Pembrolizumab and chemotherapy in high-risk, early-stage, ER/HER2 breast cancer: a randomized phase 3 trial.

Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.

Botulinum neurotoxins exploit host digestive proteases to boost their oral toxicity via activating OrfXs/P47.

Botulinum neurotoxins (BoNTs) rank among the most potent toxins and many of them are produced by bacteria carrying the orfX gene cluster that also encodes four nontoxic proteins (OrfX1, OrfX2, OrfX3 and P47). The orfX gene cluster is also found in the genomes of many non-BoNT-producing bacteria, often alongside genes encoding oral insecticidal toxins. However, the functions of these OrfXs and P47 remain elusive.

MRI features that predict progression of residual disease after ablation of extra-abdominal desmoid fibromatosis.

Objective: To identify MRI features of desmoid tumors (DTs) that predict the growth of residual disease following ablation.

Methods: Patients who underwent MRI-guided ablation for DTs between February 2013 and April 2021 were included in this single-center IRB-approved retrospective study. MRI scans assessed three suspicious tissue features: intermediate T2 signal [+iT2], nodular appearance [+NOD], and contrast enhancement [+ENH].

Effect of management system and pedoclimatic factors on Fusarium and Didymella communities associated with pea (Pisum sativum) roots in Germany.

From 2016 to 2019, 128 organic and conventional spring and winter pea fields in Germany were surveyed to determine the effects of cropping history and pedo-climatic conditions on pea root health, the diversity of Fusarium and Didymella communities and their collective effect on pea yield. Roots generally appeared healthy or showed minor disease symptoms despite the frequent occurrence of 4 Didymella and 14 Fusarium species. Soil pH interacted with the occurrence of the Fusarium oxysporum species complex (FOSC) and F.

Exposure of insects to current use pesticide residues in soil and vegetation along spatial and temporal distribution in agricultural sites.

Current use pesticides (CUPs) are recognised as the largest deliberate input of bioactive substances into terrestrial ecosystems and one of the main factors responsible for the current decline in insects in agricultural areas. To quantify seasonal insect exposure in the landscape at a regional scale (Rhineland-Palatine in Germany), we analysed the presence of multiple (93) active ingredients in CUPs across three different agricultural cultivation types (with each three fields: arable, vegetable, viticulture) and neighbouring meadows. We collected monthly soil and vegetation samples over a year.

Streptokinase is dispensable in Streptococcus dysgalactiae subspecies equisimilis infections of human dendritic cells.

In recent years, increased numbers of severe Streptococcus dysgalactiae subsp. equisimilis (SDSE) infections, including necrotizing soft tissue infections (NSTIs), have been reported. One of the main virulence factors of SDSE is streptokinase (Ska).

Insights from a century of data reveal global trends in ex situ living plant collections.

Ex situ living plant collections play a crucial role in providing nature-based solutions to twenty-first century global challenges. However, the complex dynamics of these artificial ecosystems are poorly quantified and understood, affecting biodiversity storage, conservation and utilization. To evaluate the management of ex situ plant diversity, we analysed a century of data comprising 2.

Improving ocean reanalyses of observationally sparse regions with transfer learning.

Oceanic subsurface observations are sparse and lead to large uncertainties in any model-based estimate. We investigate the applicability of transfer learning based neural networks to reconstruct North Atlantic temperatures in times with sparse observations. Our network is trained on a time period with abundant observations to learn realistic physical behavior.

The association of origin and environmental conditions with performance in professional IRONMAN triathletes.

We have (i) little knowledge about where the fastest professional IRONMAN triathletes originate from and where the fastest races take place and (ii) we have no knowledge of the optimal weather conditions for an IRONMAN triathlon. The aims of the present study were, therefore, (i) to investigate the origin and the fastest IRONMAN race courses for professional triathletes and (ii) to evaluate the best environmental conditions (i.e.

Non-invasive physical plasma improves conventional wound management of cut and bite wounds in wild European hedgehogs.

Non-invasive physical plasma (NIPP) has been used effectively for wound healing in human medicine for over two decades. The advantages are that NIPP has few side effects, is painless and gentle on the tissue. The therapeutic effect is mediated by reactive oxygen species (ROS).

Comprehensive evaluation of pure and hybrid collaborative filtering in drug repurposing.

Drug development is known to be a costly and time-consuming process, which is prone to high failure rates. Drug repurposing allows drug discovery by reusing already approved compounds. The outcomes of past clinical trials can be used to predict novel drug-disease associations by leveraging drug- and disease-related similarities.

Dengue dynamics, predictions, and future increase under changing monsoon climate in India.

The global burden of dengue disease is escalating under the influence of climate change, with India contributing a third of the total. The non-linearity and regional heterogeneity inherent in the climate-dengue relationship and the lack of consistent data makes it difficult to make useful predictions for effective disease prevention. The current study investigates these non-linear climate-dengue links in Pune, a dengue hotspot region in India with a monsoonal climate and presents a model framework for predicting both the near-term and future dengue mortalities.

Distribution of the four type VI secretion systems in Pseudomonas aeruginosa and classification of their core and accessory effectors.

Bacterial type VI secretion systems (T6SSs) are puncturing molecular machines that transport effector proteins to kill microbes, manipulate eukaryotic cells, or facilitate nutrient uptake. How and why T6SS machines and effectors differ within a species is not fully understood. Here, we applied molecular population genetics to the T6SSs in a global population of the opportunistic pathogen Pseudomonas aeruginosa.

Declining precipitation frequency may drive earlier leaf senescence by intensifying drought stress and enhancing drought acclimation.

Precipitation is an important factor influencing the date of foliar senescence, which in turn affects carbon uptake of terrestrial ecosystems. However, the temporal patterns of precipitation frequency and its impact on foliar senescence date remain largely unknown. Using both long-term carbon flux data and satellite observations across the Northern Hemisphere, we show that, after excluding impacts from of temperature, radiation and total precipitation by partial correlation analysis, declining precipitation frequency may drive earlier foliar senescence date from 1982 to 2022.

TRAF2 and RIPK1 redundantly mediate classical NFκB signaling by TNFR1 and CD95-type death receptors.

This study suggests a modified model of TNFR1-induced complex I-mediated NFκB signaling. Evaluation of a panel of five tumor cell lines (HCT116-PIK3CAmut, SK-MEL-23, HeLa-RIPK3, HT29, D10) with TRAF2 knockout revealed in two cell lines (HT29, HeLa-RIPK3) a sensitizing effect for death receptor-induced necroptosis and in one cell line (D10) a mild sensitization for TNFR1-induced apoptosis. TRAF2 deficiency inhibited death receptor-induced classical NFκB-mediated production of IL-8 only in a subset of cell lines and only partly.

Effect-based analysis of endocrine effects in surface and ground water with focus on progestagenicity using Arxula yeast-based reporter gene assays.

The use of effect-based methods in water monitoring for identifying risks to aquatic organisms and human health is important for aiding regulatory decisions. In the past decades, the database on monitoring, especially in surface waters, has grown as this aquatic environment is openly exposed to various contamination sources. With regard to endocrine disruption, estrogenic and androgenic effects have been primarily investigated.

Selenium-Substitution Strategy for Enhanced Mobility, Tunable Bandgap, and Improved Electrochemical Energy Storage in Semiconducting Conjugated Coordination Polymers.

Conjugated coordination polymers (c-CPs), a novel class of organic-inorganic hybrid materials, are distinguished by their unique structural characteristics and exceptional charge transport properties. The electronic properties of these materials are critically determined by the constituting coordination atoms, with electron-rich selenol ligands emerging as promising candidates for constructing high-mobility semiconducting c-CPs. Currently, c-CPs incorporating selenium-substituted ligands remain scarce.

Creating codes of ethics for public health professionals and institutions.

Background: The World Health Organization and the Association of Schools of Public Health in the European Region called for the professionalization of the public health workforce, including the creation of codes of ethics. In this article, the Public Health Ethics and Law Network provides guidance on creating such codes, based on values and principles commonly identified for public health.

Methods: Our interest was in codes addressing public health broadly rather than disciplines within public health.

Wear investigation of implant-supported upper removable prothesis with electroplated gold or PEKK secondary crowns.

Objectives: The aim of the present study was to investigate, whether polyetherketoneketone (PEKK) secondary crowns could be considered as alternative to gold standard in terms of their physical properties and manufacturing costs.

Methods: An upper jaw model with six implants was used. Frameworks with either 6 PEKK- or 6 electroplated secondary crowns were cemented in a wear simulator.

Leveraging computational modeling to explore epithelial and endothelial cell monolayer mechanobiology.

Endothelial cells (ENCs) and epithelial cells (EPCs) form monolayers whose barrier function is critical for the maintenance of physiological processes and extremely sensitive to mechanical cues. Computational models have emerged as powerful tools to elucidate how mechanical cues impact the behavior of these monolayers in health and disease. Herein, the importance of mechanics in regulating ENC and EPC monolayer behavior is established, highlighting similarities and differences in various biological contexts.

The Co-IMPACT Consortium: Integrating Prostate-specific Membrane Antigen Positron Emission Tomography and Radiotherapy in Prostate Cancer Care.

The Co-IMPACT consortium addresses knowledge gaps in prostate-specific membrane antigen positron emission tomography-guided radiotherapy for prostate cancer by establishing a global database (46 centres from 16 countries) to standardise and analyse data across four distinguished clinical scenarios. A collaborative model with the Advanced Prostate Cancer Consensus Conference aligns urgent clinical needs with actionable research insights.