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Platinum-based drugs induce phenotypic alterations in nucleoli and Cajal bodies in prostate cancer cells
No full textPurpose: Platinum-based drugs are cytotoxic drugs commonly used in cancer treatment. They cause DNA damage, effects of which on chromatin and cellular responses are relatively well described. Yet, the nuclear stress responses related to RNA processing are incompletely known and may be relevant for the heterogeneity with which cancer cells respond to these drugs. Here, we determine the type and extent of nuclear stress responses of prostate cancer cells to clinically relevant platinum drugs.Methods: We study nucleolar and Cajal body (CB) responses to cisplatin, carboplatin, and oxaliplatin with immunofluorescence-based methods in prostate cancer cells. We utilize organelle-specific markers NPM, Fibrillarin, Coilin, and SMN1, and study CB-regulatory proteins FUS and TDP-43 using siRNA-mediated downregulation.Results: Different types of prostate cancer cells have different sensitivities to platinum drugs. With equally cytotoxic doses, cisplatin, and oxaliplatin induce prominent nucleolar and CB stress responses while the nuclear stress phenotypes to carboplatin are milder. We find that Coilin is a stress-specific marker for platinum drug response heterogeneity. We also find that CB-associated, stress-responsive RNA binding proteins FUS and TDP-43 control Coilin and CB biology in prostate cancer cells and, further, that TDP-43 is associated with stress-responsive CBs in prostate cancer cells.Conclusion: Our findings provide insight into the heterologous responses of prostate cancer cells to different platinum drug treatments and indicate Coilin and TDP-43 as stress mediators in the varied outcomes. These results help understand cancer drug responses at a cellular level and have implications in tackling heterogeneity in cancer treatment outcomes.</p
Generating Synthetic Mechanocardiograms for Machine Learning Based Peak Detection
No full textAcquiring labeled data for machine learning algorithms in healthcare is expensive due to the laborious expert annotation and privacy concerns. This challenge is further complicated in the case of Mechanocardiogram (MCG) data, which are characterized by high inter- and intrapersonal complexity, compounded further by sensor variability. In this paper, we introduce an innovative method for generating synthetic mechanocardiogram (MCG) signals to address the scarcity of labeled data necessary for training machine learning models in healthcare. Our approach involves generating RR-intervals, adding wavelets, and incorporating noise to create realistic synthetic MCG signals. These synthetic signals were used to train a convolutional neural network (CNN) for peak detection in real MCG data. Our key contributions include developing a detailed methodology for realistic synthetic MCG signal generation, reducing the mean absolute error (MAE) in peak detection by 4.88 beats per minute (BPM) using synthetic data, enhancing the training of machine learning models, creating a new peak detection method, and addressing data scarcity in biomedical signal processing. These contributions emphasize the methodological innovations and the significance of our results, underscoring the potential impact of synthetic data in improving healthcare diagnostics
The ‘fourth wall’ and other usability issues in AI-generated personas : comparing chat-based and profile personas
Full text linkLarge Language Models (LLMs) are emerging as a powerful tool for AI-generated personas. This study evaluates the usability of AI-generated personas, comparing chat and profile formats. The findings indicate chat personas tend to be perceived more favourably, and profile personas exhibit greater variability in user perception. The increased difficulty and longer dwell time experienced by users with the profile persona, despite negative usability metrics, paradoxically resulted in better task performance. Usability issues indicate that many current limitations of AI, including verbosity, hallucinations, and empty rhetoric which was described as the persona having 'no soul', are inherited in AI-generated chat personas. However, there are also new issues. For one, the risk of information overload in an AI-generated profile persona implies that the AI does not consider human users' cognitive limitations when designing the persona (but usability scores for profile personas increase with dwell time, implying that users get used to the longer format the more time they spend). Another is the 'fourth wall' effect of AI-generated chat personas in which the user feels they are talking to someone describing the persona rather than the persona itself. Future work could address the usability paradox and the fourth wall effect of using personas.CCS CONCEPTSHuman-centered computing Human computer interaction (HCI)</p
Accumulating evidence from meta-analyses of prognostic studies on oral cancer: towards biomarker-driven patient selection
Full text linkBackgroundMany histopathologic prognostic markers, identified by routine hematoxylin and eosin (HE) staining, have been proposed for predicting the survival of patients with oral squamous cell carcinoma (OSCC). Subsequently, several meta-analyses have been conducted on these prognostic markers. We sought to analyze the accumulated evidence from these meta-analyses.MethodsAn electronic database search of PubMed, Scopus, Ovid Medline, Web of Science, and Cochrane Library was conducted to retrieve all meta-analysis articles published on histopathologic prognostic markers of OSCC. The risk of bias of the included studies was analyzed using the Risk of Bias in Systematic Reviews (ROBIS) tool. The synthesis of the results was conducted following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).ResultsThere were 16 meta-analysis articles published on the histological prognostic markers of OSSC. The accumulated evidence from these meta-analyses highlighted the powerful prognostic value of depth of invasion, tumor thickness, perineural invasion, lymphovascular invasion, worst pattern of invasion, tumor budding, and tumor-stroma ratio. The highest odds ratio (OR) of a relationship between a histopathologic prognostic marker and outcome was for the depth of invasion (OR 10.16, 95% CI 5.05-20.46) and tumor thickness (OR 7.32, 95% CI 5.3-10.1) in predicting lymph node metastasis.ConclusionThe published meta-analyses present robust evidence on the significance of emerging histopathologic markers, namely, worst pattern of invasion, tumor budding, and tumor-stroma ratio. It is time to consider such markers in daily pathology reporting and risk stratification of OSCC.</p
Short- and long-term effects of imatinib in hospitalised COVID-19 patients : A randomised trial
Full text linkObjectives We studied the short- and long-term effects of imatinib in hospitalised COVID-19 patients. Methods Participants were randomised to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomised trials studying imatinib for 30-day mortality in hospitalised COVID-19 patients. Results We randomised 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year and in SoC 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47–3.90). At 1-year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78-1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32–1.63; low certainty evidence). Conclusions The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalised COVID-19 patients.</p
Progress towards the two-thirds conjecture on locating-total dominating sets
No full textWe study upper bounds on the size of optimum locating-total dominating sets in graphs. A set S of vertices of a graph G is a locating-total dominating set if every vertex of G has a neighbor in S, and if any two vertices outside S have distinct neighborhoods within S. The smallest size of such a set is denoted by γtL(G). It has been conjectured that γtL(G)≤2n3 holds for every twin-free graph G of order n without isolated vertices. We prove that the conjecture holds for cobipartite graphs, split graphs, block graphs and subcubic graphs
Outcomes After Multimodality Treatment of Pancreatic Cancer in an Unselected Single-Center Cohort
Full text linkBackground: Pancreatic ductal adenocarcinoma (PDAC) remains a lethal and rarely resectable malignancy. Here we explore the outcomes of surgery, as compared to definitive radiotherapy (dRT) or systemic therapy only in PDAC.Methods: Pancreatic surgery and radiotherapy in Southwest Finland have been centralized to Turku University Hospital. Previously validated population-based electronic health records database was searched for all unselected PDAC patients from the years 2009– 2019. Main outcome was median overall survival (mOS). Demographics, pathology, surgery, and oncological treatment data were collected.Results: We identified 1006 patients with PDAC, 49% male, median age 71 years and 77% presenting with metastatic disease. In total, 405 patients were treated; 92 resected, 26 dRT without resection and 287 systemic therapy only. mOS was 34.6 months for resected, 26.7 months for dRT, and 7.5 months for systemic therapy patients. Among the 88 patients with locally advanced inoperable PDAC, dRT was independently associated with longer mOS (26.7 months) as compared to systemic therapy only (mOS 10.6 months). Among the 287 patients treated with systemic therapy only, combination chemotherapy was independently associated with longer mOS (11.6 months) as compared to gemcitabine-monotherapy (6.8 months). In patients progressing to second-line systemic treatment after gemcitabine failure, mOS was the same (5.0 months) with single or combination regimens.Conclusion: Surgery remains the only curative approach for PDAC. In locally advanced PDAC, dRT was associated with longer survival as compared to systemic therapy only. Concerning first-line systemic therapy, our results support the use of combination chemotherapy over single-agent therapy.</p
Ympäristöherkkyydestä lajienväliseen liittolaisuuteen: Tulkintoja kasvisuhteesta Korppoon Paljasjalkapolulla
Full text linkArtikkelissa nykytaidetta kohdataan Korppoon metsiin sijoittuvalla Paljasjalkapolulla. Elävien kasvien kanssa tehdyt – toisin sanoen kasvitaiteen teokset avaavat tässä artikkelissa näkökulmia ihmisen kasvisuhteeseen, jonka etääntymistä viime vuosisatoina voidaan pitää merkittävänä tekijänä monien ilmasto- ja ympäristökriisien taustalla. Millaisen kasvisuhteen äärelle Paljasjalkapolku ja sen teokset johdattelevat? Mitä ne kertovat ihmisen mahdollisuuksista lähentyä ja liittoutua kasvien kanssa? Kohdattavat teokset ovat Antti Laitisen Haarniska (2014) ja Hannah Streefkerkin Paikatut puut (2018), joita lähestytään ympäristölle herkistyen ja taiteen materiaalisuuksista vaikuttuen. Elävän männyn ympärille koottu metallinen Haarniska kutsuu pohtimaan ihmisen mahdollisuuksia suojella luontoa siihen kohdistuvilta uhilta. Paikatut puut korjaa puihin syntyneitä vaurioita punaisen villalangan avulla ja herättää keskustelua luontoon kohdistuvasta hoivasta sekä kasvisuhteen korjaamisesta. Artikkelille tyypillinen, maailmalle avoin tutkimusasenne tuo yhteen teoreettisia otteita posthumanismista, uusmaterialismista ja fenomenologiasta, jotka kytkeytyvät luontevasti metodologiseen lähestymistapaan: ympäristöherkkyyteen. Näin tarkasteltuna Paljasjalkapolku johdattaa entistä vastavuoroisemman ja tulevaisuuteen katsovan kasvisuhteen äärelle, jossa liittolaisuus on avain entistä elinkelpoisempien tulevaisuuksien rakentamiseen niin ihmisille kuin kasveille.</p
Role of patient characteristics in adherence to first-line treatment guidelines in breast, lung and prostate cancer: insights from the Nordic healthcare system
Full text linkObjectives This study investigates the influence of socioeconomic status, health literacy, and numeracy on treatment decisions and the occurrence of adverse events in patients with breast, lung, and prostate cancer within a Nordic healthcare setting.Design A follow-up to a cross-sectional, mixed-methods, single-centre study.Setting A Nordic, tertiary cancer clinic.Participants A total of 244 participants with breast, lung and prostate cancer were initially identified, of which 138 first-line treatment participants were eligible for this study. First-line treatment participants (n=138) surpassed the expected cases (n=108).Interventions Not applicable as this was an observational study.Primary and secondary outcome measures The study’s primary endpoint was the rate of guideline adherence. The secondary endpoint involved assessing treatment toxicity in the form of adverse events.Results Guideline-adherent treatment was observed in 114 (82.6%) cases. First-line treatment selection appeared uninfluenced by participants’ education, occupation, income or self-reported health literacy. A minority (3.6%) experienced difficulties following treatment instructions, primarily with oral cancer medications.Conclusions The findings indicated lesser cancer health disparities regarding guideline adherence and treatment toxicity within the Nordic healthcare framework. A causal connection may not be established; however, the findings contribute to discourse on equitable cancer health provision.</p
Transkraniaalinen magneettistimulaatio traumaperäisen stressihäiriön hoidossa
No full textTutkielmassa käsitellään transkraniaalisen magneettistimulaation (TMS) vaikutuksia traumaperäisen stressihäiriön hoidossa. Tutkielman toteutustapa on kirjallisuuskatsaus. TMS luo muuttuvan magneet-tikentän avulla sähkövirran aivokuoreen. Riittävän voimakas sähkövirta saa aikaan hermosolun akti-voitumisen, minkä avulla voidaan aktivoida aivojen verkostoja. Tällä hetkellä hoitoja käytetään hoito-resistenssiin masennukseen. TMS:n käyttöön vaikuttaa tietämys traumaperäisen stressihäiriön (PTSD) vaikutuksista aivoissa ja laitteen toimintaa. PTSD:n korkean samanaikaisuuden masennuksen kanssa takia esitellään sitä kevyesti myös. Laitteen toiminnassa pitää ottaa huomioon laiteen ja ihmi-sen fysiologisia rajoituksia. TMS:n muodoista käsitellään eniten sarjamagneettistimulaatiohoitoa rTMS, teeta-purskehoitoa TBS ja syvää magneettistimulaatiohoitoa dTMS. Tutkielmassa käsitellään tietoa TMS:n hoitomuotona PTSD:seen tutkimuksien ja katsausartikkelien näkökulmista dorsolateraa-liseen (dlPFC) ja mediaaliseen (mPFC) etuotsalohkoon. Näiden tuloksien tulkitsemisessa esitellään sitä ennen tilastotieteellisiä tekniikoita ja miten eri aivoalueet ovat yhteydessä toisiinsa. Useimmat katsauksien ja tutkimusten tulokset ovat olleet hyviä, mutta pieni osallistujamäärä ja vähäinen tutki-mus heikentää luotettavuutta. Esitellään muutamia tutkimuksia, joissa lumeryhmä on pärjännyt hoito-ryhmää paremmin. Näiden lisäksi esitellään muutama aivojen alueista, joiden tietoa voidaan hyödyn-tää saavuttamaan parempia hoitotuloksia