Approximating Intermediate Feature Maps of Self-Supervised Convolution Neural Network to Learn Hard Positive Representations in Chest Radiography.

Recent advances in contrastive learning have significantly improved the performance of deep learning models. In contrastive learning of medical images, dealing with positive representation is sometimes difficult because some strong augmentation techniques can disrupt contrastive learning owing to the subtle differences between other standardized CXRs compared to augmented positive pairs; therefore, additional efforts are required. In this study, we propose intermediate feature approximation (IFA) loss, which improves the performance of contrastive convolutional neural networks by focusing more on positive representations of CXRs without additional augmentations. The IFA loss encourages the feature maps of a query image and its positive pair to resemble each other by maximizing the cosine similarity between the intermediate feature outputs of the original data and the positive pairs. Therefore, we used the InfoNCE loss, which is commonly used loss to address negative representations, and the IFA loss, which addresses positive representations, together to improve the contrastive network. We evaluated the performance of the network using various downstream tasks, including classification, object detection, and a generative adversarial network (GAN) inversion task. The downstream task results demonstrated that IFA loss can improve the performance of effectively overcoming data imbalance and data scarcity; furthermore, it can serve as a perceptual loss encoder for GAN inversion. In addition, we have made our model publicly available to facilitate access and encourage further research and collaboration in the field.

Generative AI in glioma: ensuring diversity in training image phenotypes to improve diagnostic performance for IDH mutation prediction.

BACKGROUND: This study evaluated whether generative artificial intelligence-based augmentation (GAA) can provide diverse and realistic imaging phenotypes and improve deep learning-based classification of isocitrate dehydrogenase (IDH) type in glioma compared with neuroradiologists. METHODS: For model development, 565 patients (346 IDH-wildtype, 219 IDH-mutant) with paired contrast-enhanced T1 and FLAIR MRI scans were collected from tertiary hospital and The Cancer Imaging Archive. Performance was tested on internal (119, 78 IDH-wildtype, 41 IDH-mutant [IDH1 and 2]) and external test sets (108, 72 IDH-wildtype, 36 IDH-mutant). GAA was developed using score-based diffusion model and ResNet50 classifier. The optimal GAA was selected in comparison with null model. Two neuroradiologists (R1, R2) assessed realism, diversity of imaging phenotypes, and predicted IDH mutation. The performance of a classifier trained with optimal GAA was compared with that of neuroradiologists using area under the receiver operating characteristics curve (AUC). The effect of tumor size and contrast enhancement on GAA performance was tested. RESULTS: Generated images demonstrated realism (Turing's test: 47.5%-50.5%) and diversity indicating IDH type. Optimal GAA was achieved with augmentation with 110 000 generated slices (AUC: 0.938). The classifier trained with optimal GAA demonstrated significantly higher AUC values than neuroradiologists in both the internal (R1, P=.003; R2, P<.001) and external test sets (R1, P<.01; R2, P<.001). GAA with large-sized tumors or predominant enhancement showed comparable performance to optimal GAA (internal test: AUC 0.956 and 0.922; external test: 0.810 and 0.749). CONCLUSIONS: Application of generative AI with realistic and diverse images provided better diagnostic performance than neuroradiologists for predicting IDH type in glioma.

Generation and characterization of a humanized ACE2 mouse model to study long-term impacts of SARS-CoV-2 infection.

Although the COVID-19 pandemic has officially ended, the persistent challenge of long-COVID or post-acute COVID sequelae (PASC) continues to impact societies globally, highlighting the urgent need for ongoing research into its mechanisms and therapeutic approaches. Our team has recently developed a novel humanized ACE2 mouse model (hACE2ki) designed explicitly for long-COVID/PASC research. This model exhibits human ACE2 expression in tissue and cell-specific patterns akin to mouse Ace2. When we exposed young adult hACE2ki mice (6 weeks old) to various SARS-CoV-2 lineages, including WA, Delta, and Omicron, at a dose of 5 × 105 PFU/mouse via nasal instillation, the mice demonstrated distinctive phenotypes characterized by differences in viral load in the lung, trachea, and nasal turbinate, weight loss, and changes in pro-inflammatory cytokines and immune cell profiles in bronchoalveolar lavage fluid. Notably, no mortality was observed in this age group. Further, to assess the model's relevance for long-COVID studies, we investigated tau protein pathologies, which are linked to Alzheimer's disease, in the brains of these mice post SARS-CoV-2 infection. Our findings revealed the accumulation and longitudinal propagation of tau, confirming the potential of our hACE2ki mouse model for preclinical studies of long-COVID.

Ixodid ticks from wild and domestic animals in East and Central Asian flyways.

Tick-borne diseases have a significant impact on human and animal populations, posing an increasing threat to public health, particularly in the context of climate change. Along with the various natural hosts of ticks, birds play a notable role in transmitting ticks and tick-borne pathogens, indicating the importance of monitoring flyways and establishing a cooperative network for comprehensive surveillance and to collect diverse tick samples across various regions. This study aimed to develop an international network for surveillance of disease, collection of sufficient tick samples, and overall identification of the geographical distribution of host and ticks in Asian regions, especially in 11 countries on East Asian and Central Asian flyways. Ticks were collected from wild animals, domestic animals, and vegetation to identify the differences between Ixodid ticks and understand tick distribution. We collected a total 6,624 of ticks from 11 collaborating Asian countries, the Republic of Korea (ROK), Japan, Thailand, Philippines, Indonesia, Cambodia, Vietnam, Taiwan, Hong Kong, Mongolia and Pakistan. We identified 17 host animals and 47 species of both residential and migratory birds. Ticks from birds collected from four countries (ROK, Japan, Hong Kong and Mongolia) belonged to two genera, Haemaphysalis and Ixodes, including Haemaphysalis (H.) longicornis, H. flava, H. concinna, H. hystricis, H. formosensis, Ixodes (I.) nipponensis and I. persulcatus. The potential of migratory birds to cross ecological barriers with ticks and tick-borne diseases indicated the need for further investigations to understand the migration of birds as potential vectors and the new influx of zoonotic diseases along migratory bird flyways. This study suggests the potential risk of spreading tick-borne diseases through birds, thus highlighting the importance of international cooperative networking.

Discovery, validation, and prodrug design of an ACE2 activator for treating bacterial infection-induced lung inflammation.

Exacerbated inflammatory responses can be detrimental and pose fatal threats to the host, as exemplified by the global impact of the COVID-19 pandemic, resulting in millions of fatalities. Developing novel drugs to combat the damaging effects of inflammation is essential for both preventive measures and therapeutic interventions. Accumulating evidence suggests that Angiotensin Converting Enzyme 2 (ACE2) possesses the ability to optimize inflammatory responses. However, the clinical applicability of this potential is limited due to the lack of dependable ACE2 activators. In this study, we conducted a screening of an FDA-approved drug library and successfully identified a novel ACE2 activator, termed H4. The activator demonstrated the capability to mitigate lung inflammation caused by bacterial lung infections, effectively modulating neutrophil infiltration. Importantly, to improve the clinical applicability of the poorly water-soluble H4, we developed a prodrug variant with significantly enhanced water solubility while maintaining a similar level of efficacy as H4 in attenuating inflammatory responses in the lungs of mice exposed to bacterial infections. This finding highlights the potential of formulated H4 as a promising candidate for the treatment and prevention of inflammatory diseases, including lung-related conditions.

Microplastics in gastrointestinal tracts of gentoo penguin (Pygoscelis papua) chicks on King George Island, Antarctica.

Microplastics (< 5 mm) have been found in marine ecosystems worldwide, even in Antarctic ecosystems. In this study, the stomach and upper intestines of 14 dead gentoo penguin (Pygoscelis papua) chicks were collected and screened for microplastics on King George Island, a gateway to Antarctic research and tourism. A total of 378 microplastics were identified by Fourier-transform infrared spectroscopy, with 27.0 ± 25.3 microplastics per individual. The detected number of microplastics did not increase with the mass of penguin chicks, suggesting no permanent accumulation of microplastics. However, the concentration of microplastics was much higher (9.1 ± 10.8 microplastics per individual within the size range 100-5000 µm) than the previously reported concentration in the penguin feces, and a greater number of smaller microplastics were found. Marine debris surveys near the breeding colony found various plastic (79.3%) to be the most frequent type of beached debris, suggesting that local sources of marine plastic waste could have contributed to microplastic contamination of penguin chicks being fed by parents that forage in nearby seas. This finding confirms the presence of microplastics in an Antarctic ecosystem and suggests the need for stronger waste management in Antarctica and a standardized scheme of microplastic monitoring in this once-pristine ecosystem.

Global assessment of marine plastic exposure risk for oceanic birds.

Plastic pollution is distributed patchily around the world's oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species.

The mitophagy receptor NIX induces vIRF-1 oligomerization and interaction with GABARAPL1 for the promotion of HHV-8 reactivation-induced mitophagy.

Recently, viruses have been shown to regulate selective autophagy for productive infections. For instance, human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), activates selective autophagy of mitochondria, termed mitophagy, thereby inhibiting antiviral innate immune responses during lytic infection in host cells. We previously demonstrated that HHV-8 viral interferon regulatory factor 1 (vIRF-1) plays a crucial role in lytic replication-activated mitophagy by interacting with cellular mitophagic proteins, including NIX and TUFM. However, the precise molecular mechanisms by which these interactions lead to mitophagy activation remain to be determined. Here, we show that vIRF-1 binds directly to mammalian autophagy-related gene 8 (ATG8) proteins, preferentially GABARAPL1 in infected cells, in an LC3-interacting region (LIR)-independent manner. Accordingly, we identified key residues in vIRF-1 and GABARAPL1 required for mutual interaction and demonstrated that the interaction is essential for mitophagy activation and HHV-8 productive replication. Interestingly, the mitophagy receptor NIX promotes vIRF-1-GABARAPL1 interaction, and NIX/vIRF-1-induced mitophagy is significantly inhibited in GABARAPL1-deficient cells. Moreover, a vIRF-1 variant defective in GABARAPL1 binding substantially loses the ability to induce vIRF-1/NIX-induced mitophagy. These results suggest that NIX supports vIRF-1 activity as a mitophagy mediator. In addition, we found that NIX promotes vIRF-1 aggregation and stabilizes aggregated vIRF-1. Together, these findings indicate that vIRF-1 plays a role as a viral mitophagy mediator that can be activated by a cellular mitophagy receptor.

A Hospital-Based Infant Safe Sleep Intervention and Safe Sleep Practices Among Young Women: A Prospective Longitudinal Study.

INTRODUCTION: The rates of sudden unexpected infant death (SUID) are still high in the U.S. The longitudinal effects of SUID preventive education on infant safe sleep practices are less known. The current study evaluated the effects of a comprehensive hospital-based, SUID preventive intervention on safe infant sleep practices in the first six months of life and to identify factors associated with infant sleep practices. METHODS: Using a one-group pretest and multiple posttest design, the current quantitative study examined the impacts of the infant safe sleep intervention among 411 women recruited at a large, urban, university medical center. Participants were prospectively followed and completed four surveys from childbirth. Linear mixed models were used to evaluate the effects of the SUID prevention program on four sleep practice outcomes, including removing unsafe items from the sleeping environment, bed sharing, room sharing without bed sharing, and placing the infant in a supine sleep position. RESULTS: Compared to the baseline, participants were less likely to use unsafe items (e.g., soft bedding) in infants' sleeping areas over time. However, we found that participants reported more frequent bed sharing at 3-month and 6-month follow-ups, compared to the baseline. CONCLUSIONS: Overall, maternal education and family income were positively related to healthy infant safe sleep practices. A hospital-based preventive intervention pairing an educational initiative with home-visiting services might improve safe sleep practices to remove accidental suffocation risks from the infant sleep environment.

Efficacies of Potential Probiotic Candidates Isolated from Traditional Fermented Korean Foods in Stimulating Immunoglobulin A Secretion.

The aim of this study was to evaluate efficacies of selected lactic acid bacteria (LAB) in inducing immunoglobulin A (IgA) secretion. Twenty-five different LAB isolated from traditional fermented Korean foods were characterized for their probiotic properties and screened to identify those that could stimulate lamina propria cells (LPCs) from Peyer's patch to secret IgA in vitro. Among them, four strains (Lactiplantibacillus plantarum CJW55-10, Lactiplantibacillus pentosus CJW18-6, L. pentosus CJW56-11, and Pediococcus acidilactici CJN2696) were found to be strong IgA inducers. The number of IgA positive B cells and soluble IgA level were increased when LPCs were co-cultured with these LAB. Expression levels of toll-like receptor (TLR) such as TLR2 and TLR4 and secretion of interleuckin-6 were augmented in LPCs treated with these LAB. Further, we determined whether oral intake of these LAB enhanced IgA production in vivo. After one-week of daily oral administration, these LAB feed mice increased mucosal IgA and serum IgA. In conclusion, selected strains of LAB could induce systemic IgA secretion by activating lamina propria B cells in Peyer's patch and oral intake of selected strains of LAB can enhance systemic immunity by inducing mucosal IgA secretion.

Improving Birth Outcomes Among Low-Income Families: The Effect of a Home Visiting Intervention.

The American Academy of Pediatrics (AAP) recognizes the benefit of home visiting programs in promoting positive birth outcomes. Despite this recommendation, previous studies have found mixed results with respect to the impact of home visits on birth outcomes. We evaluated the impact of the Comprehensive Health Investment Project (CHIP) home visiting services on improving birth outcomes among low-income families. The present study used a sample of 1,110 children and families to examine how a team-based home visiting program influenced 2 significant birth outcomes, namely, birth weight and preterm birth. Using propensity score matching, the current study found that the home visited group had significantly lower rates of low birth weight compared with a propensity-matched comparison group (P < .01). Home visiting programs may play an important role in promoting positive birth outcomes, particularly when they are provided during pregnancy.

CheSS: Chest X-Ray Pre-trained Model via Self-supervised Contrastive Learning.

Training deep learning models on medical images heavily depends on experts' expensive and laborious manual labels. In addition, these images, labels, and even models themselves are not widely publicly accessible and suffer from various kinds of bias and imbalances. In this paper, chest X-ray pre-trained model via self-supervised contrastive learning (CheSS) was proposed to learn models with various representations in chest radiographs (CXRs). Our contribution is a publicly accessible pretrained model trained with a 4.8-M CXR dataset using self-supervised learning with a contrastive learning and its validation with various kinds of downstream tasks including classification on the 6-class diseases in internal dataset, diseases classification in CheXpert, bone suppression, and nodule generation. When compared to a scratch model, on the 6-class classification test dataset, we achieved 28.5% increase in accuracy. On the CheXpert dataset, we achieved 1.3% increase in mean area under the receiver operating characteristic curve on the full dataset and 11.4% increase only using 1% data in stress test manner. On bone suppression with perceptual loss, we achieved improvement in peak signal to noise ratio from 34.99 to 37.77, structural similarity index measure from 0.976 to 0.977, and root-square-mean error from 4.410 to 3.301 when compared to ImageNet pretrained model. Finally, on nodule generation, we achieved improvement in Fréchet inception distance from 24.06 to 17.07. Our study showed the decent transferability of CheSS weights. CheSS weights can help researchers overcome data imbalance, data shortage, and inaccessibility of medical image datasets. CheSS weight is available at https://github.com/mi2rl/CheSS .

Supramolecular filaments for concurrent ACE2 docking and enzymatic activity silencing enable coronavirus capture and infection prevention.

Coronaviruses have historically precipitated global pandemics of severe acute respiratory syndrome (SARS) into devastating public health crises. Despite the virus's rapid rate of mutation, all SARS coronavirus 2 (SARS-CoV-2) variants are known to gain entry into host cells primarily through complexation with angiotensin-converting enzyme 2 (ACE2). Although ACE2 has potential as a druggable decoy to block viral entry, its clinical use is complicated by its essential biological role as a carboxypeptidase and hindered by its structural and chemical instability. Here we designed supramolecular filaments, called fACE2, that can silence ACE2's enzymatic activity and immobilize ACE2 to their surface through enzyme-substrate complexation. This docking strategy enables ACE2 to be effectively delivered in inhalable aerosols and improves its structural stability and functional preservation. fACE2 exhibits enhanced and prolonged inhibition of viral entry compared with ACE2 alone while mitigating lung injury in vivo.

Transboundary Cooperation in the Tumen River Basin Is the Key to Amur Leopard (Panthera pardus) Population Recovery in the Korean Peninsula.

The interconnected forest regions along the lower Tumen River, at the Sino-North Korean border, provide critical habitats and corridors for the critically endangered Amur Leopard (Panthera pardus orientalis). In this region, there are two promising corridors for leopard movement between China and North Korea: the Jingxin-Dapanling (JD) and Mijiang (MJ) corridors. Past studies have confirmed the functionality of the JD corridor, but leopards' utilization of the MJ corridor has not yet been established or confirmed. In this study, we assessed the functionality of the MJ corridor. The study area was monitored using camera traps between May 2019 and July 2021. We also analyzed 33 environmental and vegetation factors affecting leopard survival and analyzed leopard movement. In the Mijiang area, the Amur leopard was mainly active in the region adjacent to the Northeast China Tiger and Leopard National Park and did not venture into area near the North Korean border. The complex forest structure allowed leopards to move into the Mijiang area. However, the high intensity of human disturbance and manufactured physical barriers restricted further southward movement. Therefore, human-induced disturbances such as grazing, mining, farming, logging, and infrastructure development must be halted and reversed to make the Mijiang region a functional corridor for the Amur leopard to reach the North Korean forest. This necessitates inter-governmental and international cooperation and is essential for the long-term survival of the Amur leopard.

Quasinatural Experiment of Postnatal Home Visiting: An Independent Impact Study of Family Connects.

INTRODUCTION: Family Connects (FC) is a postnatal nurse home visiting program that has scale-up potential because it is brief, inexpensive, and universal. Three investigations have linked Family Connects to improved maternal and family outcomes, but no independent impact studies have been conducted to date. METHODS: This study investigates a FC program in Racine County, WI that was implemented by a multimunicipal health department in partnership with a local hospital. The sampling frame included all women who gave birth at the hospital from July 1, 2018 to August 31, 2019 (N=1,511). A quasinatural experiment resulted from systematically restricting FC recruitment to weekdays. All eligible women whose birth records and addresses were obtained from a vital records office were mailed a 6-month postpartum survey. Data collected from 489 respondents (32.4%) were analyzed in February 2022 to estimate the impact of FC on maternal health, infant health and development, and parenting behavior outcomes under intent-to-treat and per protocol assumptions. RESULTS: No significant differences were observed between study groups at baseline. Despite evidence that the FC program in Racine met many model standards for implementation fidelity, null effects were observed at 6 months after delivery for most outcomes. Results suggested that parents from eligible households reported more frequent infant emergency medical episodes than parents who were not offered the program. CONCLUSIONS: This study found few significant effects associated with FC participation. Further investigation is needed to identify the populations with and conditions under which the program produces its intended effects.

The effect of natural disturbances on forest biodiversity: an ecological synthesis.

Disturbances alter biodiversity via their specific characteristics, including severity and extent in the landscape, which act at different temporal and spatial scales. Biodiversity response to disturbance also depends on the community characteristics and habitat requirements of species. Untangling the mechanistic interplay of these factors has guided disturbance ecology for decades, generating mixed scientific evidence of biodiversity responses to disturbance. Understanding the impact of natural disturbances on biodiversity is increasingly important due to human-induced changes in natural disturbance regimes. In many areas, major natural forest disturbances, such as wildfires, windstorms, and insect outbreaks, are becoming more frequent, intense, severe, and widespread due to climate change and land-use change. Conversely, the suppression of natural disturbances threatens disturbance-dependent biota. Using a meta-analytic approach, we analysed a global data set (with most sampling concentrated in temperate and boreal secondary forests) of species assemblages of 26 taxonomic groups, including plants, animals, and fungi collected from forests affected by wildfires, windstorms, and insect outbreaks. The overall effect of natural disturbances on α-diversity did not differ significantly from zero, but some taxonomic groups responded positively to disturbance, while others tended to respond negatively. Disturbance was beneficial for taxonomic groups preferring conditions associated with open canopies (e.g. hymenopterans and hoverflies), whereas ground-dwelling groups and/or groups typically associated with shady conditions (e.g. epigeic lichens and mycorrhizal fungi) were more likely to be negatively impacted by disturbance. Across all taxonomic groups, the highest α-diversity in disturbed forest patches occurred under moderate disturbance severity, i.e. with approximately 55% of trees killed by disturbance. We further extended our meta-analysis by applying a unified diversity concept based on Hill numbers to estimate α-diversity changes in different taxonomic groups across a gradient of disturbance severity measured at the stand scale and incorporating other disturbance features. We found that disturbance severity negatively affected diversity for Hill number q = 0 but not for q = 1 and q = 2, indicating that diversity-disturbance relationships are shaped by species relative abundances. Our synthesis of α-diversity was extended by a synthesis of disturbance-induced change in species assemblages, and revealed that disturbance changes the ß-diversity of multiple taxonomic groups, including some groups that were not affected at the α-diversity level (birds and woody plants). Finally, we used mixed rarefaction/extrapolation to estimate biodiversity change as a function of the proportion of forests that were disturbed, i.e. the disturbance extent measured at the landscape scale. The comparison of intact and naturally disturbed forests revealed that both types of forests provide habitat for unique species assemblages, whereas species diversity in the mixture of disturbed and undisturbed forests peaked at intermediate values of disturbance extent in the simulated landscape. Hence, the relationship between α-diversity and disturbance severity in disturbed forest stands was strikingly similar to the relationship between species richness and disturbance extent in a landscape consisting of both disturbed and undisturbed forest habitats. This result suggests that both moderate disturbance severity and moderate disturbance extent support the highest levels of biodiversity in contemporary forest landscapes.

Toxoplasma gondii and Rickettsia spp. in ticks collected from migratory birds in the Republic of Korea.

Migratory birds disperse ticks and associated tick-borne pathogens along their migratory routes. Four selected pathogens of medical importance (Coxiella burnetii, Rickettsia spp., Francisella tularensis, and Toxoplasma gondii) were targeted for detection in 804 ticks (365 pools) collected from migratory birds at Hong and Heuksan Islands in the Republic of Korea (ROK) from 2010 to 2011 and 2016. Toxoplasma gondii and Rickettsia spp., were detected in 1/365 (0.27%) and 34/365 (9.32%) pools of ticks, respectively. T. gondii and five rickettsial species were recorded in ticks collected from migratory birds for the first time in ROK. The five rickettsial species (R. monacensis, Candidatus Rickettsia longicornii, R. japonica, R. raoultii, and R. tamurae) were identified using sequence and phylogenetic analysis using ompA and gltA gene fragments. Rickettsia spp. are important pathogens that cause rickettsiosis in humans, with cases recorded in the ROK. These results provide important evidence for the potential role of migratory birds in the introduction and dispersal of T. gondii and Rickettsia spp. along their migratory routes and raise awareness of potential transmission of zoonotic tick-borne pathogens associated with migratory birds in the ROK.

Prevalence of adverse childhood experiences (ACEs) and association with dating violence and symptoms of mental illness among adolescents in the Dominican Republic.

BACKGROUND: Adolescent dating violence (ADV) and mental illness are highly prevalent, interrelated public health priorities. Increasingly, scholars are looking to adverse childhood experiences (ACEs) to explain risk for these health concerns. OBJECTIVES: Determine prevalence of ACEs, ADV perpetration and victimization, and anxiety and depression symptoms among adolescents in the Dominican Republic (DR). Evaluate the association of ACEs with these ADV and mental health outcomes. PARTICIPANTS AND SETTING: Cross-sectional survey data were collected from 142 adolescents at middle and high schools in the DR. METHODS: We assessed ACEs using the Childhood Experiences Survey, ADV using the Conflict in Dating Relationships Inventory, and depression/anxiety symptoms using Patient-Reported Outcomes Measurement Information System scales. Linear and logistic regressions were performed to test dose-response relationships between a cumulative ACE score and ADV and mental health outcomes while adjusting for age, gender, and rural/urban residence. RESULTS: 80.6% of students reported at least one ACE. The most prevalent ACEs reported were physical abuse (49%) and witnessing domestic violence (48%). After adjusting for covariates, cumulative ACE scores were significantly associated with depression symptoms, anxiety symptoms, physical and emotional ADV perpetration, and physical and emotional ADV victimization. CONCLUSIONS: Structural and community-based interventions to prevent ADV and promote mental health for adolescents in the DR should address ACEs.

Introduction of Non-Native Ticks Collected from Fresh Migratory Bird Carcasses on a Stopover Island in the Republic of Korea.

When free-ranging birds are accidentally killed or die, there may be greater potential for their associated ticks to detach, seek alternate hosts, and become established. We examined 711 carcasses of 95 avian species for ticks at a stopover island of migratory birds in the Republic of Korea where only Ixodes nipponensis and I. persulcatus were previously reported from local mammals and vegetation. A total of 16 ticks, I. turdus and Haemaphysalis flava, were collected from 8 fresh carcasses belonging to 5 avian species. Despite their known abundance on migratory birds and mainland Korea, these species had not colonized the isolated insular ecosystem possibly due to the low abundance and diversity of local hosts. The results imply that increasing human impact, such as the anthropogenic mortality of migratory birds and the introduction of non-native mammalian hosts, will increase the potential invasion and colonization risk of ticks. This finding also suggests that tick surveillance consisting of fresh carcasses of dead migratory birds may provide additional information, often ignored in surveillance of ticks on live birds, for the potential introduction of non-native ticks and associated pathogens affecting animal and human health.

Autophagy-competent mitochondrial translation elongation factor TUFM inhibits caspase-8-mediated apoptosis.

Mitochondria support multiple cell functions, but an accumulation of dysfunctional or excessive mitochondria is detrimental to cells. We previously demonstrated that a defect in the autophagic removal of mitochondria, termed mitophagy, leads to the acceleration of apoptosis induced by herpesvirus productive infection. However, the exact molecular mechanisms underlying activation of mitophagy and regulation of apoptosis remain poorly understood despite the identification of various mitophagy-associated proteins. Here, we report that the mitochondrial translation elongation factor Tu, a mitophagy-associated protein encoded by the TUFM gene, locates in part on the outer membrane of mitochondria (OMM) where it acts as an inhibitor of altered mitochondria-induced apoptosis through its autophagic function. Inducible depletion of TUFM potentiated caspase-8-mediated apoptosis in virus-infected cells with accumulation of altered mitochondria. In addition, TUFM depletion promoted caspase-8 activation induced by treatment with TNF-related apoptosis-inducing ligand in cancer cells, potentially via dysregulation of mitochondrial dynamics and mitophagy. Importantly, we revealed the existence of and structural requirements for autophagy-competent TUFM on the OMM; the GxxxG motif within the N-terminal mitochondrial targeting sequences of TUFM was required for self-dimerization and mitophagy. Furthermore, we found that autophagy-competent TUFM was subject to ubiquitin-proteasome-mediated degradation but stabilized upon mitophagy or autophagy activation. Moreover, overexpression of autophagy-competent TUFM could inhibit caspase-8 activation. These studies extend our knowledge of mitophagy regulation of apoptosis and could provide a novel strategic basis for targeted therapy of cancer and viral diseases.