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During an outbreak, infectious disease can spread among populations through host movement, potentially fueling local outbreaks with their own epidemiological dynamics. However, it is difficult to know how often infections between populations are transmitted by diseased travelers infecting healthy residents when abroad, rather than by diseased residents infecting healthy travelers, who later return home with the new pathogen. In this paper, we introduce a phylogeographic model where pathogens spread through visitor dynamics, whereby hosts visit other populations through short trips before returning home. To do so, we used the stationary properties of an epidemiological compartment model with visitor dynamics to construct an approximation that is statistically accurate and computationally tractable for phylogenetic modeling. In addition, we derive mathematical properties for the approximating model that provide a sufficient condition under which the approximation remains accurate. We applied our model to empirical infection data and travel statistics from the European SARS-CoV-2 pandemic. Inference under our model suggests that, in the early stages of the outbreak, SARS-CoV-2 was more often "pulled" into the home countries of returning travelers than "pushed" into foreign countries by visitors from abroad. Estimates of host movement-related parameter values under our visitor model suggest that alternative migration models, with trips of indefinite length, may underestimate the magnitude of outbreaks caused by visitors. This study emphasizes the importance of carefully incorporating host movement dynamics into such models.

Dengue virus is transmitted by Aedes mosquitoes, which are now prevalent in destinations commonly visited by UK travelers. Increased international travel and factors including climate change, contribute to the global increase in dengue cases. Here, we evaluate the healthcare burden of dengue in England. This retrospective, descriptive, cohort study (2010-2023) utilized data collected from National Health Service healthcare records in the Clinical Practice Research Datalink (CPRD) Aurum linked with Hospital Episode Statistics, and Office for National Statistics mortality data. The primary objective was to determine the occurrence of hospitalized dengue. Other objectives were evaluation of healthcare resource utilization and costs, characteristics of hospitalized dengue cases, and complications due to dengue. Exploratory cohorts for suspected dengue in primary care were also reported. Data from CPRD-linked records for 596 patients comprising the hospitalized dengue cohort were evaluated; the incidence rate of hospitalized dengue progressively increased from 2010 until the highest in 2019 (5.8 per million person-years); rates increased in 2022 after COVID-19 lockdowns. Approximately one-third of hospitalized dengue cases were aged 18-29 years, most were White or Asian, and the most common complication was gastrointestinal conditions (gastroenteritis/colitis; 34.7 cases per 1000 person-years). Healthcare costs in the year following hospitalized dengue cases were mostly driven by inpatient admission costs; ~20% of cases had a subsequent hospital admission (~50% were dengue-related). A total of 2286 suspected cases of dengue were reported in primary care, with 1066 unconfirmed and 1220 confirmed cases. Increasing incidence of dengue cases in England has followed global trends. The associated healthcare burden of imported dengue suggests a need for targeted public health strategies, particularly among younger travelers. Improvements in general practitioners' reporting of suspected dengue cases and associated details of symptoms and travel history are warranted.

African tick bite fever (ATBF) is a spotted fever group rickettsiosis caused by Rickettsia africae and is often identified among travelers returning from sub-Saharan Africa. Clinical presentation may be mild or nonspecific, often delaying diagnosis despite characteristic findings such as inoculation eschars. A 52-year-old male presented to the preoperative holding area prior to a scheduled left-sided inguinal hernia repair after recently returning from a game-hunting trip to Africa. During preoperative intake, he was noted to have a fever of 106 °F despite being otherwise asymptomatic. Physical examination revealed two black eschars on the patient's back and right shin. Given the presence of high-grade fever, the scheduled procedure was canceled, and the patient was discharged for outpatient evaluation. He was subsequently treated with a 10-day course of doxycycline for suspected African tick bite fever. At two-week follow-up, the patient remained asymptomatic, his fever had resolved, and repeat preoperative evaluation was unremarkable. Surgical repair of the inguinal hernia was performed without complications. Although laboratory confirmation was not obtained, the clinical presentation, including characteristic eschars, high-grade fever, and recent travel to sub-Saharan Africa, was highly suggestive of ATBF. This case underscores the importance of maintaining clinical suspicion for ATBF in returning travelers and highlights the diagnostic value of inoculation eschars, even in the absence of systemic symptoms. Early recognition of suspected ATBF and empiric doxycycline therapy may result in rapid clinical improvement and help prevent unnecessary delays in care.

Households (HH) have been traditionally described as the main environments where people are at risk of dengue and other arbovirus infections. Mounting entomological evidence suggests a larger role for environments other than HH. Recently, an agent-based model (ABM) estimated that over half of infections occur in non-household (NH) environments such as workplaces, markets, and recreational sites. Despite the inferred importance of NH sites, we do not yet know how their urban spatial configurations, and human and vector mobility between them, affects their role in dengue transmission. To address this gap, we expanded an ABM calibrated with field data from Kenya to examine movement of people and vectors under different spatial configurations of buildings. We assessed the number of people traveling between HH and NH and the distances traveled, in three urban configurations: NH distributed randomly (scattered), concentrated in a single center, or clustered in multiple centers. Across simulations, the number of people moving was the most influential variable, with higher movement between HH and NH increasing case numbers. The number of cases was also higher when NH were scattered compared to centered or clustered. Intriguingly, the distance people traveled from HH to NH had little effect on dengue burden but influenced the spatial clustering of infections. These findings underscore the role of NH as major spreaders of infections between HH and NH environments, and the importance of human movement in driving dengue dynamics.

Legionellosis is a bacterial disease caused by inhalation or aspiration of Legionella bacteria; Legionnaires disease is a type of legionellosis characterized by illness with pneumonia. During November 2024, the U.S. Virgin Islands (USVI) Department of Health (VIDOH) was notified of two confirmed Legionnaires disease cases among travelers to two different hotels on St. Croix Island. VIDOH investigated to determine exposure sources and prevent additional cases. Two additional legionellosis cases were identified. The four patients with cases were aged 53-73 years; two patients were hospitalized and none died. At hotel A, L. pneumophila was detected in three of 21 (14%) environmental samples. VIDOH required hotel A to close one guest room, remediate, and retest. At hotel B, L. pneumophila was detected in 22 of 40 (55%) samples. VIDOH required hotel B to cease hotel operations until remediation and retesting were completed. L. pneumophila was isolated from shower samples at both hotels, in the cistern and cold water system at hotel A, and in cold and hot water systems at hotel B. The two USVI outbreaks underscore the importance of reporting legionellosis among returned travelers to facilitate local public health investigations and prevent additional cases. In addition, in tropical climates, cold water systems operate at temperatures favorable for Legionella growth (77°F-113°F [25°C-45°C]), highlighting the importance of effective water management programs and water system disinfection to prevent disease spread.

The genetic basis for sperm swimming ability in humans is underinvestigated. In particular, selfish genes known as segregation distorters dramatically influence sperm swimming in organisms like mice. Segregation distorters are difficult to screen for in humans because no tool exists to compete sperm by swimming ability and collect the separated fast and slow sperm for further study. We designed, built, and tested a "sperm racetrack", a microfluidic device that races sperm against each other and allows collection of sperm based on the distance travelled. This biologically-inspired PDMS device contains a long, straight channel with counterflow against which sperm swim naturally, and contains regularly-spaced ports along the channel for collection of sperm after the race. We performed a series of test races and found that sperm in the fourth channel segment are significantly faster swimming according to video analysis than those in the second channel segment. Sperm from these same segments are significantly different in speed after extraction from the channel as well. We characterized several swimming behaviors for these faster and slower sperm, including linearity (ability to swim in a straight line) and wobble (amount of side-to-side head movement per beat), and found a significant association between higher sperm wobble and distance travelled along the channel in extracted sperm. Together, we show that the sperm racetrack separates sperm according to swimming speed, and this sorting of sperm is faithfully maintained after extraction from the device as fast- and slow-swimming groups. The sperm racetrack may prove useful in understanding the genetic and physiological causes of sperm immotility, and in identifying swimming-based segregation distorters in humans. The sperm racetrack may also serve as a tool for enriching fast-swimming sperm for selection in assisted reproductive technologies such as in vitro fertilization.

Human mobility fundamentally shapes the spatial spread of infectious diseases, yet the level of detail required from mobility data to accurately inform epidemic models remains unclear. Mobile phone records offer unprecedented resolution on population movements, but little attention has been devoted however to determining (i) which aspects of mobility are epidemiologically relevant and (ii) what level of data resolution is necessary to capture spatial invasion dynamics. Using mobile phone records from 9.5 million users in Senegal (approximately 80% of the population), we systematically compare three approaches to aggregating mobility data for epidemic modeling. These approaches span a range of resolutions: high-resolution tracking of all individual displacements between consecutive visited locations (HR), medium-resolution accounting for time spent in all visited locations (MR), and low-resolution identification of the most-visited location (LR). We incorporate these mobility representations into a metapopulation epidemic model that explicitly accounts for transmission from residents, visitors, and returning travelers, and simulate diseases with varying transmissibility corresponding to controlled epidemic conditions, seasonal influenza-like transmission, and highly transmissible pathogens. We find that preserving all observed displacements in individual trajectories does not necessarily improve the epidemiological relevance of mobility in pathogens spatial transmission. Instead, displacement-based networks fragment long-range trips and underestimate key spatial connections relevant for disease spread. In contrast, approaches that capture where individuals spend most of their time (such as home, work, or school) more accurately reproduce spatial invasion patterns. Accounting for additional daily activities beyond these primary locations provides little additional epidemiological information. Our results suggest that lower-resolution mobility indicators capturing time spent at key locations are sufficient to inform predictive epidemic models. These findings have important implications for both epidemic modeling and data governance, indicating that mobile phone data can be aggregated to reduce privacy issues while still providing the essential information needed to model spatial disease transmission.

Adult children increasingly provide care to parents from varying distances, yet the relationship between proximity and caregiver mental health is not well understood. This study characterizes caregiving activities of adult-child caregivers based on residential proximity to their parent and examines associations with depression and anxiety symptoms. Data from the 2021 National Health and Aging Trends Study Round 11 was linked with National Study of Caregiving IV. The sample included adult-child caregivers of Medicare beneficiaries aged 71 and older. Bivariate and multivariable logistic regression models assessed associations between proximity (travel time between the caregivers and their parents), caregiving activities, and symptoms of depression and anxiety. Analyses were weighted to produce nationally representative estimates. Among 932 caregivers representing more than 9 million caregivers nationwide, 26.3% co-reside with care-recipients, 47.4% live 1-20 minutes away, 13.1% live 21-59 minutes away, and 13.2% are long-distance caregivers living ≥1 hour away. Co-residing caregivers were more likely to perform health management, health care, ADL, and IADL tasks. However, proximity was not associated with differences in health system logistics, patient advocacy, and financial support activities. Proximity did not predict of depression or anxiety in adjusted models. Adult children engage in diverse caregiving activities regardless of distance, especially in logistics, advocacy, and financial support. Factors beyond proximity likely influence caregiver mental health. Findings highlight the need for tailored policies and services supporting both distance and proximal caregivers of older adults.

Causal therapy has achieved success in the treatment of epithelial tumors, which account for more than 80% of all cancers. Although frequently claimed as breakthroughs, cancer therapy has achieved limited increases in survival of only weeks to several months, and cancer incidence continues to increase while metastasis rates, which are primarily responsible for cancer mortality, remain constant. This reflects an incomplete understanding of carcinogenesis and metastatic progression. Over a 25-year timeframe, the series "Epistemology of the Origin of Cancer" has examined the biological basis of carcinogenesis and metastasis. Part I addressed carcinogenesis, Part II identified the first cancer cell, and Part III described the development of local pre-metastatic niches and traveling cancer satellites. In this fourth part, the conditions required for distant metastasis are discussed, including the sequential development of metastatic niches (MN-1, MN-2, and MN-3), transendothelial migration, dormancy, immune modulation, extracellular matrix remodeling, and metastatic niche maturation. The review proposes that metastatic progression depends on the formation of metastatic cancer satellites consisting of metastatic cancer cells, metastasis-associated fibroblasts (MAFs), stromal components, chemokine coatings, platelets, and neutrophil extracellular traps (NETs), each contributing to immune evasion and dissemination. This sequential distant metastatic niche model provides a biological framework explaining clinical observations including metastatic dormancy, relapse after surgery or anticancer therapy, tumor heterogeneity, and the limited long-term success of current therapeutic approaches.

Submacular hemorrhage (SMH), which may arise from age-related macular degeneration, retinal arterial macroaneurysm, and other causes, can result in severe vision loss and central visual field impairment. Although tissue plasminogen activator (tPA) is used off-label to treat SMH in many countries, no formulation has been approved for this indication. Because early intervention is critical when tPA is used for SMH, limited access to centers that can provide this treatment may delay care and reduce treatment opportunities. Decentralized clinical trials (DCTs) reduce or eliminate the need for participants to travel to trial sites. We therefore designed the investigator-initiated SACLA trial to evaluate subretinal tPA for SMH. The DCT framework is intended to reduce logistical barriers related to the disease severity and rarity. The SACLA trial is a phase II multicenter, open-label, single-arm surgical study with a pre-post comparison design (jRCT2071250003). Twenty eligible participants will undergo pars plana vitrectomy followed by subretinal injection of 0.1 mL (8,000 IU) of tPA. Participants will remain hospitalized at the trial site until the primary outcome, change in central foveal thickness (CFT) from baseline at Week 1, is assessed. Thereafter, follow-up visits will be conducted at either the trial site or partner sites within the DCT framework. Secondary efficacy outcomes include change in CFT from baseline, presence of a foveal hemorrhage measuring at least 1 disc diameter, best-corrected visual acuity (BCVA), and change in BCVA from baseline at Weeks 4 and 12. Adverse events will be collected throughout the 12-week observation period to assess safety. The protocol and related study documents were reviewed and approved by the Saga University Hospital Institutional Review Board. This study is designed to generate prospective evidence on the feasibility, short-term anatomical response, and safety of subretinal tPA for SMH.

By assessing public awareness, preventive behavior, and knowledge regarding invasive mosquito species in Saarland, Germany, a non-endemic region at increasing invasion risk, this study aimed to explore how the introduction of invasive mosquitoes can be addressed in non-endemic areas. A population-based anonymous questionnaire in Saarland was conducted from February to June 2024. Participants were recruited through broad public dissemination using digital and analog approaches. Nine items assessed mosquito protection practices, knowledge of invasive species, and potential for pathogen transmission. Among 1064 respondents, 623 (58.6%) met the inclusion criteria. While over half of them recognized stagnant water removal as an effective preventive measure, fewer than one fifth practiced it regularly. Travel medicine consultations were associated with greater use of protective clothing. Among participants aged 26-35, men were more likely than women to report no prior engagement with mosquito prevention measures. Although most participants had heard of Aedes albopictus, fewer than half linked it to chikungunya transmission. Marked discrepancies persist between general awareness and evidence-based preventive behavior. Targeted seasonal education campaigns represent a modifiable lever to delay vector establishment and improve outbreak preparedness.

Weather and climate variability increasingly shape urban travel behavior, yet the short-term temporal dynamics and contextual modifiers of weather-transit relationships remain poorly understood. We analyzed system-wide hourly bus ridership in the Denver metropolitan area from June 2022 through September 2023 using fixed-effects negative binomial distributed lag nonlinear models with lags up to 24 hours. Nonlinear exposure-response and lag-response functions were specified for hourly Universal Thermal Climate Index (UTCI) and precipitation, with additional indicators for daily ozone exceedance and wildfire smoke. Models adjust for hour-of-day, day-of-week, and month-year fixed effects, with standard errors clustered by day. Stratified analyses assess heterogeneity by time period, season, fare policy, and shelter availability, with interaction evaluated using Wald tests. Cold thermal stress was associated with the largest, most persistent reductions in ridership, with cumulative declines of -15.7% (95% CI: -26.0%, -4.0%) over 0-24 hours. Precipitation was associated with sharp but transient reductions concentrated within 3-6 hours (-8.4% to -9.8%), with little evidence of longer-term displacement. Heat associations were weaker and context-dependent, with modest short-run increases, but net same-day declines. Associations varied by time of day and season, were attenuated during the free-fare period, and differed by shelter availability. In contrast, ozone exceedance and wildfire smoke exhibited limited and inconsistent associations, with measurable reductions primarily during morning commute during heavier smoke conditions. Overall, transit ridership is more strongly associated with short-term weather exposure, than with ambient air quality. Fare policy and stop-level infrastructure modify these associations, highlighting actionable strategies to enhance transit resilience under increasing climate variability.

Based on cannabinoid receptor 2(CB2R) mediated Toll-like receptor 4(TLR4) signaling pathway, this study aimed to explore the mechanism of regulating the abnormal polarization of amygdala microglia in mice with anxiety disorder by Baidi Jielv Anshen Formula. The anxiety-like mouse model was established by chronic restraint stress(CRS) 21 d and randomly divided into 6 groups of a blank group, a model group, a high-dose Baidi Jielv Anshen Formula group(10.92 g·kg~(-1)), a medium-dose Baidi Jielv Anshen Formula group(5.46 g·kg~(-1)), a low-dose Baidi Jielv Anshen Formula group(2.73 g·kg~(-1)), and a positive drug diazepam group(2 mg·kg~(-1)). The mice in each group were given intragastric administration on the 8th day of modeling. After 14 days of continuous administration, anxiety-like behavior was evaluated by open field test, elevated plus maze test, and light-dark box test. The number of proto-oncogene c-fos positive cells was detected by immunofluorescence(IF), and glutamic acid(Glu) and gamma-aminobutyric acid(GABA) were detected by enzyme-linked immunosorbent assay(ELISA). Endocannabinoid system-related proteins in amygdala were detected by Western blot. Ionized calcium binding adaptor molecule 1(Iba-1), a marker protein of microglia in amygdala, was detected by IF, nitric oxide synthase(iNOS) and arginase 1(Arg-1) were detected by IF and Western blot, and the morphology and polarization of microglia were evaluated. Proinflammatory cytokines and anti-inflammatory cytokines were detected by Western blot to evaluate the amygdala inflammation. The protein associated TLR4 signaling pathway was detected by Western blot to evaluate the activation of the TLR4 pathway. The results showed that both Baidi Jielv Anshen Formula and diazepam could significantly improve the anxiety-like behavior of CRS-induced mice, and could increase the center distance and center time in open field test to varying degrees, improve OE% and OT% in the elevated plus maze test, and increase the time spent and distance traveled in the light compartment in the light-dark box test. At the same time, the level of c-fos in amygdala can be significantly reduced and the over-activation of amygdala neurons can be alleviated by Baidi Jielv Anshen Formula. The CB2R feedback protein increase induced by CRS was significantly inhibited by Baidi Jielv Anshen Formula. It also significantly reduced the excessive activation of microglia in amygdala, restored the balance of M1/M2 polarization, and inhibited the production of inflammatory cytokines. The expression of TLR4 pathway-related proteins can be down-regulated. Therefore, Baidi Jielv Anshen Formula may inhibit the TLR4 signaling pathway by activating CB2R, restore the polarization balance of microglia, inhibit neuroinflammation, improve the over-activation of amygdala, and play an anti-anxiety role.

To assess knowledge of abortion medications by mail among a sample of patients accessing abortion care at brick-and-mortar clinics. We analyze survey data from 359 patients at 6 abortion clinics across the United States. One-third of respondents knew that abortion medications could be mailed to any address in the United States. Compared to residents, a slightly lower proportion of people who traveled from out of state knew about online pills. Most respondents who knew about online pills (54%) went to a clinic because they wanted an in-person appointment. There is a continued need for campaigns to increase awareness of medication abortion by mail.

Exosomes are a subtype of extracellular vesicles, critical for intercellular communication. They are released from a cell via exocytosis, after which they travel through the extracellular fluid until they reach a target cell. Research in the fields of cellular medicine, regenerative and stem cell therapy continues to grow exponentially. Deciphering the biological properties of mesenchymal stem cells-exosomes as cell-free therapeutic tools is important for wound healing and cutaneous regeneration. The future is also bright for genetically engineering exosomes for targeted diagnostic and therapeutic applications.

Facility-based delivery is essential for reducing maternal and infant mortality, particularly in low- and middle-income countries. However, evidence remains limited on how structural and socioeconomic inequalities shape access to delivery services in Indonesia. Based on Andersen's health services utilization framework, this study examined structural and individual determinants of facility-based delivery in Indonesia using nationally representative data, with particular attention to access-related and socioeconomic inequalities. This cross-sectional study analyzed nationally representative data from the 2023 Indonesian Health Survey and included 68,884 women aged 10-54 years who had given birth. Predisposing, enabling, and need factors were analyzed according to Andersen's framework. Univariate, bivariate, and multivariate analyses were performed, and multiple logistic regression was used to identify factors associated with non-facility delivery. Substantial inequalities in facility-based delivery were observed. Overall, 7.2% of women in Indonesia delivered outside a health facility. After adjustment, rural residence (adjusted odds ratio [AOR] = 1.980; 95% CI: 1.715-2.287), lower education (AOR = 2.236; 95% CI: 2.010-2.547), longer travel time to health facilities (AOR = 2.292; 95% CI: 2.000-2.634), lack of health insurance (AOR = 2.253; 95% CI: 1.983-2.560), and inadequate antenatal care (AOR = 2.786; 95% CI: 2.461-3.154) were strong predictors of non-facility delivery. Facility-based delivery in Indonesia was shaped by contextual and enabling factors, rather than by individual characteristics alone. Integrated policies are needed to improve geographic access, increase health insurance coverage, strengthen community-based health education, and improve antenatal care programs, particularly in rural areas, to expand access to delivery services at health facilities.

Due to the abundant and increasing anthropogenic release of nanoplastics (NPs) and pharmaceutically active compounds (PhACs) into wastewater, it is critical to fully characterize the potential synergistic effects of mixtures of these emerging pollutants on freshwater organisms. In this study, we evaluated the behavioral and physiological responses of Daphnia magna exposed to NPs and an overlooked PhAC, caffeine (CAF). Namely, pregnant adult D. magna were exposed over 48 h to 50 mg/L synthesized polystyrene nanoplastics (PSNPs, 300 nm), 100 µg/L CAF, and CAF + NP mixtures. Then, the following variables were evaluated: (1) the total number of offspring produced, (2) swimming behavior, quantified as average speed (mm/s), average acceleration (mm/s2), mobility rate (%), exploration rate (%), and total distance traveled (mm) during one minute, and (3) heart rate, appendage curling rate, and post-abdominal claw movement counted during one minute. We determined significantly elevated swimming behavior for NPs and CAF + NPs treatment groups compared to the controls. The observed responses are hypothesized to be somehow related to the adherence of NPs on the carapace and digestive tract of the daphnids, verified by scanning electron microscope (SEM) imaging. Although not conclusive, the number of offspring exposed to NPs was decreased compared to the control, but not in the CAF + NPs treatment indicating an antagonistic effect of the mixture that requires further testing. This study contributes important information towards the understanding of sublethal impacts of CAF-NP mixtures on freshwater invertebrates and the corresponding ecological consequences of behavior changes.