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A new species of the genus Scincella Mittleman, 1950 is described from northern Vietnam based on morphological and molecular evidence. Scincellatruongi sp. nov. is characterized by a combination of the following characters: size medium (SVL up to 59.4 mm); primary temporals 2; external ear opening without lobules; loreals two; supralabials seven or eight; infralabials six or seven; nuchals in three pairs; midbody scales in 28 rows; dorsal scales smooth, in six rows across the back; paravertebral scales 60-67, not widened; ventral scales in 60-70 rows; ten smooth lamellae beneath finger IV and 13-15 beneath toe IV; toes not reaching to fingers when limbs adpressed along body; dorsal surface of body and tail bronze brown with few black spots, a dark stripe running from nostril to eye and extending from posterior corner of eye along upper part of flank to the middle of the tail. In the phylogenetic analyses, the new species is recovered as an independent lineage with no clear sister taxon and at least 17.3% genetic divergence from other species in the genus based on a fragment of the mitochondrial COI gene., Competing Interests: The authors have declared that no competing interests exist., (Anh Van Pham, Thomas Ziegler, Cuong The Pham, Thao Ngoc Hoang, Hanh Thi Ngo, Minh Duc Le.)

Background: Tobacco use remains a global challenge to public health, accounting for almost eight million deaths per year worldwide, with a significant portion attributable to tobacco-related cancers. Examining the epidemiology of tobacco-related cancers and assessing the trends in the incidence and mortality will allow for more effective prevention, treatment, and targeted strategies., Methods: We assessed the trends in the incidence and mortality of tobacco-related cancers among adults in the United States using data from United States Cancer Statistics (USCS) 2001-2021 and mortality data 1975-2022 from the National Center for Health Statistics (NCHS). The incidence and mortality rates of tobacco-related cancers were calculated as cases per 1,000,000 persons and age-adjusted to the 2000 United States standard population., Results: There was a recent overall decreasing trend in both the incidence (2001-2021) and mortality rate (2001-2022). Among adults 20-49 years old, there was an increasing trend from 2001 to 2021 in the incidence among non-Hispanic American Indians/Alaska Natives (APC 2.6, 95% CI 2.1-3.0) and those in the West (APC 0.2, 95% CI 0.0-0.4); in Hispanics, the incidence rate increased most recently from 2013 to 2021 (APC 1.7, 95% CI 1.0-3.0). The mortality rate first increased from 1975 to 1990 among females 50-64 years old and males 65+ years old and from 1975 to 2000 among females 65+ years old, and then decreased thereafter., Conclusions: The rising incidence in some younger groups highlights the need for targeted public health interventions to address disparities and improve cancer prevention in these vulnerable populations.

The mitochondrial outer membrane iron-sulphur ([Fe-S]) protein mitoNEET has been extensively studied as a target of the anti-inflammatory and type-2 diabetes drug pioglitazone and as a protein affecting mitochondrial respiratory rate. Despite these extensive past studies, its molecular function has yet to be discovered. Here, we applied an interdisciplinary approach and discovered an explicit nitric oxide (NO) access site to the mitoNEET [2Fe-2S] cluster. We found that O 2 and pioglitazone block NO access to the cluster, suggesting a molecular function for the mitoNEET [2Fe-2S] cluster in mitochondrial signal transduction. Our discovery hints at a new pathway via which mitochondria can sense hypoxia through O 2 protection of the mitoNEET [2Fe-2S] cluster, a new paradigm in understanding the importance of [Fe-S] clusters for gasotransmitter signal transduction in eukaryotes., (© 2025 The Author(s). FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background: Thanh Hoa Province is located in North Central Vietnam and the Province contains a large area of 393,361.33 hectares of natural forest. A complexity of landforms has given this Province a high level of biodiversity potential. However, the reptile fauna of Thanh Hoa Province is still underestimated. Previous studies documented 111 species of reptiles from this Province., New Information: As a result of our field surveys in Pu Luong and Xuan Lien Nature Reserves, we report five species of reptiles for the first time from Thanh Hoa Province, Vietnam, namely Plestiodontamdaoensis , Scincelladevorator (Scincidae), Elaphetaeniura , Pareasmacularius and Pseudoxenodonmacrops (Colubridae), with novel data about morphological characteristics. In addition, we provide an updated checklist of 116 species of reptiles from Thanh Hoa Province. The reptile fauna of Thanh Hoa Province also contains a number of species of conservation concern: 22 species listed in the Red Data Book of Vietnam, 22 species listed in the IUCN Red List, 18 species listed in the Vietnam Governmental Decree No. 84; and 21 species listed in CITES appendices., (Vinh Quang Dau, Thao Ngoc Hoang, Truong Quang Nguyen, Anh Van Pham.)

SARS-CoV-2 infects via the respiratory tract, but COVID-19 includes an array of non-respiratory symptoms, among them gastrointestinal (GI) manifestations such as vomiting and diarrhea. Here we investigated the GI pathology of SARS-CoV-2 infections in rhesus macaques and humans. Macaques experienced mild infection with USA-WA1/2020 and shed viral RNA in the respiratory tract and stool, including subgenomic RNA indicative of replication in the GI tract. Intestinal immune cell populations were disturbed, with significantly fewer proliferating (Ki67+) jejunal B cells in SARS-CoV-2-infected macaques than uninfected ones. Modest translocation of bacteria/bacterial antigen was observed across the colonic epithelium, with a corresponding significant increase in plasma soluble CD14 (sCD14) that may be induced by LPS. Human plasma demonstrated significant decreases in interleukin (IL)-6 and sCD14 upon recovery from COVID-19, suggesting resolution of inflammation and response to translocated bacteria. sCD14 significantly positively correlated with zonulin, an indicator of gut barrier integrity, and IL-6. These results demonstrate that GI perturbations such as microbial translocation can occur in even mild SARS-CoV-2 infections and may contribute to the COVID-19 inflammatory state.IMPORTANCEThis study investigates gastrointestinal (GI) barrier disruption in SARS-CoV-2 infections and how it may contribute to disease. We observed bacteria or bacterial products crossing from the colon interior (the lumen) to the lamina propria during SARS-CoV-2 infection in macaques. Bacteria/bacterial products are tolerated in the lumen but may induce immune responses if they translocate to the lamina propria. We also observed a significant increase in soluble CD14, which is associated with an immune response to bacterial products. In addition, we observed that humans recovering from COVID-19 experienced a significant decrease in soluble CD14, as well as the inflammatory marker interleukin (IL)-6. IL-6 and sCD14 correlated significantly across macaque and human samples. These findings suggest that SARS-CoV-2 infection results in GI barrier disruption that permits microbial translocation and a corresponding immune response. These findings could aid in developing interventions to improve COVID-19 patient outcomes., Competing Interests: The authors declare no conflict of interest.

Importance: To inform the design and implementation of targeted interventions to reduce the future burden of human papillomavirus (HPV)-related cancers in Texas, it is necessary to examine the county and health service region (HSR) levels of (1) the proportion of children and teenagers aged 9 to 17 years who initiated and were up to date for HPV vaccination series and (2) HPV-related cancer incidence rates (IRs)., Objective: To evaluate temporal trends and geospatial patterns of HPV vaccination initiation and up-to-date status as well as HPV-related cancer rates at county and HSR levels in Texas., Design, Setting, and Participants: This population-based cross-sectional study used data from the Texas Immunization Registry, the National Cancer Institute's Surveillance, Epidemiology, and End Results Program database, and Texas Department of State Health Services annual population counts from 2006 to 2022. The analysis of HPV vaccination rates was conducted among children and teenagers aged 9 to 17 years; the analysis of HPV-related cancer rates was conducted among adults aged 20 years and older. Data were extracted between June and July 2023 and statistical analysis was performed from February to April 2024., Main Outcomes and Measures: HPV vaccination initiation and up-to-date status rates and HPV-related cancer IR at county and HSR levels., Results: A total of 32 270 243 children and teenagers (65.8% female individuals and 34.2% male individuals) and 22 490 105 individuals aged 20 years and older (50.7% female individuals and 49.3% male individuals) were included. The mean 2021 to 2022 county-level HPV vaccination series initiation estimates ranged from 6.3% to 69.1% for female and from 7.0% to 77.6% for male children and teenagers aged 9 to 17 years. County-level vaccination up-to-date estimates were generally lower compared with those of initiation estimates and ranged from 1.6% to 30.4% for female and from 2.1% to 34.8% for male children and teenagers. The pattern of HPV vaccination rates stratified by sex were similar across counties and HSRs. The age-adjusted annual HPV-related cancer IR by county for years 2016 to 2020 ranged from 0 to 154.2 per 100 000 for female individuals and from 0 to 60.1 per 100 000 for male individuals. The counties located in North Texas, HSRs 2/3 and 4/5N, had lower HPV vaccination rates and higher IRs of HPV-related cancers for both female and male individuals compared with other regions., Conclusions and Relevance: In this study, the incidence of HPV-related cancers varied widely across the counties and HSRs of Texas. More counties in North Texas, HSRs 2/3 and 4/5N, had higher IRs of HPV-related cancers and a lower proportion of HPV vaccination rates than counties in other regions. Designing and implementing targeted interventions to increase uptake and completion of HPV vaccination series across counties with low HPV vaccination rates may help to reduce future the burden of HPV-related cancers.

Background: While cervical cancer incidence rates (IR) in the United States have dropped in the last 20 years, non-cervical human papillomavirus (HPV) associated cancers increased. Many people in Texas (TX) live in medically underserved areas and have higher risk of developing HPV-associated cancers. Since previous studies of these regions focused on cervical cancer, we included other HPV-associated cancers in our analysis of IR in East TX and the TX-Mexico Border compared to other TX regions., Methods: Cancer data from 2006 to 2019 were obtained from the TX Cancer Registry. Cases of HPV-associated cervical, vaginal, vulvar, penile, anal, and oropharyngeal cancers and corresponding patient-level demographic data were included. We calculated IR per 100,000 and drew heat maps to visualize cancer IR by county. To control potential confounders, we added county-level risk factors: rates for smoking, excessive drinking, obesity, STIs, primary care provider availability and dentist availability, from the County Health Rankings and Roadmaps program. We reported IRs by region and time and estimated unadjusted and adjusted risk ratio (RR) for association of each type of cancer and region. Lastly, we created adjusted models for each cancer by period to see time trends of regional differences., Results: Risk of anal, cervical, and oropharyngeal cancer was lower at parts of the Border than in the rest of TX in the adjusted model. We also observed increasing anal and oropharyngeal cancer risk and decreasing cervical and vaginal cancer risk over time., Conclusion: Patient sociodemographics, behavioral risk factors, and access to care may contribute to some observed differences in cancer IR across regions. This indicates that targeted prevention efforts towards these regions, especially in low socioeconomic status communities, may benefit future generations., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Human immunodeficiency virus (HIV) cure efforts are increasingly focused on harnessing CD8 + T cell functions, which requires a deeper understanding of CD8 + T cells promoting HIV control. Here we identifiy an antigen-responsive TOX hi TCF1 + CD39 + CD8 + T cell population with high expression of inhibitory receptors and low expression of canonical cytolytic molecules. Transcriptional analysis of simian immunodeficiency virus (SIV)-specific CD8 + T cells and proteomic analysis of purified CD8 + T cell subsets identified TOX hi TCF1 + CD39 + CD8 + T cells as intermediate effectors that retained stem-like features with a lineage relationship with terminal effector T cells. TOX hi TCF1 + CD39 + CD8 + T cells were found at higher frequency than TCF1 - CD39 + CD8 + T cells in follicular microenvironments and were preferentially located in proximity of SIV-RNA + cells. Their frequency was associated with reduced plasma viremia and lower SIV reservoir size. Highly similar TOX hi TCF1 + CD39 + CD8 + T cells were detected in lymph nodes from antiretroviral therapy-naive and antiretroviral therapy-suppressed people living with HIV, suggesting this population of CD8 + T cells contributes to limiting SIV and HIV persistence., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Erythroid sarcoma (ES) is exceedingly rare in the pediatric population with only a handful of reports of de novo cases, mostly occurring in the central nervous system (CNS) or orbit. It is clinically and pathologically challenging and can masquerade as a nonhematopoietic small round blue cell tumor. Clinical presentation of ES without bone marrow involvement makes diagnosis particularly difficult. We describe a 22-month-old female with ES who presented with a 2-cm mass involving the left parotid region and CNS. The presence of crush/fixation artifact from the initial biopsy made definitive classification of this highly proliferative and malignant neoplasm challenging despite an extensive immunohistochemical workup. Molecular studies including RNA-sequencing revealed a NFIA::CBFA2T3 fusion. This fusion has been identified in several cases of de novo acute erythroid leukemia (AEL) and gene expression analysis comparing this case to other AELs revealed a similar transcriptional profile. Given the diagnostically challenging nature of this tumor, clinical RNA-sequencing was essential for establishing a diagnosis., (© 2024 Wiley Periodicals LLC.)

Intercropping is an alternative farming method that maximizes crop yield and resource usage effectiveness, especially in low-input agricultural systems. Legume-based intercropping systems can effectively boost the quality and wheat yield by promoting soil functions and microbial activities. However, changes in the types of legumes and field management can alter the response of crop functions. A three-year field study was conducted on intercropping cultivation of winter wheat variety (Butterfly and Lorien) and legume species (faba bean, incarnate clover, spring pea, winter pea) to assess grain yield and wheat quality in organic farming. Based on the results, Butterfly showed higher grain quality but lower grain yield and yield components than Lorien. Mixtures of legume crops with winter wheat did not significantly differ in wheat grain yield, but grain quality variables were significantly affected. Protein content (PC) was significantly higher in wheat and legume mixtures than in sole wheat by 4 %. PC in wheat + winter pea (Wheat + Wi) and wheat + faba bean (Wheat + Fa) were higher than wheat sown alone. Wet gluten (WG) was higher in Wheat + Wi than in sole wheat and wheat + incarnate clover mixtures (Wheat + In). The rheological parameters evaluated by the Mixolab showed greater wheat quality in Butterfly and legume mixtures. Mixed and row-row intercropping of wheat and legume species did not significantly influence rheological properties. To conclude, customizing wheat yield and grain quality under the effect of winter wheat and legume mixtures requires considering the optimal solution based on different cultivates, wheat varieties and legume species to achieve the desired response., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Wheat ( Triticum aestivum L.) is a strategic agricultural crop that plays a significant role in maintaining national food security and sustainable economic development. Increasing technical performance considering lowering costs, energy, and environmental consequences are significant aims for wheat cultivation. For drylands, which cover approximately 41% of the world's land surface, water stress has a considerable negative impact on crop output. The current study aimed to assess the environmental aspects of chemical fertilizer in combination with compost in dryland and irrigated winter wheat production systems through life cycle assessment (LCA). The cradle-to-farm gate was considered as the system boundary based on one tone of wheat yield and four strategies: D-C (dryland with compost), D (dryland without compost), I-C (irrigated with compost), and I (irrigated without compost). Based on the results, the highest and lowest amounts of wheat yield were related to the I-C and D strategies with 12.2 and 6.7 ton ha -1 , respectively. The LCA result showed that the I strategy in comparison with other strategies had the highest negative impact on human health (49%), resources (59%), ecosystem quality (44%), and climate change (43%). However, the D-C strategy resulted in the lowest adverse effect of 6% on human health, 1% on resources, 10% on ecosystem quality, and 11% on climate change. Utilizing a combination of fertilizer and compost in dryland areas could ensure a higher yield of crops in addition to alleviating negative environmental indicators.

The development of therapeutics and vaccines for human diseases requires a systematic understanding of human biology. Although animal and in vitro culture models can elucidate some disease mechanisms, they typically fail to adequately recapitulate human biology as evidenced by the predominant likelihood of clinical trial failure. To address this problem, we developed AutoTransOP, a neural network autoencoder framework, to map omics profiles from designated species or cellular contexts into a global latent space, from which germane information for different contexts can be identified without the typically imposed requirement of matched orthologues. This approach was found in general to perform at least as well as current alternative methods in identifying animal/culture-specific molecular features predictive of other contexts-most importantly without requiring homology matching. For an especially challenging test case, we successfully applied our framework to a set of inter-species vaccine serology studies, where 1-to-1 mapping between human and non-human primate features does not exist., (© 2024. The Author(s).)

Nowadays, information technology (IT) has been holding a significant role in daily life worldwide. The trajectory of data science and bioinformatics promises pioneering personalized therapies, reshaping medical landscapes and patient care. For RNA therapy to reach more patients, a comprehensive understanding of the application of data science and bioinformatics to this therapy is essential. Thus, this chapter has summarized the application of data science and bioinformatics in RNA therapeutics. Data science applications in RNA therapy, such as data integration and analytics, machine learning, and drug development, have been discussed. In addition, aspects of bioinformatics such as RNA design and evaluation, drug delivery system simulation, and databases for personalized medicine have also been covered in this chapter. These insights have shed light on existing evidence and opened potential future directions. From there, scientists can elevate RNA-based therapeutics into an era of tailored treatments and revolutionary healthcare., (Copyright © 2024. Published by Elsevier Inc.)

Background: Land use and land cover changes have a significant impact on the dynamics of soil organic matter (SOM) and its fractions, as well as on overall soil health. This study conducted in Bharatpur Catchment, Chitwan District, Nepal, aimed to assess and quantify variations in total soil organic matter (T SOMC ), labile organic matter fraction (C L ), stable organic matter fraction (C S ), stability ratio (SR), and carbon management index (CMI) across seven land use types: pastureland, forestland, fruit orchards, small-scale conventional agricultural land, large-scale conventional agricultural land, large-scale alternative fallow and conventional agricultural land, and organic farming agricultural land. The study also explored the potential use of the Carbon Management Index (CMI) and stability ratio (SR) as indicators of soil degradation or improvement in response to land use changes., Results: The findings revealed significant differences in mean values of T SOMC , C L , and C S among the different land use types. Forestland and organic farming exhibited significantly higher T SOMC (3.24%, 3.12%) compared to fruit orchard lands (2.62%), small scale conventional farming (2.22%), alternative fallow and conventional farming (2.06%), large scale conventional farming (1.84%) and pastureland (1.20%). Organic farming and Forestland also had significantly higher C L (1.85%, 1.84%) and C S (1.27%, 1.39%) compared to all other land use types. Forest and organic farming lands showed higher CMI values, while pastures and forests exhibited higher SR values compared to the rest of the land use types., Conclusions: This study highlights the influence of various land use types on soil organic matter pools and demonstrates the potential of CMI and SR as indicators for assessing soil degradation or improvement in response to land use and land cover changes., (© 2023. The Author(s).)

Acute methanol intoxication is uncommon. Methanol is mildly toxic, but its metabolites are formic acid and formaldehyde, causing total metabolism, visual disturbances, and central nervous system disturbances, leading to coma and death. Magnetic resonance imaging (MRI) is very important for the diagnosis and prognosis of methanol intoxication. Putaminal necrosis with or without hemorrhage is the most frequently reported finding. Other affected areas that are reported in the literature are subcortical white matter, hippocampus, optic nerve, and cerebellum. We report 3 cases of methanol intoxication and discuss their brain lesions on MRI., (© 2023 The Authors.)

In the quest of improving the photocatalytic efficiency of photocatalysts, the combination of two and more semiconductors recently has garnered significant attention among scientists in the field. The doping of conductive metals is also an effective pathway to improve photocatalytic performance by avoiding electron/hole pair recombination and enhancing photon energy absorption. This work presented a design and fabrication of porphyrin@g-C 3 N 4 /Ag nanocomposite using acid-base neutralization-induced self-assembly approach from monomeric porphyrin and g-C 3 N 4 /Ag material. g-C 3 N 4 /Ag material was synthesized by a green reductant of Cleistocalyx operculatus leaf extract. Electron scanning microscopy (SEM), X-ray diffraction (XRD), FT-IR spectroscopy, and UV-vis spectrometer were utilized to analyse the properties of the prepared materials. The prepared porphyrin@g-C 3 N 4 /Ag nanocomposite showed well integration of porphyrin nanostructures on the g-C 3 N 4 /Ag's surface, in which porphyrin nanofiber was of the diameter in nanoscales and the length of several micrometers, and Ag NPs had an average particle size of less than 20 nm. The photocatalytic behavior of the resultant nanocomposite was tested for the degradation of Rhodamine B dye, which exhibited a remarkable RhB photodegrading percentage. The possible mechanism for photocatalysis of the porphyrin@g-C 3 N 4 /Ag nanocomposite toward Rhodamine B dye was also proposed and discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To investigate the effects of goal-directed fluid therapy (GDFT) or conventional fluid therapy (CFT) in improving postoperative outcomes in patients undergoing colorectal surgeries., Design: Evidence-Based Review., Methods: Following the guidelines outlined in the PRISMA statement, a comprehensive search was conducted using PubMed, Elsevier ScienceDirect, Oxford Academic, EBSCO, Google Scholar, Cochrane Library, and gray literature. Only randomized controlled studies and preappraised evidence such as systematic review with meta-analysis examining the effects of GDFT and CFT in colorectal surgery were included. The quality appraisal of the literature was conducted using the proposed algorithm described in the Johns Hopkins Nursing Evidence-Based Practice Evidence Level and Quality Guide., Findings: Two systematic reviews with meta-analyses and four randomized controlled trials (RCT) involving 2018 patients were included in this review. Overall, the use of GDFT did not shorten the hospital length of stay (LOS), reduce 30-day mortality, lower overall morbidity rates, or decrease incidence of postoperative ileus. Additionally, the return of bowel function was not improved using GDFT or CFT. However, when GDFT was implemented within enhanced recovery after surgery (ERAS) programs, there was a significant reduction in hospital LOS. . When GDFT was used in a non-ERAS patient care setting, there was a significant reduction in overall morbidity rate and faster time to first flatus. All studies included in the review were categorized as Level I and rated Grade A, implying strong confidence in the true effects of GDFT on all outcome measures in the review., Conclusions: The benefits of GDFT in colorectal surgery are still unclear. Considerable heterogeneity based on the types of GDFT devices, patient outcome parameters, and fluid protocols limit the application to clinical practice. Furthermore, there was limited data on the effects of GDFT in high-risk patients for colorectal surgery., (Copyright © 2022 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Type I interferons (IFN-I) are critical mediators of innate control of viral infections but also drive the recruitment of inflammatory cells to sites of infection, a key feature of severe coronavirus disease 2019. Here, IFN-I signaling was modulated in rhesus macaques (RMs) before and during acute SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection using a mutated IFN-α2 (IFN-modulator; IFNmod), which has previously been shown to reduce the binding and signaling of endogenous IFN-I. IFNmod treatment in uninfected RMs was observed to induce a modest up-regulation of only antiviral IFN-stimulated genes (ISGs); however, in SARS-CoV-2-infected RMs, IFNmod reduced both antiviral and inflammatory ISGs. IFNmod treatment resulted in a potent reduction in SARS-CoV-2 viral loads both in vitro in Calu-3 cells and in vivo in bronchoalveolar lavage (BAL), upper airways, lung, and hilar lymph nodes of RMs. Furthermore, in SARS-CoV-2-infected RMs, IFNmod treatment potently reduced inflammatory cytokines, chemokines, and CD163 + MRC1 - inflammatory macrophages in BAL and expression of Siglec-1 on circulating monocytes. In the lung, IFNmod also reduced pathogenesis and attenuated pathways of inflammasome activation and stress response during acute SARS-CoV-2 infection. Using an intervention targeting both IFN-α and IFN-β pathways, this study shows that, whereas early IFN-I restrains SARS-CoV-2 replication, uncontrolled IFN-I signaling critically contributes to SARS-CoV-2 inflammation and pathogenesis in the moderate disease model of RMs.

Sleep quality is an important indicator of treatment outcome for patients with traffic accident injuries. In Vietnam, the impacts of injury on sleep status are usually amplified in urban areas due to disproportionate distribution of mental care services between the city and less developed settings. Our study investigated deterioration in sleep quality and identified associated demographic factors among traffic injury patients in an small urban setting of Vietnam. A cross-sectional study was conducted among 408 patients in one provincial hospital and five district hospitals in Thai Binh, Vietnam from October to December 2018. A structured questionnaire was designed based on 3 standardized scales: Health-related Quality of Life, the Pittsburgh Sleep Quality Index and the Kessler Scale. Face-to-face interviews and medical records were conducted by trained health professionals on patients hospitalized in the Trauma-Orthopedic/Burn Department and Surgery and General Department. About 16.9% of respondents had sleep disturbances, and there was a statistically significant difference between age group (p < 0.01), education level (p < 0.01), and monthly household income (p < 0.01) between participants who with and without sleep disturbances. Furthermore, more than half (50.7%) of respondents sleep less than 5 h per day, while 18.7% of the sampled also reported that the habitual sleep efficiency was below 85%. Current results indicated that people being female, suffering from traumatic brain injury, being comatose at hospitalization, and having higher psychological distress scores were more likely to suffer from sleep problems. Our study is one of the first evidence in Vietnam to assess sleep disturbances in road traffic injury patients and their correlated factors. It is important to identify patients who are at risk of sleep disturbances based on socio-demographic and clinical characteristics, as well as psychological distress status. Therefore, a holistic approach should be taken to include sleep quality and psychological state in the treatment process and outcome assessment for road traffic injury patients., (© 2023. The Author(s).)

Introduction: Vietnam aims for 95% of commune health stations (CHSs) to have functional hypertension management programs by 2025. However, limited resources may impede the Central Highland region health system from achieving this goal. We assessed the availability and readiness of hypertension management services at CHSs in the Central Highland region and identified challenges to facilitate evidence-based planning., Methods: We used a mixed-methods cross-sectional design to assess hypertension management services using WHO's service availability and readiness assessment (SARA) tools in all 579 CHSs in the region, combined with twenty in-depth interviews of hypertension program focal points at communal, district, and provincial levels in all four provinces. We descriptively analyzed quantitative data and thematically analyzed qualitative data., Results: Hypertension management services were available at 65% of CHSs, and the readiness of the services was 62%. The urban areas had higher availability and readiness indices in most domains (basic amenities, basic equipment, and essential medicines) compared to rural areas, except for staff and training. The qualitative results showed a lack of trained staff and ambiguity in national hypertension treatment guidelines, insufficient essential medicines supply mechanism, and low priority and funding limitations for the hypertension program., Conclusion: The overall availability and readiness for hypertension diagnosis and management service at CHSs in the Central Highland region were low, reflecting inadequate capacity of the primary healthcare facilities. Some measures to strengthen hypertension programs in the region might include increased financial support, ensuring a sufficient supply of basic medicines, and providing more specific treatment guidelines., (© 2023. The Author(s).)

The immunopathological mechanisms driving the development of severe COVID-19 remain poorly defined. Here, we utilize a rhesus macaque model of acute SARS-CoV-2 infection to delineate perturbations in the innate immune system. SARS-CoV-2 initiates a rapid infiltration of plasmacytoid dendritic cells into the lower airway, commensurate with IFNA production, natural killer cell activation, and a significant increase of blood CD14 - CD16 + monocytes. To dissect the contribution of lung myeloid subsets to airway inflammation, we generate a longitudinal scRNA-Seq dataset of airway cells, and map these subsets to corresponding populations in the human lung. SARS-CoV-2 infection elicits a rapid recruitment of two macrophage subsets: CD163 + MRC1 - , and TREM2 + populations that are the predominant source of inflammatory cytokines. Treatment with baricitinib (Olumiant®), a JAK1/2 inhibitor is effective in eliminating the influx of non-alveolar macrophages, with a reduction of inflammatory cytokines. This study delineates the major lung macrophage subsets driving airway inflammation during SARS-CoV-2 infection., (© 2023. The Author(s).)

Type-I interferons (IFN-I) are critical mediators of innate control of viral infections, but also drive recruitment of inflammatory cells to sites of infection, a key feature of severe COVID-19. Here, and for the first time, IFN-I signaling was modulated in rhesus macaques (RMs) prior to and during acute SARS-CoV-2 infection using a mutated IFNα2 (IFN-modulator; IFNmod), which has previously been shown to reduce the binding and signaling of endogenous IFN-I. In SARS-CoV-2-infected RMs, IFNmod reduced both antiviral and inflammatory ISGs. Notably, IFNmod treatment resulted in a potent reduction in (i) SARS-CoV-2 viral load in Bronchoalveolar lavage (BAL), upper airways, lung, and hilar lymph nodes; (ii) inflammatory cytokines, chemokines, and CD163+MRC1-inflammatory macrophages in BAL; and (iii) expression of Siglec-1, which enhances SARS-CoV-2 infection and predicts disease severity, on circulating monocytes. In the lung, IFNmod also reduced pathogenesis and attenuated pathways of inflammasome activation and stress response during acute SARS-CoV-2 infection. This study, using an intervention targeting both IFN-α and IFN-β pathways, shows that excessive inflammation driven by type 1 IFN critically contributes to SARS-CoV-2 pathogenesis in RMs, and demonstrates the potential of IFNmod to limit viral replication, SARS-CoV-2 induced inflammation, and COVID-19 severity.

The utilization of plant by-products as functional food ingredients has received increasing attention in the last decade. One such by-product generated during milk thistle oil pressing is oilseed cakes, which could be used as a novel food ingredient. Therefore, the study aimed at investigating the effects of the addition of milk thistle oilseed cake (MTOC) flour fractions obtained via dry sieving, differing in particle size (unsieved; coarse: >710 µm; medium: 315−710 µm; and fine: <315 µm), on the quality of gluten-free bread and stability of silymarin during breadmaking. The 10% addition of the fractions into gluten-free bread increased the protein, fibre, fat, ash and silymarin content. The breads with the coarse fraction had the highest content of fibre, whereas the breads with the fine fraction excelled in protein, fat and ash content. The medium fraction was characterized as the richest source of silymarin, whilst the fine fraction was the poorest. Silymarin constituents were slightly released during dough rising but also partially decomposed during baking; moreover, silydianin was the most susceptible and degraded the most. The enriched breads had better sensory and textural properties compared to the control bread. The results suggest that MTOC flour fractions can improve the potential health benefits and nutritional profile of gluten-free bread.

Despite the advent of effective antiretroviral therapy (ART), human immunodeficiency virus (HIV) continues to pose major challenges, with extensive pathogenesis during acute and chronic infection prior to ART initiation and continued persistence in a reservoir of infected CD4 T cells during long-term ART. CD101 has recently been characterized to play an important role in CD4 Treg potency. Using the simian immunodeficiency virus (SIV) model of HIV infection in rhesus macaques, we characterized the role and kinetics of CD101+ CD4 T cells in longitudinal SIV infection. Phenotypic analyses and single-cell RNAseq profiling revealed that CD101 marked CD4 Tregs with high immunosuppressive potential, distinct from CD101- Tregs, and these cells also were ideal target cells for HIV/SIV infection, with higher expression of CCR5 and α4β7 in the gut mucosa. Notably, during acute SIV infection, CD101+ CD4 T cells were preferentially depleted across all CD4 subsets when compared with their CD101- counterpart, with a pronounced reduction within the Treg compartment, as well as significant depletion in mucosal tissue. Depletion of CD101+ CD4 was associated with increased viral burden in plasma and gut and elevated levels of inflammatory cytokines. While restored during long-term ART, the reconstituted CD101+ CD4 T cells display a phenotypic profile with high expression of inhibitory receptors (including PD-1 and CTLA-4), immunsuppressive cytokine production, and high levels of Ki-67, consistent with potential for homeostatic proliferation. Both the depletion of CD101+ cells and phenotypic profile of these cells found in the SIV model were confirmed in people with HIV on ART. Overall, these data suggest an important role for CD101-expressing CD4 T cells at all stages of HIV/SIV infection and a potential rationale for targeting CD101 to limit HIV pathogenesis and persistence, particularly at mucosal sites., Competing Interests: The authors have declared that no competing interests exist

Tropical lotus ( Nelumbo ) is an important and unique ecological type of lotus germplasm. Understanding the genetic relationship and diversity of the tropical lotus is necessary for its sustainable conservation and utilization. Using 42 EST-SSR (expressed sequence tag-simple sequence repeats) and 30 SRAP (sequence-related amplified polymorphism) markers, we assessed the genetic diversity and inferred the ancestry of representative tropical lotus from Thailand and Vietnam. In total, 164 and 41 polymorphic bands were detected in 69 accessions by 36 EST-SSR and seven SRAP makers, respectively. Higher genetic diversity was revealed in Thai lotus than in Vietnamese lotus. A Neighbor-Joining tree of five main clusters was constructed using combined EST-SSR and SRAP markers. Cluster I included 17 accessions of Thai lotus; cluster II contained three Thai accessions and 11 accessions from southern Vietnam; and cluster III was constituted by 13 accessions of seed lotus. Consistent with the results from the Neighbor-Joining tree, the genetic structure analysis showed that the genetic background of most Thai and Vietnamese lotus was pure, as artificial breeding has been rare in both countries. Furthermore, these analyses indicate that Thai and Vietnamese lotus germplasms belong to two different gene pools or populations. Most lotus accessions are genetically related to geographical distribution patterns in Thailand or Vietnam. Our findings showed that the origin or genetic relationships of some unidentified lotus sources can be evaluated by comparing morphological characteristics and the data of molecular markers. In addition, these findings provide reliable information for the targeted conservation of tropical lotus and parent selection in breeding novel cultivars of lotus., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Kunming Institute of Botany, Chinese Academy of Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

There is a growing interest in applying deep learning (DL) to healthcare, driven by the availability of data with multiple feature channels in rich-data environments (e.g., intensive care units). However, in many other practical situations, we can only access data with much fewer feature channels in a poor-data environments (e.g., at home), which often results in predictive models with poor performance. How can we boost the performance of models learned from such poor-data environment by leveraging knowledge extracted from existing models trained using rich data in a related environment? To address this question, we develop a knowledge infusion framework named CHEER that can succinctly summarize such rich model into transferable representations, which can be incorporated into the poor model to improve its performance. The infused model is analyzed theoretically and evaluated empirically on several datasets. Our empirical results showed that CHEER outperformed baselines by 5.60% to 46.80% in terms of the macro-F1 score on multiple physiological datasets.

The COVID-19 pandemic remains a global health crisis, yet, the immunopathological mechanisms driving the development of severe disease remain poorly defined. Here, we utilize a rhesus macaque (RM) model of SARS-CoV-2 infection to delineate perturbations in the innate immune system during acute infection using an integrated systems analysis. We found that SARS-CoV-2 initiated a rapid infiltration (two days post infection) of plasmacytoid dendritic cells into the lower airway, commensurate with IFNA production, natural killer cell activation, and induction of interferon-stimulated genes. At this early interval, we also observed a significant increase of blood CD14-CD16+ monocytes. To dissect the contribution of lung myeloid subsets to airway inflammation, we generated a novel compendium of RM-specific lung macrophage gene expression using a combination of sc-RNA-Seq data and bulk RNA-Seq of purified populations under steady state conditions. Using these tools, we generated a longitudinal sc-RNA-seq dataset of airway cells in SARS-CoV-2-infected RMs. We identified that SARS-CoV-2 infection elicited a rapid recruitment of two subsets of macrophages into the airway: a C206+MRC1-population resembling murine interstitial macrophages, and a TREM2+ population consistent with CCR2+ infiltrating monocytes, into the alveolar space. These subsets were the predominant source of inflammatory cytokines, accounting for ~75% of IL6 and TNF production, and >90% of IL10 production, whereas the contribution of CD206+MRC+ alveolar macrophages was significantly lower. Treatment of SARS-CoV-2 infected RMs with baricitinib (Olumiant ® ), a novel JAK1/2 inhibitor that recently received Emergency Use Authorization for the treatment of hospitalized COVID-19 patients, was remarkably effective in eliminating the influx of infiltrating, non-alveolar macrophages in the alveolar space, with a concomitant reduction of inflammatory cytokines. This study has delineated the major subsets of lung macrophages driving inflammatory and anti-inflammatory cytokine production within the alveolar space during SARS-CoV-2 infection., One Sentence Summary: Multi-omic analyses of hyperacute SARS-CoV-2 infection in rhesus macaques identified two population of infiltrating macrophages, as the primary orchestrators of inflammation in the lower airway that can be successfully treated with baricitinib.

Background: A retrospective chart review of liver histologies in Kasai biliary atresia BA patients operated 1/2017- 7/2019 at our institution was conducted to identify histologic prognostic factors for biliary outcome., Methods: Patients with wedge liver biopsies and portal plate biopsies (n = 85) were categorized into unfavorable and favorable outcome, based on a 3-month serum total bilirubin level of <34 μM or mortality. Hepatocellular histologies, presence of ductal plate malformation (DPM) and of large bile duct of ≥ 150 μm diameter size at the portal plate were evaluated., Results: Total Bilirubin levels> 34 μM correlates with worse 1-year survival. Age at surgery, histologic fibrosis or inflammation does not predict outcome. Potential adverse predictors are severe hepatocellular swelling, severe cholestasis, presence of DPM (n = 24), and portal plate bile duct size < 150 µm (n = 28). In multivariate analyses adjusting for age at Kasai and postop cholangitis, bile duct size and severe hepatocellular swelling remain independent histologic prognosticators (OR 3.25, p = 0.039 and OR 3.26, p = 0.006 respectively), but not DPM., Conclusion: Advanced histologic findings of portal plate bile duct size of <150 µm and severe hepatocellular damage predict poor post-Kasai jaundice clearance and short-term survival outcome, irrespective of Kasai timing., Level of Evidence: Level III., (Copyright © 2021. Published by Elsevier Inc.)

Lifetime exposure to stress leads to risk of suffering from cumulative detrimental physiological and psychological ailments. Due to the nature of healthcare and exposure to trauma, medical professionals are particularly susceptible to the negative impacts of high stress environments. emotional intelligence plays a role in ameliorating the risk of being negatively impacted by these stressors. As such, there is special interest to develop and implement training interventions for medical personnel that would allow them to improve emotional intelligence potential with the goal of enabling them to handle stress better and mitigate burnout. A hyper-realistic surgical simulation training session, replicating the intensity of a Mass-Casualty Event scenario, was implemented to allow medical professionals to experience this in real time. Overall, the training led to increased emotional intelligence, correlating with decreased hypothalamus-pituitary-adrenal axis and sympathetic nervous system stress biomarkers, cortisol and α-amylase. This novel training provides, at least, short-term improvements in emotional intelligence that is reflected with a physiological response. These results guide the ongoing effort to develop therapeutic tools to improve long term stress management, mitigate burnout and reduce post-traumatic stress risk after an exposure to a Mass-Casualty event scenario., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

SARS-CoV-2-induced hypercytokinemia and inflammation are critically associated with COVID-19 severity. Baricitinib, a clinically approved JAK1/JAK2 inhibitor, is currently being investigated in COVID-19 clinical trials. Here, we investigated the immunologic and virologic efficacy of baricitinib in a rhesus macaque model of SARS-CoV-2 infection. Viral shedding measured from nasal and throat swabs, bronchoalveolar lavages, and tissues was not reduced with baricitinib. Type I interferon (IFN) antiviral responses and SARS-CoV-2-specific T cell responses remained similar between the two groups. Animals treated with baricitinib showed reduced inflammation, decreased lung infiltration of inflammatory cells, reduced NETosis activity, and more limited lung pathology. Importantly, baricitinib-treated animals had a rapid and remarkably potent suppression of lung macrophage production of cytokines and chemokines responsible for inflammation and neutrophil recruitment. These data support a beneficial role for, and elucidate the immunological mechanisms underlying, the use of baricitinib as a frontline treatment for inflammation induced by SARS-CoV-2 infection., Competing Interests: Declaration of interests R.F.S. served as an unpaid consultant for Eli Lilly whose drugs are being evaluated in the research described in this paper. In addition, R.F.S. owns shares in Eli Lilly. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies. Eli Lilly had no role in the design of this study and did not have any role during its execution, analyses, interpretation of the data, or decision to submit results. All other authors do not have any conflicts to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world. Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details underlying these processes remain to be determined. In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of lungs from both humans and rhesus macaques infected with SARS-CoV-2. To define key molecular pathways associated with SARS-CoV-2 pathogenesis in macaques, we performed transcriptomic analyses of bronchoalveolar lavage and peripheral blood and proteomic analyses of serum. We observed macrophage infiltrates in lung and upregulation of macrophage, complement, platelet activation, thrombosis, and proinflammatory markers, including C-reactive protein, MX1, IL-6, IL-1, IL-8, TNFα, and NF-κB. These results suggest a model in which critical interactions between inflammatory and thrombosis pathways lead to SARS-CoV-2-induced vascular disease. Our findings suggest potential therapeutic targets for COVID-19., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Burnout is being experienced by medical students, residents, and practicing physicians at significant rates. Higher levels of Hardiness and Emotional Intelligence may protect individuals against burnout symptoms. Previous studies have shown both Hardiness and Emotional IntelIigence protect against detrimental effects of stress and can be adapted through training; however, there is limited research on how training programs affect both simultaneously. Therefore, the objective of this study was to define the association of Hardiness and Emotional Intelligence and their potential improvement through hyper realistic immersion simulation training in military medical students., Methods: Participants in this study consisted of 68 second year medical students representing five medical schools who were concurrently enrolled in the United States military scholarship program. During a six day hyper-realistic surgical simulation training course, students rotated through different roles of a medical team and responded to several mass-casualty scenarios. Hardiness and Emotional Intelligence were assessed using the Hardiness Resilience Gauge (HRG) and the Emotional Quotient Inventory (EQ-I 2.0) respectively, at two time points: on arrival (pre-event) and after completion of the course (post-event)., Results: Hardiness and Emotional Intelligence scores and sub scores consistently improved from pre-event to post-event assessments. No difference in training benefit was observed between genders but differences were observed by age where age was more often associated with Emotional Intelligence. In addition, factor analysis indicated that the HRG and EQ-I 2.0 assessment tools measured predominately different traits although they share some commonalities in some components., Conclusion: This study indicates that Hardiness and Emotional Intelligence scores can be improved through immersion training in military medical students. Results from this study support the use of training course interventions and prompt the need for long term evaluation of improvement strategies on mitigating burnout symptoms., (Copyright © 2020 White, Zapata, Lenz, Ryznar, Nevins, Hoang, Franciose, Safaoui, Clegg and LaPorta.)

Effective therapeutics aimed at mitigating COVID-19 symptoms are urgently needed. SARS-CoV-2 induced hypercytokinemia and systemic inflammation are associated with disease severity. Baricitinib, a clinically approved JAK1/2 inhibitor with potent anti-inflammatory properties is currently being investigated in COVID-19 human clinical trials. Recent reports suggest that baricitinib may also have antiviral activity in limiting viral endocytosis. Here, we investigated the immunologic and virologic efficacy of baricitinib in a rhesus macaque model of SARS-CoV-2 infection. Viral shedding measured from nasal and throat swabs, bronchoalveolar lavages and tissues was not reduced with baricitinib. Type I IFN antiviral responses and SARS-CoV-2 specific T cell responses remained similar between the two groups. Importantly, however, animals treated with baricitinib showed reduced immune activation, decreased infiltration of neutrophils into the lung, reduced NETosis activity, and more limited lung pathology. Moreover, baricitinib treated animals had a rapid and remarkably potent suppression of alveolar macrophage derived production of cytokines and chemokines responsible for inflammation and neutrophil recruitment. These data support a beneficial role for, and elucidate the immunological mechanisms underlying, the use of baricitinib as a frontline treatment for severe inflammation induced by SARS-CoV-2 infection.

Objectives: The aim of this study was to report the draft genome sequences of two multidrug-resistant bacteria (Bacteroides thetaiotaomicron F9-2 and Escherichia coli 09-02E) isolated from stool samples of a healthy resident in Vietnam., Methods: Genome sequences were determined using MiSeq and MinION platforms. Genome assembly was performed using Platanus Assembler v.1.2.4 and Canu v.1.7. The DDBJ Fast Annotation and Submission Tool were used for genome annotation., Results: The genome of B. thetaiotaomicron F9-2 comprised 6 283 774 bp with a GC content of 42.7% and 4802 protein coding sequences (CDS), whereas the genome of E. coli 09-02E comprised 5 246 320 bp with a GC content of 50.6% and 4991 protein CDS. Both strains harboured common antimicrobial resistance genes, such as those for sulfonamides (sul2) and aminoglycosides (strA, strB). However, the sul2-strA-strB cassette was located on the chromosome of B. thetaiotaomicron F9-2, whereas it was located on a plasmid in E. coli 09-02E. These genes were flanked by different insertion sequences., Conclusion: Considering their diversities in the human gut resistome, these strains would be of considerable interest for detailed comparative genomic analysis. Notably, the same sul2 cassette was found in facultative and obligate anaerobic bacterial isolates (resident in humans). However, the different location of the cassette indicates a possible mechanism of gene transfer among gut microbes., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Falls and recurrent falls cause great health and social consequences in older people. However, these problems are poorly understood in Vietnam. A cross-sectional study was performed at seven hospitals in Thai Binh province, Vietnam, to investigate the individual and environmental factors associated with recurrent falls among elderly patients hospitalized due to fall injuries in Vietnam. A history of recurrent falls within the last 12 months, sociodemographic, health, and clinical characteristics, as well as environmental conditions, were obtained via self-reported interviews. Multivariate logistic and Poisson regression models were used to identify associated factors. Overall, the mean fall episodes in the last 12 months were 1.8 (Standard deviation-SD = 1.2) episodes, and the 12-month prevalence of recurrent falls was 40.5%. The individual risk factors included not receiving fall prevention guidelines, walking with devices, loss of sensation in hand or foot, and using pain relief medications. The environmental risk factors comprised having too-high stairs and not having dry, clean, and nonslippery bathrooms. This study highlights a significantly high 12-month prevalence of recurrent falls in older patients hospitalized after falls in Vietnam. Moreover, regular assessments of functional disabilities and hazardous environmental conditions, as well as the provision of prevention programs, have potential to prevent falls and recurrent falls.

Background: Surgical trauma care requires excellent multidisciplinary team skills and communication to ensure the highest patient survival rate. This study investigated the effects of Hyper-realistic immersive surgical team training to improve individual and team performance. A Hyper-realistic surgical training environment is defined as having a high degree of fidelity in the replication of battlefield conditions in a training environment, so participants willingly suspend disbelief that they become totally immersed and eventually stress inoculated in a way that can be measured physiologically., Methods: Six multispecialty member US Navy Fleet Surgical/US Army Forward Surgical Teams (total n=99 evaluations) underwent a 6-day surgical training simulation using movie industry special effects and role players wearing the Human Worn Surgical Simulator (Cut Suit). The teams were immersed in trauma care scenarios requiring multiple complex interventions and decision making in a realistic, fast-paced, intensive combat trauma environment., Results: Hyper-realistic immersive simulation training enhanced performance between multidisciplinary healthcare team members. Key efficacy quantitative measurements for the same simulation presented on day 1 compared with day 6 showed a reduction in resuscitation time from 24 minutes to 14 minutes and critical error decrease from 5 to 1. Written test scores improved an average of 21% (Medical Doctors 11%, Registered Nurses 25%, and Corpsman/Medics 26%). Longitudinal psychometric survey results showed statistically significant increases in unit readiness (17%), combat readiness (12%), leadership quality (7%), vertical cohesion (7%), unit cohesion (5%), and team communication (3%). An analysis of salivary cortisol and amylase physiologic biomarkers indicated an adaptive response to the realistic environment and a reduction in overall team stress during performance evaluations., Conclusions: Hyper-realistic immersive simulation training scenarios can be a basis for improved military and civilian trauma training., Level of Evidence: Level III., Competing Interests: Competing interests: KL is Executive Vice President, Strategic Operations, San Diego, California., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Soft body armor is typically comprised of materials such as aramid. Recently, copolymer fibers based on the combination of 5-amino-2-(p-aminophenyl) benzimidazole (PBIA) and PPTA were introduced to the body armor marketplace. The long-term stability of these copolymer fibers have not been the subject of much research, however they may be sensitive to hydrolysis due to elevated humidity because they are condensation polymers. Efforts to evaluate the impact of environmental conditions on fiber strength is very important for the adoption of these materials in armor systems. Three PBIA-based fibers were selected for the study, and were aged at 25 °C, 75 % RH; 43 °C, 41 % RH; 55 °C, 60 % RH; and 70 °C, 76 % RH for up to 524 d. Molecular spectroscopy, scanning electron microscopy, and single fiber tensile testing were performed to characterize changes in their chemical structure, tensile strength, and failure strain as a function of exposure time to different conditions. The fibers were all found to have some reduction in strength at high humidity conditions, with an approximately 14 % reduction for the copolymers and a 29 % reduction for the homopolymer. Molecular spectroscopy revealed some changes which suggest that hydrolysis of the benzimidazole ring is occurring at these elevated temperatures, possibly explaining the observed change in strength.

Predictive phenotyping is about accurately predicting what phenotypes will occur in the next clinical visit based on longitudinal Electronic Health Record (EHR) data. While deep learning (DL) models have recently demonstrated strong performance in predictive phenotyping, they require access to a large amount of labeled data, which are expensive to acquire. To address this label-insufficient challenge, we propose a deep dictionary learning framework (DDL) for phenotyping, which utilizes unlabeled data as a complementary source of information to generate a better, more succinct data representation. Our empirical evaluations on multiple EHR datasets demonstrated that DDL outperforms the existing predictive phenotyping methods on a wide variety of clinical tasks that require patient phenotyping. The results also show that unlabeled data can be used to generate better data representation that helps improve DDL's phenotyping performance over existing methods that only uses labeled data.

Cryptococcosis causes approximately 180 000 deaths each year in patients with human immunodeficiency virus (HIV). Patients with other forms of immunosuppression are also at risk, and disease is increasingly recognized in apparently immunocompetent individuals. Cryptococcus neoformans var. grubii, responsible for the majority of cases, is distributed globally. We used the consensus ISHAM Multilocus sequence typing (MLST) scheme to define the population structure of clinical C. neoformans var. grubii isolates from Laos (n = 81), which we placed into the global context using published MLST data from other countries (total N = 1047), including a reanalysis of 136 Vietnamese isolates previously reported. We observed a phylogeographical relationship in which the Laotian population was similar to its neighbor Thailand, being dominated (83%) by Sequence Types (ST) 4 and 6. This phylogeographical structure changed moving eastwards, with Vietnam's population consisting of an admixture of isolates dominated by the ST4/ST6 (35%) and ST5 (48%) lineages. The ST5 lineage is the predominant ST reported from China and East Asia, where it accounts for >90% of isolates. Analysis of genetic distance (Fst) between different populations of C. neoformans var. grubii supports this intermediate structure of the Vietnamese population. The pathogen and host diversity reported from Vietnam provide the strongest epidemiological evidence of the association between ST5 and HIV-uninfected patients. Regional anthropological genetic distances suggest diversity in the C. neoformans var. grubii population across Southeast Asia is driven by ecological rather than human host factors. Where the ST5 lineage is present, disease in HIV-uninfected patients is to be expected., (© The Author(s) 2018. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Purpose of Review: The current article describes the current status of the use of cytokines and immune-checkpoint inhibitors as therapeutic strategies toward HIV remission., Recent Findings: Clinical trials using IL-2 and IL-7 showed increased levels of circulating T cells, although no reduction to the viral reservoir was observed. Studies in nonhuman primates (NHP) demonstrated that experimental IL-15 administration increased proliferation and cytotoxicity of simian immunodeficiency virus (SIV)-specific CD8 T cells, and promoted their localization to the lymph node (LN) B cell follicles. Immune checkpoint modulators targeting programed cell death-1 and cytotoxic T-lymphocyte associated protein 4, successfully used in oncologic diseases, have shown potential to restore HIV-specific function in early stage clinical trials, while also transiently increasing plasma and cell-associated viral RNA. Due to the complexity of the mechanisms regulating HIV persistence, it is very likely that combinatorial approaches, including cytokines with immune checkpoint blockades (ICBs), will be needed to achieve HIV remission., Summary: The present review covers approaches based on cytokine agonists and immune checkpoint inhibitors that have shown promise toward therapeutic pathways for HIV remission. These strategies have been tested preclinically in animal models of HIV infection to determine their safety, activity, and mechanisms of action, with the goal to inform the design of the most synergistic combinatorial strategies. Several of these interventions are included in ongoing or planned clinical trials in HIV infection; these trials will elucidate the clinical efficacy of these innovative immunotherapy approaches toward HIV remission.

The bone marrow (BM) is the key anatomic site for hematopoiesis and plays a significant role in the homeostasis of mature T cells. However, very little is known on the phenotype of BM-derived CD4 + T cells, their fate during simian immunodeficiency virus (SIV) infection, and their contribution to viral persistence during antiretroviral therapy (ART). In this study, we characterized the immunologic and virologic status of BM-derived CD4 + T cells in rhesus macaques prior to SIV infection, during the early chronic phase of infection, and during ART. We found that BM memory CD4 + T cells are significantly depleted following SIV infection, at levels that are similar to those measured in the peripheral blood (PB). In addition, BM-derived memory CD4 + T cells include a high frequency of cells that express the coinhibitory receptors CTLA-4 and PD-1, two subsets previously shown to be enriched in the viral reservoir; these cells express Ki-67 at levels similar to or higher than the same cells in PB. Finally, when we analyzed SIV-infected RMs in which viral replication was effectively suppressed by 12 months of ART, we found that BM CD4 + T cells harbor SIV DNA and SIV RNA at levels comparable to those of PB CD4 + T cells, including replication-competent SIV. Thus, BM is a largely understudied anatomic site of the latent reservoir which contributes to viral persistence during ART and needs to be further characterized and targeted when designing therapies for a functional or sterilizing cure to HIV. IMPORTANCE The latent viral reservoir is one of the major obstacles in purging the immune system of HIV. It is paramount that we elucidate which anatomic compartments harbor replication-competent virus, which upon ART interruption results in viral rebound and pathogenesis. In this study, using the rhesus macaque model of SIV infection and ART, we examined the immunologic status of the BM and its role as a potential sanctuary for latent virus. We found that the BM compartment undergoes a similar depletion of memory CD4 + T cells as PB, and during ART treatment the BM-derived memory CD4 + T cells contain high levels of cells expressing CTLA-4 and PD-1, as well as amounts of cell-associated SIV DNA, SIV RNA, and replication-competent virus comparable to those in PB. These results enrich our understanding of which anatomic compartments harbor replication virus and suggest that BM-derived CD4 + T cells need to be targeted by therapeutic strategies aimed at achieving an HIV cure., (Copyright © 2018 American Society for Microbiology.)

Background: The US Navy initiated design concepts for a Medical Mission Module Support Container (M3SC), a mobile operating room capable of rapid installation aboard maneuverable ships within proximity of active combat units. The M3SC provides an alternative echelon of care in the current trauma system by decreasing the time between point of injury, arrival, and surgical intervention. The mobile ships used as M3SC platforms, however, are more susceptible to oceanic conditions that can induce detrimental physiologic motion sickness in medical personnel and patients aboard the vessels. This study investigated the effects of different sea-state motion conditions on the performance of surgical teams., Methods: Six four-person surgical teams performed 144 procedures in an M3SC aboard a Stewart motion table that simulated motion profiles of sea states 0, 3, and 4. A modified human-worn partial- task surgical simulator was used as a surgical surrogate to simulate the four most common, wartime, improvised explosive device injuries in the past 10 years. Electroencephalographs and heart rate variability (HRV) data were collected from surgeons and surgical technologists during each procedure to assess real-time physiologic responses to motion. Two postprocedure surveys, a Surgical Task Load Index and a Motion Sickness Assessment Questionnaire, were given to assess subjective responses of workload stress and motion-induced kinetosis. Surgical subject matter experts quantified surgical performance after each procedure by measuring blood loss and orthopedic pin placement to evaluate each intervention., Results: Motion did not significantly influence overall performance (ρ = .002). Surgical procedure was the strongest predictor of performance. HRV was used to measure stress and was increased in surgical technologists; however, HRV was decreased for surgeons and technologists in motion. There was a significant interaction between role and motion (ρ = .002): Surgeons had higher workloads than did surgical technologists and neither demonstrated differences between motion and no motion. Surgeons demonstrated significantly decreased workloads under motion conditions (ρ = 0.002); however, surgeons perceived their workload to be higher. We attribute this to their increased critical thinking and physical execution of procedures. Surgeons and surgical technologists showed a trend toward HRV suppression within the motion conditions. This may indicate a coping response to the increased stress of the motion setting. Procedure and team dynamic were the strongest predictors of overall performance, suggesting a learning curve exists and that added focus on training should be enforced., Conclusion: Based on data collected in this study, similar surgical procedures should be implemented aboard these classes of ships. By doing so, injured military personnel would have more timely access to care. Surgical team members were aware of craft motion, used compensatory measures, and exhibited some physiological response., (2018.)

Acrylic bone cements, although successful in the field of orthopedics, suffer from a lack of bioactivity, not truly integrating with surrounding bone. Bioactive fixation is expected to enhance cement performance because of the natural interlocking and bonding with bone, which can improve the augmentative potential of the material in applications such as vertebroplasty (VP). In a recent study, two composite cements (PMMA-hydroxyapatite and PMMA-brushite) showed promising results demonstrating no deterioration in rheological and mechanical properties after CaP filler addition. In this study, the dynamic properties of the cements were investigated in vitro and in vivo. The hypothesis was that these composite cements will provide osseointegration around the implanted cement and increase new bone formation, thus decreasing the risk of bone structural failure. The effects of CaP elution were thus analyzed in vitro using these cements. Mass-loss, pore formation, and mechanical changes were tracked after cement immersion in Hank's salt solution. PMMA-brushite was the only cement with a significant mass loss; however it showed low bulk porosity. Surface porosity increases were observed in both composite cements. Mechanical properties were maintained after cement immersion. In vitro culture studies tested preosteoblast cell viability and differentiation on the cement surface. Cell viability was demonstrated with MTT assay and confirmed on the cement surface. ALP assays showed no inhibition of osteoblast differentiation on the cement surface. In vivo experiments were performed using a rat tibiae model to demonstrate bone ingrowth around the implanted cements. Critical size defects were created and then filled with the cements. The animal studies showed no loss in mechanical strength after implantation and increased bone ingrowth around the composite cements. In summary, the composite cements provided bioactivity without sacrificing mechanical strength.

The otherwise harmless skin inhabitant Staphylococcus epidermidis is a major cause of healthcare-associated medical device infections. The species' selective pathogenic potential depends on its production of surface adherent biofilms. The Cell wall-anchored protein Aap promotes biofilm formation in S. epidermidis, independently from the polysaccharide intercellular adhesin PIA. Aap requires proteolytic cleavage to act as an intercellular adhesin. Whether and which staphylococcal proteases account for Aap processing is yet unknown. Here, evidence is provided that in PIA-negative S. epidermidis 1457Δica, the metalloprotease SepA is required for Aap-dependent S. epidermidis biofilm formation in static and dynamic biofilm models. qRT-PCR and protease activity assays demonstrated that under standard growth conditions, sepA is repressed by the global regulator SarA. Inactivation of sarA increased SepA production, and in turn augmented biofilm formation. Genetic and biochemical analyses demonstrated that SepA-related induction of biofilm accumulation resulted from enhanced Aap processing. Studies using recombinant proteins demonstrated that SepA is able to cleave the A domain of Aap at residue 335 and between the A and B domains at residue 601. This study identifies the mechanism behind Aap-mediated biofilm maturation, and also demonstrates a novel role for a secreted staphylococcal protease as a requirement for the development of a biofilm., (© 2016 John Wiley & Sons Ltd.)

Staphylococcus epidermidis is a leading cause of hospital-associated infections, including those of intravascular catheters, cerebrospinal fluid shunts, and orthopedic implants. Multiple biofilm matrix molecules with heterogeneous characteristics have been identified, including proteinaceous, polysaccharide, and nucleic acid factors. Two of the best-studied components in S. epidermidis include accumulation-associated protein (Aap) and polysaccharide intercellular adhesin (PIA), produced by the enzymatic products of the icaADBC operon. Biofilm composition varies by strain as well as environmental conditions, and strains producing PIA-mediated biofilms are more robust. Clinically, biofilm-mediated infections occur in a variety of anatomical sites with diverse physiological properties. To test the hypothesis that matrix composition exhibits niche specificity, biofilm-related genetic and physical properties were compared between S. epidermidis strains isolated from high-shear and low-shear environments. Among a collection of 105 clinical strains, significantly more isolates from high-shear environments carried the icaADBC operon than did those from low-shear settings (43.9% versus 22.9%, P < 0.05), while there was no significant difference in the presence of aap (77.2% versus 75.0%, P > 0.05). Additionally, a significantly greater number of high-shear isolates were capable of forming biofilm in vitro in a microtiter assay (82.5% versus 45.8%, P < 0.0001). However, even among high-shear clinical isolates, less than half contained the icaADBC locus; therefore, we selected for ica -negative variants with increased attachment to abiotic surfaces to examine PIA-independent biofilm mechanisms. Sequencing of selected variants identified substitutions capable of enhancing biofilm formation in multiple genes, further highlighting the heterogeneity of S. epidermidis biofilm molecules and mechanisms. IMPORTANCE Staphylococcus epidermidis is a leading cause of infections related to biomaterials, mostly due to their ability to form biofilm. Biofilm accumulation mechanisms vary, including those that are dependent on specific proteins, environmental DNA (eDNA), or polysaccharide intercellular adhesin (PIA). We found that those isolates obtained from high-shear environments, such as the lumen of a catheter, are more likely to produce PIA-mediated biofilms than those isolates obtained from a low-shear biomaterial-related infection. This suggests that PIA functions as a mechanism that is protective against shear flow. Finally, we performed selection experiments documenting the heterogeneity of biofilm accumulation molecules that function in the absence of PIA, further documenting the biofilm-forming potential of S. epidermidis .