaging and Medical Big Data Analysis

Medical imaging has evolved from a pure visualization tool to representing a primary source of analytic approaches toward in vivo disease characterization. Hybrid imaging is an integral part of this approach, as it provides complementary visual and quantitative information in the form of morphological and functional insights into the living body. As such, non-invasive imaging modalities no longer provide images only, but data, as stated recently by pioneers in the field. Today, such information, together with other, non-imaging medical data creates highly heterogeneous data sets that underpin the concept of medical big data. While the exponential growth of medical big data challenges their processing, they inherently contain information that benefits a patient-centric personalized healthcare. Novel machine learning approaches combined with high-performance distributed cloud computing technologies help explore medical big data. Such exploration and subsequent generation of knowledge require a profound understanding of the technical challenges. These challenges increase in complexity when employing hybrid, aka dual- or even multi-modality image data as input to big data repositories. This paper provides a general insight into medical big data analysis in light of the use of hybrid imaging information. First, hybrid imaging is introduced (see further contributions to this special Research Topic), also in the context of medical big data, then the technological background of machine learning as well as state-of-the-art distributed cloud computing technologies are presented, followed by the discussion of data preservation and data sharing trends. Joint data exploration endeavors in the context of in vivo radiomics and hybrid imaging will be presented. Standardization challenges of imaging protocol, delineation, feature engineering, and machine learning evaluation will be detailed. Last, the paper will provide an outlook into the future role of hybrid imaging in view of personalized medicine, whereby a focus will be given to the derivation of prediction models as part of clinical decision support systems, to which machine learning approaches and hybrid imaging can be anchored.(VLID)473888

Assessment of PSMA Expression of Healthy Organs in Different Stages of Prostate Cancer Using [⁶⁸Ga]Ga-PSMA-11-PET Examinations

The efficacy of radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is currently being investigated for its application in patients with early-stage prostate cancer (PCa). However, little is known about PSMA expression in healthy organs in this cohort. Collectively, 202 [68Ga]Ga-PSMA-11 positron emission tomography (PET) scans from 152 patients were studied. Of these, 102 PET scans were from patients with primary PCa and hormone-sensitive biochemically recurrent PCa and 50 PET scans were from patients with metastatic castration-resistant PCa (mCRPC) before and after three cycles of [177Lu]Lu-PSMA-RLT. PSMA-standardized uptake values (SUV) were measured in multiple organs and PSMA-total tumor volume (PSMA-TTV) was determined in all cohorts. The measured PET parameters of the different cohorts were normalized to the bloodpool and compared using t- or Mann–Whitney U tests. Patients with early-stage PCa had lower PSMA-TTVs (10.39 mL vs. 462.42 mL, p p 177Lu]Lu-PSMA-RLT (462.42 mL vs. 276.29 mL, p = 0.023), no significant organ differences in PET parameters were detected. These suggest different degrees of PSMA-ligand binding among patients with different stages of PCa that could influence radiotoxicity during earlier stages of disease in different organs when PSMA-RLT is administered

Morpho-Molecular Metabolic Analysis and Classification of Human Pituitary Gland and Adenoma Biopsies Based on Multimodal Optical Imaging

Pituitary adenomas count among the most common intracranial tumors. During pituitary oncogenesis structural, textural, metabolic and molecular changes occur which can be revealed with our integrated ultrahigh-resolution multimodal imaging approach including optical coherence tomography (OCT), multiphoton microscopy (MPM) and line scan Raman microspectroscopy (LSRM) on an unprecedented cellular level in a label-free manner. We investigated 5 pituitary gland and 25 adenoma biopsies, including lactotroph, null cell, gonadotroph, somatotroph and mammosomatotroph as well as corticotroph. First-level binary classification for discrimination of pituitary gland and adenomas was performed by feature extraction via radiomic analysis on OCT and MPM images and achieved an accuracy of 88%. Second-level multi-class classification was performed based on molecular analysis of the specimen via LSRM to discriminate pituitary adenomas subtypes with accuracies of up to 99%. Chemical compounds such as lipids, proteins, collagen, DNA and carotenoids and their relation could be identified as relevant biomarkers, and their spatial distribution visualized to provide deeper insight into the chemical properties of pituitary adenomas. Thereby, the aim of the current work was to assess a unique label-free and non-invasive multimodal optical imaging platform for pituitary tissue imaging and to perform a multiparametric morpho-molecular metabolic analysis and classification

Mitochondrial polymorphism m.3017C>T of SHLP6 relates to heterothermy

Heterothermic thermoregulation requires intricate regulation of metabolic rate and activation of pro-survival factors. Eliciting these responses and coordinating the necessary energy shifts likely involves retrograde signalling by mitochondrial-derived peptides (MDPs). Members of the group were suggested before to play a role in heterothermic physiology, a key component of hibernation and daily torpor. Here we studied the mitochondrial single-nucleotide polymorphism (SNP) m.3017C>T that resides in the evolutionarily conserved gene MT-SHLP6. The substitution occurring in several mammalian orders causes truncation of SHLP6 peptide size from twenty to nine amino acids. Public mass spectrometric (MS) data of human SHLP6 indicated a canonical size of 20 amino acids, but not the use of alternative translation initiation codons that would expand the peptide. The shorter isoform of SHLP6 was found in heterothermic rodents at higher frequency compared to homeothermic rodents (p< 0.001). In heterothermic mammals it was associated with lower minimal body temperature (Tb, p< 0.001). In the thirteen-lined ground squirrel, brown adipose tissue-a key organ required for hibernation, showed dynamic changes of the steady-state transcript level of mt-Shlp6. The level was significantly higher before hibernation and during interbout arousal and lower during torpor and after hibernation. Our finding argues to further explore the mode of action of SHLP6 size isoforms with respect to mammalian thermoregulation and possibly mitochondrial retrograde signalling