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The application of artificial intelligence (AI) approaches to drug discovery for G protein‐coupled receptors (GPCRs) is a rapidly expanding area. Artificial intelligence can be used at multiple stages during the drug discovery process, from aiding our understanding of the fundamental actions of GPCRs to the discovery of new ligand‐GPCR interactions or the prediction of clinical responses. Here, we provide an overview of the concepts behind artificial intelligence, including the subfields of machine learning and deep learning. We summarise the published applications of artificial intelligence to different stages of the GPCR drug discovery process. Finally, we reflect on the benefits and limitations of artificial intelligence and share our vision for the exciting potential for further development of applications to aid GPCR drug discovery. In addition to making the drug discovery process "faster, smarter and cheaper," we anticipate that the application of artificial intelligence will create exciting new opportunities for GPCR drug discovery. LINKED ARTICLES: This article is part of a themed issue Therapeutic Targeting of G Protein‐Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.14/issuetoc [ABSTRACT FROM AUTHOR]

François' langur is an Endangered colobine inhabiting limestone habitats in southern China and northern Vietnam. Its global population has been estimated to be just more than 2000 mature individuals. Populations in Vietnam are highly fragmented with reportedly fewer than 200 adults in total and 50 in a single location. Although the François' langur in Vietnam is highly imperiled as remnant populations persist in only three to four sites, little research has been carried out to provide a reliable estimate of its remaining population. In this study, we conducted field surveys in Lam Binh District, Tuyen Quang Province, northeastern Vietnam. In total, we recorded at least 16 groups of François' langurs, with 156 individuals, raising the total number of individuals by approximately 10% compared to a previous study. The group structure, group size, activity budget, and density of the Lam Binh population resemble those reported in François' langurs in China and other limestone langur species. The results show that the behavior ecology of limestone langurs significantly differs from that of forest langurs probably because they occupy separate habitats with distinctly different environmental variables. During our surveys, we detected a number of direct threats to this population, namely illegal logging, hunting, firewood collecting, hydropower development, grazing, and mining. It is recommended that the protection forest be elevated to the nature reserve status to better protect the most important population of the François' langur in Vietnam. [ABSTRACT FROM AUTHOR]

As the proportion of the elderly population in the USA expands, so will the demand for rehabilitation and social care, which play an important role in maintaining function and mediating motor and cognitive decline in older adults. The use of social robotics and telemedicine are each potential solutions but each have limitations. To address challenges with classical telemedicine for rehabilitation, we propose to use a social robot-augmented telepresence (SRAT), Flo, which was deployed for long-term use in a community-based rehabilitation facility catering to older adults. Our goals were to explore how clinicians and patients would use and respond to the robot during rehab interactions. In this pilot study, three clinicians were recruited and asked to rate usability after receiving training for operating the robot and two of them conducted multiple rehab interactions with their patients using the robot (eleven patients with cognitive impairment and/or motor impairment and 23 rehab sessions delivered via SRAT in total). We report on the experience of both therapists and patients after the interactions. [ABSTRACT FROM AUTHOR]

Concerns over water availability and water quality increasingly require more efficient use of water resources in irrigated agriculture. Center pivot (CP) systems designed with variable rate irrigation (VRI) technology have the potential to improve application and water-use efficiency while reducing environmental impacts from excess runoff and poor water quality. The objective of this study was to develop a computer model (MOPivot) to automate management zone delineation for irrigation scheduling based on the minimum area that can be controlled by the CP system (based on sprinkler spacing and location, and wetted diameter) matched to VRI capabilities and GIS site-specific grid-based field data affecting water storage and runoff. To ensure that the CP was capable of meeting scheduled VRI prescriptions, application uniformity was validated along the lateral length for sprinkler pulse percentages of 20 to 100 percent using catch collectors spaced 3-m apart along thirteen radial lines (82 m long, beginning 68 m from the pivot point and covering 10° of pivot rotation) for both clockwise and counter-clockwise rotation. Results indicated that the system achieved high application uniformity over a range of VRI application depths. The MOPivot management zones were in close agreement with GIS grid-based soil survey geographic database (SSURGO) and soil apparent electrical conductivity (ECa) derived soil texture input data (82.8% and 93.5% overall accuracy, respectively). The model successfully established the minimum azimuthal angle and sector length for VRI zone-control VRI and automatically delineated management zones useful in developing VRI irrigation prescriptions. [ABSTRACT FROM AUTHOR]

The majority of people who contract COVID-19 experience a short period of symptomatic infection. However, symptoms persist for months or years following initial exposure to the virus in some cases. This has been described as long COVID. Little is known about the lived experience of this condition, as it has only recently emerged. This study aimed to explore the experiences of mental health, quality of life, and coping among people living with long COVID. A sample of 47 adults with lived experience participated in web-based focus groups. Separate focus groups were held for 24 individuals with pre-existing mental health conditions and 23 individuals without pre-existing mental health conditions. Data were analyzed using a codebook thematic analysis approach. Five themes were identified as integral to the long COVID experience: The Emotional Landscape of Long COVID, New Limits to Daily Functioning, Grief and Loss of Former Identity, Long COVID-related Stigmatization, and Learning to Cope with Persisting Symptoms. These findings illustrate the immense impact of long COVID on mental health and quality of life. Minimal differences were found between those with and those without pre-existing mental health conditions, as both groups were substantially impacted by the condition. Attention to the perspectives of people with lived experience of long COVID is necessary to inform future directions for research and clinical practice. [ABSTRACT FROM AUTHOR]

Background: A constellation of often disabling long-term physical symptoms enduring after an acute SARS-COV-2 infection is commonly referred to as Long COVID. Since Long COVID is a new clinical entity, research is required to clarify treatment needs and experiences of individuals affected. This qualitative descriptive study aimed to provide insight into Long COVID treatment and service experiences and preferences of individuals experiencing Long COVID and the intersections with mental health. Methods: The study was conducted out of a tertiary care mental health hospital, with online recruitment from the community across Canada. A total of 47 individuals (average age = 44.9) participated in one of 11 focus groups between June and December 2022. Five focus groups were conducted with participants who had pre-existing mental health concerns prior to contracting SARS-CoV-2, and six were with people with Long COVID but without pre-existing mental health concerns. A semi-structured interview guide asked about service experiences and service preferences, including mental health and well-being services. Discussions were recorded, transcribed, and analyzed using codebook thematic analysis. Results: When accessing services for Long COVID, patients experienced: (1) systemic barriers to accessing care, and (2) challenges navigating the unknowns of Long COVID, leading to (3) negative impacts on patient emotional well-being and recovery. Participants called for improvements in Long COVID care, with a focus on: (1) developing Long COVID-specific knowledge and services, (2) enhancing support for financial well-being, daily living, and building a Long COVID community, and (3) improving awareness and the public representation of Long COVID. Conclusions: Substantial treatment barriers generate considerable burden for individuals living with Long COVID. There is a pressing need to improve treatment, social supports, and the social representation of Long COVID to create integrated, accessible, responsive, and ongoing support systems. [ABSTRACT FROM AUTHOR]

Background: Among patients diagnosed with COVID-19, a substantial proportion are experiencing ongoing symptoms for months after infection, known as 'long COVID'. Long COVID is associated with a wide range of physical and neuropsychological symptoms, including impacts on mental health, cognition, and psychological wellbeing. However, intervention research is only beginning to emerge. This systematic review synthesizes currently registered trials examining interventions for mental health, cognition, and psychological wellbeing in patients with long COVID. Methods: Standard systematic review guidelines were followed. Trials registered in two large trial registries in 2020 to May 2022 were reviewed. Included studies were narratively synthesized by type of intervention and a risk-of-bias assessment was conducted. Results: Forty-two registered trials were included, with a total target sample size of 5814 participants. These include 11 psychological interventions, five pharmacological and other medical interventions, and five evaluating herbal, nutritional, or natural supplement interventions. An additional nine trials are examining cognitive and neurorehabilitation interventions and 12 are examining physiotherapy or physical rehabilitation. Most trials are randomized, but many are feasibility trials; trials are evaluating a wide spectrum of outcomes. Conclusions: While there is a newly emerging body of research testing interventions for mental health, cognition, and psychological wellbeing in long COVID, the breadth and scope of the research remains limited. It is urgently incumbent on researchers to expand upon the intervention research currently under way, in order to generate high-quality evidence on a wide range of candidate interventions for diverse long COVID patient populations. [ABSTRACT FROM AUTHOR]

Phytolith is widely known as a silica structure in numerous silicon (Si) accumulator plants, e.g., rice, and it contains various nutrients and other beneficial elements. When rice straw is returned to paddy fields, the silica structure of phytolith can be dissolved, thereby releasing its occluded nutrients. While the intrinsic characteristics and dissolution properties of phytoliths under the effect of solution chemistry have been intensively studied, the effect of gas phases, especially CO2, on phytolith stability and the implications for nutrient release are not fully known. Here, dissolution properties of phytolith ashes obtained from dry ashing of rice straw at 400, 600 and 800 °C were investigated by quantifying Si release together with other nutrients under two atmospheric conditions, i.e., without and with CO2 support (aeration). In a time span of 6 days, the releases of nutrients (K, P, Ca, Mg) showed high dependence on the overall dissolution of the phytolith ashes. CO2 significantly reduced the dissolution rate of the phytolith ashes but increased the release rates of cationic as well as anionic nutrients. The aeration of CO2 shifted the carbonate equilibrium (H2CO3, HCO3− and CO32−) towards H2CO3, reducing solution pH, thereby decreasing the dissolution rate of phytoliths. Following this, intensification of H+ exchange promoted nutrient releases from the phytolith ashes. This indicates contrasted responses of phytoliths and their occluded nutrients to CO2, and provides a better insight on the fate of soil phytoliths and the tendency of nutrient budgets from rice straw phytoliths in soils. [ABSTRACT FROM AUTHOR]

Introduction: Penile size has long been an important fixation in men's lives. Establishing what the normal size of the penis is very important to have a yardstick for men, which is a challenge and depends on the culture, race, and form of measurement applied. Objective: To evaluate the size of the penis in flaccidity, erection, and stretch of Vietnamese men. Methods: A total of 259 men who visited the Andrology and Fertility Hospital of Hanoi, VietNam were involved in the study between October 2022 and April 2023. Penile measurements (flaccid, erect length/circumference, stretched length) were predominantly taken by 1 investigator using a tape measure and the same measurement technique. All statistical analyses were completed using STATA 17.0. Statistical analysis was performed with the Spearman correlation as tested by the Kolmogorov–Smirnov test (p<0.05). Results: The mean age of 259 patients was 29,24 (range: 15–48). The mean penile lengths were: flaccid length 9.21 cm (SD 1.71 cm), flaccid circumference at the middle of the shaft 8.25 cm (SD 0.96 cm), erect length 13.22 (SD 1.46cm), erect circumference at the middle of the shaft 10.42 cm (SD 0.94 cm), and stretched length 12.47 cm (SD 1.61 cm). The mean testicular volume was 12.47 mL (SD 6.37 mL) and 12.65 (SD 4.03 mL) for the left and right testicles, respectively. Stretched length is most closely correlated with erect length with r=0.68. We also observed that the testicular volume, erect length was a significant inverse correlation with age, which ranged from r = -0.14 to -0.21. Conclusions: The results of this study help to establish a reference range for male genital size in Vietnam, which should be helpful for urologists and andrologist in counseling patient Disclosure: No. [ABSTRACT FROM AUTHOR]

Introduction: Penile size has long been an important fixation in men's lives. Establishing what the normal size of the penis is very important to have a yardstick for men, which is a challenge and depends on the culture, race, and form of measurement applied. Objective: To evaluate the size of the penis in flaccidity, erection, and stretch of Vietnamese men. Methods: A total of 259 men who visited the Andrology and Fertility Hospital of Hanoi, VietNam were involved in the study between October 2022 and April 2023. Penile measurements (flaccid, erect length/circumference, stretched length) were predominantly taken by 1 investigator using a tape measure and the same measurement technique. All statistical analyses were completed using STATA 17.0. Statistical analysis was performed with the Spearman correlation as tested by the Kolmogorov–Smirnov test (p<0.05). Results: The mean age of 259 patients was 29,24 (range: 15–48). The mean penile lengths were: flaccid length 9.21 cm (SD 1.71 cm), flaccid circumference at the middle of the shaft 8.25 cm (SD 0.96 cm), erect length 13.22 (SD 1.46cm), erect circumference at the middle of the shaft 10.42 cm (SD 0.94 cm), and stretched length 12.47 cm (SD 1.61 cm). The mean testicular volume was 12.47 mL (SD 6.37 mL) and 12.65 (SD 4.03 mL) for the left and right testicles, respectively. Stretched length is most closely correlated with erect length with r=0.68. We also observed that the testicular volume, erect length was a significant inverse correlation with age, which ranged from r = -0.14 to -0.21. Conclusions: The results of this study help to establish a reference range for male genital size in Vietnam, which should be helpful for urologists and andrologist in counseling patient Disclosure: No. [ABSTRACT FROM AUTHOR]

Heart failure remains a leading cause of morbidity and mortality worldwide. Current treatment for patients with heart failure include drugs targeting G protein‐coupled receptors such as β‐adrenoceptor antagonists (β‐blockers) and angiotensin II type 1 receptor antagonists (or angiotensin II receptor blockers). However, many patients progress to advanced heart failure with persistent symptoms, despite treatment with available therapeutics that have been shown to reduce mortality and mortality. GPCR targets currently being explored for the development of novel heart failure therapeutics include adenosine receptor, formyl peptide receptor, relaxin/insulin‐like family peptide receptor, vasopressin receptor, endothelin receptor and the glucagon‐like peptide 1 receptor. Many GPCR drug candidates are limited by insufficient efficacy and/or dose‐limiting unwanted effects. Understanding the current challenges hindering successful clinical translation and the potential to overcome existing limitations will facilitate the future development of novel heart failure therapeutics. LINKED ARTICLES: This article is part of a themed issue Therapeutic Targeting of G Protein‐Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.14/issuetoc [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate genetic structures and expression of blaOXA-58 gene in five Acinetobacter baumannii clinical isolates recovered from two hospitals in southern Vietnam during 2012-2014. A. baumannii isolates were identified by automated microbiology systems and confirmed by PCR. All isolates were characterized as multidrug resistant by antimicrobial testing using the disk diffusion method. Four imipenem susceptible and one nonsusceptible isolates (MIC > 32 μ g ·ml-1) were identified by E-test. PCR amplification of blaOXA-58 gene upstream and downstream sequences revealed the presence of ISAba3 at both locations in one multidrug-resistant isolate. Semiquantitation of blaOXA-51 and blaOXA-58 gene expression was performed by the 2-ΔΔCt method. The blaOXA-51 gene expression of five isolates showed little difference, but the isolate bearing ISAba3-blaOXA-58-ISAba3 exhibited significantly higher blaOXA-58 mRNA level. Higher β-lactamases activity in periplasmic than cytoplasmic fraction was found in most isolates. The isolate overexpressing blaOXA-58 gene possessed very high periplasmic enzyme activity. In conclusion, the A. baumannii isolate bearing ISAba3-blaOXA-58 gene exhibited high resistance to imipenem, corresponding to an overexpression of blaOXA-58 gene and very high periplasmic β-lactamase activity. [ABSTRACT FROM AUTHOR]

While recognition of transgender people has increased in Vietnam, this population continues to face significant stigma and discrimination within their families and in public, including in medical settings. Understanding of transgender health is limited, especially regarding the provision of care to transgender people. This paper explores providers' preparedness for delivering transgender care using data from qualitative interviews with twelve healthcare professionals in Hanoi and Ho Chi Minh City. Drawing on the socio-ecological model, we illustrated multi-level factors that influenced the provision of medical services to transgender people, including restrictive legislation (policy level); shortage of transgender-specific services, and lack of training and guidelines (organisational level); and ambiguous perceptions, inappropriate provider-patient communication, and medical knowledge gaps (individual level). Overall, our study has identified a healthcare environment that is under-prepared to meet the complex health needs of transgender individuals. With this study, we call for intervention strategies beyond individual-level support and emphasise the urgency of allowing medical institutions to provide transgender-specific health services including gender-affirming surgery and hormonal treatments. [ABSTRACT FROM AUTHOR]

Rice production helps feed at least half of the world's population but generates approximately one billion tonnes of straw residue per annum. On-site open burning of rice straw after harvesting is common in recent times because there has been less demand for rice straw to use as fuel and fodder. Due to health and climate change concerns, open burning, which results in biomass losses, smog and emissions of green house gases, e.g., CO2, has been widely criticized and banned in many countries. Little is known about the positive benefits of straw burning, such as field care (eradication of biotic diseases) or nutrient cycling. Herein, we propose a new viewpoint in which the burning of rice straw followed by cycling of the burned materials, including silica material (so-called phytolith), into soil is demonstrated as a CO2-sequestration strategy via buffering the soil CO2 flux and coupling CO2 with the silicon cycle. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic and social distancing measures elevated stress levels globally, exacerbating mental health challenges for people with HIV (PWH). We examined the effect of COVID-19-related stress on mental health among PWH in western Washington, exploring whether social support and coping self-efficacy were protective. Data on COVID-19-related stress, mental health, social support, and coping self-efficacy were collected using online surveys during the pandemic. Pre-COVID-19 mental health data were available for a subset of participants and were linked with the survey data. In the total sample (N = 373), COVID-19-stress was associated with elevated depression (PHQ-8, β = 0.21, 95%CI [0.10, 0.32]) and anxiety (GAD-7, β = 0.28, 95%CI [0.17, 0.39]). Among the subset of respondents with pre-pandemic mental health data (N = 103), COVID-19-related stress was associated with elevated PHQ-8 scores (β = 0.35, 95%CI [0.15, 0.56]) and GAD-7 scores (β = 0.35, 95%CI [0.16, 0.54]), adjusted for baseline mental health and other confounders. Coping self-efficacy was negatively associated with GAD-7 scores (β = −0.01, 95%CI [−0.01, 0.00]), while social support was negatively associated with PHQ-8 scores (β = −0.06, 95%CI [−0.12, −0.01]). Viral suppression before and during the pandemic did not differ among participants with available data. While COVID-19-related stress predicted elevated depression and anxiety symptoms among PWH, social support and coping self-efficacy were protective. [ABSTRACT FROM AUTHOR]

Recent smooth muscle cell (SMC) lineage-tracing studies have revealed that SMCs undergo remarkable changes in phenotype during development of atherosclerosis. Of major interest, we demonstrated that Kruppel-like factor 4 (KLF4) in SMCs is detrimental for overall lesion pathogenesis, in that SMC-specific conditional knockout of the KLF4 gene (Klf4) resulted in smaller, more-stable lesions that exhibited marked reductions in the numbers of SMC-derived macrophage- and mesenchymal stem cell-like cells. However, since the clinical consequences of atherosclerosis typically occur well after our reproductive years, we sought to identify beneficial KLF4-dependent SMC functions that were likely to be evolutionarily conserved. We tested the hypothesis that KLF4-dependent SMC transitions play an important role in the tissue injury-repair process. Using SMC-specific lineage-tracing mice positive and negative for simultaneous SMC-specific conditional knockout of Klf4, we demonstrate that SMCs in the remodeling heart after ischemia-reperfusion injury (IRI) express KLF4 and transition to a KLF4-dependent macrophage-like state and a KLF4-independent myofibroblast-like state. Moreover, heart failure after IRI was exacerbated in SMC Klf4 knockout mice. Surprisingly, we observed a significant cardiac dilation in SMC Klf4 knockout mice before IRI as well as a reduction in peripheral resistance. KLF4 chromatin immunoprecipitation- sequencing analysis on mesenteric vascular beds identified potential baseline SMC KLF4 target genes in numerous pathways, including PDGF and FGF. Moreover, microvascular tissue beds in SMC Klf4 knockout mice had gaps in lineage-traced SMC coverage along the resistance arteries and exhibited increased permeability. Together, these results provide novel evidence that Klf4 has a critical maintenance role within microvascular SMCs: it is required for normal SMC function and coverage of resistance arteries. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this article is to review and discuss theories of working memory with special attention to their relevance to language processing. Method: We begin with an overview of the concept of working memory itself and review some of the major theories. Then, we show how theories of working memory can be organized according to their stances on 3 major issues that distinguish them: modularity (on a continuum from domaingeneral to very modular), attention (on a continuum from automatic to completely attention demanding), and purpose (on a continuum from idiographic, or concerned with individual differences, to nomothetic, or concerned with group norms). We examine recent research that has a bearing on these distinctions. Results: Our review shows important differences between working memory theories that can be described according to positions on the 3 continua just noted. Conclusion: Once properly understood, working memory theories, methods, and data can serve as quite useful tools for language research. [ABSTRACT FROM AUTHOR]

In this paper, we develop a long memory orthogonal factor (LMOF) multivariate volatility model for forecasting the covariance matrix of financial asset returns. We evaluate the LMOF model using the volatility timing framework of Fleminget al. [J. Finance, 2001,56, 329–352] and compare its performance with that of both a static investment strategy based on the unconditional covariance matrix and a range of dynamic investment strategies based on existing short memory and long memory multivariate conditional volatility models. We show that investors should be willing to pay to switch from the static strategy to a dynamic volatility timing strategy and that, among the dynamic strategies, the LMOF model consistently produces forecasts of the covariance matrix that are economically more useful than those produced by the other multivariate conditional volatility models, both short memory and long memory. Moreover, we show that combining long memory volatility with the factor structure yields better results than employing either long memory volatility or the factor structure alone. The factor structure also significantly reduces transaction costs, thus increasing the feasibility of dynamic volatility timing strategies in practice. Our results are robust to estimation error in expected returns, the choice of risk aversion coefficient, the estimation window length and sub-period analysis. [ABSTRACT FROM PUBLISHER]

Arsenic (As) in rice has been known as a worldwide human health threat that results originally from the accumulation of As in soil in many rice cultivation regions. This study aims to evaluate As levels in the soil–rice system in the Mekong River delta (MRD) with special focuses on the geographical distribution and the relation to soil physio-chemical properties. It was found that soil As contents varied from 0.3 to 15.9 mg kg−1 ( x ˜ = 7.22 ± 0.3 mg kg−1), whereas straw As content was about one order of magnitude lower ( x ˜ = 0.92 ± 0.1 mg kg−1). The content of As in grain varied from "not detectable" to 1115 µg kg−1 ( x ˜ = 73 ± 19 µg kg−1). Relatively similar geographical distribution patterns were observed for soil As and straw As, meanwhile grain As did not reveal a clear association with straw As and soil As. The accumulation of As in rice (straw and grain) were likely affected by various factors, but the mutual effects of soil As pool and soil properties were the most obvious. The East coastal area of the MRD has been identified as a vulnerable area to As threat. This finding suggests that in addition to the action plans to preserve coastal paddy soils from the threats of sea level rise and salt intrusion, contamination of As should also be considered. [ABSTRACT FROM AUTHOR]

Superparamagnetic CuFe2O4 nanoparticles were synthesized from CuCl2 and FeCl3 by a co-precipitation method in ethylene glycol and characterized by several techniques, which included vibrating sample magnetometry, XRD, SEM, TEM, atomic absorption spectrometry, and nitrogen physisorption measurements. The CuFe2O4 nanoparticles could be used as a solid catalyst for the α-arylation reaction of acetylacetone with iodobenzene to form phenylacetone as the principal product and 3-phenyl-2,4-pentanedione as the byproduct. The reaction that used the CuFe2O4 nanoparticles as catalyst could proceed to completion with 95 % selectivity to phenylacetone. The CuFe2O4 nanoparticles could be separated easily from the reaction mixture by magnetic decantation and could be reused several times for the α-arylation reaction without a significant degradation in catalytic activity. [ABSTRACT FROM AUTHOR]

Synthetic hexaploid wheat is an effective genetic resource for transferring agronomically important genes from Aegilops tauschii to common wheat. Wide variation in grain size and shape, one of the main targets for wheat breeding, has been observed among Ae. tauschii accessions. To identify the quantitative trait loci (QTLs) responsible for grain size and shape variation in the wheat D genome under a hexaploid genetic background, six parameters related to grain size and shape were measured using SmartGrain digital image software and QTL analysis was conducted using four F2 mapping populations of wheat synthetic hexaploids. In total, 18 QTLs for the six parameters were found on five of the seven D-genome chromosomes. The identified QTLs significantly contributed to the variation in grain size and shape among the synthetic wheat lines, implying that the D-genome QTLs might be at least partly functional in hexaploid wheat. Thus, synthetic wheat lines with diverse D genomes from Ae. tauschii are useful resources for the identification of agronomically important loci that function in hexaploid wheat. [ABSTRACT FROM AUTHOR]

Wheat landraces carry abundant genetic variation in heading and flowering times. Here, we studied flowering-related traits of two Nepalese varieties, KU-4770 and KU-180 and a Japanese wheat cultivar, Shiroganekomugi (SGK). These three wheat varieties showed similar flowering time in a common garden experiment. In total, five significant quantitative trait loci (QTLs) for three examined traits, the heading, flowering and maturation times, were detected using an F2 population of SGK/KU-4770. The QTLs were found at the Ppd-1 loci on chromosomes 2B and 2D and the 2B QTL was also confirmed in another F2 population of SGK/KU-180. The Ppd-D1 allele from SGK and the Ppd-B1 alleles from the two Nepalese varieties might be causal for early-flowering phenotype. The SGK Ppd-D1 allele contained a 2-kb deletion in the 5′ upstream region, indicating a photoperiod-insensitive Ppd-D1a allele. Real-time PCR analysis estimating the Ppd-B1 copy number revealed that the two Nepalese varieties included two intact Ppd-B1 copies, putatively resulting in photoperiod insensitivity and an early-flowering phenotype. The two photoperiod-insensitive Ppd-1 homoeoalleles could independently contribute to segregation of early-flowering individuals in the two F2 populations. Therefore, wheat landraces are genetic resources for discovery of alleles useful for improving wheat heading or flowering times. [ABSTRACT FROM AUTHOR]

Background Highly trained vascular sonographers make up a significant cost of abdominal aortic aneurysm (AAA) ultrasound screening. However, they are over-trained for this very limited task. Others have reported that health workers (e.g. emergency room staff and nurses) with far less training may be able to perform these scans. The national AAA screening programme in the UK uses staff with limited training. Whether individuals without a health professional qualification could be trained to perform the scan accurately to improve cost-effectiveness is not known. We aimed to investigate whether a short, well-supervised course in ultrasonography could train novices to detect AAA for screening purposes. Methods Three novices were trained by an experienced sonographer for 15 days to perform abdominal aortic ultrasound examinations and detect AAA using a portable ultrasound system. The examination included four anterior-posterior aortic measurements: a maximal diameter in the coronal plane and three diameters of the suprarenal, mid and distal infrarenal aorta in the transverse plane. The novices independently scanned 215 subjects following training; experienced sonographers repeated the measurements on the same subject in the same session. Using Bland-Altman plots and CUSUM analysis, the novices' and experienced sonographers' accuracy and efficiency measurements were compared. Factors influencing performance were recorded. Results The novices measured the maximal coronal aortic diameter accurately, to within 0.46-0.52 cm of the true diameter; 85-97% of their coronal measurements were within 0.5 cm of the assessors; kappa statistic and Bland-Altman plots show a high agreement with the assessor's measurements. However, the novices' measurements of the three diameters in the transverse plane were outside clinically acceptable limits. Assuming a referral policy for a second scan for scans recorded as 'difficult', only one novice missed a 3.13 cm aneurysm. A CUSUM quality improvement analysis demonstrated substantial improvements in the scanning efficiency of the novices with continued scanning experience. Conclusion This study showed that novices could be trained to screen for AAA over 15 days. However, the need for continuing quality improvement is critical, especially in more technically demanding cases. Measuring the maximal infrarenal diameter instead of specific segmental diameters may be more appropriate for AAA screening using novices. [ABSTRACT FROM AUTHOR]

Background: With growing fertilizer prices and fertilizer-related environmental concerns, Basmati 370 holds a unique position in the rice world due to its price, fragrance, quality and low fertilizer demands as compared to hybrid varieties; thus, shifting this crop to an organic or integrated nutrient management system is a feasible option. Methods: A field experiment was carried out at Jammu (J and K) during the Kharif season of 2014 to evaluate the performance of Basmati 370 transplanted at three different dates with five integrated nutrient sources. Result: The results of this investigation indicated that the rice transplanted on June 30 produced significantly higher dry matter accumulation (857.61 g/m2) with a concomitant increase in the grain yield (3.3 t/ha) over July 15 (3.0 t/ha) and July 30 (2.8 t/ha). The application of 100% RDF in the form of inorganic fertilizer recorded significantly higher grain yield (3.3 t/ha) and straw yield (5.6 t/ha) being at par with VC+FYM+NOC and GM+VC. The highest net returns were recorded on June 30 transplanting ('80,501) with a benefit-cost ratio of 2.8. In the case of nutrient sources, higher net returns were fetched with 100% RDF (84,892) with a benefit-cost ratio of 3.4. [ABSTRACT FROM AUTHOR]

Degenerative retinopathies, including age-related macular degeneration, diabetic retinopathy, and hereditary retinal disorders-major causes of world blindness-are potentially treatable by using low-molecular weight neuroprotective, antiapoptotic, or antineovascular drugs. These agents are, however, not in current systemic use owing to, among other factors, their inability to passively diffuse across the microvasculature of the retina because of the presence of the inner blood-retina barrier (1BRB). Moreover, preclinical assessment of the efficacies of new formulations in the treatment of such conditions is similarly compromised. We describe here an experimental process for RNAi-mediated, size-selective, transient, and reversible modulation of the iBRB in mice to molecules up to 800 Da by suppression of transcripts encoding claudin-5, a protein component of the tight junctions of the inner retinal vasculature. MRI produced no evidence indicative of brain or retinal edema, and the process resulted in minimal disturbance of global transcriptional patterns analyzed in neuronal tissue. We show that visual function can be improved in lMPDH1-/- mice, a model of autosomal recessive retinitis pigmentosa, and that the rate of photoreceptor cell death can be reduced in a model of light-induced retinal degeneration by systemic drug delivery after reversible barrier opening. These findings provide a platform for high-throughput drug screening in models of retinal degeneration, and they ultimately could result in the development of a novel "humanized" approach to therapy for conditions with little or no current forms of treatment. [ABSTRACT FROM AUTHOR]

Abstract: We have generated and characterized a murine monoclonal antibody (mAb) that binds to both mouse apolipoprotein (apo) B48 and apoB100. We immunized “apoB39-only” mice (mice that synthesize a truncated form of apoB, apoB39, but no apoB48 or apoB100) with lipoproteins containing mouse apoB48 and then used splenocytes from the immunized mice to create hybridomas. We identified a hybridoma, 2G11, that secretes a mAb that binds to mouse apoB48 and apoB100 but not to apoB39. Antibody 2G11 also binds apoB48 and apoB100 from rats and hamsters but not from humans. The mAb recognizes mouse apoB equally in very low and low density lipoproteins and was used to quantify apoB in wild-type, apoE-deficient and low-density lipoprotein receptor-deficient mice and in mice treated with an antisense drug that lowers plasma apoB levels. The antibody will be an important reagent for studying mouse models of atherosclerosis. The study also underscores the utility of genetically modified mice for generating mouse mAbs against mouse proteins. [Copyright &y& Elsevier]

Flavonoids and stilbenoids, crucial secondary metabolites abundant in plants and fungi, display diverse biological and pharmaceutical activities, including potent antioxidant, anti-inflammatory, and antimicrobial effects. However, conventional production methods, such as chemical synthesis and plant extraction, face challenges in sustainability and yield. Hence, there is a notable shift towards biological production using microorganisms like Escherichia coli and yeast. Yet, the drawbacks of using E. coli and yeast as hosts for these compounds persist. For instance, yeast's complex glycosylation profile can lead to intricate protein production scenarios, including hyperglycosylation issues. Consequently, Corynebacterium glutamicum emerges as a promising alternative, given its adaptability and recent advances in metabolic engineering. Although extensively used in biotechnological applications, the potential production of flavonoid and stilbenoid in engineered C. glutamicum remains largely untapped compared to E. coli. This review explores the potential of metabolic engineering in C. glutamicum for biosynthesis, highlighting its versatility as a cell factory and assessing optimization strategies for these pathways. Additionally, various metabolic engineering methods, including genomic editing and biosensors, and cofactor regeneration are evaluated, with a focus on C. glutamicum. Through comprehensive discussion, the review offers insights into future perspectives in production, aiding researchers and industry professionals in the field. [ABSTRACT FROM AUTHOR]

The zebrafish (Danio rerio) has become a widely used vertebrate model for bacterial, fungal, viral, and protozoan infections. Due to its genetic tractability, large clutch sizes, ease of manipulation, and optical transparency during early life stages, it is a particularly useful model to address questions about the cellular microbiology of host–microbe interactions. Although its use as a model for systemic infections, as well as infections localised to the hindbrain and swimbladder having been thoroughly reviewed, studies focusing on host–microbe interactions in the zebrafish gastrointestinal tract have been neglected. Here, we summarise recent findings regarding the developmental and immune biology of the gastrointestinal tract, drawing parallels to mammalian systems. We discuss the use of adult and larval zebrafish as models for gastrointestinal infections, and more generally, for studies of host–microbe interactions in the gut. [ABSTRACT FROM AUTHOR]

Background: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Streptococcus pneumoniae and Staphylococcus aureus are major bacterial causes of lower respiratory tract infections (LRTIs) globally, leading to substantial morbidity and mortality. The rapid increase of antimicrobial resistance (AMR) in these pathogens poses significant challenges for their effective antibiotic therapy. In low-resourced settings, patients with LRTIs are prescribed antibiotics empirically while awaiting several days for culture results. Rapid pathogen and AMR gene detection could prompt optimal antibiotic use and improve outcomes. Methods: Here, we developed multiplex quantitative real-time PCR using EvaGreen dye and melting curve analysis to rapidly identify six major pathogens and fourteen AMR genes directly from respiratory samples. The reproducibility, linearity, limit of detection (LOD) of real-time PCR assays for pathogen detection were evaluated using DNA control mixes and spiked tracheal aspirate. The performance of RT-PCR assays was subsequently compared with the gold standard, conventional culture on 50 tracheal aspirate and sputum specimens of ICU patients. Results: The sensitivity of RT-PCR assays was 100% for K. pneumoniae, A. baumannii, P. aeruginosa, E. coli and 63.6% for S. aureus and the specificity ranged from 87.5% to 97.6%. The kappa correlation values of all pathogens between the two methods varied from 0.63 to 0.95. The limit of detection of target bacteria was 1600 CFU/ml. The quantitative results from the PCR assays demonstrated 100% concordance with quantitative culture of tracheal aspirates. Compared to culture, PCR assays exhibited higher sensitivity in detecting mixed infections and S. pneumoniae. There was a high level of concordance between the detection of AMR gene and AMR phenotype in single infections. Conclusions: Our multiplex quantitative RT-PCR assays are fast and simple, but sensitive and specific in detecting six bacterial pathogens of LRTIs and their antimicrobial resistance genes and should be further evaluated for clinical utility. [ABSTRACT FROM AUTHOR]

We acquire a lot of information about the world through texts, which can be categorized at the broadest level into two primary genres: narratives and exposition. Stories and essays differ across a variety of dimensions, including structure and content, with numerous theories hypothesizing that stories are easier to understand and recall than essays. However, empirical work in this area has yielded mixed results. To synthesize research in this area, we conducted a meta-analysis of experiments in which memory and/or comprehension of narrative and expository texts was investigated. Based on over 75 unique samples and data from more than 33,000 participants, we found that stories were more easily understood and better recalled than essays. Moreover, this result was robust, not influenced by the inclusion of a single effect-size or single study, and not moderated by various study characteristics. This finding has implications for any domain in which acquiring and retaining information is important. [ABSTRACT FROM AUTHOR]

This work is concerned with the energy harvesting of mono-stable Duffing oscillators with piezoelectric coupling under white noise excitation. This is the first time that the higher-order averaging procedure is extended to find the first-, second- and third-order approximate stationary joint probability density functions of amplitude and full phase by solving the corresponding Fokker-Planck-Kolmogorov (FPK) equation. Then the mean-square electric voltage and mean output power are derived through the approximate relation between the electric voltage and the mechanical states. The analytical results are verified by Monte Carlo simulation. The effects of system parameters, such as excitation intensity, mechanical damping term, nonlinear stiffness coefficients, and the resistance ratio of the resistive–capacitive circuit on the mean-square displacement and mean output power are discussed in detail. It has been shown that the averaging procedure of the averaging method of coefficients in FPK equation can be considered as a particular case of the proposed higher-order averaging procedure and the higher-order approximate solutions are much more accurate than the one obtained by the averaging method of coefficients in FPK equation. © 2022 The Authors. Published by Elsevier Ltd. [ABSTRACT FROM AUTHOR]

Objective: To examine U.S. obstetrics and gynecology residents' perceptions of wellness, burnout, and perceived effectiveness of wellness programming.Methods: In January 2017, a six-item survey was administered at the time of the Council on Resident Education in Obstetrics and Gynecology in-training examination. Respondents voluntarily completed the survey electronically before starting the examination, and responses were anonymous and only linked to postgraduate year.Results: Of the 5,376 eligible U.S. examinees, 4,999 (93%) completed the survey, provided residency year status, and were included in the analysis. There was a high prevalence of self-identified wellness problems (burnout 51.2%, depression 32.0%, binge drinking 12.6%, eating disorder 4.7%, drug use 1.1%, and suicide attempt 0.4%). First-year residents were most likely to state that wellness was a priority in their program. The number of residents reporting any problem with wellness increases significantly between the first year (49.8%) and second year (63.7%, P<.001), after which it remains elevated throughout training. Residents who responded that wellness was not a priority in their program were more likely to report wellness issues and burnout (P<.001). When asked what single intervention all residency programs should provide, 41.2% (2,059) felt that dedicated time for wellness maintenance was the most important intervention.Conclusion: These findings highlight the high prevalence of wellness problems in obstetrics and gynecology residents, and how essential it will be to engage learners in the development of effective, evidence-based interventions. [ABSTRACT FROM AUTHOR]

Adenosine receptors are a family of GPCRs containing four subtypes (A1 , A2A , A2B and A3 receptors), all of which bind the ubiquitous nucleoside adenosine. These receptors play an important role in physiology and pathophysiology and therefore represent attractive drug targets for a range of conditions. The theoretical framework surrounding drug action at adenosine receptors now extends beyond the notion of prototypical agonism and antagonism to encompass more complex pharmacological concepts. New paradigms include allostery, in which ligands bind a topographically distinct receptor site from that of the endogenous agonist, homomeric or heteromeric interactions across receptor oligomers and biased agonism, that is, ligand-dependent differential intracellular signalling. This review provides a concise overview of allostery, oligomerization and biased agonism at adenosine receptors and outlines how these paradigms may enhance future drug discovery endeavours focussed on the development of novel therapeutic agents acting at adenosine receptors.Linked Articles: This article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.21/issuetoc. [ABSTRACT FROM AUTHOR]

Abstract: We test people's ability to optimize performance across two concurrent tasks. Participants performed a number entry task while controlling a randomly moving cursor with a joystick. Participants received explicit feedback on their performance on these tasks in the form of a single combined score. This payoff function was varied between conditions to change the value of one task relative to the other. We found that participants adapted their strategy for interleaving the two tasks, by varying how long they spent on one task before switching to the other, in order to achieve the near maximum payoff available in each condition. In a second experiment, we show that this behavior is learned quickly (within 2–3 min over several discrete trials) and remained stable for as long as the payoff function did not change. The results of this work show that people are adaptive and flexible in how they prioritize and allocate attention in a dual‐task setting. However, it also demonstrates some of the limits regarding people's ability to optimize payoff functions. [ABSTRACT FROM AUTHOR]

Sexually transmitted diseases are major causes of infertility, ectopic pregnancy, and premature birth. Here, we developed a new multiplex real-time polymerase chain reaction (PCR) assay for the simultaneous detection of nine major sexually transmitted infections (STIs) found in Vietnamese women, including Chlamydia trachomatis, Neisseria gonorrhoeae, Gardnerella vaginalis, Trichomonas vaginalis, Candida albicans, Mycoplasma hominis, Mycoplasma genitalium, and human alphaherpesviruses 1 and 2. A panel containing three tubes × three pathogens/tube was predesigned based on double-quenched TaqMan probes to increase detection sensitivity. There was no cross-reactivity among the nine STIs and other non-targeted microorganisms. Depending on each pathogen, the agreement with commercial kits, sensitivity, specificity, repeatability and reproducibility coefficient of variation (CV), and limit of detection of the developed real-time PCR assay were 99.0%–100%, 92.9%–100%, 100%, <3%, and 8–58 copies/reaction, respectively. One assay cost only 2.34 USD. Application of the assay for the detection of the nine STIs in 535 vaginal swab samples collected from women in Vietnam yielded 532 positive cases (99.44%). Among the positive samples, 37.76% had one pathogen, with G. vaginalis (33.83%) as the most prevalent; 46.36% had two pathogens, with G. vaginalis + C. albicans as the most prevalent combination (38.13%); and 11.78%, 2.99%, and 0.56% had three, four, and five pathogens, respectively. In conclusion, the developed assay represents a sensitive and cost-effective molecular diagnostic tool for the detection of major STIs in Vietnam and is a model for the development of panel detections of common STIs in other countries. [ABSTRACT FROM AUTHOR]

Histone methylation plays an important role in regulating gene expression. One such methylation occurs at Lys 79 of histone H3 (H3K79) and is catalyzed by the yeast DOT1 (disruptor of telomeric silencing) and its mammalian homolog, DOT1L. Previous studies have demonstrated that germline disruption of Dot1L in mice resulted in embryonic lethality. Here we report that cardiac-specific knockout of Dot1L results in increased mortality rate with chamber dilation, increased cardiomyocyte cell death, systolic dysfunction, and conduction abnormalities. These phenotypes mimic those exhibited in patients with dilated cardiomyopathy (DCM). Mechanistic studies reveal that DOT1L performs its function in cardiomyocytes through regulating Dystrophin (Dmd) transcription and, consequently, stability of the Dystrophin--"glycoprotein complex important for cardiomyocyte viability. Importantly, expression of a miniDmd can largely rescue the DCM phenotypes, indicating that Dmd is a major target mediating DOT1L function in cardiomyocytes. Interestingly, analysis of available gene expression data sets indicates that DOT1L is down-regulated in idiopathic DCM patient samples compared with normal controls. Therefore, our study not only establishes a critical role for DOT1L-mediated H3K79 methylation in cardiomyocyte function, but also reveals the mechanism underlying the role of DOT1L in DCM. In addition, our study may open new avenues for the diagnosis and treatment of human heart disease. [ABSTRACT FROM AUTHOR]

Introduction: Sexual function plays a crucial role in women's psychosocial and overall well-being, significantly impacting their quality of life. Any decline in sexual function can have detrimental effects on the affected individuals' quality of life Objective: (i) To describe the prevalence of sexual dysfunction in women seeking infertility treatment at the Andrology and Fertility Hospital of Hanoi, Viet Nam, and (ii) to analyze the factors associated with sexual dysfunction in the study population. Methods: This was a cross-sectional descriptive study. All women (1.039) seeking infertility treatment at the Andrology and Fertility Hospital from December 30, 2022, to March 30, 2023 participate in the study. They were invited to scan a QR code and complete the research questionnaire. Female sexual dysfunction is assessed based on the FSFI scale included six domains: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain (comprising 19 questions). The data were extracted into Excel, cleaned, and analyzed using STATA 17.0 software. The analysis of factors associated with female sexual dysfunction was conducted using logistic regression models. Results: Among the 1039 participants in the study, the mean age was 30.9±5.3 years. The overall score for female sexual dysfunction was 25.09 ± 6.20, with individual component scores. The prevalence of female sexual dysfunction was 49.7%. There is a positive correlation among the six components of female sexual dysfunction, p<0.01. In the multivariate regression model, the risk of female sexual dysfunction is higher among individuals who work away from home, have an underweight body mass index, have a poor relationship with their partner, have had no sexual intercourse in the past 4 weeks, experience fear of pain, anxiety, and body image concerns during sexual activity, have infrequent or no discussions with their partner regarding sexual desires, preferred positions, and stimulation, and are dissatisfied with their sexual life. Conclusions: Half of the women seeking infertility in late-stage medical care experience sexual dysfunction. Factors that increase the risk of sexual dysfunction include having a job far from home, being underweight based on body mass index, having a poor overall relationship with a partner, not engaging in sexual activity in the past four weeks, fear of pain, anxiety, body image concerns during sexual intercourse, and limited or lack of communication with a partner about sexual issues such as desires, preferred positions, and stimulation. Additionally, dissatisfaction with one's sexual life contributes to the occurrence of sexual dysfunction. Therefore, early screening and timely intervention are necessary for this group of individuals. Disclosure: Any of the authors act as a consultant, employee or shareholder of an industry for: Andrology and Fertility Hospital of Hanoi. [ABSTRACT FROM AUTHOR]

Introduction: Sexual function plays a crucial role in women's psychosocial and overall well-being, significantly impacting their quality of life. Any decline in sexual function can have detrimental effects on the affected individuals' quality of life Objective: (i) To describe the prevalence of sexual dysfunction in women seeking infertility treatment at the Andrology and Fertility Hospital of Hanoi, Viet Nam, and (ii) to analyze the factors associated with sexual dysfunction in the study population. Methods: This was a cross-sectional descriptive study. All women (1.039) seeking infertility treatment at the Andrology and Fertility Hospital from December 30, 2022, to March 30, 2023 participate in the study. They were invited to scan a QR code and complete the research questionnaire. Female sexual dysfunction is assessed based on the FSFI scale included six domains: sexual desire, arousal, lubrication, orgasm, satisfaction, and pain (comprising 19 questions). The data were extracted into Excel, cleaned, and analyzed using STATA 17.0 software. The analysis of factors associated with female sexual dysfunction was conducted using logistic regression models. Results: Among the 1039 participants in the study, the mean age was 30.9±5.3 years. The overall score for female sexual dysfunction was 25.09 ± 6.20, with individual component scores. The prevalence of female sexual dysfunction was 49.7%. There is a positive correlation among the six components of female sexual dysfunction, p<0.01. In the multivariate regression model, the risk of female sexual dysfunction is higher among individuals who work away from home, have an underweight body mass index, have a poor relationship with their partner, have had no sexual intercourse in the past 4 weeks, experience fear of pain, anxiety, and body image concerns during sexual activity, have infrequent or no discussions with their partner regarding sexual desires, preferred positions, and stimulation, and are dissatisfied with their sexual life. Conclusions: Half of the women seeking infertility in late-stage medical care experience sexual dysfunction. Factors that increase the risk of sexual dysfunction include having a job far from home, being underweight based on body mass index, having a poor overall relationship with a partner, not engaging in sexual activity in the past four weeks, fear of pain, anxiety, body image concerns during sexual intercourse, and limited or lack of communication with a partner about sexual issues such as desires, preferred positions, and stimulation. Additionally, dissatisfaction with one's sexual life contributes to the occurrence of sexual dysfunction. Therefore, early screening and timely intervention are necessary for this group of individuals. Disclosure: Any of the authors act as a consultant, employee or shareholder of an industry for: Andrology and Fertility Hospital of Hanoi. [ABSTRACT FROM AUTHOR]

A crystalline copper-based metal-organic framework Cu-MOF-74 was synthesized, and was characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR), atomic absorption spectrophotometry (AAS), and nitrogen physisorption measurements. The Cu-MOF-74 exhibited high catalytic activity in the synthesis of indolizines through aldehyde–amine–alkyne three-component coupling transformation and higher than those of other Cu-MOFs such as Cu 2 (BDC) 2 (DABCO), Cu 3 (BTC) 2 , Cu(BDC), Cu 2 (NDC) 2 (DABCO), and Cu 4 I 4 (DABCO) 2 . The reactions could only proceed to produce indolizines in the presence of the solid Cu-MOF catalyst, and contribution from active copper species leached from the solid Cu-MOF-74, if any, was negligible. The Cu-MOF catalyst be recovered and reused several times for the synthesis of indolizines without a significant degradation in catalytic activity. To the best of our knowledge, the synthesis of indolizines using a recyclable heterogeneous catalyst was not previously mentioned in the literature. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease and related dementias (AD/ADRD) are a public health challenge for Vietnam because of its rapidly aging population. However, very few community-based programs exist to support people living with AD/ADRD and their family caregivers. Resources for Enhancing Alzheimer's Caregiver Health in Vietnam (REACH VN) is a culturally adapted family caregiver intervention shown in a pilot study to be feasible and promising in terms of preliminary efficacy. We describe the protocol for a larger cluster randomized controlled trial (RCT) to test the efficacy of REACH VN among family caregivers of people living with dementia in a semi-rural area outside of Hanoi, Vietnam.Methods: Thirty-two clusters with approximately 350 caregivers will be randomized to either REACH VN intervention or enhanced usual care. REACH VN is a multicomponent intervention delivered in-home or by phone over the course of 2 to 3 months. To be eligible, family caregivers need to be ≥18 years old, be the person who provides the most day-to-day care for people living with dementia, and have a score ≥ 6 on the Zarit Burden Interview-4. The primary outcomes are caregiver burden (Zarit Burden Interview-12) and psychological distress (Patient Health Questionnaire-4). Secondary outcomes include caregiver somatic symptoms (Patient Health Questionnaire-15) and perceived stress (Perceived Stress Scale-10). These outcomes will be assessed at baseline, 3 months, and 6 months. Exploratory analyses to examine potential mediators of primary outcomes are also planned.Discussion: To our knowledge, this is the first large-scale study to test the efficacy of a community-based family dementia caregiver intervention in Vietnam. Results from this study will help inform efforts to widely deliver the REACH VN intervention or similar community-based family dementia caregiver support programs in Vietnam and other low- and middle-income countries (LMIC).Trial Registration: ClinicalTrials.gov NCT04542317 . Registered on 9 September 2020. [ABSTRACT FROM AUTHOR]

Objectives. We demonstrated the effectiveness of an accelerated hepatitis B vaccination schedule in drug users. Methods. We compared the long-term effectiveness of accelerated (0–1–2 months) and standard (0–1–6 months) hepatitis B vaccination schedules in preventing hepatitis B virus (HBV) infections and anti-hepatitis B (anti-HBs) antibody loss during 2-year follow-up in 707 drug users (HIV and HBV negative at enrollment and completed 3 vaccine doses) from February 2004 to October 2009. Results. Drug users in the accelerated schedule group had significantly lower HBV infection rates, but had a similar rate of anti-HBs antibody loss compared with the standard schedule group over 2 years of follow-up. No chronic HBV infections were observed. Hepatitis C positivity at enrollment and age younger than 40 years were independent risk factors for HBV infection and antibody loss, respectively. Conclusions. An accelerated vaccination schedule was more preferable than a standard vaccination schedule in preventing HBV infections in drug users. To overcome the disadvantages of a standard vaccination schedule, an accelerated vaccination schedule should be considered in drug users with low adherence. Our study should be repeated in different cohorts to validate our findings and establish the role of an accelerated schedule in hepatitis B vaccination guidelines for drug users. [ABSTRACT FROM AUTHOR]

Chromatin immunoprecipitation assays have contributed greatly to our understanding of the role of histone modifications in gene regulation. However, they do not permit analysis with single-cell resolution, thus confounding analyses of heterogeneous cell populations. Here we present a method that permits visualization of histone modifications of single genomic loci with single-cell resolution in formaldehyde-fixed paraffin-embedded tissue sections based on combined use of in situ hybridization and proximity ligation assays. We show that dimethylation of lysine 4 of histone H3 (H3K4me2) at the MYH11 locus is restricted to the smooth muscle cell (SMC) lineage in human and mouse tissue sections and that the mark persists even in phenotypically modulated SMC in atherosclerotic lesions that show no detectable expression of SMC marker genes. This methodology has promise for broad applications in the study of epigenetic mechanisms in complex multicellular tissues in development and disease. [ABSTRACT FROM AUTHOR]

The role of calcium in blood pressure has been widely studied among hypertensive patients; however, no study has explored the role of calcium in hypertensive crises. The primary objective of this study is to evaluate the differences in serum calcium levels between hypertensive crises patients and a 1:1 random matched controls (age‐, sex‐, race‐, diabetes, and body mass index matched). This study is a single‐center, retrospective, chart review, case‐control study of patients with hypertensive crises (case group) and patients without hypertensive crises (control group). Patients were included in the case group if they were 18 years of age or older with hypertensive crises and have a documented calcium level. The control group patients were required to be 18 years of age or older, have a documented calcium level, and have no diagnosis of hypertensive crises. The primary outcome of the study was to compare the mean serum calcium in patients with hypertensive crises vs patients without hypertensive crises. Five hundred and sixty‐six patients were included in the study: 283 patients in both the case group and control group. The primary outcome results showed that serum calcium concentration was not significantly different between the case group (8.99 ± 0.78 mg/dL) and control group (8.96 ± 0.75 mg/dL) (P =.606). This study found no significant difference in serum calcium levels in patients with hypertensive crises compared to a random matched control group. Larger observational or experimental studies may be useful to evaluate the effect of calcium on blood pressure in hypertensive crises. [ABSTRACT FROM AUTHOR]

Reports on a study to determine whether individual response to dietary modification for reducing cholesterol is a familial trait. Design; Setting; Participants; Results; Conclusion that individual variation in response to a cholesterol lowering diet is a familial trait.

This study was conducted to evaluate the routine medical check-up and self-treatment behaviors of people living in a remote and mountainous setting in Northern Vietnam and identify their associations. A cross-sectional study was conducted on 175 people in August 2018 in Cao Son commune, Da Bac district, Hoa Binh. Information regarding routine medical check-ups and self-treatment behaviors was collected by using a structured questionnaire. Multivariate logistic regression was used to examine the associations. Results show that 24% of the mountainous people had routine medical check-ups in the last 12 months. The rate of self-treatment in the past three months was 33.7%. The number of chronic diseases (OR = 1.5 , 95% CI = 1.0 ‐ 2.3), health information sources from radio/television (OR = 3.3 , 95% CI = 1.2 ‐ 9.5), or social media (OR = 24.8 , 95% CI = 1.2 ‐ 512.4) was related to routine medical check-up. People who did not have routine medical check-up were more likely to have self-treatment practice (OR = 6.3 , 95% CI = 1.9 ‐ 21.1) than those who had a regular health check. Promoting health education and communication through mass media to raise people's awareness about regular health check-ups is a promising way to improve people's self-treatment status. [ABSTRACT FROM AUTHOR]

Background: Rupture and erosion of advanced atherosclerotic lesions with a resultant myocardial infarction or stroke are the leading worldwide cause of death. However, we have a limited understanding of the identity, origin, and function of many cells that make up late-stage atherosclerotic lesions, as well as the mechanisms by which they control plaque stability.Methods: We conducted a comprehensive single-cell RNA sequencing of advanced human carotid endarterectomy samples and compared these with single-cell RNA sequencing from murine microdissected advanced atherosclerotic lesions with smooth muscle cell (SMC) and endothelial lineage tracing to survey all plaque cell types and rigorously determine their origin. We further used chromatin immunoprecipitation sequencing (ChIP-seq), bulk RNA sequencing, and an innovative dual lineage tracing mouse to understand the mechanism by which SMC phenotypic transitions affect lesion pathogenesis.Results: We provide evidence that SMC-specific Klf4- versus Oct4-knockout showed virtually opposite genomic signatures, and their putative target genes play an important role regulating SMC phenotypic changes. Single-cell RNA sequencing revealed remarkable similarity of transcriptomic clusters between mouse and human lesions and extensive plasticity of SMC- and endothelial cell-derived cells including 7 distinct clusters, most negative for traditional markers. In particular, SMC contributed to a Myh11-, Lgals3+ population with a chondrocyte-like gene signature that was markedly reduced with SMC-Klf4 knockout. We observed that SMCs that activate Lgals3 compose up to two thirds of all SMC in lesions. However, initial activation of Lgals3 in these cells does not represent conversion to a terminally differentiated state, but rather represents transition of these cells to a unique stem cell marker gene-positive, extracellular matrix-remodeling, "pioneer" cell phenotype that is the first to invest within lesions and subsequently gives rise to at least 3 other SMC phenotypes within advanced lesions, including Klf4-dependent osteogenic phenotypes likely to contribute to plaque calcification and plaque destabilization.Conclusions: Taken together, these results provide evidence that SMC-derived cells within advanced mouse and human atherosclerotic lesions exhibit far greater phenotypic plasticity than generally believed, with Klf4 regulating transition to multiple phenotypes including Lgals3+ osteogenic cells likely to be detrimental for late-stage atherosclerosis plaque pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Bronchopulmonary dysplasia (BPD) is a severe condition in premature infants that compromises lung function and necessitates oxygen support. Despite major improvements in perinatal care minimizing the devastating effects, BPD remains the most frequent complication of extreme preterm birth. Our study reports the safety of the allogeneic administration of umbilical cord-derived mesenchymal stem/stromal cells (allo-UC-MSCs) and the progression of lung development in four infants with established BPD.Methods: UC tissue was collected from a healthy donor, followed by propagation at the Stem Cell Core Facility at Vinmec Research Institute of Stem Cell and Gene Technology. UC-MSC culture was conducted under xeno- and serum-free conditions. Four patients with established BPD were enrolled in this study between May 25, 2018, and December 31, 2018. All four patients received two intravenous doses of allo-UC-MSCs (1 million cells/kg patient body weight (PBW) per dose) with an intervening interval of 7 days. Safety and patient conditions were evaluated during hospitalization and at 7 days and 1, 6 and 12 months postdischarge.Results: No intervention-associated severe adverse events or prespecified adverse events were observed in the four patients throughout the study period. At the time of this report, all patients had recovered from BPD and were weaned off of oxygen support. Chest X-rays and CT scans confirmed the progressive reductions in fibrosis.Conclusions: Allo-UC-MSC administration is safe in preterm infants with established BPD. Trial registration This preliminary study was approved by the Vinmec International Hospital Ethics Board (approval number: 88/2019/QĐ-VMEC; retrospectively registered March 12, 2019). [ABSTRACT FROM AUTHOR]

Background: Delirium tremens is a severe form of alcohol withdrawal syndrome. Literature documenting acute coronary events in the setting of alcohol withdrawal remains scarce. An accepted hypothesis for the underlying process is focused on the hyperadrenergic state that leads to coronary vasospasm and increased myocardial oxygen demand.Case Presentation: A 47-year-old Caucasian man with a past medical history of tobacco and alcohol abuse, hypertension, and anxiety presented to the emergency department for crampy epigastric abdominal pain with intractable nausea and vomiting for the past 2 days. His reported last alcoholic intake was about 10 days prior; however, outpatient records indicated otherwise. He was admitted for electrolyte replacement and fluid resuscitation secondary to gastrointestinal losses from presumed early alcohol withdrawal syndrome. The following night, he developed acute substernal chest pain with elevated cardiac enzymes. Electrocardiography showed an acute inferoposterior infarct with reciprocal changes in leads V1-V4. The patient was taken for emergent catheterization, and a drug-eluting stent was placed in the middle of the left anterior descending artery. Postcatheterization electrocardiography showed sustained inferolateral ST elevations consistent with acute injury pattern. The patient had not required any benzodiazepines until this point. On the morning of catheterization, the patient's Clinical Institute Withdrawal Assessment for Alcohol-Revised score was 19 with a high of 25, and he was actively hallucinating. He was treated for delirium tremens and an acute coronary event along with an incidental pneumonia. He did not require any benzodiazepines during the last 4 days of admission, and he made a full recovery.Conclusions: The prevalence of alcohol dependence in hospitalized patients is substantial. Although our patient was being treated with the standard protocols for alcohol withdrawal, he rapidly developed delirium tremens, which led to an acute inferior ST-elevation myocardial infarction in the setting of nonoccluded coronary vessels. This case report adds to the sparse literature documenting acute coronary events in the setting of alcohol withdrawal and suggests that our patient's ST-elevation myocardial infarction is not fully explained by the current coronary vasospasm hypothesis, but rather was in part the result of direct catecholamine-associated myocardial injury. Further research should be conducted on prophylactic agents such as β-blockers and calcium channel blockers. [ABSTRACT FROM AUTHOR]

Objectives: The taxonomic status of isolated hominoid teeth from the Asian Pleistocene has long been controversial due to difficulties distinguishing between pongine and hominin molars given their high degree of morphometrical variation and overlap. Here, we combine nonmetric and geometric morphometric data to document a dental pattern that appears to be taxonomically diagnostic among Pongo. We focus on the protoconule, a cuspule of well‐documented evolutionary history, as well as on shape differences of the mesial fovea of the upper molars. Materials and methods: We examined 469 upper molars of eight hominid genera (Australopithecus, Paranthropus, Homo, Meganthropus, Sivapithecus, Pan, Gorilla, and Pongo), including representatives of Homo erectus and extinct and recent Pongo. Analyses were conducted at the enamel‐dentine junction to overcome the limitations introduced by dental wear. Results: We found that a moderate or large protoconule is present in ~80% of Pleistocene and extant Pongo. Conversely, a moderate to pronounced protoconule in hominins, Meganthropus, and African great apes occurs in low frequencies (~0–20%). Canonical variate analyses for the mesial fovea show that Pleistocene and extant Pongo cluster together and are clearly differentiated from all other groups, except for Sivapithecus. Discussion: This study suggests that the protoconule and the shape of the mesial fovea in upper molars are useful features for the taxonomic identification of isolated hominid teeth. By identifying these new features, our results can contribute to the better understanding of hominoid evolutionary history and biogeography during the Asian Pleistocene. However, we emphasize that the reported features should be used in combination with other diagnostic variables for the most accurate taxonomic assessments. [ABSTRACT FROM AUTHOR]

We consider the topic of arrogance from a cross-disciplinary viewpoint. To stimulate further research, we suggest three types of arrogance (individual, comparative, and antagonistic) and six components contributing to them, each logically related to the next. The components progress from imperfect knowledge and abilities to an unrealistic assessment of them, an unwarranted attitude of superiority over other people, and related derisive behavior. Although each component presumably is present to some degree when the next one operates, causality might flow between components in either direction. The classification of components of arrogance should reduce miscommunication among researchers, as the relevant concepts and mechanisms span cognitive, motivational, social, and clinical domains and literatures. Arrogance is an important concept warranting further study for both theoretical and practical reasons, in both psychopathology and normal social interaction. Everyone seems to have qualities of arrogance to some degree, and we consider the importance of arrogance on a spectrum. We contend that humankind can benefit from a better understanding of the cognitive limitations and motivational biases that, operating together, appear to contribute to arrogance. We bring together information and questions that might lead to an invigorating increase in the rate and quality of cross-disciplinary research on arrogance. [ABSTRACT FROM AUTHOR]