ACVR1/ALK2-p21 signaling axis modulates proliferation of the venous endothelium in the retinal vasculature.

The proliferation of the endothelium is a highly coordinated process to ensure the emergence, expansion, and homeostasis of the vasculature. While Bone Morphogenetic Protein (BMP) signaling fine-tunes the behaviors of endothelium in health and disease, how BMP signaling influences the proliferation of endothelium and therefore, modulates angiogenesis remains largely unknown. Here, we evaluated the role of Activin A Type I Receptor (ACVR1/ALK2), a key BMP receptor in the endothelium, in modulating the proliferation of endothelial cells. We show that ACVR1/ALK2 is a key modulator for the proliferation of endothelium in the retinal vessels. Loss of endothelial ALK2 leads to a significant reduction in endothelial proliferation and results in fewer branches/endothelial cells in the retinal vessels. Interestingly, venous endothelium appears to be more susceptible to ALK2 deletion. Mechanistically, ACVR1/ALK2 inhibits the expression of CDKN1A/p21, a critical negative regulator of cell cycle progression, in a SMAD1/5-dependent manner, thereby enabling the venous endothelium to undergo active proliferation by suppressing CDKN1A/p21. Taken together, our findings show that BMP signaling mediated by ACVR1/ALK2 provides a critical yet previously underappreciated input to modulate the proliferation of venous endothelium, thereby fine-tuning the context of angiogenesis in health and disease.

Coparenting Profiles and Children's Socioemotional Outcomes in Unmarried Parents with Low-Income.

Objective: This study aimed to examine patterns of mother-father coparenting relationship quality and their associations with child empathy, emotional insecurity, and behavior problems in families with low income. Background: Given the growing number of nonmarital births and the high risk of relationship dissolution among cohabiting couples living with low income, it is important to examine the coparenting relationships among racially diverse unmarried couples from low-income contexts. To date, little research has assessed patterns of coparenting relationships and their associations with child socioemotional outcomes among this population. Method: Participants were 4,266 unmarried couples and their preschool-aged children from the Building Strong Families study. Latent profile analysis was conducted. Results: Latent profile analysis of survey data from mothers and fathers revealed four coparenting patterns: Profile 1: low quality, more negative maternal coparenting perceptions (7.2%); Profile 2: moderate-high quality, high congruence, slightly more negative paternal coparenting perceptions (25.2%); Profile 3: low congruence, severely more negative maternal coparenting perceptions (11.8%); and Profile 4: mutual high-quality coparenting (55.8%). Conclusion: Children of parents with the mutual high-quality coparenting profile had the most positive outcomes according to maternal reports of child socioemotional development. Highly congruent and positive perceptions of the other parent as a coparent were found to be significant promotive factors for positive child socioemotional development. Implications: Family strengthening policies and programs for unmarried couples with low income should target and support the development of mutually satisfying, high-quality coparenting relationships, with the ultimate goal to improve developmental outcomes for young children in such families.

A study of the effect of testing for diversification of healthcare waste sterilization and crushing facilities.

This study conducted sterilization testing under different conditions using different strains for sterilization and crushing, the intermediate healthcare waste treatment phase, and proposed strategies for diversifying corresponding facilities in addition to promoting their installation. Five indicator microorganisms were selected to test the sterilization efficiency of steam, microwave, and chemical methods. Steam sterilization testing was conducted in accordance with legal and technological standards, microwave testing was carried out according to the legal standard, and chemical sterilization employed three typical compounds. Steam and microwave sterilization achieved 99.9999 % inactivation rates for all five strains under both conditions used; whereas under the chemical sterilization analyses, sodium hypochlorite (1000 ppm) failed to meet the inactivation requirement of the fungal strain Candida albicans, requiring further investigation. Based on these findings, this study presents strategies for diversifying sterilization·crushing facilities and promoting their installation.

Deep learning model integrating cfDNA methylation and fragment size profiles for lung cancer diagnosis.

Detecting aberrant cell-free DNA (cfDNA) methylation is a promising strategy for lung cancer diagnosis. In this study, our aim is to identify methylation markers to distinguish patients with lung cancer from healthy individuals. Additionally, we sought to develop a deep learning model incorporating cfDNA methylation and fragment size profiles. To achieve this, we utilized methylation data collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. Then we generated methylated DNA immunoprecipitation sequencing and genome-wide Enzymatic Methyl-seq (EM-seq) form lung cancer tissue and plasma. Using these data, we selected 366 methylation markers. A targeted EM-seq panel was designed using the selected markers, and 142 lung cancer and 56 healthy samples were produced with the panel. Additionally, cfDNA samples from healthy individuals and lung cancer patients were diluted to evaluate sensitivity. Its lung cancer detection performance reached an accuracy of 81.5% and an area under the receiver operating characteristic curve of 0.87. In the serial dilution experiment, we achieved tumor fraction detection of 1% at 98% specificity and 0.1% at 80% specificity. In conclusion, we successfully developed and validated a combination of methylation panel and a deep learning model that can distinguish between patients with lung cancer and healthy individuals.

Assessment of the occurrence of the second generation of Mythimna loreyi Duponchel (Lepidoptera: Noctuidae) using temperature-dependent developmental and oviposition models.

A significant crop pest, Mythimna loreyi, migrates annually to Korea and has been frequently observed in rice and corn fields. However, the phenology of this pest, particularly in relation to its ecological interactions and host crop seasons in Korea, remains poorly understood. This study aims to clarify the timing of the second generation of M. loreyi in Korea to enhance pest management strategies. To achieve this, we developed temperature-dependent models for developmental and ovipositional rates, studying these processes across five constant temperatures (15, 20, 25, 30, and 35°C). Our models, which showed a high correlation with observed data (r2 ≥ 0.93), include a theoretical approach that combines the developmental variation of immatures with the necessary degree-days for 50% egg laying and complete egg development. These predictions allow for the forecasting of the second generation's occurrence, with relatively small deviations (one to three days) observed at two different field sites. The insights from this study are critical for both understanding the ecology of M. loreyi and for informing practical management decisions, such as optimal placement of barriers to prevent immigration and strategies for controlling local populations.

HIGH PLOIDY2-mediated SUMOylation of transcription factor ARR1 controls two-component signaling in Arabidopsis.

Cytokinins regulate plant growth, development, and responses to environmental stresses such as cold via phosphorelay from cytokinin receptors to the ARABIDOPSIS RESPONSE REGULATORs (ARRs). However, the molecular mechanisms underlying the activation of type-B ARR transcriptional activity in Arabidopsis (Arabidopsis thaliana) remain unclear. Here, we show that the E3 SUMO ligase HIGH PLOIDY2 SUMOylates ARR1, a type-B ARR, at K236, triggering its activation. Cold- or cytokinin-induced phosphorylation of ARR1 at D89 is crucial for its interaction with HPY2. Lysine 236 is critical for ARR1's transactivation without compromising its DNA-binding ability, while D89 is crucial for ARR1's binding to target gene promoters. Cytokinin enhances ARR1's chromatin binding, but cold does not. ARR1 K236 plays a critical role in promoting histone H3 acetylation in response to both cytokinin and cold without affecting chromatin binding. The K236R mutation in ARR1 reduces target gene expression and alters cytokinin and cold response phenotypes. This study unveils a mechanism of ARR1 activation wherein phosphorylated ARR1 interacts with HPY2 and binds to chromatin in response to cytokinin. Cold triggers a phosphorelay targeting chromatin-bound ARR1. HPY2 then catalyzes ARR1 SUMOylation at K236, enhancing histone H3 acetylation and leading to transcriptional activation of ARR1 in response to both cold and cytokinin.

Exercise-induced signaling activation by Chrysanthemum zawadskii and its active compound, linarin, ameliorates age-related sarcopenia through Sestrin 1 regulation.

BACKGROUND: Exercise is an effective strategy to prevent sarcopenia, but high physical inactivity in the elderly requires alternative therapeutic approaches. Exercise mimetics are therapeutic compounds that simulate the beneficial effects of exercise on skeletal muscles. However, the toxicity and adverse effects of exercise mimetics raise serious concerns. PURPOSE: We aimed to search novel plant-based alternatives to activate exercise induced-signaling. METHODS: We used open databases and luciferase assays to identify plant-derived alternatives to activate exercise-induced signaling and compared its efficacy to mild intensity continuous training (MICT) in aged C57BL/6 mice. The nineteen-month-old mice were either fed an experimental diet supplemented with the isolated alternative or subjected to MICT for up to 21 mo of age. RESULTS: Our analysis revealed that Chrysanthemum zawadskii Herbich var latillobum (Maxim.) Kitamura (CZH), a medicinal plant rich in linarin, is a novel activator of peroxisome proliferator-activated receptor δ (PPARδ) and estrogen-related receptor γ (ERRγ), key regulators of exercise-induced positive effects on muscles. CZH supplementation ameliorated the loss of muscle function and mass, and increased PPARδ and ERRγ expression in mouse muscles. CZH also improved mitochondrial functions and proteostasis in aged mice, similar to MICT. Furthermore, CZH and linarin induced the activation of Sestrin 1, a key mediator of exercise benefits, in muscle. Silencing Sestrin 1 negated the increase in myogenesis and mitochondrial respiration by CZH and linarin in primary myoblasts from old mice. CONCLUSION: Our findings suggest the potential of CZH as a novel plant-derived alternative to activate exercise-induced signaling for preventing sarcopenia in sedentary older adults. This could offer a safer therapeutic option for sarcopenia treatment.

Multi-Granularity Aggregation with Spatiotemporal Consistency for Video-Based Person Re-Identification.

Video-based person re-identification (ReID) aims to exploit relevant features from spatial and temporal knowledge. Widely used methods include the part- and attention-based approaches for suppressing irrelevant spatial-temporal features. However, it is still challenging to overcome inconsistencies across video frames due to occlusion and imperfect detection. These mismatches make temporal processing ineffective and create an imbalance of crucial spatial information. To address these problems, we propose the Spatiotemporal Multi-Granularity Aggregation (ST-MGA) method, which is specifically designed to accumulate relevant features with spatiotemporally consistent cues. The proposed framework consists of three main stages: extraction, which extracts spatiotemporally consistent partial information; augmentation, which augments the partial information with different granularity levels; and aggregation, which effectively aggregates the augmented spatiotemporal information. We first introduce the consistent part-attention (CPA) module, which extracts spatiotemporally consistent and well-aligned attentive parts. Sub-parts derived from CPA provide temporally consistent semantic information, solving misalignment problems in videos due to occlusion or inaccurate detection, and maximize the efficiency of aggregation through uniform partial information. To enhance the diversity of spatial and temporal cues, we introduce the Multi-Attention Part Augmentation (MA-PA) block, which incorporates fine parts at various granular levels, and the Long-/Short-term Temporal Augmentation (LS-TA) block, designed to capture both long- and short-term temporal relations. Using densely separated part cues, ST-MGA fully exploits and aggregates the spatiotemporal multi-granular patterns by comparing relations between parts and scales. In the experiments, the proposed ST-MGA renders state-of-the-art performance on several video-based ReID benchmarks (i.e., MARS, DukeMTMC-VideoReID, and LS-VID).

The mediating effect of attentional impulsivity between mindfulness and problematic smartphone use.

OBJECTIVE: Problematic smartphone use has been linked to lower levels of mindfulness, impaired attentional function, and higher impulsivity. This study aimed to identify the psychological mechanisms of problematic smartphone use by exploring the relationship between addictive smartphone use, mindfulness, attentional function and impulsivity. METHODS: Ninety participants were evaluated with the smartphone addiction proneness scale and classified into the problematic smartphone use group (n = 42; 24 women; mean age: 27.6 ± 7.2 years) or normal use group (n = 48; 22 women; mean age: 30.1 ± 5.7 years). All participants completed self-report questionnaires evaluating their trait impulsivity and mindfulness and attention tests that assessed selective, sustained and divided attention. We compared the variables between the groups and explored the relationship between mindfulness, attentional function, impulsivity and addictive smartphone use through mediation analysis. RESULTS: The problematic smartphone use group showed higher trait impulsivity and lower mindfulness than the normal use group. There were no significant group differences in performance on attention tests. Levels of addictive smartphone use were significantly correlated with higher levels of trait impulsivity and lower levels of mindfulness, but not with performance on attention tests. Mediation analysis showed that acting with awareness, an aspect of mindfulness, reduces the degree of addictive smartphone use through attentional impulsivity, one of the trait impulsivity. CONCLUSION: Acting without sufficient awareness could influence addictive smartphone use by mediating attentional impulsivity. This supports that executive control deficits, reflected in high attentional impulsivity, contribute to problematic smartphone use. Our findings imply that mindfulness-based interventions can enhance executive control over smartphone use by promoting awareness.

Phenology model development for Neodryinus typhlocybae: Evaluation of phenological synchrony with its host, Metcalfa pruinosa.

The invasive species Metcalfa pruinosa has inflicted significant economic losses in various European and Asian regions. To combat this pest, the parasitoid wasp Neodryinus typhlocybae has been effectively introduced in Europe. Despite its success, research on the field occurrence patterns of N. typhlocybae, particularly its phenology, remains scarce. This study aims to develop a degree-day model for predicting the adult emergence of N. typhlocybae from overwintering cocoons and to assess the phenological synchrony between N. typhlocybae adults and the nymphal stages of M. pruinosa in Korea. In this study, we estimated the thermal parameters of N. typhlocybae under field temperatures and six constant temperatures (13.92, 17.71, 18.53, 20.53, 22.78, and 24.03 °C) conditions. The lower developmental temperature was estimated using the values of the coefficient of variation for the cumulative degree days of emerged individual adults. The estimated lower developmental threshold temperature was 12.3 °C. With this developmental threshold, a degree-day model was developed, and this model well-predicted emergence in field conditions. By simulating this developed model with the actual occurrence of the nymphal stages of its host, M. pruinosa, adult wasp emergence was estimated to be 1.5 weeks later than the first instar nymph of the host but faster than other nymphal stages of M. pruinosa. Thus, the findings in this study would be helpful in determining the possibility of establishing N. typhlocybae and improving the management efficiency of M. pruinosa.

Smartphone-Based Speech Therapy for Poststroke Dysarthria: Pilot Randomized Controlled Trial Evaluating Efficacy and Feasibility.

BACKGROUND: Dysarthria is a common poststroke speech disorder affecting communication and psychological well-being. Traditional speech therapy is effective but often poses challenges in terms of accessibility and patient adherence. Emerging smartphone-based therapies may offer promising alternatives for the treatment of poststroke dysarthria. OBJECTIVE: This study aimed to assess the efficacy and feasibility of smartphone-based speech therapy for improving speech intelligibility in patients with acute and early subacute poststroke dysarthria. This study also explored the impact of the intervention on psychological well-being, user experience, and overall feasibility in a clinical setting. METHODS: Participants were divided into 2 groups for this randomized, evaluator-blinded trial. The intervention group used a smartphone-based speech therapy app for 1 hour per day, 5 days per week, for 4 weeks, with guideline-based standard stroke care. The control group received standard guideline-based stroke care and rehabilitation. Speech intelligibility, psychological well-being, quality of life, and user acceptance were assessed using repeated measures ANOVA. RESULTS: In this study, 40 patients with poststroke dysarthria were enrolled, 32 of whom completed the trial (16 in each group). The intervention group showed significant improvements in speech intelligibility compared with the control group. This was evidenced by improvements from baseline (F1,30=34.35; P<.001), between-group differences (F1,30=6.18; P=.02), and notable time-by-group interactions (F1,30=6.91; P=.01). Regarding secondary outcomes, the intervention led to improvements in the percentage of correct consonants over time (F1,30=5.57; P=.03). In addition, significant reductions were noted in the severity of dysarthria in the intervention group over time (F1,30=21.18; P<.001), with a pronounced group effect (F1,30=5.52; P=.03) and time-by-group interaction (F1,30=5.29; P=.03). Regarding quality of life, significant improvements were observed as measured by the EQ-5D-3L questionnaire (F1,30=13.25; P<.001) and EQ-VAS (F1,30=7.74; P=.009) over time. The adherence rate to the smartphone-based app was 64%, with over half of the participants completing all the sessions. The usability of the app was rated high (system usability score 80.78). In addition, the intervention group reported increased self-efficacy in using the app compared with the control group (F1,30=10.81; P=.003). CONCLUSIONS: The smartphone-based speech therapy app significantly improved speech intelligibility, articulation, and quality of life in patients with poststroke dysarthria. These findings indicate that smartphone-based speech therapy can be a useful assistant device in the management of poststroke dysarthria, particularly in the acute and early subacute stroke stages. TRIAL REGISTRATION: ClinicalTrials.gov NCT05146765; https://clinicaltrials.gov/ct2/show/NCT05146765.

Amine-Rich Hydrogels for Molecular Nanoarchitectonics of Photosystem II and Inverse Opal TiO2 toward Solar Water Oxidation.

Solar water oxidation is a crucial process in light-driven reductive synthesis, providing electrons and protons for various chemical reductions. Despite advances in light-harvesting materials and cocatalysts, achieving high efficiency and stability remains challenging. In this study, we present a simple yet effective strategy for immobilizing natural photosystems (PS) made of abundant and inexpensive elements, using amine-rich polyethylenimine (PEI) hydrogels, to fabricate organic/inorganic hybrid photoanodes. Natural PS II extracted from spinach was successfully immobilized on inverse opal TiO2 photoanodes in the presence of PEI hydrogels, leading to greatly enhanced solar water oxidation activity. Photoelectrochemical (PEC) analyses reveal that PS II can be immobilized in specific orientations through electrostatic interactions between the positively charged amine groups of PEI and the negatively charged stromal side of PS II. This specific orientation ensures efficient photogenerated charge separation and suppresses undesired side reactions such as the production of reactive oxygen species. Our study provides an effective immobilization platform and sheds light on the potential utilization of PS II in PEC water oxidation.

COVID-19, Influenza, and RSV in Children and Adults: A Clinical Comparative Study of 12,000 Cases.

(1) Background: Respiratory virus infections, including Coronavirus disease 2019 (COVID-19), seasonal influenza (FLU), and respiratory syncytial virus (RSV) as prominent examples, can severely affect both children and adults. This study aimed to investigate the clinical characteristics of respiratory viral infections in pediatric and adult populations and to identify determinants influencing patient hospitalization. (2) Methods: This retrospective study analyzed the electronic medical records of patients admitted to a regional hospital's emergency department from 1 January 2015 to 31 December 2022, to investigate the clinical characteristics and hospitalization risk factors associated with these three viruses. (3) Results: Infants aged 1 to 11 months were most affected by COVID-19 and RSV, whereas FLU more commonly infected children aged 3 to 5 years. Key factors influencing hospitalization included age and abnormal chest X-ray findings, with higher risks observed in younger children and adults over 65. Notably, the presence of abnormal chest x-ray findings significantly increased the hospitalization risk by 1.9 times [1.5-2.4] in children and 21.4 times [2.4-189.0] in adults. (4) Conclusions: This analysis underscores the impact of COVID-19, FLU, and RSV on hospitalization risk, offering insights for managing these respiratory viral infections (RVIs). Age-related risk differences highlight the necessity for tailored strategies, improving understanding of and treatment development for RVIs.

Ceramide-1-phosphate is a regulator of Golgi structure and is co-opted by the obligate intracellular bacterial pathogen Anaplasma phagocytophilum.

Many intracellular pathogens structurally disrupt the Golgi apparatus as an evolutionarily conserved promicrobial strategy. Yet, the host factors and signaling processes involved are often poorly understood, particularly for Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis. We found that A. phagocytophilum elevated cellular levels of the bioactive sphingolipid, ceramide-1-phosphate (C1P), to promote Golgi fragmentation that enables bacterial proliferation, conversion from its non-infectious to infectious form, and productive infection. A. phagocytophilum poorly infected mice deficient in ceramide kinase, the Golgi-localized enzyme responsible for C1P biosynthesis. C1P regulated Golgi morphology via activation of a PKCα/Cdc42/JNK signaling axis that culminates in phosphorylation of Golgi structural proteins, GRASP55 and GRASP65. siRNA-mediated depletion of Cdc42 blocked A. phagocytophilum from altering Golgi morphology, which impaired anterograde trafficking of trans-Golgi vesicles into and maturation of the pathogen-occupied vacuole. Cells overexpressing phosphorylation-resistant versions of GRASP55 and GRASP65 presented with suppressed C1P- and A. phagocytophilum-induced Golgi fragmentation and poorly supported infection by the bacterium. By studying A. phagocytophilum, we identify C1P as a regulator of Golgi structure and a host factor that is relevant to disease progression associated with Golgi fragmentation.IMPORTANCECeramide-1-phosphate (C1P), a bioactive sphingolipid that regulates diverse processes vital to mammalian physiology, is linked to disease states such as cancer, inflammation, and wound healing. By studying the obligate intracellular bacterium Anaplasma phagocytophilum, we discovered that C1P is a major regulator of Golgi morphology. A. phagocytophilum elevated C1P levels to induce signaling events that promote Golgi fragmentation and increase vesicular traffic into the pathogen-occupied vacuole that the bacterium parasitizes. As several intracellular microbial pathogens destabilize the Golgi to drive their infection cycles and changes in Golgi morphology is also linked to cancer and neurodegenerative disorder progression, this study identifies C1P as a potential broad-spectrum therapeutic target for infectious and non-infectious diseases.

The Impact of the Physical Activity Level on Sarcopenic Obesity in Community-Dwelling Older Adults.

Previous studies have reported that low levels of physical activity result in sarcopenic obesity (SO). However, the effects of specific intensities of physical activity on SO and the optimal amount of physical activity for lowering the prevalence of SO have not been well studied. This study aimed to identify the effects of physical activity levels and intensity on SO and the optimal amount of physical activity related to a lower prevalence of SO. This cross-sectional study used data from the nationwide Korean Frailty and Aging Cohort Study (KFACS), which included 2071 older adults (1030 men, 1041 women). SO was defined according to the criteria of the European Society for Clinical Nutrition Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO). Multivariate logistic regression analysis was performed to investigate the association between the physical activity level and SO. The high activity group had a significantly lower prevalence of SO than the non-high activity (low and moderate activity) group. On the other hand, moderate-intensity physical activity was associated with a lower prevalence of SO. A total physical activity energy expenditure of > 3032 kcal/week (433 kcal/day) for men and 2730 kcal/week (390 kcal/day) for women was associated with a reduced prevalence of SO. The high physical activity and total physical energy expenditure described above may be beneficial for reducing the prevalence of SO.

Efficacy and feasibility of a digital speech therapy for post-stroke dysarthria: protocol for a randomized controlled trial.

Background: Dysarthria is a motor speech disorder caused by various neurological diseases, particularly stroke. Individuals with post-stroke dysarthria experience impaired speech intelligibility, communication difficulties, and a reduced quality of life. However, studies on the treatment of post-stroke dysarthria are lacking. Digital speech therapy applications have the advantages of being personalized and easily accessible. However, evidence for their efficacy is not rigorous. Moreover, no studies have investigated both the acute to subacute, and chronic phases of stroke. This study aims to investigate the efficacy and feasibility of digital speech therapy applications in addressing these gaps in dysarthria treatment. Methods and design: This study is a multicenter, prospective, randomized, evaluator-blinded non-inferiority trial. We aim to recruit 76 participants with post-stroke dysarthria. Eligible participants will be stratified based on the onset period of stroke into acute to subacute, and chronic phases. Participants will be randomized in a 1:1 to receive either a personalized digital speech therapy application or conventional therapy with a workbook for 60 min daily, 5 days a week, for 4 weeks. The primary outcome is the improvement in speech intelligibility. This will be measured by how accurately independent listeners can transcribe passages read by the participants. Secondary outcomes, which include speech function, will be evaluated remotely by speech-language pathologists. This includes the maximum phonation time, oral diadochokinetic rate, and percentage of consonants correct. Participants' psychological well-being will also be assessed using self-report questionnaires, such as depressive symptoms (Patient Health Questionnaire-9) and quality of life (Quality of Life in the Dysarthric Speaker scale). The trial will also assess the feasibility, participant adherence, and usability of the application. Rigorous data collection and monitoring will be implemented to ensure patient safety. Conclusion: This trial aims to investigate the efficacy and feasibility of digital speech therapy applications for treating post-stroke dysarthria. The results could establish foundational evidence for future clinical trials with larger sample sizes. Clinical trial registration: Clinicaltrials.gov, identifier: NCT05865106.

CXCL10 upregulation in radiation-exposed human peripheral blood mononuclear cells as a candidate biomarker for rapid triage after radiation exposure.

PURPOSE: In case of a nuclear accident, individuals with high-dose radiation exposure (>1-2 Gy) should be rapidly identified. While ferredoxin reductase (FDXR) was recently suggested as a radiation-responsive gene, the use of a single gene biomarker limits radiation dose assessment. To overcome this limitation, we sought to identify reliable radiation-responsive gene biomarkers. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from mice after total body irradiation, and gene expression was analyzed using a microarray approach to identify radiation-responsive genes. RESULTS: In light of the essential role of the immune response following radiation exposure, we selected several immune-related candidate genes upregulated by radiation exposure in both mouse and human PBMCs. In particular, the expression of ACOD1 and CXCL10 increased in a radiation dose-dependent manner, while remaining unchanged following lipopolysaccharide (LPS) stimulation in human PBMCs. The expression of both genes was further evaluated in the blood of cancer patients before and after radiotherapy. CXCL10 expression exhibited a distinct increase after radiotherapy and was positively correlated with FDXR expression. CONCLUSIONS: CXCL10 expression in irradiated PBMCs represents a potential biomarker for radiation exposure.

Automatic Assessment of Upper Extremity Function and Mobile Application for Self-Administered Stroke Rehabilitation.

Rehabilitation training is essential for a successful recovery of upper extremity function after stroke. Training programs are typically conducted in hospitals or rehabilitation centers, supervised by specialized medical professionals. However, frequent visits to hospitals can be burdensome for stroke patients with limited mobility. We consider a self-administered rehabilitation system based on a mobile application in which patients can periodically upload videos of themselves performing reach-to-grasp tasks to receive recommendations for self-managed exercises or progress reports. Sensing equipment aside from cameras is typically unavailable in the home environment. A key contribution of our work is to propose a deep learning-based assessment model trained only with video data. As all patients carry out identical tasks, a fine-grained assessment of task execution is required. Our model addresses this difficulty by learning RGB and optical flow data in a complementary manner. The correlation between the RGB and optical flow data is captured by a novel module for modality fusion using cross-attention with Transformers. Experiments showed that our model achieved higher accuracy in movement assessment than existing methods for action recognition. Based on the assessment model, we developed a patient-centered, solution-based mobile application for upper extremity exercises for hemiplegia, which can recommend 57 exercises with three levels of difficulty. A prototype of our application was evaluated by potential end-users and achieved a good quality score on the Mobile Application Rating Scale (MARS).

Reepithelialization of Diabetic Skin and Mucosal Wounds Is Rescued by Treatment With Epigenetic Inhibitors.

Wound healing is a complex, highly regulated process and is substantially disrupted by diabetes. We show here that human wound healing induces specific epigenetic changes that are exacerbated by diabetes in an animal model. We identified epigenetic changes and gene expression alterations that significantly reduce reepithelialization of skin and mucosal wounds in an in vivo model of diabetes, which were dramatically rescued in vivo by blocking these changes. We demonstrate that high glucose altered FOXO1-matrix metallopeptidase 9 (MMP9) promoter interactions through increased demethylation and reduced methylation of DNA at FOXO1 binding sites and also by promoting permissive histone-3 methylation. Mechanistically, high glucose promotes interaction between FOXO1 and RNA polymerase-II (Pol-II) to produce high expression of MMP9 that limits keratinocyte migration. The negative impact of diabetes on reepithelialization in vivo was blocked by specific DNA demethylase inhibitors in vivo and by blocking permissive histone-3 methylation, which rescues FOXO1-impaired keratinocyte migration. These studies point to novel treatment strategies for delayed wound healing in individuals with diabetes. They also indicate that FOXO1 activity can be altered by diabetes through epigenetic changes that may explain other diabetic complications linked to changes in diabetes-altered FOXO1-DNA interactions. ARTICLE HIGHLIGHTS: FOXO1 expression in keratinocytes is needed for normal wound healing. In contrast, FOXO1 expression interferes with the closure of diabetic wounds. Using matrix metallopeptidase 9 as a model system, we found that high glucose significantly increased FOXO1-matrix metallopeptidase 9 interactions via increased DNA demethylation, reduced DNA methylation, and increased permissive histone-3 methylation in vitro. Inhibitors of DNA demethylation and permissive histone-3 methylation improved the migration of keratinocytes exposed to high glucose in vitro and the closure of diabetic skin and mucosal wounds in vivo. Inhibition of epigenetic enzymes that alter FOXO1-induced gene expression dramatically improves diabetic healing and may apply to other conditions where FOXO1 has a detrimental role in diabetic complications.

Understanding the Burden of 30-Day Readmission in Patients With Both Primary and Secondary Diagnoses of Heart Failure: Causes, Timing, and Impact of Co-Morbidities.

Although efforts to reduce 30-day readmission rates have mainly focused on patients with heart failure (HF) as a primary diagnosis at index hospitalization, patients with HF as a secondary diagnosis remain common, costly, and understudied. This study aimed to determine the incidence, etiology, and patterns of 30-day readmissions after discharge for HF as a primary and secondary diagnosis and investigate the impact of co-morbidities on HF readmission. The National Readmission Database from 2014 to 2016 was used to identify HF patients with a linked 30-day readmission. Patient and hospital characteristics, admission features, and Elixhauser-related co-morbidities were compared between the 2 groups. Readmitted patients in both groups were younger, male, with lower household income, higher mortality risk, and higher hospitalization costs. Over 60% of readmissions were for reasons other than HF, and greater than 1/3 had more than 2 readmissions within 30 days, with a median time to readmission of 12 days. Both cohorts had high readmission rates and high rates of readmission for causes other than HF. Our findings suggest that efforts to reduce 30-day readmission rates should be extended to patients with secondary HF diagnosis, with surveillance extending to 2 weeks postdischarge to identify patients at risk.