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Jesse Demuytere,1,* Charlotte Carlier,1,* Leen Van de Sande,1 Anne Hoorens,2 Kaat De Clercq,3 Silvia Giordano,4 Lavinia Morosi,4 Cristina Matteo,4 Massimo Zucchetti,4 Enrico Davoli,4 Jo Van Dorpe,2 Chris Vervaet,3 Wim Ceelen1 1Department of GI Surgery, Ghent University Hospital, and Cancer Research Institute Ghent (CRIG), Ghent, Belgium; 2Department of Pathology, Ghent University Hospital, Ghent, Belgium; 3Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium; 4Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri - IRCCS, Milano, Italy*These authors contributed equally to this workCorrespondence: Wim Ceelen, Department of GI Surgery, Ghent University Hospital, Route 1275, Corneel Heymanslaan 10, Ghent, B-9000, Belgium, Tel +32 9 332 6251, Email Wim.ceelen@ugent.beBackground: Epithelial ovarian cancer is associated with high mortality due to diagnosis at later stages associated with peritoneal involvement. Several trials have evaluated the effect of intraperitoneal treatment. In this preclinical study, we report the efficacy, pharmacokinetics and pharmacodynamics of intraperitoneal treatment with two approved nanomolecular formulations of paclitaxel (nab-PTX and mic-PTX) in a murine ovarian cancer xenograft model.Methods: IC50 was determined in vitro on three ovarian cancer cell lines (OVCAR-3, SK-OV-3 and SK-OV-3-Luc IP1). EOC xenografts were achieved using a modified subperitoneal implantation technique. Drug treatment was initiated 2 weeks after engraftment, and tumor volume and survival were assessed. Pharmacokinetics and drug distribution effects were assessed using UHPLC-MS/MS and MALDI imaging mass spectrometry, respectively. Pharmacodynamic effects were analyzed using immunohistochemistry and transmission electron microscopy using standard protocols.Results: We demonstrated sub-micromolar IC50 concentrations for both formulations on three EOC cancer cell lines in vitro. Furthermore, IP administration of nab-PTX or mic-PTX lead to more than 2-fold longer survival compared to a control treatment of IP saline administration (30 days in controls, 66 days in nab-PTX treated animals, and 76 days in mic-PTX animals, respectively). We observed higher tissue uptake of drug following nab-PTX administration when compared to mic-PTX, with highest uptake after 4 hours post-treatment, and confirmed this lower uptake of mic-PTX using HPLC on digested tumor samples. Furthermore, apoptosis was not increased in tumor implants up to 24h post-treatment.Conclusion: Intraperitoneal administration of both nab-PTX and mic-PTX results in a significant anticancer efficacy and survival benefit in a mouse OC xenograft model.Keywords: ovarian, peritoneal, paclitaxel, nanomedicine

Among the technologies for climate change mitigation, carbon capture and storage is considered as a technically and economically viable option to reduce CO2 emissions from hard-to-abate industrial sectors. When it comes to CO2 logistics, ship-based chains are emerging as an attractive alternative to other CO2 transport modes (e.g., pipelines), as these could exhibit lower operational risk, higher infrastructural flexibility, and lower costs. This work provides insights into the cost of optimal ship-based CO2 transport chains at a European level, by proposing a detailed economic model of CO2 transport by ship, including all the echelons of the infrastructure (i.e., liquefaction, buffer storage, loading, ship, conditioning, and unloading). The final aim is to determine the minimum CO2 transport cost from Southern Europe to North Sea sequestration. Different unloading scenarios (port-to-port, port-to-floating storage and injection, and port-to-direct offshore unloading) and carbon reduction targets are investigated. The minimum unitary transport cost is 26 €/t of CO2 for transporting 103 Mt/y.

Carbon capture, utilisation, and sequestration is key for the decarbonisation of hard-to-abate industries, as it allows avoiding the direct release of CO2 to the atmosphere and generating carbon-based products. However, for these products to be truly carbon-neutral, intermittent renewable electricity must be deployed at scale, leading to the necessity of optimising flexible plants with potential for local buffer storages, geological sequestration, and conversion units. The scope of this work is to provide a mathematical framework for the economic optimisation of a carbon capture, utilisation, and sequestration system, to decarbonise a cement plant located in the Puglia region (Italy), via CO2 geological confinement and/or power and CO2-to-methanol conversion. The final aim is to determine the optimal sizing and cost of the process units of the plant, depending on economic conditions such as the methanol sale price and different perspective costs scenarios. The main outcome is an economic convenience of geological sequestration, as opposed to utilisation, while a long-term scenario would allow for a cost-effective production of methanol when the sale price is above 550 €/t.

Abstract Background The challenging factors that elite athletes perceive for combining their sportive career with planning a pregnancy and motherhood need to be identified in order to develop supportive measures. Therefore, this phenomenological qualitative study aimed to explore challenges associated with planning a pregnancy among female, non-pregnant elite athletes. Methods Semi-structured skype-interviews were performed among female elite athletes (athletes competing on national or international level) aged 28 years or older. Using Mayring’s qualitative content analysis approach, anchor examples served to identify potential challenges of planning a pregnancy which were categorized independently by two researchers. Results Interviews of 16 elite athletes (mean age 30.7 years) entered analysis. Eleven challenges of planning a pregnancy were identified, categorized into organizational / environmental, financial, personal, and physical factors. Conclusions With regard to financial challenges, we propose mandatory maternity leave and continuation of the contracts and salary. Furthermore, mentoring programs may help to provide support and advice to new generations of female elite athletes and help to reduce concerns regarding the wish of becoming pregnant during a sportive career. In order to reduce physical concerns regarding pregnancy and exercise, we see a need for scientific studies investigating the association of sport discipline specific characteristics on sportive performance and the mother´s, fetus’ and child´s health. Finally, the results of the current study may be used in future quantitative studies to test specific hypotheses.

Abstract This paper is written in response to the paper “How green is blue hydrogen?” by R. W. Howarth and M. Z. Jacobson. It aims at highlighting and discussing the method and assumptions of that paper, and thereby providing a more balanced perspective on blue hydrogen, which is in line with current best available practices and future plant specifications aiming at low CO2 emissions. More specifically, in this paper, we show that: (i) the simplified method that Howarth and Jacobson used to compute the energy balance of blue hydrogen plants leads to significant overestimation of CO2 emissions and natural gas (NG) consumption and (ii) the assumed methane leakage rate is at the high end of the estimated emissions from current NG production in the United States and cannot be considered representative of all‐NG and blue hydrogen value chains globally. By starting from the detailed and rigorously calculated mass and energy balances of two blue hydrogen plants in the literature, we show the impact that methane leakage rate has on the equivalent CO2 emissions of blue hydrogen. On the basis of our analysis, we show that it is possible for blue hydrogen to have significantly lower equivalent CO2 emissions than the direct use of NG, provided that hydrogen production processes and CO2 capture technologies are implemented that ensure a high CO2 capture rate, preferably above 90%, and a low‐emission NG supply chain.

The decarbonisation of carbon-intensive sectors is a fundamental task for the achievement of future environmental goals. Within the challenge of industrial decarbonisation, oil refining represents a hard-to-abate sector, considering that it is characterised by CO2 emissions deriving from multiple units and at different levels of concentration and flow rate. Therefore, pathways for the separation and conversion of such CO2 into products (e.g., synthetic fuels) may cover an important role in the reduction of CO2 emissions from refineries. The objective of this study is the technical design and economic evaluation of a conversion pathway for the production of CO2 and green H2-based e-Fuel methanol (i.e., based on conventional electrolysis), as juxtaposed to an alternative process concept based on electrified reforming er-Fuel methanol. Such plants are modelled in terms of mass and energy balances in Aspen Plus® software to produce methanol. Then, an economic assessment is carried out to highlight the best design configurations and compare the production costs. Optimal plants configurations are determined by fine-tuning the level of light products recycles, to minimise the feed of green H2 and maximise the performance indicators. Results demonstrate how the er-Fuel configuration allows better conversion efficiencies and lower production costs, in the order of 30-40 % reduction with respect to the e-Fuel design.

b Innovhub SSI, Via Galilei, 3 - San Donato Milanese (MI)c Politecnico di Milano, Dipartimento di Energia, Via Lambruschini, 4, 20156 Milano (MI)d Politecnico di Milano, Energy & Strategy Group, Via Lambruschini, 4, 20156 Milano (MI)The production of e-fuels is mainly based on the synthesis processes of green hydrogen produced by the electrolysis of water (using renewable energy sources) and carbon dioxide (CO2) which can be captured from a concentrated source (fumes of an industrial site), from the air (through Direct Air Capture, DAC solutions) or by exploiting the CO2 of biogenic origin deriving from the production of biofuels. E-fuels can be considered climate-neutral fuels since the production process don’t release incremental CO2 and, thanks to their compatibility with internal combustion engines, they can be used to power road vehicles, airplanes and ships, helping to decarbonise the transport sector. E-fuels have an energy density much higher than that of batteries and therefore allow for the reduction of greenhouse gas emissions in transport, while preserving the current circulating fleet of vehicles. It is also possible to continue to use the transport, distribution and sales infrastructures nowadays in use for current liquid fuels as they are also perfectly compatible with e-fuels. The project presented in this paper aimed to define the technical-economic parameters of a demonstrative pilot plant, able to produce sufficient quantities of e-fuels (Fischer-Tropsch) to carry out performance tests, as well as to evaluate the technical and economic potential for a future development in the Italian energy landscape.

Most countries affected by the COVID-19 pandemic have repeatedly restricted public life to control the contagion. However, the health impact of confinement measures is hitherto unclear. We performed a multinational survey investigating changes in mental and physical well-being (MWB/PWB) during the first wave of the pandemic. A total of 14,975 individuals from 14 countries provided valid responses. Compared to pre-restrictions, MWB, as measured by the WHO-5 questionnaire, decreased considerably during restrictions (68.1 ± 16.9 to 51.9 ± 21.0 points). Whereas 14.2% of the participants met the cutoff for depression screening pre-restrictions, this share tripled to 45.2% during restrictions. Factors associated with clinically relevant decreases in MWB were female sex (odds ratio/OR = 1.20, 95% CI: 1.11–1.29), high physical activity levels pre-restrictions (OR = 1.29, 95% CI 1.16–1.42), decreased vigorous physical activity during restrictions (OR = 1.14, 95% CI: 1.05–1.23), and working (partially) outside the home vs. working remotely (OR = 1.29, 95% CI: 1.16–1.44/OR = 1.35, 95% CI: 1.23–1.47). Reductions, although smaller, were also seen for PWB. Scores in the SF-36 bodily pain subscale decreased from 85.8 ± 18.7% pre-restrictions to 81.3 ± 21.9% during restrictions. Clinically relevant decrements of PWB were associated with female sex (OR = 1.62, 95% CI: 1.50–1.75), high levels of public life restrictions (OR = 1.26, 95% CI: 1.18–1.36), and young age (OR = 1.10, 95% CI: 1.03–1.19). Study findings suggest lockdowns instituted during the COVID-19 pandemic may have had substantial adverse public health effects. The development of interventions mitigating losses in MWB and PWB is, thus, paramount when preparing for forthcoming waves of COVID-19 or future public life restrictions.

Background: Sleep disturbances are common early warning signs of an episode of bipolar disorder, and early recognition can favorably impact the illness course. Symptom monitoring via a smartphone app is an inexpensive and feasible method to detect an early indication of changes such as sleep. The study aims were (1) to assess the acceptance of apps and (2) to validate sleeping times measured by the smartphone app UP!.Methods:UP! was used by 22 individuals with bipolar disorder and 23 controls. Participants recorded their time of falling asleep and waking-up using UP! for 3 weeks. Results were compared to a validated accelerometer and the Pittsburgh Sleep Quality Index. Additionally, participants were interviewed regarding early warning signs and their feedback for apps as monitoring tools in bipolar disorder (NCT03275714).Results: With UP!, our study did not find strong reservations concerning data protection or continual smartphone usage. Correlation analysis demonstrates UP! to be a valid tool for measuring falling asleep and waking-up times.Discussion: Individuals with bipolar disorder assessed the measurement of sleep disturbances as an early warning sign with a smartphone as positive. The detection of early signs could change an individual's behavior and strengthen self-management. The study showed that UP! can be used to measure changes in sleep durations accurately. Further investigation of smartphone apps' impact to measure other early signs could significantly contribute to clinical treatment and research in the future through objective, continuous, and individual data collection.

Abstract. The knowledge of cancer origin and the subsequent tracking of disease evolution represent unmet needs that will soon be within clinical reach. This will provide the opportunity to improve patient's stratification and to personalize treatments based on cancer biology along its life history. In this review, we focus on the molecular pathogenesis of multiple myeloma (MM), a hematologic malignancy with a well-known multi-stage disease course, where such approach can sooner translate into a clinical benefit. We describe novel insights into modes and timing of disease initiation. We dissect the biology of the preclinical and pre-malignant phases, elucidating how knowledge of the genomics of the disease and the composition of the microenvironment allow stratification of patients based on risk of disease progression. Then, we explore cell-intrinsic and cell-extrinsic drivers of MM evolution to symptomatic disease. Finally, we discuss how this may relate to the development of refractory disease after treatment. By integrating an evolutionary view of myeloma biology with the recent acquisitions on its clonal heterogeneity, we envision a way to drive the clinical management of the disease based on its detailed biological features more than surrogates of disease burden.

Interactions of malignant multiple myeloma (MM) plasma cells (MM-cells) with the microenvironment control MM-cell growth, survival, drug-resistance and dissemination. As in MM microvascular density increases in the bone marrow (BM), we investigated whether BM MM endothelial cells (MMECs) control disease progression via the junctional adhesion molecule A (JAM-A). Membrane and cytoplasmic JAM-A levels were upregulated in MMECs in 111 newly diagnosed (NDMM) and 201 relapsed-refractory (RRMM) patients compared to monoclonal gammopathy of undetermined significance (MGUS) and healthy controls. Elevated membrane expression of JAM-A on MMECs predicted poor clinical outcome. Mechanistically, addition of recombinant JAM-A to MMECs increased angiogenesis whereas its inhibition impaired angiogenesis and MM growth in 2D and 3D in vitro cell culture and chorioallantoic membrane-assays. To corroborate these findings, we treated MM bearing mice with JAM-A blocking mAb and demonstrated impaired MM progression corresponding to decreased MM-related vascularity. These findings support JAM-A as an important mediator of MM progression through facilitating MM-associated angiogenesis. Collectively, elevated JAM-A expression on bone marrow endothelial cells is an independent prognostic factor for patient survival in both NDMM and RRMM. Blocking JAM-A restricts angiogenesis in vitro, in embrio and in vivo and represents a suitable druggable molecule to halt neoangiogenesis and MM progression.

Abstract Background Depression during pregnancy is associated with higher maternal morbidity and mortality, and subsequent possible adverse effects on the cognitive, emotional and behavioral development of the child. The aim of the study was to identify maternal characteristics associated with poor mental health, in a group of overweight/obese pregnant women in nine European countries, and thus, to contribute to better recognition and intervention for maternal depression. Methods In this cross-sectional observational study, baseline data from early pregnancy (< 20 weeks) of the DALI (Vitamin D and Lifestyle Intervention for gestational diabetes mellitus prevention) study were analyzed. Maternal mental health was assessed with the World Health Organization Well-Being Index (WHO–5). Women were classified as having a low (WHO–5 ≤ 50) or high wellbeing. Results. A total of 735 pregnant women were included. The prevalence of having a low wellbeing was 27.2%, 95% CI [24.0, 30.4]. Multivariate analysis showed independent associations between low wellbeing and European ethnicity, OR = .44, 95% CI [.25, .77], shift work, OR = 1.81, 95% CI [1.11, 2.93], insufficient sleep, OR = 3.30, 95% CI [1.96, 5.55], self-efficacy, OR = .95, 95% CI [.92, .98], social support, OR = .94, 95% CI [.90, .99], and pregnancy-related worries (socioeconomic: OR = 1.08, 95% CI [1.02, 1.15]; health: OR = 1.06, 95% CI [1.01, 1.11]; relationship: OR = 1.17, 95% CI [1.05, 1.31]). Conclusions Mental health problems are common in European overweight/obese pregnant women. The identified correlates might help in early recognition and subsequent treatment of poor mental health problems during pregnancy. This is important to reduce the unfavorable effects of poor mental health on pregnancy outcomes. Trial registration ISRCTN70595832 , 02.12.2011.

(1): Heart rate performance curve (HRPC) in incremental exercise was shown to be not uniform, causing false intensity estimation applying percentages of maximal heart rate (HRmax). HRPC variations are mediated by β-adrenergic receptor sensitivity. The aim was to study age and sex dependent differences in HRPC patterns in adults with β-blocker treatment (BB) and healthy controls (C). (2): A total of 535 (102 female) BB individuals were matched 1:1 for age and sex (male 59 ± 11 yrs, female 61 ± 11 yrs) in C. From the maximum incremental cycle ergometer exercise a first and second heart rate (HR) threshold (Th1 and Th2) was determined. Based on the degree of the deflection (kHR), HRPCs were categorized as regular (downward deflection (kHR > 0.1)) and non-regular (upward deflection (kHR < 0.1), linear time course). (3): Logistic regression analysis revealed a higher odds ratio to present a non-regular curve in BB compared to C (females showed three times higher odds). The odds for non-regular HRPC in BB versus C decreased with older age (OR interaction = 0.97, CI = 0.94–0.99). Maximal and submaximal performance and HR variables were significantly lower in BB (p < 0.05). %HRmax was significantly lower in BB versus C at Th2 (male: 77.2 ± 7.3% vs. 80.8 ± 5.0%; female: 79.2 ± 5.1% vs. 84.0 ± 4.3%). %Pmax at Th2 was similar in BB and C. (4): The HRPC pattern in incremental cycle ergometer exercise is different in individuals receiving β-blocker treatment compared to healthy individuals. The effects were also dependent on age and sex. Relative HR values at Th2 varied substantially depending on treatment. Thus, the percentage of Pmax seems to be a stable and independent indicator for exercise intensity prescription.

High systemic blood lactate (La) was shown to inhibit glycolysis and to increase oxidative metabolism in subsequent anaerobic exercise. Aim of this study was to examine the effect of a metabolic pre-conditioning (MPC) on net La increase and performance in subsequent pull-up exercise (PU). Nine trained students (age: 25.1 ± 1.9 years; BMI: 21.7 ± 1.4) performed PU on a horizontal bar with legs placed on a box (angular hanging) either without or with MPC in a randomized order. MPC was a 26.6 ± 2 s all out shuttle run. Each trial started with a 15-min warm-up phase. Time between MPC and PU was 8 min. Heart rate (HR) and gas exchange measures (VO2, VCO2, and VE) were monitored, La and glucose were measured at specific time points. Gas exchange measures were compared by area under the curve (AUC). In PU without MPC, La increased from 1.24 ± 0.4 to 6.4 ± 1.4 mmol⋅l−1, whereas with MPC, PU started at 9.28 ± 1.98 mmol⋅l−1 La which increased to 10.89 ± 2.13 mmol⋅l−1. With MPC, net La accumulation was significantly reduced by 75.5% but performance was significantly increased by 1 rep (4%). Likewise, net oxygen uptake VO2 (50% AUC), pulmonary ventilation (VE) (34% AUC), and carbon dioxide VCO2 production (26% AUC) were significantly increased during PU but respiratory exchange ratio (RER) was significantly blunted during work and recovery. MPC inhibited glycolysis and increased oxidative metabolism and performance in subsequent anaerobic upper-body strength-endurance exercise.

The physiological and biomechanical changes that occur during pregnancy make accurate measurement of physical activity (PA) a challenge during this unique period. The Global Physical Activity Questionnaire (GPAQ) has been used extensively in low-to-middle income countries, but has never been validated in a pregnant population. In this longitudinal study, 95 pregnant women (mean age: 29.5±5.7 years; BMI: 26.9±5.0 kg/m2) completed the GPAQ and were asked to wear an accelerometer for 7 days at two time points during pregnancy (14-18 and 29-33 weeks gestation). There was a significant difference between accelerometry and GPAQ when measuring moderate-to-vigorous physical activity (MVPA) at 29-33 weeks gestation (16.6 vs 21.4 min/day; p = 0.02) as well as sedentary behaviour (SB) at both 14-18 weeks (457.0 vs 300 min/day; p < 0.01) and 29-33 weeks gestation (431.5 vs 300 min/day; p < 0.01). There was poor agreement between the GPAQ and accelerometry for both PA and SB at both time points (ICC: -0.05-0.08). Bland Altman plots indicated that the GPAQ overestimates PA by 14.8 min/day at 14-18 weeks and by 15.8 min/day at 29-33 weeks gestation. It underestimates SB by 127.5 min/day at 14-18 weeks and by 89.2 min/day at 29-33 weeks gestation. When compared to accelerometry, the GPAQ shows poor agreement and appears to overestimate PA and underestimate SB during pregnancy.

Somatic mutations of the RNA splicing machinery have been recently identified in myelodysplastic syndromes. In particular, a strong association has been found between SF3B1 mutation and refractory anemia with ring sider-oblasts, a condition characterized by ineffective erythropoiesis and parenchymal iron overload. We studied the relationship between SF3B1 mutation, erythroid activity and hepcidin levels in myelodysplastic syndrome patients. Erythroid activity was evaluated through the proportion of marrow erythroblasts, soluble transferrin receptor and serum growth differentiation factor 15. Significant relationships were found between SF3B1 mutation and marrow erythroblasts (P=0.001), soluble transferrin receptor (P=0.003) and serum growth differentiation factor 15 (P=0.033). Serum hepcidin varied considerably, and multivariable analysis showed that the hepcidin to ferritin ratio, a measure of adequacy of hepcidin levels relative to body iron stores, was inversely related to the SF3B1 mutation (P=0.013). These observations suggest that patients with SF3B1 mutation have inappropriately low hepcidin levels, which may explain their propensity to parenchymal iron loading.

Under what conditions do citizens support restrictive and punitive measures to curb global crises? This article investigates the role of political trust in supporting different interventions across three types of crises—pandemics, climate change, and terrorism—both directly and in conjunction with issue‐related anxiety. We test the hypothesis that political trust positively affects the likelihood of accepting restrictive measures during crisis, focusing on Italy as a relevant case study due to its comparatively low levels of political trust. According to affective intelligence theory, we also expect that individual anxiety moderates such a relationship: Political trust should have an effect primarily when people are not anxious. To examine this, we conducted a conjoint experiment administered to a nationally representative sample of 1000 Italian citizens. Respondents were presented with a “crisis vignette” where the nature of the crisis, its severity, and the state measures implemented to curb the threat were randomly allocated as attributes. They were then asked to rate their support for the proposed measure. Results confirm that political trust matters. Citizens with high levels of trust are generally more willing to accept restrictions. However, as predicted, political trust only influences non‐anxious voters. [ABSTRACT FROM AUTHOR]

Author(s): Matteo C. Da Vià [sup.1] , Oliver Dietrich [sup.2] , Marietta Truger [sup.3] , Panagiota Arampatzi [sup.4] , Johannes Duell [sup.1] , Anke Heidemeier [sup.5] , Xiang Zhou [sup.1] [...], B cell maturation antigen (BCMA) is a target for various immunotherapies and a biomarker for tumor load in multiple myeloma (MM). We report a case of irreversible BCMA loss in a patient with MM who was enrolled in the KarMMa trial (NCT03361748) and progressed after anti-BCMA CAR T cell therapy. We identified selection of a clone with homozygous deletion of TNFRSF17 (BCMA) as the underlying mechanism of immune escape. Furthermore, we found heterozygous TNFRSF17 loss or monosomy 16 in 37 out of 168 patients with MM, including 28 out of 33 patients with hyperhaploid MM who had not been previously treated with BCMA-targeting therapies, suggesting that heterozygous TNFRSF17 deletion at baseline could theoretically be a risk factor for BCMA loss after immunotherapy. Biallelic loss of BCMA caused a patient with multiple myeloma to relapse after anti-BCMA CAR T cell treatment. Baseline heterozygous BCMA deletions might be a risk factor for this form of resistance.