julilili42/papers huggingface dataset:
Potential of Lesion‐to‐Fat Elasticity Ratio Measured by Shear Wave Elastography to Reduce Benign Biopsies in BI‐RADS 4 Breast Lesions
2023-02-15

Objectives We evaluated whether lesion‐to‐fat ratio measured by shear wave elastography in patients with Breast Imaging Reporting and Data System (BI‐RADS) 3 or 4 lesions has the potential to further refine the assessment of B‐mode ultrasound alone in breast cancer diagnostics. Methods This was a secondary analysis of an international diagnostic multicenter trial (NCT02638935). Data from 1288 women with breast lesions categorized as BI‐RADS 3 and 4a–c by conventional B‐mode ultrasound were analyzed, whereby the focus was placed on differentiating lesions categorized as BI‐RADS 3 and BI‐RADS 4a. All women underwent shear wave elastography and histopathologic evaluation functioning as reference standard. Reduction of benign biopsies as well as the number of missed malignancies after reclassification using lesion‐to‐fat ratio measured by shear wave elastography were evaluated. Results Breast cancer was diagnosed in 368 (28.6%) of 1288 lesions. The assessment with conventional B‐mode ultrasound resulted in 53.8% (495 of 1288) pathologically benign lesions categorized as BI‐RADS 4 and therefore false positives as well as in 1.39% (6 of 431) undetected malignancies categorized as BI‐RADS 3. Additional lesion‐to‐fat ratio in BI‐RADS 4a lesions with a cutoff value of 1.85 resulted in 30.11% biopsies of benign lesions which correspond to a reduction of 44.04% of false positives. Conclusions Adding lesion‐to‐fat ratio measured by shear wave elastography to conventional B‐mode ultrasound in BI‐RADS 4a breast lesions could help reduce the number of benign biopsies by 44.04%. At the same time, however, 1.98% of malignancies were missed, which would still be in line with American College of Radiology BI‐RADS 3 definition of &lt;2% of undetected malignancies.
Non-Fock Ground States in the Translation-Invariant Nelson Model Revisited Non-Perturbatively
2023-02-15

The Nelson model, describing a quantum mechanical particle linearly coupled to a bosonic field, exhibits the infrared problem in the sense that no ground state exists at arbitrary total momentum. However, passing to a non-Fock representation, one can prove the existence of so-called dressed one-particle states. In this article, we give a simple non-perturbative proof for the existence of such one-particle states at arbitrary coupling strength and for almost all total momenta in a physically motivated momentum region. Our results hold both for the non- and the semi-relativistic Nelson model.
Western diet increases brain metabolism and adaptive immune responses in a mouse model of amyloidosis
2023-02-15

Abstract Diet-induced body weight gain is a growing health problem worldwide, leading to several serious systemic diseases such as diabetes. Because it is often accompanied by a low-grade metabolic inflammation that alters systemic function, dietary changes may also contribute to the progression of neurodegenerative diseases. Here we demonstrate disrupted glucose and fatty acid metabolism and a disrupted plasma metabolome in a mouse model of Alzheimer’s disease following a western diet using a multimodal imaging approach and NMR-based metabolomics. We did not detect glial-dependent neuroinflammation, however using flow cytometry we observed T cell recruitment in the brains of western diet-fed mice. Our study highlights the role of the brain-liver-fat-axis and the adaptive immune system in the disruption of brain homeostasis due to a Western diet.
Drosophila melanogaster as a versatile model organism to study genetic epilepsies: An overview
2023-02-16

Epilepsy is one of the most prevalent neurological disorders, affecting more than 45 million people worldwide. Recent advances in genetic techniques, such as next-generation sequencing, have driven genetic discovery and increased our understanding of the molecular and cellular mechanisms behind many epilepsy syndromes. These insights prompt the development of personalized therapies tailored to the genetic characteristics of an individual patient. However, the surging number of novel genetic variants renders the interpretation of pathogenetic consequences and of potential therapeutic implications ever more challenging. Model organisms can help explore these aspects in vivo . In the last decades, rodent models have significantly contributed to our understanding of genetic epilepsies but their establishment is laborious, expensive, and time-consuming. Additional model organisms to investigate disease variants on a large scale would be desirable. The fruit fly Drosophila melanogaster has been used as a model organism in epilepsy research since the discovery of “bang-sensitive” mutants more than half a century ago. These flies respond to mechanical stimulation, such as a brief vortex, with stereotypic seizures and paralysis. Furthermore, the identification of seizure-suppressor mutations allows to pinpoint novel therapeutic targets. Gene editing techniques, such as CRISPR/Cas9, are a convenient way to generate flies carrying disease-associated variants. These flies can be screened for phenotypic and behavioral abnormalities, shifting of seizure thresholds, and response to anti-seizure medications and other substances. Moreover, modification of neuronal activity and seizure induction can be achieved using optogenetic tools. In combination with calcium and fluorescent imaging, functional alterations caused by mutations in epilepsy genes can be traced. Here, we review Drosophila as a versatile model organism to study genetic epilepsies, especially as 81% of human epilepsy genes have an orthologous gene in Drosophila . Furthermore, we discuss newly established analysis techniques that might be used to further unravel the pathophysiological aspects of genetic epilepsies.
Toward Large‐Scale Soil Moisture Monitoring Using Rail‐Based Cosmic Ray Neutron Sensing
2023-02-16

Abstract Cosmic ray neutron sensing (CRNS) has become a promising method for soil water content (SWC) monitoring. Stationary CRNS offers hectare‐scale average SWC measurements at fixed locations maintenance‐free and continuous in time, while car‐borne CRNS roving can reveal spatial SWC patterns at medium scales, but only on certain survey days. The novel concept of a permanent mobile CRNS system on rails promises to combine the advantages of both methods, while its technical implementation, data processing and interpretation raised a new level of complexity. This study introduced a fully automatic CRNS rail‐borne system as the first of its kind, installed within the locomotive of a cargo train. Data recorded from September 2021 to July 2022 along an ∼9 km railway segment were analyzed, as repeatedly used by the train, supported by local SWC measurements (soil samples and dielectric methods), car‐borne and stationary CRNS. The results revealed consistent spatial SWC patterns and temporary variation along the track at a daily resolution. The observed variability was mostly related to surface features, seasonal dynamics and different responses of the railway segments to wetting and drying periods, while some variations were related to measurement uncertainties. The achieved medium scale of SWC mapping could support large scale hydrological modeling and detection of environmental risks, such as droughts and wildfires. Hence, rail‐borne CRNS has the chance to become a central tool of continuous SWC monitoring for larger scales (≤10‐km), with the additional benefit of providing root‐zone soil moisture, potentially even in sub‐daily resolution.
The compressed baryonic matter (CBM) experiment at FAIR—physics, status and prospects
2023-02-16

Abstract The Compressed Baryonic Matter (CBM) experiment is one of the major scientific pillars of the Facility for Antiproton and Ion Research (FAIR). The physics programme of CBM is centred around the exploration of the QCD phase diagram and nuclear matter equation-of-state in the region of high baryon densities. The respective rare probes will be accessed by using nucleus-nucleus collisions in the energy range <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:msqrt> <mml:mrow> <mml:msub> <mml:mrow> <mml:mi>s</mml:mi> </mml:mrow> <mml:mrow> <mml:mi mathvariant="italic">NN</mml:mi> </mml:mrow> </mml:msub> </mml:mrow> </mml:msqrt> <mml:mo>=</mml:mo> <mml:mn>2.9</mml:mn> <mml:mo>−</mml:mo> <mml:mn>4.9</mml:mn> <mml:mspace width="0.25em"/> <mml:mi>GeV</mml:mi> </mml:math> at peak interaction rates of up to 10 MHz and a trigger-less data acquisition scheme. This article reviews CBM physics goals with the experimental observables. The progress and current status (as of January 2022 before sanctions imposed on Russia and suspension of collaboration with Russian institutes) of the comprising detector sub‐systems, including their performance in FAIR Phase‐0 experiments will also be presented.
Spatiotemporal ITCZ dynamics during the last three millennia in Northeastern Brazil and related impacts in modern human history
2023-02-16

Abstract. Changes in tropical precipitation over the past millennia have usually been associated with latitudinal displacements of the Intertropical Convergence Zone (ITCZ). Recent studies provide new evidence that contraction and expansion of the tropical rainbelt may also have contributed to ITCZ variability on centennial time scales. Over tropical South America few records point to a similar interpretation, which prevents a clear diagnosis of ITCZ changes in the region. In order to improve our understanding of the equatorial rainbelt variability, our study presents a reconstruction of precipitation for the last 3200 years from the Northeast Brazil (NEB) region, an area solely influenced by ITCZ precipitation. We analyze oxygen isotopes in speleothems that serve as a faithful proxy for the past location of the southern margin of the ITCZ. Our results, in comparison with other ITCZ proxies, indicate that the range of seasonal migration, contraction and expansion of the ITCZ was not symmetrical around the equator. A new NEB ITCZ pattern emerged based on the comparison between two distinct proxies that characterize the ITCZ behavior during the last 2500 years, with an ITCZ zonal pattern between NEB and the eastern Amazon. In NEB, the period related to the Medieval Climate Anomaly (MCA) was characterized by an abrupt transition from wet to dry conditions. These drier conditions persisted until the onset of the period corresponding to the Little Ice Age (LIA), representing the longest dry period over the last 3200 years in NEB. The ITCZ was apparently forced by teleconnections between Atlantic Multidecadal Variability and Pacific Decadal Variability that controlled the position, intensity and width of Walker cell over South America changing the ITCZ zonally, and sea surface temperature changes in both the Pacific and Atlantic, stretching/weaking the ITCZ-related rainfall meridionally over NEB. Wetter conditions started around 1500 CE in NEB. During the last 500 years, our speleothems document the occurrence of some of the strongest drought events for the last millennia, which drastically affected population and environment of NEB during the Portuguese colonial period. The historical droughts were able to affect the karst system, and led to significant impacts over the entire NEB region.
Interconnected sub-networks of the macaque monkey gustatory connectome
2023-02-16

Macroscopic taste processing connectivity was investigated using functional magnetic resonance imaging during the presentation of sour, salty, and sweet tastants in anesthetized macaque monkeys. This examination of taste processing affords the opportunity to study the interactions between sensory regions, central integrators, and effector areas. Here, 58 brain regions associated with gustatory processing in primates were aggregated, collectively forming the gustatory connectome . Regional regression coefficients (or β-series) obtained during taste stimulation were correlated to infer functional connectivity. This connectivity was then evaluated by assessing its laterality, modularity and centrality. Our results indicate significant correlations between same region pairs across hemispheres in a bilaterally interconnected scheme for taste processing throughout the gustatory connectome. Using unbiased community detection, three bilateral sub-networks were detected within the graph of the connectome. This analysis revealed clustering of 16 medial cortical structures, 24 lateral structures, and 18 subcortical structures. Across the three sub-networks, a similar pattern was observed in the differential processing of taste qualities. In all cases, the amplitude of the response was greatest for sweet, but the network connectivity was strongest for sour and salty tastants. The importance of each region in taste processing was computed using node centrality measures within the connectome graph, showing centrality to be correlated across hemispheres and, to a smaller extent, region volume. Connectome hubs exhibited varying degrees of centrality with a prominent leftward increase in insular cortex centrality. Taken together, these criteria illustrate quantifiable characteristics of the macaque monkey gustatory connectome and its organization as a tri-modular network, which may reflect the general medial-lateral-subcortical organization of salience and interoception processing networks.
Performance of T-Track® TB, a Novel Dual Marker RT-qPCR-Based Whole-Blood Test for Improved Detection of Active Tuberculosis
2023-02-16

Tuberculosis (TB) is one of the leading causes of death by an infectious disease. It remains a major health burden worldwide, in part due to misdiagnosis. Therefore, improved diagnostic tests allowing the faster and more reliable diagnosis of patients with active TB are urgently needed. This prospective study examined the performance of the new molecular whole-blood test T-Track® TB, which relies on the combined evaluation of IFNG and CXCL10 mRNA levels, and compared it to that of the QuantiFERON®-TB Gold Plus (QFT-Plus) enzyme-linked immunosorbent assay (ELISA). Diagnostic accuracy and agreement analyses were conducted on the whole blood of 181 active TB patients and 163 non-TB controls. T-Track® TB presented sensitivity of 94.9% and specificity of 93.8% for the detection of active TB vs. non-TB controls. In comparison, the QFT-Plus ELISA showed sensitivity of 84.3%. The sensitivity of T-Track® TB was significantly higher (p &lt; 0.001) than that of QFT-Plus. The overall agreement of T-Track® TB with QFT-Plus to diagnose active TB was 87.9%. Out of 21 samples with discordant results, 19 were correctly classified by T-Track® TB while misclassified by QFT-Plus (T-Track® TB-positive/QFT-Plus-negative), and two samples were misclassified by T-Track® TB while correctly classified by QFT-Plus (T-Track® TB-negative/QFT-Plus-positive). Our results demonstrate the excellent performance of the T-Track® TB molecular assay and its suitability to accurately detect TB infection and discriminate active TB patients from non-infected controls.
Muscle Preflex Response to Perturbations in locomotion: In-vitro experiments and simulations with realistic boundary conditions
2023-02-16

1 Abstract Neuromuscular control loops feature substantial communication delays, but mammals run robustly even in the most adverse conditions. In-vivo experiments and computer simulation results suggest that muscles’ preflex—an immediate mechanical response to a perturbation—could be the critical contributor. Muscle preflexes act within a few milliseconds, an order of magnitude faster than neural reflexes. Their short-lasting activity makes mechanical preflexes hard to quantify in-vivo. Muscle models, on the other hand, require further improvement of their prediction accuracy during the non-standard conditions of perturbed locomotion. Additionally, muscles mechanically adapt by increased damping force. Our study aims to quantify the mechanical preflex work and test its mechanical force adaptation. We performed in-vitro experiments with biological muscle fibers under physiological boundary conditions, which we determined in computer simulations of perturbed hopping. Our findings show that muscles initially resist impacts with a stereotypical stiffness response—identified as short-range stiffness—regardless of the exact perturbation condition. We then observe a velocity adaptation to the force related to the amount of perturbation. The main contributor to the preflex work adaptation is not the force difference but the muscle fiber stretch difference. We find that both muscle stiffness and damping are activity-dependent properties. These results indicate that neural control could tune the preflex properties of muscles in expectation of ground conditions leading to previously inexplicable neuromuscular adaptation speeds.
Carbon signaling protein SbtB possesses atypical redox-regulated apyrase activity to facilitate regulation of bicarbonate transporter SbtA
2023-02-17

The PII superfamily consists of widespread signal transduction proteins found in all domains of life. In addition to canonical PII proteins involved in C/N sensing, structurally similar PII-like proteins evolved to fulfill diverse, yet poorly understood cellular functions. In cyanobacteria, the bicarbonate transporter SbtA is co-transcribed with the conserved PII-like protein, SbtB, to augment intracellular inorganic carbon levels for efficient CO 2 fixation. We identified SbtB as a sensor of various adenine nucleotides including the second messenger nucleotides cyclic AMP (cAMP) and c-di-AMP. Moreover, many SbtB proteins possess a C-terminal extension with a disulfide bridge of potential redox-regulatory function, which we call R-loop. Here, we reveal an unusual ATP/ADP apyrase (diphosphohydrolase) activity of SbtB that is controlled by the R-loop. We followed the sequence of hydrolysis reactions from ATP over ADP to AMP in crystallographic snapshots and unravel the structural mechanism by which changes of the R-loop redox state modulate apyrase activity. We further gathered evidence that this redox state is controlled by thioredoxin, suggesting that it is generally linked to cellular metabolism, which is supported by physiological alterations in site-specific mutants of the SbtB protein. Finally, we present a refined model of how SbtB regulates SbtA activity, in which both the apyrase activity and its redox regulation play a central role. This highlights SbtB as a central switch point in cyanobacterial cell physiology, integrating not only signals from the energy state (adenyl-nucleotide binding) and the carbon supply via cAMP binding but also from the day/night status reported by the C-terminal redox switch.
MicroRNA-21 mediated cross-talk between cardiomyocytes and fibroblasts in patients with atrial fibrillation
2023-02-17

Background Atrial fibrosis represents a major hallmark in disease progression of atrial fibrillation (AF). We have previously shown that circulating microRNA-21 (miR-21) correlates with the extent of left atrial fibrosis in patients undergoing catheter ablation for AF and can serve as a biomarker to predict ablation success. In this study, we aimed to validate the role of miR-21-5p as a biomarker in a large cohort of AF patients and to investigate its pathophysiological role in atrial remodeling. Methods For the validation cohort, we included 175 patients undergoing catheter ablation for AF. Bipolar voltage maps were obtained, circulating miR-21-5p was measured, and patients were followed-up for 12 months including ECG holter monitoring. AF was simulated by tachyarrhythmic pacing of cultured cardiomyocytes, the culture medium was transferred to fibroblast, and fibrosis pathways were analysed. Results 73.3% of patients with no/minor LVAs, 51.4% of patients with moderate LVAs and only 18.2% of patients with extensive LVAs were in stable sinus rhythm (SR) 12 months after ablation ( p &amp;lt; 0.01). Circulating miR-21-5p levels significantly correlated with the extent of LVAs and event-free survival. In-vitro tachyarrhythmic pacing of HL-1 cardiomyocytes resulted in an increased miR-21-5p expression. Transfer of the culture medium to fibroblasts induced fibrosis pathways and collagen production. The HDAC1 inhibitor mocetinostat was found to inhibit atrial fibrosis development. Conclusion We validated miR-21-5p as a biomarker that reflects the extent of left atrial fibrosis in AF patients. Furthermore, we found that miR-21-5p is released in-vitro from cardiomyocytes under tachyarrhythmic conditions and stimulates fibroblasts in a paracrine mode to induce collagen production.
Genetic forms of primary progressive aphasia within the GENetic Frontotemporal dementia Initiative (GENFI) cohort: comparison with sporadic primary progressive aphasia
2023-02-17

Abstract Primary progressive aphasia is most commonly a sporadic disorder, but in some cases, it can be genetic. This study aimed to understand the clinical, cognitive and imaging phenotype of the genetic forms of primary progressive aphasia in comparison to the canonical nonfluent, semantic and logopenic subtypes seen in sporadic disease. Participants with genetic primary progressive aphasia were recruited from the international multicentre GENetic Frontotemporal dementia Initiative study and compared with healthy controls as well as a cohort of people with sporadic primary progressive aphasia. Symptoms were assessed using the GENetic Frontotemporal dementia Initiative language, behavioural, neuropsychiatric and motor scales. Participants also underwent a cognitive assessment and 3 T volumetric T1-weighted MRI. One C9orf72 (2%), 1 MAPT (6%) and 17 GRN (44%) symptomatic mutation carriers had a diagnosis of primary progressive aphasia. In the GRN cohort, 47% had a diagnosis of nonfluent variant primary progressive aphasia, and 53% had a primary progressive aphasia syndrome that did not fit diagnostic criteria for any of the three subtypes, called primary progressive aphasia-not otherwise specified here. The phenotype of the genetic nonfluent variant primary progressive aphasia group largely overlapped with that of sporadic nonfluent variant primary progressive aphasia, although the presence of an associated atypical parkinsonian syndrome was characteristic of sporadic and not genetic disease. The primary progressive aphasia -not otherwise specified group however was distinct from the sporadic subtypes with impaired grammar/syntax in the presence of relatively intact articulation, alongside other linguistic deficits. The pattern of atrophy seen on MRI in the genetic nonfluent variant primary progressive aphasia group overlapped with that of the sporadic nonfluent variant primary progressive aphasia cohort, although with more posterior cortical involvement, whilst the primary progressive aphasia-not otherwise specified group was strikingly asymmetrical with involvement particularly of the insula and dorsolateral prefrontal cortex but also atrophy of the orbitofrontal cortex and the medial temporal lobes. Whilst there are overlapping symptoms between genetic and sporadic primary progressive aphasia syndromes, there are also distinct features. Future iterations of the primary progressive aphasia consensus criteria should encompass such information with further research needed to understand the earliest features of these disorders, particularly during the prodromal period of genetic disease.