Human papillomavirus: pathogenesis and barriers to prevention

Cervical cancer is one of the most common forms of cancer in the world, and human papillomavirus (HPV) is a cause of the vast majority of these patient cases. With many HPV types being oncogenic in nature, HPV as a whole is responsible for over 5% of all cancers worldwide and 15% of cancer in women in developing countries. HPV is a sexually transmitted infection that is spread through contact with infected genital skin, mucosa, or bodily fluids from a partner with acute or subclinical viral infection. While less frequent, various strains of the virus are also responsible for anal and vaginal warts, anal cancer, and cancer of the vulva and penis – these account for approximately 50,000 cases per year worldwide. Data also suggest a potential implication of HPV in oropharyngeal cancers, especially among younger adults. Various behavioral and prophylactic approaches are recommended for the prevention of HPV infection and cancer. For example, there is evidence that behavioral change can be effective, such as condom use and limitation on the number of sexual partners. Besides this, in recent years we have seen the development of various prophylactic or therapeutic vaccines that are highly effective in the prevention of HPV pathogenesis. Despite this, barriers to treatment and prevention exist, making HPV a continuing threat to individuals most at-risk across the globe. Thus, this study reviewed a large collection of current HPV and related cancer literature to understand the process of infection and pathogenesis in various human sites as well as potential barriers to prevention and treatment that may be perpetuating the survival of the virus across the world. Analyzing current and past research on such barriers, this paper delves into important variables that can affect early detection and treatment of HPV, and also explores a novel and promising therapy currently in development that could be valuable in overcoming many of these issues

Global Education in Anatomy and Physiology During COVID-19: Lessons Learnt and Future Recommendations

The Coronavirus Infectious Disease 2019 (COVID-19) pandemic has disrupted several essential aspects of anatomy and physiology education worldwide. With this pandemic, dynamic instructional and technological interventions have been taking place rapidly in an effort to minimize the adverse repercussions of moving away from the traditional means of education in these critical scientific disciplines. COVID-19 has necessitated higher educational administrations, faculty, and students to pursue teaching, learning, and assessment of anatomy and physiology courses/curricula through innovative strategies without compromising on the quality or rigor of education. Our study encapsulates, for the first time, globally published reports on the key implications of COVID-19 in anatomy and physiology education, along with future recommendations. The analysis would help improve education worldwide in anatomy and physiology, and foster better preparation for future pandemics

The Grim Realities of a Doctoral Student in Aotearoa

This article explores the multifaceted challenges confronting PhD students in Aotearoa New Zealand’s universities. In contrast to the advertised three-year completion timelines, evidence reveals extended PhD durations and a disconnect between enrolments and academic opportunities. The often unrecognised hurdles faced by PhD students include financial strains stemming from low stipends that do not cover the local cost of living, difficulty accessing additional income, and ambiguous student status. The complex phase at the completion of PhD represents a separate narrative with new challenges including the end of stipend funding and a significant gap in employment prospects while waiting months for the PhD to be examined. By documenting the poorly documented difficulties and realities, the authors aim to offer insights to stakeholders and prospective PhD students, fostering awareness and advocating for improvements in the doctoral education system

Heat exposure and multiple sclerosis—a regional and temporal analysis

Multiple sclerosis (MS) is a neurological disorder that progressively distorts the myelination of axons within the central nervous system (CNS). Increased core body temperature or metabolism as a result of exercise are common causes of short-term exacerbations of neurological symptoms in MS. About 60–80% of patients with MS experience a worsening of their symptoms when exposed to heat. In comparison, less data are available on the relationship between ambient meteorological conditions (e.g., temperature and relative humidity (RH)) and fluctuations in such variables in relation to MS symptoms. Thus, this study examined associations between time-lagged exposure to meteorological conditions and risk of a clinic visit due to MS among US veterans between 2010 and 2013. This study leveraged data from the Veterans Affairs (VA) and National Climactic Data Center (NCDC) for the continental US, partitioned into eight climate zones. We used a case crossover design to assess the risk of a MS clinic visit with respect to several meteorological conditions. Location-specific time-lagged daily (ambient) exposure to temperature, RH, and temperature variations (standard deviation (SD) of temperature) were computed (up to 30 days) for each case (i.e., day of MS visit) and control (a randomly assigned date ± 90–270 days prior to visit). Statistical analyses were conducted to examine independent associations between the selected meteorological conditions and risk of MS visits at the national and regional levels. A total of 533,066 patient visits received a MS diagnosis (International Classifications of Diseases (ICD)-9 code = 340). The Northeast (NE) and Upper Midwest (UMW) regions reported the highest frequency of clinic visits due to MS. Clinic visits were 9% more likely to occur in the spring, summer, and fall months (March–October) than in the winter (OR = 1.089; 95% CI = 1.076–1.103; p \u3c 0.01). In the univariate analyses, the SD of temperature, temperature, and temperature–RH interaction were positively associated with an elevated risk of a MS clinic visit, while the RH was negatively associated with the risk for a clinic visit. In multivariate analyses, the strongest association of a MS clinic visit was observed with the SD of the temperature (OR = 1.012; 95% CI 1.008–1.017; p \u3c 0.01). These associations between MS clinic visits and meteorological conditions varied across climate regions, with the strongest associations being observed in the LMW, UMW, DSW, and NE zones. The SD of the temperature was again the strongest associated predictor when examined regionally. Temperature variations and temperature–RH interactions (a proxy of the heat index) showed significant associations with MS clinic visits. These associations varied across climate regions when examined geographically. Our findings have implications for the management of MS in severe or recurrent cases, especially considering the impending changes in the daily temperature variations and intensity of the heatwaves expected with the intensification of global warming

E(2) Equivariant Neural Networks for Robust Galaxy Morphology Classification

We propose the use of group convolutional neural network architectures (GCNNs) equivariant to the 2D Euclidean group, $E(2)$, for the task of galaxy morphology classification by utilizing symmetries of the data present in galaxy images as an inductive bias in the architecture. We conduct robustness studies by introducing artificial perturbations via Poisson noise insertion and one-pixel adversarial attacks to simulate the effects of limited observational capabilities. We train, validate, and test GCNNs equivariant to discrete subgroups of $E(2)$ - the cyclic and dihedral groups of order $N$ - on the Galaxy10 DECals dataset and find that GCNNs achieve higher classification accuracy and are consistently more robust than their non-equivariant counterparts, with an architecture equivariant to the group $D_{16}$ achieving a $95.52 \pm 0.18\%$ test-set accuracy. We also find that the model loses $<6\%$ accuracy on a $50\%$-noise dataset and all GCNNs are less susceptible to one-pixel perturbations than an identically constructed CNN. Our code is publicly available at https://github.com/snehjp2/GCNNMorphology.Comment: 10 pages, 4 figures, 3 tables, Accepted to the Machine Learning and the Physical Sciences Workshop at NeurIPS 202

The environment and dry eye—manifestations, mechanisms, and more

Dry eye disease (DED) is a multifactorial condition that often presents with chronic symptoms of pain (that can be characterized as “dryness,” “burning,” and “irritation,” to name a few) and/or fluctuating or poor-quality vision. Given its multifactorial nature, several pathophysiologic mechanisms have been identified that can underlie symptoms, including tear film, ocular surface, and/or corneal somatosensory nerve abnormalities. Research has focused on understanding how environmental exposures can increase the risk for DED flares and negatively impact the tear film, the ocular surface, and/or nerve health. Given that DED is a common condition that negatively impacts physical and mental functioning, managing DED requires multiple strategies. These can include both medical approaches and modulating adverse environmental conditions, the latter of which may be a cost-effective way to avoid DED flares. Thus, an understanding of how environmental exposures relate to disease is important. This Review summarizes research on the relationships between environmental exposures and DED, in the hope that this information will engage healthcare professionals and patients to consider environmental manipulations in their management of DED

Spatial Context of Tumor Immune Microenvironment of Matched Primary and Recurrent Glioblastomas

https://openworks.mdanderson.org/sumexp22/1078/thumbnail.jp

Monocytes mediate homing of circulating microvesicles to the pulmonary vasculature during low-grade systemic inflammation

Microvesicles (MVs), a plasma membrane-derived subclass of extracellular vesicles, are produced and released into the circulation during systemic inflammation, yet little is known of cell/tissue-specific uptake of MVs under these conditions. We hypothesized that monocytes contribute to uptake of circulating MVs and that their increased margination to the pulmonary circulation and functional priming during systemic inflammation produces substantive changes to the systemic MV homing profile. Cellular uptake of i.v.-injected, fluorescently labelled MVs (J774.1 macrophage-derived) in vivo was quantified by flow cytometry in vascular cell populations of the lungs, liver and spleen of C57BL6 mice. Under normal conditions, both Ly6Chigh and Ly6Clow monocytes contributed to MV uptake but liver Kupffer cells were the dominant target cell population. Following induction of sub-clinical endotoxemia with low-dose i.v. LPS, MV uptake by lung-marginated Ly6Chigh monocytes increased markedly, both at the individual cell level (~2.5-fold) and through substantive expansion of their numbers (~8-fold), whereas uptake by splenic macrophages was unchanged and uptake by Kupffer cells actually decreased (~50%). Further analysis of MV uptake within the pulmonary vasculature using a combined model approach of in vivo macrophage depletion, ex vivo isolated perfused lungs and in vitro lung perfusate cell-based assays, indicated that Ly6Chigh monocytes possess a high MV uptake capacity (equivalent to Kupffer cells), that is enhanced directly by endotoxemia and ablated in the presence of phosphatidylserine (PS)-enriched liposomes and β3 integrin receptor blocking peptide. Accordingly, i.v.-injected PS-enriched liposomes underwent a redistribution of cellular uptake during endotoxemia similar to MVs, with enhanced uptake by Ly6Chigh monocytes and reduced uptake by Kupffer cells. These findings indicate that monocytes, particularly lung-marginated Ly6Chigh subset monocytes, become a dominant target cell population for MVs during systemic inflammation, with significant implications for the function and targeting of endogenous and therapeutically administered MVs, lending novel insights into the pathophysiology of pulmonary vascular inflammation

Levels of Transforming Growth Factor Beta and Programmed Cell Death 1 in Normal and Cancerous Pancreatic Cells

Pancreatic cancer is the fourth deadliest cancer in America and it continues to take more lives every year. However, there are not many viable options to treat this pernicious cancer. We tested for levels of Transforming Growth Factor Beta (TGFB) and Programmed Cell Death 1 (PD-1) using Western blots. TGFB is used to suppress T cells which are responsible for targeting and destroying cancerous cells, so if we suppress TGFB there should be increased T cell activity. Furthermore, PD-1 also regulates T-cells, and inhibition of PD-1 should lead to specific targeting of the cancerous tumor. Therefore before clinical trials proceed, the levels of these two proteins in cancer cells need to be determined. Results showed that levels of TGFB did not increase significantly in cancerous cells and PD-1 was only expressed in the cancerous cells. Based on these results, we have concluded that TGFB is not necessarily an anticancerous agent and that PD-1 supports the growth of pancreatic cancer. Thus, further studies will need to be completed to analyze the relationship between TGFB and pancreatic cancer’s progression