Differential utilization of the online patient portal for completion of health-related social needs screening during routine gynecologic cancer care.

BACKGROUND: Telehealth technologies offer efficient ways to deliver health-related social needs (HRSN) screening in cancer care, but these methods may not reach all populations. The authors examined patient characteristics associated with using an online patient portal (OPP) to complete HRSN screening as part of gynecologic cancer care. METHODS: From June 2021 to June 2023, patients in a gynecologic oncology clinic completed validated HRSN screening questions either (1) using the OPP (independently before the visit) or (2) in person (verbally administered by clinic staff). The authors examined the prevalence of HRSN according to activated OPP status and, in a restricted subgroup, used stepwise multivariate Poisson regression to identify associations between patient and visit characteristics and using the OPP. RESULTS: Of 1616 patients, 87.4% (n = 1413) had an activated OPP. Patients with inactive OPPs (vs. activated OPPs) more frequently reported two or more needs (10% vs 5%; p < .01). Of 986 patients in the restricted cohort, 52% used the OPP to complete screening. The final multivariable model indicated that patients were less likely to use the OPP if they were Black (vs. White; adjusted relative risk [aRR], 0.70; 95% confidence interval [CI], 0.59-0.83); not employed (vs. employed; aRR, 0.81; 95% CI, 0.68-0.97), or had low measures of OPP engagement (aRR, 0.80; 95% CI, 0.68-0.92). New versus established patients were 21% more likely to use the OPP (aRR, 1.21; 95% CI, 1.06-1.38). CONCLUSIONS: Differential use of the OPP suggested that over-reliance on digital technologies could limit the ability to reach those populations that have social factors already associated with cancer outcome disparities. Cancer centers should consider using multiple delivery methods for HRSN screening to maximize reach to all populations.

Lung Cancer Survivorship: Physical, Social, Emotional, and Medical Needs of NSCLC Survivors.

BACKGROUND: Newer therapies prolong survival for patients with lung cancer. Beyond extending survival, the needs of lung cancer (LC) survivors are poorly described. METHODS: We conducted a single-institution needs assessment survey of LC survivors alive ≥1 year from diagnosis. Needs were rated on a 5-point Likert scale for 4 domains (physical, social, emotional, and medical). Multiple regression models identified demographic or treatment characteristics associated with more needs in each category. A subset analysis of survivors with metastatic LC was performed. RESULTS: Of 360 patients approached, 235 surveys were completed. Among completed survey respondents, the median age was 69 years; most were female (62%), married (71%), and White (74%); and 41% had stage IV cancer. Finding support resources (34%) was the most common medical need. Fatigue (70%), sleep disturbance (60%), memory and concentration (57.5%), weakness (54%), and trouble breathing (51%) were physical needs affecting more than half of respondents. The most common social need was managing daily activities (42%). Emotional needs were highly prevalent, with 79% of respondents reporting a fear of recurrence and 74.5% reporting living with uncertainty. Multiple regression analysis identified that receipt of multiple lines of systemic therapy and lower household income were associated with higher physical and social needs. Younger age was associated with having a greater number of social and emotional needs. Similar results were found in the subset of survivors with metastatic disease at diagnosis. CONCLUSIONS: The needs of LC survivors are diverse across multiple domains. Several clinical and demographic factors are independently associated with higher numbers of patient-reported needs. Our study identifies critical gaps in survivorship care for LC survivors with all stages of disease and highlights areas of future intervention.

Fibrinogen Fragment X Mediates Endothelial Barrier Disruption via Suppression of VE-Cadherin.

INTRODUCTION: Major traumatic injury is associated with early hemorrhage-related and late-stage deaths due to multiple organ failure (MOF). While improvements to hemostatic resuscitation have significantly reduced hemorrhage-related deaths, the incidence of MOF among trauma patients remains high. Dysregulation of vascular endothelial cell (EC) barrier function is a central mechanism in the development of MOF; however, the mechanistic triggers remain unknown. Accelerated fibrinolysis occurs in a majority of trauma patients, resulting in high circulating levels of fibrin(ogen) degradation products, such as fragment X. To date, the relationship between fragment X and EC dysregulation and barrier disruption is unknown. The goal of this study was to determine the effects of fragment X on EC barrier integrity and expression of paracellular junctional proteins that regulate barrier function. METHODS: Human lung microvascular endothelial cells (HLMVECs) were treated with increasing concentrations of fragment X (1, 10, and 100 µg/mL), and barrier function was monitored using the xCELLigence live-cell monitoring system. Quantitative PCR (qPCR) was performed to measure changes in EC expression of 84 genes. Immunofluorescent (IF) cytostaining was performed to validate qPCR findings. RESULTS: Fragment X treatment significantly increased endothelial permeability over time (P < 0.05). There was also a significant reduction in VE-cadherin mRNA expression in fragment X-treated HLMVECs compared to control (P = 0.01), which was confirmed by IF staining. CONCLUSIONS: Fragment X may induce EC hyperpermeability by reducing VE-cadherin expression. This suggests that a targeted approach to disrupting EC-fragment X interactions could mitigate EC barrier disruption, organ edema, and MOF associated with major trauma.

Termination counseling among US perinatal genetic counselors in the setting of second trimester fetal anomalies.

Many pregnant people learn of fetal anomalies in the second trimester and subsequently present to prenatal genetic counselors (PGCs) for counseling, including but not limited to a nuanced discussion about whether to continue or terminate pregnancy. In those who choose to terminate, the decision between dilation and evacuation (D&E) or induction is often one of patient preference and as such, is heavily influenced by the quality of counseling received. PGCs are expertly trained to provide values-based counseling, yet little is known about their termination counseling practices, referral practice patterns, and perceived responsibilities in caring for this group of pregnant people. To gain this knowledge, we surveyed a national sample of PGCs in early 2022 and received 70 completed responses. The survey contained open- and closed-ended questions. Data were analyzed using descriptive statistics, and free response data were analyzed using inductive content analysis. Eighty percent (n = 56) of respondents reported that <50% of their patients had previously received termination options counseling. Most strikingly, 15% of respondents provided termination counseling that was beyond their self-identified comfort level. Scenario-based questions assessed respondents' counseling practice patterns in seven real-world situations, presented in order of decreasing severity for the fetus. Respondents were 50% less likely to provide termination options counseling to patients between the most lethal to the least lethal proposed fetal anomaly. The scenario-based analysis revealed two distinct termination counseling approaches: (1) all options counseling with an explicit discussion of options to continue or terminate and (2) discretionary options counseling focused on identifying patient preferences to guide counseling and not explicitly stating all available options. This study highlights the need to ensure PGCs feel well-trained to discuss the general features of second trimester pregnancy termination and, if unable to do so, to practice in systems with timely referral to providers well-versed in the counseling about all methods of termination.

Ranking the risk of animal-to-human spillover for newly discovered viruses.

The death toll and economic loss resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are stark reminders that we are vulnerable to zoonotic viral threats. Strategies are needed to identify and characterize animal viruses that pose the greatest risk of spillover and spread in humans and inform public health interventions. Using expert opinion and scientific evidence, we identified host, viral, and environmental risk factors contributing to zoonotic virus spillover and spread in humans. We then developed a risk ranking framework and interactive web tool, SpillOver, that estimates a risk score for wildlife-origin viruses, creating a comparative risk assessment of viruses with uncharacterized zoonotic spillover potential alongside those already known to be zoonotic. Using data from testing 509,721 samples from 74,635 animals as part of a virus discovery project and public records of virus detections around the world, we ranked the spillover potential of 887 wildlife viruses. Validating the risk assessment, the top 12 were known zoonotic viruses, including SARS-CoV-2. Several newly detected wildlife viruses ranked higher than known zoonotic viruses. Using a scientifically informed process, we capitalized on the recent wealth of virus discovery data to systematically identify and prioritize targets for investigation. The publicly accessible SpillOver platform can be used by policy makers and health scientists to inform research and public health interventions for prevention and rapid control of disease outbreaks. SpillOver is a living, interactive database that can be refined over time to continue to improve the quality and public availability of information on viral threats to human health.

Comparison of Serial Amnioinfusion Strategies for Isolated Early-Onset Fetal Renal Anhydramnios.

INTRODUCTION: The optimal protocol for serial amnioinfusions to maintain amniotic fluid in pregnancies with early-onset fetal renal anhydramnios before 22 weeks is not known. We compared the performance of two different approaches. METHODS: A secondary analysis was conducted of serial amnioinfusions performed by a single center during the external pilot and feasibility phases of the Renal Anhydramnios Fetal Therapy (RAFT) trial. During the external pilot, higher amnioinfusion volumes were given less frequently; in the feasibility study, smaller volume amnioinfusions were administered more frequently. Procedural details, complications, and obstetric outcomes were compared between the two groups using Pearson's χ2 or Fisher's exact tests for categorical variables and Student's t tests or Wilcoxon rank-sum tests for continuous variables. The adjusted association between procedural details and chorioamniotic separation was obtained through a multivariate repeated measure logistic regression model. RESULTS: Eleven participants underwent 159 amnioinfusions (external pilot: 3 patients, 21 amnioinfusions; feasibility: 8 patients, 138 amnioinfusions). External pilot participants had fewer amnioinfusions (7 vs. 19.5 in the feasibility group, p = 0.04), larger amnioinfusion volume (750 vs. 500 mL, p < 0.01), and longer interval between amnioinfusions (6 [4-7] vs. 4 [3-5] days, p < 0.01). In the external pilot, chorioamniotic separation was more common (28.6% vs. 5.8%, p < 0.01), preterm prelabor rupture of membranes (PPROM) occurred sooner after amnioinfusion initiation (28 ± 21.5 vs. 75.6 ± 24.1 days, p = 0.03), and duration of maintained amniotic fluid between first and last amnioinfusion was shorter (38 ± 17.3 vs. 71 ± 19 days, p = 0.03), compared to the feasibility group. While delivery gestational age was similar (35.1 ± 1.7 vs. 33.8 ± 1.5 weeks, p = 0.21), feasibility participants maintained amniotic fluid longer. CONCLUSION: Small volume serial amnioinfusions performed more frequently maintain normal amniotic fluid volume longer because of delayed occurrence of PPROM.

Delivering vaping cessation interventions to adolescents and young adults on Instagram: protocol for a randomized controlled trial.

BACKGROUND: Adolescent and young adult use of electronic nicotine delivery systems ("vaping") has increased rapidly since 2018. There is a dearth of evidence-based vaping cessation interventions for this vulnerable population. Social media use is common among young people, and smoking cessation groups on social media have shown efficacy in the past. The objective of this study is to describe the protocol for a randomized controlled trial (RCT) testing the efficacy of an Instagram-based vaping cessation intervention for adolescents and young adults. METHODS: Adolescents and young adults aged 13-21 residing in California who have vaped at least once per week in the past 30 days will be recruited through social media ads, community partners, and youth serving organizations. Participants will be randomly assigned to intervention or control conditions: the intervention group takes place on Instagram, where participants receive up to 3 posts per weekday for 25 days over 5 weeks; the control group will be directed to kickitca.org, a website offering links to chatline and texting cessation services operated by the California Smokers' Helpline. The primary outcome is biochemically verified 7-day point prevalence abstinence for nicotine vaping; secondary outcomes are vaping reduction by 50% or more, vaping quit attempts, readiness to quit vaping, confidence in ability to quit, desire to quit, commitment to abstinence, and use of evidence-based cessation strategies. Both the primary outcome and secondary outcomes will be assessed immediately, 3 months, and 6 months after the treatment. DISCUSSION: This is the first RCT to test a vaping cessation intervention delivered through Instagram. If effective, it will be one of the first evidence-based interventions to address vaping among adolescents and young adults and add to the evidence base for social media interventions for this population. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04707911, registered on January 13, 2021.

Neurotrauma, COVID and the rationing of intensive care: an ethical approach.

The advent of the COVID-19 pandemic with its extreme pressure on resources and intensive care beds has prompted many healthcare providers to consider more fully the potentially futile nature of some treatments and how resources might be better managed. This is especially relevant in the context of neurosurgery which is highly resource dependent in terms of technology, funding, and manpower and it may be difficult to balance fair, equitable and sustainable resource allocation, especially in circumstances where those healthcare resources become limited or completely exhausted. Indeed, it may be necessary to consider limiting the availability of certain neurosurgical services or perhaps reconsider the utility or otherwise of performing procedures that commit very restricted resources, such as intensive care beds, to patients who are arguably receiving limited long-term benefit. In these circumstances, the decision-making paradigm is challenging and there are several ethically disparate viewpoints that need to be reconciled. These include but are not limited to, Futility, Utilitarianism and the Rule of rescue.

Modeling reveals cortical dynein-dependent fluctuations in bipolar spindle length.

Proper formation and maintenance of the mitotic spindle is required for faithful cell division. Although much work has been done to understand the roles of the key molecular components of the mitotic spindle, identifying the consequences of force perturbations in the spindle remains a challenge. We develop a computational framework accounting for the minimal force requirements of mitotic progression. To reflect early spindle formation, we model microtubule dynamics and interactions with major force-generating motors, excluding chromosome interactions that dominate later in mitosis. We directly integrate our experimental data to define and validate the model. We then use simulations to analyze individual force components over time and their relationship to spindle dynamics, making it distinct from previously published models. We show through both model predictions and biological manipulation that rather than achieving and maintaining a constant bipolar spindle length, fluctuations in pole-to-pole distance occur that coincide with microtubule binding and force generation by cortical dynein. Our model further predicts that high dynein activity is required for spindle bipolarity when kinesin-14 (HSET) activity is also high. To the best of our knowledge, our results provide novel insight into the role of cortical dynein in the regulation of spindle bipolarity.

Incorporating multiple sets of eQTL weights into gene-by-environment interaction analysis identifies novel susceptibility loci for pancreatic cancer.

It is of great scientific interest to identify interactions between genetic variants and environmental exposures that may modify the risk of complex diseases. However, larger sample sizes are usually required to detect gene-by-environment interaction (G × E) than required to detect genetic main association effects. To boost the statistical power and improve the understanding of the underlying molecular mechanisms, we incorporate functional genomics information, specifically, expression quantitative trait loci (eQTLs), into a data-adaptive G × E test, called aGEw. This test adaptively chooses the best eQTL weights from multiple tissues and provides an extra layer of weighting at the genetic variant level. Extensive simulations show that the aGEw test can control the Type 1 error rate, and the power is resilient to the inclusion of neutral variants and noninformative external weights. We applied the proposed aGEw test to the Pancreatic Cancer Case-Control Consortium (discovery cohort of 3,585 cases and 3,482 controls) and the PanScan II genome-wide association study data (replication cohort of 2,021 cases and 2,105 controls) with smoking as the exposure of interest. Two novel putative smoking-related pancreatic cancer susceptibility genes, TRIP10 and KDM3A, were identified. The aGEw test is implemented in an R package aGE.

The relationship between early post-operative ACTH / cortisol following pituitary surgery and long-term glucocorticoid requirement - Do ultradian rhythms matter?

OBJECTIVE: To determine whether early (4-8h) post-operative ACTH after trans-sphenoidal surgery (TSS) predicts long-term hypothalamic-pituitary-adrenal (HPA) axis function and to investigate early morning day 1 ACTH/cortisol variability using rapid sampling. DESIGN: Prospective observational study. METHODS: Participants undergoing TSS were included; those treated with glucocorticoids pre-operatively received 100 mg intravenous hydrocortisone on anaesthetic induction. ACTH and cortisol were measured post-operatively at + 4h and + 8h after induction and on day 1 every 10 minutes between 0700h and 0900h. PRIMARY OUTCOME: glucocorticoid requirement at 6 months. RESULTS: Nineteen participants (10F, 9M): 6/19 (32%) were treated with replacement glucocorticoids pre-operatively; 4 had ceased by 6 weeks post-operatively. One patient developed new hypopituitarism post-operatively meaning 3/19 (16%) required glucocorticoids at 6 months. Post-operative + 4h ACTH < 14.3 pmol/L (65 ng/L) predicted secondary adrenal insufficiency (SAI) (sensitivity 100%, specificity 75%), whilst no participant with a post-operative + 4h ACTH ≥ 14.3 pmol/L (65 ng/L) required glucocorticoids at 6 months. Day 1 ACTH and cortisol showed a significant circadian fall between 0700h-0900h; ACTH 4.2 pmol/L (IQR 2.9-5.9) to 3.7 pmol/L (IQR 2.9-5.1) P = .006 and cortisol 549 nmol/L (IQR 337-618) to 439 nmol/L (IQR 315-606) P < .001, with clinically insignificant ultradian secretory pulses. CONCLUSIONS: No participant with a post-operative + 4h ACTH ≥ 14.3 pmol/L (65 ng/L) required glucocorticoids at 6 months; however, given only 3/19 participants had the primary outcome of interest, this must be confirmed in a larger cohort. The timing of a day 1 morning cortisol between 0700h and 0900h influences the accuracy of a single cut-off to diagnose SAI after pituitary surgery.

Pregnancy alters interleukin-1 beta expression and antiviral antibody responses during severe acute respiratory syndrome coronavirus 2 infection.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2, the disease-causing pathogen of the coronavirus disease 2019 pandemic, has resulted in morbidity and mortality worldwide. Pregnant women are more susceptible to severe coronavirus disease 2019 and are at higher risk of preterm birth than uninfected pregnant women. Despite this evidence, the immunologic effects of severe acute respiratory syndrome coronavirus 2 infection during pregnancy remain understudied. OBJECTIVE: This study aimed to assess the impact of severe acute respiratory syndrome coronavirus 2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to severe acute respiratory syndrome coronavirus 2 among pregnant and nonpregnant women. STUDY DESIGN: Immune responses to severe acute respiratory syndrome coronavirus 2 were analyzed using samples from pregnant (n=33) and nonpregnant (n=17) women who tested either positive (pregnant, 22; nonpregnant, 17) or negative for severe acute respiratory syndrome coronavirus 2 (pregnant, 11) at Johns Hopkins Hospital. We measured proinflammatory and placental cytokine messenger RNAs, neonatal Fc receptor expression, and tetanus antibody transfer in maternal and cord blood samples. In addition, we evaluated antispike immunoglobulin G, antispike receptor-binding domain immunoglobulin G, and neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 in serum or plasma collected from nonpregnant women, pregnant women, and cord blood. RESULTS: Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection expressed more interleukin-1 beta, but not interleukin 6, in blood samples collected within 14 days vs >14 days after performing severe acute respiratory syndrome coronavirus 2 test. Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection also had reduced antispike receptor-binding domain immunoglobulin G titers and were less likely to have detectable neutralizing antibody than nonpregnant women. Although severe acute respiratory syndrome coronavirus 2 infection did not disrupt neonatal Fc receptor expression in the placenta, maternal transfer of severe acute respiratory syndrome coronavirus 2 neutralizing antibody was inhibited by infection during pregnancy. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of coronavirus disease 2019 treatment in pregnancy. In addition, the long-term implications of placental inflammation for neonatal health require greater consideration.

A Bayesian Framework to Estimate Fluid and Material Parameters in Micro-swimmer Models.

To advance our understanding of the movement of elastic microstructures in a viscous fluid, techniques that utilize available data to estimate model parameters are necessary. Here, we describe a Bayesian uncertainty quantification framework that is highly parallelizable, making parameter estimation tractable for complex fluid-structure interaction models. Using noisy in silico data for swimmers, we demonstrate the methodology's robustness in estimating fluid and elastic swimmer parameters, along with their uncertainties. We identify correlations between model parameters and gain insight into emergent swimming trajectories of a single swimmer or a pair of swimmers. Our proposed framework can handle data with a spatiotemporal resolution representative of experiments, showing that this framework can be used to aid in the development of artificial micro-swimmers for biomedical applications, as well as gain a fundamental understanding of the range of parameters that allow for certain motility patterns.

The role of the genital hiatus and prolapse symptom bother.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) severity is poorly correlated with prolapse symptoms. The objective of this study was to investigate the association between genital hiatus (GH) size and presence and severity of bulge symptoms. METHODS: This analysis utilized data from a longitudinal study of parous women. Women underwent annual assessment of POP, GH size, and bulge symptoms. "Bother" was scored by participants reporting bulge symptoms. Three analyses evaluated the association between GH size and bulge symptoms, each using linear mixed models. First, we compared case visits (bulge symptoms reported) to control visits (bulge symptoms never reported), matching for stage. Second, among women who reported bulge sensation at least once during the study, we compared GH size at visits with and without bulge symptoms. Third, among women who reported bulge sensation, we investigated whether GH size was associated with "bother" score, controlling for stage. RESULTS: Of 1528 women (7440 visits), 148 women (803 visits) reported bulge symptoms at ≥ 1 visit and 1380 women never reported bulge symptoms (6637 visits). Comparing 315 case visits (bulge symptoms reported) to 1260 control visits (bulge symptoms never reported), GH size was significantly greater among case visits (3.05 cm versus 2.85 cm, p ≤ 0.0001). In the case-crossover analysis, GH size was similar for visits with and without bulge symptoms (p = 0.63). When evaluating GH size and degree of bulge symptom bother, bother severity was significantly associated with GH size (p = 0.003). CONCLUSIONS: Independent of stage, GH size was significantly associated with prolapse bulge symptoms and bother severity.

Evidence of dose-response following hypofractionated stereotactic radiotherapy to the cavity after surgery for brain metastases.

BACKGROUND AND OBJECTIVE: A retrospective review of consecutive patients between January 2012 and December 2018 receiving hypofractionated stereotactic radiotherapy (HSRT) to the cavity after resection for brain metastases was performed. METHODS: Treatment was delivered using an appropriately commissioned linear accelerator. The primary outcome was time to radiological or histological confirmation of local recurrence following completion of HSRT. Dose-fractionation regimens were converted to biologically 2 Gy-equivalent doses assuming α/ß = 10 (EQD2[10]). Multivariate Cox proportional hazards modelling was performed to determine hazard ratios (HR) with respective 95% confidence intervals (CI). The Log-rank test was used to determine p values taking statistical significance p < 0.05. RESULTS: There were 134 patients and 144 cavities identified. The most common primary histologies were melanoma (n = 49) and lung (n = 32). 116 patients (87%) underwent a gross total resection. Median planning target volume (PTV) was 28 cm3 (range 2.4-149.2). Median EQD2[10] was 38.4 Gy (range 22.3-59.7) and 24 Gy in 3 fractions was the most common regimen. 12 (9%) patients demonstrated local recurrence at median interval 215 days (range 4-594). 7 (5%) patients experienced grade 3 or higher toxicities. In multivariate analysis, EQD2[10] was associated with local failure such that increased equivalent doses improved local control [HR = 0.79 and 95% CI 0.65-0.96, p = 0.0192]. There were no significant associations for primary histology, patient age, volume of residual disease, PTV volume or location. CONCLUSION: This large series demonstrates that HSFRT to the surgical resection cavity for brain metastases has improved local control with increasing dose. Rates of grade 3 or higher toxicity were low overall.

Coronavirus surveillance of wildlife in the Lao People's Democratic Republic detects viral RNA in rodents.

Coronaviruses can become zoonotic, as in the case of COVID-19, and hunting, sale, and consumption of wild animals in Southeast Asia increases the risk for such incidents. We sampled and tested rodents (851) and other mammals and found betacoronavirus RNA in 12 rodents. The sequences belong to two separate genetic clusters and are closely related to those of known rodent coronaviruses detected in the region and distantly related to those of human coronaviruses OC43 and HKU1. Considering the close human-wildlife contact with many species in and beyond the region, a better understanding of virus diversity is urgently needed for the mitigation of future risks.

A Hybrid Model of Cartilage Regeneration Capturing the Interactions Between Cellular Dynamics and Porosity.

To accelerate the development of strategies for cartilage tissue engineering, models are necessary to investigate the interactions between cellular dynamics and the local microenvironment. We use a discrete framework to capture the individual behavior of cells, modeling experiments where cells are seeded in a porous scaffold or hydrogel and over the time course of a month, the scaffold slowly degrades while cells divide and synthesize extracellular matrix constituents. The movement of cells and the ability to proliferate is a function of the local porosity, defined as the volume fraction of fluid in the surrounding region. A phenomenological approach is used to capture a continuous profile for the degrading scaffold and accumulating matrix, which will then change the local porosity throughout the construct. We parameterize the model by first matching total cell counts in the construct to chondrocytes seeded in a polyglycolic acid scaffold (Freed et al. in Biotechnol Bioeng 43:597-604, 1994). We investigate the influence of initial scaffold porosity on the total cell count and spatial profiles of cell and ECM in the construct. Cell counts were higher at day 30 in scaffolds of lower initial porosity, and similar cell counts were obtained using different models of scaffold degradation and matrix accumulation (either uniform or cell-specific). Using this modeling framework, we study the interplay between a phenomenological representation of scaffold architecture and porosity as well as the potential continuous application of growth factors. We determine parameter regimes where large cellular aggregates occur, which can hinder matrix accumulation and cellular proliferation. The developed modeling framework can easily be extended and can be used to identify optimal scaffolds and culture conditions that lead to a desired distribution of extracellular matrix and cell counts throughout the construct.

Peer crowd-based targeting in E-cigarette advertisements: a qualitative study to inform counter-marketing.

BACKGROUND: Cigarette lifestyle marketing with psychographic targeting has been well documented, but few studies address non-cigarette tobacco products. This study examined how young adults respond to e-cigarette advertisements featuring diverse peer crowds - peer groups with shared identities and lifestyles - to inform tobacco counter-marketing design. METHODS: Fifty-nine young adult tobacco users in California participated in interviews and viewed four to five e-cigarette advertisements that featured characters from various peer crowd groups. For each participant, half of the advertisements they viewed showed characters from the same peer crowd as their own, and the other half of the advertisements featured characters from a different peer crowd. Advertisements were presented in random order. Questions probed what types of cues are noticed in the advertisements, and whether and how much participants liked or disliked the advertisements. RESULTS: Results suggest that participants liked and provided richer descriptions of characters and social situations in the advertisements featuring their own peer crowd more than the advertisements featuring a different peer crowd. Mismatching age or device type was also noted: participants reported advertisements showing older adults were not intended for them. Participants who used larger vaporizers tended to dislike cigalike advertisements even if they featured a matching peer crowd. CONCLUSION: Peer crowd and lifestyle cues, age and device type are all salient features of e-cigarette advertising for young adults. Similarly, educational campaigns about e-cigarettes should employ peer crowd-based targeting to engage young adults, though messages should be carefully tested to ensure authentic and realistic portrayals.

First evidence of a new simian adenovirus clustering with Human mastadenovirus F viruses.

BACKGROUND: Adenoviruses play an important role as human pathogens, though most infections are believed to be asymptomatic. The over 100 human adenovirus types are classified into seven species (A-G), some of which include simian adenoviruses. Recent findings have highlighted that simian adenoviruses have a zoonotic potential and that some human adenoviruses are likely the result of relatively recent spillover events. METHODS: In order to evaluate the risks associated with primates hunted and sold as bushmeat, multiple samples from 24 freshly killed monkeys were collected in the Republic of the Congo and tested for adenovirus DNA by PCRs targeting the conserved DNA polymerase and hexon genes. RESULTS: The DNA of a novel simian adenovirus was detected in a moustached monkey (Cercopithecus cephus) by the DNA polymerase PCR, but not by the hexon PCR. The 275 nucleotide amplicon was most closely related to members of the Human mastadenovirus F species (93% HAdV-40 and 89% HAdV-41 amino acid identity), rather than to other known simian adenoviruses. CONCLUSIONS: The phylogenetic clustering with Human mastadenovirus F sequences suggests a common ancestor, more recent than the last common ancestor of humans and moustached monkeys. The findings increase concerns about the zoonotic potential of simian adenoviruses and highlight the need for more research and surveillance on the issue.

Extent of surrounding edema does not correlate with acute complications after radiosurgery for melanoma brain metastases.

AIM: To assess whether extent of surrounding edema correlates with acute adverse clinical outcomes within 3 months after stereotactic radiosurgery (SRS) for melanoma brain metastases (BM). METHODS: Patients with melanoma BM treated with SRS were included in a single center retrospective analysis. A contrast-enhanced magnetic resonance image (MRI) brain was acquired on the day of treatment and used to calculate the volume of the largest lesion (the index BM) and total volume of all BM. Their corresponding volume of surrounding edema was defined based on the fluid attenuated inversion recovery (FLAIR) sequence. After SRS, MRI was performed every 3 months for at least 2 years if the patient remained well enough to do so. Adverse neurologic events after SRS were defined using common terminology criteria for adverse events (CTCAE) version 5.0. Multivariate regression analyses assessed for associations between BM size and edema at baseline with increasing edema and neurologic adverse events within 3 months after SRS. RESULTS: Mean volume of the index BM reduced from 2.2 to 0.5 cm3 at 3 months after SRS (p = 0.03). Mean volume of edema surrounding the index BM was 6.4 cm3 at baseline, 10.2 cm3 at 3 months and 5.5 cm3 at 6 months. There were 7/43 (16%) patients that experienced an adverse neurological event within 3 months (attributable to any cause) and 4/43 (9%) were associated with an increase in BM edema. On univariate and multivariate analyses, there were no correlations between any baseline factors and volume of edema at 3 months. However, SRS dose delivered and systemic therapy use within 4 weeks of SRS both correlated with a reduction in edema surrounding the index BM. CONCLUSION: A transient increase in mean volume of edema was apparent at 3 months after SRS. However, this resolved by 6 months and did not correlate with adverse events or dexamethasone requirement. Thus, the clinical significance is uncertain.