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IntroductionTraditional risk factors do not fully explain the increased risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). The Haptoglobin (Hp) 2-2 genotype confers a lower anti-oxidant and higher inflammatory effect on the vasculature compared to the non-Hp 2-2 genotype. This study investigates the association of the Hp genotype with CVD in patients with RA.MethodsData from 69 RA patients with CVD and 207 sex- and ethnicity-matched RA patients without CVD, collected from 1 January 2000 to 31 December 2020, were retrieved from the Tan Tock Seng Hospital RA Registry. CVD was examined against demographics, clinical and laboratory variables in univariate models. Associations between the Hp genotypes and CVD were analyzed using conditional logistic regression.ResultsWe studied 276 patients (65.2% female, 82.6% Chinese, median age 60.9 years). Most participants were in low disease activity or remission (79.3%). The Hp 2-2 genotype was present in 49.6% (137/276). In the group with CVD, the prevalence of the Hp 2-2 genotype was 50.9% (29/57) in the Chinese, 100% (5/5) in the Indians, and 28.6% (2/7) in the Malays. In the non-CVD group, the respective prevalence was 46.8% (80/171), 66.7% (10/15), and 52.4% (11/21). In univariate analysis, the matched odds ratio (OR) of the Hp 2-2 genotype for CVD in RA was 1.34 [95% confidence interval (CI): 1.22–1.47; p

To evaluate four novel SARS-CoV-2 neutralizing antibody assay kits' application in neutralizing antibodies of population. Questionnaires from the voluntary participating researchers and selected the qualified questionnaires to analyse. For negative and positive coincidence rate, four novel SARS-Cov-2 neutralization antibody assay kits were tested. For within-run and between-run Precision verification study, four serum samples with two high and two low titer neutralizing antibodies were used to analyse. Based on the questionnaires, 175 qualified samples were divided into two groups. (1) negative neutralizing antibodies group: 31 samples had not been infected with the novel SARS-Cov-2 nor received the vaccine within the past one year; (2) positive neutralizing antibodies group: 144 samples were infected by COVID-19. There was 28 negative and 3 positive neutralizing antibodies of the individuals among the 31 negative samples which based on the questionnaires. The negative rates of 28 negative individules tested by GenScript, Vazyme and Hygeianey were 82.14 %, 60.71 % and 17.85 %, while the positive rates of the 147 positive samples were 93.87 %, 95.23 % and 100 %. The within-run coefficient of variations (C·V) of PBNAs, GenScript, Vazyme and Hygeianey were 11.49 %, 9.12 %, 7.97 % and 7.48 %, while the between-run coefficient of variations (C·V) were 21.37 %, 14.21 %, 12.29 % and 11.78 %. Due to the large within-run and between-run coefficient of variations, PBNAs was not suitable for large-scale promotion, while ELISAs could be leveraged for routine monitoring the titer of neutralizing antibodies against SARS-CoV-2.

ABSTRACT: Objectives: The objective of this randomised controlled trial was to compare the periodontal healing at the distal of the adjacent second molar after coronectomy or surgical removal and the surgical morbidities of the 2 techniques. Methods: This is a pilot study of a split-mouth randomised clinical trial comparing the periodontal healing of the adjacent second molar after coronectomy or total removal of lower third molars, which was registered with the University of Hong Kong Clinical Trial Centre as HKUCTR-2948 on 21 February 2020. Cone beam computed tomography (CBCT) scans were taken preoperatively and at 6 months postoperatively. Changes in the bone level from the cemento-enamel junction, periodontal probing depth (PPD), and clinical attachment level (CAL) at the distal of the adjacent second molar were compared. Surgical morbidities in terms of pain, infection, neurologic deficit, root exposure, and need for second surgery for removal were assessed. Results: Forty patients (22 male, 18 female) with mean age of 26.7 years were evaluated at 6 months postoperatively. Both coronectomy and total removal groups demonstrated statistically significant reduction in PPD and CAL. There was an alveolar bone gain of 1.28 ± 0.88 mm in the coronectomy group and 1.13 ± 0.73mm in the control group, which was statistically significant (P < .001 for both groups). Conclusions: Early findings show the periodontal healing at the adjacent second molar of coronectomy was as good as that of total removal of lower third molar. There were no differences in terms of surgical morbidities between both groups.

Background: Uptake to anastrozole for breast cancer prevention is low, partly due to women’s concerns about side effects including gains in weight and specifically gains in body fat. Previous evidence does not link anastrozole with gains in weight, but there is a lack of data on any effects on body composition i.e. changes in fat and fat free mass. Here we assess association of anastrozole with body composition changes in a prospective sub-study from the second international breast intervention trial (IBIS-II). Methods: Participants had DXA scans at baseline and for five years of anastrozole/placebo and beyond (between March 2004 and September 2017. Primary outcomes were changes in body weight, body fat and fat free mass at 9–18 months. A linear model was used to estimate the size of a differential effect in these outcomes by randomised treatment allocation adjusted for baseline value and time since last scan, age, 10-year breast cancer risk, smoking and HRT status. Results: 203 postmenopausal women were recruited (n = 95 anastrozole, n = 108 placebo), mean age 58 years (SD = 5.4), BMI 28.0 kg/m2 (SD = 5.5). There was no evidence of a strong association between anastrozole or placebo and endpoints at 9–18 months; effect size (95 %CI) for anastrozole minus placebo for body weight (per/kg) −0.11 (−1.29–1.08); body fat 0.11 (−0.75–0.96) and fat free mass −0.30 (−0.79–0.19). Conclusions: There is unlikely to be a clinically significant change to body composition with anastrozole for breast cancer prevention.

The lysosome protein RAGA interacts with and promotes lysosome localization and degradation of the macrophage-specific immune checkpoint protein CD47, with possible relevance to lung adenocarcinoma

Background: The establishment of the anterior-posterior (A-P) axis is a crucial step during tissue repair and regeneration. Despite the association reported recently of N6-methyladenosine (m6A) with regeneration, the mechanism underlying the regulation of m6A in A-P axis specification during regeneration remains unknown. Herein, we deciphered the m6A landscape at a single-base resolution at multiple time points during A-P axis regeneration and constructed the de novo transcriptome assembly of the Dugesia japonica planarian. Results: Immunofluorescence staining and comparative analysis revealed that m6A is widespread across the planarian and dynamically regulated during regeneration along the A-P axis, exhibiting a strong spatiotemporal feature. The resulting datasets of m6A-modified genes identified 80 anterior-specific genes and 13 posterior-specific genes, respectively. In addition, we showed that YTHDC1 serves as the primary m6A reader to be involved in the m6A-mediated specification of A-P axis during regeneration in Dugesia japonica planarian. Conclusions: Our study provides an RNA epigenetic explanation for the specification of the A-P axis during tissue regeneration in planarian.

Summary: Aedes albopictus is a successful disease vector due to its ability to survive in a wide range of habitats. Despite its ubiquity and impact on public health, little is known about its differential gene flow capabilities across different city habitats. We obtained a comprehensive dataset of >27,000 genome-wide DNA markers across 105 wild-caught Ae. albopictus individuals from Singapore, a dengue-endemic tropical city with heterogeneous landscapes from densely populated urban areas to forests. Despite Singapore’s challenging small-scale heterogeneity, our landscape-genomic approach indicated that dense urban areas are characterized by higher Aedes gene flow rates than managed parks and forests. We documented the incidence of Wolbachia infections of Ae. albopictus involving two strains (wAlbA and wAlbB). Our results dispel the misconception that substantial dispersal of Ae. albopictus is limited to urban greenery, with wide implications for vector management and critical insights into urban planning strategies to combat dengue transmission.

Understanding the relative contributions of historical and anthropogenic factors to declines in genetic diversity is important for informing conservation action. Using genome-wide DNA of fresh and historic specimens, including that of two species widely thought to be extinct, we investigated fluctuations in genetic diversity and present the first complete phylogenomic tree for all nine species of the threatened shorebird genus Numenius, known as whimbrels and curlews. Most species faced sharp declines in effective population size, a proxy for genetic diversity, soon after the Last Glacial Maximum (around 20,000 years ago). These declines occurred prior to the Anthropocene and in spite of an increase in the breeding area predicted by environmental niche modeling, suggesting that they were not caused by climatic or recent anthropogenic factors. Crucially, these genetic diversity declines coincide with mass extinctions of mammalian megafauna in the Northern Hemisphere. Among other factors, the demise of ecosystem-engineering megafauna which maintained open habitats may have been detrimental for grassland and tundra-breeding Numenius shorebirds. Our work suggests that the impact of historical factors such as megafaunal extinction may have had wider repercussions on present-day population dynamics of open habitat biota than previously appreciated.

Cancer survivors have reduced health-related quality of life (HRQOL) and high levels of distress during and after active treatment, due to physical, psychological, and social problems. Understanding the prevalence and associations of HRQOL and distress in a patient population in the community is important when designing rehabilitation programs. This was a cross-sectional observational study conducted at a community-based cancer rehabilitation center, with the aim of investigating the prevalence and associations of HRQOL and distress in cancer patients. There were 304 patients who were recruited. We found low levels of HRQOL and high levels of distress in patients, with a mean FACT-G7 total score of 11.68, and a mean distress thermometer score of 3.51. In the multivariate regression model, significant factors for low HRQOL were metastatic disease (p = 0.025) and Malay ethnicity (p < 0.001). Regression analyses also found that significant distress was associated with family health issues (p = 0.003), depression (p = 0.001), worry (p = 0.005), breathing (p = 0.007), getting around (p = 0.012) and indigestion (p = 0.039). A high prevalence of impaired HRQOL and distress was reported in cancer survivors even in a community rehabilitation setting. The physical and psychosocial well-being of cancer survivors should be monitored and managed as part of community-based cancer rehabilitation.

Abstract Resource partitioning may facilitate the coexistence of sympatric species with similar ecological requirements. Here, we study a colony of unusual echolocating birds called swiftlets, which nest underground on an island off the coast of Singapore. The colony comprises two congeneric swiftlet species, black‐nest swiftlets (Aerodramus maximus) and edible‐nest swiftlets (A. fuciphagus), nesting at high densities and in close proximity. Bioacoustic recordings and monitoring of nesting biology at the site across multiple seasons revealed significant differences in echolocation calls as well as survival rates between the species, with the larger black‐nest swiftlet nesting at locations with the highest fledging rates. We also observe an additional off‐season breeding peak by the smaller species, the edible‐nest swiftlet. Unexpectedly, off‐season egg‐hatching rates were significantly higher compared with the rates during the shared breeding season (mean difference = 14%). Our study on the breeding biology of these echolocating cave‐dwelling birds provides an example of spatial and temporal strategies that animals employ to partition resources within a confined habitat.

Abstract Background Patients who have breast cancer surgery are at risk of axillary web syndrome (AWS), an under-recognized postsurgical complication which can result in shoulder morbidity and functional impairment. Emerging studies have indicated that AWS may persist beyond the first few months after surgery, although few studies have assessed the prevalence and association of AWS beyond a year after diagnosis. Therefore, the aim of this study was to investigate the prevalence and associations for AWS in post-operative breast cancer patients up to 3 years after surgery. Methods This cross sectional observational study was conducted at a community-based cancer rehabilitation center. Patients were evaluated for the presence of AWS via physical examination. Disease-related data was obtained from clinical review and medical records. Descriptive statistics were utilized to illustrate patient demographics and clinical characteristics. Logistic regression analyses were used to determine associations of AWS. Results There were 111 Asian women who were recruited, who had undergone breast surgery and were referred to a national outpatient rehabilitation center. The prevalence of AWS in this population was 28.9%. In the multivariate regression model, significant factors were age

Disturbances in the excitatory/inhibitory balance of brain neural circuits are the main source of encephalopathy during neurodevelopment. Changes in the function of neural circuits can lead to depolarization or repeat rhythmic firing of neurons in a manner similar to epilepsy. GABAergic neurons are inhibitory neurons found in all the main domains of the CNS. Previous studies suggested that DjCamkII and DjCaln play a crucial role in the regulation of GABAergic neurons during planarian regeneration. However, the mechanisms behind the regeneration of GABAergic neurons have not been fully explained. Herein, we demonstrated that DjCamkII and DjCaln were mutual negative regulation during planarian head regeneration. DjNFAT exerted feedback positive regulation on both DjCaln and DjCamkII. Whole-mount in situ hybridization (WISH) and fluorescence in situ hybridization (FISH) revealed that DjNFAT was predominantly expressed in the pharynx and parenchymal cells in intact planarian. Interestingly, during planarian head regeneration, DjNFAT was predominantly located in the newborn brain. Down-regulation of DjNFAT led to regeneration defects in the brain including regenerative brain became small and the lateral nerves cannot be regenerated completely, and a decreasein the number of GABAergic neurons during planarian head regeneration. These findings suggest that the feedback loop between DjCaln, DjCamkII, and DjNFAT is crucial for the formation of GABAergic neurons during planarian head regeneration.

Abstract Background Acting as a cellular cleaner by packaging and transporting defective proteins and organelles to lysosomes for breakdown, autophagic process is involved in the regulation of cell remodeling after cell damage or cell death in both vertebrate and invertebrate. In human, limitations on the regenerative capacity of specific tissues and organs make it difficult to recover from diseases. Comprehensive understanding on its mechanism within invertebrate have strong potential provide helpful information for challenging these diseases. Method In this study, recent findings on the autophagy function in three invertebrates including planarian, hydra and leech with remarkable regenerative ability were summarized. Furthermore, molecular phylogenetic analyses of DjATGs and HvATGs were performed on these three invertebrates compared to that of Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus and Homo sapiens. Results In comparison with Scerevisiae, C elegans, D melanogaster, M musculus and human, our analysis exhibits the following characteristics of autophagy and its function in regeneration within invertebrate. Phylogenetical analysis of ATGs revealed that most autophagy-related genes (ATGs) were highly similar to their homologs in other species, which indicates that autophagy is a highly conservative biological function in both vertebrate and invertebrate. Structurally, almost all the core amino acids necessary for the function of ATG8 in mammal were observed in invertebrate HvATG8s and DjATG8s. For instance, ubiquitin-like domain as a signature structure in each ATG8, was observed in all ATG8s in three invertebrates. Basically, autophagy plays a key role in the regulation of regeneration in planarian. DjATG8-2 and DjATG8-3 associated with mTOR signaling pathway are sophisticated in the invertebrate tissue/organ regeneration. Furthermore, autophagy is involved in the pathway of neutralization of toxic molecules input from blood digestion in the leech. Conclusions The recent investigations on autophagy in invertebrate including planarian, hydra and leech suggest that autophagy is evolutionally conserved from yeast to mammals. The fundamental role of its biological function in the invertebrate contributing to the regeneration and maintenance of cellular homeostasis in these three organisms could make tremendous information to confront life threatening diseases in human including cancers and cardiac disorders.

MicroRNAs (miRNAs) are a class of evolutionarily conserved small non-coding RNAs that regulate gene expression at the translation level in cell growth, proliferation and differentiation. In addition, some types of miRNAs have been proven to be key modulators of both CNS development and plasticity, such as let-7, miR-9 and miR-124. In this research, we found miR-8b acts as an important regulator involved in brain and eyespot regeneration in Dugesia japonica. miR-8b was highly conserved among species and was abundantly expressed in central nervous system. Here, we detected the expression dynamics of miR-8b by qPCR during the head regeneration of D. japonica. Knockdown miR-8b by anti-MIRs method caused severe defects of eyes and CNS. Our study revealed the evolutionary conserved role of miR-8b in the planarian regeneration process, and further provided more research ideas and available information for planarian miRNAs.

The assembly line biosynthesis of the powerful anticancer-antiviral didemnin cyclic peptides is proposed to follow a prodrug release mechanism in Tristella bacteria. This strategy commences with the formation of N-terminal prodrug scaffolds and culminates in their cleavage during the cellular export of the mature products. In this study, a comprehensive exploration of the genetic and biochemical aspects of the enzymes responsible for both the assembly and cleavage of the acylated peptide prodrug scaffolds is provided. This process involves the assembly of N-acyl-polyglutamine moieties orchestrated by the nonribosomal peptide synthetase DidA and the cleavage of these components at the post-assembly stage by DidK, a transmembrane CAAX hydrolase homolog. The findings not only shed light on the complex prodrug mechanism that underlies the synthesis and secretion of didemnin compounds but also offer novel insights into the expanded role of CAAX hydrolases in microbes. Furthermore, this knowledge can be leveraged for the strategic design of genome mining approaches aimed at discovering new bioactive natural products that employ similar prodrug biochemical strategies.