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The Warburg effect, which describes the fermentation of glucose to lactate even in the presence of oxygen, is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production in cells for bioprocessing have failed as lactate
The Warburg effect is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production, as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production via knockout have failed in mammalian bioprocessing since lactate dehydrogenase has proven essential. However, here we eliminated the Wa
Background: Somatic and germline genetic alterations are significant drivers of cancer. Increasing integration of new technologies which profile these alterations requires timely, equitable and high-quality genetic counselling to facilitate accurate diagnoses and informed decision-making by patients and their families in preventive and clinical settings. This article aims to provide an overview of
Purpose: Childhood cancer is rare, and treatment is frequently associated with long-term morbidity. Disparities in survival and long-term side effects encourage the establishment of networks to increase access to complex organ-conservative strategies, such as brachytherapy. We report our experience of an international cooperation model in childhood cancers. Methods and Materials: We examined the o
Background: Since the first version of the dietary inflammatory index (DII®) developed in the past decade, several other versions have been developed. However, to date no study has attempted to compare these versions with respect to their associations with biomarkers of inflammation. Objective: We aimed to investigate the relationship between four dietary inflammatory scores [DII, two energy-adjus
BACKGROUND: Among infants with isolated cleft palate, whether primary surgery at 6 months of age is more beneficial than surgery at 12 months of age with respect to speech outcomes, hearing outcomes, dentofacial development, and safety is unknown. METHODS: We randomly assigned infants with nonsyndromic isolated cleft palate, in a 1:1 ratio, to undergo standardized primary surgery at 6 months of ag
BACKGROUND: What baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score.METHOD
Background: The globally dominant treatment with curative intent for locally advanced esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemoradiotherapy (nCRT) with subsequent esophagectomy. This multimodal treatment leads to around 60% overall 5-year survival, yet with impaired post-surgical quality of life. Observational studies indicate that curatively intended chemoradiotherapy, so-cal
The COVID-19 pandemic caught the world largely unprepared, including scientific and policy communities. On April 10-13, 2022, researchers across academia, industry, government, and nonprofit organizations met at the Keystone symposium "Lessons from the Pandemic: Responding to Emerging Zoonotic Viral Diseases" to discuss the successes and challenges of the COVID-19 pandemic and what lessons can be
Background: Survivors of childhood cancer are at risk of subsequent primary malignant neoplasms (SPNs), but the risk for rarer types of SPNs, such as oral cancer, is uncertain. Previous studies included few oral SPNs, hence large-scale cohorts are required to identify groups at risks. Methods: The PanCareSurFup cohort includes 69,460 5-year survivors of childhood cancer across Europe. Risks of ora
K2-146 is a cool, 0.358M⊙ dwarf that was found to host a mini-Neptune with a 2.67 day period. The planet exhibited strong transit timing variations (TTVs) of greater than 30 minutes, indicative of the presence of an additional object in the system. Here we report the discovery of the previously undetected outer planet in the system, K2-146 c, using additional photometric data. K2-146 c was found t
We report the discovery of two transiting planets orbiting K2-290 (EPIC 249624646), a bright (V = 11.11) late F-type star residing in a triple-star system. It was observed during Campaign 15 of the K2 mission, and in order to confirm and characterize the system, follow-up spectroscopy and AO imaging were carried out using the FIES, HARPS, HARPS-N, and IRCS instruments. From AO imaging and Gaia dat
Quantitative reconstructions of past land cover are necessary to determine the processes involved in climate-human-land-cover interactions. We present the first temporally continuous and most spatially extensive pollen-based land-cover reconstruction for Europe over the Holocene (last 11g€¯700g€¯calg€¯yrg€¯BP). We describe how vegetation cover has been quantified from pollen records at a 11 spatia
Background: Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest ever cohort. Methods: Using data from 69,460 5-year childhood cancer survivors (diagnosed 1940–2008), across Europe, standardized incidence ratios (SIRs) and cumulative incidence were calculated. Results: In total, 279 g
Birds are hosts for several zoonotic pathogens. Because of their high mobility, especially of longdistance migrants, birds can disperse these pathogens, affecting their distribution and phylogeography. We focused on Borrelia burgdorferi sensu lato, which includes the causative agents of Lyme borreliosis, as an example for tick-borne pathogens, to address the role of birds as propagation hosts of z
Lymphotoxin β-receptor (LTβR) signalling promotes lymphoid neogenesis and the development of tertiary lymphoid structures1,2, which are associated with severe chronic inflammatory diseases that span several organ systems3-6. How LTβR signalling drives chronic tissue damage particularly in the lung, the mechanism(s) that regulate this process, and whether LTβR blockade might be of therapeutic value
The lack of energy balance closure in Eddy-Covariance (EC) measurements is a well-known, still unresolved challenge in micrometeorology, with energy balance closure (EBC) rates typically ranging between 60% and 80%. While numerous hypotheses have been proposed to explain this imbalance, the relative contributions of neglected energy storage terms, data quality and flux processing options remain in
Background & Aims Microscopic colitis (MC) is a leading cause of chronic diarrhea, particularly in older adults. Although many patients respond to budesonide, refractory and dependent cases pose major therapeutic challenges. Although the off-label use of advanced inflammatory bowel disease therapies is expanding, robust real-world data remain scarce. Methods Through the ECCO CONFER network, we
The number of individuals suffering from neuropsychiatric disorders (NPDs) has increased worldwide, with 3 million disability-adjusted life-years calculated in 2019. Though research using various approaches including genetics, imaging, clinical and animal models has advanced our knowledge regarding NPDs, we still lack basic knowledge regarding the underlying pathophysiological mechanisms. Moreover
Objective: To investigate whether tangential versus segmental portomesenteric venous resection (PVR) impacts surgical and oncological outcome in patients undergoing pancreatoduodenectomy for pancreatic cancer with portomesenteric vein (PMV) involvement. Summary Background Data: Current comparative studies on tangential versus segmental PVR as part of pancreatoduodenectomy for pancreatic cancer inc
