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- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 5. |
- Kostecka, A, et al.
(författare)
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High prevalence of somatic PIK3CA and TP53 pathogenic variants in the normal mammary gland tissue of sporadic breast cancer patients revealed by duplex sequencing
- 2022
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 8:1, s. 76-
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Tidskriftsartikel (refereegranskat)abstract
- The mammary gland undergoes hormonally stimulated cycles of proliferation, lactation, and involution. We hypothesized that these factors increase the mutational burden in glandular tissue and may explain high cancer incidence rate in the general population, and recurrent disease. Hence, we investigated the DNA sequence variants in the normal mammary gland, tumor, and peripheral blood from 52 reportedly sporadic breast cancer patients. Targeted resequencing of 542 cancer-associated genes revealed subclonal somatic pathogenic variants of: PIK3CA, TP53, AKT1, MAP3K1, CDH1, RB1, NCOR1, MED12, CBFB, TBX3, and TSHR in the normal mammary gland at considerable allelic frequencies (9 × 10−2– 5.2 × 10−1), indicating clonal expansion. Further evaluation of the frequently damaged PIK3CA and TP53 genes by ultra-sensitive duplex sequencing demonstrated a diversified picture of multiple low-level subclonal (in 10−2–10−4 alleles) hotspot pathogenic variants. Our results raise a question about the oncogenic potential in non-tumorous mammary gland tissue of breast-conserving surgery patients.
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| 7. |
- Orejas, C, et al.
(författare)
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Cold-water corals in aquaria: advances and challenges. A focus on the Mediterranean
- 2019
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Ingår i: Mediterranean Cold-Water Corals: Past, Present and Future. - : Springer. - 2213-719X. - 9783319916071
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Bokkapitel (refereegranskat)abstract
- Knowledge on basic biological functions of organisms is essential to understand not only the role they play in the ecosystems but also to manage and protect their populations. The study of biological processes, such as growth, reproduction and physiology, which can be approached in situ or by collecting exemplars and rearing them in aquaria, is particularly challenging for deep-sea organisms such as cold-water corals (CWCs). Present experimental work and monitoring of deep-sea populations is still a chimera. Only a handful of research institutes or companies have been able to install in situ marine observatories in the Mediterranean Sea or elsewhere, which facilitate for a continuous monitoring of deep-sea ecosystems. Hence, today’s best way to obtain basic biological information on these organisms is (1) working with collected samples and analysing them post-mortem and / or (2) cultivating corals in aquaria in order to monitor biological processes and investigate coral behaviour and physiological responses under different experimental treatments. The first challenging aspect is the collection process, which implies the use of oceanographic research vessels in most occasions, since these organisms inhabit areas between ca. 150 m to more than 1,000 m depth, and specific sampling gears. The next challenge is the maintenance of the animals on board (in situations where cruises may take weeks) and their transport to home laboratories. Maintenance in the home labs is also extremely challenging since special conditions and set ups are needed to conduct experimental studies to obtain information on the biological processes of these animals. The complexity of the natural environment from which the corals were collected cannot be exactly replicated within the laboratory setting; a fact which has led some researchers to question the validity of work and conclusions drawn from such undertakings. It is evident that aquaria experiments cannot perfectly reflect the real environmental and trophic conditions where these organisms occur, but: (1) in most cases we do not have the possibility to obtain equivalent in situ information and (2) even with limitations, they produce relevant information about 117 the biological limits of the species, which is especially valuable when considering potential future climate change scenarios. This chapter includes many contributions from different authors and it intends to be both, a practical “handbook” for conducting CWC aquaria work, while at the same time, to offer an overview on the CWC research conducted in Mediterranean labs equipped with aquaria infrastructure. Experiences from Atlantic and Pacific laboratories with extensive experience with CWC work have also contributed to this chapter, as their procedures are valuable to any researcher interested in conducting experimental work with CWC in aquaria. It was impossible to include contributions from all labs in the world currently working experimentally with CWCs in the laboratory, but at the conclusion of the chapter we attempt, to our best of our knowledge, to supply a list of laboratories with operational CWC aquaria facilities.
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| 10. |
- Barth, Claudia, et al.
(författare)
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In vivo white matter microstructure in adolescents with early-onset psychosis : a multi-site mega-analysis
- 2023
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 28, s. 1159-1169
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Tidskriftsartikel (refereegranskat)abstract
- Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls using diffusion tensor imaging (DTI). Our sample included 321 adolescents with EOP (median age=16.6 years, interquartile range (IQR)=2.14, 46.4% females) and 265 adolescent healthy controls (median age=16.2 years, IQR=2.43, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for 25 white matter regions of interest per participant. ComBat harmonization was performed for all DTI measures to adjust for scanner differences. Multiple linear regression models were fitted to investigate case-control differences and associations with clinical variables in regional DTI measures. We found widespread lower FA in EOP compared to healthy controls, with the largest effect sizes in the superior longitudinal fasciculus (Cohen's d=0.37), posterior corona radiata (d=0.32), and superior fronto-occipital fasciculus (d=0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. Using the largest EOP DTI sample to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male individuals with early-onset schizophrenia and individuals with a shorter duration of illness.
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| 11. |
- Filipowicz, Natalia, et al.
(författare)
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Comprehensive cancer-oriented biobanking resource of human samples for studies of post-zygotic genetic variation involved in cancer predisposition
- 2022
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:4
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Tidskriftsartikel (refereegranskat)abstract
- The progress in translational cancer research relies on access to well-characterized samples from a representative number of patients and controls. The rationale behind our biobanking are explorations of post-zygotic pathogenic gene variants, especially in non-tumoral tissue, which might predispose to cancers. The targeted diagnoses are carcinomas of the breast (via mastectomy or breast conserving surgery), colon and rectum, prostate, and urinary bladder (via cystectomy or transurethral resection), exocrine pancreatic carcinoma as well as metastases of colorectal cancer to the liver. The choice was based on the high incidence of these cancers and/or frequent fatal outcome. We also collect age-matched normal controls. Our still ongoing collection originates from five clinical centers and after nearly 2-year cooperation reached 1711 patients and controls, yielding a total of 23226 independent samples, with an average of 74 donors and 1010 samples collected per month. The predominant diagnosis is breast carcinoma, with 933 donors, followed by colorectal carcinoma (383 donors), prostate carcinoma (221 donors), bladder carcinoma (81 donors), exocrine pancreatic carcinoma (15 donors) and metachronous colorectal cancer metastases to liver (14 donors). Forty percent of the total sample count originates from macroscopically healthy cancer-neighboring tissue, while contribution from tumors is 12%, which adds to the uniqueness of our collection for cancer predisposition studies. Moreover, we developed two program packages, enabling registration of patients, clinical data and samples at the participating hospitals as well as the central system of sample/data management at coordinating center. The approach used by us may serve as a model for dispersed biobanking from multiple satellite hospitals. Our biobanking resource ought to stimulate research into genetic mechanisms underlying the development of common cancers. It will allow all available "-omics" approaches on DNA-, RNA-, protein- and tissue levels to be applied. The collected samples can be made available to other research groups.
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| 12. |
- Hauke, DJ, et al.
(författare)
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Multimodal prognosis of negative symptom severity in individuals at increased risk of developing psychosis
- 2021
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1, s. 312-
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Tidskriftsartikel (refereegranskat)abstract
- Negative symptoms occur frequently in individuals at clinical high risk (CHR) for psychosis and contribute to functional impairments. The aim of this study was to predict negative symptom severity in CHR after 9 months. Predictive models either included baseline negative symptoms measured with the Structured Interview for Psychosis-Risk Syndromes (SIPS-N), whole-brain gyrification, or both to forecast negative symptoms of at least moderate severity in 94 CHR. We also conducted sequential risk stratification to stratify CHR into different risk groups based on the SIPS-N and gyrification model. Additionally, we assessed the models’ ability to predict functional outcomes in CHR and their transdiagnostic generalizability to predict negative symptoms in 96 patients with recent-onset psychosis (ROP) and 97 patients with recent-onset depression (ROD). Baseline SIPS-N and gyrification predicted moderate/severe negative symptoms with significant balanced accuracies of 68 and 62%, while the combined model achieved 73% accuracy. Sequential risk stratification stratified CHR into a high (83%), medium (40–64%), and low (19%) risk group regarding their risk of having moderate/severe negative symptoms at 9 months follow-up. The baseline SIPS-N model was also able to predict social (61%), but not role functioning (59%) at above-chance accuracies, whereas the gyrification model achieved significant accuracies in predicting both social (76%) and role (74%) functioning in CHR. Finally, only the baseline SIPS-N model showed transdiagnostic generalization to ROP (63%). This study delivers a multimodal prognostic model to identify those CHR with a clinically relevant negative symptom severity and functional impairments, potentially requiring further therapeutic consideration.
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