Changes over time in the course of advanced pancreatic cancer treatment with systemic chemotherapy: a pooled analysis of five clinical trials from two decades of the German AIO study group.

Background: Over the past two decades, our group has conducted five multicenter trials focusing on first-line systemic therapy for patients with advanced pancreatic cancer. The current pooled analysis was designed to evaluate prognosis over time and the impact of clinical characteristics on survival.

Patients And Methods: Individual patient data were derived from five prospective, controlled, multicenter trials conducted by the 'Arbeitsgemeinschaft Internistische Onkologie' (AIO): 'Gem/Cis', 'Ro96', 'RC57', 'ACCEPT' and 'RASH', which recruited patients between December 1997 and January 2017.

Corrigendum: Modeled energetics of bacterial communities in ancient subzero brines.

[This corrects the article DOI: 10.3389/fmicb.2023.

Three-month life expectancy as inclusion criterion for clinical trials in advanced pancreatic cancer: is it really a valid tool for patient selection?

Purpose: To analyze the 3-month life expectancy rate in pancreatic cancer (PC) patients treated within prospective trials from the German AIO study group.

Patients And Methods: A pooled analysis was conducted for patients with advanced PC that were treated within five phase II/III studies conducted between 1997 and 2017 (Gem/Cis, Ro96, RC57, ACCEPT, RASH). The primary goal for the current report was to identify the actual 3-month survival rate, a standard inclusion criterion in oncology trials.

Modeled energetics of bacterial communities in ancient subzero brines.

Cryopeg brines are isolated volumes of hypersaline water in subzero permafrost. The cryopeg system at Utqiaġvik, Alaska, is estimated to date back to 40 ka BP or earlier, a remnant of a late Pleistocene Ocean. Surprisingly, the cryopeg brines contain high concentrations of organic carbon, including extracellular polysaccharides, and high densities of bacteria.

The metabolic rate of the biosphere and its components.

We assessed the relationship between rates of biological energy utilization and the biomass sustained by that energy utilization, at both the organism and biosphere level. We compiled a dataset comprising >10,000 basal, field, and maximum metabolic rate measurements made on >2,900 individual species, and, in parallel, we quantified rates of energy utilization, on a biomass-normalized basis, by the global biosphere and by its major marine and terrestrial components. The organism-level data, which are dominated by animal species, have a geometric mean among basal metabolic rates of 0.

Phosphate availability and implications for life on ocean worlds.

Several moons in the outer solar system host liquid water oceans. A key next step in assessing the habitability of these ocean worlds is to determine whether life's elemental and energy requirements are also met. Phosphorus is required by all known life and is often limited to biological productivity in Earth's oceans.

Science Objectives for Flagship-Class Mission Concepts for the Search for Evidence of Life at Enceladus.

revealed that Saturn's Moon Enceladus hosts a subsurface ocean that meets the accepted criteria for habitability with bio-essential elements and compounds, liquid water, and energy sources available in the environment. Whether these conditions are sufficiently abundant and collocated to support life remains unknown and cannot be determined from data. However, thanks to the plume of oceanic material emanating from Enceladus' south pole, a new mission to Enceladus could search for evidence of life without having to descend through kilometers of ice.

Call for a framework for reporting evidence for life beyond Earth.

Our generation could realistically be the one to discover evidence of life beyond Earth. With this privileged potential comes responsibility. The magnitude of the question of whether we are alone in the Universe, and the public interest therein, opens the possibility that results may be taken to imply more than the observations support, or than the observers intend.

Microbial Communities in a Serpentinizing Aquifer Are Assembled through Strong Concurrent Dispersal Limitation and Selection.

In recent years, our appreciation of the extent of habitable environments in Earth's subsurface has greatly expanded, as has our understanding of the biodiversity contained within. Most studies have relied on single sampling points, rather than considering the long-term dynamics of subsurface environments and their microbial populations. One such habitat are aquifers associated with the aqueous alteration of ultramafic rocks through a process known as serpentinization.

A dynamic microbial sulfur cycle in a serpentinizing continental ophiolite.

Serpentinization is the hydration and oxidation of ultramafic rock, which occurs as oceanic lithosphere is emplaced onto continental margins (ophiolites), and along the seafloor as faulting exposes this mantle-derived material to circulating hydrothermal fluids. This process leads to distinctive fluid chemistries as molecular hydrogen (H ) and hydroxyl ions (OH ) are produced and reduced carbon compounds are mobilized. Serpentinizing ophiolites also serve as a vector to transport sulfur compounds from the seafloor onto the continents.

Carbon Assimilation Strategies in Ultrabasic Groundwater: Clues from the Integrated Study of a Serpentinization-Influenced Aquifer.

Serpentinization is a low-temperature metamorphic process by which ultramafic rock chemically reacts with water. Such reactions provide energy and materials that may be harnessed by chemosynthetic microbial communities at hydrothermal springs and in the subsurface. However, the biogeochemistry mediated by microbial populations that inhabit these environments is understudied and complicated by overlapping biotic and abiotic processes.

Probing the geological source and biological fate of hydrogen in Yellowstone hot springs.

Hydrogen (H ) is enriched in hot springs and can support microbial primary production. Using a series of geochemical proxies, a model to describe variable H concentrations in Yellowstone National Park (YNP) hot springs is presented. Interaction between water and crustal iron minerals yields H that partition into the vapour phase during decompressional boiling of ascending hydrothermal fluids.

The NASA Roadmap to Ocean Worlds.

In this article, we summarize the work of the NASA Outer Planets Assessment Group (OPAG) Roadmaps to Ocean Worlds (ROW) group. The aim of this group is to assemble the scientific framework that will guide the exploration of ocean worlds, and to identify and prioritize science objectives for ocean worlds over the next several decades. The overarching goal of an Ocean Worlds exploration program as defined by ROW is to "identify ocean worlds, characterize their oceans, evaluate their habitability, search for life, and ultimately understand any life we find.

Perioperative chemotherapy with or without epidermal growth factor receptor blockade in unselected patients with locally advanced oesophagogastric adenocarcinoma: Randomized phase II study with advanced biomarker program of the German Cancer Society (AIO/CAO STO-0801).

Background: Perioperative chemotherapy significantly improves survival in patients with locally advanced oesophagogastric cancer (EGC). However, as approximately 60% of patients will die from their disease, new therapeutic agents such as molecular-targeted drugs are needed.

Patients And Methods: To evaluate the role of panitumumab with perioperative chemotherapy, previously untreated patients with locally advanced EGC received, in an open-label randomised phase II study (NEOPECX), standard epirubicin, cisplatin, capecitabine (ECX) chemotherapy with or without panitumumab.

Panitumumab in Combination With Preoperative Radiation Therapy in Patients With Locally Advanced RAS Wild-type Rectal Cancer: Results of the Multicenter Explorative Single-Arm Phase 2 Study NEORIT.

Purpose: Studies investigating combinations of anti-epidermal growth factor receptor monoclonal antibodies such as panitumumab or cetuximab with standard chemoradiation therapy protocols in rectal cancer have yielded disappointing results. Because of the supposed negative interaction of epidermal growth factor receptor inhibition and chemoradiation therapy, we conducted a phase 2 study using single-agent panitumumab in combination with radiation therapy in patients with RAS wild-type locally advanced rectal cancer.

Methods And Materials: Patients with RAS wild-type locally advanced (clinical stage II or III) rectal cancer localized 0 to 12 cm from the anus were eligible for study participation.

Serpentinization-Influenced Groundwater Harbors Extremely Low Diversity Microbial Communities Adapted to High pH.

Serpentinization is a widespread geochemical process associated with aqueous alteration of ultramafic rocks that produces abundant reductants (H and CH) for life to exploit, but also potentially challenging conditions, including high pH, limited availability of terminal electron acceptors, and low concentrations of inorganic carbon. As a consequence, past studies of serpentinites have reported low cellular abundances and limited microbial diversity. Establishment of the Coast Range Ophiolite Microbial Observatory (California, U.

Drivers of Bacterial Maintenance and Minimal Energy Requirements.

Microbes maintain themselves through a variety of processes. Several of these processes can be reduced or shut down entirely when resource availability declines. In pure culture conditions with ample substrate supply, a relationship between the maximum growth rate and the energy invested in maintenance has been reported widely.

Evolutionary tradeoffs in cellular composition across diverse bacteria.

One of the most important classic and contemporary interests in biology is the connection between cellular composition and physiological function. Decades of research have allowed us to understand the detailed relationship between various cellular components and processes for individual species, and have uncovered common functionality across diverse species. However, there still remains the need for frameworks that can mechanistically predict the tradeoffs between cellular functions and elucidate and interpret average trends across species.

Life under extreme energy limitation: a synthesis of laboratory- and field-based investigations.

The ability of microorganisms to withstand long periods with extremely low energy input has gained increasing scientific attention in recent years. Starvation experiments in the laboratory have shown that a phylogenetically wide range of microorganisms evolve fitness-enhancing genetic traits within weeks of incubation under low-energy stress. Studies on natural environments that are cut off from new energy supplies over geologic time scales, such as deeply buried sediments, suggest that similar adaptations might mediate survival under energy limitation in the environment.

Carbon source preference in chemosynthetic hot spring communities.

Rates of dissolved inorganic carbon (DIC), formate, and acetate mineralization and/or assimilation were determined in 13 high-temperature (>73 °C) hot springs in Yellowstone National Park (YNP), Wyoming, in order to evaluate the relative importance of these substrates in supporting microbial metabolism. While 9 of the hot spring communities exhibited rates of DIC assimilation that were greater than those of formate and acetate assimilation, 2 exhibited rates of formate and/or acetate assimilation that exceeded those of DIC assimilation. Overall rates of DIC, formate, and acetate mineralization and assimilation were positively correlated with spring pH but showed little correlation with temperature.

Methane cycling. Nonequilibrium clumped isotope signals in microbial methane.

Methane is a key component in the global carbon cycle, with a wide range of anthropogenic and natural sources. Although isotopic compositions of methane have traditionally aided source identification, the abundance of its multiply substituted "clumped" isotopologues (for example, (13)CH3D) has recently emerged as a proxy for determining methane-formation temperatures. However, the effect of biological processes on methane's clumped isotopologue signature is poorly constrained.

Insights into environmental controls on microbial communities in a continental serpentinite aquifer using a microcosm-based approach.

Geochemical reactions associated with serpentinization alter the composition of dissolved organic compounds in circulating fluids and potentially liberate mantle-derived carbon and reducing power to support subsurface microbial communities. Previous studies have identified Betaproteobacteria from the order Burkholderiales and bacteria from the order Clostridiales as key components of the serpentinite-hosted microbiome, however there is limited knowledge of their metabolic capabilities or growth characteristics. In an effort to better characterize microbial communities, their metabolism, and factors limiting their activities, microcosm experiments were designed with fluids collected from several monitoring wells at the Coast Range Ophiolite Microbial Observatory (CROMO) in northern California during expeditions in March and August 2013.