Gaetano Santulli ¹ Markus W Hollmann ² Christina M Pabelick ³ Johannes Van Lieshout ^4*

• ¹ Albert Einstein College of Medicine, New York City, New York, United States
• ² Department of Anesthesiology, Academic Medical Centers, Division Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands, Amsterdam, Netherlands
• ³ Mayo Clinic, Rochester, Minnesota, United States
• ⁴ University of Amsterdam, Amsterdam, Netherlands

Lung cancer is the main cause of cancer-related death, with non-small-cell lung cancer (NSCLC) as the common variant. Hitherto the paucity of tumour-related symptoms precludes early diagnosis in NSCLC (1).The first paper of this topic by Xin et al. reports on advances in the diagnostic approach of patient with a NSCLC. The authors discuss the present state of art regarding the applicability and trustworthiness in early diagnosis and typing of circulating tumour DNA (ctDNA) as a liquid -rather than the usual solid -biopsy modality in patients with lung cancer.In the second paper, Zheng et al. review role and potential impact of membrane proteins capable of responding to mechanical stress initiated by external mechanical stimuli with a focus on a variety of lung diseases. Many excitable tissues are sensitive to mechanical stimulation. A classical example of transmission of mechanical forces is the effect of intravascular pressure that is transduced into tension as sensed in the high-and low pressure areas by cardio-and pulmonary baroreceptors (2-5). It was foundfor the first time in cultured chick muscle tissue -that membrane stress activates an ionic channel (2).Zheng et al. discuss the effects of mechanosensitive ion channels in lung cells in a variety of lung diseases including pulmonary hypertension, asthma, acute respiratory distress syndrome, chronic obstructive lung disease and lung fibrosis. Shenkin et al. wrote in their 1944 sentinel paper on detection of haemorrhage in humans '..That hemorrhage can be diagnosed by a rapid pulse and a low blood pressure is a concept so widely accepted that it seems almost an impertinence to question it' (6). This was subsequently verified in consecutive patients during resuscitation from haemorrhagic shock (7). In general, providing volume treatment based on cardiovascular variables is heavily debated (8). Traditional patient monitoring in the emergency ward and the operating room includes heart rate and blood pressure but their use as predictors for incipient central hypovolemia is rather limited (9).During World War II, the observation was repeatedly made that air raid victims in London City suffering from major blood loss presented with relative bradycardia rather than the expected tachycardia (10). It is problematic that no single physiological variable responds exclusively to a reduced central blood volume (11). In the battle field, haemorrhage is a major cause of soldier death (12) and recently machine-learning algorithms for determination of blood volume status have been developed (9,13,14). Against that background Jin et al. consider the potential for incorporating neural network-based AI technologies applied to created synthetic vital-sign data in hemorrhage detection and treatment.Sedentary behavior has been defined as an immobile state of the body (eg, sitting) resulting in energy expenditure close to the resting metabolic rate. In a study in 1084 Finnish women and 909 men aged 30-3 markers in adults (15) and in a twin study the impact of physical activity on the circulating metabolome was verified (16). In the fourth paper in this series Illka Heinonen considers the clinical and physiological advances of modifying sedentary behavior. The data were gathered from a randomized controlled trial investigating the physiological and clinical benefits of reduced daily sitting in metabolic syndrome patients during a 6-month intervention. Not unexpectedly, replacing sitting by movement rather than by standing seems more beneficial for fitness and health.