julilili42/papers huggingface dataset:
Species Difference? Bovine, Trout, and Human Plasma Protein Binding of Per- and Polyfluoroalkyl Substances
2024-05-28

Per- and polyfluoroalkyl substances (PFAS) strongly bind to proteins and lipids in blood, which govern their accumulation and distribution in organisms. Understanding the plasma binding mechanism and species differences will facilitate the quantitative <i>in vitro</i>-to-<i>in vivo</i> extrapolation and improve risk assessment of PFAS. We studied the binding mechanism of 16 PFAS to bovine serum albumin (BSA), trout, and human plasma using solid-phase microextraction. Binding of anionic PFAS to BSA and human plasma was found to be highly concentration-dependent, while trout plasma binding was linear for the majority of the tested PFAS. At a molar ratio of PFAS to protein ν < 0.1 mol<sub>PFAS</sub>/mol<sub>protein</sub>, the specific protein binding of anionic PFAS dominated their human plasma binding. This would be the scenario for physiological conditions (ν < 0.01), whereas in <i>in vitro</i> assays, PFAS are often dosed in excess (ν > 1) and nonspecific binding becomes dominant. BSA was shown to serve as a good surrogate for human plasma. As trout plasma contains more lipids, the nonspecific binding to lipids affected the affinities of PFAS for trout plasma. Mass balance models that are parameterized with the protein-water and lipid-water partitioning constants (chemical characteristics), as well as the protein and lipid contents of the plasma (species characteristics), were successfully used to predict the binding to human and trout plasma.
Epstein-Barr Virus Lytic Transcripts Correlate with the Degree of Myocardial Inflammation in Heart Failure Patients
2024-05-28

The Epstein-Barr virus (EBV) is frequently found in endomyocardial biopsies (EMBs) from patients with heart failure, but the detection of EBV-specific DNA has not been associated with progressive hemodynamic deterioration. In this paper, we investigate the use of targeted next-generation sequencing (NGS) to detect EBV transcripts and their correlation with myocardial inflammation in EBV-positive patients with heart failure with reduced ejection fraction (HFrEF). Forty-four HFrEF patients with positive EBV DNA detection and varying degrees of myocardial inflammation were selected. EBV-specific transcripts from EMBs were enriched using a custom hybridization capture-based workflow and, subsequently, sequenced by NGS. The short-read sequencing revealed the presence of EBV-specific transcripts in 17 patients, of which 11 had only latent EBV genes and 6 presented with lytic transcription. The immunohistochemical staining for CD3+ T lymphocytes showed a significant increase in the degree of myocardial inflammation in the presence of EBV lytic transcripts, suggesting a possible influence on the clinical course. These results imply the important role of EBV lytic transcripts in the pathogenesis of inflammatory heart disease and emphasize the applicability of targeted NGS in EMB diagnostics as a basis for specific treatment.
Trianionic Carbocyclic NCN Pincer Ligand: Coordination Chemistry and Reactivity Studies
2024-05-28

(BCHT-NCN)H<sub>3</sub> (<b>1</b>) [1,6-bis(methylene(bis-2,6-di<i>iso</i>propylaniline)(benzo)cycloheptatriene)] was synthesized by nucleophilic substitution treating 1,6-bis(methylenebromide)(benzo)cycloheptatriene with 2 equiv of Li[2,6-<sup><i>i</i></sup>Pr<sub>2</sub>C<sub>6</sub>H<sub>3</sub>NH], Li[Dipp-NH]. Triple deprotonation of (BCHT-NCN)H<sub>3</sub> (<b>1</b>) using <i>n</i>-BuLi yields the deprotonation product [(BCHT-NCN)Li<sub>3</sub>] (<b>2</b>), which crystallizes as a dimer [{[BCHT-NCN]Li<sub>3</sub>(Et<sub>2</sub>O)<sub>2</sub>}<sub>2</sub>] (<b>2</b>)<sub>2</sub>. Coordination compounds of the trianionic pincer ligand were obtained with SnCl<sub>2</sub>, YCl<sub>3</sub>(THF)<sub>3.5</sub>, and HfCl<sub>4</sub>(THF)<sub>2</sub>: [(BCHT-NCN)SnLi] (<b>3</b>), [(BCHT-NCN)Y(THF)<sub>2</sub>] (<b>4</b>), [(BCHT-NCN)HfCl<sub>2</sub>][Li(THF)<sub>4</sub>] (<b>5</b>), respectively. A hafnium hydride complex [(BCHT-NCN)HfH(HBEt<sub>3</sub>)][K(Et<sub>2</sub>O)<sub>2</sub>] (<b>6</b>) was isolated after reaction of <b>5</b> with K[HBEt<sub>3</sub>]. A <sup>Me</sup>NHC substitution product [(BCHT-NCN)HfCl(<sup>Me</sup>NHC)] (<b>7</b>) was synthesized treating compound <b>5</b> with <sup>Me</sup>NHC at rt. Following an <i>n</i>-BuLi reaction of <b>7</b> gives an alkyl complex [(BCHT-NCN)Hf(<i>n</i>-Bu)(<sup>Me</sup>NHC)] (<b>8</b>). Thermolysis of <b>7</b> yields the isomerization product [(BCHT-NCN<sup>#</sup>)HfCl(<sup>Me</sup>NHC)] (<b>9</b>), which was transferred into a methyl complex [(BCHT-NCN<sup>#</sup>)HfMe(<sup>Me</sup>NHC)] (<b>10</b>) upon treatment with MeMgBr. Hydride abstraction from complex <b>9</b> leads to a cationic complex [(BCHT-NCN<sup>+</sup>)HfCl(<sup>Me</sup>NHC)][Al(O<sup><i>t</i></sup>Bu<sup>F</sup>)<sub>4</sub>] (<b>11</b>).
90 years of Gödel’s incompleteness theorems: Logic and computation
2024-05-28

Abstract This volume is one of two special issues collecting articles by invited speakers of the conference ‘Celebrating 90 Years of Gödel’s Incompleteness Theorems’ held in Nürtingen (Germany) in July 2021. The conference was organized by the Carl Friedrich von Weizsäcker Center at the University of Tübingen with support by the ERC-funded project Gödel Enigma: Rediscovering Kurt Gödel through his unpublished works at the University of Helsinki and by the Kurt Gödel Society in Vienna.
From Learning to Optimize to Learning Optimization Algorithms
2024-05-28

Towards designing learned optimization algorithms that are usable beyond their training setting, we identify key principles that classical algorithms obey, but have up to now, not been used for Learning to Optimize (L2O). Following these principles, we provide a general design pipeline, taking into account data, architecture and learning strategy, and thereby enabling a synergy between classical optimization and L2O, resulting in a philosophy of Learning Optimization Algorithms. As a consequence our learned algorithms perform well far beyond problems from the training distribution. We demonstrate the success of these novel principles by designing a new learning-enhanced BFGS algorithm and provide numerical experiments evidencing its adaptation to many settings at test time.
Random Forest-Based Soil Moisture Estimation Using Sentinel-2, Landsat-8/9, and UAV-Based Hyperspectral Data
2024-05-29

Accurate spatiotemporal monitoring and modeling of soil moisture (SM) is of paramount importance for various applications ranging from food production to climate change adaptation. This study deals with modeling SM with the random forest (RF) algorithm using datasets comprising multispectral data from Sentinel-2, Landsat-8/9, and hyperspectral data from the CoSpectroCam sensor (CSC, licensed to AgriWatch BV, Enschede, The Netherlands) mounted on an unmanned aerial vehicle (UAV) in Iran. The model included nine bands from Landsat-8/9, 11 bands from Sentinel-2, and 1252 bands from the CSC (covering the wavelength range between 420 and 850 nm). The relative feature importance and band sensitivity to SM variations were analyzed. In addition, four indices, including the perpendicular index (PI), ratio index (RI), difference index (DI), and normalized difference index (NDI) were calculated from the different bands of the datasets, and their sensitivity to SM was evaluated. The results showed that the PI exhibited the highest sensitivity to SM changes in all datasets among the four indices considered. Comparisons of the performance of the datasets in SM estimation emphasized the superior performance of the UAV hyperspectral data (R2 = 0.87), while the Sentinel-2 and Landsat-8/9 data showed lower accuracy (R2 = 0.49 and 0.66, respectively). The robust performance of the CSC data is likely due to its superior spatial and spectral resolution as well as the application of preprocessing techniques such as noise reduction and smoothing filters. The lower accuracy of the multispectral data from Sentinel-2 and Landsat-8/9 can also be attributed to their relatively coarse spatial resolution compared to the CSC, which leads to pixel non-uniformities and impurities. Therefore, employing the CSC on a UAV proves to be a valuable technology, providing an effective link between satellite observations and ground measurements.
The SURVIVE study: Liquid biopsy guided surveillance after intermediate- to high-risk early breast cancer.
2024-05-29

TPS620 Background: Current guidelines limit routine breast cancer (BC) follow-up to clinical examinations and breast imaging. This is based on the results of two large cohort studies conducted in the 1980s that showed no improvement in overall survival (OS) by an intensified screening for distant metastases. Thus, imaging for distant metastases should currently only be performed in patients with specific symptoms. To detect distant relapse in a pre-symptomatic stage, we suggest the evaluation of a liquid biopsy-guided intensified surveillance, analyzing tumor markers (CA 27.29, CA 125 and CEA), circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Methods: Funded by the German Federal Ministry of Education and Research, the SURVIVE study is the first large, randomized BC surveillance trial to investigate the potential survival benefit of a liquid biopsy guided follow-up care in intermediate- to high-risk early breast cancer patients. The trial is a German multicenter, controlled phase 3 superiority study, in which 3500 patients are randomized in a 1:1 ratio to standard vs. liquid biopsy guided intensified follow-up care. Eligible patients are adults with confirmed primary invasive intermediate to high-risk early BC, defined as an indication for (neo-)adjuvant chemotherapy, and/or large tumor size (&gt; 50 mm), and/or positive lymph nodes (≥ pN1mi), and/or high grade (≥ G3). Primary anti-tumor therapy (surgery, adjuvant chemo- or radiotherapy) must have been completed previously. Patient enrollment during adjuvant endocrine, antibody- or targeted therapy is allowed. The total study duration is 144 months. Stratification factors are study site as well as HR-, HER2- and nodal status at surgery.Both study arms receive standard follow-up according to national guidelines, and the intensified surveillance arm will be tested for standard tumor markers, CTCs and ctDNA via tumor-informed approach (RaDaR assay). Pre-specified abnormal findings of any of the liquid biopsy markers indicative of minimal residual disease trigger complete staging. In the event of confirmed disease recurrence, guideline-based treatment follows, otherwise, liquid biopsy testing continues. If applicable, study participants may enter interventional trials. Statistics:The two primary objectives are to determine whether intensified, liquid biopsy-guided surveillance leads to better OS or an overall lead-time effect, compared to standard surveillance. OS will be analyzed in the ITT population using Kaplan Meier methods and cox regression models, the overall lead time effect is a purely descriptive composite measure. Secondary objectives include IDFS, DDFS, DRFS, BCSS and quality of life (QoL). Aims: We propose a liquid biopsy guided follow-up method, with high sensitivity and specificity for the earlier detection of distant (oligo-)metastases, to enable earlier initiation of therapy. Clinical trial information: NCT05658172 .
Molecular characterization of human adenoviruses associated with pediatric respiratory infections in Karachi, Pakistan
2024-05-29

Abstract Human adenoviruses (HAdVs) are a diverse group of viruses associated with respiratory infections in humans worldwide. However, there is a lack of research on the genetic diversity and epidemiology of HAdVs in Pakistan. This study characterized HAdVs in pediatric patients with respiratory tract infections in Karachi, Pakistan, between 2022 and 2023. We analyzed 762 nasopharyngeal samples of children ≤ 5 years. DNA extraction, followed by PCR targeting E2B and hexon genes, was carried out. Data analysis was performed on SPSS 25.0, and phylogenetic analysis of hexon gene was performed on MEGA 11. HAdV was detected in 7.34% (56/762) of patients round the year, but at a significantly higher rate during the winter season. Age was insignificantly associated with HAdV incidence ( p = 0.662), but more than 62.5% (35/56) of positive cases were younger than 10 months. The circulating HAdVs were identified as six different types from species B (78.57%) and C (21.42%), with the majority of isolates found to be like B3. HAdV was found to be co-infected with bocavirus (5.4%) and measles (7.14%). These findings revealed a high frequency and genetic diversity of respiratory HAdVs in Karachi, Pakistan. We conclude that periodic and continuous surveillance of adenoviruses and other respiratory pathogens is necessary to improve the prognosis and management of respiratory diseases, thereby reducing the child mortality rate in Pakistan.
Spectral Signatures of Vibronic Coupling in Trapped Cold Ionic Rydberg Systems
2024-05-29

Atoms and ions confined with electric and optical fields form the basis of many current quantum simulation and computing platforms. When excited to high-lying Rydberg states, long-ranged dipole interactions emerge which strongly couple the electronic and vibrational degrees of freedom through state-dependent forces. This vibronic coupling and the ensuing hybridization of internal and external degrees of freedom manifest through clear signatures in the many-body spectrum. We illustrate this by considering the case of two trapped Rydberg ions, for which the interaction between the relative vibrations and Rydberg states realizes a quantum Rabi model. We proceed to demonstrate that the aforementioned hybridization can be probed by radio frequency spectroscopy and discuss observable spectral signatures at finite temperatures and for larger ion crystals.
Neoadjuvant dynamic marker-adjusted personalized therapy comparing trastuzumab-deruxtecan versus pacli-/docetaxel + carboplatin + trastuzumab + pertuzumab in HER2+ early breast cancer: WSG-ADAPT-HER2-IV.
2024-05-29

TPS631 Background: In HER2+ early breast cancer (EBC), combination of standard chemotherapy (CTx) with anti-HER2-antibodies has shown higher efficacy versus CTx alone and/or anti-HER2-antibodies alone. Next to a need for treatment escalation in high-risk disease, there is also a substantial subset of patients (pts) (e.g., elderly pts; those with low - intermediate clinical risk) who need de-escalated but still effective treatment. Based on results from WSG ADAPT HER2+ subtrials, antibody-drug-conjugates (e.g., trastuzumab-emtansine (T-DM1), trastuzumab-deruxtecan (T-DXd)) are excellent candidates for de-escalation approaches in HER2+ EBC due to their high efficacy and low toxicity. Methods: WSG-ADAPT-HER2-IV (NCT05704829) is a multicenter, interventional, prospective, two-arm, randomized, open-label, controlled (neo-)adj., phase-II trial evaluating the efficacy and safety of T-DXd vs. standard-of-care (SOC) PAC+T+P in low-intermediate-risk or DOC/PAC+CARBO+T+P in intermediate-high-risk HER2+ EBC in pre- and postmenopausal pts. Pts will be assigned to 2 treatment groups, depending on risk of recurrence: Cohort 1 (HER2+ EBC, low-intermediate risk of recurrence per Investigator ́s decision, 12 wks treatment) and cohort 2 (HER2+ EBC, intermediate-high risk, 18 wks treatment) will be randomized 2:1 to either T-DXd or SOC neoadj. treatment. After 12/18-wks of neoadj. treatment, pathological response (pCR) assessment is performed. Pts with pCR will receive further SOC post-neoadj. treatment according to AGO guidelines. Those with non-pCR qualify for a cross-over treatment: Pts with neoadj. T-DXd will receive SOC CTx + anti-HER2-treatment. Pts. with neoadj. SOC treatment and non-pCR (≥ 5mm residual tumor) receive T-DXd until completion of 52 wks of treatment. After post-neoadj. Treatment, 2 – 5.5 years follow-up will be performed, during which pts may receive any SOC treatment according. Co-primary objectives are comparison of pCR-rates after 12/18 wks of neoadj. treatment with T-DXd vs. SOC (PAC+T+P or PAC/DOC+Carbo+T+P) in pooled risk cohorts and to evaluate whether 3-year dDFS equals or exceeds 92% in T-DXd-treated pts from both risk cohorts. It is planned to randomize 402 pts (269 pts to cohort 1; 133 to cohort 2). Study start was in January 2024 (45 sites, enrollment period 24 months). Estimated trial duration of is 5.5 years. Translational analyses:Potential resistance markers and molecular alterations will be assessed in tumor tissue from primary diagnosis, after 3 wks and after neoadj. treatment, and at recurrence. ctDNA/ctRNA from optional blood samples will be assessed for mutations and gene expression relevant in HER2+ EBC. Clinical trial information: NCT05704829 .
Reliable Long-Term Serial Evaluation of Cochlear Function Using Pulsed Distortion-Product Otoacoustic Emissions: Analyzing Levels and Pressure Time Courses
2024-05-29

Objectives: To date, there is no international standard on how to use distortion-product otoacoustic emissions (DPOAEs) in serial measurements to accurately detect changes in the function of the cochlear amplifier due, for example, to ototoxic therapies, occupational noise, or the development of regenerative therapies. The use of clinically established standard DPOAE protocols for serial monitoring programs appears to be hampered by multiple factors, including probe placement and calibration effects, signal-processing complexities associated with multiple sites of emission generation as well as suboptimal selection of stimulus parameters. Design: Pulsed DPOAEs were measured seven times within 3 months for f 2 = 1 to 14 kHz and L 2 = 25 to 80 dB SPL in 20 ears of 10 healthy participants with normal hearing (mean age = 32.1 ± 9.7 years). L 1 values were computed from individual optimal-path parameters derived from the corresponding individual DPOAE level map in the first test session. Three different DPOAE metrics for evaluating the functional state of the cochlear amplifier were investigated with respect to their test-retest reliability: (1) the interference-free, nonlinear-distortion component level ( L OD ), (2) the time course of the DPOAE-envelope levels, L DP ( t ), and (3) the squared, zero-lag correlation coefficient ( ) between the time courses of the DPOAE-envelope pressures, p DP ( t ), measured in two sessions. The latter two metrics include the two main DPOAE components and their state of interference. Results: Collated over all sessions and frequencies, the median absolute difference for L OD was 1.93 dB and for L DP ( t ) was 2.52 dB; the median of was 0.988. For the low ( f 2 = 1 to 3 kHz), mid ( f 2 = 4 to 9 kHz), and high ( f 2 = 10 to 14 kHz) frequency ranges, the test-retest reliability of L OD increased with increasing signal to noise ratio (SNR). Conclusions: On the basis of the knowledge gained from this study on the test-retest reliability of pulsed DPOAE signals and the current literature, we propose a DPOAE protocol for future serial monitoring applications that takes into account the following factors: (1) separation of DPOAE components, (2) use of individually optimal stimulus parameters, (3) SNR of at least 15 dB, (4) accurate pressure calibration, (5) consideration of frequency- and level-dependent test-retest reliabilities and corresponding reference ranges, and (6) stimulus levels L 2 that are as low as possible with sufficient SNR to capture the nonlinear functional state of the cochlear amplifier operating at its highest gain.
Case report: Boundaries of oncological and traumatological medical care in ancient Egypt: new palaeopathological insights from two human skulls
2024-05-29

The present case studies report malignant neoplastic and traumatic lesions observed on two ancient Egyptian skulls held at the Duckworth Collection (Cambridge University). The analysis aims to characterise the lesions and provide a diagnosis using a methodology based on micro-CT scanning and microscopic bone surface analysis. Results pointed towards neoplastic lesions in both cases and healed severe skull trauma in one of them suggesting successful traumatological therapy. Interestingly, our analysis has identified the presence of perimortem cutmarks associated with metastatic lytic lesions in one of the skulls, indicating a potential surgical treatment attempt or postmortem medical exploration. We argue that the two cases, although not contemporary, allow a palaeopathological discussion on oncological and traumatological understanding and management of such conditions in the past. The confrontation of two potential managements represented by two different types of lesions represent a clear boundary in ancient Egyptian medical care and a milestone in the history of medicine.
The impact of presentation modes on mental rotation processing: a comparative analysis of eye movements and performance
2024-05-29

Abstract Mental rotation is the ability to rotate mental representations of objects in space. Shepard and Metzler’s shape-matching tasks, frequently used to test mental rotation, involve presenting pictorial representations of 3D objects. This stimulus material has raised questions regarding the ecological validity of the test for mental rotation with actual visual 3D objects. To systematically investigate differences in mental rotation with pictorial and visual stimuli, we compared data of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>N</mml:mi> <mml:mo>=</mml:mo> <mml:mn>54</mml:mn> </mml:mrow> </mml:math> university students from a virtual reality experiment. Comparing both conditions within subjects, we found higher accuracy and faster reaction times for 3D visual figures. We expected eye tracking to reveal differences in participants’ stimulus processing and mental rotation strategies induced by the visual differences. We statistically compared fixations (locations), saccades (directions), pupil changes, and head movements. Supplementary Shapley values of a Gradient Boosting Decision Tree algorithm were analyzed, which correctly classified the two conditions using eye and head movements. The results indicated that with visual 3D figures, the encoding of spatial information was less demanding, and participants may have used egocentric transformations and perspective changes. Moreover, participants showed eye movements associated with more holistic processing for visual 3D figures and more piecemeal processing for pictorial 2D figures.