julilili42/papers huggingface dataset:
In Vitro Sensitivity of Neuroendocrine Neoplasms to an Armed Oncolytic Measles Vaccine Virus
2024-01-23

Neuroendocrine neoplasms represent a heterogenous group of rare tumors whose current therapeutic options show only limited efficacy. Oncolytic viruses exert their mode of action through (onco-)lysis of infected tumor cells and the induction of a systemic antitumoral immune response in a virus-induced inflammatory micromilieu. Here, we investigated the potential of our well-established second-generation suicide-gene armed oncolytic measles vaccine virus (MeV-SCD) in five human NEN cell lines. First, (i) expression of the MeV receptor CD46 and (ii) its correlation with primary infection rates were analyzed. Next, (iii) promising combination partners for MeV-SCD were tested by employing either the prodrug 5-fluorocytosine, which is converted into the chemotherapeutic compound 5-fluorouracil, or the mTOR-inhibitor everolimus. As a result, MeV-SCD was found to kill all NEN tumor cell lines efficiently in a dose-dependent manner. This oncolytic effect was further enhanced by exploiting the prodrug-converting system, which was found to be highly instrumental in overcoming the partial resistance found in a single NEN cell line. Furthermore, viral replication was unaffected by everolimus, which is a basic requirement for combined use in NEN patients. These data suggest that MeV-SCD has profound potential for patients with NEN, thus paving the way for early clinical trials.
Nickel Catalyzed C–S Cross Coupling of Sterically Hindered Aryl Triflates with Alkyl Thiols
2024-01-23

Due to the smaller size of nickel compared to palladium, the C–S cross-coupling of sterically challenging aryl electrophiles with alkyl thiols under nickel catalysis remained elusive. Herein, we report the nickel-catalyzed cross-coupling of alkyl thiols with aryl triflates bearing functional groups in ortho-position relative to the leaving group using Ni(cod)2/DPEphos (L1) or dppbz (L2) as the catalytic system. For substrates featuring non-coordinating ortho-substituents, the reaction operates under mild conditions using L1, while for electrophiles bearing coordinating groups, the ligand L2 and elevated temperatures are required. The synthetic utility could be demonstrated on numerous examples, including biologically relevant compounds, and on larger scale. Instead of Ni(cod)2, more cost-efficient Ni(OAc)2 can also be employed in the presence of zinc as reductant. Furthermore, insights into the reaction mechanism were obtained by competition experiments, isolation of organometallic intermediates and computations.
An anti-virulence drug targeting the evolvability protein Mfd protects against infections with antimicrobial resistant ESKAPE pathogens
2024-01-23

Abstract The increased incidence of antibiotic resistance and declining discovery of new antibiotics have created a global health crisis, especially for the treatment of infections caused by Gram-negative bacteria. Here, we identify and characterize a molecule, NM102, that displays antimicrobial activity exclusively in the context of infection. NM102 inhibits the activity of the non-essential Mutation Frequency Decline (Mfd) protein by competing with ATP binding to its active site. Inhibition of Mfd by NM102 sensitizes pathogenic bacteria to the host immune response and blocks infections with clinically- relevant Klebsiella pneumoniae and Pseudomonas aeruginosa , without inducing host toxicity. Finally, NM102 inhibits the function of Mfd as a mutation and evolvability factor, thus reducing the bacterial capacity to develop antimicrobial resistance. These data provide a potential roadmap to expand the arsenal of drugs to combat antimicrobial resistance. Highlight NM102 is a “first in class” molecule specifically targeting the active site of the bacterial Mfd protein NM102 has a new mode of action: it inhibits Mfd function during immune stress response NM102 also inhibits Mfd evolvability function and thereby decreases bacterial resistance to known antibiotics NM102 effectively treats Gram-negative infections in animal models NM102 is efficient against clinically relevant resistant bacteria and provides an increased efficacy in combination with the β-lactam meropenem
Electronic Structure and Transport in the Potential Luttinger Liquids CsNb$_3$Br$_7$S and RbNb$_3$Br$_7$S
2024-01-23

The crystal structures of ANb Br S (A = Rb and Cs) have been refined by single crystal X-ray diffraction, and are found to form highly anisotropic materials based on chains of the triangular Nb cluster core. The Nb cluster core contains seven valence electrons, six of them being assigned to Nb-Nb bonds within the Nb triangle and one unpaired d electron. The presence of this surplus electron gives rise to the formation of correlated electronic states. The connectivity in the structures is represented by one-dimensional [Nb Br S] chains, containing a sulphur atom capping one face ( ) of the triangular niobium cluster, which is believed to induce an important electronic feature. Several types of studies are undertaken to obtain deeper insight into the understanding of this unusual type of material: the crystal structure, morphology and elastic properties are analysed, as well the (photo-) electrical properties and NMR relaxation. Electronic structure (DFT) calculations are performed in order to understand the electronic structure and transport in these compounds, and, based on the experimental and theoretical results, we propose that the electronic interactions along the Nb chains are sufficiently one-dimensional to give rise to Luttinger liquid (rather than Fermi liquid) behaviour of the metallic electrons.
A head-mounted Tilted Reality Device for the treatment of pusher syndrome: A usability study
2024-01-23

Abstract Pusher syndrome is a disorder of postural control after stroke. Patients show a mismatch in their perception of (almost preserved) visual and (pathologically tilted) postural verticality. In order to reduce this mismatch, we developed a novel head-mounted ‘Tilted Reality Device (TRD)’. It presents patients visual footage of their actual surroundings but tilted to one side rather than upright. We investigated its usability and possible limitations in its use for the treatment of pusher patients in two samples of healthy participants with an average age of 26.4 years and 63.9 years respectively. Individuals from both age groups showed similar levels of tolerance to prolonged exposure to the tilted visual environment for an average of 40.4 minutes while walking around in the hospital. The TRD was found to be comfortable and not frustrating whilst wearing, but somewhat challenging in terms of technical handling, particularly for older participants. At the end of the maximally tolerated exposure time participants of both groups experienced some feelings of discomfort, like dizziness or increased stomach awareness, which disappeared rapidly after terminating TRD exposure. Our TRD appears to be a practical device especially for an older population, like pusher patients. While users must be aware of the possibility of side effects, these should be balanced against the benefits of future use for rehabilitation purposes.
Andexanet alfa versus non-specific treatments for intracerebral hemorrhage in patients taking factor Xa inhibitors — Individual patient data analysis of ANNEXA-4 and TICH-NOAC
2024-01-24

Background: Data comparing the specific reversal agent andexanet alfa with non-specific treatments in patients with non-traumatic intracerebral hemorrhage (ICH) associated with factor-Xa inhibitor (FXaI) use are scarce. Aim: The study aimed to determine the association between the use of andexanet alfa compared with non-specific treatments with the rate of hematoma expansion and thromboembolic complications in patients with FXaI-associated ICH. Methods: We performed an individual patient data analysis combining two independent, prospective studies: ANNEXA-4 (180 patients receiving andexanet alfa, NCT02329327) and TICH-NOAC (63 patients receiving tranexamic acid or placebo ± prothrombin complex concentrate, NCT02866838). The primary efficacy outcome was hematoma expansion on follow-up imaging. The primary safety outcome was any thromboembolic complication (ischemic stroke, myocardial infarction, pulmonary embolism, or deep vein thrombosis) at 30 days. We used binary logistic regression models adjusted for baseline hematoma volume, age, calibrated anti-Xa activity, times from last intake of FXaI, and symptom onset to treatment, respectively. Results: Among 243 participants included, the median age was 80 (IQR 75–84) years, baseline hematoma volume was 9.1 (IQR 3.4–21) mL and anti-Xa activity 118 (IQR 78–222) ng/mL. Times from last FXaI intake and symptom onset to treatment were 11 (IQR 7–16) and 4.7 (IQR 3.0–7.6) h, respectively. Overall, 50 patients (22%) experienced hematoma expansion (ANNEXA-4: n=24 (14%); TICH-NOAC: n=26 (41%)). After adjusting for pre-specified confounders (baseline hematoma volume, age, calibrated anti-Xa activity, times from last intake of FXaI, and symptom onset to treatment, respectively), treatment with andexanet alfa was independently associated with decreased odds for hematoma expansion (aOR 0.33, 95% CI 0.13–0.80, p = 0.015). Overall, 26 patients (11%) had any thromboembolic complication within 30 days (ANNEXA-4: n=20 (11%); TICH-NOAC: n=6 (10%)). There was no association between any thromboembolic complication and treatment with andexanet alfa (aOR 0.70, 95% CI 0.16–3.12, p = 0.641). Conclusion: The use of andexanet alfa compared to any other non-specific treatment strategy was associated with decreased odds for hematoma expansion, without increased odds for thromboembolic complications.
Personalized Chronomodulated 5‐Fluorouracil Treatment: A Physiologically‐Based Pharmacokinetic Precision Dosing Approach for Optimizing Cancer Therapy
2024-01-24

The discovery of circadian clock genes greatly amplified the study of diurnal variations impacting cancer therapy, transforming it into a rapidly growing field of research. Especially, use of chronomodulated treatment with 5‐fluorouracil (5‐FU) has gained significance. Studies indicate high interindividual variability (IIV) in diurnal variations in dihydropyrimidine dehydrogenase (DPD) activity – a key enzyme for 5‐FU metabolism. However, the influence of individual DPD chronotypes on chronomodulated therapy remains unclear and warrants further investigation. To optimize precision dosing of chronomodulated 5‐FU, this study aims to: (i) build physiologically‐based pharmacokinetic (PBPK) models for 5‐FU, uracil, and their metabolites, (ii) assess the impact of diurnal variation on DPD activity, (iii) estimate individual DPD chronotypes, and (iv) personalize chronomodulated 5‐FU infusion rates based on a patient's DPD chronotype. Whole‐body PBPK models were developed with PK‐Sim (R) and MoBi (R) . Sinusoidal functions were used to incorporate variations in enzyme activity and chronomodulated infusion rates as well as to estimate individual DPD chronotypes from DPYD mRNA expression or DPD enzymatic activity. Four whole‐body PBPK models for 5‐FU, uracil, and their metabolites were established utilizing data from 41 5‐FU and 10 publicly available uracil studies. IIV in DPD chronotypes was assessed and personalized chronomodulated administrations were developed to achieve (i) comparable 5‐FU peak plasma concentrations, (ii) comparable 5‐FU exposure, and (iii) constant 5‐FU plasma levels via “noise cancellation” chronomodulated infusion. The developed PBPK models capture the extent of diurnal variations in DPD activity and can help investigate individualized chronomodulated 5‐FU therapy through testing alternative personalized dosing strategies.
Classification and Incidence of Heterotopic Ossifications in Relation to NSAID Prophylaxis after Elbow Trauma
2024-01-24

Heterotopic ossification (HO) after elbow trauma can be responsible for significant motion restrictions. The study’s primary aim was to develop a new X-ray-based classification for HO of the elbow. This retrospective study analyzed elbow injury radiographs from 138 patients aged 6–85 years (mean 45.9 ± 18) who underwent operative treatment. The new classification was applied at 6 weeks, 12 weeks, and 6 months postoperatively. The severity of HO was graded from 0 to 4 and localization was defined as r (radial), p (posterior), u (ulnar) or a (anterior) by two observers. The patients were categorized based on injury location and use of non-steroidal anti-inflammatory drugs (NSAIDs) for HO prophylaxis. The correlations between the generated data sets were analyzed using Chi-square tests (χ2) with a significance level of p &lt; 0.05. The inter- and intraobserver reliability was assessed using Cohen’s Kappa. In 50.7% of the evaluated X-rays, the formation of HO could be detected after 12 weeks, and in 60% after 6 months. The analysis showed a significant correlation between the injury’s location and the HO’s location after 12 weeks (p = 0.003). The use of an NSAID prophylaxis did not show a significant correlation with the severity of HO. The classification showed nearly perfect inter- (κ = 0.951, p &lt; 0.001) and intrareliability (κ = 0.946, p &lt; 0.001) according to the criteria of Landis and Koch. Based on the presented classification, the dimension and localization of HO in the X-ray image can be described in more detail compared to previously established classifications and, thus, can increase the comparability of results across studies.
Orientation of Cobalt-Phthalocyanines on Molybdenum Disulfide: Distinguishing between Single Crystals and Small Flakes
2024-01-24

Heterostructures consisting of transition metal dichalcogenides (TMDCs) and organic molecules are currently of enormous interest for a variety of applications. Comparably weakly interacting molecules, like phthalocyanines, exhibit a high potential for tuning the electronic properties of TMDCs. Knowledge of the molecular orientation is a prerequisite for understanding the nature and strength of the interfacial interaction. We study the molecular orientation of cobalt phthalocyanine (CoPc) and perfluorinated cobalt phthalocyanine (CoPcF16, also denoted F16CoPc), on both large molybdenum disulfide (MoS2) single crystals and small MoS2 flakes, using synchrotron-based techniques: X-ray absorption spectroscopy (XAS) at the Co L3 edge and spectromicroscopy in a photoemission electron microscope (PEEM). We show that the orientation can be radically different on both substrates. Whereas on large crystals an almost flat-lying orientation is observed, significant tilt angles were found on smaller flakes. It is proposed that the orientation depends crucially on the number of MoS2 layers and/or the smaller size of atomically flat terraces on flakes compared to bulk crystals.
Gravitational radiation from a particle plunging into a Schwarzschild black hole: Frequency-domain and semirelativistic analyses
2024-01-24

We revisit the classic problem of gravitational wave emission by a test particle plunging into a Schwarzschild black hole both in the frequency-domain Regge-Wheeler-Zerilli formalism and in the semirelativistic approximation. We use, and generalize, a transformation due to Nakamura, Sasaki, and Shibata to improve the falloff of the source term of the Zerilli function. The faster decay improves the numerical convergence of quantities of interest, such as the energy radiated at spatial infinity through gravitational waves. As a test of the method, we study the gravitational radiation produced by test particles that plunge into the black hole with impact parameters close to the threshold for scattering. We recover and expand upon previous results that were obtained using the Sasaki-Nakamura equation. In particular, we study the relative contributions to the total energy radiated due to waves of axial and polar parity, and uncover an universal behavior in the waveforms at late times. We complement our study with a semirelativistic analysis of the problem, and we compare the two approaches. The generalized Nakamura-Sasaki-Shibata transformation presented here is a simple and practical alternative for the analysis of gravitational-wave emission by unbound orbits in the Schwarzschild spacetime using the frequency-domain Regge-Wheeler-Zerilli formalism. Published by the American Physical Society 2024
The Use of Magnetic Resonance Imaging in Radiation Therapy Treatment Simulation and Planning
2024-01-24

Ever since its introduction as a diagnostic imaging tool the potential of magnetic resonance imaging (MRI) in radiation therapy (RT) treatment simulation and planning has been recognized. Recent technical advances have addressed many of the impediments to use of this technology and as a result have resulted in rapid and growing adoption of MRI in RT. The purpose of this article is to provide a broad review of the multiple uses of MR in the RT treatment simulation and planning process, identify several of the most used clinical scenarios in which MR is integral to the simulation and planning process, highlight existing limitations and provide multiple unmet needs thereby highlighting opportunities for the diagnostic MR imaging community to contribute and collaborate with our oncology colleagues. Evidence Level 5 Technical Efficacy Stage 5
The Predominance of the Health-Promoting Patterns of Work Behavior and Experience in General Practice Teams—Results of the IMPROVEjob Study
2024-01-24

This study aims to identify the distribution of the “Work-related behavior and experience patterns” (Arbeitsbezogenes Verhaltens-und Erlebnismuster, AVEM) in general practitioners and their teams by using baseline data of the IMPROVEjob study. Members of 60 general practices with 84 physicians in a leadership position, 28 employed physicians, and 254 practice assistants participated in a survey in 2019 and 2020. In this analysis, we focused on AVEM variables. Age, practice years, work experience, and working time were used as control variables in the Spearman Rho correlations and analysis of variance. The majority of the participants (72.1%) revealed a health-promoting pattern (G or S). Three of eleven AVEM dimensions were above the norm for the professional group “employed physicians”. The AVEM dimensions “striving for perfection” (p &lt; 0.001), “experience of success at work” (p &lt; 0.001), “satisfaction with life” (p = 0.003), and “experience of social support” (p = 0.019) differed significantly between the groups’ practice owners and practice assistants, with the practice owners achieving the higher values, except for experience of social support. Practice affiliation had no effect on almost all AVEM dimensions. We found a high prevalence of AVEM health-promoting patterns in our sample. Nearly half of the participants in all professional groups showed an unambitious pattern (S). Adapted interventions for the represented AVEM patterns are possible and should be utilized for maintaining mental health among general practice teams.
Multi-technique investigation of silicon nitride/aluminum membranes as optical blocking filters for high-energy space missions
2024-01-24

X-ray detectors for space astrophysics missions are susceptible to noise caused by photons with energies outside the operating energy range; for this reason, efficient external optical blocking filters are required to shield the detector from the out-of-band radiation. These filters play a crucial role in meeting the scientific requirements of the X-ray detectors, and their proper operation over the life of the mission is essential for the success of the experimental activity. We studied thin sandwich membranes made of silicon nitride and aluminum as optical blocking filters for high-energy detectors in space missions. Here, we report the results of a multi-technique characterization of SiN membranes with thicknesses in the range from 40 nm to 145 nm coated with few tens of nanometers of aluminum on both sides. In particular, we have measured the X-ray transmission at synchrotron radiation beamlines, the rejection of ultraviolet, visible, and near-infrared radiation, the amount of native oxide on the aluminum surfaces by X-ray photoelectron spectroscopy, the morphology of the sample surfaces by atomic force microscopy, and the aging effects under proton irradiation.
Machine Learning Estimators: Implementation and Comparison in Python
2024-01-24

Abstract We compare different machine learning estimators and present details about their implementation in Python. The computational studies are conducted for classification as well as regression problems. Moreover, as one of the founding problems of machine learning, we present the specific classification task of handwritten digit recognition . In this connection, we discuss the mathematical formulation and of course the implementation details of this problem. All corresponding Python code is fully provided on request and can be downloaded from the author’s GitHub page https://github.com/Fab1Fatal .
Bayesian evidence for the neural dissociation between finger and hand imitation skills
2024-01-24

Abstract Introduction For limb apraxia ‒ a heterogeneous disorder of higher motor cognition following stroke ‒ an enduring debate has arisen regarding the existence of dissociating neural correlates for finger and hand gestures in the left hemisphere. We re-assessed this question asking whether previous attempts analysing pooled samples of patients with deficits in only one and patients with deficits in both imitation types might have led to systematically biased results. Methods We conducted frequentist and Bayesian, voxelwise and regionwise lesion symptom mappings on a pooled sample (N=96) and subsamples containing only shared and only isolated hand and finger imitation deficits and respective controls. Results Anatomical analyses on the isolated sample reinforced a cortical dissociation of finger deficits (located more anteriorly) and hand deficits (located more posteriorly). The presence of patients with shared deficits did indeed dilute associations that appeared stronger in the respective isolated samples. Also, brain regions truly associated with hand imitation deficits showed a positive bias for finger imitation deficits, when the sample contained patients with shared deficits. In addition, our frequentist parameters uncovered that some of our Bayesian evidence supported reverse associations (damage protecting from rather than increasing the deficit). Discussion Joint analyses of patients with shared and isolated imitation deficits do indeed lead to biases, which may explain why some previous studies have failed to detect the actual neural dissociation between hand and finger imitation deficits.
Acceleration and transport of relativistic electrons in the jets of the microquasar SS 433
2024-01-25

SS 433 is a microquasar, a stellar binary system that launches collimated relativistic jets. We observed SS 433 in gamma rays using the High Energy Stereoscopic System (H.E.S.S.) and found an energy-dependent shift in the apparent position of the gamma-ray emission from the parsec-scale jets. These observations trace the energetic electron population and indicate that inverse Compton scattering is the emission mechanism of the gamma rays. Our modeling of the energy-dependent gamma-ray morphology constrains the location of particle acceleration and requires an abrupt deceleration of the jet flow. We infer the presence of shocks on either side of the binary system, at distances of 25 to 30 parsecs, and that self-collimation of the precessing jets forms the shocks, which then efficiently accelerate electrons.