cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.6845096
title: Improved efficacy of mitochondrial disrupting agents upon inhibition of autophagy in a mouse model of BRCA1-deficient breast cancer

description: Breast cancer is a heterogeneous disease, and stratification of patients is fundamental to the success of treatment modalities. Breast tumors deficient in BRCA1 are mostly associated with basal-like breast cancers and targeted therapeutics for this disease subtype are still lacking. In order to address whether macroautophagy/autophagy inhibition will be effective in BRCA1-deficient mammary tumors, we generated mice with conditional deletion of an essential autophagy gene, <i>Rb1cc1</i>, along with <i>Brca1</i> and <i>Trp53</i>, through utilization of the K14-<i>Cre</i> transgene. We found that <i>Rb1cc1</i> deletion suppressed tumorigenesis in the BRCA1-deficient model when compared to wild type and heterozygous <i>Rb1cc1</i> controls. However, in contrast to previous studies in the mouse mammary tumor virus (MMTV)-polyoma middle T antigen (PyMT) model, tumor growth and the distribution of histological subtypes were not affected by loss of RB1CC1. Interestingly, loss of RB1CC1 decreased mitochondrial mass and oxidative respiratory capacity of these tumor cells, along with a decrease in the phosphorylation of MTOR substrates and transcript levels of genes involved in mitochondrial biogenesis. Importantly, we observed an increased sensitivity to mitochondrial disrupting agents upon loss of RB1CC1. Consequently, our data showed that combination of an autophagy inhibitor, spautin-1, along with a mitochondrial complex I inhibitor, metformin, was more effective in limiting oxidative respiratory capacity, colony-forming ability and tumor growth. Altogether, our results indicate that inhibition of autophagy can increase the benefits of metformin treatment in BRCA1-deficient breast cancers.
DOI: 10.6084/m9.figshare.6845093.v1
title: Kinship analysis and allelic dropout: a forensic approach on an archaeological case

description: <b>Background:</b> This study relies on the discovery of two pit burials (LTA and LTB) of the Bronze Age Cogotas I archaeological culture (<i>circa</i> 3600–2950 BP) in Spain. LTA was a single burial and LTB contained three skeletal remains of two adults and a newborn or foetus at term. <b>Aim:</b> The central question posed by this find was whether the LTB tomb constituted a traditional nuclear family (father, mother and son or daughter). <b>Methods:</b> Ancient and forensic DNA protocols were employed to obtain reliable results. Autosomal, X-STR markers and mitochondrial DNA were amplified. Subsequently, different kinship probabilities were estimated by means of LR values calculated using the Familias 3 software. Furthermore, an allelic dropout sensitivity test was developed in order to evaluate the influence of allelic dropout phenomena on the results. <b>Results:</b> It was possible to determine the molecular sex of all individuals and to establish a maternal relationship between the perinatal individual and one of the adults. <b>Conclusion:</b> The remains in the LTB tomb were not a traditional nuclear family (father, mother and son/daughter) and it was probably a tomb where two women, one of them pregnant, were buried.
DOI: 10.6084/m9.figshare.6845096.v1
title: Improved efficacy of mitochondrial disrupting agents upon inhibition of autophagy in a mouse model of BRCA1-deficient breast cancer

description: Breast cancer is a heterogeneous disease, and stratification of patients is fundamental to the success of treatment modalities. Breast tumors deficient in BRCA1 are mostly associated with basal-like breast cancers and targeted therapeutics for this disease subtype are still lacking. In order to address whether macroautophagy/autophagy inhibition will be effective in BRCA1-deficient mammary tumors, we generated mice with conditional deletion of an essential autophagy gene, <i>Rb1cc1</i>, along with <i>Brca1</i> and <i>Trp53</i>, through utilization of the K14-<i>Cre</i> transgene. We found that <i>Rb1cc1</i> deletion suppressed tumorigenesis in the BRCA1-deficient model when compared to wild type and heterozygous <i>Rb1cc1</i> controls. However, in contrast to previous studies in the mouse mammary tumor virus (MMTV)-polyoma middle T antigen (PyMT) model, tumor growth and the distribution of histological subtypes were not affected by loss of RB1CC1. Interestingly, loss of RB1CC1 decreased mitochondrial mass and oxidative respiratory capacity of these tumor cells, along with a decrease in the phosphorylation of MTOR substrates and transcript levels of genes involved in mitochondrial biogenesis. Importantly, we observed an increased sensitivity to mitochondrial disrupting agents upon loss of RB1CC1. Consequently, our data showed that combination of an autophagy inhibitor, spautin-1, along with a mitochondrial complex I inhibitor, metformin, was more effective in limiting oxidative respiratory capacity, colony-forming ability and tumor growth. Altogether, our results indicate that inhibition of autophagy can increase the benefits of metformin treatment in BRCA1-deficient breast cancers.
DOI: 10.6084/m9.figshare.6845087
title: A metabolic energy expenditure model with a continuous first derivative and its application to predictive simulations of gait

description: Whether humans minimize metabolic energy in gait is unknown. Gradient-based optimization could be used to predict gait without using walking data but requires a twice differentiable metabolic energy model. Therefore, the metabolic energy model of Umberger et al. (2003) was adapted to be twice differentiable. Predictive simulations of a reaching task and gait were solved using this continuous model and by minimizing effort. The reaching task simulation showed that energy minimization predicts unrealistic movements when compared to effort minimization. The predictive gait simulations showed that objectives other than metabolic energy are also important in gait.
DOI: 10.6084/m9.figshare.6845087.v1
title: A metabolic energy expenditure model with a continuous first derivative and its application to predictive simulations of gait

description: Whether humans minimize metabolic energy in gait is unknown. Gradient-based optimization could be used to predict gait without using walking data but requires a twice differentiable metabolic energy model. Therefore, the metabolic energy model of Umberger et al. (2003) was adapted to be twice differentiable. Predictive simulations of a reaching task and gait were solved using this continuous model and by minimizing effort. The reaching task simulation showed that energy minimization predicts unrealistic movements when compared to effort minimization. The predictive gait simulations showed that objectives other than metabolic energy are also important in gait.
DOI: 10.6084/m9.figshare.6845012
title: Should Intravesical Bacillus Calmette-Guerin(BCG) Treatment be Administered to Patients with T0 after Repeat Transurethral Resection of Bladder Tumor in Patients with High-risk Non-muscle Invasive Bladder Cancer?

description: We evaluated the effect of intravesical Bacillus Calmette–Guerin (BCG) and BCG maintenance therapy on the prognosis of patients with T0 after repeat transurethral resection of bladder mass (TURBT). This retrospective analysis involved 427 patients who underwent repeat TURBT within 6 weeks after initial TURBT from 2007 to 2016. Repeat TURBT was performed in patients with high-risk criteria. Patients who achieved T0 after repeat TURBT did or did not receive intravesical BCG therapy. Patients were divided into three groups: non-BCG, BCG induction, and BCG maintenance groups. The study included 106 patients who achieved T0 after repeat TURBT. The median follow-up was 63 months. There were no significant differences in T stage among the three groups. High grade ratio (p = 0.001) and concomitant CIS ratio (p=0.037) were significantly higher in the BCG maintenance than in the other two groups. The recurrence rates in the non-BCG, BCG induction, and BCG maintenance groups were 46.2%, 28.3%, and 19.2%, respectively (p=0.043). Recurrence-free survival was significantly higher in the BCG maintenance group than in the BCG induction group (p=0.032). Progression-free survival was also higher in the BCG maintenance group than in the BCG induction group, but the difference was not significant (p=0.056). Multivariate Cox regression analysis showed that only intravesical BCG maintenance therapy was significantly associated with recurrence (hazard ratio 0.016, p=0.016). In high risk NMIBC patients, intravesical BCG maintenance treatment is required even at T0 after repeat TURBT. Intravesical BCG maintenance therapy of patients with T0 after TURBT reduces recurrence.<br>
DOI: 10.6084/m9.figshare.6845012.v1
title: Predictive value of systemic inflammatory response markers before treatment of non-muscle invasive bladder cancer patients, initial intravesical Bacillus Calmette-Guerin treatment after transurethral resection of bladder tumor

description: The study investigated the pretreatment systemic inflammatory response (SIR) markers of patients who underwent initial intravesical treatment for high-risk non-muscle invasive bladder cancer (NMIBC). 385 patients who underwent initial intravesical Bacillus Calmette-Guerin treatment after transurethral resection of bladder tumor were included. We analyzed the relationship between standardized incidence ratio of SIR markers, such as neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR) and platelet-to-lymphocyte ratio (PLR), and oncological outcomes. Each SIR marker was used for analysis by determining the cut-off value through receiver operation characteristics curves analysis. Patients were divided into two groups according to pretreatment NLR (&lt;1.5 vs ≥1.5), dNLR (&lt;1.2 vs ≥1.2) and PLR values (171 Cox multivariate analysis revealed that age. NLR, dNLR, hemoglobin, and pathologic T stage were important factors for predicting overall survival. Age, NLR, and pathologic T stage were important factors for predicting cancer-specific survival, NLR and tumor number were the most important predictors of bladder preserving survival.<b> </b>NLR before treatment was correlated with both oncological outcomes and survival outcome in NMIBC patients undergoing initial intravesical BCG treatment after TURB. Increased NLR reflects a poor prognosis of these outcomes.
DOI: 10.6084/m9.figshare.6845012.v2
title: Predictive value of systemic inflammatory response markers before treatment of non-muscle invasive bladder cancer patients, initial intravesical Bacillus Calmette-Guerin treatment after transurethral resection of bladder tumor

description: The study investigated the pretreatment systemic inflammatory response (SIR) markers of patients who underwent initial intravesical treatment for high-risk non-muscle invasive bladder cancer (NMIBC). 385 patients who underwent initial intravesical Bacillus Calmette-Guerin treatment after transurethral resection of bladder tumor were included. We analyzed the relationship between standardized incidence ratio of SIR markers, such as neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR) and platelet-to-lymphocyte ratio (PLR), and oncological outcomes. Each SIR marker was used for analysis by determining the cut-off value through receiver operation characteristics curves analysis. Patients were divided into two groups according to pretreatment NLR (&lt;1.5 vs ≥1.5), dNLR (&lt;1.2 vs ≥1.2) and PLR values (171 Cox multivariate analysis revealed that age. NLR, dNLR, hemoglobin, and pathologic T stage were important factors for predicting overall survival. Age, NLR, and pathologic T stage were important factors for predicting cancer-specific survival, NLR and tumor number were the most important predictors of bladder preserving survival.<b> </b>NLR before treatment was correlated with both oncological outcomes and survival outcome in NMIBC patients undergoing initial intravesical BCG treatment after TURB. Increased NLR reflects a poor prognosis of these outcomes.
DOI: 10.6084/m9.figshare.6845012.v4
title: Should Intravesical Bacillus Calmette-Guerin(BCG) Treatment be Administered to Patients with T0 after Repeat Transurethral Resection of Bladder Tumor in Patients with High-risk Non-muscle Invasive Bladder Cancer?

description: We evaluated the effect of intravesical Bacillus Calmette–Guerin (BCG) and BCG maintenance therapy on the prognosis of patients with T0 after repeat transurethral resection of bladder mass (TURBT). This retrospective analysis involved 427 patients who underwent repeat TURBT within 6 weeks after initial TURBT from 2007 to 2016. Repeat TURBT was performed in patients with high-risk criteria. Patients who achieved T0 after repeat TURBT did or did not receive intravesical BCG therapy. Patients were divided into three groups: non-BCG, BCG induction, and BCG maintenance groups. The study included 106 patients who achieved T0 after repeat TURBT. The median follow-up was 63 months. There were no significant differences in T stage among the three groups. High grade ratio (p = 0.001) and concomitant CIS ratio (p=0.037) were significantly higher in the BCG maintenance than in the other two groups. The recurrence rates in the non-BCG, BCG induction, and BCG maintenance groups were 46.2%, 28.3%, and 19.2%, respectively (p=0.043). Recurrence-free survival was significantly higher in the BCG maintenance group than in the BCG induction group (p=0.032). Progression-free survival was also higher in the BCG maintenance group than in the BCG induction group, but the difference was not significant (p=0.056). Multivariate Cox regression analysis showed that only intravesical BCG maintenance therapy was significantly associated with recurrence (hazard ratio 0.016, p=0.016). In high risk NMIBC patients, intravesical BCG maintenance treatment is required even at T0 after repeat TURBT. Intravesical BCG maintenance therapy of patients with T0 after TURBT reduces recurrence.<br>
DOI: 10.6084/m9.figshare.6845012.v3
title: Should Intravesical Bacillus Calmette-Guerin(BCG) Treatment be Administered to Patients with T0 after Repeat Transurethral Resection of Bladder Tumor in Patients with High-risk Non-muscle Invasive Bladder Cancer?

description: We evaluated the effect of intravesical Bacillus Calmette–Guerin (BCG) and BCG maintenance therapy on the prognosis of patients with T0 after repeat transurethral resection of bladder mass (TURBT). This retrospective analysis involved 427 patients who underwent repeat TURBT within 6 weeks after initial TURBT from 2007 to 2016. Repeat TURBT was performed in patients with high-risk criteria. Patients who achieved T0 after repeat TURBT did or did not receive intravesical BCG therapy. Patients were divided into three groups: non-BCG, BCG induction, and BCG maintenance groups. The study included 106 patients who achieved T0 after repeat TURBT. The median follow-up was 63 months. There were no significant differences in T stage among the three groups. High grade ratio (p = 0.001) and concomitant CIS ratio (p=0.037) were significantly higher in the BCG maintenance than in the other two groups. The recurrence rates in the non-BCG, BCG induction, and BCG maintenance groups were 46.2%, 28.3%, and 19.2%, respectively (p=0.043). Recurrence-free survival was significantly higher in the BCG maintenance group than in the BCG induction group (p=0.032). Progression-free survival was also higher in the BCG maintenance group than in the BCG induction group, but the difference was not significant (p=0.056). Multivariate Cox regression analysis showed that only intravesical BCG maintenance therapy was significantly associated with recurrence (hazard ratio 0.016, p=0.016). In high risk NMIBC patients, intravesical BCG maintenance treatment is required even at T0 after repeat TURBT. Intravesical BCG maintenance therapy of patients with T0 after TURBT reduces recurrence.<br>
DOI: 10.6084/m9.figshare.6844874
title: Factors related to water quality and thresholds for microcystin concentrations in subtropical Brazilian reservoirs

description: Studies of the environmental factors that lead to cyanotoxic blooms in tropical/subtropical reservoirs are limited. While technological advances for water treatment and remediation techniques can mitigate the effects of cyanobacterial blooms, the identification of initial drivers and tipping points for minimizing cyanotoxin concentrations could be more cost effective. We studied factors related to microcystin (MC) concentrations and estimated thresholds to limit MC using a water quality dataset from 6 subtropical Brazilian reservoirs. Reservoirs varied by water chemistry and toxin concentrations (MC yearly means &lt;0.1–17 µg/L). Phytoplankton community composition in most reservoirs was dominated by cyanobacteria, and both nitrogen-fixing and non-fixing genera were common. We found positive correlations (<i>p</i> a (Chl-<i>a</i>, ρ = 0.65) and a negative correlation between MC and total nitrogen/total phosphorus (TN/TP, ρ = −0.49). While no association between MC and water temperature was observed, MC normalized to Chl-<i>a</i> values were positively related to higher temperatures and lower wind velocities, indicating warmer and more stable waters had a higher probability of toxic blooms. We found thresholds for MC ≥0.1 and ≥1 µg/L related to cyanobacterial cell counts of 20 060–136 165 cells/mL, respectively, and for turbidity (5–12 NTU) and TP (0.016–0.028 mg/L), respectively. We considered these MC concentrations (0.1 and 1 µg/L) to account for different levels of toxin production. The thresholds were different from those published for temperate ecosystems but not consistently lower or higher. TN/TP molar ratios favored toxin concentration when ≤121, suggesting that less phosphorus in relation to nitrogen is necessary to allow MC production in subtropical freshwaters. High phosphorus concentrations can increase concentration of cyanotoxins in subtropical reservoirs, and our data confirm that global warming could exacerbate problems associated with toxic algal blooms.
DOI: 10.6084/m9.figshare.6844874.v1
title: Factors related to water quality and thresholds for microcystin concentrations in subtropical Brazilian reservoirs

description: Studies of the environmental factors that lead to cyanotoxic blooms in tropical/subtropical reservoirs are limited. While technological advances for water treatment and remediation techniques can mitigate the effects of cyanobacterial blooms, the identification of initial drivers and tipping points for minimizing cyanotoxin concentrations could be more cost effective. We studied factors related to microcystin (MC) concentrations and estimated thresholds to limit MC using a water quality dataset from 6 subtropical Brazilian reservoirs. Reservoirs varied by water chemistry and toxin concentrations (MC yearly means &lt;0.1–17 µg/L). Phytoplankton community composition in most reservoirs was dominated by cyanobacteria, and both nitrogen-fixing and non-fixing genera were common. We found positive correlations (<i>p</i> a (Chl-<i>a</i>, ρ = 0.65) and a negative correlation between MC and total nitrogen/total phosphorus (TN/TP, ρ = −0.49). While no association between MC and water temperature was observed, MC normalized to Chl-<i>a</i> values were positively related to higher temperatures and lower wind velocities, indicating warmer and more stable waters had a higher probability of toxic blooms. We found thresholds for MC ≥0.1 and ≥1 µg/L related to cyanobacterial cell counts of 20 060–136 165 cells/mL, respectively, and for turbidity (5–12 NTU) and TP (0.016–0.028 mg/L), respectively. We considered these MC concentrations (0.1 and 1 µg/L) to account for different levels of toxin production. The thresholds were different from those published for temperate ecosystems but not consistently lower or higher. TN/TP molar ratios favored toxin concentration when ≤121, suggesting that less phosphorus in relation to nitrogen is necessary to allow MC production in subtropical freshwaters. High phosphorus concentrations can increase concentration of cyanotoxins in subtropical reservoirs, and our data confirm that global warming could exacerbate problems associated with toxic algal blooms.
DOI: 10.17028/rd.lboro.6844844
title: Integrated 12-well plate Bioreactor

description: 12-well plate bioreactor with integrated scaffolds for tissue engineered skeletal muscle.
DOI: 10.17028/rd.lboro.6844844.v1
title: Integrated 12-well plate Bioreactor

description: 12-well plate bioreactor with integrated scaffolds for tissue engineered skeletal muscle.
DOI: 10.6084/m9.figshare.6844817
title: Supplementary Material for: Multifokale Neoplasien der Haut: Biologie, Ätiologie und zielgerichtete Therapien von nicht-melanozytärem Hautkrebs

description: Neoplastische Hautläsionen sind multifokal auftretende, diffuse Hautinfiltrationen, die besonders in der Differentialdiagnose ulzerativer, nodulärer oder verkrustender Hautläsionen von Bedeutung sind. Nicht-melanozytäre Hautkrebsformen (nonmelanoma skin cancers, NMSC) wie das Basalzellkarzinom (basal cell carcinoma, BCC), das Plattenepithelkarzinom (squamous cell carcinoma, SCC) und die aktinische Keratose (AK) sind die häufigsten malignen Tumoren beim Menschen. BCC wachsen langsam und bilden meist keine Metastasen, wohingegen SCC ein stärker infiltrierendes, destruierendes Wachstum zeigen und Metastasen bilden. AK sind Vorstufen des kutanen SCC. Bei der klassischen NMSC-Therapie kommt die photodynamische Therapie in Verbindung mit Chemotherapeutika zur Anwendung. Das zunehmende Verständnis der Pathomechanismen, die bei der Tumorentstehung, -progression und -differenzierung eine Rolle spielen, stützt die Anwendung zielgerichteter Chemotherapien zur Verringerung der Zytotoxizität klassischer Therapien. Die vorliegende Übersichtsarbeit beschreibt den aktuellen Wissensstand über NMSC, einschließlich der Risikofaktoren, Onkogene und Karzinogenese von Hautkrebs und erörtert die herkömmliche Behandlung im Vergleich zu neuartigen therapeutischen Optionen. Übersetzung aus Skin Pharmacol Physiol 2018;31:59-73 (DOI: 10.1159/000479529)
DOI: 10.6084/m9.figshare.6844817.v1
title: Supplementary Material for: Multifokale Neoplasien der Haut: Biologie, Ätiologie und zielgerichtete Therapien von nicht-melanozytärem Hautkrebs

description: Neoplastische Hautläsionen sind multifokal auftretende, diffuse Hautinfiltrationen, die besonders in der Differentialdiagnose ulzerativer, nodulärer oder verkrustender Hautläsionen von Bedeutung sind. Nicht-melanozytäre Hautkrebsformen (nonmelanoma skin cancers, NMSC) wie das Basalzellkarzinom (basal cell carcinoma, BCC), das Plattenepithelkarzinom (squamous cell carcinoma, SCC) und die aktinische Keratose (AK) sind die häufigsten malignen Tumoren beim Menschen. BCC wachsen langsam und bilden meist keine Metastasen, wohingegen SCC ein stärker infiltrierendes, destruierendes Wachstum zeigen und Metastasen bilden. AK sind Vorstufen des kutanen SCC. Bei der klassischen NMSC-Therapie kommt die photodynamische Therapie in Verbindung mit Chemotherapeutika zur Anwendung. Das zunehmende Verständnis der Pathomechanismen, die bei der Tumorentstehung, -progression und -differenzierung eine Rolle spielen, stützt die Anwendung zielgerichteter Chemotherapien zur Verringerung der Zytotoxizität klassischer Therapien. Die vorliegende Übersichtsarbeit beschreibt den aktuellen Wissensstand über NMSC, einschließlich der Risikofaktoren, Onkogene und Karzinogenese von Hautkrebs und erörtert die herkömmliche Behandlung im Vergleich zu neuartigen therapeutischen Optionen. Übersetzung aus Skin Pharmacol Physiol 2018;31:59-73 (DOI: 10.1159/000479529)
DOI: 10.17028/rd.lboro.6844802
title: Modular 6-well plate Bioreactor

description: Modular perfusion system in 6-well plate format.
DOI: 10.17028/rd.lboro.6844799
title: Integrated Tissue Engineered Perfusion System

description: Perfusion system which incorporates integrated scaffold for tissue engineered skeletal muscle
DOI: 10.17028/rd.lboro.6844802.v1
title: Modular 6-well plate Bioreactor

description: Modular perfusion system in 6-well plate format.