Review of next generation hydrogen production from offshore wind using water electrolysis

\ua9 2023 The Author(s)Hydrogen produced using renewable energy from offshore wind provides a versatile method of energy storage and power-to-gas concepts. However, few dedicated floating offshore electrolyser facilities currently exist and therefore conditions of the offshore environment on hydrogen production cost and efficiency remain uncertain. Therefore, this review focuses on the conversion of electrical energy to hydrogen, using water electrolysis located in offshore areas. The challenges associated with the remote locations, fluctuating power and harsh conditions are highlighted and recommendations for future electrolysis system designs are suggested. The latest research in polymer electrolyte membrane, alkaline and membraneless electrolysis are evaluated in order to understand their capital costs, efficiency and current research status for achieving scaled manufacturing to the GW scale required in the next three decades. Operating fundamentals that govern the performance of each device are investigated and future recommendations of research specifically for the integration of water electrolysers with offshore wind turbines is presented

Quality of life in metastatic pancreatic cancer patients receiving liposomal irinotecan plus 5-fluorouracil and leucovorin

Abstract Background The NAPOLI-1 study (NCT01494506) reported that liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI+5-FU/LV) improved overall survival vs 5-FU/LV with manageable toxicity in patients with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-based therapy. Yet, clinicians need treatment strategies that also maintain the patient's health-related quality of life (HRQOL). Here, we report the HRQOL data. Methods Patients completed the European Organisation for Research and Treatment of Cancer QOL core questionnaire C30 (EORTC QLQ-C30) at baseline, every 6 weeks, and at 30 days after discontinuation of study treatment. Patient-reported outcomes (PROs) were scored according to EORTC guidelines. nal-IRI+5-FU/LV HRQOL was compared with 5-FU/LV. The PRO population comprised intent-to-treat patients who completed baseline and at least one subsequent assessment on the EORTC QLQ-C30. Data were also analysed for missingness. Results Of 236 patients in the intent-to-treat population, 128 (54.2%) comprised the PRO population (71 in the nal-IRI+5-FU/LV arm; 57 the in 5-FU/LV arm). Of the remaining 108 patients (45.8%) not included in the PRO population, most progressed rapidly, making participation difficult. Median change from baseline was ≤10 points at weeks 6 and 12 in global health status or functional and symptom scale scores, except for fatigue, which deteriorated by 11.1 points with nal-IRI+5-FU/LV but did not change vs 5-FU/LV. The proportion of patients whose HRQOL improved or deteriorated was not significantly different between the arms. Conclusion In the NAPOLI-1 study, HRQOL was maintained with nal-IRI+5-FU/LV in patients with metastatic pancreatic adenocarcinoma previously treated with a gemcitabine-based regimen, while survival was significantly extended

Metabolic status differentiates Trp53inp2 function in pressure-overload induced heart failure

Cardiometabolic disorders encompass a broad range of cardiovascular complications associated with metabolic dysfunction. These conditions have an increasing share in the health burden worldwide due to worsening endemic of hypertension, obesity, and diabetes. Previous studies have identified Tumor Protein p53-inducible Nuclear Protein 2 (Trp53inp2) as a molecular link between hyperglycemia and cardiac hypertrophy. However, its role in cardiac pathology has never been determined in vivo. In this study, we generated a cardiac specific knockout model of Trp53inp2 (Trp53inp2-cKO) and investigated the impact of Trp53inp2 inactivation on the pathogenesis of heart failure under mechanic or/and metabolic stresses. Based on echocardiography assessment, inactivation of Trp53inp2 in heart led to accelerated onset of HFrEF in response to pressure-overload, with significantly reduced ejection fraction and elevated heart failure marker genes comparing to the control mice. In contrast, inactivation of Trp53inp2 ameliorated cardiac dysfunction induced by combined stresses of high fat diet and moderate pressure overload (Cardiometabolic Disorder Model). Moreover, Trp53inp2 inactivation led to reduced expression of glucose metabolism genes in lean, pressure-overloaded hearts. However, the same set of genes were significantly induced in the Trp53inp2-cKO hearts under both mechanical and metabolic stresses. In summary, we have demonstrated for the first time that cardiomyocyte Trp53inp2 has diametrically differential roles in the pathogenesis of heart failure and glucose regulation under mechanical vs. mechanical plus metabolic stresses. This insight suggests that Trp53inp2 may exacerbate the cardiac dysfunction during pressure overload injury but have a protective effect in cardiac diastolic function in cardiometabolic disease

Metabolic status differentiates Trp53inp2 function in pressure-overload induced heart failure

Cardiometabolic disorders encompass a broad range of cardiovascular complications associated with metabolic dysfunction. These conditions have an increasing share in the health burden worldwide due to worsening endemic of hypertension, obesity, and diabetes. Previous studies have identified Tumor Protein p53-inducible Nuclear Protein 2 (Trp53inp2) as a molecular link between hyperglycemia and cardiac hypertrophy. However, its role in cardiac pathology has never been determined in vivo. In this study, we generated a cardiac specific knockout model of Trp53inp2 (Trp53inp2-cKO) and investigated the impact of Trp53inp2 inactivation on the pathogenesis of heart failure under mechanic or/and metabolic stresses. Based on echocardiography assessment, inactivation of Trp53inp2 in heart led to accelerated onset of HFrEF in response to pressure-overload, with significantly reduced ejection fraction and elevated heart failure marker genes comparing to the control mice. In contrast, inactivation of Trp53inp2 ameliorated cardiac dysfunction induced by combined stresses of high fat diet and moderate pressure overload (Cardiometabolic Disorder Model). Moreover, Trp53inp2 inactivation led to reduced expression of glucose metabolism genes in lean, pressure-overloaded hearts. However, the same set of genes were significantly induced in the Trp53inp2-cKO hearts under both mechanical and metabolic stresses. In summary, we have demonstrated for the first time that cardiomyocyte Trp53inp2 has diametrically differential roles in the pathogenesis of heart failure and glucose regulation under mechanical vs. mechanical plus metabolic stresses. This insight suggests that Trp53inp2 may exacerbate the cardiac dysfunction during pressure overload injury but have a protective effect in cardiac diastolic function in cardiometabolic disease

Acetic Acid Bacteria: Physiology and Carbon Sources Oxidation

Acetic acid bacteria (AAB) are obligately aerobic bacteria within the family Acetobacteraceae, widespread in sugary, acidic and alcoholic niches. They are known for their ability to partially oxidise a variety of carbohydrates and to release the corresponding metabolites (aldehydes, ketones and organic acids) into the media. Since a long time they are used to perform specific oxidation reactions through processes called “oxidative fermentations”, especially in vinegar production. In the last decades physiology of AAB have been widely studied because of their role in food production, where they act as beneficial or spoiling organisms, and in biotechnological industry, where their oxidation machinery is exploited to produce a number of compounds such as l-ascorbic acid, dihydroxyacetone, gluconic acid and cellulose. The present review aims to provide an overview of AAB physiology focusing carbon sources oxidation and main products of their metabolism

Rectal Carriage of Extended-Spectrum Beta-Lactamase-Producing Gram-Negative Bacilli in Community Settings in Madagascar

BACKGROUND: Extended-spectrum ß-lactamase-producing Enterobacteria (ESBL-PE) emerged at the end of the 1980s, causing nosocomial outbreaks and/or hyperendemic situations in hospitals and long-term care facilities. In recent years, community-acquired infections due to ESBL-PE have spread worldwide, especially across developing countries including Madagascar. OBJECTIVES: This study aimed to determine the prevalence and risk factors of intestinal carriage of ESBL-PE in the community of Antananarivo. METHODS: Non-hospitalized patients were recruited in three health centers in different socio economic settings. Fresh stool collected were immediately plated on Drigalski agar containing 3 mg/liter of ceftriaxone. Gram-negative bacilli species were identified and ESBL production was tested by a double disk diffusion (cefotaxime and ceftazidime +/- clavulanate) assay. Characterization of ESBLs were perfomed by PCR and direct sequencing . Molecular epidemiology was analysed by Rep-PCR and ERIC-PCR. RESULTS: 484 patients were screened (sex ratio  = 1.03, median age 28 years). 53 ESBL-PE were isolated from 49 patients (carrier rate 10.1%). The isolates included Escherichia coli (31), Klebsiella pneumoniae (14), Enterobacter cloacae (3), Citrobacter freundii (3), Kluyvera spp. (1) and Pantoae sp.(1). In multivariate analysis, only the socioeconomic status of the head of household was independently associated with ESBL-PE carriage, poverty being the predominant risk factor. CONCLUSIONS: The prevalence of carriage of ESBL in the community of Antananarivo is one of the highest reported worldwide. This alarming spread of resistance genes should be stopped urgently by improving hygiene and streamlining the distribution and consumption of antibiotics

Mitogen-activated protein kinase activity drives cell trajectories in colorectal cancer

In colorectal cancer, oncogenic mutations transform a hierarchically organized and homeostatic epithelium into invasive cancer tissue lacking visible organization. We sought to define transcriptional states of colorectal cancer cells and signals controlling their development by performing single-cell transcriptome analysis of tumors and matched non-cancerous tissues of twelve colorectal cancer patients. We defined patient-overarching colorectal cancer cell clusters characterized by differential activities of oncogenic signaling pathways such as mitogen-activated protein kinase and oncogenic traits such as replication stress. RNA metabolic labeling and assessment of RNA velocity in patient-derived organoids revealed developmental trajectories of colorectal cancer cells organized along a mitogen-activated protein kinase activity gradient. This was in contrast to normal colon organoid cells developing along graded Wnt activity. Experimental targeting of EGFR-BRAF-MEK in cancer organoids affected signaling and gene expression contingent on predictive KRAS/BRAF mutations and induced cell plasticity overriding default developmental trajectories. Our results highlight directional cancer cell development as a driver of non-genetic cancer cell heterogeneity and re-routing of trajectories as a response to targeted therapy

Survival with nal-IRI (liposomal irinotecan) plus 5-fluorouracil and leucovorin versus 5-fluorouracil and leucovorin in per-protocol and non-per-protocol populations of NAPOLI-1: Expanded analysis of a global phase 3 trial.

Background In the phase 3 randomised NAPOLI-1 clinical study, a 45% increase in median overall survival (OS) was shown with liposomal irinotecan, 5-fluorouracil and leucovorin (nal-IRI+5-FU/LV) versus 5-FU/LV in patients with metastatic pancreatic cancer progressing after gemcitabine-based therapy. Here, we report data from a pre-specified, expanded analysis of outcomes in the per-protocol (PP) population.Materials and methods The PP population comprised patients receiving ≥80% of planned treatment during the first 6 weeks, with no major protocol violations. A post-hoc analysis of the non-PP population was also performed.Results For PP patients, median OS was 8.9 (95% confidence interval: 6.4-10.5) months with nal-IRI+5-FU/LV (n = 66) vs 5.1 (4.0-7.2) months with 5-FU/LV (n = 71; unstratified hazard ratio [HR] 0.57, p = 0.011). For non-PP patients, it was 4.4 (3.3-5.3) months with nal-IRI+5-FU/LV (n = 51) vs 2.8 (1.7-3.2) months with 5-FU/LV (n = 48; unstratified HR 0.64, p = 0.0648).Conclusion A statistically significant survival advantage was observed with nal-IRI+5-FU/LV vs 5-FU/LV in the PP patient population

Acute kidney injury in patients treated with immune checkpoint inhibitors

Background: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. Methods: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. Results: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. Conclusions: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery