Miracle-dz/UniFAR-FTUs huggingface dataset:
Motivation for Longevity Across the Life Span: An Emerging Issue

Abstract Over the past decades, increases in life expectancy in most modern societies have raised questions about whether and to what extent individuals value possible extensions of their personal lifetime. In this vein, a new field of research emerged that investigates the determinants, concomitants, and consequences of longevity values and personal preferences for an extended lifetime across adulthood. Based on a review of available theoretical and empirical work, we identified 3 mindsets on the challenges and potentials of human longevity common in research as well as personal views: (a) an essentialist mindset that builds on ideal principles of an infinite life, aimed at conquering or significantly postponing a biologically determined aging process, (b) a medicalist mindset that appraises aging as being primarily based on quality of health, and (c) a stoicist mindset that associates longevity and lifetime extension with the experience of grace and meaning. In this regard, we submit that motivation for longevity and its behavioral consequences differ depending on what mindsets individuals adopt in a given developmental context. We suggest that mindsets of longevity motivation are embedded in personal belief systems (e.g., death acceptance) that may depend on health, and on context influences (e.g., culture). Mindsets of longevity motivation may be related to differences in health behavior and late-life preparation. We illustrate such ideas with an exploratory analysis from a cross-cultural data set. We discuss the possible implications of these mindsets of longevity motivation for the aging sciences, and with regard to individual ways of approaching old age.
Combination pembrolizumab plus chemotherapy: a new standard of care for patients with advanced non-small-cell lung cancer

Abstract Until recently, the treatment of patients with advanced non-small-cell lung cancer (NSCLC) whose tumors did not have a targetable genetic alteration was cytotoxic chemotherapy alone. This treatment provided only modest survival benefit. The introduction of immune checkpoint inhibitors targeting programmed cell death 1 protein (PD-1) signaling pathway in the treatment of patients with NSCLC has had significant effect on patient survival. Atezolizumab, nivolumab and pembrolizumab have been shown to be superior to chemotherapy in patients with recurrent NSCLC. Recently, pembrolizumab has been combined with chemotherapy in the front-line setting and has demonstrated an improvement in overall survival in NSCLC patients as compared to chemotherapy alone. In this review we will focus on the clinical trials that led to approval of combination pembrolizumab and chemotherapy as first-line treatment for patients with advanced NSCLC as well as discuss other combinations of immunotherapy and chemotherapy that have also been evaluated.
The Lived Experience of Global Public Health Practice

Abstract There is a dearth of research that aims to understand graduate students’ lived experience of global health practice. Difficulties, distress, and trauma occur before and after these students’ placement abroad, and they often increase when returning home. Moreover, few articles address the increased vulnerabilities faced by women, such as sexual violence and gender-based discrimination. We conducted a phenomenological study to understand the lived experience of Canadian and US women graduate students participating in global public health practice. Eight participants participated in 21 in-depth interviews, while 17 participants created 35 lived experience descriptions through a guided writing exercise. Our findings reveal participants’ underlying discomfort with privilege while conducting fieldwork abroad, as well as depressive feelings once they return home. According to participants, while their global health fieldwork challenged previous ways of thinking and being, limited spaces and avenues for openly sharing these processes contributed to mental health challenges. Participants reported that these interviews were their first opportunity to fully share their global health experiences. Based on our analysis of these shared experiences, we argue that academic institutions participating in global health should provide appropriate and accessible resources, adequate financial compensation, safe spaces for authentic conversations, and time for processing experiences throughout the research cycle and especially in the months and years following fieldwork.
An integrated prediction model of recurrence in endometrial endometrioid cancers

Objectives: Endometrial cancer incidence and mortality are rising in the US. Disease recurrence has been shown to have a significant impact on mortality. However, to date, there are no accurate and validated prediction models that would discriminate which individual patients are likely to recur. Reliably predicting recurrence would be of benefit for treatment decisions following surgery. We present an integrated model constructed with comprehensive clinical, pathological and molecular features designed to discriminate risk of recurrence for patients with endometrioid endometrial adenocarcinoma. Subjects and methods: A cohort of endometrioid endometrial cancer patients treated at our institution was assembled. Clinical characteristics were extracted from patient charts. Primary tumors from these patients were obtained and total tissue RNA extracted for RNA sequencing. A prediction model was designed containing both clinical characteristics and molecular profiling of the tumors. The same analysis was carried out with data derived from The Cancer Genome Atlas for replication and external validation. Results: Prediction models derived from our institutional data predicted recurrence with high accuracy as evidenced by areas under the curve approaching 1. Similar trends were observed in the analysis of TCGA data. Further, a scoring system for risk of recurrence was devised that showed specificities as high as 81% and negative predictive value as high as 90%. Lastly, we identify specific molecular characteristics of patient tumors that may contribute to the process of disease recurrence. Conclusion: By constructing a comprehensive model, we are able to reliably predict recurrence in endometrioid endometrial cancer. We devised a clinically useful scoring system and thresholds to discriminate risk of recurrence. Finally, the data presented here open a window to understanding the mechanisms of recurrence in endometrial cancer.
3D Cardiac Cell Culture: A Critical Review of Current Technologies and Applications

Three-dimensional (3D) cell culture is often mentioned in the context of regenerative medicine, for example, for the replacement of ischemic myocardium with tissue-engineered muscle constructs. Additionally, 3D cell culture is used, although less commonly, in basic research, toxicology, and drug development. These applications have recently benefited from innovations in stem cell technologies allowing the mass-production of hiPSC-derived cardiomyocytes or other cardiovascular cells, and from new culturing methods including organ-on-chip and bioprinting technologies. On the analysis side, improved sensors, computer-assisted image analysis, and data collection techniques have lowered the bar for switching to 3D cell culture models. Nevertheless, 3D cell culture is not as widespread or standardized as traditional cell culture methods using monolayers of cells on flat surfaces. The many possibilities of 3D cell culture, but also its limitations, drawbacks and methodological pitfalls, are less well-known. This article reviews currently used cardiovascular 3D cell culture production methods and analysis techniques for the investigation of cardiotoxicity, in drug development and for disease modeling.
Effect of Ultrasound Combined With Microbubble Therapy on Interstitial Fluid Pressure and VX2 Tumor Structure in Rabbit

Interstitial fluid pressure (IFP) in tumor tissue is significantly higher than that in normal tissue, which reduces the effectiveness of therapeutic drugs. There are several methods to decrease the IFP, such as normalizing blood vessel, decreasing hyaluronic acid and collagen fiber content in the extracellular matrix (ECM), and recovering lymphatic function. Reducing tumor IFP might be developed as a novel approach in cancer therapy. In this study, we aimed to elucidate the relationship between ultrasound combined with microbubble therapy and IFP, and the associated mechanism. VX2 tumor in rabbit was treated with ultrasound combined with microbubbles at different intensities. The IFP was measured using the wick-in-needle (WIN) method. The collagen and reticular fibers were stained by Masson and Gordon–Sweets, respectively. The results showed that low-frequency non-focus ultrasound combined with microbubbles therapy influences the IFP in tumor tissues; low-frequency non-focus ultrasound with low pressure increased the IFP, whereas middle–high pressure decreased the IFP. The results showed that the structure and content of collagen and reticular fibers in tumor tissue were rarely influenced by the treatment. Our study provides a novel approach of reduced IFP antitumor therapy.
Embracing Diversity: Differences in Virulence Mechanisms, Disease Severity, and Host Adaptations Contribute to the Success of Nontyphoidal Salmonella as a Foodborne Pathogen

Not all Salmonella enterica serovars cause the same disease. S. enterica represents an incredibly diverse species comprising >2,600 unique serovars. While some S. enterica serovars are host-restricted, others infect a wide range of hosts. The diseases that nontyphoidal Salmonella (NTS) serovars cause vary considerably, with some serovars being significantly more likely to cause invasive disease in humans than others. Furthermore, while genomic analyses have advanced our understanding of the genetic diversity of these serovars, they have not been able to fully account for the observed clinical differences. One overarching challenge is that much of what is known about Salmonella’s general biology and virulence strategies is concluded from studies examining a select few serovars, especially serovar Typhimurium. As targeted control strategies have been implemented to control select serovars, an increasing number of foodborne outbreaks involving serovars that are less frequently associated with human clinical illness are being detected. Harnessing what is known about the diversity of NTS serovars represents an important factor in achieving the ultimate goal of reducing salmonellosis-associated morbidity and mortality worldwide. In this review we summarize the current understanding of the differences and similarities among NTS serovars, highlighting the virulence mechanisms, genetic differences, and sources that characterize S. enterica diversity and contribute to its success as a foodborne pathogen.
Sustained Release of Phosphates From Hydrogel Nanoparticles Suppresses Bacterial Collagenase and Biofilm Formation in vitro

Intestinal disease or surgical intervention results in local changes in tissue and host-derived factors triggering bacterial virulence. A key phenotype involved in impaired tissue healing is increased bacterial collagenase expression which degrades intestinal collagen. Antibiotic administration is ineffective in addressing this issue as it inadvertently eliminates normal flora while allowing pathogenic bacteria to “bloom” and acquire antibiotic resistance. Compounds that could attenuate collagenase production while allowing commensal bacteria to proliferate normally would offer major advantages without the risk of the emergence of resistance. We have previously shown that intestinal phosphate depletion in the surgically stressed host is a major cue that triggers P. aeruginosa virulence which is suppressed under phosphate abundant conditions. Recent findings indicate that orally administered polyphosphate, hexametaphosphate, (PPi) suppresses collagenase, and biofilm production of P. aeruginosa and S. marcescens in animal models of intestinal injury but does not attenuate E. faecalis induced collagenolytic activity (Hyoju et al., 2017). Systemic administration of phosphates, however, is susceptible to rapid clearance. Given the diversity of collagenase producing bacteria and the variation of phosphate metabolism among microbial species, a combination therapy involving different phosphate compounds may be required to attenuate pathogenic phenotypes. To address these barriers, we present a drug delivery approach for sustained release of phosphates from poly(ethylene) glycol (PEG) hydrogel nanoparticles. The efficacy of monophosphate (Pi)- and PPi-loaded NPs (NP-Pi and NP-PPi, respectively) and a combination treatment (NP-Pi + NP-PPi) in mitigating collagenase and biofilm production of gram-positive and gram-negative pathogens expressing high collagenolytic activity was investigated. NP-PPi was found to significantly decrease collagenase and biofilm production of S. marcescens and P. aeruginosa. Treatment with either NP-Pi or NP-Pi + NP-PPi resulted in more prominent decreases in E. faecalis collagenase compared to NP-PPi alone. The combination treatment was also found to significantly reduce P. aeruginosa collagenase production. Finally, significant attenuation in biofilm dispersal was observed with NP-PPi or NP-Pi + NP-PPi treatment across all test pathogens. These findings suggest that sustained release of different forms of phosphate confers protection against gram-positive and gram-negative pathogens, thereby providing a promising treatment to attenuate expression of tissue-disruptive bacterial phenotypes without eradicating protective flora over the course of intestinal healing.
Phylogeographic Analyses Reveal the Early Expansion and Frequent Bidirectional Cross-Border Transmissions of Non-pandemic HIV-1 Subtype B Strains in Hispaniola

The human immunodeficiency virus-type 1 (HIV-1) subtype B has probably been circulating on the island of Hispaniola since the 1960s, but information about the early viral history on this Caribbean island is scarce. In this study, we reconstruct the dissemination dynamics of early divergent non-pandemic subtype B lineages (designated BCAR) on Hispaniola by analyzing a country-balanced dataset of HIV-1 BCAR pol sequences from Haiti (n = 103) and the Dominican Republic (n = 123). Phylogenetic analyses supported that BCAR strains from Haiti and the Dominican Republic were highly intermixed between each other, although the null hypothesis of completely random mixing was rejected. Bayesian phylogeographic analyses placed the ancestral BCAR virus in Haiti and the Dominican Republic with the same posterior probability support. These analyses estimate frequent viral transmissions between Haiti and the Dominican Republic since the early 1970s onwards, and the presence of local BCAR transmission networks in both countries before first AIDS cases was officially recognized. Demographic reconstructions point that the BCAR epidemic in Hispaniola grew exponentially until the 1990s. These findings support that the HIV-1 epidemics in Haiti and the Dominican Republic have been connected by a recurrent bidirectional viral flux since the initial phase, which poses a great challenge in tracing the geographic origin of the BCAR epidemic within Hispaniola using only genetic data. These data also reinforce the notion that prevention programs have successfully reduced the rate of new HIV-1 transmissions in Hispaniola since the end of the 1990s.
The Genome-Wide Study of Human Social Behavior and Its Application in Sociology

Recent years have seen a push for the integration of modern genomic methodologies with sociological inquiry. The inclusion of genomic approaches promises to help address long-standing issues in sociology (e.g., selection effects), as well as open up new avenues for future research. This article reviews the substantive findings of behavior genetic/genomic research, both from the recent past (e.g., twin/adoption studies, candidate gene studies) and from contemporary genomic analyses. The article primarily focuses on modern genomic methods available to sociologists (e.g., polygenic score analysis) and their various applications for answering sociological questions. The article concludes by considering a number of areas to which genomic researchers and sociologists should pay close attention if a consilience between genomic methods and sociological research is to be fully realized.
Applying Answer Set Programming for Knowledge-Based Link Prediction on Social Interaction Networks

Link prediction targets the prediction of possible future links in a social network, i. e. , we aim to predict the next most likely links of the network given the current state. However, predicting the future solely based on (scarce) historic data is often challenging. In this paper, we investigate, if we can make use of additional (domain) knowledge to tackle this problem. For this purpose, we apply answer set programming (ASP) for formalizing the domain knowledge for social network (and graph) analysis. In particular, we investigate link prediction via ASP based on node proximity and its enhancement with background knowledge, in order to test intuitions that common features, e. g. , a common educational background of students, imply common interests. In addition, then the applied ASP formalism enables explanation-aware prediction approaches.
Is Searching for Meaning in Life Related to Civic Engagement?: Individual- and Society-Level Moderators

Going beyond previous research suggesting that the search for meaning in life (hereafter “search for meaning”) is associated with civic engagement, this study investigated the moderating effects of personal and cultural values on the associations between the search for meaning and two kinds of civic engagement (i.e., pro-environmental engagement and political engagement). Based on the dataset of the sixth wave of the World Values Survey (WVS), multi-level analyses showed that the association between the search for meaning (in terms of thinking about meaning and purpose of life) and pro-environmental engagement was stronger when people held stronger values of openness to change (vs. conservation) and prioritized environmental wellness. The association between the search for meaning and political engagement was stronger when people endorsed stronger values of openness to change, showed a greater interest in politics and attributed greater importance to politics. At the society level, the association between the search for meaning and civic engagement was stronger in societies with a lower power distance. Implications for individual differences of the meaning search are discussed.
Growth Hormone and Reproduction: Lessons Learned From Animal Models and Clinical Trials

Growth Hormone (GH) has been considered as a therapeutic option to increase the number of growing follicles during Assisted Reproductive Technology (ART) for more than 30 years. In this review the biological rationale for therapeutic GH usage is explained through evidence in animal models, aiming to put this into a clinical context. First, we explain the GH—Insulin like Growth Factor (IGF)-1—gonadal axis and its role in reproduction. Evidence suggests that GH can stimulate the secretion of IGF1 not only in the liver but also in the peripheral target structures, including the ovary. Moreover, IGF-1 can be secreted locally under the influence of stimuli other than GH. In the case of the ovary, steroid hormones, gonadotropins or the combination of both seems to be involved. Even more interesting, the ovary itself can secret GH locally and exert a paracrine action modulating the intracellular signaling pathway of GH, i.e., not by the systemic pathway where GH binds to the extracellular domain of the GH receptor. Finally, these aspects from animal models are put into clinical perspective by discussing results and shortcomings of studies and meta-analyses in order to put forth the state-of-the-art rationale for therapeutic GH usage in modern ART.
Truncating Variant in Myof Gene Is Associated With Limb-Girdle Type Muscular Dystrophy and Cardiomyopathy

Even though genetic studies of individuals with neuromuscular diseases have uncovered the molecular background of many cardiac disorders such as cardiomyopathies and inherited arrhythmic syndromes, the genetic cause of a proportion of cardiomyopathies associated with neuromuscular phenotype still remains unknown. Here, we present an individual with a combination of cardiomyopathy and limb-girdle type muscular dystrophy where whole exome sequencing identified myoferlin (MYOF)—a member of the Ferlin protein family and close homolog of DYSF—as the most likely candidate gene. The disease-causative role of the identified variant c. [2576delG; 2575G>C], p.G859QfsTer8 is supported by functional studies in vitro using the primary patient’s skeletal muscle mesenchymal progenitor cells, including both RNA sequencing and morphological studies, as well as recapitulating the muscle phenotype in vivo in zebrafish. We provide the first evidence supporting a role of MYOF in human muscle disease.
Spotlight on the Energy Harvest of Electroactive Microorganisms: The Impact of the Applied Anode Potential

Electroactive microorganisms (EAM) harvest energy by reducing insoluble terminal electron acceptors (TEA) including electrodes via extracellular electron transfer (EET). Therefore, compared to microorganisms respiring soluble TEA, an adapted approach is required for thermodynamic analyses. In EAM, the thermodynamic frame (i.e., maximum available energy) is restricted as only a share of the energy difference between electron donor and TEA is exploited via the electron-transport chain to generate proton-motive force being subsequently utilized for ATP synthesis. However, according to a common misconception, the anode potential is suggested to co-determine the thermodynamic frame of EAM. By comparing the model organism Geobacter spp. and microorganisms respiring soluble TEA, we reason that a considerable part of the electron-transport chain of EAM performing direct EET does not contribute to the build-up of proton-motive force and thus, the anode potential does not co-determine the thermodynamic frame. Furthermore, using a modeling platform demonstrates that the influence of anode potential on energy harvest is solely a kinetic effect. When facing low anode potentials, NADH is accumulating due to a slow direct EET rate leading to a restricted exploitation of the thermodynamic frame. For anode potentials ≥ 0.2 V (vs. SHE), EET kinetics, NAD+/NADH ratio as well as exploitation of the thermodynamic frame are maximized, and a further potential increase does not result in higher energy harvest. Considering the limited influence of the anode potential on energy harvest of EAM is a prerequisite to improve thermodynamic analyses, microbial resource mining, and to transfer microbial electrochemical technologies (MET) into practice.