Search Results (20)

Objective: High-resolution computed tomography (HRCT) may lack sensitivity for the early detection of interstitial lung disease associated with systemic sclerosis (SSc-ILD). Lung ultrasound is an emerging technique for the diagnosis of SSc-ILD. This cross-sectional study aimed to describe the prevalence of ultrasound interstitial syndrome in SSc patients with normal HRCT and pulmonary function tests (PFT). Methods: Thirty SSc patients with normal HRCT, FVC > 80% predicted and DLCO > 70% predicted were included. Echocardiography and PFT including impulse oscillometry and cardiopulmonary exercise testing were performed. Lung ultrasound was analyzed by two blinded operators. Patients were classified into two groups, according to the presence or absence of ultrasound interstitial syndrome, defined as the sum of B-lines in all thoracic areas ≥10 and/or pleural line thickness >3 mm on at least one thoracic area and/or a pleural line irregularity score >16%. Results: Ultrasound interstitial syndrome was present in 12 patients (40%). Inter-reader agreement for the diagnosis of ultrasound interstitial syndrome defined by the Kappa coefficient was 0.93 (95%CI 0.79–1.00). Patients with ultrasound interstitial syndrome were younger (37 years vs. 53 years, p = 0.009), more often had pitting scars (n = 7/12 vs. 3/18, p = 0.045) and had lower FVC (102 vs. 110% pred, p = 0.009), TLC (114 vs. 122% pred, p = 0.042) and low-frequency respiratory system reactance (Xrs5 Z-score 0.16 vs. 1.02, p = 0.018), while pulmonary gas exchange was similar. Conclusions: Ultrasound interstitial syndrome was detected in 12/30 SSc patients with normal HRCT and PFT. Patients with ultrasound interstitial syndrome had differences in lung function consistent with reduced respiratory compliance, suggesting minimal and/or early suspected SSc-ILD. Full article

Respiratory viruses are the causative agents responsible for seasonal epidemics and occasional pandemic outbreaks and are a leading cause of death worldwide. Type I interferon (IFNα/β) signaling in the lung epithelial cells plays a major role in the innate immunity to respiratory viruses. Gene signatures are a set of differentially expressed genes in a particular disease or condition and are used to diagnose, monitor, and predict disease progression. These signatures can be used to identify regulatory modules and gene regulatory networks (GRNs) in mammalian signal transduction pathways. Considerable progress has been made in the identification of type I interferon-regulated gene signatures in the host response to respiratory viruses, including antiviral, immunomodulatory, apoptosis, and transcription factor signatures. Respiratory virus infections and host defenses require a dramatic change in the metabolic flux of macromolecules involved in nucleotide, lipid, and protein metabolism. The profiling of IFN-stimulated metabolic genes induced in the host response to several respiratory viruses led to the identification of a common gene signature in human lung epithelial cells and in the lungs of mouse models of respiratory virus infection. The regulation of the metabolic gene signature was correlated with the induction of IFN-beta (IFN-β) and IFN-inducible transcription factors at the RNA level in lung epithelial cells. Furthermore, the gene signature was also detected in response to bacterial lipopolysaccharide-induced acute lung injury. A protein interaction network analysis revealed that metabolic enzymes interact with IFN-regulated transcription factors and members of the unfolded protein response (UPR) to form a module and potentially regulate type I interferon signaling, constituting a feedback loop. In addition, components of the metabolic gene expression signature were differentially regulated in the lung tissues of COVID-19 patients compared with healthy controls. These results suggest that the metabolic gene signature is a potential therapeutic target for the treatment of respiratory virus infections and inflammatory diseases. Full article

Very rich scholarly works have been produced to perform a comparative study between Emerson and Zhuang Zi. Many scholars in their comparative research have tried to find how Emerson and the transcendentalists such as Thoreau borrow ideas from Daoism. In this article, I will take a different approach. I aim to find how Emerson and Zhuang Zi’s pursuit of spirituality in nature shapes different types of sense of place. The concept of spirituality is related to the pursuit of meaning in life and self-transcendence. This concept has gradually gained attention from the branches of religion, philosophy, geography, and psychology since, currently, due to the fast urbanization process, more people are separated from their land and move into cities. I will make a comparison between Emerson and Zhuang Zi from the concepts of spirituality, nature, and place. This perspective will shed light on the question of the conservation of various places due to their value and meaning, although I will not discuss conservation issues in this paper. In this article, I will first give a brief introduction to the meaning of spirituality by focusing on the three dimensions of this concept, which include meaning, self-transcendence, and spiritual practices. Then, I will discuss how the concept of nature in Emerson and Zhuang Zi’s works is related to these three dimensions. Finally, I will examine why Emerson and Zhuang Zi treat wilderness and agricultural land, respectively, as a place. Full article

A fundamental question of the 21st century centers around the role and place of humans in their environment. Given the great acceleration of consumptive practices engaged in the 20th century, humans stand on the brink of a 6th extinction event. In order to determine our place and role in our global environment, we need to reflect on where we are and what the future will be—we need to focus on the habits of our “co-inhabitation” of the planet. Given the positive and negative impacts of international and global activities, intercultural dialogues are necessary for the care of the ecology of the planet, and one of the most prescient dialogues is between Eastern and Western world views. While much comparative research has been conducted regarding the connection between American Transcendentalism and Chinese ancient philosophy, relatively little philosophical work has been conducted to demonstrate the connectivity between Henry David Thoreau and Taoism. Yet there are, in fact, profound similarities between the American naturalist and Chinese philosophy, in particular Taoism. This paper aimed to discover and manifest the connection and similarities between the philosophy of Thoreau and the ancient worldview of Taoism. Through this comparative study and intercultural dialogue, we seek to trace historical precedents and intercultural dialogue between American Transcendentalism and ancient Chinese philosophy in order to explore the groundwork for a new vision of environmental awareness in order to promote a better future with a community of co-inhabitants and emphasis on the well-being of all. Full article

My central claim is that resonances between Transcendentalist and Chinese philosophies are so strong that the former cannot be adequately appreciated without the latter. I give attention to the Analects, the Mengzi and the Tiantai Lotus Sutra, which Transcendentalists read. Because there was conceptual sharing across Chinese traditions, plus evidence suggesting Transcendentalists explored other texts, my analysis includes discussions of Daoism and Weishi, Huayan and Chan Buddhism. To name just some similarities between the targeted outlooks, Transcendentalists adopt something close to wu-wei or effortless action; though hostile to hierarchy, they echo the Confucian stress on rituals or habits; Thoreau’s individualistic libertarianism is moderated by a radical causal holism found in many Chinese philosophies; and variants of Chinese Buddhism get close to Transcendentalist metaphysics and epistemologies, which anticipate radical embodied cognitive science. A specific argument is that Transcendentalists followed some of their Chinese counterparts by conserving the past and converting it into radicalism. A meta-argument is that ideas were exchanged via trade from Europe through North Africa to Western Asia and India into the Far East, and contact with Indigenous Americans led to the same. This involved degrees of misrepresentation, but it nonetheless calls upon scholars to adopt more global approaches. Full article

RGD peptides have received a lot of attention over the two last decades, in particular to improve tumor therapy through the targeting of the αVβ3 integrin receptor. This review focuses on the molecular design of multimeric RGD compounds, as well as the design of suitable linkers for drug delivery. Many examples of RGD–drug conjugates have been developed, and we show the importance of RGD constructs to enhance binding affinity to tumor cells, as well as their drug uptake. Further, we also highlight the use of RGD peptides as theranostic systems, promising tools offering dual modality, such as tumor diagnosis and therapy. In conclusion, we address the challenging issues, as well as ongoing and future development, in comparison with large molecules, such as monoclonal antibodies. Full article

Japanologists have identified the intellectual movement called Kokugaku (“national learning”) as early modern Japan’s version of nativism, even though it bears no resemblance to the original American version of nativism from the 1840s, namely Know-Nothingism. Instead, Kokugaku had striking intellectual and institutional similarities with pre-Civil War Transcendentalism. Americanists have associated Transcendentalism with the broader ideological phenomenon known as exceptionalism, rather than with nativism. For this reason, this article proposes to reclassify Kokugaku as exceptionalism, instead of nativism, via a comparison between it and Transcendentalism. The intellectual linchpin between Transcendentalism and exceptionalism is Fichte, whose ideas influenced Japan’s literary genre known as Nihonjinron (“theories of Japanese[-ness]”), the modern successor of Kokugaku, a connection that bolsters the intellectual legitimacy of the view that Kokugaku and Transcendentalism are analogous versions of exceptionalism. Full article

A project model is presented that weaves together ideas from earned value project management and systems dynamics. It is able to adjust to increasingly unhealthy actual project behaviors in ways that preserve the signature pattern of the staffing histograms observed in the real world and provide a tool for managers to correct projects that are not meeting the plan. Starting from the planned staffing histogram and the project performance baseline, the model captures the delay and cost of experience dilution, includes the unplanned-for effort that is revealed in the typical pattern of the Cost Performance Index, assesses progress using the actual cost to date and the earned value to date, and adjusts staffing, scope, or both, to complete the project on schedule. A new method of approximating work remaining, called project-to-date, is shown to track the planned staffing histogram better than the commonly used fraction-complete method. Full article

Many articles have shown the benefits of operant conditioning training techniques in the care and welfare of several species of nonhuman primates; however, the information regarding their use in strepsirrhine species is scarce. We assessed the development and current status of training programs with these species in North American institutions. An online survey was distributed through members of the Association of Zoos and Aquariums using a multiple-choice format. We collected information related to training program details; animals, behaviors, and techniques; the evaluation process; and the impact of training. Seventy-one organizations completed the survey, with the results showing that 97% of respondents trained their strepsirrhines with the main objective of husbandry and veterinary care (around 80%). Sixty-eight percent of organizations did not report any risk in training these species. The benefits reported include increases in positive human–animal interactions (97%), psychological well-being (88%), and staff awareness of animal behaviors (90%). However, a multi-dimensional approach to measure the efficacy of training could provide a deeper understanding of its impact on the welfare of strepsirrhine primates. We hope that the data offered in this survey can help in this future assessment. Full article

Cancer immunotherapy harnesses the immune system by targeting tumor cells that express antigens recognized by immune system cells, thus leading to tumor rejection. These tumor-associated antigens include tumor-specific shared antigens, differentiation antigens, protein products of mutated genes and rearrangements unique to tumor cells, overexpressed tissue-specific antigens, and exogenous viral proteins. However, the development of effective therapeutic approaches has proven difficult, mainly because these tumor antigens are shielded, and cells primarily express self-derived antigens. Despite innovative and notable advances in immunotherapy, challenges associated with variable patient response rates and efficacy on select tumors minimize the overall effectiveness of immunotherapy. Variations observed in response rates to immunotherapy are due to multiple factors, including adaptative resistance, competency, and a diversity of individual immune systems, including cancer stem cells in the tumor microenvironment, composition of the gut microbiota, and broad limitations of current immunotherapeutic approaches. New approaches are positioned to improve the immune response and increase the efficacy of immunotherapies, highlighting the challenges that the current global COVID-19 pandemic places on the present state of immunotherapy. Full article

Therapeutic targeting of stem cells needs to be strategically developed to control tumor growth and prevent metastatic burden successfully. Breast cancer presents a unique clinical problem because of the variety of cellular subtypes present, including cancer stem cells (CSCs). The development of 3D stem-like properties of human breast tumor spheroids in stem cell factor conditioned media was investigated in orthotopic xenografts for enhanced tumorgenicity in the athymic nude rat model. MCF-7, ZR-75-1, and MDA-MB-231 breast cancer cell lines were cultured in serum-free, stem cell factor-supplemented medium under non-adherent conditions and passaged to generate 3rd generation spheroids. The spheroids were co-cultured with fetal lung fibroblast (FLF) cells before orthotopic heterotransplantation into the mammary fat pads of athymic nude rats. Excised xenografts were assessed histologically by H&E staining and immunohistochemistry for breast cancer marker (ERB1), proliferation marker (Ki67), mitotic marker (pHH3), hypoxia marker (HIF-2α), CSC markers (CD47, CD44, CD24, and CD133), and vascularization markers (CD31, CD34). Breast cancer cells cultured in stem cell factor supplemented medium generated 3D spheroids exhibited increased stem-like characteristics. The 3D stem-like spheroids co-cultured with FLF as supporting stroma reproducibly and efficiently established orthotopic breast cancer xenografts in the athymic nude rat. Full article

The incidence of pulmonary embolism (PE) is high during severe Coronavirus Disease 2019 (COVID-19). We aimed to identify predictive and prognostic factors of PE in non-ICU hospitalized COVID-19 patients. In the retrospective multicenter observational CLOTVID cohort, we enrolled patients with confirmed RT-PCR COVID-19 who were hospitalized in a medicine ward and also underwent a CT pulmonary angiography for a PE suspicion. Baseline data, laboratory biomarkers, treatments, and outcomes were collected. Predictive and prognostics factors of PE were identified by using logistic multivariate and by Cox regression models, respectively. A total of 174 patients were enrolled, among whom 86 (median [IQR] age of 66 years [55–77]) had post-admission PE suspicion, with 30/86 (34.9%) PE being confirmed. PE occurrence was independently associated with the lack of long-term anticoagulation or thromboprophylaxis (OR [95%CI], 72.3 [3.6–4384.8]) D-dimers ≥ 2000 ng/mL (26.3 [4.1–537.8]) and neutrophils ≥ 7.0 G/L (5.8 [1.4–29.5]). The presence of these two biomarkers was associated with a higher risk of PE (p = 0.0002) and death or ICU transfer (HR [95%CI], 12.9 [2.5–67.8], p < 0.01). In hospitalized non-ICU severe COVID-19 patients with clinical PE suspicion, the lack of anticoagulation, D-dimers ≥ 2000 ng/mL, neutrophils ≥ 7.0 G/L, and these two biomarkers combined might be useful predictive markers of PE and prognosis, respectively. Full article

Anomalies in constitutive calcium entry (CCE) have been commonly attributed to cell dysfunction in pathological conditions such as cancer. Calcium influxes of this type rely on channels, such as transient receptor potential (TRP) channels, to be constitutively opened and strongly depend on membrane potential and a calcium driving force. We developed an optogenetic approach based on the expression of the halorhodopsin chloride pump to study CCE in non-excitable cells. Using C2C12 cells, we found that halorhodopsin can be used to achieve a finely tuned control of membrane polarization. Escalating the membrane polarization by incremental changes in light led to a concomitant increase in CCE through transient receptor potential vanilloid 2 (TRPV2) channels. Moreover, light-induced calcium entry through TRPV2 channels promoted cell migration. Our study shows for the first time that by modulating CCE and related physiological responses, such as cell motility, halorhodopsin serves as a potentially powerful tool that could open new avenues for the study of CCE and associated cellular behaviors. Full article

This essay explores a philosophical tradition that Stanley Cavell has traced out and which he emphasizes as being American inasmuch as it is arises out of the thinking of Ralph Waldo Emerson and Henry David Thoreau. It then investigates how the poems of the avant-garde poet Michael Palmer link with, overlap with, this strain of American philosophy in terms of how it enacts an understanding of what we might call “philosophical mood,” on outlook based on the navigation of representation, generative self-consciousness, and doubt that amounts to a form of epistemology. The essay does not trace the influence—direct or otherwise of Cavell and his arguments for philosophy on the poems, despite a biographical connection between Cavell and Palmer, his former student. Instead it brings out the way that one might fruitfully locate Palmer’s work within an American literary/philosophical continuum. The article shows how that context opens up the work to a range of important existential and ethical implications. I endeavor to show that Notes for Echo Lake, Palmer’s most important collection, locates itself, its language, within such a frame so as to provide a place for readerly encounters with the limitations of language. These encounters then are presented as an opportunity for a deeper understanding of subjectivity and for attuning oneself to the role that active reading and interpretation might play in moral perfectionism. Full article

For both Emerson and Thoreau, ocular attentiveness was a crucial means of at least disposing the soul toward experiencing moments of otherwise unpredictable, ecstatic encounter with the divine soul of Nature. But the eye alone was not the sole sensory pathway toward receiving such revelations. Especially in later writing, Thoreau focused special attention on eating and drinking as key bodily—yet also spiritual—modes of experiencing communion with the earth. He applied this sacramental understanding to the several processes of obtaining, preparing, and consuming food, but above all to the thankful appreciation of locally gathered, wild fruits and nuts. Such gifts, freely given, presumably invite “us to picnic with Nature,” thereby dramatizing how “man at length stands in such a relation to Nature as the animals which pluck and eat as they go.” Though Emerson never embraced a comparably sacramental vision of Nature, or showed the same interest in gustatory encounter with wildness, one might interpret his attraction toward other diverse and often spiritualized concepts of communion as a compensatory outcome of his ministerial decision in 1832 to cease administering the Christian church’s sacrament of the Lord’s Supper. Full article