Modulation of the neuronal response in human primary visual cortex by re-entrant projections during retinal input processing as manifest in the visual evoked potential.

Initial deflections in the visual evoked potential (VEP) reflect the neuronal process of extracting features from the retinal input; a process not modulated by re-entrant projections. Later deflections in the VEP reflect the neuronal process of combining features into an object, a process referred to as 'object closure' and modulated by re-entrant projections. Our earlier work indicated that the VEP reflects independent neuronal responses processing temporal - and spatial luminance contrast and that these responses arise from an interaction between forward and re-entrant input. In this earlier work, changing the temporal luminance contrast property of a stimulus altered its spatial luminance contrast property. We recorded the VEP in 12 volunteers viewing image pairs of a windmill, regular dartboard or an RMS dartboard rotated by either Π/4, Π/2, 3Π/4 or Π radians with respect to each other. The windmill and regular dartboard had identical white to black ratio, while the two dartboards identical contrast edges per unit area. Rotation varied temporal luminance contrast of a stimulus without affecting its spatial luminance contrast. N75, P100, N135 and P240 amplitude and latency were compared and a source localisation and temporal frequency analysis performed. P100 amplitude signals a neuronal response processing temporal luminance contrast that is modulated by re-entrant projections with fast axonal conduction velocities. N135 and P240 signal the neuronal response processing spatial luminance contrast and is modulated by re-entrant projections with slow axonal conduction velocities. The dorsal stream is interconnected by fast axonal conduction velocities, the ventral stream by slow axonal conduction velocities.

Spiral packing and chiral selectivity in model membranes probed by phase-resolved sum-frequency generation microscopy.

Since the lipid raft model was developed at the end of the last century, it became clear that the specific molecular arrangements of phospholipid assemblies within a membrane have profound implications in a vast range of physiological functions. Studies of such condensed lipid islands in model systems using fluorescence and Brewster angle microscopies have shown a wide range of sizes and morphologies, with suggestions of substantial in-plane molecular anisotropy and mesoscopic structural chirality. Whilst these variations can significantly alter many membrane properties including its fluidity, permeability and molecular recognition, the details of the in-plane molecular orientations underlying these traits remain largely unknown. Here, we use phase-resolved sum-frequency generation microscopy on model membranes of mixed chirality phospholipid monolayers to fully determine the three-dimensional molecular structure of the constituent micron-scale condensed domains. We find that the domains possess curved molecular directionality with spiralling mesoscopic packing, where both the molecular and spiral turning directions depend on the lipid chirality, but form structures clearly deviating from mirror symmetry for different enantiomeric mixtures. This demonstrates strong enantioselectivity in the domain growth process and indicates fundamental thermodynamic differences between homo- and heterochiral membranes, which may be relevant in the evolution of homochirality in all living organisms.

Development of A Micro-CT Scanner with Dual-Energy Option and Endovascular Contrast Agent Administration Protocol for Fetal and Neonatal Virtual Autopsy.

The rate of parental consent for fetal and perinatal autopsy is decreasing, whereas parents are more likely to agree to virtual autopsy by non-invasive imaging methods. Fetal and perinatal virtual autopsy needs high-resolution and good soft-tissue contrast for investigation of the cause of death and underlying trauma or pathology in fetuses and stillborn infants. This is offered by micro-computed tomography (CT), as opposed to the limited resolution provided by clinical CT scanners, and this is one of the most promising tools for non-invasive perinatal postmortem imaging. We developed and optimized a micro-CT scanner with a dual-energy imaging option. It is dedicated to post-mortem CT angiography and virtual autopsy of fetuses and stillborn infants in that the chamber can be cooled down to around 5 °C; this increases tissue rigidity and slows decomposition of the native specimen. This, together with the dedicated gantry-based architecture, attempts to reduce potential motion artifacts. The developed methodology is based on prior endovascular injection of a BaSO4-based contrast agent. We explain the design choices and considerations for this scanner prototype. We give details of the treatment of the optimization of the dual-energy and virtual mono-energetic imaging option that has been based on minimizing noise propagation and maximizing the contrast-to-noise ratio for vascular features. We demonstrate the scanner capabilities with proof-of-concept experiments on phantoms and stillborn piglets.

Advances in Extracellular Vesicle Research Over the Past Decade: Source and Isolation Method are Connected with Cargo and Function.

The evolution of extracellular vesicle (EV) research has introduced nanotechnology into biomedical cell communication science while recognizing what is formerly considered cell "dust" as constituting an entirely new universe of cell signaling particles. To display the global EV research landscape, a systematic review of 20 364 original research articles selected from all 40 684 EV-related records identified in PubMed 2013-2022 is performed. Machine-learning is used to categorize the high-dimensional data and further dissected significant associations between EV source, isolation method, cargo, and function. Unexpected correlations between these four categories indicate prevalent experimental strategies based on cargo connectivity with function of interest being associated with certain EV sources or isolation strategies. Conceptually relevant association of size-based EV isolation with protein cargo and uptake function will guide strategic conclusions enhancing future EV research and product development. Based on this study, an open-source database is built to facilitate further analysis with conventional or AI tools to identify additional causative associations of interest.

Precision and normal values of cerebral blood volume in preterm neonates using time-resolved near-infrared spectroscopy.

AIM: To investigate cerebral blood volume (CBV) in preterm neonates using time-resolved near-infrared spectroscopy. METHODS: In this prospective observational study, time-resolved near-infrared spectroscopy measurements of CBV using tNIRS-1 were performed in 70 preterm neonates. For measurements, a sensor was placed for a duration of 1 min, followed by four further reapplications of the sensor, overall five measurements. RESULTS: In this study, 70 preterm neonates with a mean ± SD gestational age of 33.4 ± 1.7 weeks and a birthweight of 1931 ± 398 g were included with a postnatal age of 4.7 ± 2.0 days. Altogether, 2383 CBV values were obtained with an overall mean of 1.85 ± 0.30 mL/100 g brain. A total of 95% of the measured CBV values varied in a range from -0.31 to 0.33 from the overall individual mean. Taking the deviation of the mean of each single application for each patient, this range reduced from -0.07 to 0.07. The precision of the measurement defined as within-variation in CBV was 0.24 mL/100 g brain. CONCLUSION: The overall mean CBV in stable preterm neonates was 1.85 ± 0.30 mL/100 g brain. The within-variation in CBV was 0.24 mL/100 g brain. Based on the precision obtained by our data, CBV of 1.85 ± 0.30 mL/100 g brain may be assumed as normal value for this cohort.

Coherent light control of a metastable hidden state.

Metastable phases present a promising route to expand the functionality of complex materials. Of particular interest are light-induced metastable phases that are inaccessible under equilibrium conditions, as they often host new, emergent properties switchable on ultrafast timescales. However, the processes governing the trajectories to such hidden phases remain largely unexplored. Here, using time- and angle-resolved photoemission spectroscopy, we investigate the ultrafast dynamics of the formation of a hidden quantum state in the layered dichalcogenide 1T-TaS2 upon photoexcitation. Our results reveal the nonthermal character of the transition governed by a collective charge-density-wave excitation. Using a double-pulse excitation of the structural mode, we show vibrational coherent control of the phase-transition efficiency. Our demonstration of exceptional control, switching speed, and stability of the hidden state are key for device applications at the nexus of electronics and photonics.

Obtaining extended insight into molecular systems by probing multiple pathways in second-order nonlinear spectroscopy.

Second-order nonlinear spectroscopy is becoming an increasingly important technique in the study of interfacial systems owing to its marked ability to study molecular structures and interactions. The properties of such a system under investigation are contained within their intrinsic second-order susceptibilities which are mapped onto the measured nonlinear signals (e.g. sum-frequency generation) through the applied experimental settings. Despite this yielding a plethora of information, many crucial aspects of molecular systems typically remain elusive, for example the depth distributions, molecular orientation and local dielectric properties of its constituent chromophores. Here, it is shown that this information is contained within the phase of the measured signal and, critically, can be extracted through measurement of multiple nonlinear pathways (both the sum-frequency and difference-frequency output signals). Furthermore, it is shown that this novel information can directly be correlated to the characteristic vibrational spectra, enabling a new type of advanced sample characterization and a profound analysis of interfacial molecular structures. The theory underlying the different contributions to the measured phase of distinct nonlinear pathways is derived, after which the presented phase disentanglement methodology is experimentally demonstrated for model systems of self-assembled monolayers on several metallic substrates. The obtained phases of the local fields are compared to the corresponding phases of the nonlinear Fresnel factors calculated through the commonly used theoretical model, the three-layer model. It is found that, despite its rather crude assumptions, the model yields remarkable similarity to the experimentally obtained values, thus providing validation of the model for many sample classes.

[Prevention, Diagnosis, Therapy, and Follow-up of Lung Cancer - Interdisciplinary Guideline of the German Respiratory Society and the German Cancer Society - Abridged Version]. / Prävention, Diagnostik, Therapie und Nachsorge des Lungenkarzinoms.

The current S3 Lung Cancer Guidelines are edited with fundamental changes to the previous edition based on the dynamic influx of information to this field:The recommendations include de novo a mandatory case presentation for all patients with lung cancer in a multidisciplinary tumor board before initiation of treatment, furthermore CT-Screening for asymptomatic patients at risk (after federal approval), recommendations for incidental lung nodule management , molecular testing of all NSCLC independent of subtypes, EGFR-mutations in resectable early stage lung cancer in relapsed or recurrent disease, adjuvant TKI-therapy in the presence of common EGFR-mutations, adjuvant consolidation treatment with checkpoint inhibitors in resected lung cancer with PD-L1 ≥ 50%, obligatory evaluation of PD-L1-status, consolidation treatment with checkpoint inhibition after radiochemotherapy in patients with PD-L1-pos. tumor, adjuvant consolidation treatment with checkpoint inhibition in patients withPD-L1 ≥ 50% stage IIIA and treatment options in PD-L1 ≥ 50% tumors independent of PD-L1status and targeted therapy and treatment option immune chemotherapy in first line SCLC patients.Based on the current dynamic status of information in this field and the turnaround time required to implement new options, a transformation to a "living guideline" was proposed.

Infradian Rhythms in Cerebrovascular Oxygenation and Blood Volume in Humans at Rest: A 5-Year Study.

BACKGROUND: All parameters of human physiology show chronobiological variability. While circadian (cycle length ~ 24 h) rhythms of the neuronal, hemodynamic and metabolic aspects of human brain activity are increasingly being explored, infradian (cycle length > 24 h) rhythms are largely unexplored. AIM: We investigated if cerebrovascular oxygen saturation (StO2) and blood volume ([tHb]) values measured over many years in many subjects during resting show infradian rhythmicity. SUBJECTS AND METHODS:  Absolute StO2 and [tHb] values (median over a 5 min resting-phase while sitting) were measured in 220 healthy subjects (age: 24.7 ± 3.6 years, 87 males, 133 females) 2-4 times on different days over the right and left frontal lobe (FL) and occipital lobe (OL) by employing frequency-domain NIRS as part of different systemic physiology augmented functional near-infrared spectroscopy, SPA-fNIRS, studies. The data set consisted of 708 single measurements performed over a timespan of 5 years (2017-2021). General additive models (GAM) and cosinor modelling were used to analyze the data. RESULTS:  The GAM analysis revealed (i) a non-linear trend in the StO2 and [tHb] values over the 5-year span, (ii) a circannual (cycle length ~ 12 months) rhythm in StO2 at the FL (amplitude (A): 3.4%, acrophase (φ): June) and OL (A: 1.5%, φ: May) as well as in [tHb] at the OL (A: 1.2 µM, bathyphase (θ): June), and (iii) a circasemiannual (cycle length ~ 6 months) rhythm in [tHb] at the FL (A: 2.7 µM, φ: March and September, respectively). Furthermore, the circannual oscillations of StO2 (at the FL) and [tHb] (at the OL) were statistically significantly correlated with the day length, outdoor temperature, humidity and air pressure. DISCUSSION AND CONCLUSION:  We conclude that absolute values of StO2 and [tHb] show chronobiological variability on the group-level with a long-term nonlinear trend as well as circannual/circasemiannual rhythmicity. These rhythms need to be taken into account when defining reference values for StO2 and [tHb] and may correlate with the variability of cerebrovascular disease incidents over the year.

Image Reconstruction Using Deep Learning for Near-Infrared Optical Tomography: Generalization Assessment.

Time is one of the most critical factors in preventing brain lesions due to hypoxic ischemia in preterm infants. Since early detection of low oxygenation is vital and the time window for therapy is narrow, near-infrared optical tomography (NIROT) must be able to process the high-dimensional data provided by today's advanced systems in the shortest possible time. Deep learning approaches are attractive because they can exploit such high information density while reducing inference time. The aim of this study was to evaluate the performance of a hybrid convolutional neural network, designed for NIROT image reconstruction and trained on synthetic data. Generalization capability was assessed using measurements on phantoms of a surface topology more divergent than the range of variation in the geometries of the in-silico data, with unseen, non-spherical inclusion shapes, and with source and detector arrangements different from those used for data generation. Substantial gains in speed, localization accuracy, and high image quality were achieved even under the highly varied measurement conditions.

Time Domain Near-Infrared Optical Tomography Utilizing Full Temporal Data: A Simulation Study.

The analysis of full temporal data in time-domain near-infrared optical tomography (TD NIROT) measurements enables valuable information to be obtained about tissue properties with good temporal and spatial resolution. However, the large amount of data obtained is not easy to handle in the image reconstruction. The goal of the project is to employ full-temporal data from a TD NIROT modality. We improved TD data-based 3D image reconstruction and compared the performance with other methods using frequency domain (FD) and temporal moments. The iterative reconstruction algorithm was evaluated in simulations with both noiseless and noisy in-silico data. In the noiseless cases, a superior image quality was achieved by the reconstruction using full temporal data, especially when dealing with inclusions at 20 mm and deeper in the tissue. When noise similar to measured data was present, the quality of the recovered image from full temporal data was no longer superior to the one obtained from the analysis of FD data and temporal moments. This indicates that denoising methods for TD data should be developed. In conclusion, TD data contain richer information and yield better image quality.

BIAN: A Multilayer Microfluidic-Based Tissue-Mimicking Phantom for Near-Infrared Imaging.

Near-infrared spectroscopy (NIRS) is a non-invasive optical method for monitoring cerebral oxygenation. Changes in regional blood flow and oxygenation due to neurovascular coupling are important biomarkers of neuronal activation. So far, there has been little research on multilayer tissue phantoms with tuneable blood flow, blood volume, and optical properties to simulate local changes in oxygenation at different depths. The aim of this study is to design, fabricate and characterize a complex dynamic phantom based on multilayer microfluidics with controllable blood flow, blood volume, and optical properties for testing NIRS instruments. We developed a phantom prototype with two microfluidic chips embedded at two depths inside a solid silicone phantom to mimic the vessels in the scalp and in the cortex. To simulate the oxygenation and perfusion of tissue, a solution with blood-like optical properties was sent into the microchannels by a pump with a programmable pressure controller. The pressure adjusted the volume of the microfluidic chips representing a distension of blood vessels. The optical changes in the superficial and deep layers were measured by a commercially available frequency domain NIRS instrument. The NIRS successfully detected the changes in light intensity elicited by the changes in the pressure input to the two layers. In conclusion, the microfluidics-based imaging phantom was successfully designed and fabricated and mimics brain functional activity. This technique has great potential for testing other optical devices, e.g., diffuse correlation spectroscopy, pulse oximetry, and optical coherence tomography.

Compact oblique-incidence nonlinear widefield microscopy with paired-pixel balanced imaging.

Nonlinear (vibrational) microscopy has emerged as a successful tool for the investigation of molecular systems as it combines label-free chemical characterization with spatial resolution on the sub-micron scale. In addition to the molecular recognition, the physics of the nonlinear interactions allows in principle to obtain structural information on the molecular level such as molecular orientations. Due to technical limitations such as the relatively complex imaging geometry with the required oblique sample irradiation and insufficient sensitivity of the instrument this detailed molecular information is typically not accessible using widefield imaging. Here, we present, what we believe to be, a new microscope design that addresses both challenges. We introduce a simplified imaging geometry that enables the measurement of distortion-free widefield images with free space oblique sample irradiation achieving high spatial resolution (∼1 µm). Furthermore, we present a method based on a paired-pixel balanced detection system for sensitivity improvement. With this technique, we demonstrate a substantial enhancement of the signal-to-noise ratio of up to a factor of 10. While both experimental concepts presented in this work are very general and can, in principle, be applied to various microscopy techniques, we demonstrate their performance for the specific case of heterodyned, sum frequency generation (SFG) microscopy.

Controlling the propagation asymmetry of hyperbolic shear polaritons in beta-gallium oxide.

Structural anisotropy in crystals is crucial for controlling light propagation, particularly in the infrared spectral regime where optical frequencies overlap with crystalline lattice resonances, enabling light-matter coupled quasiparticles called phonon polaritons (PhPs). Exploring PhPs in anisotropic materials like hBN and MoO3 has led to advancements in light confinement and manipulation. In a recent study, PhPs in the monoclinic crystal ß-Ga2O3 (bGO) were shown to exhibit strongly asymmetric propagation with a frequency dispersive optical axis. Here, using scanning near-field optical microscopy (s-SNOM), we directly image the symmetry-broken propagation of hyperbolic shear polaritons in bGO. Further, we demonstrate the control and enhancement of shear-induced propagation asymmetry by varying the incident laser orientation and polariton momentum using different sizes of nano-antennas. Finally, we observe significant rotation of the hyperbola axis by changing the frequency of incident light. Our findings lay the groundwork for the widespread utilization and implementation of polaritons in low-symmetry crystals.

Kinematic Lie Algebras from Twistor Spaces.

We analyze theories with color-kinematics duality from an algebraic perspective and find that any such theory has an underlying BV^{▪}-algebra, extending the ideas of Reiterer [A homotopy BV algebra for Yang-Mills and color-kinematics, arXiv:1912.03110.]. Conversely, we show that any theory with a BV^{▪}-algebra features a kinematic Lie algebra that controls interaction vertices, both on shell and off shell. We explain that the archetypal example of a theory with a BV^{▪}-algebra is Chern-Simons theory, for which the resulting kinematic Lie algebra is isomorphic to the Schouten-Nijenhuis algebra on multivector fields. The BV^{▪}-algebra implies the known color-kinematics duality of Chern-Simons theory. Similarly, we show that holomorphic and Cauchy-Riemann Chern-Simons theories come with BV^{▪}-algebras and that, on the appropriate twistor spaces, these theories organize and identify kinematic Lie algebras for self-dual and full Yang-Mills theories, as well as the currents of any field theory with a twistorial description. We show that this result extends to the loop level under certain assumptions.

Observation of ultrafast interfacial Meitner-Auger energy transfer in a Van der Waals heterostructure.

Atomically thin layered van der Waals heterostructures feature exotic and emergent optoelectronic properties. With growing interest in these novel quantum materials, the microscopic understanding of fundamental interfacial coupling mechanisms is of capital importance. Here, using multidimensional photoemission spectroscopy, we provide a layer- and momentum-resolved view on ultrafast interlayer electron and energy transfer in a monolayer-WSe2/graphene heterostructure. Depending on the nature of the optically prepared state, we find the different dominating transfer mechanisms: while electron injection from graphene to WSe2 is observed after photoexcitation of quasi-free hot carriers in the graphene layer, we establish an interfacial Meitner-Auger energy transfer process following the excitation of excitons in WSe2. By analysing the time-energy-momentum distributions of excited-state carriers with a rate-equation model, we distinguish these two types of interfacial dynamics and identify the ultrafast conversion of excitons in WSe2 to valence band transitions in graphene. Microscopic calculations find interfacial dipole-monopole coupling underlying the Meitner-Auger energy transfer to dominate over conventional Förster- and Dexter-type interactions, in agreement with the experimental observations. The energy transfer mechanism revealed here might enable new hot-carrier-based device concepts with van der Waals heterostructures.

Two-layered blood-lipid phantom and method to determine absorption and oxygenation employing changes in moments of DTOFs.

Near-infrared spectroscopy (NIRS) is an established technique for measuring tissue oxygen saturation (StO2), which is of high clinical value. For tissues that have layered structures, it is challenging but clinically relevant to obtain StO2 of the different layers, e.g. brain and scalp. For this aim, we present a new method of data analysis for time-domain NIRS (TD-NIRS) and a new two-layered blood-lipid phantom. The new analysis method enables accurate determination of even large changes of the absorption coefficient (Δµa) in multiple layers. By adding Δµa to the baseline µa, this method provides absolute µa and hence StO2 in multiple layers. The method utilizes (i) changes in statistical moments of the distributions of times of flight of photons (DTOFs), (ii) an analytical solution of the diffusion equation for an N-layered medium, (iii) and the Levenberg-Marquardt algorithm (LMA) to determine Δµa in multiple layers from the changes in moments. The method is suitable for NIRS tissue oximetry (relying on µa) as well as functional NIRS (fNIRS) applications (relying on Δµa). Experiments were conducted on a new phantom, which enabled us to simulate dynamic StO2 changes in two layers for the first time. Two separate compartments, which mimic superficial and deep layers, hold blood-lipid mixtures that can be deoxygenated (using yeast) and oxygenated (by bubbling oxygen) independently. Simultaneous NIRS measurements can be performed on the two-layered medium (variable superficial layer thickness, L), the deep (homogeneous), and/or the superficial (homogeneous). In two experiments involving ink, we increased the nominal µa in one of two compartments from 0.05 to 0.25 cm-1, L set to 14.5 mm. In three experiments involving blood (L set to 12, 15, or 17 mm), we used a protocol consisting of six deoxygenation cycles. A state-of-the-art multi-wavelength TD-NIRS system measured simultaneously on the two-layered medium, as well as on the deep compartment for a reference. The new method accurately determined µa (and hence StO2) in both compartments. The method is a significant progress in overcoming the contamination from the superficial layer, which is beneficial for NIRS and fNIRS applications, and may improve the determination of StO2 in the brain from measurements on the head. The advanced phantom may assist in the ongoing effort towards more realistic standardized performance tests in NIRS tissue oximetry. Data and MATLAB codes used in this study were made publicly available.

How our hearts beat together: a study on physiological synchronization based on a self-paced joint motor task.

Cardiac physiological synchrony is regarded as an important component of social interaction due to its putative role in prosocial behaviour. Yet, the processes underlying physiological synchrony remain unclear. We aim to investigate these processes. 20 dyads (19 men, 21 women, age range 18-35) engaged in a self-paced interpersonal tapping synchronization task under different levels of tapping synchrony due to blocking of sensory communication channels. Applying wavelet transform coherence analysis, significant increases in heart rate synchronization from baseline to task execution were found with no statistically significant difference across conditions. Furthermore, the control analysis, which assessed synchrony between randomly combined dyads of participants showed no difference from the original dyads' synchrony. We showed that interindividual cardiac physiological synchrony during self-paced synchronized finger tapping resulted from a task-related stimulus equally shared by all individuals. We hypothesize that by applying mental effort to the task, individuals changed into a similar mental state, altering their cardiac regulation. This so-called psychophysiological mode provoked more uniform, less variable fluctuation patterns across all individuals leading to similar heart rate coherence independent of subsequent pairings. With this study, we provide new insights into cardiac physiological synchrony and highlight the importance of appropriate study design and control analysis.

Intraoperative assessment of resection margins by Raman spectroscopy to guide oral cancer surgery.

Patients with oral cavity cancer are almost always treated with surgery. The goal is to remove the tumor with a margin of more than 5 mm of surrounding healthy tissue. Unfortunately, this is only achieved in about 15% to 26% of cases. Intraoperative assessment of tumor resection margins (IOARM) can dramatically improve surgical results. However, current methods are laborious, subjective, and logistically demanding. This hinders broad adoption of IOARM, to the detriment of patients. Here we present the development and validation of a high-wavenumber Raman spectroscopic technology, for quick and objective intraoperative measurement of resection margins on fresh specimens. It employs a thin fiber-optic needle probe, which is inserted into the tissue, to measure the distance between a resection surface and the tumor. A tissue classification model was developed to discriminate oral cavity squamous cell carcinoma (OCSCC) from healthy oral tissue, with a sensitivity of 0.85 and a specificity of 0.92. The tissue classification model was then used to develop a margin length prediction model, showing a mean difference between margin length predicted by Raman spectroscopy and histopathology of -0.17 mm.