Improving completion rate of advance care planning at a tertiary rheumatological centre in Singapore: a quality improvement project.

Advanced care planning (ACP) is a series of ongoing voluntary discussions between patients, families and healthcare professionals to plan for their future healthcare needs. Despite patients with rheumatic diseases having high symptom burden and disease complications, the ACP completion rates in patients with rheumatic diseases remain low. In this quality improvement project, we aimed to increase the number of completed ACP in a tertiary referral rheumatology centre in Singapore from 0 to 1 per month. We showed a statistically significant increase in ACP completion across 1 year with two Plan-Do-Study-Act cycles. Further studies are needed to explore further interventions for ACP completion in patients with rheumatic diseases.

[Focal therapy combined with immunotherapy for prostate cancer: Advances in studies].

Prostate cancer (PCa) ranks as the second most prevalent malignancy among males worldwide at present, and its prevalence keeps rising. Focal therapy not only results in tumor necrosis but also encourages the release of autoantigens originating from the tumor into the bloodstream and activates the host immune system to effectively fight the tumor. However, focal therapy alone may not achieve the total ablation of cancer cells and may cause locoregional recurrence. Immunotherapy, by boosting the body's immune response, destroys tumor cells and prevents immune escape. Recent studies show that focal therapy combined with immunotherapy can produce a better clinical efficacy by enhancing the initial immune response, especially for low- to intermediate-risk confined PCa. This article offers some fresh perspectives on the management of PCa by reviewing the etiology and progression of the malignancy, focal therapeutic options, and advantages and vista of focal therapy combined with immunotherapy.

Pulmonary adverse reaction caused by furazolidone: Two case reports and a literature review.

RATIONALE: As one of the drugs used to treat Helicobacter pylori, furazolidone has been reported to cause gastrointestinal reactions, allergies, dizziness, and more. However, its related drug-induced lung injury has been rarely reported. Furthermore, there have been no reports of the timing for initiating hormone therapy when a pulmonary adverse reaction occurs. PATIENT CONCERNS: We report 2 cases, both of them showed interlobular septal thickening and nodules on the chest computed tomography. One had more discomfort symptoms and had a higher eosinophil count than the normal range, while the other only had fever symptoms and had an eosinophil count within the normal range. DIAGNOSES: Pulmonary adverse reaction caused by furazolidone was diagnosed. INTERVENTIONS: Furazolidone was discontinued, and the person with increased eosinophils received hormone therapy, while the other person did not. OUTCOMES: After discontinuation of medication and treatment, the symptoms of the 2 patients gradually improved. LESSONS: This report suggests that furazolidone may cause pulmonary adverse reactions to raise clinical awareness, and for the first time indicates that hormone therapy is needed for patients whose eosinophils continue to increase after discontinuation.

Effects of loneliness and isolation on cardiovascular diseases: a two sample Mendelian Randomization Study.

BACKGROUND: Loneliness and isolation are associated with multiple cardiovascular diseases (CVDs), but there is a lack of research on whether they were causally linked. We conducted a Mendelian Randomization (MR) study to explore causal relationships between loneliness and isolation and multiple CVDs. METHODS: Single nucleotide polymorphisms associated with loneliness and isolation were identified from a genome-wide association study (GWAS) of 455,364 individuals of European ancestry in the IEU GWAS database. Summary data for 15 CVDs were also obtained from the IEU GWAS database. We used three MR methods including inverse variance weighting, MR-Egger, and weighted median estimation to assess the causal effect of exposure on outcomes. Cochran's Q test and MR-Egger intercept test were used to evaluate the heterogeneity and pleiotropy. RESULTS: MR analysis showed that loneliness and isolation were significantly associated with essential hypertension (OR = 1.07, 95% CI: 1.03-1.12), atherosclerotic heart disease (OR = 1.04; 95% CI: 1.02-1.06), myocardial infarction (OR = 1.02; 95% CI: 1-1.04) and angina (OR = 1.04; 95% CI =1.02-1.06). No heterogeneity and pleiotropy effects were found in this study. CONCLUSIONS: Causal relationship of loneliness and isolation with CVDs were found in this study.

Characterization of the DUF868 gene family in Nicotiana and functional analysis of NtDUF868-E5 involved in pigment metabolism.

Domains of unknown function (DUF) proteins represent a large group of uncharacterized protein families. The DUF868 gene family in Nicotiana has not yet been described. In the present study, we identified 12, 11, and 25 DUF868 family members in the genome of Nicotiana sylvestris, N. tomentosiformis, and N. tabacum, respectively. Based on phylogenetic analysis, these were categorized into five groups (A-E). Within each group, the gene structures, motifs, and tertiary structures showed high similarity. NtDUF868 family expansion during evolution was mainly driven by segmental duplication events. MicroRNA (miRNA) target site prediction identified 12 miRNA members that target 16 NtDUF868 family genes. The promoters of these genes contain cis-regulatory elements responsive to light, phytohormones, and abiotic stresses. Expression profiling revealed their tissue- and stage-specific expression patterns. RNA-sequencing and quantitative reverse transcription PCR revealed that the NtDUF868 family genes are potentially involved in the response to abiotic and biotic stresses, particularly drought and hormone stresses, and in the resistance to black shank and bacterial wilt. We generated transformed plants using NtDUF868-E5 overexpression and gene-editing vectors. NtDUF868-E5 overexpression resulted in enhanced tobacco plant growth and development, leading to increased leaf photosynthetic capacity and higher chlorophyll and carotenoid contents. This study provided a comprehensive genome-wide analysis of the DUF868 gene family, shedding light on their potential roles in plant growth and stress responses.

Study on the Permeability and Absorption Performance of the Crotch Layer in Seamless Knitted Period Underwear.

During the physiological period, women have the problem of lateral and posterior leakage, and they expect to have period underwear that can reduce lateral and posterior leakage. This study is combined with menstrual needs, and in the crotch penetration layer, three types of yarns are used, seaweed viscose yarn, apocynum viscose yarn, and viscose yarn, as well as two fabric structures: honeycomb-shaped convex-concave stitching and grid-shaped convex point stitching. In the crotch absorption layer, three types of yarns are used, modal yarn, bamboo yarn, and viscose yarn, as well as two fabric structures: plush stitching and plain stitching. The above two parts establish a sample scheme according to full-factor experimental tests, and 12 knitted fabric samples were knitted. The experimental data were analyzed through SPSS one-way ANOVA. The results indicate that in terms of veil raw materials, the crotch penetration layer with seaweed viscose yarn has better penetration performance, while the crotch absorption layer with bamboo yarn has better absorption performance. In terms of fabric structure, the crotch penetration layer with grid-shaped convex point stitching has better penetration performance, while the crotch absorption layer with plush stitching has better absorption performance. This study provides a theoretical basis for the development of period underwear.

Tailoring nonuniform local orbital angular momentum density.

As is well known, a light beam with a helical phase carries an optical orbital angular momentum (OAM), which can cause the orbital motion of trapped microparticles around the beam axis. Usually, the speed of the orbital motion is uniform along the azimuthal direction and depends on the amount of OAM and the light intensity. Here, we present the reverse customized method to tailor the nonuniform local OAM density along the azimuthal direction of the focal field, which has a hybrid polarization distribution and maintains a doughnut-shaped intensity profile. Theoretical analysis and experimental results about the orbital motion of the trapped polystyrene sphere show that the nonuniform local OAM density can be tailored by manipulating the polarization states of the focal field. Our results provide an ingenious way to control the local tangential optical force and the speed of the orbital motion of particles driven by the local OAM density and will promote exciting possibilities for exploring ways to control the mechanical dynamics of microparticles in optical trapping and microfluidics.

Hashimoto's thyroiditis-related myopathy in a patient with SARS-CoV-2 infection: A case report and systematic literature review.

RATIONALE: Hashimoto's thyroiditis (HT) is a common autoimmune disease. However, its presentation and management in the context of COVID-19 are unclear, and COVID-19-triggered HT, along with myopathy and persistent creatine kinase (CK) levels, have not been previously reported. Moreover, no literature review is currently available on HT in the context of COVID-19. This study is a case report and systematic review of the literature. PATIENT CONCERNS: A 33-year-old man was admitted with acute-onset myalgia, anosmia, loss of taste, fever, and upper respiratory tract symptoms. DIAGNOSES: He was diagnosed with coronavirus disease (COVID-19) during hospitalization and had abnormal CK levels. The elevated CK level persisted even after the resolution of COVID-19. After excluding myopathies and cardiac factors, HT was diagnosed. INTERVENTIONS: CK levels did not decrease appreciably until 14 d after levothyroxine administration. OUTCOMES: The patient was discharged from the hospital in good health. In the systematic literature review, 7 case reports on COVID-19-associated HT were observed, although no incidence of associated myopathy or persistent elevation of CK was noted. LESSONS: This case report highlights the potential link between COVID-19 and autoimmune thyroid diseases. In particular, this study underscores the significance of recognizing new-onset autoimmune thyroid disease in COVID-19-positive patients with elevated CK levels that cannot be attributed to other factors. This systematic review offers additional perspectives for diagnosing and managing HT in COVID-19 settings. Overall, the findings of this study could have important clinical implications for the care of COVID-19 patients, as early identification and treatment of autoimmune thyroid disease could help prevent long-term complications. Additional research is essential to elucidate the fundamental correlations between COVID-19 and HT and assess the effectiveness of therapeutic approaches for autoimmune thyroid conditions related to COVID-19.

Optical coherence tomography angiography metrics in diabetes: Focusing on diabetic retinopathy and carotid atherosclerosis.

BACKGROUND: To explore the value of Optical Coherence Tomography Angiography (OCTA) metrics in the early diagnosis of vascular complications in diabetes. METHODS: All participants underwent OCTA with a swept-source OCT device. Automated measurements of the foveal avascular zone (FAZ) area, vessel density (VD), and blood flow density (BFD) of both 3 × 3 and 6 × 6 windows were then obtained after a quality check. RESULTS: Diagnostic models based on multiple risk factors were developed separately for diabetic retinopathy and carotid atherosclerosis using random forest and multivariate logistic regression methods. The addition of specific OCTA metrics improved the diagnostic prediction of DR compared with the models of risk factors alone (Inner Retinal Blood Flow Density in 3 × 3 window, IRBFD; Brier score 0.124 vs. 0.149; AUC, 0.887 vs. 0.836) (Central Retinal Blood Flow Density in 3 × 3 window, CRBFD; Brier score 0.142 vs. 0.149; AUC, 0.851 vs. 0.836). Adding diabetic peripheral vascular disease (DPVD) indicator improved the prediction of carotid atherosclerosis (Brier score, 0.180 vs. 0.192; AUC, 0.802 vs. 0.781. The FAZ in the 3 × 3 window also achieved this effect when targeting only T2DM patients (AUC, 0.797 vs. 0.766; Brier score, 0.183 vs. 0.195). CONCLUSIONS: Focusing on IRBFD and CRBFD in the 3 × 3 window of OCTA allows for a more sensitive prediction of the occurrence of DR in diabetic patients. Meanwhile, the quantitative microvascular information provided by OCTA and the occurrence of DPVD may be crucial for diagnosing carotid atherosclerosis. For T2DM patients, we also propose the possibility of FAZ in the 3 × 3 window as a potential diagnostic indicator.

Activation of mGlu2/3 receptors in the striatum alleviates L-DOPA-induced dyskinesia and inhibits abnormal postsynaptic molecular expression.

Group II metabotropic glutamate receptors (mGlu2/3 receptors) have been regarded as promising candidates for the treatment of L-DOPA-induced dyskinesia (LID); however, confirmation is still lacking. As the hub of the basal ganglia circuit, the striatum plays a critical role in action control. Supersensitive responsiveness of glutamatergic corticostriatal input may be the key mechanism for the development of LID. In this study, we first examined the potency of LY354740 (12 mg/kg, i.p.) in modulating glutamate and dopamine release in lesioned striatum of stable LID rats. Then, we injected LY354740 (20nmoL or 40nmoL in 4 µL of sterile 0.9 % saline) directly into the lesioned striatum to verify its ability to reduce or attenuate L-DOPA-induced abnormal involuntary movements. In experiment conducted in established LID rats, after continuous injection for 4 days, we found that LY354740 significantly reduced the expression of dyskinesia. In another experiment conducted in parkinsonism rat models, we found that LY354740 attenuated the development of LID with an inverted-U dose-response curve. The role of LY354740 in modulating striatal expressions of LID-related molecular changes was also assessed after these behavioral experiments. We found that LY354740 significantly inhibited abnormal expressions of p-Fyn/p-NMDA/p-ERK1/2/p-HistoneH3/ΔFosB, which is in line with its ability to alleviate abnormal involuntary movements in both LID expression and induction phase. Our study indicates that activation of striatal mGlu2/3 receptors can attenuate the development of dyskinesia in parkinsonism rats and provide some functional improvements in LID rats by inhibiting LID-related molecular changes.

A Flexible Bi-Stable Composite Antenna with Reconfigurable Performance and Light-Responsive Behavior.

An integrated solution providing a bi-stable antenna with reconfigurable performance and light-responsive behavior is presented in this paper for the first time. The proposed antenna includes a radiation layer with conductivity, which is integrated onto the bi-stable substrate. First, the effect of the radiation layer material and substrate layer parameters on antenna performance was studied. The experiment showed that an antenna with CNTF has a wider impedance bandwidth than one with CSP, namely 10.37% versus 3.29%, respectively. The resonance frequency increases gradually with the increase in fiber laying density and fiber linear density. Second, the influence of state change of the substrate layer on the antenna radiation pattern was studied. The measured results showed that the maximum radiation angle and gain of states I and II are at 90°, 1.21 dB and 225°, 1.53 dB, respectively. The gain non-circularities of the antenna at states I and II are 4.48 dB and 8.35 dB, respectively, which shows that the antenna has good omnidirectional radiation performance in state I. The display of the array antenna, which shows that the array antenna has good omnidirectional radiation performance in state A, with gain non-circularities of 4.20 dB, proves the feasibility of this bi-stable substrate in reconfigurable antennas. Finally, the antenna deforms from state I to state II when the illumination stimulus reaches 22 s, showing good light-responsive behavior. Moreover, the bi-stable composite antenna has the characteristics of small size, light weight, high flexibility, and excellent integration.

The Singapore Experience With Uncontrolled Gout: Unmet Needs in the Management of Patients.

Gout is the most common type of inflammatory arthritis, and its impact on cardiovascular health and quality of life is often underestimated. The prevalence and incidence of gout are increasing globally. Further, ischemic heart disease (IHD) and chronic kidney disease (CKD) are prevalent in gout patients. Some unmet needs for gout management include physicians' low initiation rate of urate-lowering therapy (ULT) and poor treatment adherence in patients with gout. There is also a lack of randomized controlled trials that establish safe doses of acute and long-term treatment for gout, particularly in patients with IHD and stage 4 CKD and above (including end-stage renal failure). Furthermore, there is also a lack of studies showing optimal serum uric acid (SUA) target and validated clinical outcome measures, including disease activity and remission criteria for gout tailored to treat-to-target approaches and the high cost of newer gout medications. The causal relationship between asymptomatic hyperuricemia or gout with comorbidities such as IHD and CKD has yet to be fully elucidated. There is a pressing need for collaborative international efforts to address the overall suboptimal management of gout.

Knockdown of NtCPS2 promotes plant growth and reduces drought tolerance in Nicotiana tabacum.

Drought stress is one of the primary environmental stress factors that gravely threaten crop growth, development, and yields. After drought stress, plants can regulate the content and proportion of various hormones to adjust their growth and development, and in some cases to minimize the adverse effects of drought stress. In our previous study, the tobacco cis-abienol synthesis gene (NtCPS2) was found to affect hormone synthesis in tobacco plants. Unfortunately, the role of NtCPS2 genes in the response to abiotic stress has not yet been investigated. Here, we present data supporting the role of NtCPS2 genes in drought stress and the possible underlying molecular mechanisms. NtCPS2 gene expression was induced by polyethylene glycol, high-temperature, and virus treatments. The results of subcellular localization showed that NtCPS2 was localized in the cell membrane. The NtCPS2-knockdown plants exhibited higher levels of gibberellin (GA) content and synthesis pathway genes expression but lower abscisic acid (ABA) content and synthesis pathway genes expression in response to drought stress. In addition, the transgenic tobacco lines showed higher leaf water loss and electrolyte loss, lower soluble protein and reactive oxygen species content (ROS), and lower antioxidant enzyme activity after drought treatment compared to wild type plants (WT). In summary, NtCPS2 positively regulates drought stress tolerance possibly by modulating the ratio of GA to ABA, which was confirmed by evidence of related phenotypic and physiological indicators. This study may provide evidence for the feedback regulation of hormone to abiotic and biotic stresses.

Different visual evoked potentials in neuromyelitis optica spectrum disorder-related optic neuritis and idiopathic demyelinating optic neuritis: a prospective longitudinal analysis.

BACKGROUND: To investigate different visual evoked potential (VEP) patterns in neuromyelitis optica spectrum disorder-related optic neuritis (NMOSD-ON) and idiopathic demyelinating optic neuritis (IDON). METHODS: This was a longitudinal, prospective, case-control study. Eighty-four Chinese patients with acute optic neuritis were enrolled, including 26 NMOSD-ON patients and 58 IDON patients. All the patients underwent best-corrected visual acuity (BCVA) and full-field pattern reversal VEP recordings at the onset, 1 month, 3 months, and 6 months. RESULTS: Within 15' checks, the NMOSD-ON patients had more severe VEP amplitude reduction at 6 months (2.39 ± 4.63 µV vs. 6.96 ± 8.88 µV, P = 0.034). However, the IDON patients showed more frequently normal VEP response at 3 months (24.0% vs. 4.5%, P = 0.017), and only prolonged P100 peak latency with normal amplitude (L) at 6 months (30.0% vs. 57.8%, P = 0.048). Within 60' checks, no significant difference in VEP parameters between the two groups was found at each follow-up (P > 0.05). CONCLUSIONS: The NMOSD-ON patients showed more severe axonal damage and worse axonal recovery than the IDON patients. VEP elicited by smaller check size was more sensitive to visual pathway abnormality in NMOSD-ON.

A modification-centric assessment tool for the performance of chemoproteomic probes.

Chemoproteomics has emerged as a key technology to expand the functional space in complex proteomes for probing fundamental biology and for discovering new small-molecule-based therapies. Here we report a modification-centric computational tool termed pChem to provide a streamlined pipeline for unbiased performance assessment of chemoproteomic probes. The pipeline starts with an experimental setting for isotopically coding probe-derived modifications that can be automatically recognized by pChem, with masses accurately calculated and sites precisely localized. pChem exports on-demand reports by scoring the profiling efficiency, modification homogeneity and proteome-wide residue selectivity of a tested probe. The performance and robustness of pChem were benchmarked by applying it to eighteen bioorthogonal probes. These analyses reveal that the formation of unexpected probe-derived modifications can be driven by endogenous reactive metabolites (for example, bioactive aldehydes and glutathione). pChem is a powerful and user-friendly tool that aims to facilitate the development of probes for the ever-growing field of chemoproteomics.

Recognition of Bookmark Aging Degree Based on Probabilistic Neural Network.

Bookmarks are the basis for librarians to get books on and off shelves and borrowers to borrow books. In order to solve the problem of time-consuming and labor-consuming manual checking of bookmark aging, this paper proposes a method of bookmark aging recognition based on image processing technology. First, we perform image preprocessing, Otsu threshold segmentation, and morphological processing on the acquired bookmark image to obtain the effective area of the bookmark, then acquire the aging features for the bookmark, and finally input the acquired features into the trained neural network for defect recognition. The experimental results show that the method proposed in this paper can achieve 96% recognition, which can more accurately identify the aging defects of bookmarks.

The Relationship between the Mechanism of Sarcopenia and Exercise Based on Data Mining.

Due to the increasing prosperity of human life science and technology, many huge research results have been obtained, and the scientific research of molecular biology is developing rapidly. Therefore, the output of biological genome data has increased exponentially, which constitutes a huge amount of data analysis. The seemingly chaotic and massive amount of data information actually contains a large amount of data and information of great key scientific significance and value. Therefore, this kind of genomic data information not only contains the information content that describes the characteristics of human life but also contains the information content that can express the essence of the biological organism. It includes macroeconomic information that can reflect the basic structure and capabilities of living organisms and microinformation in related fields of molecular biology. This massive amount of genetic data is usually closely related to each other, can influence each other, and does not exist alone. In the article, the causes of uncertain data and the classification of uncertain data are introduced, and the basic concepts and related algorithms of data mining are explained. Focusing on the research and analysis of abnormal point detection and clustering algorithms in uncertain data mining technology, this paper solves the problem of how to obtain more diverse and accurate outlier detection and cluster analysis results in uncertain data. The results showed that whether it was related to obesity or not, the Lp(a) level of the sarcopenia group was significantly higher than that of the nonsarcopenia group. At the same time, the correlation analysis showed that ASM/height was negatively correlated with Lp(a). ASM/height is one of the criteria for diagnosing sarcoidosis, and it is also the core of the analysis. Among the 1956 tumor patients collected in this study, 432 had sarcopenia, accounting for 22.08%, and the incidence of sarcopenia in patients with gastrointestinal tumors increased.

Causal Relationships Between Social Isolation and Osteoarthritis: A Mendelian Randomization Study in European Population.

OBJECTIVE: We aimed to investigate the causal relationships between social isolation and osteoarthritis. METHODS: Publicly available genome-wide association study (GWAS) summary statistics of social isolation and osteoarthritis in European population were obtained from the Neale lab Consortium and the Medical Research Council-Integrative Epidemiology Unit (MRC-IEU) consortium, respectively. Single nucleotide polymorphisms (SNPs) associated with the traits were identified by P < 5×10-8 and linkage disequilibrium r2 < 0.1. Three Mendelian randomization (MR) methods including the inverse-variance weighted (IVW) method, weighted median estimator, and MR-Egger regression were used to assess the potential causal effect of social isolation on osteoarthritis and the potential causal effect of osteoarthritis on social isolation. Leave-one-out analysis and test of directional horizontal pleiotropy via MR-Egger regression were performed as sensitivity analyses. RESULTS: When evaluating the causal effect of social isolation on osteoarthritis, five SNPs (rs12364432, rs13291079, rs2352075, rs4958586, rs599550) significantly associated with social isolation were studied as instruments, and social isolation was found to be causally associated with increased risk of osteoarthritis (odds ratio [OR] 1.197 (95% confidence interval (CI) 1.096-1.308) estimated by the IVW method). When evaluating the causal effect of osteoarthritis on social isolation, six SNPs (rs10405617, rs12133235, rs13107325, rs2290573, rs3771501, rs75621460) significantly associated with osteoarthritis were studied as instruments but no causal effect of osteoarthritis on social isolation was found (OR 1.104 (95% CI 0.887-1.375) estimated by the IVW method). Consistent causal relationships were observed when estimated by the weighted median estimator and MR-Egger regression. Leave-one-out analysis and test of directional horizontal pleiotropy suggested the robustness of the above findings. CONCLUSION: Social isolation is causally associated with osteoarthritis, and further work is needed to investigate the potential mechanisms.

Identification and Functional Characterization of a Low-Density Lipoprotein Receptor Gene Pathogenic Variant in Familial Hypercholesterolemia.

We report a single-point variant of low-density lipoprotein receptor (LDLR) in a Chinese proband with a clinical diagnosis of familial hypercholesterolemia (FH) with a comprehensive functional analysis. Target exome capture-based next-generation sequencing was used for sequencing and identification of genomic variants in the LDLR gene. The expression, cellular location, and function of the mutant LDLR were analyzed. Sequencing of LDLR in FH patients indicated a point variant of single-base substitution (G < A) at a position of 2389 in the 16th exon, which led to a loss of the 16th exon in the LDLR messenger RNA. This genomic variant was found to cause exon 16 deletion in the mutant LDLR protein. Subsequent functional analyses showed that the mutant LDLR was retained in the Golgi apparatus and rarely expressed in the cellular membranes of HepG2 cells. Accordingly, the intake ability of HepG2 cells with the mutant LDLR was significantly reduced (P < 0.05). In conclusion, our results suggest that a mutant with a single-base substitution (c. 2389G > A) in the 16th exon of the LDLR gene was associated with miscleavage of messenger RNA and the retention of mutant LDLR in the Golgi apparatus, which revealed a pathogenic variant in LDLR underlying the pathogenesis of FH.