Neoadjuvant radiochemotherapy for locally advanced gastric cancer: a phase I-II study

Background: To study in a phase I-II trial the maximum tolerated dose, the toxicity, and the tolerance of adding radiotherapy to systemic chemotherapy administered preoperatively in patients with locoregionally advanced gastric adenocarcinoma. Patients and methods: Patients with adenocarcinoma of the stomach (T3-4Nany or TanyN+), performance status ≤1, normal hematological, hepatic and renal functions received two cycles of cisplatin 100 mg/m2 on day 1, 5-FU 800 mg/m2 on days 1 to 4 and leucovorin 60 mg b.i.d. on days 1 to 4 q3w, concomitantly with radiation therapy escalated in three dose tiers (31.2, 38.4 and 45.6 Gy). Results: Nineteen patients were accrued and 18 completed neoadjuvant therapy. Major toxicity consisted of grade 3/4 leucopenia and mucositis in 89% and 36% of the patients, respectively. Only one episode of febrile neutropenia was recorded. Dose level number 2 (38.4 Gy) with the chemotherapy given q4w is the recommended dose level. All patients were subsequently operated and no fatalities occurred. Pathological assessment showed one complete and eight partial responses. Two- and 3-year relapse-free survival rates were 57% and 50%, respectively. Only one patient relapsed locally. The peritoneum was the most frequent site of relapse. Conclusions: This neoadjuvant therapeutic program is relatively well tolerated, does not seem to increase the operative risk, and might increase the locoregional control of the disease. The frequency of peritoneal involvement in relapsing patients underscores the need for a more effective systemic treatmen

Movement of Artificial Bacterial Flagella in Heterogeneous Viscous Environments at the Microscale

Swimming microrobots have the potential to be used in medical applications such as targeted drug delivery. The challenges for navigating microrobots in the human body lie not only in the viscosity of body fluids but also in the existence of different types of fibers and cells such as blood cells or protein strands. This paper investigates artificial bacterial flagella (ABFs), which are helical microrobots actuated by an external magnetic field, in methyl cellulose solutions of different concentrations. It can be shown that the microrobots can be propelled in these gel-like heterogeneous solutions and successful swimming was demonstrated in solutions with a viscosity of more than 20 times that of water. Furthermore, results indicate that the existence of fibers can help ABFs swim more effectively, which agrees with previous experimental results reported for natural bacteria

A new genus of dipnoiformes from the Cretaceous of Brazil

The Alcântara Formation, an important stratigraphic unit from the early Cenomanian of Brazil, was deposited under transitional (estuarine) conditions, and its fossil record includes fragmentary remains of plants, fishes, crocodylomorphs, pterosaurs and dinosaurs, with a noteworthy diversity of dipnoiformes tooth plates. The dipnoiformes material reported here comprises a new taxon, Equinoxiodus alcantarensis, gen. et sp. nov. Most of the identified morphotypes of continental vertebrates collected in the Alcântara Formation are similar to chronocorrelative faunas from Northern Africa, but this new genus of Dipnoiformes indicates some degree of paleogeographic isolation and endemism. This was probably caused by the widening of the equatorial Atlantic Ocean during the early Cenomanian, which may have selectively affected some species.A Formação Alcântara, uma importante unidade estratigráfica do início do Cenomaniano no Brasil, foi depositada sob condições transicionais (estuarinas), e o seu registro fóssil inclui restos fragmentários de vegetais, peixes, crocodilomorfos, pterossauros e dinossauros, com uma notável diversidade de placas dentárias de dipnoiformes. O material de dipnoiformes aqui reportado compreende um novo taxon, Equinoxiodus alcantarensis gen. et sp. nov. A maioria dos morfótipos de vertebrados continentais coletados na Formação Alcântara são similares a faunas cronocorrelatas do norte da África, mas este novo gênero de Dipnoiformes indica algum grau de isolamento paleogeográfico e endemismo, provavelmente causado pelo alargamento do Oceano Atlântico equatorial no início do Cenomaniano, que pode ter afetado, de forma seletiva, algumas espécies

Meeting Report: Aging Research and Drug Discovery

Aging is the single largest risk factor for most chronic diseases, and thus possesses large socioeconomic interest to continuously aging societies. Consequently, the field of aging research is expanding alongside a growing focus from the industry and investors in aging research. This year’s 8th Annual Aging Research and Drug Discovery (ARDD) meeting was organized as a hybrid meeting from August 30th to September 3rd 2021 with more than 130 attendees participating on-site at the Ceremonial Hall at University of Copenhagen, Denmark, and 1800 engaging online. The conference comprised of presentations from 75 speakers focusing on new research in topics including mechanisms of aging and how these can be modulated as well as the use of AI and new standards of practices within aging research. This year, a longevity workshop was included to build stronger connections with the clinical community

The Sail-Backed Reptile Ctenosauriscus from the Latest Early Triassic of Germany and the Timing and Biogeography of the Early Archosaur Radiation

Background Archosaurs (birds, crocodilians and their extinct relatives including dinosaurs) dominated Mesozoic continental ecosystems from the Late Triassic onwards, and still form a major component of modern ecosystems (>10,000 species). The earliest diverse archosaur faunal assemblages are known from the Middle Triassic (c. 244 Ma), implying that the archosaur radiation began in the Early Triassic (252.3–247.2 Ma). Understanding of this radiation is currently limited by the poor early fossil record of the group in terms of skeletal remains. Methodology/Principal Findings We redescribe the anatomy and stratigraphic position of the type specimen of Ctenosauriscus koeneni (Huene), a sail-backed reptile from the Early Triassic (late Olenekian) Solling Formation of northern Germany that potentially represents the oldest known archosaur. We critically discuss previous biomechanical work on the ‘sail’ of Ctenosauriscus, which is formed by a series of elongated neural spines. In addition, we describe Ctenosauriscus-like postcranial material from the earliest Middle Triassic (early Anisian) Röt Formation of Waldhaus, southwestern Germany. Finally, we review the spatial and temporal distribution of the earliest archosaur fossils and their implications for understanding the dynamics of the archosaur radiation. Conclusions/Significance Comprehensive numerical phylogenetic analyses demonstrate that both Ctenosauriscus and the Waldhaus taxon are members of a monophyletic grouping of poposauroid archosaurs, Ctenosauriscidae, characterised by greatly elongated neural spines in the posterior cervical to anterior caudal vertebrae. The earliest archosaurs, including Ctenosauriscus, appear in the body fossil record just prior to the Olenekian/Anisian boundary (c. 248 Ma), less than 5 million years after the Permian–Triassic mass extinction. These earliest archosaur assemblages are dominated by ctenosauriscids, which were broadly distributed across northern Pangea and which appear to have been the first global radiation of archosaurs

Private Enforcement, Corruption, and Antitrust Design

Recent adoption of competition laws across the globe has highlighted the importance of institutional considerations for antitrust effectiveness and the need for comparative institutional analyses of antitrust that extend beyond matters of substantive law. Contributing to the resulting nascent research agenda, we examine how the rationale for enabling versus precluding private antitrust enforcement as one salient choice in antitrust design depends on whether antitrust enforcement is corruption-free or plagued by corruption. Contingent on the nature of adjudicatory bias, bribery either discourages private antitrust lawsuits or incentivizes firms to engage in frivolous litigation. Corruption expectedly reduces the effectiveness of antitrust enforcement at deterring antitrust violations. Yet private antitrust enforcement as a complement to public enforcement can be social welfare-enhancing even in the presence of corruption. Under some circumstances, corruption actually increases the relative social desirability of private antitrust enforcement. Our analysis highlights that the appropriate design of antitrust institutions is context-specific

Longevity biotechnology:bridging AI, biomarkers, geroscience and clinical applications for healthy longevity

The recent unprecedented progress in ageing research and drug discovery brings together fundamental research and clinical applications to advance the goal of promoting healthy longevity in the human population. We, from the gathering at the Aging Research and Drug Discovery Meeting in 2023, summarised the latest developments in healthspan biotechnology, with a particular emphasis on artificial intelligence (AI), biomarkers and clocks, geroscience, and clinical trials and interventions for healthy longevity. Moreover, we provide an overview of academic research and the biotech industry focused on targeting ageing as the root of age-related diseases to combat multimorbidity and extend healthspan. We propose that the integration of generative AI, cutting-edge biological technology, and longevity medicine is essential for extending the productive and healthy human lifespan