julilili42/papers huggingface dataset:
Image quality and quantitative PET parameters of low-dose [18F]FDG PET in a Total-Body PET/CT scanner.
2023-10-04

Total-body PET/CT scanners provide increased sensitivity, enabling the adjustment of imaging parameters by reducing injected activity or shortening acquisition time. This study aimed to evaluate the limitations of reduced [18F]FDG activity doses on image quality, lesion detectabil-ity, and quantification of lesion uptake in the Biograph Vision Quadra, as well as to assess the benefits of the recently introduced ultra-high sensitivity mode in a clinical setting. A number of 26 patients who underwent [18F]FDG-PET/CT (3.0 MBq/kg, 5 min. scan time) were included in this analysis. PET raw data was rebinned for shorter frame durations to simulate 5 min. scans with lower activities in high sensitivity (HS) and ultra-high sensitivity (UHS) modes. Image quality, noise, and lesion detectability (n=82) were assessed using a 5-point Likert scale. The co-efficient of variation (CoV), signal-to-noise ratio (SNR), tumor-to-background ratio (TBR), and standardized uptake values (SUV) including SUVmean, SUVmax, and SUVpeak were evaluated. Sub-jective image ratings were generally superior in UHS compared to HS mode. At 0.5 MBq/kg, le-sion detectability decreased to 95% (HS) and 98% (UHS). SNR was comparable at 1.0 MBq/kg in HS (5.7±0.6) and 0.5 MBq/kg in UHS (5.5±0.5). With lower doses, there were negligible reductions in SUVmean and SUVpeak, whereas SUVmax increased steadily. Reducing [18F]FDG activity to 1.0 MBq/kg (HS/UHS) in a total-body PET/CT provides diagnostic image quality without statistical-ly significant changes in uptake parameters. UHS mode improves image quality, noise, and le-sion detectability compared to HS mode.
Evaluation of a 12-week app-guided exercise intervention in patients with knee osteoarthritis (re.flex): a study protocol for a randomized controlled trial
2023-10-04

Abstract Background Current health care demonstrates an insufficient provision and utilization of physical exercises despite their recommendation as a first-line treatment in clinical guidelines for patients with knee osteoarthritis (OA). Mobile health (m-health) technologies offer new opportunities to guide and monitor home-based exercise programs by using mobile devices and inertial sensors in combination with a digital application (app). This study will evaluate patient benefits resulting from the use of the specific digital health application re.flex for patients with knee OA. Methods This monocentric, two-arm, randomized controlled parallel-group trial will evaluate the effectiveness of the app- and sensor-guided exercise program re.flex for patients with moderate-to-severe knee OA. We aim to recruit 200 participants via newspapers, newsletters and information events. Participants will be randomly allocated to the intervention group and the control group in a 1:1 ratio. Participants in the control group will not receive any study intervention or instruction for any change to their previous health care utilization. Despite this, they are allowed to make use of usual care provided by their treating physician. The intervention group comprises a 12-week home training program with three sessions per week in addition to usual care. Exercises will be guided and monitored by use of the training app (re.flex) and two accelerometers that are attached proximally and distally to the affected knee joint. Pre- and postmeasurements will take place at baseline (t0) and after 12 weeks (t1). Primary outcomes will be osteoarthritis-specific pain and physical function measured with the Knee Osteoarthritis Outcome Score (KOOS) subscales Pain and Function in daily living (ADL). Second, further self-reported health outcomes, a performance measurement, app logfiles and safety will be assessed. Intervention effects will be calculated by baseline-adjusted analysis of covariance (ANCOVA) using an intention-to-treat approach. Multiple imputation will be applied. Discussion Re.flex can bridge part of the gap between recommendations for strengthening exercises in patients with knee OA and the insufficient actual care situation. This randomized controlled trial is designed to provide conclusions on the effectiveness of the health application re.flex for the population under study and will provide further insight into adherence rates and the safety of its use. Trial registration The trial was registered on 20/01/2023 at www.drks.de (ID: DRKS00030932).
Field and Laboratory Evidence for Manganese Redox Cycling Controlling Iron and Arsenic Retention in Household Sand Filters
2023-10-04

Application of household sand filters (SFs) is widespread in low-income regions, such as West Bengal, Bangladesh, and Vietnam, for the removal of groundwater contaminants including Fe, Mn, and As. SF operation typically transitions from (oxic) unsaturated conditions to saturated conditions, creating oxygen-limited zones within sand layers. To ensure the safe and effective use of SFs, understanding filter performance and spatiotemporal changes of solid-associated Fe, As, and Mn in different saturation conditions is crucial but remains unknown. Therefore, column experiments were conducted to follow Fe, As, and Mn removal and their distribution and speciation on sand grain surfaces under unsaturated and saturated conditions. On average, 99 ± 0.2, 93 ± 0.7, and 91 ± 8% of Fe(II)aq, As(III)aq, and Mn(II)aq were removed under unsaturated conditions. Under saturated conditions, Fe and As removal remained constant, whereas up to 5 mg/L Mn(II)aq was leached from columns. μXANES analysis showed that solid-associated Fe(III), As(V), and Mn(III)/(IV) dominated in unsaturated sand. However, under saturated conditions, up to 46 and 15% of Fe(III) and As(V) were reduced, and the presence of Mn(II) was confirmed in the anoxic zones. The results suggest that Mn(IV) oxides formed during unsaturated conditions, serving as hosts and oxidants for Fe and As in SFs under reducing conditions.
mitoBKCais functionally expressed in murine and human breast cancer cells and potentially contributes to metabolic reprogramming
2023-10-04

Summary Alterations in the function of K + channels such as the voltage- and Ca 2+ activated K + channel of large conductance (BK Ca ) reportedly promote breast cancer (BC) development and progression. Underlying molecular mechanisms remain, however, elusive. Here, we provide electrophysiological evidence for a BK Ca splice variant localized to the inner mitochondrial membrane of murine and human BC cells (mitoBK Ca ). Through a combination of genetic knockdown and knockout along with cell permeable BK Ca channel blocker, we show that mitoBK Ca modulates overall cellular and mitochondrial energy production and mediates the metabolic rewiring referred to as the “Warburg effect”, thereby promoting BC cell proliferation in the presence and absence of oxygen. Additionally, we detect mitoBK Ca and BK Ca transcripts in low or high abundance, respectively, in clinical BC specimens. Together, our results emphasize, that targeting mitoBK Ca could represent a treatment strategy for selected BC patients in future.
Attractive sets of periodic integrodifference equations under discretization
2023-10-04

We consider periodic difference equations in infinite-dimensional Banach spaces possessing compact asymptotically stable set A. It is established that such A persists under spatial discretizations by means of projection methods as nearby closed and bounded uniformly asymptotically stable sets, which moreover converge to A in the Hausdorff metric for increasingly more accurate schemes. The proof is based on a Lyapunov function guaranteed by an ambient converse theorem and a pullback construction. As application serves integrodifference equations on spaces of continuous and p-integrable functions over a compact habitat.
Effects of Different Container Types on (1→3)-β-D-glucan Recovery
2023-10-04

It has long been known that containers for sample analysis or storage can play a role in endotoxin recovery and have to be taken into account when determining endotoxin concentrations. However, there is little data on the effects of containers regarding (1→3)-β-D-glucan, which plays a role as a contaminant in endotoxin measurements. To determine the effect of the container on (1→3)-β-D-glucan measurements, four different types of containers were investigated at different temperatures and stored for up to 28 days. For short-term storage for 3 h at room temperature, no effect of the container on the (1→3)-β-D-glucan recovery could be observed, but for storage at −20 °C, the results indicate that the storage time and temperature influences (1→3)-β-D-glucan detection. All containers showed a trend of lower recoveries over time, but the polyethylene container showed a significantly lower recovery compared to the other containers. We also showed that freeze/thaw cycles had a strong influence on the recovery of (1→3)-β-D-glucan in polyethylene containers. Our study showed that the container can affect not only the detection of endotoxins but also the detection of (1→3)-β-D-glucans.
Front Cover: Exploring the Translational Gap of a Novel Class of Escherichia coli IspE Inhibitors (ChemMedChem 19/2023)
2023-10-04

The Front Cover illustrates the methylerythritol phosphate (MEP) pathway as a source of drug targets for novel anti-infectives. The MEP pathway is composed of seven underexploited enzymes involved in the biosynthesis of universal isoprenoid precursors that are essential for important pathogens like Gram-negative bacteria (e.g., Pseudomonas aeruginosa, Mycobacterium tuberculosis or Plasmodium falciparum). Specifically, here the authors focused on the kinase IspE. Cover design by Antoine Lacour. More information can be found in the Research Article by Henni-Karoliina Ropponen, Eleonora Diamanti, Anna K. H. Hirsch et al.
Emission Dipole and Pressure‐Driven Tunability of Second Harmonic Generation in vdWs Ferroelectric NbOI2
2023-10-05

Abstract 2D in‐plane ferroelectric NbOI 2 exhibits strong second harmonic generation (SHG) and ultrahigh effective susceptibility. To push forward their applications in nonlinear photonics and optoelectronics, it is highly desirable to understand the emission dipole orientation and tunability of SHG, which is not achieved. Here, by integrating tight focusing from parabolic mirror with back focal plane (BFP) imaging technique, for the first time it is demonstrated that SHG emission of NbOI 2 presents purely in‐plane dipole orientation in consistent with numerical simulations, suggesting the in‐plane components of the SHG susceptibility tensor in NbOI 2 dominate the emission. Moreover, with the aid of ab‐initio calculations, it is found that the hydrostatic pressure can dramatically change the structure and resultant SHG intensity of NbOI 2 . Explicitly, SHG intensity endures a slight increase due to the distortion of octahedral at low pressure pressure, and then monotonously decreases due to the improvement of structural symmetry with further increasing pressure, and drastically quenching resulting from the ferroelectric to paraelectric phase transition. This work unambiguously demonstrates the dipole emission behavior of SHG and the relationship between structural evolution and SHG intensity, which provides an avenue for tunable nonlinear optics and optoelectronics.
Eco-evolutionary dynamics in two-species mutualistic systems: one-sided population decline triggers joint interaction disinvestment
2023-10-05

Abstract The interplay between ecological and evolutionary dynamics can create feedback that reinforces external disturbances and potentially threatens species’ coexistence. For example, plants might invest less into attracting insect pollinators (decreased flower or nectar production) and more into independence (increased selfing or vegetative reproduction) when faced with pollinator decline. This adaptive response saves plant resources at the cost of further threatening the pollinator population. We ask under which conditions such self-reinforcing feedback occurs in two-species mutualistic systems when considering one-sided population decline and whether it can be counteracted by self-dampening feedback if co-evolution of both interaction partners is considered. Based on a mathematical model and in line with previous studies, we find that the described pattern of accelerated population decline occurs for a wide range of parameter values if a concave allocation trade-off between independent growth and interaction investment is assumed. The undisturbed population typically disinvests first, which then forces the declining population to also disinvest, in favour of other energy sources. However, a decelerated population decline can occur if the adaptation of the undisturbed partner is relatively slow compared to environmental decay, reducing the speed of its disinvestment, or if the initial investment into the interaction was very high. Our results suggest that if actions are taken to save endangered populations, not only the evolution of the target species but also of their interaction partner, as well as the interaction between them should be considered.
Defect Emission and Its Dipole Orientation in Layered Ternary Znln2S4 Semiconductor
2023-10-05

Abstract Defect engineering is promising to tailor the physical properties of 2D semiconductors for function‐oriented electronics and optoelectronics. Compared with the extensively studied 2D binary materials, the origin of defects and their influence on physical properties of 2D ternary semiconductors are not clarified. Here, the effect of defects on the electronic structure and optical properties of few‐layer hexagonal Znln 2 S 4 is thoroughly studied via versatile spectroscopic tools in combination with theoretical calculations. It is demonstrated that the Zn–In antistructural defects induce the formation of a series of donor and acceptor energy levels and sulfur vacancies induce donor energy levels, leading to rich recombination paths for defect emission and extrinsic absorption. Impressively, the emission of donor–acceptor pair in Znln 2 S 4 can be significantly tailored by electrostatic gating due to efficient tunability of Fermi level ( E f ). Furthermore, the layer‐dependent dipole orientation of defect emission in Znln 2 S 4 is directly revealed by back focal plane imagining, where it presents obviously in‐plane dipole orientation within a dozen‐layer thickness of Znln 2 S 4 . These unique features of defects in Znln 2 S 4 including extrinsic absorption, rich recombination paths, gate tunability, and in‐plane dipole orientation are definitely a benefit to the advanced orientation‐functional optoelectronic applications.
What helps hospital staff in times of crisis: qualitative results of a survey on psychosocial resources and stressors in German hospitals during the COVID-19 pandemic
2023-10-05

Background Even before the COVID-19 pandemic, hospital workers faced a tremendous workload. The pandemic led to different and additional strain that negatively affected the well-being of employees. This study aims to explore psychosocial resources and strategies that were used by hospital staff. Methods In the context of an intervention study, employees of three German hospitals were questioned in writing in summer and fall 2020. Five open-ended questions about the pandemic were asked to capture corresponding effects on daily work routine. Answers of 303 participants were evaluated using structuring qualitative content analysis. Results Significant stressors and resources were identified in the areas of work content and task, social relations at work, organization of work, work environment and individual aspects. Stressors included, for example, emotional demands, conflicts, an increased workload, time and performance pressure. Important resources mentioned were, among others, the exchange with colleagues and mutual support. Sound information exchange, clear processes and guidelines and a positive work atmosphere were also important. In addition, the private environment and a positive mindset were perceived as helpful. Conclusion This study contributes to a differentiated understanding of existing psychosocial resources of hospital staff in times of crisis. Identifying and strengthening these resources could reduce stress and improve well-being, making hospital staff better prepared for both normal operations and further crisis situations.
Axonopathy and altered synaptic development in early hippocampal epileptogenesis of Dravet syndrome
2023-10-05

Abstract Dravet syndrome caused by SCN1A variants is a severe developmental epileptic encephalopathy (DEE) characterized by pharmaco-resistant epileptic seizures and progressive neurodevelopmental decline with cognitive impairment and autism-spectrum-traits. Numerous preceding studies indicate that the initial pathophysiology due to impaired Na V 1.1 function mainly derives from reduced interneuron firing leading to a network hyperexcitability (Bender et al. 2012). However, little is known how epileptogenesis and generally disease pathogenesis progress from the inborn molecular defect to infantile seizure onset. We address this question in a Dravet mouse model by comprehensive single-cell RNA sequencing and selected downstream analysis via single-cell electrophysiology, histology, live cell imaging and electron microscopy. Our data reveal a continuum of early primary (preseizure) and secondary (post-seizure onset) transcriptomic changes in various cell populations in the hippocampus. Focusing on cornu ammonis , we find a number of transcriptional pathways that are dysregulated including synaptic transmembrane adhesion molecules of the neurexin superfamily and voltage-gated ion channels. Further investigations support an ultrastructural and functional axonopathy and synaptopathy of parvalbumin interneurons. These processes precede somatic firing impairment and seizures suggesting they underlie fundamental early-phase disease mechanisms. Taken together we provide a cellularly resolved transcriptomic resource of early disease phases of Dravet syndrome and demonstrate epileptogenesis beyond Na V 1.1 loss-of-function during an early developmental time window of CNS maturation. Altogether these data establish proof-of principle that the concept of epileptogenesis, originally devised for acquired forms of epilepsy, similarly applies to genetic epilepsies and DEEs.
Manipulation of force geometry using optical tweezers reveals novel features of biomolecular interactions
2023-10-05

Optical tweezers have greatly impacted the development of mechanobiology by enabling high precision sub-piconewton measurements of mechanical forces developed by force generating proteins, called molecular motors, at the single-molecule level. Molecular motors, such as kinesins hydrolyze ATP to generate force (10 pN) and transport in a directional manner intracellular cargoes along cytoskeletal filamentous tracks called microtubules. The force developed by kinesins have been mainly studied using the "single-bead" assay, where an optically trapped bead is pulled by a bead-attached kinesin molecule as it steps along a surface immobilized microtubule. This assay, besides forces parallel to the long axis of the filament on which the kinesin processes, forces perpendicular to the filament due to the bead interacting with the underlying microtubule. These perpendicular forces, which cannot be directly measured, can accelerate the detachment of the molecular motor from its filamentous track. An alternative approach is the "three-bead" assay, in which the vertical force component is minimized, and the total opposing force is mainly parallel to the microtubule. Experiments with kinesin sho
Parietal theta burst TMS does not modulate bistable perception
2023-10-05

The role of the parietal cortex in perceptual awareness and in resolving perceptual ambiguity is unsettled. Early influential TMS studies have revealed differences in conscious perception following parietal stimulation, fuelling the notion that parietal cortex causally contributes to resolving perceptual ambiguity. However, central to this conclusion is the reliability of the method employed. Several prior studies have revealed opposing effects, such as shortening, lengthening, or no effect on multistable perceptual transitions following parietal stimulation. Here we addressed the reliability of continuous theta-burst stimulation (cTBS) on parietal cortex on the perception of bistable stimuli. We conducted three cTBS experiments that were matched to prior experiments in terms of stimuli, stimulation protocol, and target site, and used a higher number of participants. None of our cTBS experiments replicated prior cTBS results. The only experiment using individual functional localizers led to weak effects, while the two others led to null results. Individual variability of motor cortex cTBS did not predict parietal cTBS effects. In view of recent reports of highly variable cTBS effects over motor cortex, our results suggest that cTBS is particularly unreliable in modulating bistable perception when applied over parietal cortex.
Genomic analysis of advanced breast cancer tumors from talazoparib-treated gBRCA1/2mut carriers in the ABRAZO study
2023-10-06

Abstract These analyses explore the impact of homologous recombination repair gene mutations, including BRCA1/2 mutations and homologous recombination deficiency (HRD), on the efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor talazoparib in the open-label, two-cohort, Phase 2 ABRAZO trial in germline BRCA1/2 -mutation carriers. In the evaluable intent-to-treat population ( N = 60), 58 (97%) patients harbor ≥1 BRCA1/2 mutation(s) in tumor sequencing, with 95% (53/56) concordance between germline and tumor mutations, and 85% (40/47) of evaluable patients have BRCA locus loss of heterozygosity indicating HRD. The most prevalent non- BRCA tumor mutations are TP53 in patients with BRCA1 mutations and PIK3CA in patients with BRCA2 mutations. BRCA1- or BRCA2 -mutated tumors show comparable clinical benefit within cohorts. While low patient numbers preclude correlations between HRD and efficacy, germline BRCA1/2 mutation detection from tumor-only sequencing shows high sensitivity and non- BRCA genetic/genomic events do not appear to influence talazoparib sensitivity in the ABRAZO trial. ClinicalTrials.gov identifier: NCT02034916.
Learning of Generalizable and Interpretable Knowledge in Grid-Based Reinforcement Learning Environments
2023-10-06

Understanding the interactions of agents trained with deep reinforcement learning is crucial for deploying agents in games or the real world. In the former, unreasonable actions confuse players. In the latter, that effect is even more significant, as unexpected behavior cause accidents with potentially grave and long-lasting consequences for the involved individuals. In this work, we propose using program synthesis to imitate reinforcement learning policies after seeing a trajectory of the action sequence. Programs have the advantage that they are inherently interpretable and verifiable for correctness. We adapt the state-of-the-art program synthesis system DreamCoder for learning concepts in grid-based environments, specifically, a navigation task and two miniature versions of Atari games, Space Invaders and Asterix. By inspecting the generated libraries, we can make inferences about the concepts the black-box agent has learned and better understand the agent's behavior. We achieve the same by visualizing the agent's decision-making process for the imitated sequences. We evaluate our approach with different types of program synthesizers based on a search-only method, a neural-guided search, and a language model fine-tuned on code.