Notes

Unfolding Systems as well as Conformational Stability with the Dimeric Endophilin N-BAR Site.
Codeswitching experience modulated the LPC, but not the N400. The results suggest that early access to semantic memory during comprehension happens independent of the language in which the words are presented. Codeswitching affects a separate stage of comprehension with switching experience modulating the brain's response to experiencing a language switch.
Age is the most significant risk factor for ovarian cancer (OvCa), the deadliest gynecologic malignancy. Metastasizing OvCa cells adhere to the omentum, a peritoneal structure rich in collagen, adipocytes, and immune cells. Ultrastructural changes in the omentum and the omental collagen matrix with aging have not been evaluated.

The aim of this study was to test the hypothesis that age-related changes in collagen in the ovarian tumor microenvironment promote OvCa metastatic success in the aged host.

Young (3-6 months) and aged mice (20-23 months) were used to study the role of aging in metastatic success. Intra-peritoneal (IP) injection of ID8

ovarian cancer cells showed enhanced IP dissemination in aged
young mice. SP-2577 inhibitor
assays using purified collagen demonstrated reduced collagenolysis of aged fibers, as visualized using scanning electron microscopy (SEM) and quantified with a hydroxyproline release assay. Omental tumors in young and aged mice showed similar collagen deposition; however enhanced static success in the aged host.
Our results demonstrate that tumors in an aged host can grow with minimal collagen remodeling, while tumors in the young host must remodel peri-tumoral collagen to enable effective proliferation, providing a mechanism whereby age-induced ultrastructural changes in collagen and collagen-rich omenta establish a permissive pre-metastatic niche contributing to enhanced OvCa metastatic success in the aged host.
The intersection of cancer and aging is an emerging public health challenge in developed countries because of the aging and expansion of the population.

We convened a panel of experts to share their insights on this topic at the inaugural University of Florida Health Cancer Center's (UFHCC's) Cancer and Aging Symposium, which was held virtually in February 2022.

We featured presentations from four leading scientists, whose research spans multiple disciplines including basic science, translational research, geriatric oncology, and population science.

Each speaker offered their unique perspective and insight on the intersection between cancer and aging and discussed their current and ongoing research in this field. In addition to this panel of experts, scientists from the National Institutes of Health and the National Cancer Institute, as well as a UFHCC-affiliated citizen scientist, shared their perspectives on strategies to move the field forward. Some of the key open questions and opportunities for future research offered by these presenters in aging and cancer include but are not limited to infusing health disparities research into the field of cancer and aging, assessing the value of geriatric assessment in identifying early vulnerabilities that may affect response to emerging cancer therapies in older patients, and assessing biological age and other biomarkers (e.g., clonal hematopoiesis) in relation to clinical endpoints and the development of primary, secondary, and tertiary cancer prevention interventions.

Research is needed to accelerate knowledge regarding the dynamic interplay of cancer and aging and optimize care in diverse older adults to achieve equity in cancer outcomes.
Research is needed to accelerate knowledge regarding the dynamic interplay of cancer and aging and optimize care in diverse older adults to achieve equity in cancer outcomes.Inhibiting the biological activity of SARS-CoV-2 Mpro can prevent viral replication. In this context, a hybrid approach using knowledge- and physics-based methods was proposed to characterize potential inhibitors for SARS-CoV-2 Mpro. Initially, supervised machine learning (ML) models were trained to predict a ligand-binding affinity of ca. 2 million compounds with the correlation on a test set of R = 0.748 ± 0.044 . Atomistic simulations were then used to refine the outcome of the ML model. Using LIE/FEP calculations, nine compounds from the top 100 ML inhibitors were suggested to bind well to the protease with the domination of van der Waals interactions. Furthermore, the binding affinity of these compounds is also higher than that of nirmatrelvir, which was recently approved by the US FDA to treat COVID-19. In addition, the ligands altered the catalytic triad Cys145 - His41 - Asp187, possibly disturbing the biological activity of SARS-CoV-2.Malnutrition is an often-overlooked challenge for patients with cancer. It is associated with muscle mass reduction, poor compliance and response to cancer treatments, decreased quality of life, and reduced survival time. The nutritional assessment and intervention should be a vital part of any comprehensive cancer treatment plan. However, data on artificial nutrition supplied based on caloric needs during cancer care are scarce. In this review, we discuss the recommendations of the European and American societies for clinical nutrition on the use of nutritional interventions in malnourished patients with cancer in the context of current clinical practice. In particular, when enteral nutrition (oral or tube feeding) is not feasible or fails to meet the complete nutritional needs, supplemental parenteral nutrition (SPN) can bridge the gap. We report the available evidence on SPN in cancer patients and identify the perceived barriers to the wider application of this intervention. Finally, we suggest a 'permissive' role of SPN in cancer care but highlight the need for rigorous clinical studies to further evaluate the use of SPN in different populations of cancer patients.Point mutations of the fibroblast growth factor receptor (FGFR)2 receptor in intrahepatic cholangiocarcinoma (iCC) are mainly of unknown functional significance compared to FGFR2 fusions. Pemigatinib, a tyrosine kinase inhibitor, is approved for the treatment of cholangiocarcinoma with FGFR2 fusion/rearrangement. Although it is hypothesized that FGFR2 mutations may cause uncontrolled activation of the signaling pathway, the data for targeted therapies for FGFR2 mutations remain unclear. In vitro analyses demonstrated the importance of the p.C382R mutation for ligand-independent constitutive activation of FGFR2 with transforming potential. The following report describes the clinical case of a patient diagnosed with an iCC carrying a FGFR2 p.C382R point mutation which was detected in liquid, as well as in tissue-based biopsies. The patient was treated with pemigatinib, resulting in a sustained complete functional remission in fluorodeoxyglucose-positron emission tomography/computed tomography over 10 months to date. The reported case is the first description of a complete functional remission under the treatment with pemigatinib in a patient with p.C383R mutation.
The circulating tumor DNA (ctDNA) diagnostic accuracy for detecting phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (
) mutations in breast cancer (BC) is under discussion. We aimed to compare plasma and tissue
alterations, encompassing factors that could affect the results.

Two reviewers selected studies from different databases until December 2020. We considered BC patients with matched tumor tissue and plasma ctDNA. We performed meta-regression and subgroup analyses to explore sources of heterogeneity concerning tumor burden, diagnostic technique, sample size, sampling time, biological subtype, and hotspot mutation. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the related area under the curve (AUC) were elaborated for the overall population and each subgroup.

The pooled analysis was carried out on 25 cohorts for a total of 1966 patients. The overall ctDNA sensitivity and specificity were esenting the preferable strategy at diagnosis of metastatic BC in patients who present with visceral involvement and at least two metastatic lesions, primarily given low clinical compliance or inaccessible metastatic sites.
These findings reliably estimate the high ctDNA accuracy for the detection of PIK3CA mutations. A ctDNA-first approach for the assessment of PIK3CA mutational status by NGS may accurately replace tissue tumor sampling, representing the preferable strategy at diagnosis of metastatic BC in patients who present with visceral involvement and at least two metastatic lesions, primarily given low clinical compliance or inaccessible metastatic sites.Many studies have illustrated the close relationship between anxiety disorders and attentional functioning, but the relationship between trait anxiety and attentional bias remains controversial. This study examines the effect of trait anxiety on the time course of attention to emotional stimuli using materials from the International Affective Picture System. Participants with high vs. low trait anxiety (HTA vs. LTA) viewed four categories of pictures simultaneously dysphoric, threatening, positive, and neutral. Their eye-movements for each emotional stimulus were recorded for static and dynamic analysis. Data were analyzed using a mixed linear model and growth curve analysis. Specifically, the HTA group showed a greater tendency to avoid threatening stimuli and more pupil diameter variation in the early period of stimulus presentation (0-7.9 s). The HTA group also showed a stronger attentional bias toward positive and dysphoric stimuli in the middle and late period of stimulus presentation (7.9-30 s). These results suggest that trait anxiety has a significant temporal effect on attention to emotional stimuli, and that this effect mainly manifests after 7 s. In finding stronger attentional avoidance of threatening stimuli and more changes in neural activity, as well as a stronger attentional bias toward positive stimuli, this study provides novel insights on the relationship between trait anxiety and selective attention.Brain tumor segmentation in multimodal MRI volumes is of great significance to disease diagnosis, treatment planning, survival prediction and other relevant tasks. However, most existing brain tumor segmentation methods fail to make sufficient use of multimodal information. The most common way is to simply stack the original multimodal images or their low-level features as the model input, and many methods treat each modality data with equal importance to a given segmentation target. In this paper, we introduce multimodal image fusion technique including both pixel-level fusion and feature-level fusion for brain tumor segmentation, aiming to achieve more sufficient and finer utilization of multimodal information. At the pixel level, we present a convolutional network named PIF-Net for 3D MR image fusion to enrich the input modalities of the segmentation model. The fused modalities can strengthen the association among different types of pathological information captured by multiple source modalities, leading to a modality enhancement effect. At the feature level, we design an attention-based modality selection feature fusion (MSFF) module for multimodal feature refinement to address the difference among multiple modalities for a given segmentation target. A two-stage brain tumor segmentation framework is accordingly proposed based on the above components and the popular V-Net model. Experiments are conducted on the BraTS 2019 and BraTS 2020 benchmarks. The results demonstrate that the proposed components on both pixel-level and feature-level fusion can effectively improve the segmentation accuracy of brain tumors.
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