What is to Come?

It’s about life after the pandemic, especially as college students. We have been working so hard to graduate and succeed in life and now we wonder if that is even still and option.https://digitalcommons.csumb.edu/hcom434_spring2021/1043/thumbnail.jp

Lockdown

The feelings experienced throughout the lockdown. The pessimistic side of the pandemic, and hitting rock bottom during the lockdown. I felt it was necessary to show that there were some hard feelings and dark thoughts experienced throughout this time and nobody should feel like they were alone in having these sort of feelings.https://digitalcommons.csumb.edu/hcom434_spring2021/1044/thumbnail.jp

In-depth project: The Nature of Now and the Future

Brushfire Living in the Central Valley, I have become very familiar with hearing about fires. We get very little rain and everything is very dry surrounding the valley, making it very for the land to be set ablaze. I wanted to share a piece that sort of described the setting of how a fire around here starts and the lifespan of the fire. A Future Without People I wanted to write about the earth long into the future when humans have died off and it is just animals left to roam the world. I feel like there are so many ways to look at the future since no one can truly predict what\u27s going to happen, I wanted to write about just one of the infinite possibilities of the future.https://digitalcommons.csumb.edu/hcom434_spring2021/1045/thumbnail.jp

Gender-specific aspects of epidemiology, molecular genetics and outcome: lung cancer.

Lung cancer remains the leading cause of cancer-related deaths worldwide in women and men. In incidence, lung cancer ranks second, surpassed by breast cancer in women and prostate cancer in men. However, the historical differences in mortality and incidence rate between both sexes have changed in the last years. In the last decades, we have also witnessed an increased number of lung cancer in female never-smokers. These disparities have grown our interest in studying the impact of the gender and sex in the presentation of lung cancer. The aetiology is yet to be fully elucidated, but the data are clear so far: there is a growing divide between lung cancer presentation in women and men that will change our management and study of lung cancer. This article aims to review the sex and gender differences in lung cancer

Personalized Cytokine-Directed Therapy With Tocilizumab for Refractory Immune Checkpoint Inhibitor-Related Cholangiohepatitis.

For patients with corticosteroid (CS)-refractory immune checkpoint inhibitor-related cholangiohepatitis (irCH), no consensus exists regarding treatment, and outcomes remain poor. We evaluated the possibility of personalized treatment according to the patient's cytokine profile and the immunohistopathologic assessment of the predominant immune infiltrate type of liver tissue. NSCLCs with CS-refractory irCH were analyzed by immunohistochemistry of liver biopsy specimen, serum cytokine panel, and assessment of peripheral blood mononuclear cell immune cell monitoring by mass cytometry. A total of three consecutive patients with irCH were identified. We found a predominant T-cell infiltrate and an interferon-gamma or T helper 1 proinflammatory cytokine profile. Here, we report for the first time that a T-cell-targeted therapy with the interleukin (IL)-6 receptor-neutralizing antibody tocilizumab, which inhibits signaling downstream of interferon-gamma and several other Janus kinase-dependent cytokines, is an effective single cytokine-directed therapy for CS-refractory irCH. Three patients with severe, CS-refractory irCH who were treated with tocilizumab were found to have persistent clinical and biological remission. Dysregulation of the IL-6/T-cell axis may contribute to the pathogenesis of CS-refractory irCH. Our observations suggest that IL-6 blockade seems to have promise in the treatment of CS-refractory irCH. The results from our three patients need to be confirmed in a larger patient population

Testing a Model of Care for Patients on Immune Checkpoint Inhibitors Based on Electronic Patient-Reported Outcomes: Protocol for a Randomized Phase II Controlled Trial.

Management of severe symptomatic immune-related adverse events (IrAEs) related to immune checkpoint inhibitors (ICIs) can be facilitated by timely detection. As patients face a heterogeneous set of symptoms outside the clinical setting, remotely monitoring and assessing symptoms by using patient-reported outcomes (PROs) may result in shorter delays between symptom onset and clinician detection. We assess the effect of a model of care for remote patient monitoring and symptom management based on PRO data on the time to detection of symptomatic IrAEs from symptom onset. The secondary objectives are to assess its effects on the time between symptomatic IrAE detection and intervention, IrAE grade (severity), health-related quality of life, self-efficacy, and overall survival at 6 months. For this study, 198 patients with cancer receiving systemic treatment comprising ICIs exclusively will be recruited from 2 Swiss university hospitals. Patients are randomized (1:1) to a digital model of care (intervention) or usual care (control group). Patients are enrolled for 6 months, and they use an electronic app to complete weekly Functional Assessment of Cancer Therapy-General questionnaire and PROMIS (PROs Measurement Information System) Self-Efficacy to Manage Symptoms questionnaires. The intervention patient group completes a standard set of 37 items in a weekly PROs version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) questionnaire, and active symptoms are reassessed daily for the first 3 months by using a modified 24-hour recall period. Patients can add items from the full PRO-CTCAE item library to their questionnaire. Nurses call patients in the event of new or worsening symptoms and manage them by using a standardized triage algorithm based on the United Kingdom Oncology Nursing Society 24-hour triage tool. This algorithm provides guidance on deciding if patients should receive in-person care, if monitoring should be increased, or if self-management education should be reinforced. The Institut Suisse de Recherche Expérimentale sur le Cancer Foundation and Kaiku Health Ltd funded this study. Active recruitment began since November 2021 and is projected to conclude in November 2023. Trial results are expected to be published in the first quarter of 2024 and will be disseminated through publications submitted at international scientific conferences. This trial is among the first trials to use PRO data to directly influence routine care of patients treated with ICIs and addresses some limitations in previous studies. This trial collects a wider spectrum of self-reported symptom data daily. There are some methodological limitations brought by changes in evolving treatment standards for patients with cancer. This trial's results could entail further academic discussions on the challenges of diagnosing and managing symptoms associated with treatment remotely by providing further insights into the burden symptoms represent to patients and highlight the complexity of care procedures involved in managing symptomatic IrAEs. ClinicalTrials.gov NCT05530187; https://www.clinicaltrials.gov/study/NCT05530187. DERR1-10.2196/48386

Rectangular Coordination Polymer Nanoplates: Large-Scale, Rapid Synthesis and Their Application as a Fluorescent Sensing Platform for DNA Detection

In this paper, we report on the large-scale, rapid synthesis of uniform rectangular coordination polymer nanoplates (RCPNs) assembled from Cu(II) and 4,4′-bipyridine for the first time. We further demonstrate that such RCPNs can be used as a very effective fluorescent sensing platform for multiple DNA detection with a detection limit as low as 30 pM and a high selectivity down to single-base mismatch. The DNA detection is accomplished by the following two steps: (1) RCPN binds dye-labeled single-stranded DNA (ssDNA) probe, which brings dye and RCPN into close proximity, leading to fluorescence quenching; (2) Specific hybridization of the probe with its target generates a double-stranded DNA (dsDNA) which detaches from RCPN, leading to fluorescence recovery. It suggests that this sensing system can well discriminate complementary and mismatched DNA sequences. The exact mechanism of fluorescence quenching involved is elucidated experimentally and its use in a human blood serum system is also demonstrated successfully

Real-time visualization of heterotrimeric G protein Gq activation in living cells

Contains fulltext : 97296.pdf (publisher's version ) (Open Access)BACKGROUND: Gq is a heterotrimeric G protein that plays an important role in numerous physiological processes. To delineate the molecular mechanisms and kinetics of signalling through this protein, its activation should be measurable in single living cells. Recently, fluorescence resonance energy transfer (FRET) sensors have been developed for this purpose. RESULTS: In this paper, we describe the development of an improved FRET-based Gq activity sensor that consists of a yellow fluorescent protein (YFP)-tagged Ggamma2 subunit and a Galphaq subunit with an inserted monomeric Turquoise (mTurquoise), the best cyan fluorescent protein variant currently available. This sensor enabled us to determine, for the first time, the kon (2/s) of Gq activation. In addition, we found that the guanine nucleotide exchange factor p63RhoGEF has a profound effect on the number of Gq proteins that become active upon stimulation of endogenous histamine H1 receptors. The sensor was also used to measure ligand-independent activation of the histamine H1 receptor (H1R) upon addition of a hypotonic stimulus. CONCLUSIONS: Our observations reveal that the application of a truncated mTurquoise as donor and a YFP-tagged Ggamma2 as acceptor in FRET-based Gq activity sensors substantially improves their dynamic range. This optimization enables the real-time single cell quantification of Gq signalling dynamics, the influence of accessory proteins and allows future drug screening applications by virtue of its sensitivity

Think globally, measure locally: The MIREN standardized protocol for monitoring plant species distributions along elevation gradients

Climate change and other global change drivers threaten plant diversity in mountains worldwide. A widely documented response to such environmental modifications is for plant species to change their elevational ranges. Range shifts are often idiosyncratic and difficult to generalize, partly due to variation in sampling methods. There is thus a need for a standardized monitoring strategy that can be applied across mountain regions to assess distribution changes and community turnover of native and non-native plant species over space and time. Here, we present a conceptually intuitive and standardized protocol developed by the Mountain Invasion Research Network (MIREN) to systematically quantify global patterns of native and non-native species distributions along elevation gradients and shifts arising from interactive effects of climate change and human disturbance. Usually repeated every five years, surveys consist of 20 sample sites located at equal elevation increments along three replicate roads per sampling region. At each site, three plots extend from the side of a mountain road into surrounding natural vegetation. The protocol has been successfully used in 18 regions worldwide from 2007 to present. Analyses of one point in time already generated some salient results, and revealed region-specific elevational patterns of native plant species richness, but a globally consistent elevational decline in non-native species richness. Non-native plants were also more abundant directly adjacent to road edges, suggesting that disturbed roadsides serve as a vector for invasions into mountains. From the upcoming analyses of time series, even more exciting results can be expected, especially about range shifts. Implementing the protocol in more mountain regions globally would help to generate a more complete picture of how global change alters species distributions. This would inform conservation policy in mountain ecosystems, where some conservation policies remain poorly implemented