julilili42/papers huggingface dataset:
Data from Bevacizumab May Differentially Improve Prognosis of Advanced Ovarian Cancer Patients with Low Expression of VEGF-A<sub>165</sub>b, an Antiangiogenic VEGF-A Splice Variant
2023-04-01

&lt;div&gt;AbstractPurpose:&lt;p&gt;The identification of a robust IHC marker to predict the response to antiangiogenic bevacizumab in ovarian cancer is of high clinical interest. VEGF-A, the molecular target of bevacizumab, is expressed as multiple isoforms with pro- or antiangiogenic properties, of which VEGF-A&lt;sub&gt;165&lt;/sub&gt;b is the most dominant antiangiogenic isoform. The balance of VEGF-A isoforms is closely related to the angiogenic capacity of a tumor and may define its vulnerability to antiangiogenic therapy. We investigated whether the expression of VEGF-A&lt;sub&gt;165&lt;/sub&gt;b could be related to the effect of bevacizumab in advanced ovarian cancer patients.&lt;/p&gt;Experimental Design:&lt;p&gt;Formalin-fixed paraffin-embedded tissues from 413 patients of the ICON7 multicenter phase III trial, treated with standard platinum-based chemotherapy with or without bevacizumab, were probed for VEGF-A&lt;sub&gt;165&lt;/sub&gt;b expression by IHC.&lt;/p&gt;Results:&lt;p&gt;In patients with low VEGF-A&lt;sub&gt;165&lt;/sub&gt;b expression, the addition of bevacizumab to standard platinum-based chemotherapy significantly improved progression-free (HR: 0.727; 95% CI, 0.538–0.984; &lt;i&gt;P&lt;/i&gt; = 0.039) and overall survival (HR: 0.662; 95% CI, 0.458–0.958; &lt;i&gt;P&lt;/i&gt; = 0.029). Multivariate analysis showed that the addition of bevacizumab in low VEGF-A&lt;sub&gt;165&lt;/sub&gt;b–expressing patients conferred significant improvements in progression-free survival (HR: 0.610; 95% CI, 0.446–0.834; &lt;i&gt;P&lt;/i&gt; = 0.002) and overall survival (HR: 0.527; 95% CI, 0.359–0.775; &lt;i&gt;P&lt;/i&gt; = 0.001), independently from established risk factors.&lt;/p&gt;Conclusions:&lt;p&gt;We demonstrate for the first time that bevacizumab may differentially improve the prognosis of advanced ovarian cancer patients with low expression of VEGF-A&lt;sub&gt;165&lt;/sub&gt;b, an antiangiogenic VEGF-A splice variant. We envision that this novel biomarker could be implemented into routine diagnostics and may have direct clinical implications for guiding bevacizumab-related treatment decisions in advanced ovarian cancer patients.&lt;/p&gt;&lt;/div&gt;
Data from Impact of RNA Signatures on pCR and Survival after 12-Week Neoadjuvant Pertuzumab plus Trastuzumab with or without Paclitaxel in the WSG-ADAPT HER2<sup>+</sup>/HR<sup>−</sup> Trial
2023-04-01

&lt;div&gt;AbstractPurpose:&lt;p&gt;To identify associations of biological signatures and stromal tumor-infiltrating lymphocytes (sTIL) with pathological complete response (pCR; ypT0 ypN0) and survival in the Phase II WSG-ADAPT HER2&lt;sup&gt;+&lt;/sup&gt;/HR&lt;sup&gt;−&lt;/sup&gt; trial (NCT01817452).&lt;/p&gt;Experimental Design:&lt;p&gt;Patients with cT1-cT4c, cN0–3 HER2&lt;sup&gt;+&lt;/sup&gt;/HR&lt;sup&gt;−&lt;/sup&gt; early breast cancer (EBC) were randomized to pertuzumab+trastuzumab (P+T, &lt;i&gt;n&lt;/i&gt; = 92) or P+T+paclitaxel (&lt;i&gt;n&lt;/i&gt; = 42). Gene expression signatures were analyzed in baseline biopsies using NanoString Breast Cancer 360 panel (&lt;i&gt;n&lt;/i&gt; = 117); baseline and on-treatment (week 3) sTIL levels were available in 119 and 76 patients, respectively. Impacts of standardized gene expression signatures on pCR and invasive disease-free survival (iDFS) were estimated by logistic and Cox regression.&lt;/p&gt;Results:&lt;p&gt;In all patients, &lt;i&gt;ERBB2&lt;/i&gt; [OR, 1.70; 95% confidence interval (CI), 1.08–2.67] and estrogen receptor (ER) signaling (OR, 1.72; 95% CI, 1.13–2.61) were favorable, whereas &lt;i&gt;PTEN&lt;/i&gt; (OR, 0.57; 95% CI, 0.38–0.87) was unfavorable for pCR. After 60 months median follow-up, 13 invasive events occurred (P+T: &lt;i&gt;n&lt;/i&gt; = 11, P+T+paclitaxel: &lt;i&gt;n&lt;/i&gt; = 2), none following pCR. Gene signatures related to immune response (IR) and ER signaling were favorable for iDFS, all with similar HR about 0.43–0.55. These patterns were even more prominent in the neoadjuvant chemotherapy-free group, where additionally BRCAness signature was unfavorable (HR, 2.00; 95% CI, 1.04–3.84). IR signatures were strongly intercorrelated. sTILs (baseline/week 3/change) were not associated with pCR or iDFS, though baseline sTILs correlated positively with IR signatures.&lt;/p&gt;Conclusions:&lt;p&gt;Distinct gene signatures were associated with pCR versus iDFS in HER2&lt;sup&gt;+&lt;/sup&gt;/HR&lt;sup&gt;−&lt;/sup&gt; EBC. The potential role of IR in preventing recurrence suggests that patients with upregulated IR signatures could be candidates for de-escalation concepts in HER2&lt;sup&gt;+&lt;/sup&gt; EBC.&lt;/p&gt;&lt;/div&gt;
The anti-inflammatory metabolite 3-phenyllactic acid is released from skeletal muscle and could contribute to the improvement of insulin sensitivity by physical exercise in subjects with overweight and obesity
2023-04-01

Background Physical exercise causes pronounced changes in circulating metabolites that could act as "exerkines" mediating its well-known beneficial effects, such as improvement of chronic low-grade inflammation, glucose homeostasis and insulin sensitivity.
Breastfeeding duration associates with lower intima media thickness in women without history of gestational diabetes
2023-04-01

Epidemiological studies demonstrate a long-lasting protective effect of breastfeeding on cardiovascular risk. We hypothesize that a history of prolonged breastfeeding would positively affects intima media thickness (IMT) in mothers with and without GDM history (hGDM).
Plasma proteomic profiles in prediabetes reversing to normoglycemia or progressing to diabetes in a year – a cross-sectional and prospective analysis
2023-04-01

Aim To compare the fasting plasma proteome profiles of patients with normal glucose tolerance (NGT), prediabetes or type 2 diabetes (T2DM) at-onset, and one-year before, when all subjects had prediabetes.
Engineering of functionally active human myotubes and myobundles in vitro
2023-04-01

Skeletal muscle mediates beneficial effects of exercise, thereby improving insulin sensitivity and reducing the risk for type 2 diabetes. Current skeletal-muscle-models in vitro are incapable of fully recapitulating its physiological functions, especially contraction. Supplementation of IGF-1, a growth factor secreted by myofibers in vivo, might help to overcome these limitations.
Structural changes in human myotubes lead to impaired human myotube contractility under metformin treatment
2023-04-01

Background Physical activity is a cornerstone in the prevention and treatment of type 2 diabetes and metformin is a first-line oral glucose-lowering drug. There is clinical evidence that health beneficial effects of exercise, like improvement of insulin sensitivity or increase in muscle mass, are blunted or even antagonized under metformin therapy. However, skeletal muscle has been poorly investigated in this context from a molecular perspective.
Time perception in suspenseful films
2023-04-01

Dataset of an experimental study in which participants (N = 50) watched short video clips from horror films. Participants were asked to estimate perceived suspense levels and to do a time estimation task.
Time perception in suspenseful films
2023-04-01

&lt;p&gt;Dataset of an experimental study in which participants (N = 50) watched short video clips from horror films. Participants were asked to estimate perceived suspense levels and to do a time estimation task.&nbsp;&lt;/p&gt;
POSEIDON: A Data Augmentation Tool for Small Object Detection Datasets in Maritime Environments
2023-04-02

Certain fields present significant challenges when attempting to train complex Deep Learning architectures, particularly when the available datasets are limited and imbalanced. Real-time object detection in maritime environments using aerial images is a notable example. Although SeaDronesSee is the most extensive and complete dataset for this task, it suffers from significant class imbalance. To address this issue, we present POSEIDON, a data augmentation tool specifically designed for object detection datasets. Our approach generates new training samples by combining objects and samples from the original training set while utilizing the image metadata to make informed decisions. We evaluate our method using YOLOv5 and YOLOv8 and demonstrate its superiority over other balancing techniques, such as error weighting, by an overall improvement of 2.33% and 4.6%, respectively.
Meta-Reflexivity and Teacher Professionalism: Facilitating Multiparadigmatic Teacher Education to Achieve a Future-Proof Profession
2023-04-02

The present work discusses the relevance of meta-reflexivity, both for the professionalization of the teaching profession and for teacher education. Meta-reflexivity is based on the multiparadigmatic system of teacher education, which finds itself grounded in diverse scientific disciplines. The approach takes uncertainty as an essential element characterizing the act of teaching. Inherent rationales of specific theories and empirical findings are made explicit, thus creating a referential framework for situation-specific interpretations and professional action. Based on a theoretical reconstruction, we propose meta-reflexivity as an essential element of pedagogic practice and, consequently, teacher professionalism. Such professionalism is characterized by teachers being able to undertake exemplary-typifying interpretations of situations, based on a deep understanding of multiple approaches. While assessing specific situations in school, a teacher can refer to these interpretations. Possible principles of a meta-reflexive teacher education are proposed that can potentially enrich the practice of teacher education for a future-proof profession.
Uncovering the organization of neural circuits with Generalized Phase Locking Analysis
2023-04-03

Despite the considerable progress of in vivo neural recording techniques, inferring the biophysical mechanisms underlying large scale coordination of brain activity from neural data remains challenging. One obstacle is the difficulty to link high dimensional functional connectivity measures to mechanistic models of network activity. We address this issue by investigating spike-field coupling (SFC) measurements, which quantify the synchronization between, on the one hand, the action potentials produced by neurons, and on the other hand mesoscopic “field” signals, reflecting subthreshold activities at possibly multiple recording sites. As the number of recording sites gets large, the amount of pairwise SFC measurements becomes overwhelmingly challenging to interpret. We develop Generalized Phase Locking Analysis (GPLA) as an interpretable dimensionality reduction of this multivariate SFC. GPLA describes the dominant coupling between field activity and neural ensembles across space and frequencies. We show that GPLA features are biophysically interpretable when used in conjunction with appropriate network models, such that we can identify the influence of underlying circuit properties on these features. We demonstrate the statistical benefits and interpretability of this approach in various computational models and Utah array recordings. The results suggest that GPLA, used jointly with biophysical modeling, can help uncover the contribution of recurrent microcircuits to the spatio-temporal dynamics observed in multi-channel experimental recordings.
Ovarian tissue cryopreservation in the pediatric with rare diseases- experience from China’s first and the largest ovarian tissue cryobank
2023-04-03

Background There is limited information about the efficacy of ovarian tissue cryopreservation (OTC) in children. In the present study, we report eight patients with rare diseases who underwent OTC in China’s first and largest ovarian tissue cryobank. Procedure Data from girls with rare diseases who underwent OTC between September 2020 and November 2022 were retrospectively analyzed. We also compared the number of cryopreserved cortex pieces, follicle number, and AMH in those with rare diseases and age-matched children with non-rare diseases who also underwent OTC in our cryobank. Results The median age of the children was 5.88 ± 3.52 (range 2-13) years old. Unilateral oophorectomy was undertaken via laparoscopy in all of the children. The diseases in the 8 patients were: 4 mucopolysaccharidoses (MPS I two cases, IVA two cases), 1 Diamond-Blackfan anemia (DBA), 1 Fanconi anemia (FA), 1 hyperimmunoglobulin E syndrome (HIES), 1 Niemann-Pick disease. The number of cryopreserved cortex pieces was 17.13 ± 6.36, and the follicle count per 2 mm biopsy was 447.38 ± 524.35. No significant difference in age, the count of cryopreserved cortex pieces, follicle number per 2 mm biopsy, and AMH level was seen between the 20 children with non-rare diseases and those with rare diseases. Conclusions The reports help practitioners counsel girls with rare diseases about fertility preservation. The demand for OTC in pediatrics will likely grow as a standard of care.
Prevalence of the SigB-Deficient Phenotype among Clinical Staphylococcus aureus Isolates Linked to Bovine Mastitis
2023-04-03

Phenotypic adaptation has been associated with persistent, therapy-resistant Staphylococcus aureus infections. Recently, we described within-host evolution towards a Sigma factor B (SigB)-deficient phenotype in a non-human host, a naturally infected dairy cow with chronic, persistent mastitis. However, to our knowledge, the prevalence of SigB deficiency among clinical S. aureus isolates remains unknown. In this study, we screened a collection of bovine mastitis isolates for phenotypic traits typical for SigB deficiency: decreased carotenoid pigmentation, increased proteolysis, secretion of α-hemolysin and exoproteins. Overall, 8 out of 77 (10.4%) isolates of our bovine mastitis collection exhibited the SigB-deficient phenotype. These isolates were assigned to various clonal complexes (CC8, CC9, CC97, CC151, CC3666). We further demonstrated a strong positive correlation between asp23-expression (a marker of SigB activity) and carotenoid pigmentation (r = 0.6359, p = 0.0008), underlining the role of pigmentation as a valuable predictor of the functional status of SigB. Sequencing of the sigB operon (mazEF-rsbUVW-sigB) indicated the phosphatase domain of the RsbU protein as a primary target of mutations leading to SigB deficiency. Indeed, by exchanging single nucleotides in rsbU, we could either induce SigB deficiency or restore the SigB phenotype, demonstrating the pivotal role of RsbU for SigB functionality. The data presented highlight the clinical relevance of SigB deficiency, and future studies are needed to exploit its role in staphylococcal infections.
Data from Spontaneous Peripheral T-cell Responses toward the Tumor-Associated Antigen Cyclin D1 in Patients with Clear Cell Renal Cell Carcinoma
2023-04-03

&lt;div&gt;Abstract&lt;p&gt;Renal cell carcinoma (RCC) is a heterogeneous group of kidney cancers with clear cell RCC (ccRCC) as the major subgroup. To expand the number of clinically relevant tumor-associated antigens (TAA) that can be targeted by immunotherapy, we analyzed samples from 23 patients with primary ccRCC for the expression and immunogenicity of various TAAs. We found high-frequency expression of &lt;i&gt;MAGE-A9&lt;/i&gt; and &lt;i&gt;NY-ESO-1&lt;/i&gt; in 36% and 55% of samples, respectively, and overexpression of &lt;i&gt;PRAME&lt;/i&gt;, &lt;i&gt;RAGE-1&lt;/i&gt;, &lt;i&gt;CA-IX&lt;/i&gt;, &lt;i&gt;Cyclin D1&lt;/i&gt;, &lt;i&gt;ADFP&lt;/i&gt;, &lt;i&gt;C-MET&lt;/i&gt;, and &lt;i&gt;RGS-5&lt;/i&gt; in many of the tumor samples. We analyzed the blood of patients with HLA-A2&lt;sup&gt;+&lt;/sup&gt; ccRCC for the presence of CD8&lt;sup&gt;+&lt;/sup&gt; T cells specific for TAA-derived HLA-A2–restricted peptides and found spontaneous responses to cyclin D1 in 5 of 6 patients with &lt;i&gt;Cyclin D1&lt;/i&gt;–positive tumors. Cyclin D1–specific CD8&lt;sup&gt;+&lt;/sup&gt; T cells secreted TNF-α, IFN-γ, and interleukin-2 (IL-2), and degranulated, indicating the presence of polyfunctional tumor-specific CD8&lt;sup&gt;+&lt;/sup&gt; T cells in the blood of these patients with ccRCC. The high frequency (43%) of &lt;i&gt;Cyclin D1&lt;/i&gt; overexpression and the presence of functional cyclin D1–specific T cells in 83% of these patients with ccRCC suggest that cyclin D1 may be a target for immunotherapeutic strategies. &lt;i&gt;Cancer Immunol Res; 1(5); 288–95. ©2013 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Data from Preexisting and Post–COVID-19 Immune Responses to SARS-CoV-2 in Patients with Cancer
2023-04-03

&lt;div&gt;Abstract&lt;p&gt;Patients with cancer, in particular patients with hematologic malignancies, are at increased risk for critical illness upon COVID-19. We here assessed antibody as well as CD4&lt;sup&gt;+&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt; T-cell responses in unexposed and SARS-CoV-2–infected patients with cancer to characterize SARS-CoV-2 immunity and to identify immunologic parameters contributing to COVID-19 outcome. Unexposed patients with hematologic malignancies presented with reduced prevalence of preexisting SARS-CoV-2 cross-reactive CD4&lt;sup&gt;+&lt;/sup&gt; T-cell responses and signs of T-cell exhaustion compared with patients with solid tumors and healthy volunteers. Whereas SARS-CoV-2 antibody responses did not differ between patients with COVID-19 and cancer and healthy volunteers, intensity, expandability, and diversity of SARS-CoV-2 T-cell responses were profoundly reduced in patients with cancer, and the latter associated with a severe course of COVID-19. This identifies impaired SARS-CoV-2 T-cell immunity as a potential determinant for dismal outcome of COVID-19 in patients with cancer.&lt;/p&gt;Significance:&lt;p&gt;This first comprehensive analysis of SARS-CoV-2 immune responses in patients with cancer reports on the potential implications of impaired SARS-CoV-2 T-cell responses for understanding pathophysiology and predicting severity of COVID-19, which in turn might allow for the development of therapeutic measures and vaccines for this vulnerable patient population.&lt;/p&gt;&lt;p&gt;&lt;i&gt;See related commentary by Salomé and Horowitz, p. 1877&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;i&gt;This article is highlighted in the In This Issue feature, p. 1861&lt;/i&gt;&lt;/p&gt;&lt;/div&gt;
The Economics of the Global Minimum Tax1
2023-04-03

Abstract This paper shows that the OECD inclusive framework of Pillar Two fails to implement the claimed 15% minimum corporate tax for subsidiaries of multinational corporations. The reason is that the Substance-based Income Exclusion of Pillar Two allows to tax-deduct payroll costs and user costs of intangible assets twice from the tax base of the top-up tax. Employing a standard multinational firm model, we show that Pillar Two dampens tax motivated transfer pricing, but changes the employment, investment and import incentives. For a sufficiently large cost share of labor and/or capital, the Substance-based Income Exclusion is equivalent to a production subsidy. Keywords: Corporate taxation, BEPS, Pillar~Two, minimum tax. JEL Classification: F23, F55, H25, H73.
LIGHT-SABRE Hyperpolarizes 1-13C-Pyruvate Continuously without Magnetic Field Cycling
2023-04-04

Nuclear spin hyperpolarization enables real-time observation of metabolism and intermolecular interactions <i>in vivo</i>. 1-<sup>13</sup>C-pyruvate is the leading hyperpolarized tracer currently under evaluation in several clinical trials as a promising molecular imaging agent. Still, the quest for a simple, fast, and efficient hyperpolarization technique is ongoing. Here, we describe that continuous, weak irradiation in the audio-frequency range of the <sup>13</sup>C spin at the 121 μT magnetic field (approximately twice Earth's field) enables spin order transfer from parahydrogen to <sup>13</sup>C magnetization of 1-<sup>13</sup>C-pyruvate. These so-called LIGHT-SABRE pulses couple nuclear spin states of parahydrogen and pyruvate via the <i>J</i>-coupling network of reversibly exchanging Ir-complexes. Using ∼100% parahydrogen at ambient pressure, we polarized 51 mM 1-<sup>13</sup>C-pyruvate in the presence of 5.1 mM Ir-complex continuously and repeatedly to a polarization of 1.1% averaged over free and catalyst-bound pyruvate. The experiments were conducted at -8 °C, where almost exclusively bound pyruvate was observed, corresponding to an estimated 11% polarization on bound pyruvate. The obtained hyperpolarization levels closely match those obtained via SABRE-SHEATH under otherwise identical conditions. The creation of three different types of spin orders was observed: transverse <sup>13</sup>C magnetization along the applied magnetic field, <sup>13</sup>C <i>z</i>-magnetization along the main field <i>B</i> <sub>0</sub>, and <sup>13</sup>C-<sup>1</sup>H <i>zz</i>-spin order. With a superconducting quantum interference device (SQUID) for detection, we found that the generated spin orders result from <sup>1</sup>H-<sup>13</sup>C <i>J</i>-coupling interactions, which are not visible even with our narrow linewidth below 0.3 Hz and at -8 °C.
The transformation of theology in the present climate crisis
2023-04-04

Humanity is facing an ecological catastrophe. Culprits include a linear understanding of time which looks only to the future and the human belief in progress. This ideology has remained the same in the search for solutions; technological progress must provide the answer. However, the article argued that a green transformation is needed. Ecological justice is required. Not only the rights of humans but also of nature, the earth and animals should be respected. Ecological justice and social justice are connected. This pertains to the rights of future generations to achieve a green transformation of urban life (Moltmann 2019:87).The article proposed three changes. Firstly, nature should no longer be seen and treated by humans as an object to be exploited but instead as a fellow subject in the green creation community. Secondly, humanity should be seen as embedded in this community of creation. Thirdly, a new cosmic spirituality with a deep respect for life and everything that lives is needed.Contribution: This article exposed and overturned the much taken-for-granted paradigm of progress towards the future that currently dominates humanity. It illustrated the consequences of this way of thinking. It proposed a radically different yet simple, spiritual and highly respectful alternative view of creation.