Harmonic FMCW Radar System: Passive Tag Detection and Precise Ranging Estimation.

This paper details the design and implementation of a harmonic frequency-modulated continuous-wave (FMCW) radar system, specialized in detecting harmonic tags and achieving precise range estimation. Operating within the 2.4-2.5 GHz frequency range for the forward channel and 4.8-5.0 GHz for the backward channel, this study delves into the various challenges faced during the system's realization. These challenges include selecting appropriate components, calibrating the system, processing signals, and integrating the system components. In addition, we introduce a single-layer passive harmonic tag, developed specifically for assessing the system, and provide an in-depth theoretical analysis and simulation results. Notably, the system is characterized by its low power consumption, making it particularly suitable for short-range applications. The system's efficacy is further validated through experimental evaluations in a real-world indoor environment across multiple tag positions. Our measurements underscore the system's robust ranging accuracy and its ability to mitigate self-interference, showcasing its significant potential for applications in harmonic tag detection and ranging.

FEP Augmentation as a Means to Solve Data Paucity Problems for Machine Learning in Chemical Biology.

In the realm of medicinal chemistry, the primary objective is to swiftly optimize a multitude of chemical properties of a set of compounds to yield a clinical candidate poised for clinical trials. In recent years, two computational techniques, machine learning (ML) and physics-based methods, have evolved substantially and are now frequently incorporated into the medicinal chemist's toolbox to enhance the efficiency of both hit optimization and candidate design. Both computational methods come with their own set of limitations, and they are often used independently of each other. ML's capability to screen extensive compound libraries expediently is tempered by its reliance on quality data, which can be scarce especially during early-stage optimization. Contrarily, physics-based approaches like free energy perturbation (FEP) are frequently constrained by low throughput and high cost by comparison; however, physics-based methods are capable of making highly accurate binding affinity predictions. In this study, we harnessed the strength of FEP to overcome data paucity in ML by generating virtual activity data sets which then inform the training of algorithms. Here, we show that ML algorithms trained with an FEP-augmented data set could achieve comparable predictive accuracy to data sets trained on experimental data from biological assays. Throughout the paper, we emphasize key mechanistic considerations that must be taken into account when aiming to augment data sets and lay the groundwork for successful implementation. Ultimately, the study advocates for the synergy of physics-based methods and ML to expedite the lead optimization process. We believe that the physics-based augmentation of ML will significantly benefit drug discovery, as these techniques continue to evolve.

Diet-induced shifts in the gut microbiota influence anastomotic healing in a murine model of colonic surgery.

Host diet and gut microbiota interact to contribute to perioperative complications, including anastomotic leak (AL). Using a murine surgical model of colonic anastomosis, we investigated how diet and fecal microbial transplantation (FMT) impacted the intestinal microbiota and if a predictive signature for AL could be determined. We hypothesized that a Western diet (WD) would impact gut microbial composition and that the resulting dysbiosis would correlate with increased rates of AL, while FMT from healthy, lean diet (LD) donors would reduce the risk of AL. Furthermore, we predicted that surgical outcomes would allow for the development of a microbial preclinical translational tool to identify AL. Here, we show that AL is associated with a dysbiotic microbial community characterized by increased levels of Bacteroides and Akkermansia. We identified several key taxa that were associated with leak formation, and developed an index based on the ratio of bacteria associated with the absence and presence of leak. We also highlight a modifiable connection between diet, microbiota, and anastomotic healing, potentially paving the way for perioperative modulation by microbiota-targeted therapeutics to reduce AL.

Clutter Effect Investigation on Co-Polarized Chipless RFID Tags and Mitigation Using Cross-Polarized Tags, Analytical Model, Simulation, and Measurement.

Chipless radio frequency identification (RFID) technology is expected to replace barcode technology due to its ability to read in non-line-of-sight (NLOS) situations, long reading range, and low cost. Currently, there is extensive research being conducted on frequency-coded (FC) co-polarized radar cross-section (RCS)-based tags, which are widely used. However, detecting co-polarized chipless RFID tags in cluttered environments is still a challenge, as confirmed by measuring two co-polarized tags in front of a perfect metal reflector (30.5cm×22.5cm). To address this challenge, a realistic mathematical model for a chipless RFID system has been developed that takes into account the characteristics of the reader and the tag, as well as reflections from cluttered objects. This extensive mathematical model developed for linear chipless RFID systems in clutter scenarios holds the potential to greatly assist researchers in their exploration of RCS-based tags. By relying solely on simulations, this model provides a tool to effectively analyze and understand RCS-based tags, ultimately simplifying the process of generating more authentic tag designs. This model has been simulated and verified with measurement results by placing a single flat metal reflector behind two co-polarized one-bit designs: a dipole array tag and a square patch tag. The results showed that the interfering signal completely overlaps the ID of the co-polarized tag, severely limiting its detectability. To solve this issue, the proposed solution involves reading the tag in cross-polarization mode by etching a diagonal slot in the square patch tag. This proposed tag provides high immunity to the environment and can be detected in front of both dielectric and metallic objects.

Fecal Microbiota Restoration Modulates the Microbiome in Inflammation-Driven Colorectal Cancer.

Chronic inflammation of the colon (colitis) is a known risk factor for inflammatory-driven colorectal cancers (id-CRCs), and intestinal microbiota has been implicated in the etiology of id-CRCs. Manipulation of the microbiome is a clinically viable therapeutic approach to limiting id-CRCs. To understand the microbiome changes that occur over time in id-CRCs, we used a mouse model of id-CRCs with the treatment of azoxymethane (AOM) and dextran sodium sulfate (DSS) and measured the microbiome over time. We included cohorts where the microbiome was restored using cage bedding swapping and where the microbiome was depleted using antibiotics to compare to untreated animals. We identified consistent increases in Akkermansia in mice receiving horizontal microbiome transfer (HMT) via cage bedding swapping, while the control cohort had consistent longitudinal increases in Anaeroplasma and Alistipes. Additionally, fecal lipocalin-2 (Lcn-2), a marker of intestinal inflammation, was elevated in unrestored animals compared to restored and antibiotic-treated counterparts following HMT. These observations suggest a potential role for Akkermansia, Anaeroplasma, and Alistipes in regulating colonic inflammation in id-CRCs.

Osteo-pathological analysis provides evidence for a survived historical ship strike in a Southern Hemisphere fin whale (Balaenoptera physalus).

The life history of a fin whale (Balaenoptera physalus) caught during whaling operations in the 1950s was partly reconstructed. 3D surface models of the bones of the skeleton curated at the Zoological Museum of Hamburg were used for an osteopathological analysis. The skeleton revealed multiple healed fractures of ribs and a scapula. Moreover, the processus spinosi of several vertebrae were deformed and arthrosis was found. Together, the pathological findings provide evidence for large blunt trauma and secondary effects arising from it. Reconstruction of the likely cause of events suggests collision with a ship inflicting the fractures and leading to post traumatic posture damage as indicated by skeletal deformations. The injured bones had fully healed before the fin whale was killed by a whaler in the South Atlantic in 1952. This study is the first in-detail reconstruction of a historical whale-ship collision in the Southern Hemisphere, dating back to the 1940s, and the first documentation of a healed scapula fracture in a fin whale. The skeleton provides evidence for survival of a ship strike by a fin whale with severe injuries causing long-term impairment.

[Routine Practice Data for Health Care Analyses: Part 3 of the Manual]. / Versorgungsnahe Daten für Versorgungsanalysen ­ Teil 3 des Manuals.

Analyses of health and health care (hereafter referred to as "health care analyses") usually aim to make transparent the structures, processes, results and interrelationships of health care and to record the degree to which health care systems and their actors have achieved their goals. Health care-related data are an indispensable source of data for many health care analyses. A prerequisite for the examination of a degree of goal achievement is first of all an agreement on those goals that are to be achieved by the system and its substructures, as well as the identification of the determinants of the achievement of the objectives. Primarily it must be examined how safely, effectively and patient-centred systems, facilities and service providers are operating. It also addresses issues of need, accessibility, utilisation, timeliness, appropriateness, patient safety, coordination, continuity, and health economic efficiency and equity of health care. The results of health care include system services (outputs), on the one hand, and results (outcomes), on the other, whereby the results (patient-reported outcomes) and experiences (patient-reported experiences) reported are of particular importance. Health care analyses answer basic questions of health care research: who does what, when, how, why and with which resources and effects in routine health care. Health care analyses thus provide the necessary findings and key figures to further develop health care in order to improve the quality of health care. The applications range from capacity analyses to following innovations up to the concept of regional and supra-regional monitoring of the quality of care given to the population. Given the progress of digitalisation in Health Care, direct data from the care processes will be increasingly available for health care research. This can support care givers significantly if the findings of the studies are applied precisely and correctly within an adequate methodological frame. This can lead to measurable improved health care quality for patients. Data from the process of health care provision have a high potential. Their use needs the same scientific scrutiny as in all other scientific studies.

[Further Development and Interoperability in Oncological Care Structures, Quality Control and Research]. / Weiterentwicklung und Vernetzung der onkologischen Versorgungsstrukturen, der Qualitätssicherung und der Forschung.

How can we improve the interoperability of medical guidelines and the implementation and measurement of outcomes in medical health care for cancer patients as well as for care providers? This is the aim of the working group "Quality and Cross-linking". The following publication gives an overview of the targets reached in the development of guidelines together with quality indicators and documentation in cancer registries.

[Evidence-based health care with pharmaceuticals for rare diseases: the role of digitalisation]. / Evidenzbasierte Arzneimittelversorgung bei Seltenen Erkrankungen: die Rolle der Digitalisierung.

Knowledge generation in the field of drug development for people with rare diseases (RDs) faces particular difficulties. This paper will show what improvements are expected from increasing digitalisation from the perspective of three healthcare institutions: the Federal Institute for Drugs and Medical Devices, the Institute for Quality and Efficiency in Health Care and the Federal Joint Committee.First, the potential of digitalisation to increase the efficiency of clinical development and regulatory decision-making through earlier collaboration of all stakeholders is proposed. Subsequently, it is argued that digitalisation should be used to reduce barriers to the implementation of care-associated randomised controlled trials, including those based on registries. High-quality registry studies should not only be started after approval but during the approval process, so that the evidence necessary for therapy decisions is available promptly after approval. Finally, it is stated that improving the evidence base through qualitative improvement of the data sources and their linkages directly benefits patients. Usable evidence that can be generated over a longer period of time - also beyond approval - and contribute to decisions within healthcare system ensures effective drug provision.The institutions agree that high-quality indication registries should be developed as product-independent, standing infrastructures so that high-quality data can be accessed early in the development of medicines for RD.

Compilation of longitudinal gut microbiome, serum metabolome, and clinical data in acute myeloid leukemia.

Induction chemotherapy for patients with acute myeloid leukemia (AML) is a unique clinical scenario. These patients spend several weeks in the hospital, receiving multiple antibiotics, experiencing gastrointestinal mucosal damage, and suffering severe impairments in their immune system and nutrition. These factors cause major disruptions to the gut microbiota to a level rarely seen in other clinical conditions. Thus, the study of the gut microbiota in these patients can reveal novel aspects of microbiota-host relationships. When combined with the circulating metabolome, such studies could shed light on gut microbiota contribution to circulating metabolites. Collectively, gut microbiota and circulating metabolome are known to regulate host physiology. We have previously deposited amplicon sequences from 566 fecal samples from 68 AML patients. Here, we provide sample-level details and a link, using de-identified patient IDs, to additional data including serum metabolomics (260 samples from 36 patients) and clinical metadata. The detailed information provided enables comprehensive multi-omics analysis. We validate the technical quality of these data through 3 examples and demonstrate a method for integrated analysis.

Interpolation Methods with Phase Control for Backprojection of Complex-Valued SAR Data.

Time-domain backprojection algorithms are widely used in state-of-the-art synthetic aperture radar (SAR) imaging systems that are designed for applications where motion error compensation is required. These algorithms include an interpolation procedure, under which an unknown SAR range-compressed data parameter is estimated based on complex-valued SAR data samples and backprojected into a defined image plane. However, the phase of complex-valued SAR parameters estimated based on existing interpolators does not contain correct information about the range distance between the SAR imaging system and the given point of space in a defined image plane, which affects the quality of reconstructed SAR scenes. Thus, a phase-control procedure is required. This paper introduces extensions of existing linear, cubic, and sinc interpolation algorithms to interpolate complex-valued SAR data, where the phase of the interpolated SAR data value is controlled through the assigned a priori known range time that is needed for a signal to reach the given point of the defined image plane and return back. The efficiency of the extended algorithms is tested at the Nyquist rate on simulated and real data at THz frequencies and compared with existing algorithms. In comparison to the widely used nearest-neighbor interpolation algorithm, the proposed extended algorithms are beneficial from the lower computational complexity perspective, which is directly related to the offering of smaller memory requirements for SAR image reconstruction at THz frequencies.

Object Recognition in High-Resolution Indoor THz SAR Mapped Environment.

Synthetic aperture radar (SAR) at the terahertz (THz) spectrum has emerging short-range applications. In comparison to the microwave spectrum, the THz spectrum is limited in propagation range but benefits from high spatial resolution. The THz SAR is of significant interest for several applications which necessitate the mapping of indoor environments to support various endeavors such as rescue missions, map-assisted wireless communications, and household robotics. This paper addresses the augmentation of the high-resolution indoor mapped environment for object recognition, which includes detection, localization, and classification. Indoor object recognition is currently dominated by the usage of optical and infrared (IR) systems. However, it is not widely explored by radar technologies due to the limited spatial resolution at the most commonly used microwave frequencies. However, the THz spectrum provides a new paradigm of possible adaptation of object recognition in the radar domain by providing image quality in good compliance to optical/IR systems. In this paper, a multi-object indoor environment is foremost mapped at the THz spectrum ranging from 325 to 500 GHz in order to investigate the imaging in highly scattered environments and accordingly create a foundation for detection, localization, and classification. Furthermore, the extraction and clustering of features of the mapped environment are conducted for object detection and localization. Finally, the classification of detected objects is addressed with a supervised machine learning-based support vector machine (SVM) model.

Reduced Enterohepatic Recirculation of Mycophenolate and Lower Blood Concentrations Are Associated with the Stool Bacterial Microbiome after Hematopoietic Cell Transplantation.

Mycophenolate mofetil (MMF) is an important immunosuppressant used after allogeneic hematopoietic cell transplantation (HCT). MMF has a narrow therapeutic index, and blood concentrations of mycophenolic acid (MPA), the active component of MMF, are highly variable. Low MPA concentrations are associated with the risk of graft-versus-host disease (GVHD), whereas high concentrations are associated with toxicity. Reasons for variability are not well known and may include the presence of ß-glucuronidase-producing bacteria in the gastrointestinal tract, which enhance MPA enterohepatic recirculation (EHR) by transforming MPA metabolites formed in the liver back to MPA. This study was conducted to determine whether individuals with high MPA EHR have a greater abundance of ß-glucuronidase-producing bacteria in their stool and higher MPA concentrations compared with those with low EHR. We conducted a pharmacomicrobiomics study in 20 adult HCT recipients receiving a myeloablative or reduced-intensity preparative regimen. Participants received MMF 1 g i.v. every 8 hours with tacrolimus. Intensive pharmacokinetic sampling of MMF was conducted before hospital discharge; total MPA, MPA glucuronide (MPAG), and acyl-glucuronide metabolite (acylMPAG) were measured. EHR was defined as the ratio of MPA area under the concentration-versus-time curve (AUC)4-8 to MPA AUC0-8. Differences in stool microbiome diversity and composition, determined by shotgun metagenomic sequencing, were compared above and below the median EHR (22%; range, 5% to 44%). The median EHR was 12% in the low EHR group and 29% in the high EHR group. MPA troughs, MPA AUC4-8, and acyl-glucuronide metabolite (acylMPAG) AUC4-8/AUC0-8 ratio were greater in the high EHR group compared with the low EHR group (1.53 µg/mL versus .28 µg/mL [P = .0001], 7.33 hour·µg/mL versus 1.79 hour·µg/mL [P = .0003], and .33 hour·µg/mL versus .24 hour·µg/mL [P = .0007], respectively). MPA AUC0-8 was greater in the high EHR group than in the low EHR group, and the difference trended toward significance (22.8 hour·µg/mL versus 15.3 hour·µg/mL; P = .06). Bacteroides vulgatus, Bacteroides stercoris, and Bacteroides thetaiotaomicron were 1.2- to 2.4-fold more abundant (P = .039, .024, and .046, respectively) in the high EHR group. MPA EHR was positively correlated with B. vulgatus (⍴ = .58; P ≤ .01) and B. thetaiotaomicron (⍴ = .46; P < .05) and negatively correlated with Blautia hydrogenotrophica (⍴ = -.53; P < .05). Therapeutic MPA troughs were achieved in 80% of patients in the high EHR group but in no patients in the low EHR group. There was a trend toward differences in MPA AUC0-8 and MPA concentration at steady-state (µg/mL) between the high EHR group versus the low EHR group (P = .06). MPA EHR was variable. Patients with high MPA EHR had greater abundance of Bacteroides species in stool and higher MPA exposure compared with patients with low MPA EHR. Therefore, Bacteroides may be protective against poor outcomes, such as graft-versus-host disease, in some patients but may increase the risk of MPA adverse effects in others. These data need to be confirmed and studied after oral MMF therapy.

Protective Effect of Intestinal Blautia Against Neutropenic Fever in Allogeneic Transplant Recipients.

BACKGROUND: Neutropenic fever (NF) occurs in >70% of hematopoietic cell transplant (HCT) recipients, without a documented cause in most cases. Antibiotics used to prevent and treat NF disrupt the gut microbiota; these disruptions predict a higher posttransplantation mortality rate. We hypothesized that specific features in the gut microbial community may mediate the risk of NF. METHODS: We searched a large gut microbiota database in allogeneic HCT recipients (12 546 stool samples; 1278 patients) to find pairs with NF (cases) versus without NF (controls) on the same day relative to transplantation and with a stool sample on the previous day. A total of 179 such pairs were matched as to the underlying disease and graft source. Several other important clinical variables were similar between the groups. RESULTS: The gut microbiota of cases on the day before NF occurrence had a lower abundance of Blautia than their matched controls on the same day after transplantation, suggesting a protective role for Blautia. Microbiota network analysis did not find any differences in community structure between the groups, suggesting a single-taxon effect. To identify putative mechanisms, we searched a gut microbiome and serum metabolome database of patients with acute leukemia receiving chemotherapy and identified 139 serum samples collected within 24 hours after a stool sample from the same patient. Greater Blautia abundances predicted higher levels of next-day citrulline, a biomarker of total enterocyte mass. CONCLUSIONS: These findings support a model in which Blautia protects against NF by improving intestinal health. Therapeutic restoration of Blautia may help prevent NF, thus reducing antibiotic exposures and transplantation-related deaths.

Network-based approaches for the investigation of microbial community structure and function using metagenomics-based data.

Network-based approaches offer a powerful framework to evaluate microbial community organization and function as it relates to a variety of environmental processes. Emerging studies are exploring network theory as a method for data integration that is likely to be critical for the integration of 'omics' data using systems biology approaches. Intricacies of network theory and methodological and computational complexities in network construction, however, impede the use of these tools for translational science. We provide a perspective on the methods of network construction, interpretation and emerging uses for these techniques in understanding host-microbiota interactions.

The study of the contribution of the microbiome to health and disease offers a promising avenue to better understand disease processes and offer more personalized therapies. These communities comprise thousands of species and strains that interact among each other and with the host in a variety of complex ways to influence patient health. Studying these communities as a network of interactions, rather than looking at specific species or functions individually, will provide a more comprehensive understanding of how the microbiome contributes to disease processes. Here, we describe the current methods for studying microbiome networks and interpreting how network features may be related to health outcomes.

Post-mortem enamel surface texture alteration during taphonomic processes-do experimental approaches reflect natural phenomena?

Experimental approaches are often used to better understand the mechanisms behind and consequences of post-mortem alteration on proxies for diet reconstruction. Dental microwear texture analysis (DMTA) is such a dietary proxy, using dental wear features in extant and extinct taxa to reconstruct feeding behaviour and mechanical food properties. In fossil specimens especially, DMTA can be biased by post-mortem alteration caused by mechanical or chemical alteration of the enamel surface. Here we performed three different dental surface alteration experiments to assess the effect of common taphonomic processes by simplifying them: (1) tumbling in sediment suspension to simulate fluvial transport, (2) sandblasting to simulate mechanical erosion due to aeolian sediment transport, (3) acid etching to simulate chemical dissolution by stomach acid. For tumbling (1) we found alteration to be mainly dependent on sediment grain size fraction and that on specimens tumbled with sand fractions mainly post-mortem scratches formed on the dental surface, while specimens tumbled with a fine-gravel fraction showed post-mortem formed dales. Sandblasting (2) with loess caused only negligible alteration, however blasting with fine sand quartz particles resulted in significant destruction of enamel surfaces and formation of large post-mortem dales. Acid etching (3) using diluted hydrochloric acid solutions in concentrations similar to that of predator stomachs led to a complete etching of the whole dental surface, which did not resemble those of teeth recovered from owl pellets. The experiments resulted in post-mortem alteration comparable, but not identical to naturally occurring post-mortem alteration features. Nevertheless, this study serves as a first assessment and step towards further, more refined taphonomic experiments evaluating post-mortem alteration of dental microwear texture (DMT).

Lasting shift in the gut microbiota in patients with acute myeloid leukemia.

Previous studies have shown that the gut microbiota of patients with acute myeloid leukemia (AML) is disrupted during induction chemotherapy; however, the durability of microbiota changes is unknown. This is an important knowledge gap, because reduced microbiota diversity at the time of stem cell transplantation weeks to months after the initial chemotherapy has been associated with higher mortality after transplantation. By sequencing the gut microbiota in 410 longitudinal stool samples from 52 patients with AML, we found that, during inpatient chemotherapy, the gut microbiota is stressed beyond its ability to recover its original state. Despite major reductions in antibiotic pressure and other disturbances to the microbiota after hospital discharge, the trajectory of microbiota recovery yields new communities that are highly dissimilar to baseline. This lasting shift in the gut microbiota is relevant for subsequent phases of curative therapy and is a potential target for novel microbiota protective/restorative interventions. This trial was registered at www.clinicaltrials.gov as #NCT03316456.