julilili42/papers huggingface dataset:
TROPHY-U-01 cohort 6: Sacituzumab govitecan (SG), SG plus zimberelimab (ZIM), SG plus ZIM plus domvanalimab (DOM), or carboplatin (CARBO) + gemcitabine (GEM) in cisplatin-ineligible patients (pts) with treatment-naive metastatic urothelial cancer (mUC).
2023-02-20

TPS592 Background: SG is an antibody-drug conjugate composed of an anti-trophoblast cell-surface antigen-2 (Trop-2) antibody coupled to SN-38 via a proprietary hydrolyzable linker. In Cohort 1 of the phase 2 TROPHY-U-01 trial, SG monotherapy resulted in a 27% objective response rate (ORR) and median overall survival (OS) of 10.9 months with an overall manageable toxicity profile in pts with locally advanced or mUC who previously received platinum-based therapy and a checkpoint inhibitor (CPI; Tagawa S, et al. J Clin Oncol. 2021). The results led to accelerated FDA approval of SG for this population. ZIM (anti-PD-1) and DOM (anti-TIGIT) are CPIs under clinical investigation for anti-tumor activity. Cohort 6 of TROPHY-U-01 trial (C6) will assess SG monotherapy vs SG plus CPI combinations (SG + ZIM; SG + ZIM + DOM) vs CARBO/GEM followed by avelumab maintenance in treatment naive cis-ineligible pts with locally advanced or mUC. Methods: TROPHY-U-01 (NCT03547973) is a multicohort, open-label, global, phase 2 trial. C6 includes pts with cis-ineligible unresectable locally advanced or mUC who are ≥18 y; have an ECOG performance status 0-1; have available tissue for biomarker testing; have no prior mUC therapy, except (neo)adjuvant chemotherapy with recurrence &gt;12 mo from completion; are CPI-naive or &gt;12 mo from completion; have adequate hematologic and hepatic function; and have creatinine clearance ≥30 mL/min. A safety lead-in will occur where 6-8 pts will be treated with SG 10 mg/kg on D1 and D8 of a 21-D cycle + ZIM 360 mg q3wk. A second safety lead-in will occur where 6-8 pts will be treated with SG 10 mg/kg on D1 and D8 of a 21-D cycle + ZIM 360 mg q3wk + DOM 1200 mg q3wk. After the safety lead-in, pts will be randomized 1:2:2:2 to: Arm 1: SG 10 mg/kg on D1 and D8 of a 21-D cycle; Arm 2: SG 10 mg/kg on D1 and D8 of a 21-D cycle and ZIM 360 mg q3wk; Arm 3: SG 10 mg/kg on D1 and D8 of a 21-D cycle and ZIM 360 mg q3wk and DOM 1200 mg q3wk; and Arm 4: CARBO (AUC 4.5-5) on D1 of each 21-D cycle + GEM 1000 mg/m 2 on D1 and D8 of each 21-D cycle for the first 4-6 cycles followed by switch maintenance avelumab 800 mg q2wk in the absence of progression. All pts will continue treatment until progression, unacceptable toxicity, or loss of clinical benefit. Primary endpoint is ORR per central review based on RECIST 1.1. Secondary endpoints include progression-free survival, duration of response, and clinical benefit rate by central review and investigator review, as well as ORR by investigator review, and OS, and safety and tolerability (Arms 1-3). C6 aims to enroll an estimated 226 pts. With 60 subjects each in Arms 2-4, a comparison of Arm 2 or 3 vs Arm 4 will have ~88% power at one-sided α of 0.05 to demonstrate an improvement in ORR, with a null hypothesis of ORR 40% for Arms 2-3 and an alternative hypothesis of ORR at 65% for Arms 2-4. Clinical trial information: NCT03547973 .
Progression through time: Development of birdwatcher careers based on propensity score matching
2023-02-20

Recreation specialization postulates that people progress through a career when engaging in a leisure activity. This has been studied by cross-sectional and few panel studies, but both methods have some shortcomings. Here, I studied German birdwatchers from the 16 federal states of Germany by employing the propensity score matching method. Data were collected using the online research tool SoSciSurvey between 14 February 2020 and 15 June 2020 include study population, sampling, data collection, and analysis in short. Three career stages of the same size were defined according to birdwatching experience in years. Then, respondents were matched according to age, gender, federal state, and educational level but differed in their leisure career stages by propensity score matching, thus birders of the same age, gender, educational level, and federal state were identified that differed in their birding experience in years. Stage 1 was birders with ≤10 years of birding, stage 2 with 11–34, and stage 3 with ≥35 years. This led to 177 pairs in the stage 1–2 comparison and 113 pairs in the group 2–2 comparison. The recreation specialization construct based on the dimensions behavior, skill, and commitment was applied. There was a highly significant effect concerning skill/knowledge and behavior between stage 1 and 2 (p < .001 for both). However, no differences were found concerning personal and behavioral commitment (p > .5). Skill/knowledge increased again between stage 2 and 3 (F = 4.554, df = 112, p = .035), no significant changes concerning the other three dimensions behavior, personal, and behavioral commitments were found (p > .2). The study provides evidence for a career development in leisure.
Phase 3 LITESPARK-022: Pembrolizumab (pembro) plus hypoxia-inducible factor 2α (HIF-2α) inhibitor belzutifan as adjuvant treatment for clear cell renal cell carcinoma (ccRCC).
2023-02-20

TPS748 Background: Treatment with the PD-1 inhibitor pembro produced significant improvement in disease-free survival after surgery for patients (pts) with ccRCC in the phase 3 KEYNOTE-564 trial. Based on these results, pembro was approved by the US Food and Drug Administration and the European Medicines Agency for adjuvant treatment of pts with RCC at increased risk of recurrence following nephrectomy or following nephrectomy and resection of metastatic lesions. Despite advances in the treatment landscape for RCC, more effective adjuvant treatment strategies are needed for pts at risk of recurrence after surgery. HIF-2α is an established oncogenic driver in ccRCC, and promising antitumor activity in advanced ccRCC and von Hippel-Lindau disease–associated RCC has been demonstrated with the HIF-2α inhibitor belzutifan. The multicenter, double-blind, randomized, phase 3 LITESPARK-022 study (NCT05239728) will evaluate the efficacy and safety of pembro plus belzutifan compared with placebo plus pembro as adjuvant treatment following nephrectomy in pts with ccRCC. Methods: Key eligibility criteria include adults with histologically or cytologically confirmed intermediate-high risk, high risk, or M1 with no evidence of disease (NED) RCC with a clear cell component; pts with no prior systemic therapy, nephrectomy, and/or metastasectomy ≤12 weeks before randomization; and pts who are tumor free per computed tomography/magnetic resonance imaging. Approximately 1600 pts will be randomly assigned to receive belzutifan 120 mg orally once daily plus pembro 400 mg intravenously (IV) every 6 weeks (Q6W) for ≤9 administrations (~54 weeks) or oral placebo plus pembro 400 mg IV Q6W for ≤9 administrations (~54 weeks) or until verified disease recurrence by blinded independent central review, start of new anticancer treatment, unacceptable toxicity, or decision to withdraw. Stratification factors are tumor grade (1 or 2 vs 3 or 4) and risk type (intermediate-high risk versus high risk versus M1 NED). Pts will be radiologically evaluated Q12W from randomization through year 2, Q16W in years 3 to 5, and Q24W in years 6 and beyond. Adverse events will be monitored throughout the study and for 30 days following cessation of study treatment (90 days for serious adverse events). The primary end point is disease-free survival. Secondary end points include overall survival, safety, disease recurrence–specific survival, and patient-reported outcomes. Recruitment is underway in Asia, Australia, Europe, North America, and South America. © 2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. All rights reserved. Clinical trial information: NCT05239728 .
TROPHU-U-01 cohort 5: Evaluation of maintenance sacituzumab govitecan (SG) plus zimberelimab (ZIM), ZIM, or avelumab in cisplatin-eligible patients (pts) with unresectable or metastatic urothelial cancer (mUC).
2023-02-20

TPS598 Background: SG is an antibody-drug conjugate composed of an anti-trophoblast cell-surface antigen-2 (Trop-2) antibody coupled to a topoisomerase-I inhibitor, SN-38, via a hydrolyzable linker. In Cohort 1 of the phase 2 TROPHY-U-01 trial, SG monotherapy resulted in a 27% objective response rate (ORR) and median overall survival (OS) of 10.9 months with an overall manageable toxicity profile in pts with locally advanced or mUC who previously received platinum-based therapy and a checkpoint inhibitor (CPI; Tagawa S, et al. J Clin Oncol. 2021). These results led to accelerated FDA approval of SG in this population. The CPI ZIM is a fully human IgG4 monoclonal antibody targeting PD-1. CPIs are active in mUC, including avelumab that is FDA-approved as switch maintenance therapy for locally advanced or mUC that has not progressed with first-line platinum-based chemotherapy. Cohort 5 of the TROPHY-U-01 trial will evaluate the safety, tolerability, and efficacy of SG + ZIM vs ZIM alone vs avelumab as switch maintenance in pts with mUC who have received gemcitabine (GEM)/cisplatin without progressive disease (PD). Methods: TROPHY-U-01 (NCT03547973) is a multicohort, open-label, global, phase 2 trial. Cohort 5 includes pts who have not progressed after completion of 4-6 cycles of GEM/cisplatin. Key eligibility requirements include ≥18 y; ECOG PS 0-1; available tissue for biomarker testing; adequate blood counts without transfusion or growth factor within 2 weeks of study drug initiation; creatinine clearance ≥30 mL/min. A safety lead-in of 6-8 pts will be conducted, where pts will be treated with SG 10 mg/kg IV on D1 and D8 of a 21-D cycle plus ZIM 360 mg IV q3wk on a 21-D cycle. On safety lead-in, if SG + ZIM is deemed safe, pts will be randomized 1:1:1. Those in Arm 1 will receive SG 10 mg/kg IV on D1 and D8 of a 21-D cycle followed by ZIM 360 mg IV, q3wk (D1 of a 21-D cycle). Pts in Arm 2 will receive avelumab 800 mg IV q2wk (D1 of a 14-D cycle). Pts in Arm 3 will receive ZIM 360 mg IV q3wk. All pts will continue treatment until PD, unacceptable toxicity, or loss of clinical benefit. The primary endpoint is progression-free survival based on central review by RECIST 1.1 criteria. Secondary endpoints include OS (all arms), safety/tolerability of SG in combination with ZIM (Arm 1). Cohort 5 aims to enroll an estimated 158 pts. A sample size of 50 pts per randomized arm is determined based on clinical consideration for exploring the activity of anticancer agents. Clinical trial information: NCT03547973 .
Crows protect visual working memory against interference
2023-02-20

ABSTRACT Working memory, the ability to actively maintain and manipulate information across time, is key to intelligent behavior. Because of the limited capacity of working memory, relevant information needs to be protected against distracting representations. Whether birds can resist distractors and safeguard memorized relevant information is unclear. We trained carrion crows in a delayed match-to-sample task to memorize an image while resisting other, interfering stimuli. We found that the repetition of the sample stimulus during the memory delay improved performance accuracy and accelerated reaction time relative to a reference condition with a neutral interfering stimulus. In contrast, the presentation of the image that constituted the subsequent non-match test stimulus mildly weakened performance. However, the crows' robust performance in this most demanding distractor condition indicates that sample information was actively protected from being overwritten by the distractor. These data show that crows can cognitively control and safeguard behaviorally relevant working memory contents.
Low-Coordinate Mixed Ligand NacNac Complexes of Rare Earth Metals
2023-02-20

We report the synthesis and characterization of two types of new mixed-ligand rare earth complexes: tetracoordinate (NacNacMes)Ln(BIANdipp) (Ln = Dy (1), Er (2) and Y (3)) and pentacoordinate (NacNacMes)Ln(APdipp)(THF) (Ln = Dy (4), Er (5) and Y (6)). The first three compounds were prepared by the reaction of [(BIANDipp)LnI] with potassium β-diketiminate. The salt metathesis of β-diketiminato-supported rare earth dichlorides (NacNacMes)LnCl2(THF)2 with sodium o-amidophenolate results in compounds 4–6. The crystal structures of complexes 1–6 were determined by single-crystal analysis. The combination of bulky monoanionic N-mesityl-substituted β-diketiminates with sterically hindered redox-active ligands led to the very low coordination numbers of rare earths and strong distortion of the chelate ligands.
SBOannotator: a Python Tool for the Automated Assignment of Systems Biology Ontology Terms
2023-02-20

The number and size of computational models in biology have drastically increased over the past years and continue to grow. Modeled networks are becoming more complex, and reconstructing them from the beginning in an exchangeable and reproducible manner is challenging. Using precisely defined ontologies enables the encoding of field-specific knowledge and the association of disparate data types. In computational modeling, the medium for representing domain knowledge is the set of orthogonal structured controlled vocabularies named Systems Biology Ontology ( SBO). The SBO terms enable modelers to explicitly define and unambiguously describe model entities, including their roles and characteristics. Here, we present the first standalone tool that automatically assigns SBO terms to multiple entities of a given SBML model, named the SBOannotator. The main focus lies on the reactions, as the correct assignment of precise SBO annotations requires their extensive classification. Our implementation does not consider only top-level terms but examines the functionality of the underlying enzymes to allocate precise and highly specific ontology terms to biochemical reactions. Transport reactions are examined separately and are classified based on the mechanism of molecule transport. Pseudo-reactions that serve modeling purposes are given reasonable terms to distinguish between biomass production and the import or export of metabolites. Finally, other model entities, such as metabolites and genes, are annotated with appropriate terms. Including SBO annotations in the models will enhance the reproducibility, usability, and analysis of biochemical networks. Availability: The open-source project SBOannotator is freely available under the terms of LGPL version 3.0 from https://github.com/draeger-lab/SBOannotator/.
How to do biodiversity-related science communication
2023-02-20

Biodiversity is the foundation of our lives. Yet we destroy ecosystems and drive species to extinction. Human-induced biodiversity loss does not yet receive sufficient public attention, although biodiversity is fundamental for dealing with global environmental crises. Effective communication of biodiversity-related knowledge is challenging but crucial and should contribute to evidence-based decision-making transparent to the public. It is essential to promote science communication on biodiversity, and to stimulate dialogue between science, policy, and society. We emphasize the role of science journalism in critically mediating the complexity of scientific knowledge and suggest Dos and Don'ts for scientists to guide biodiversity-related science communication.
Efficient coding of natural scenes improves neural system identification
2023-02-20

Dataset for Qiu et al., 2022. This work was supported by the German Research Foundation (DFG; SFB 1233, Robust Vision: Inference Principles and Neural Mechanisms, projects 10 and 12, project number 276693517; GRK2381, project number 335549539), the Germany’s Excellence Strategy (EXC 2064/1, project number 390727645), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant (agreement No 674901); the Max Planck Society (M.FE.A.KYBE0004); the German Ministry of Education and Research (BMBF; FKZ: 01GQ1002), and the Tübingen AI Center (FKZ: 01IS18039A). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Carbon and mineral data of organic matter fractions in Siberian Yedoma permafrost
2023-02-20

This file contains carbon and mineral data of organic matter fractions obtained from two permafrost drill cores L14-02 (73.33616° N; 141.32776° E) and L14-05 (73.34994° N; 141.24156° E) from Bol’shoy Lyakhovsky Island in NE Siberia in 2014. The datasets contain mass fractions of different size and density fractions, OC concentrations, OC/N ratios, data on organic matter composition based on <sup>13</sup>C-NMR, radiocarbon (<sup>14</sup>C) data, as well as data on iron (Fe) mineral phases and CO<sub>2</sub> production rates of mineral-associated organic matter. Further, carbon and organic biomarker data (<em>n</em>-alkanes) of the bulk sediment are included. The data were created to study mass partitioning of Pleistocene permafrost OC among different organic matter fractions to assess the bioavailability and stability of the organic matter. Please refer to the publication listed below for more information.
Efficient coding of natural scenes improves neural system identification
2023-02-20

Dataset for Qiu et al., 2022.\\n\\n\\n\\n\\nThis work was supported by the German Research Foundation (DFG; SFB 1233, Robust Vision: Inference Principles and Neural Mechanisms, projects 10 and 12, project number 276693517; GRK2381, project number 335549539), the Germany&amp;rsquo;s Excellence Strategy (EXC 2064/1, project number 390727645), the European Union&amp;rsquo;s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant (agreement No 674901);&amp;nbsp;the Max Planck Society (M.FE.A.KYBE0004); the German Ministry of Education and Research (BMBF; FKZ: 01GQ1002), and the T&amp;uuml;bingen AI Center (FKZ: 01IS18039A). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.\\n
Free-breathing Arterial Spin Labeling MRI for the Detection of Pulmonary Embolism
2023-02-21

Background Arterial spin labeling (ASL) MRI can be used to assess organ perfusion but has yet to be implemented for perfusion evaluation of the lung. Purpose To evaluate pseudo-continuous ASL (PCASL) MRI for the detection of acute pulmonary embolism (PE) and its potential as an alternative to CT pulmonary angiography (CTPA). Materials and Methods Between November 2020 and November 2021, 97 patients (median age, 61 years; 48 women) with suspected PE were enrolled in this prospective study. PCASL MRI was performed within a 72-hour period following CTPA under free-breathing conditions and included three orthogonal planes. The pulmonary trunk was labeled during systole, and the image was acquired during diastole of the subsequent cardiac cycle. Additionally, multisection, coronal, balanced, steady-state free-precession imaging was carried out. Two radiologists blindly assessed overall image quality, artifacts, and diagnostic confidence (five-point Likert scale, 5 = best). Patients were categorized as positive or negative for PE, and a lobe-wise assessment in PCASL MRI and CTPA was conducted. Sensitivity and specificity were calculated on a patient level with the final clinical diagnosis serving as the reference standard. Interchangeability between MRI and CTPA was also tested with use of an individual equivalence index (IEI). Results PCASL MRI was performed successfully in all patients with high scores for image quality, artifact, and diagnostic confidence (κ ≥ .74). Of the 97 patients, 38 were positive for PE. PCASL MRI depicted PE correctly in 35 of 38 patients with three false-positive and three false-negative findings, resulting in a sensitivity of 35 of 38 patients (92% [95% CI: 79, 98]) and a specificity of 56 of 59 patients (95% [95% CI: 86, 99]). Interchangeability analysis revealed an IEI of 2.6% (95% CI: 1.2, 3.8). Conclusion Free-breathing pseudo-continuous arterial spin labeling MRI depicted abnormal lung perfusion caused by acute pulmonary embolism and may be useful as a contrast material-free alternative to CT pulmonary angiography for selected patients. German Clinical Trials Register no. DRKS00023599 © RSNA, 2023.
A MALDI-TOF MS library for rapid identification of human commensal gut bacteria from the class Clostridia
2023-02-21

Introduction Microbial isolates from culture can be identified using 16S or whole-genome sequencing which generates substantial costs and requires time and expertise. Protein fingerprinting via Matrix-assisted Laser Desorption Ionization–time of flight mass spectrometry (MALDI-TOF MS) is widely used for rapid bacterial identification in routine diagnostics but shows a poor performance and resolution on commensal bacteria due to currently limited database entries. The aim of this study was to develop a MALDI-TOF MS plugin database (CLOSTRI-TOF) allowing for rapid identification of non-pathogenic human commensal gastrointestinal bacteria. Methods We constructed a database containing mass spectral profiles (MSP) from 142 bacterial strains representing 47 species and 21 genera within the class Clostridia . Each strain-specific MSP was constructed using &amp;gt;20 raw spectra measured on a microflex Biotyper system (Bruker-Daltonics) from two independent cultures. Results For validation, we used 58 sequence-confirmed strains and the CLOSTRI-TOF database successfully identified 98 and 93% of the strains, respectively, in two independent laboratories. Next, we applied the database to 326 isolates from stool of healthy Swiss volunteers and identified 264 (82%) of all isolates (compared to 170 (52.1%) with the Bruker-Daltonics library alone), thus classifying 60% of the formerly unknown isolates. Discussion We describe a new open-source MSP database for fast and accurate identification of the Clostridia class from the human gut microbiota. CLOSTRI-TOF expands the number of species which can be rapidly identified by MALDI-TOF MS.
Identifying the distinct spectral dynamics of laminar-specific interhemispheric connectivity with bilateral line-scanning fMRI
2023-02-21

Despite extensive efforts to identify interhemispheric functional connectivity (FC) with resting-state (rs-) fMRI, correlated low-frequency rs-fMRI signal fluctuation across homotopic cortices originates from multiple sources. It remains challenging to differentiate circuit-specific FC from global regulation. Here, we developed a bilateral line-scanning fMRI method to detect laminar-specific rs-fMRI signals from homologous forepaw somatosensory cortices with high spatial and temporal resolution in rat brains. Based on spectral coherence analysis, two distinct bilateral fluctuation spectral features were identified: ultra-slow fluctuation (&lt;0.04 Hz) across all cortical laminae versus Layer (L) 2/3-specific evoked BOLD at 0.05 Hz based on 4 s on/16 s off block design and resting-state fluctuations at 0.08–0.1 Hz. Based on the measurements of evoked BOLD signal at corpus callosum (CC), this L2/3-specific 0.05 Hz signal is likely associated with neuronal circuit-specific activity driven by the callosal projection, which dampened ultra-slow oscillation less than 0.04 Hz. Also, the rs-fMRI power variability clustering analysis showed that the appearance of L2/3-specific 0.08–0.1 Hz signal fluctuation is independent of the ultra-slow oscillation across different trials. Thus, distinct laminar-specific bilateral FC patterns at different frequency ranges can be identified by the bilateral line-scanning fMRI method.