Diagnostic Potential of Supplemental Static and Dynamic 68Ga-FAPI-46 PET for Primary 18F-FDG-Negative Pulmonary Lesions.

PET using 68Ga-labeled fibroblast activation protein (FAP) inhibitors (FAPIs) holds high potential for diagnostic imaging of various malignancies, including lung cancer (LC). However, 18F-FDG PET is still the clinical gold standard for LC imaging. Several subtypes of LC, especially lepidic LC, are frequently 18F-FDG PET-negative, which markedly hampers the assessment of single pulmonary lesions suggestive of LC. Here, we evaluated the diagnostic potential of static and dynamic 68Ga-FAPI-46 PET in the 18F-FDG-negative pulmonary lesions of 19 patients who underwent surgery or biopsy for histologic diagnosis after PET imaging. For target validation, FAP expression in lepidic LC was confirmed by FAP immunohistochemistry. Methods: Hematoxylin and eosin staining and FAP immunohistochemistry of 24 tissue sections of lepidic LC from the local tissue bank were performed and analyzed visually. Clinically, 19 patients underwent static and dynamic 68Ga-FAPI-46 PET in addition to 18F-FDG PET based on individual clinical indications. Static PET data of both examinations were analyzed by determining SUVmax, SUVmean, and tumor-to-background ratio (TBR) against the blood pool, as well as relative parameters (68Ga-FAPI-46 in relation to18F-FDG), of histologically confirmed LC and benign lesions. Time-activity curves and dynamic parameters (time to peak, slope, k 1, k 2, k 3, and k 4) were extracted from dynamic 68Ga-FAPI-46 PET data. The sensitivity and specificity of all parameters were analyzed by calculating receiver-operating-characteristic curves. Results: FAP immunohistochemistry confirmed the presence of strongly FAP-positive cancer-associated fibroblasts in lepidic LC. LC showed markedly elevated 68Ga-FAPI-46 uptake, higher TBRs, and higher 68Ga-FAPI-46-to-18F-FDG ratios for all parameters than did benign pulmonary lesions. Dynamic imaging analysis revealed differential time-activity curves for LC and benign pulmonary lesions: initially increasing time-activity curves with a decent slope were typical of LC, and steadily decreasing time-activity curve indicated benign pulmonary lesions, as was reflected by a significantly increased time to peak and significantly smaller absolute values of the slope for LC. Relative 68Ga-FAPI-46-to-18F-FDG ratios regarding SUVmax and TBR showed the highest sensitivity and specificity for the discrimination of LC from benign pulmonary lesions. Conclusion: 68Ga-FAPI-46 PET is a powerful new tool for the assessment of single 18F-FDG-negative pulmonary lesions and may optimize patient stratification in this clinical setting.

[Modern individualized diagnostics and treatment of non-small cell lung cancer]. / Moderne individualisierte Diagnostik und Behandlung des nichtkleinzelligen Lungenkarzinoms.

Approximately one half of patients with non-small cell lung cancer (NSCLC) are diagnosed at resectable tumor stages (I-IIIA), which can potentially be curatively treated. In the early tumor stages (tumor diameter ≤2 cm) sublobar resection (segmentectomy or atypical wedge resection) leads to a 5­year long-term survival comparable to lobectomy. The use of immunotherapy, especially within the framework of neoadjuvant treatment, is anticipated to change the surgical treatment of NSCLC in the future. With the introduction of lung cancer screening for certain risk groups in Germany planned for 2024, lung tumors can be expected to be diagnosed at earlier stages and more frequently curatively treated. This article provides an overview of the potential impact of lung cancer screening, modern minimally invasive surgical techniques and neoadjuvant treatment concepts for the surgical treatment of NSCLC.

In Situ Regolith Seismic Velocity Measurement at the InSight Landing Site on Mars.

Interior exploration using Seismic Investigations, Geodesy and Heat Transport's (InSight) seismometer package Seismic Experiment for Interior Structure (SEIS) was placed on the surface of Mars at about 1.2 m distance from the thermal properties instrument Heat flow and Physical Properties Package (HP3) that includes a self-hammering probe. Recording the hammering noise with SEIS provided a unique opportunity to estimate the seismic wave velocities of the shallow regolith at the landing site. However, the value of studying the seismic signals of the hammering was only realized after critical hardware decisions were already taken. Furthermore, the design and nominal operation of both SEIS and HP3 are nonideal for such high-resolution seismic measurements. Therefore, a series of adaptations had to be implemented to operate the self-hammering probe as a controlled seismic source and SEIS as a high-frequency seismic receiver including the design of a high-precision timing and an innovative high-frequency sampling workflow. By interpreting the first-arriving seismic waves as a P-wave and identifying first-arriving S-waves by polarization analysis, we determined effective P- and S-wave velocities of v P = 11 9 - 21 + 45 m/s and v S = 6 3 - 7 + 11 m/s, respectively, from around 2,000 hammer stroke recordings. These velocities likely represent bulk estimates for the uppermost several 10s of cm of regolith. An analysis of the P-wave incidence angles provided an independent v P /v S ratio estimate of 1.8 4 - 0.35 + 0.89 that compares well with the traveltime based estimate of 1.8 6 - 0.25 + 0.42 . The low seismic velocities are consistent with those observed for low-density unconsolidated sands and are in agreement with estimates obtained by other methods.

Thoracic surgery in the non-intubated spontaneously breathing patient.

BACKGROUND: The interest in non-intubated video-assisted thoracic surgery (NIVATS) has risen over the last decade and numerous terms have been used to describe this technique. They all have in common, that the surgical procedure is performed in a spontaneously breathing patient under locoregional anaesthesia in combination with intravenous sedation but have also been performed on awake patients without sedation. Evidence has been generated favouring NIVATS compared to one-lung-ventilation under general anaesthesia. MAIN BODY: We want to give an overview of how NIVATS is performed, and which different techniques are possible. We discuss advantages such as shorter length of hospital stay or (relative) contraindications like airway difficulties. Technical aspects, for instance intraoperative handling of the vagus nerve, are considered from a thoracic surgeon's point of view. Furthermore, special attention is paid to the cohort of patients with interstitial lung diseases, who seem to benefit from NIVATS due to the avoidance of positive pressure ventilation. Whenever a new technique is introduced, it must prove noninferiority to the state of the art. Under this aspect current literature on NIVATS for lung cancer surgery has been reviewed. CONCLUSION: NIVATS technique may safely be applied to minor, moderate, and major thoracic procedures and is appropriate for a selected group of patients, especially in interstitial lung disease. However, prospective studies are urgently needed.

The Specific Heat of Astro-materials: Review of Theoretical Concepts, Materials, and Techniques.

We provide detailed background, theoretical and practical, on the specific heat of minerals and mixtures thereof, 'astro-materials,' as well as background information on common minerals and other relevant solid substances found on the surfaces of solar system bodies. Furthermore, we demonstrate how to use specific heat and composition data for lunar samples and meteorites as well as a new database of endmember mineral heat capacities (the result of an extensive literature review) to construct reference models for the isobaric specific heat c P as a function of temperature for common solar system materials. Using a (generally linear) mixing model for the specific heat of minerals allows extrapolation of the available data to very low and very high temperatures, such that models cover the temperature range between 10 K and 1000 K at least (and pressures from zero up to several kbars). We describe a procedure to estimate c P (T) for virtually any solid solar system material with a known mineral composition, e.g., model specific heat as a function of temperature for a number of typical meteorite classes with known mineralogical compositions. We present, as examples, the c P (T) curves of a number of well-described laboratory regolith analogs, as well as for planetary ices and 'tholins' in the outer solar system. Part II will review and present the heat capacity database for minerals and compounds and part III is going to cover applications, standard reference compositions, c P (T) curves, and a comparison with new and literature experimental data. Supplementary Information: The online version contains supplementary material available at 10.1007/s10765-022-03046-5.

Surgical Lung Biopsy for Interstitial Lung Disease: A Two Center Propensity Score Matching Analysis.

BACKGROUND: Surgical lung biopsy (SLB) is recommended for patients with nonclassified interstitial lung disease (nILD) if high resolution computed tomography and/or transbronchial lung biopsy did not achieve a definitive diagnosis. Current literature suggests better patient tolerability and less postoperative complications if surgery is performed under spontaneous ventilation. OBJECTIVES: We conducted a propensity score matching (PSM) analysis of our nILD patients undergoing SLB under spontaneous ventilation or general anesthesia to investigate postprocedural AE-ILD, 30-/90-day mortality and perioperative variables in two academic high-volume centers (Hannover, Heidelberg). METHODS: All patients undergoing SLB for nILD under general anesthesia (GAVATS) and spontaneous ventilation (NIVATS) at both centers from February 2013 until April 2021 were analyzed retrospectively. Data of 132 patients were used for PSM resulting in 40 pairs. RESULTS: There was one death in the NIVATS group 60 days after SLB and one AE-ILD in each cohort. Chest tube indwelling time, chest tube total effusion, length of hospital stay, and operative time were all in favor of NIVATS. CONCLUSIONS: In our PSM analysis, NIVATS is associated with faster postprocedural recovery. However, a reduction in postoperative AE-ILD or 30-/90-day mortality was not observed.

A Reconstruction Algorithm for Temporally Aliased Seismic Signals Recorded by the InSight Mars Lander.

In December 2018, the NASA InSight lander successfully placed a seismometer on the surface of Mars. Alongside, a hammering device was deployed at the landing site that penetrated into the ground to attempt the first measurements of the planetary heat flow of Mars. The hammering of the heat probe generated repeated seismic signals that were registered by the seismometer and can potentially be used to image the shallow subsurface just below the lander. However, the broad frequency content of the seismic signals generated by the hammering extends beyond the Nyquist frequency governed by the seismometer's sampling rate of 100 samples per second. Here, we propose an algorithm to reconstruct the seismic signals beyond the classical sampling limits. We exploit the structure in the data due to thousands of repeated, only gradually varying hammering signals as the heat probe slowly penetrates into the ground. In addition, we make use of the fact that repeated hammering signals are sub-sampled differently due to the unsynchronized timing between the hammer strikes and the seismometer recordings. This allows us to reconstruct signals beyond the classical Nyquist frequency limit by enforcing a sparsity constraint on the signal in a modified Radon transform domain. In addition, the proposed method reduces uncorrelated noise in the recorded data. Using both synthetic data and actual data recorded on Mars, we show how the proposed algorithm can be used to reconstruct the high-frequency hammering signal at very high resolution.

Soil Thermophysical Properties Near the InSight Lander Derived From 50 Sols of Radiometer Measurements.

Measurements from the InSight lander radiometer acquired after landing are used to characterize the thermophysical properties of the Martian soil in Homestead hollow. This data set is unique as it stems from a high measurement cadence fixed platform studying a simple well-characterized surface, and it benefits from the environmental characterization provided by other instruments. We focus on observations acquired before the arrival of a regional dust storm (near Sol 50), on the furthest observed patch of soil (i.e., ∼3.5 m away from the edge of the lander deck) where temperatures are least impacted by the presence of the lander and where the soil has been least disrupted during landing. Diurnal temperature cycles are fit using a homogenous soil configuration with a thermal inertia of 183 ± 25 J m-2 K-1 s-1/2 and an albedo of 0.16, corresponding to very fine to fine sand with the vast majority of particles smaller than 140 µm. A pre-landing assessment leveraging orbital thermal infrared data is consistent with these results, but our analysis of the full diurnal temperature cycle acquired from the ground further indicates that near surface layers with different thermophysical properties must be thin (i.e., typically within the top few mm) and deep layering with different thermophysical properties must be at least below ∼4 cm. The low thermal inertia value indicates limited soil cementation within the upper one or two skin depths (i.e., ∼4-8 cm and more), with cement volumes <<1%, which is challenging to reconcile with visible images of overhangs in pits.

Highly porous nature of a primitive asteroid revealed by thermal imaging.

Carbonaceous (C-type) asteroids1 are relics of the early Solar System that have preserved primitive materials since their formation approximately 4.6 billion years ago. They are probably analogues of carbonaceous chondrites2,3 and are essential for understanding planetary formation processes. However, their physical properties remain poorly known because carbonaceous chondrite meteoroids tend not to survive entry to Earth's atmosphere. Here we report on global one-rotation thermographic images of the C-type asteroid 162173 Ryugu, taken by the thermal infrared imager (TIR)4 onboard the spacecraft Hayabusa25, indicating that the asteroid's boulders and their surroundings have similar temperatures, with a derived thermal inertia of about 300 J m-2 s-0.5 K-1 (300 tiu). Contrary to predictions that the surface consists of regolith and dense boulders, this low thermal inertia suggests that the boulders are more porous than typical carbonaceous chondrites6 and that their surroundings are covered with porous fragments more than 10 centimetres in diameter. Close-up thermal images confirm the presence of such porous fragments and the flat diurnal temperature profiles suggest a strong surface roughness effect7,8. We also observed in the close-up thermal images boulders that are colder during the day, with thermal inertia exceeding 600 tiu, corresponding to dense boulders similar to typical carbonaceous chondrites6. These results constrain the formation history of Ryugu: the asteroid must be a rubble pile formed from impact fragments of a parent body with microporosity9 of approximately 30 to 50 per cent that experienced a low degree of consolidation. The dense boulders might have originated from the consolidated innermost region or they may have an exogenic origin. This high-porosity asteroid may link cosmic fluffy dust to dense celestial bodies10.

Progesterone and estrogen prevent cisplatin-induced apoptosis of lung cancer cells.

Metastatic non-small cell lung cancer (NSCLC) remains the most common cause of tumor mortality despite the introduction of novel agents. Female sex hormones play a role in NSCLC pathogenesis and negatively influence the course of this disease. Herein, we present data on possible underlying mechanisms. Both estrogen and progesterone pre-treatment led to chemoresistance of A549 NSCLC cells in vitro by attenuating cisplatin-induced apoptosis. These effects were not antagonized by the estrogen or progesterone receptor antagonists ICI 182,780 and RU486 (mifepristone). Cisplatin induced apoptosis via activation of caspases -3/7, -8 and -9. Estrogen and progesterone attenuated levels of caspase activation. Interestingly, copper-transporter-1, which is responsible for the intracellular accumulation of cisplatin, was not modulated by sex hormones and the effects of estrogen and progesterone were neither additive nor synergistic. Our results suggest that estrogen and progesterone contribute to the development of chemotherapy resistance in NSCLC via non-classical sex hormone signaling pathways.

In situ methods for measuring thermal properties and heat flux on planetary bodies.

The thermo-mechanical properties of planetary surface and subsurface layers control to a high extent in which way a body interacts with its environment, in particular how it responds to solar irradiation and how it interacts with a potentially existing atmosphere. Furthermore, if the natural temperature profile over a certain depth can be measured in situ, this gives important information about the heat flux from the interior and thus about the thermal evolution of the body. Therefore, in most of the recent and planned planetary lander missions experiment packages for determining thermo-mechanical properties are part of the payload. Examples are the experiment MUPUS on Rosetta's comet lander Philae, the TECP instrument aboard NASA's Mars polar lander Phoenix, and the mole-type instrument HP(3) currently developed for use on upcoming lunar and Mars missions. In this review we describe several methods applied for measuring thermal conductivity and heat flux and discuss the particular difficulties faced when these properties have to be measured in a low pressure and low temperature environment. We point out the abilities and disadvantages of the different instruments and outline the evaluation procedures necessary to extract reliable thermal conductivity and heat flux data from in situ measurements.