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Chronic infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) affects an estimated 35 million and 75 million individuals worldwide, respectively. These viruses induce persistent inflammation which often drives the development or progression of organ-specific diseases and even cancer including Hepatocellular Carcinoma (HCC). In this study, we sought to examine inflammatory responses following HIV or HCV stimulation of macrophages or Kupffer cells (KCs), that may contribute to virus mediated inflammation and subsequent liver disease. KCs are liver-resident macrophages and reports have provided evidence that HIV can stimulate and infect them. In order to characterize HIV-intrinsic innate immune responses that may occur in the liver, we performed microarray analyses on KCs following HIV stimulation. Our data demonstrate that KCs upregulate several innate immune signaling pathways involved in inflammation, myeloid cell maturation, stellate cell activation, and Triggering Receptor Expressed on Myeloid cells 1 (TREM1) signaling. TREM1 is a member of the immunoglobulin superfamily of receptors and it is reported to be involved in systemic inflammatory responses due to its ability to amplify activation of host defense signaling pathways. Our data demonstrate that stimulation of KCs with HIV or HCV induces the upregulation of TREM1. Additionally, HIV viral proteins can upregulate expression of TREM1 mRNA through NF-кB signaling. Furthermore, activation of the TREM1 signaling pathway, with a targeted agonist, increased HIV or HCV-mediated inflammatory responses in macrophages due to enhanced activation of the ERK1/2 signaling cascade. Silencing TREM1 dampened inflammatory immune responses elicited by HIV or HCV stimulation. Finally, HIV and HCV infected patients exhibit higher expression and frequency of TREM1 and CD68 positive cells. Taken together, TREM1 induction by HIV contributes to chronic inflammation in the liver and targeting TREM1 signaling may be a therapeutic option to minimize HIV induced chronic inflammation.

The IPCC has been successful at building its scientific authority, but it will require institutional reform for staying relevant to new and changing political contexts. Exploring a range of alternative future pathways for the IPCC can help guide crucial decisions about redefining its purpose.

The role of parathyroid hormone (PTH)-related protein (PTHrP) in breast cancer remains controversial, with reports of PTHrP inhibiting or promoting primary tumor growth in preclinical studies. Here, we provide insight into these conflicting findings by assessing the role of specific biological domains of PTHrP in tumor progression through stable expression of PTHrP (-36-139aa) or truncated forms with deletion of the nuclear localization sequence (NLS) alone or in combination with the C-terminus. Although the full-length PTHrP molecule (-36-139aa) did not alter tumorigenesis, PTHrP lacking the NLS alone accelerated primary tumor growth by downregulating p27, while PTHrP lacking the NLS and C-terminus repressed tumor growth through p27 induction driven by the tumor suppressor leukemia inhibitory factor receptor (LIFR). Induction of p27 by PTHrP lacking the NLS and C-terminus persisted in bone disseminated cells, but did not prevent metastatic outgrowth, in contrast to the primary tumor site. These data suggest that the PTHrP NLS functions as a tumor suppressor, while the PTHrP C-terminus may act as an oncogenic switch to promote tumor progression through differential regulation of p27 signaling.

Understanding how phenotypes emerge from genotypes is a foundational goal in biology. As challenging as this task is when considering cellular life, it is further complicated in the case of viruses. During replication, a virus as a discrete entity (the virion) disappears and manifests itself as a metabolic amalgam between the virus and the host (the virocell). Identifying traits that unambiguously constitute a virus’s phenotype is straightforward for the virion, less so for the virocell. Here, we present a framework for categorizing virus phenotypes that encompasses both virion and virocell stages and considers functional and performance traits of viruses in the context of fitness. Such an integrated view of virus phenotype is necessary for comprehensive interpretation of viral genome sequences and will advance our understanding of viral evolution and ecology.Linking genotype to phenotype is particularly challenging for viruses because of their small size, sparse phenotypic data and interlinked viral, host and environmental factors. In this Review, DeLong and colleagues discuss traits of virions and virocells and phenotypic plasticity.

This research highlighted the critical importance of colleges and universities to prioritize the education of diverse students, foster inclusive communities, and cultivate awareness of inclusive learning environments. As higher education continues to evolve with an increasingly diverse student body, a one-size-fits-all institutional model is inadequate. Universal design for learning (UDL) offers a comprehensive framework for ensuring education is inclusive, equitable, accessible, and in alignment with disability legislation. This study, conducted among a diverse group of educators from various disciplines and experience levels, sought to investigate their perceptions of UDL and its integration into course design and teaching methods in their pedagogy to accommodate diverse learners. Qualtrics was the digital platform used to administer the survey, gather responses, and manage data for analysis. The research focused on examining a subset of faculty and instructional staff within a major urban university system in New York state. Thematic analysis emerged as the chosen methodological approach to systematically analyze and code the data obtained from the Qualtrics survey. The methods outlined the preliminary stage of the study’s research journey, highlighting the methodological deliberations and the chosen approach to analyzing data. The findings emphasized UDL serves as a comprehensive framework for promoting accessibility, inclusivity, and flexibility in education, thereby catering to the diverse needs and preferences of students. Empowering educators to enhance their ability and, in some cases, their proficiency in providing appropriate accommodations for students with disabilities is crucial for fostering a supportive learning environment.

Despite the persistence of breastfeeding racial and ethnic disparities in the United States, little is known about Black fathers' perceptions of breastfeeding and breastfeeding support services (e.g., maternity hospital‐based care and lactation management care). This qualitative, community‐based participatory research study reports Black fathers' perceptions of barriers and facilitators to breastfeeding, including the provision of breastfeeding support services in Connecticut. A focus group guide was co‐developed with community partners and adapted from the Barrier Analysis Tool to identify breastfeeding facilitators, barriers, and service improvement areas. Four focus groups were conducted with 30 Black fathers who were Connecticut residents with a child under 3 years old. Qualitative data were analyzed using rapid template analysis involving deductive and inductive coding. We identified factors influencing breastfeeding and fathers' ability to support breastfeeding across all levels of the Socio‐Ecological Model. Facilitators included high paternal breastfeeding knowledge, paternal breastfeeding involvement, parents' shared decision‐making, extensive maternity hospital discharge support, ongoing breastfeeding support into the postnatal period, availability of community breastfeeding resources, and designated spaces for public breastfeeding. Barriers included low paternal breastfeeding knowledge, familial discouragement, insufficient prenatal breastfeeding education, exclusion of the father from breastfeeding support services, and stigma against breastfeeding in public. Understanding breastfeeding perceptions among members of a mother's support network, including their partners, is key for developing effective person‐ and family‐centered breastfeeding education and counseling services that are well coordinated from the prenatal to postnatal periods with strong direct engagement from fathers. Summary Black fathers in Connecticut and their partners experience barriers to successful breastfeeding, especially access to effective breastfeeding support across levels of the Socio‐Ecological model. Lack of paternal knowledge about breastfeeding, familial discouragement, insufficient breastfeeding education, and social stigma were identified by fathers as key barriers to supporting breastfeeding. High paternal knowledge about breastfeeding, generational breastfeeding, engagement of the father by breastfeeding education services, and designated spaces to breastfeed in public were identified by fathers as key facilitators to supporting breastfeeding. Effective breastfeeding promotion will require a multi‐faceted approach that addresses barriers to breastfeeding from the individual to community levels, with the inclusion of fathers across the continuum of care.

Purpose Tumour blood vessels are structurally and functionally abnormal, resulting in areas of hypoxia and heterogeneous blood supply. Aerobic exercise may modulate tumour blood flow and normalise the tumour microenvironment to improve chemotherapy delivery. This systematic review and meta-analysis aimed to evaluate the effect of the aerobic exercise mode on tumour hypoxia, vascularisation and blood flow. Methods Four online databases were searched. Preclinical and clinical randomised controlled trials examining the effects of aerobic exercise training on hypoxia, vascularisation or blood flow in solid tumours were included. The risk of bias was assessed and a meta-analysis performed. Results Seventeen preclinical studies and one clinical study met criteria. Eleven studies assessed hypoxia, 15 studies assessed vascularisation and seven evaluated blood flow. There was large variability in measurement methods, tumour types and exercise program designs. The overall risk of bias was unclear in clinical and preclinical studies, owing to poor reporting. There was no significant effect of aerobic exercise on hypoxia (SMD = −0.17; 95% CI = −0.62, 0.28; I 2 = 60%), vascularisation (SMD = 0.07; 95% CI = −0.40, 0.55; I 2 = 71%) or blood flow (SMD = 0.01; 95% CI = −0.59, 0.61; I 2 = 63%). Conclusion There is heterogeneity in methodology, resulting in evidence that is inconsistent and inconclusive for the effects of aerobic exercise on hypoxia, vascularisation and blood flow. Most evidence of aerobic exercise effects on tumour blood flow is in animal models, with very limited evidence in humans.

Abstract Objective. Music has been shown to modulate pain, although the impact of music on specific aspects of nociceptive processing is less well understood. Using quantitative sensory testing (QST), we assessed the impact of a novel music app on specific aspects of nociceptive processing. Design. Within-subjects paired comparison of pain processing in control vs music condition. Setting. Human psychophysical laboratory. Subjects. Sixty healthy adult volunteers. Methods. Subjects were assessed for baseline anxiety, depression, and catastrophizing using validated questionnaires. QSTs measured included 1) pain threshold and tolerance to deep muscle pressure, 2) pain with mechanical pinprick, 3) temporal summation of pain (TSP) with a repeated pain stimulus, and 4) conditioned pain modulation (CPM) with a second painful stimulus. QSTs were performed in the absence and presence of music delivered through a music app. Results. We found an increase in pressure pain thresholds in both the forearm (P = 0.007) and trapezius (P = 0.002) with music, as well as a decrease in the amount of pinprick pain (P < 0.001) and TSP (P = 0.01) with music. Interestingly, CPM was also significantly diminished (P < 0.001) in the music condition. No significant difference in cold pain, anxiety, or situational catastrophizing was observed with music. Higher baseline pain catastrophizing scores were associated with less music-induced pressure pain reduction. Conclusions. Several measures of mechanical pain sensitivity were reduced with music. TSP, a measure of central sensitization, also decreased with music, but CPM, a measure of descending modulation of pain, was not further augmented by music.

Purpose: We examined whether supplementation of zinc magnesium aspartate (ZMA), while partially sleep deprived, was beneficial to sleep quality and subsequent morning (07:00 h) submaximal weightlifting. Methods: Using a double-blinded, randomized counterbalanced design, sixteen trained males were recruited and completed six sessions: (i) one repetition max (1 RM) for bench press and back squat; (ii) two familiarisation sessions; (iii) three conditions with 4 h sleep and either: ZMA, placebo (PLA), or NoPill control (NoPill). Submaximal exercise session consisted of three repetitions at 40, 60 and 80% of 1 RM for bench press and back squat. Average power (AP), average velocity (AV), peak velocity (PV), displacement (D) and time-to-peak velocity (tPV) were recorded using MuscleLab linear encoders. Data were analysed using a general linear model with repeated measures and linear correlation. Results: No significant main effect for condition was found for performance values or subjective ratings of fatigue. Main effect for “load” on the bar was found, where AP and tPV values increased with load (p < 0.05). No significant relationship between dose of zinc or magnesium ingested and change in performance for 80% 1 RM power-outputs was found. Conclusion: Supplementation of ZMA for two nights of partial sleep deprivation had no effect on sleep or subsequent morning performance.

Technology encourages collaboration in creative ways in the classroom. Specifically, social robots may offer new opportunities for greater innovation in teaching. In this study, we combined the established literature on co-teaching teams with the developing field of machine actors used in education to investigate the impressions students had of different team configurations that included both a human and a robot. Participants (N = 215, age: M = 24, SD = 8.67, range 18-69) saw one of three teams composed of a human and a social robot with different responsibilities present a short, prerecorded lecture (i.e., human as lead teacher-robot as teaching assistant, robot as lead teacher-human as teaching assistant, human and robot as co-teachers). Overall, students rated the human-led team as more appealing and having more credibility than the robot-led team. The data suggest that participants would be more likely to take a course led by a human instructor than a social robot. Previous studies have investigated machine actors in the classroom, but the current findings are unique in that they compare the individual roles and power structures of human-robot teams leading a course.